 Ischemia : depressed ST, Inverted T in ( VI, 2, 3 )  Infarction : Raised ST, ( VI , 2 , 3 )    Ischemia : depressed ST, Inverted T,in ( V4,5,6 )  Infarction : Raised ST , ( V 4,5,6 )   The following steps provide an overview of how to take your left arm blood pressure on either a  manual or digital blood pressure monitor. Simply reverse the sides to take a blood pressure in your  right arm.   Locate your pulse by lightly pressing your index and middle fingers slightly to the inside center of the  bend of your elbow (where the brachial artery is). If you cannot locate your pulse, place the head of  the stethoscope (on a manual monitor) or the arm cuff (on a digital monitor) in the same general area.   Thread the cuff end through the metal loop and slide the cuff onto your arm, making sure that the  stethoscope head is over the artery (when using a manual monitor.) The cuff may be marked with an  arrow to show the location of the stethoscope head. The lower edge of the cuff should be about 1  inch above the bend of your elbow. Use the fabric fastener to make the cuff snug, but not too tight.   Place the stethoscope in your ears. Tilt the ear pieces slightly forward to get the best sound.   3. Inflate and deflate the cuff If you are using a manual monitor:   Hold the pressure gauge in your left hand and the bulb in your right.   Inflate the cuff by squeezing the bulb with your right hand. You may hear your pulse in the  stethoscope.   Watch the gauge. Keep inflating the cuff until the gauge reads about 30 points (mm Hg) above your  expected systolic pressure. At this point, you should not hear your pulse in the stethoscope.   Keeping your eyes on the gauge, slowly release the pressure in the cuff by opening the airflow valve  counterclockwise. The gauge should fall only 2 to 3 points with each heartbeat. (You may need to  practice turning the valve slowly.)   Listen carefully for the first pulse beat. As soon as you hear it, note the reading on the gauge. This  reading is your systolic pressure (the force of the blood against the artery walls as your heart beats).  Continue to slowly deflate the cuff.   Listen carefully until the sound disappears. As soon as you can no longer hear your pulse, note the  reading on the gauge. This reading is your diastolic pressure (the blood pressure between  heartbeats).   (_pa*J ^^gJaLu Ajj i" IaIc. dli pj jjfd 'j ^^gJulL !_jjlpla _ . dli (_Jj 3 c-ljl (_£ I j^l (_Ja ^jlLmS _ ^^dlL l^jtpli   C-La (_L aC- ^»J a\I (_^i ji cL^j Jj-aC. jl Jj-ujI JjjjC. ^pjJ (_Ja jl ^LuaJ ^.La (_J-a*J (_JaVI   NB: If you infuse 25% infuse 200 ml & if 50 % infuse 100 ml   ? (jalj-uij! .iklaj (_Ja ? jfLa (_ja ^cJlsuaj Ja _ _ ^-»g jlc. ^ jV Jl j^j-u (Jji    R/ Diphenhydramine 25 - 50 mg IV q6hr  R/ Hydrocortisone 300 mg IV bolus   - Administer 0.3 - 0.5 ml of 1 :1000solution subcutaneously .... And could  repeat after 20 minutes if necessary   l . 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(jjjta.L I g'vW ^^ j-ujI d*J l^dljj  jj-^e ^1 (ja ^gjLi (_ 5 iiil A3dl t^ill SjC-dll (_Ja^.l La jj^l jj'~i^ll j jj''i^ll 1 ___ alat \i (_Ja^.l LaS    Side-effects Side-effects of thiazides and related diur-  etics include mild gastro-intestinal disturbances, postur-  al hypotension, altered plasma-lipid concentrations,  metabolic and electrolyte disturbances including hypo-  kalaemia (see also notes above), hyponatraemia, hypo-  magnesaemia, hypercalcaemia, hyperglycaemia, hypo-  chloraemic alkalosis, hyperuricaemia, andB ggiH Less  common side-effects include blood disorders such as  agranulocytosis, leucopenia, and thrombocytopenia,  and impotence. Pancreatitis, intrahepatic cholestasis,  cardiac arrhythmias, headache, dizziness, paraesthesia,  visual disturbances, and hypersensitivity reactions  (including pneumonitis, pulmonary oedema, photo-  sensitivity. and severe skin reactions) have also been  reported.   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Ajlj __ J_jia  l^j^as^uiv ^aJJ V (jVI CluiaSj C—UflalL A_L^aljaJ! AlLlj^)]! (j! lljlj ^1^1*11   Lj^j-aaa (Jilall dljllj AjV a ^al Aa!j __ i_S^>C.I V (Jl£a ? Ajlllj Alia-saS L_S^)*j (JIj^jjaJ AjjJLiS   (Uncomplicated MI)  Gradual supervision  2 wk: walk around  4 wk: — > 2 mile/d  6wk: 2 miles in < 30 min/d  Return to sedentary work  Driving may be allowed  Resume sexual activity  8 wk: return to light manual  work   Flying > 2 wk if can climb 1  floor without difficulty   C VD: postural hypotension  Digestive: jaundice diarrhea,  vomiting, constipation, gastric  irritation, nausea, anorexia.  Hematologic: leukopenia,  hemolytic anemia,  thrombocytopenia.  Hypersensitivity   Proteinuria >2g/d  Creatinine >2mg/dL  Platelets <100.000/mm3  Hemolysis  Abdominal Pain  Severe headache  Congestive HF  Retinal hemorrhage/  exudates/papilloedema  Intrauterine fetal growth  retardation    Gastroenteritis  Streptococcal  Pharyngitis in children  Meningitis  Otitis media  Any febrile illness    Plain x-ray  of the abdomen and  upright for free air under  diaphragm   Hypertension is one of the most common worldwide diseases afflicting humans and is  a major risk factor for stroke, myocardial infarction, vascular disease, and chronic  kidney disease. Due to the associated morbidity and mortality and cost to society,  preventing and treating hypertension is an important public health challenge.   Hypertension is the most important modifiable risk factor for coronary heart disease  (the leading cause of death in North America), stroke (the third leading cause),  congestive heart failure, end-stage renal disease, and peripheral vascular disease.  Therefore, health care professionals must not only identify and treat patients with  hypertension but also promote a healthy lifestyle and preventive strategies to decrease  the prevalence of hypertension in the general population.   Based on recommendations of the JNC 7, the classification of BP (expressed in mm  Hg) for adults aged 1 8 years or older is as follows 1 :   Normal : systolic lower than 120 mm Hg, diastolic lower than 80 mm Hg  Prehypertension : systolic 120-139 mm Hg, diastolic 80-89 mm Hg  Stage 1 : systolic 140-159 mm Hg, diastolic 90-99 mm Hg  Stage 2 : systolic 160 mm Hg or greater, diastolic 100 mm Hg or greater  The classification above is based on the average of 2 or more readings taken at each  of 2 or more visits after initial screening.   Prehypertension, a new category designated in the JNC 7 report, emphasizes that  patients with prehypertension are at risk for progression to hypertension and that  lifestyle modifications are important preventive strategies.   Primary (essential) hypertension is diagnosed in the absence of an identifiable  secondary cause. Approximately 90-95% of adults with hypertension have primary  hypertension, whereas secondary hypertension accounts for around 5-1 0% of the  cases.   Especially severe cases of hypertension, or hypertensive crises , are defined as a BP  of more than 180/120 mm Hg and may be further categorized as hypertensive  emergencies or urgencies. Hypertensive emergencies are characterized by evidence  of impending or progressive target organ dysfunction, whereas hypertensive urgencies  are those situations without progressive target organ dysfunction.   In hypertensive emergencies, the BP should be aggressively lowered within minutes to   an hour by no more than 25%. and then lowered to 1 60/1 00-1 1 0 mm Hg within the   Acute end-organ damage in the setting of a hypertensive emergency may include the  following:   Neurologic: hypertensive encephalopathy, cerebral vascular accident/cerebral  infarction, subarachnoid hemorrhage, intracranial hemorrhage  Cardiovascular: myocardial ischemia/infarction, acute left ventricular dysfunction,  acute pulmonary edema, aortic dissection, unstable angina pectoris  Other: acute renal failure/insufficiency, retinopathy, eclampsia, microangiopathic  hemolytic anemia   The pathogenesis of essential hypertension is multifactorial and highly complex.  Multiple factors modulate the blood pressure (BP) for adequate tissue perfusion and  include humoral mediators, vascular reactivity, circulating blood volume, vascular  caliber, blood viscosity, cardiac output, blood vessel elasticity, and neural stimulation.  A possible pathogenesis of essential hypertension has been proposed in which  multiple factors, including genetic predisposition, excess dietary salt intake, and  adrenergic tone, may interact to produce hypertension. Although genetics appears to  contribute to essential hypertension, the exact mechanism has not been established.   Hypertension may be primary, which may develop as a result of environmental or  genetic causes, or secondary, which has multiple etiologies, including renal, vascular,  and endocrine causes. Primary or essential hypertension accounts for 90-95% of adult  cases, and a small percentage of patients (2-10%) have a secondary cause.  Hypertensive emergencies are most often precipitated by inadequate medication or  poor compliance.   Renal causes (2.5-6%) of hypertension include the renal parenchymal diseases and  renal vascular diseases, as follows:   Polycystic kidney disease  Chronic kidney disease  Urinary tract obstruction  Renin-producing tumor  Liddle syndrome   Endocrine causes exogenous or endogenous hormonal imbalances. Exogenous  causes include - administration of steroids.   The most common form of secondary hypertension is a renal cause   Activation of the renin-angiotensin-aldosterone system (RAAS) is the likely  mechanism, because hepatic synthesis of angiotensinogen is induced by the estrogen   component of oral contraceptives. Approximately 5% of women taking oral  contraceptives may develop hypertension, which abates within 6 months after  discontinuation. The risk factors for oral contraceptive-associated hypertension include  mild renal disease, familial history of essential hypertension, age older than 35 years,  and obesity. It would be better to group oral contraceptives and steroids with drug-  induced hypertension .   Exogenous administration of the other steroids used for therapeutic purposes also  increases blood pressure (BP), especially in susceptible individuals, mainly by volume  expansion.   Nonsteroidal anti-inflammatory drugs (NSAIDs) may also have adverse effects on BP.  NSAIDs block both cyclooxygenase-1 (COX-1) and COX-2 enzymes. The inhibition of  COX-2 can inhibit its natriuretic effect, which, in turn, increases sodium retention.  NSAIDs also inhibit the vasodilating effects of prostaglandins and the production of  vasoconstricting factors — namely, endothelin-1 . These effects can contribute to the  induction of hypertension in a normotensive or controlled hypertensive patient.   Alcohol - Cocaine - Cyclosporine, tacrolimus - NSAIDs  Erythropoietin - Adrenergic medications - Decongestants ( ephedrine)   Herbal remedies containing licorice (including licorice root) or ephedrine (and  ephedra)   Hyperthyroidism and hypothyroidism - Hypercalcemia - Hyperparathyroidism  Acromegaly - Obstructive sleep apnea - Pregnancy-induced HPN   The most common hypertensive emergency is a rapid unexplained rise in BP in a  patient with chronic essential hypertension. Most patients who develop hypertensive  emergencies have a history of inadeguate hypertensive treatment or an abrupt  discontinuation of their medications .   Hypertension is a lifelong disorder. For optimal control, a long-term commitment to  lifestyle modifications and pharmacologic therapy is required.   Prevention and treatment of obesity: an increase in body mass index (BMI) and waist  circumference is associated with an increased risk of developing conditions with high  cardiovascular risk, such as hypertension, diabetes mellitus, impaired fasting glucose,  and left ventricular hypertrophy [LVH]   Following the documentation of hypertension, which is confirmed after an elevated  blood pressure (BP) on at least 3 separate occasions (based on the average of 2 or  more readings taken at each of >2 follow-up visits after initial screening), a detailed  history should extract the following information:   Patients may have undiagnosed hypertension for years without having had their BP  checked. Therefore, a careful history of end-organ damage should be obtained. The  Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,  and Treatment of High Blood Pressure (JNC 7) identifies the following as targets of  end-organ damage:   The JNC 7 identifies the following as major cardiovascular risk factor :   Elevated LDL cholesterol (or total cholesterol >240 mg/dL) or low HDL cholesterol:   Age greater than 55 years for men or greater than 65 years for women: increased risk  begins at the respective ages; the Adult Treatment Panel III used earlier age cut  points to suggest the need for earlier action  Estimated glomerular filtration rate < 60 mL/min  Microalbuminuria   Family history of premature cardiovascular disease (men < 55 years; women < 65  years)   Obtain a history of the patient’s use of over-the-counter medications; herbal medicines  such as herbal tea containing licorice   The historical and physical findings that suggest the possibility of secondary  hypertension are a history of known renal disease, abdominal masses, anemia, and  urochrome pigmentation.   - A history of sweating, labile hypertension, and palpitations suggests the diagnosis of  pheochromocytoma.   - A history of cold or heat tolerance, sweating, lack of energy, and bradycardia or  tachycardia may indicate hypothyroidism or hyperthyroidism.   - A history of obstructive sleep apnea may be noted. A history of weakness suggests  hyperaldosteronism.   An accurate measurement of blood pressure is the key to diagnosis. Several  determinations should be made over a period of several weeks. At any given visit, an  average of 3 blood pressure readings taken 2 minutes apart using a mercury  manometer is preferable. On the first visit, blood pressure should be checked in both  arms and in one leg to avoid missing the diagnosis of coarctation of aorta or  subclavian artery stenosis.   The patient should rest quietly for at least 5 minutes before the measurement. Blood  pressure should be measured in both the supine and sitting positions, auscultating with  the bell of the stethoscope. As the improper cuff size may influence blood pressure  measurement, a wider cuff is preferable, particularly if the patient’s arm circumference  exceeds 30 cm. Although somewhat controversial, the common practice is to  document phase V (a disappearance of all sounds) of Korotkoff sounds as the diastolic  pressure.   Ambulatory or home blood pressure monitoring provides a more accurate prediction of  cardiovascular risk than do office blood pressure readings. "Non-dipping" is the loss of  the usual physiologic nocturnal drop in blood pressure and is associated with an  increased cardiovascular risk.   A study by Wong and Mitchell indicated that independent of other risk factors, there is  a link between the presence of certain signs of hypertensive retinopathy (eg, retinal  hemorrhages, microaneurysms, cotton-wool spots) and an increased cardiovascular  risk (eg, stroke, stroke mortality). Therefore, a funduscopic evaluation of the eyes  should be performed to detect any evidence of early or late, chronic or acute  hypertensive retinopathy, including arteriovenous nicking or changes in the vessel wall  (eg, copper wiring, silver wiring, SOT , hard exudates, flame-shaped hemorrhages,  papilledema). Indeed, ocular changes can be the initial finding in an asymptomatic  patient necessitating a primary care referral; acute and chronic changes may manifest   in the eyes. Alternatively, a symptomatic patient may be referred to the  ophthalmologist for visual changes due to hypertensive changes.    Palpation of all peripheral pulses should be performed. Absent, weak, or delayed  femoral pulses suggests coarctation of the aorta or severe peripheral vascular disease.  In addition, examine the neck for carotid bruits, distended veins, or enlarged thyroid  gland. Listen for renal artery bruit over the upper abdomen; the presence of a bruit with  both a systolic and diastolic component suggests renal artery stenosis.   A careful cardiac examination is performed to evaluate signs of LVH. These include  displacement of apex, a sustained and enlarged apical impulse, and the presence of  an S 4 . Occasionally, a tambour S 2 is heard with aortic root dilatation.   The history and physical examination determine the nature, severity, and management  of the hypertensive event. The history should focus on the presence of end-organ  dysfunction . The physical examination should assess whether end-organ dysfunction  is present (eg, neurologic, cardiovascular). BP should be measured in both the supine  position and the standing position (assess volume depletion). BP should also be  measured in both arms   The most common clinical presentations of hypertensive emergencies are cerebral  infarction (24.5%), pulmonary edema (22.5%), hypertensive encephalopathy (16.3%),  and congestive heart failure (12%). Other clinical presentations associated with  hypertensive emergencies include intracranial hemorrhage, aortic dissection ,  and eclampsia as well as acute myocardial infarction. Hypertension is also one of  several conditions that have been increasingly recognized as having an association  with posterior reversible encephalopathy syndrome (PRES), a condition characterized  by headache, altered mental status, visual disturbances, and seizures.   Uncontrolled and prolonged BP elevation can lead to a variety of changes in the  myocardial structure, coronary vasculature, and conduction system of the heart. These  changes in turn can lead to the development of left ventricular hypertrophy (LVH),  coronary artery disease, various conduction system diseases, and systolic and  diastolic dysfunction of the myocardium, which manifest clinically  as angina or mvocardial infarction , cardiac arrhythmias (especially atrial fibrillation),  and conqestive heart failure (CHF) . Thus, hypertensive heart disease is a term applied  generally to heart diseases — such as LVH, coronary artery disease , cardiac  arrhythmias, and CHF — that are caused by direct orindirect effects of elevated BP.   Although these diseases generally develop in response to chronically elevated BP,  marked and acute elevation of BP can also lead to accentuation of an underlying  predisposition to any of the symptoms traditionally associated with chronic  hypertension.   In a study by Tymchak et al, patients presenting with acute heart failure as a  manifestation of hypertensive emergency were more likely to be black and have a  history of heart failure; they were also more likely to have higher B-type natriuretic  peptide (BNP) and creatinine levels and lower left ventricular ejection fraction. Note  that BNP is inversely proportional to the degree of a patient’s obesity.   Systemic hypertension is less common in children than in adults, but the incidence of  hypertension in children is approximately 1-5%. The presence of hypertension in  younger children is usually indicative of an underlying disease process (secondary  hypertension). In children, approximately 5-25% of cases of secondary hypertension  are attributed to renovascular disease.   Hypertension is the most common medical problem encountered during pregnancy,  complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are  classified into the 4 following categories, as recommended by the National High Blood  Pressure Education Program Working Group on High Blood Pressure in Pregnancy:   pregnancy-induced hypertension (transient hypertension of pregnancy or chronic  hypertension identified in the latter half of pregnancy.   Mineralocorticoid excess secondary to primary hyperaldosteronism is infrequently  observed and is characterized by excessive production of aldosterone. Renal sodium  retention, kaliuresis, hypokalemia, and hypochloremic metabolic alkalosis are the  common manifestations. It should be considered in patients who have an exaggerated  hypokalemic response to a thiazide diuretic or who have hypokalemia unprovoked by a  diuretic. These patients develop increased intravascular volume, resulting in  hypertension. The BP increase may vary from mild hypertension to marked elevation in  primary hyperaldosteronism. Patients may have underlying adenoma or hyperplasia of  the adrenal gland and rarely have an extra-adrenal source for aldosterone.   In contrast, inappropriately high output of aldosterone for a given salt state of a patient  (ie, not meeting criteria for a diagnosis of primary aldosteronism) is much more  common, especially in patients with metabolic syndrome.   Many guidelines exist for the management of hypertension. Two of the most widely  used recommendations are those from the American Diabetes Association (ADA) and  the Seventh Report of the Joint National Committee on Prevention, Detection,  Evaluation, and Treatment of High Blood Pressure (JNC 7).   The ADA 201 1 standards of medical care in diabetes also indicate that a majority of  patients with diabetes mellitus have hypertension. In patients with type 1 diabetes ,   nephropathy is often the cause of hypertension, whereas in type 2 diabetes ,  hypertension is one of a group of related cardiometabolic factors. Hypertension remains  one of the most common causes of congestive heart failure (CHF). Antihypertensive  therapy has been demonstrated to significantly reduce the risk of death from stroke   The goals of antihypertensive therapy is the reduction of cardiovascular and renal  morbidity and mortality, with the focus on controlling the systolic BP, as most patients  will achieve diastolic BP control when the systolic BP is achieved  Prehypertension (systolic 120-139 mm Hg, diastolic 80-89 mm Hg) requires health-  promoting lifestyle modifications to prevent the progressive rise in blood pressure and  cardiovascular disease   In uncomplicated hypertension, a thiazide diuretic, either alone or combined with  drugs from other classes, should be used for the pharmacologic treatment of most  cases   In specific high-risk conditions, there are compelling indications for the use of other  antihypertensive drug classes (eg, angiotensin-converting enzyme [ACE] inhibitors,  angiotensin receptor blockers [ARBs], beta blockers, calcium channel blockers)   Two or more antihypertensive medications will be required to achieve goal BP (<  140/90 mm Hg or < 130/80 mm Hg) for patients with diabetes and chronic kidney  disease   For patients whose BP is more than 20 mm Hg above the systolic BP goal or more  than 10 mm Hg above the diastolic BP goal, initiation of therapy using 2 agents, one  of which usually will be a thiazide diuretic, should be considered  Regardless of therapy or care, hypertension will be controlled only if patients are  motivated to stay on their treatment plan  Note that the JNC 8 is expected to be released in 201 2.   Joint National Committee of Prevention, Detection, Evaluation, and Treatment of High  Blood Pressure (JNC 7) recommendations to lower blood pressure :   (Dietary Approaches to Stop Hypertension) diet which is rich in fruits and vegetables  and encourages the use of fat-free or low-fat milk and milk products  Stop alcohol  Reduce sodium intake   Maintain adequate intake of dietary calcium and magnesium for general health  Stop smoking and reduce intake of dietary saturated fat and cholesterol for overall  cardiovascular health   The 201 0 American Heart Association-American Stroke Association (AHA-ASA)  guidelines for the primary prevention of stroke makes the following recommendations:   Hypertension: the AHA-ASA guidelines recommend regular blood pressure  screening, lifestyle modification, and drug therapy; lower risk of stroke and  cardiovascular events are seen when systolic blood pressure levels are lower than  140 mm Hg and diastolic blood pressure levels are less than 90 mm Hg  Diet and nutrition: a diet that is low in sodium and high in potassium is  recommended to reduce BP; diets that promote the consumption of fruits, vegetables,  and low-fat dairy products, help lower BP and may lower the risk of stroke  Physical inactivity: increasing physical activity is associated with a reduction in the  risk of stroke; the goal is to engage in 30 minutes or more of moderate intensity  activity on a daily basis   Obesity and body fat distribution: weight reduction in overweight and obese  persons is recommended to reduce BP and the risk of stroke   A number of studies have documented an association between sodium chloride intake  and BP. The effect of sodium chloride is particularly important in individuals who are  middle-aged to elderly with a family history of hypertension. A moderate reduction in  sodium chloride intake can lead to a small reduction in blood pressure. The American  Heart Association recommends that the average daily consumption of sodium chloride  not exceed 6 g; this may lower BP by 2-8 mm Hg.   The DASH eating plan encompasses a diet rich in fruits, vegetables, and low-fat dairy  products and may lower blood pressure by 8-14 mm Hg. The 201 1 ADA standard of  care supports the DASH diet, with the caution that high-quality studies of diet and  exercise to lower blood pressure have not been performed on individuals with  diabetes.   Weight reduction may lower blood pressure by 5-20 mm Hg per 1 0 kg of weight loss in  a patient whose weight is more than 10% of ideal body weight.   Regular aerobic physical activity can facilitate weight loss, decrease BP, and reduce  the overall risk of cardiovascular disease. Blood pressure may be lowered by 4-9 mm  Hg with moderately intense physical activity. These activities include brisk walking for  30 minutes a day, 5 days per week. More intense workouts of 20-30 minutes, 3-4 times  a week, may also lower BP and have additional health benefits.   The 201 1 ADA diabetes standards support increasing physical activity. The  recommendations emphasize that exercise is an important part of diabetes  management in addition to reducing cardiovascular risk factors, contributing to weight  loss, and improving overall well-being. Moreover, patients with diabetes and severe  hypertension (SBP >140 mm Hg or DBP >90 mm Hg) at diagnosis or afterward should  receive drug therapy along with lifestyle modifications.   If lifestyle modifications are insufficient to achieve the goal blood pressure (BP), there  are several drug options for the treatment and management of hypertension.   Heart failure: diuretic, beta-blocker, ACE inhibitor, ARB, aldosterone antagonist  Postmyocardial infarction: beta-blocker, ACE inhibitor, aldosterone antagonist  High coronary disease risk: diuretic, beta-blocker, ACE inhibitor, CCB  Diabetes: diuretic, beta-blocker, ACE inhibitor, ARB, CCB  Chronic kidney disease: ACE inhibitor, ARB  Recurrent stroke prevention: diuretic, ACE inhibitor  Note that different stages of these diseases may alter their treatment management.   Multiple clinical trials suggest that most antihypertensive drugs provide the same  degree of cardiovascular protection for the same level of BP control.   In addition, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack  Trial (ALLHAT) study concluded that there were no differences in primary coronary  heart disease outcome or mortality for the thiazide-like diuretic chlorthalidone, the ACE  inhibitor lisinopril, and the CCB amlodipine. In a systematic review and meta-analysis,  investigators also determined that in patients with essential hypertension without  preexisting renal disease, no significant difference was found between Ras inhibitors  and other antihypertensive agents in preventing renal dysfunction.   Hypertension and diabetes are both risk factors for cardiovascular disease, stroke,  progression of renal disease, and diabetic retinopathy.   In general, patients with diabetes type 1 or type 2 and hypertension have shown  clinical improvement with diuretics, ACE inhibitors, beta-blockers, ARBs, and   calcium antagonists . Most studies, however, have shown superiority of ACE  inhibitors or ARBs over calcium antagonists in diabetic patients.   Two or more antihypertensive drugs at maximal doses should be used to achieve  optimal BP targets in patients with diabetes and hypertension. Either an ACE inhibitor  or an ARB is usually required in patients with diabetes and hypertension.   Hypertensive emergencies are characterized by severe elevations in BP (>180/120  mm Hg) associated with acute end-organ damage.   Initial treatment goals are to reduce the mean arterial BP by no more than 25% within  minutes to 1 hour. I   f the patient is stable, reduce the BP to 1 60/1 00-1 1 0 mm Hg within the next 2-6 hours.  Several parenteral and oral therapies can be used to treat hypertensive emergencies,  such as nitroprusside sodium, hydralazine, nicardipine, fenoldopam, nitroglycerin, or  enalaprilat. Other agents that may be used include labetalol, esmolol, and   phentolamine. Avoid using short-acting nifedipine in the initial treatment of this  condition because of the risk of rapid, unpredictable hypotension and the possibility of  precipitating ischemic events.   Once the patient’s condition is stabilized, the patient’s BP may be gradually reduced  over the next 24-48 hours.   • Patients with an ischemic stroke (currently, no clear evidence exists for immediate  antihypertensive treatment)   • Patients with aortic dissection (their systolic BP should be lowered to < 100 mm Hg, if  tolerated)   • Patients in whom BP is lowered to allow thrombolytic therapy (eg, stroke patients)   In patients who are pregnant, the goal of antihypertensive treatment is to minimize the  risk of maternal cardiovascular or cerebrovascular events. Hypertensive disorders —  categorized as chronic hypertension, preeclampsia , chronic hypertension with  superimposed preeclampsia, gestational hypertension, and transient hypertension (see  Table 3, below) — may contribute to maternal, fetal, or neonatal morbidity and  mortality, particularly in the first trimester.   Although reducing maternal risk is the goal of treating chronic hypertension in  pregnancy, it is fetal safety that largely directs the choice of antihypertensive agent.  Methyldopa is generally the preferred first-line agent because of its safety profile. Other   drugs that may be considered include labetalol, beta-blockers, and diuretics . Data are  limited regarding the use of clonidine and calcium antagonists in pregnant women with  chronic hypertension; however, angiotensin-converting enzyme (ACE) inhibitors and  angiotensin II receptor (ARB) antagonists should be avoided because of the risk of  fetal toxicity and death.   Despite low plasma renin activity (PRA), blood pressure responds well to ACE inhibitor  and ARB therapy. Low doses of diuretics may also be effective. Thiazide-type diuretics  may be particularly beneficial for patients aged 55 years or older with hypertension or  CVD risk factors and for patients aged 60 years or older with isolated systolic  hypertension. The SHEP trial found that chlorthalidone stepped-care therapy for 4.5  years was associated with a longer life expectancy at 22-year follow-up in patients with  isolated systolic hypertension. The Syst-Eur trial used a study design and sample size  similar to those of the SHEP trial, in which treatment with the CCB nitrendipine resulted  in significant reduction in stroke and overall CVD events.   Calcium antagonists are quite useful because of their strong antihypertensive effects.  Often, combining 2 drugs at a lower dose may be preferable to using a single drug at a  high dose, because of the potential for adverse effects with the higher dose. Beta-  blockers may not be as effective as other first-line agents in patients aged 60 years  and older, especially for stroke prevention, and should probably be used when other   indications are present, such as heart failure, previous myocardial infarction, and  angina.   Elderly patients should also be encouraged to lose weight if necessary, be more  physically active, reduce their salt intake, and avoid excessive alcohol intake.   According to the ACCF/AHA consensus, lifestyle modifications may be all that is  necessary to treat milder forms of hypertension in elderly patients. However, drug  treatment for elderly patients with hypertension is generally recommended and should  be started at the lowest dose possible, with gradual increases depending on response.   Hypertension, especially stage 2 hypertension, can affect the retina, choroid, and optic  nerve, as well as increase intraocular pressure (IOP). In hypertensive retinopathy, the  most common finding is generalized or focal narrowing of the retinal arterioles;  occlusion or leakage of the retinal vessels may occur with acute or advanced  hypertension. Hypertensive choroidopathy most commonly manifests in young patients  with acute elevated blood pressure (BP), such as that which occurs in eclampsia or  pheochromocytoma.   Treatment of ocular hypertension varies. Depending on the severity of the ocular  hypertension, management may include observation or initiation of antihypertensive  therapy. In general, pharmacologic treatment is initiated in patients who have an  increased risk of developing glaucoma.   Blood pressure control may result in regression of signs of hypertensive retinopathy,  but spontaneous resolution may also be possible. Among the issues that still need to  be clarified are the following:   Whether antihypertensive agents with potential direct beneficial microvascular effects  (eg, ACE inhibitors) would reduce the damage of retinopathy beyond the reduction  caused by lowered blood pressure   Whether the specific reduction of hypertensive retinopathy also leads to reduction in  cardiovascular disease morbidity and mortality   Whether established risk-reducing interventions in targeted persons with hypertensive  retinopathy would lead to additional advantages, as compared to the use of strategies  without regard to retinal findings   In the presence of hypertensive optic neuropathy, a rapid reduction of BP may pose a  risk of worsening ischemic damage to the optic nerve. The optic nerve demonstrates  autoregulation, so there is an adjustment in perfusion based on BP. A precipitous  reduction in BP will reduce perfusion to the optic nerve and central nervous system as  a result of their autoregulatory changes, resulting in infarction of the optic nerve head  and, potentially, acute ischemic neurologic lesions of the CNS.   The goals of therapy for renovascular hypertension (RVHT are maintenance of normal  blood pressure (BP) and prevention of end-stage renal disease (ESRD   It is important to note that the presence of renal artery stenosis or fibromuscular  dysplasias are not always associated with renovascular hypertension.   ACE inhibitors are effective in patients with unilateral renal artery stenosis; however,  ACE inhibitors need to be avoided in patients with bilateral renal artery stenosis or  stenosis of a solitary kidney. A diuretic can be combined with an ACE inhibitor.   Because of their glomerular vasodilatory effect, calcium antagonists are effective in  renal artery stenosis and do not compromise renal function.   For most patients with RVHT, with the exception of persons with fibromuscular  dysplasia, it is unclear whether revascularization will be beneficial. Fibromuscular  dysplasia responds well to angioplasty. The causes of renovascular hypertension  include atherosclerosis, fibromuscular dysplasia, coarctation of the aorta, embolic renal  artery occlusion, aneurysm of the renal artery, and diffuse arteritis. Additionally, causes  of diffuse bilateral renal ischemia (eg, accelerated hypertension, vasculitis, hepatitis B,  and IV drug abuse) may also lead to hypertension.   Causes of resistant hypertension include improper BP measurement, volume overload,  drug-induced or other causes, and associated conditions such as obesity or excessive  alcohol intake.   Improper BP measurement may result in falsely high readings, such as when the   wrong-sized cuff is used , when patients have heavily calcified or arteriosclerotic  brachial arteries, or in cases of white-coat hypertension (observed in 20-30% of  patients).   Inadequate treatment is common in cases of resistant hypertension ; in several  published series, this has been described as the most common cause of resistant  hypertension. Patients may not be on an effective drug or drug dose, or concomitant  volume expansion may occur as a side effect of the drug.   Noncompliance with medical therapy or dietary modifications (eg, salt restriction) may  play a role in causing resistant hypertension. Address noncompliance with extensive  patient education, simplification of the drug regimen, use of fixed-dose combinations,  and use of drugs with the fewest adverse effects.   Limited data suggest better compliance with ACE inhibitors and ARBs than with some  of the other antihypertensive medications.   Extracellular volume expansion may contribute to the inability to lower systemic BP.  The volume expansion may occur because of renal insufficiency or because of sodium  retention due to treatment with vasodilators, a high-salt diet, or insufficient dosing of a  diuretic. This condition can be treated with more aggressive diuretic therapy until  clinical signs of extracellular volume depletion (eg, orthostatic hypotension) develop.   The JNC 7 recommends a thiazide-type diuretic for the majority of hypertensive  patients but notes that patients with a decreased GFR or who are in heart failure often  require therapy with a loop diuretic.   Resistant hypertension may be encountered in patients who are ingesting vasoactive  substances despite taking antihypertensive drugs regularly. Salt and alcohol are  common examples; others include cocaine, amphetamines, anabolic steroids, oral  contraceptives, cyclosporine, antidepressants, and nonsteroidal anti-inflammatory  drugs.   Whenever confronted with resistant hypertension, try to exclude any secondary causes  of hypertension. A reevaluation of the patient’s history, physical examination, and  laboratory results may provide clues to secondary hypertension (eg, renal artery  stenosis, primary hyperaldosteronism, obstructive sleep apnea). Primary  hyperaldosteronism is estimated to have a prevalence of 20% in this population.   Pseudohypertension in an overestimation of intra-arterial pressure by cuff blood  pressure (BP) measurement. This may be observed in elderly individuals who have  thickened, calcified arteries, as the BP has relatively more difficulty compressing such  arteries; much higher cuff pressure may be required to occlude a thickened brachial  artery. The diastolic BP may also be overestimated.   Consider pseudohypertension in situations in which no organ damage occurs despite  marked hypertension, when patients develop hypotensive symptoms on medications,  and when calcification of the brachial artery is observed on radiologic examination.  Direct measurement of intra-arterial pressure may be required in this setting.   Hypokalemia (an unprovoked or an exaggerated hypokalemic response to a thiazide)  and metabolic alkalosis are important clues to the presence of primary  hyperaldosteronism. However, these are relatively late manifestations; in a large  subset of patients, the serum potassium concentration and bicarbonate are within the  reference range, and additional screening testing is needed in patients with high index  of suspicion for primary hyperaldosteronism.   Measurement of the ratio of plasma aldosterone to renin activity ratio is the best initial  screening test for primary hyperaldosteronism. A ratio of over 20-30 suggests that  primary hyperaldosteronism may be present. Some labs require a minimum plasma  aldosterone level of 12 ng/dL.   The diagnosis of primary hyperaldosteronism can be confirmed by the determination of  the aldosterone excretion rate in a 24-hour urine following IV or oral salt loading (ie,  urinary aldosterone excretion rate greater than 12-14 pg/24 hours, with urine sodium at    least 200 mEq/24 hours). Saline suppression testing can also be used to confirm the  diagnosis.   The appropriate therapy depends on the cause of excessive aldosterone production. A  CT scan with dynamic protocol may help localize an adrenal mass, indicating adrenal  adenoma, which may be a nonsecreting incidentaloma or a hypersecreting adenoma.   If the results of the CT scan are inconclusive, adrenal venous sampling for aldosterone  and cortisol levels should be performed.   Medical therapy is indicated in patients with adrenal hyperplasia, patients with  adenoma who are poor surgical risks, and patients with bilateral adenomas. These  patients are best treated with sustained salt and water depletion. Hydrochlorothiazide  or furosemide in combination with either spironolactone or amiloride corrects  hypokalemia and normalizes the blood pressure. Some patients may require the  addition of a vasodilator or a beta-blocker for better control of hypertension.   Adrenal adenomas may be resected via a laparoscopic procedure. Surgical resection  often leads to the control of blood pressure and the reversal of biochemical  abnormalities. These patients may develop hypoaldosteronism during the  postoperative follow-up period and require supplementation with fludrocortisone.   A diet rich in fruits and vegetables and low-fat meat, fish, and dairy products   Many therapeutic agents can be used for the pharmacologic management of  hypertension. The general recommendation established by JNC-7 is to initiate a  thiazide-type diuretic initially for stage 1 hypertensives without compelling indications  for other therapies.   Drugs such as angiotensin converting enzyme (ACE) inhibitors, calcium channel  blockers (CCBs), angiotensin receptor blockers (ARBs), beta-blockers, and diuretics  are all considered acceptable alternative therapies in patients with hypertension.   The available antihypertensive agents are generally equally effective in lowering blood  pressure however; there may be interpatient variability that can affect the way a patient  will respond to one treatment over another.    Thiazide diuretics are used as monotherapy, or they can be administered adjunctively  with other antihypertensive agents. Thiazide diuretics inhibit reabsorption of sodium   and chloride mostly in the distal tubules. Long-term use of these drugs may result in  hyponatremia.   They also increase potassium and bicarbonate excretion and decrease calcium  excretion and uric acid retention. Thiazides do not affect normal blood pressure.   Keep in mind that all available loop and thiazide diuretic agents, except ethacrynic  acid, possess a sulfonamide group, which has important clinical relevance to those  individuals with allergies to sulfonamide agents.   Hydrochlorothiazide is approved for the management of hypertension, alone or in  combination with other antihypertensive agents. Unlike potassium-sparing combination  diuretic products, hydrochlorothiazide may be used in patients who cannot risk the  development of hyperkalemia, including patients taking ACE inhibitors.   Hydrochlorothiazide is available as oral tablets or capsules in doses ranging from 12.5-  50 mg. The usual dose is 12.5 mg given alone or in combination with other  antihypertensives, with a maximum dose of 50 mg daily. Doses greater than 50 mg are  associated with hypokalemia.   Chlorthalidone is indicated for the management of hypertension either alone or in  combination with other antihypertensives. The initial dosage is 25 mg as a single daily  dose. Dosage can be titrated to 50 mg if the clinical response is not adequate. If  additional control is required, increase the dosage to 1 00 mg once daily, or a second  antihypertensive drug may be added. Doses greater than 100 mg daily usually do not  increase effectiveness. Increases in serum uric acid and hypokalemia are dose-related  over the 25-1 00 mg/day range.   Metolazone is approved for the treatment of hypertension either alone (uncommon) or  in combination with other antihypertensives. The initial dosage for hypertension is 2.5  to 5 mg given once daily. Metolazone does not decrease glomerular filtration rate or  the renal plasma flow and may be a more effective option for patients with impaired  renal function.   Indapamide is chemically not a thiazide, although its structure and function are very  similar. The drug enhances the excretion of sodium, chloride, and water by inhibiting  the transport of sodium ions across the renal tubule.   The hypovolemic action of indapamide is believed to be responsible for the drug's  beneficial cardiovascular effects. The half-life of indapamide is approximately 14 hours,  so the drug can be taken just once daily. Adverse effects tend to be somewhat milder  than with thiazides.   The potassium-sparing diuretics interfere with sodium reabsorption at the distal tubules  (primarily in the collecting duct region of the nephron), decreasing potassium secretion.  Potassium-sparing diuretics have a weak diuretic and antihypertensive effect when  used alone.   Triamterene is used alone or with other medications (often a kaliuretic diuretic such as  hydrochlorothiazide) to treat edema and high blood pressure. Because triamterene  increases potassium levels, caution is required when combining triamterene with ACE  inhibitors, angiotensin receptor blockers, aliskiren, and other drugs that increase  potassium levels. Potassium level should be monitored at start of treatment, dose  change, and during illness that affects renal function. The recommended dose is 100  mg twice daily (maximum dose is 300 mg/d).   Amiloride is a potassium-conserving (antikaliuretic) drug that, compared with thiazide  diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity. It is  approved as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic  agents for hypertension or congestive heart failure. It is unrelated chemically to other  known antikaliuretic or diuretic agents. Amiloride has little additive diuretic or  antihypertensive effect when added to a thiazide diuretic. Amiloride can be given at a  dose of 5-10 mg daily in 1-2 divided doses for hypertension. Amiloride has a black box  warning for hyperkalemia, which, if not corrected, is potentially fatal. This incidence is  greater in patients with renal impairment or diabetes mellitus and in the elderly.   Loop diuretics act on the ascending limb of the loop of Henle, inhibiting the  reabsorption of sodium and chloride. The loop diuretics are highly protein-bound and  therefore enter the urine primarily by tubular secretion in the proximal tubule, rather  than by glomerular filtration.   Loop diuretics are commonly used to control volume retention. Generally, thiazide  diuretics are recommended for most patients with a diagnosis of hypertension;  however, loop diuretics are more commonly prescribed for patients with decreased  glomerular filtration rate or heart failure. Loop diuretics do not reduce blood pressure  as effectively as thiazide diuretics when they are used as monotherapy, especially if  they are dosed once daily.   Keep in mind that all available loop and thiazide diuretic agents, except ethacrynic  acid, possess a sulfonamide group, which has important clinical relevance to those  individuals with allergies to sulfonamide agents.   Furosemide is approved for the treatment of hypertension alone (uncommon) or in  combination with other antihypertensive agents. Hypertensive patients who cannot be  adequately controlled with thiazides will probably also not be adequately controlled  with furosemide alone. The initial dosing recommendations for hypertension are  usually 80 mg (divided into 40 mg twice a day). If clinical response is not sufficient,  additional antihypertensives may be added. Patients should be monitored carefully  because furosemide is a potent diuretic. If given in excessive amounts, it can cause  profound diuresis with water and electrolyte depletion. Furosemide is available as an  oral tablet and injection solution.   Torsemide can be used as monotherapy or in combination with other antihypertensive  agents. The initial dose is 5 mg once daily. The dose can be titrated to 10 mg once  daily. If adequate response is not seen, an additional antihypertensive agent may be  needed. Torsemide is available as an oral tablet and injection solution.   Bumetanide is FDA approved for the treatment of edema. It is also used off-label for  the treatment of hypertension. The usual dosage range for bumetanide for  hypertension is 0.5-2 mg/day given once or twice a day.   Angiotensin converting enzyme (ACE) inhibitors are the treatment of choice in patients  with hypertension, chronic kidney disease, and proteinuria. ACE inhibitors reduce  morbidity and mortality rates in patients with heart failure, patients with recent  myocardial infarctions, and patients with proteinuric renal disease. ACE inhibitors  appear to act primarily through suppression of the renin-angiotensin-aldosterone  system. ACE inhibitors prevent the conversion of angiotensin I to angiotensin II and  block the major pathway of bradykinin degradation by inhibiting ACE. Accumulation of  bradykinin has been proposed as an etiologic mechanism for the side effects of cough  and angioedema. ACE inhibitors can cause injury or even death to a developing fetus.  In pregnant patients, ACE inhibitors should be discontinued as soon as possible.   It is important to note that the blood-pressure-lowering effects of ACE inhibitors and  thiazides are approximately additive, and there is also the potential for hyperkalemia  when ACE inhibitors are coadministered with potassium supplements or potassium-  sparing diuretics. In addition, a study by Harel et al found an increased risk for  hyperkalemia when aliskiren, a direct renin inhibitor, and ACE inhibitors or angiotensin  receptor blockers were used together. Careful monitoring of serum potassium levels is  warranted when these agents are used in combination. Furthermore, in patients with  hypertension plus type 2 diabetes and renal impairment who are at high risk of  cardiovascular and renal events, there is an increased risk of nonfatal stroke, renal  complications, hypokalemia, and hypotension when aliskiren is added to ACE inhibitor  or ARB therapy.   Fosinopril may be used alone or in combination with other antihypertensive agents.  Initial dose is 5 mg daily up to a maximum of 40 mg daily. May be divided into twice  daily dosing. Unlike most ACE inhibitors that are primarily excreted by the kidneys,  fosinopril is eliminated by both renal and hepatic pathways, making it a safer choice in  patients with renal failure and heart failure patients with impaired kidney function.   Captopril is indicated for the treatment of hypertension. It can be used alone or in  combination with other antihypertensive drugs, such as diuretics or beta-adrenergic-  blocking agents. The initial dose is 25 mg given 2 to 3 times daily. If reduction of blood  pressure is not achieved after 1 or 2 weeks, the dose can be titrated to 50 mg 2 or 3  times daily. If further blood reduction is required after addition of a diuretic, the dose of  captopril may be increased to 100 mg 2 or 3 times daily and then, if necessary, to 150  mg 2 or 3 times daily (while continuing the diuretic).   Ramipril is indicated for the treatment of hypertension alone or in combination with  thiazide diuretics. The initial dosing recommendation for ramipril is 2.5 mg daily for  patients who are not receiving a diuretic. Doses can range from 2.5-20 mg/day given  once or twice a day.   Enalapril is effective alone or in combination with other antihypertensive agents,  especially thiazide-type diuretics. The initial dose of enalapril is 5 mg daily. Dosage  can range from 10-40 mg/day administered as a single dose or in 2 divided doses.   Lisinopril may be used as monotherapy or concomitantly with other classes of  antihypertensive agents. The initial dose of lisinopril is 10 mg daily. The dosage can  range from 20-40 mg/day as a single daily dose. Doses up to 80 mg/day have been  used; however, they do not show a greater effect.   Quinapril may be used alone or in combination with thiazide diuretics. The initial dose  is 10 to 20 mg daily for patients not on diuretics. If blood pressure is not controlled with  quinapril monotherapy, adding a diuretic should be considered.   Generally, ACE inhibitors should remain the initial treatment of choice for hypertension.  Angiotensin II receptor antagonists or angiotensin receptor blockers (ARBs) are used  for patients who are unable to tolerate ACE inhibitors. ARBs competitively block  binding of angiotensin-ll to angiotensin type I (AT^ receptors, thereby reducing effects  of angiotensin ll-induced vasoconstriction, sodium retention, and aldosterone release;   the breakdown of bradykinin should not be inhibited. If monotherapy with an ARB is not  sufficient, adding a diuretic should be considered.   Losartan may be used alone or in combination with other antihypertensive agents,  including diuretics. The initial dose is 50 mg daily; however, in patients on diuretic  therapy, the initial dose is 25 mg daily. A low-dose diuretic (eg, hydrochlorothiazide)  may be added if blood pressure is not controlled. Losartan can be titrated up to 100 mg  daily.   Valsartan is approved for the treatment of hypertension in adults and in children 6-16  years of age. It may be used alone or in combination with other antihypertensive  agents. The initial dose is 80 or 160 mg once daily when used as monotherapy in  patients who are not volume depleted. The valsartan dose may be increased  (maximum 320 mg/day), or a diuretic may be added if additional blood pressure  reduction is required. The addition of a diuretic has a greater effect than dose  increases above 80 mg.   Beta-blockers are generally not recommended as first-line agents for the treatment of  hypertension; however, they are suitable alternatives when a compelling cardiac  indication (eg, heart failure, myocardial infarction, diabetes) is present. Selective beta-  blockers specifically block beta-1 receptors alone, although they can be nonselective  at higher doses.   Caution should be used in administering these agents in the setting of asthma or  severe chronic obstructive pulmonary disease (COPD), regardless of beta-selectivity  profile. In addition, exacerbations of angina and, in some cases, myocardial infarction  have been reported following abrupt discontinuance of beta-blocker therapy. The  doses should be gradually reduced over at least a few weeks.   Atenolol is approved for the management of hypertension used alone or concomitantly  with other antihypertensive agents, particularly with a thiazide-type diuretic. The initial  dose is 50 mg daily, alone or added to diuretic therapy. If adequate clinical effect is not  seen, the dose can be titrated to 100 mg daily. Other studies suggest that atenolol  lacks specific potential for stroke reduction.   Metoprolol is approved for the management of hypertension alone or concomitantly  with other antihypertensive agents. The initial dose for metoprolol immediate release is  1 00 mg daily in single or divided doses, with or without a diuretic (maximum 450  mg/day). Metoprolol extended-release formulation can be started at a dose of 25-100  mg daily in a single dose, with or without a diuretic (maximum 400 mg/day).   Propranolol is approved for the management of hypertension alone or concomitantly  with other antihypertensive agents. The initial dose is 40 mg given twice daily, alone or  added to diuretic therapy. Dose can be titrated based on a patient's clinical response.  The maintenance dose can range from 120-240 mg/day (maximum 640 mg/day).  Exacerbations of angina and, in some cases, myocardial infarction, following abrupt  discontinuance of propranolol therapy have been reported. The propranolol dose  should be gradually reduced over at least a few weeks.   Bisoprolol is approved for the management of hypertension alone or in combination  with other antihypertensive agents. This agent is a more specific beta-1 blocker than  other beta-blockers. The initial dose is 5 mg once daily (reduce to 2.5 mg for patients  with bronchospastic disease). The dosage can be titrated to 1 0 mg/day and then to 20  mg/day if necessary.   Timolol is indicated for the treatment of hypertension. It is used alone or in combination  with other antihypertensive agents, especially thiazide-type diuretics. The initial dose is  1 0 mg given twice daily. The total daily dose can be titrated to a maximum of 30 mg  administered in divided doses. Avoid abrupt cessation of therapy, because of the risk  of exacerbation of ischemic heart disease.   Beta-blockers, such as labetalol and carvedilol, have peripheral vasodilatory effects  that act via antagonism of the alpha-1 receptor in addition to beta-receptors.   Labetalol is indicated for the management of hypertension. Labetalol tablets may be  used alone or in combination with other antihypertensive agents, especially thiazide  and loop diuretics. The initial dose is 100 mg given twice daily. The dose may be  titrated after 2-3 days in increments of 100 mg twice a day every 2-3 days (maximum  2400 mg/day).   Labetalol's actions at alpha-1 and beta-receptors lead to vasodilation and decreased  total peripheral resistance, which results in decreased blood pressure without a  substantial decrease in resting heart rate, cardiac output, or stroke volume.   Carvedilol is approved for the management of essential hypertension. It can be used  as monotherapy or in combination with other antihypertensive agents, especially  thiazide-type diuretics. The initial dose is 6.25 mg given twice daily. The dose can be  titrated at intervals of 7-14 days to 12.5 mg twice daily, then to 25 mg twice daily as  needed (maximum 50 mg/day).   Similar to labetalol, carvedilol antagonizes both alpha-1 and beta-receptors. Carvedilol  lowers standing blood pressure more than supine blood pressure; orthostatic  hypotension may occur.   Agents such as acebutolol and pindolol possess intrinsic sympathomimetic activity  (ISA). These agents can be used alone or in combination with other antihypertensive  agents, particularly with a thiazide-type diuretic.   Vasodilators relax blood vessels to improve blood flow, thus decreasing blood  pressure.   Oral hydralazine is indicated for essential hypertension, alone or as an adjunct. Initial  dose is 1 0 mg given 4 times daily for the first 2 to 4 days, then 25 mg 4 times a day for  1 week. Hydralazine IV or IM is indicated for severe essential hypertension when the  drug cannot be given orally or when there is an urgent need to lower BP.   Hydralazine may lower blood pressure by exerting a peripheral, vasodilating effect  through a direct relaxation of vascular smooth muscle. Caution should be used when  hydralazine is administered in patients with concomitant coronary artery disease.   Minoxidil is indicated in severe hypertension that is symptomatic or associated with  end-organ damage and is not manageable with maximum therapeutic doses of a  diuretic plus 2 other antihypertensives. The initial dose is 5 mg/day as a single dose  and can be titrated to 10, 20, and then 40 mg in single or divided doses as needed  (maximum 100 mg/day). Minoxidil reduces elevated systolic and diastolic blood  pressure by decreasing peripheral vascular resistance. The blood pressure response  to minoxidil is dose-related and proportional to the extent of hypertension. Concomitant  therapy with an antiadrenergic agent and loop diuretic is generally required.   Calcium channel blockers (CCBs) can be divided into dihydropyridines and  nondihydropyridines. Dihydropyridines bind to L-type calcium channels in the vascular  smooth muscle, which results in vasodilatation and a decrease in blood pressure. They  are effective as monotherapy in black patients and elderly patients. Some examples of  dihydropyridines include amlodipine, nifedipine, clevidipine, and felodipine. Non-  dihydropyridines such as verapamil and diltiazem bind to L-type calcium channels in  the sinoatrial and atrioventricular node, as well as exerting effects in the myocardium  and vasculature. These agents may constitute a more effective class of medication for  black patients.   Nifedipine extended-release is indicated for the treatment of hypertension alone or in  combination with other antihypertensive agents. The usual dose for nifedipine is 30-60  mg once daily (maximum 90 mg/day); when used for hypertension, nifedipine can be  administered to a maximum of 120 mg/day.   Amlodipine is a dihydropyridine CCB that has antianginal and antihypertensive effects.  Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth  muscle to cause a reduction in peripheral vascular resistance and reduction in blood  pressure.   Diltiazem is a nondihydropyridine CCB that produces its antihypertensive effect  primarily by relaxation of vascular smooth muscle and the resultant decrease in  peripheral vascular resistance. The magnitude of blood pressure reduction is related to  the degree of hypertension.   Verapamil is a nondihydropyridine that produces its antihypertensive effect by a  combination of vascular and cardiac effects. It acts as a vasodilator with selectivity for  the arterial portion of the peripheral vasculature. As a result, the systemic vascular  resistance is reduced, usually without orthostatic hypotension or reflex tachycardia.   Aldosterone antagonists compete with aldosterone receptor sites, reducing blood  pressure and sodium reabsorption.   Spironolactone is usually used in combination with other drugs for patients who cannot  be treated adequately with other agents or for whom other agents are considered  inappropriate. The initial dose ranges from 50-100 mg daily in single or divided doses.  Spironolactone can cause hyperkalemia; therefore, potassium supplementation should  not be given concurrently. Other adverse effects include gynecomastia and impotence,  which often mitigates the use of spironolactone in younger men.   Centrally acting alpha2-agonists stimulate presynaptic alpha2-adrenergic receptors in  the brain stem, which reduces sympathetic nervous activity.   Methyldopa stimulates central alpha-adrenergic receptors by a false transmitter,  exerting a direct effect on peripheral sympathetic nerves. Decreases in blood pressure  are greatest when the patient is standing but are also significant when the patient is   supine. Postural hypotension has been reported in patients receiving methyldopa.  Methyldopa is not associated with a rebound effect, as with clonidine.   Clonidine stimulates alpha2-adrenoreceptors in the brain stem, activating an inhibitory  neuron, which in turn results in reduced sympathetic outflow. These effects result in a  decrease in peripheral resistance, renal vascular resistance, blood pressure, and heart  rate. Clonidine can be used alone or in combination with other antihypertensives.  Clonidine is associated with a rebound effect, especially at higher doses or with more  severe hypertension.   Renin inhibitors act within the renin-angiotensin system (RAS), a hormone system  important in the regulation of blood pressure, electrolyte homeostasis, and vascular  growth. Renin inhibitors have an additive effect when used with diuretics. Avoid the  use of these agents in pregnancy.   Aliskiren decreases plasma renin activity and inhibits conversion of angiotensinogen to  angiotensin I (as a result, also decreasing angiotensin II) and thereby disrupts the  renin-angiotensin-aldosterone system feedback loop. It is indicated for hypertension as  monotherapy or in combination with other antihypertensive drugs. This agent remains  under investigation.   Alpha-blockers are generally not recommended as initial monotherapy. They  selectively block postsynaptic alpha! -adrenergic receptors. They dilate arterioles and  veins, thus lowering blood pressure. These drugs can be combined with any of the  other antihypertensives in other drug classes. Common side effects seen in this drug  class include dizziness, headache, and drowsiness, in addition to orthostatic and first-  dose hypotension.   Prazosin is a competitive antagonist at postsynaptic alphal -receptors. Prazosin  causes peripheral vasodilation by selective, competitive inhibition of vascular  postsynaptic alphal -adrenergic receptors, thus reducing peripheral vascular resistance  and blood pressure.   Terazosin causes peripheral vasodilation by selective, competitive inhibition of  vascular postsynaptic alphal -adrenergic receptors, thereby reducing peripheral  vascular resistance and blood pressure. Terazosin reduces blood pressure in both the  supine and the standing positions, with more dramatic effects on diastolic blood  pressure.   Doxazosin is a selective alphal -adrenergic antagonist. It inhibits postsynaptic alpha-  adrenergic receptors, resulting in vasodilation of veins and arterioles and a decrease in  total peripheral resistance and blood pressure. The antihypertensive effect of  doxazosin mesylate results from a decrease in systemic vascular resistance.   Reserpine is a peripherally acting adrenergic agent. It is indicated for mild  hypertension and can be used as adjunctive therapy with other antihypertensive  agents in more severe forms of hypertension.   The result of reserpine's effects on biogenic amines is sympathetic dysfunction, with a  subsequent decrease in peripheral vascular resistance and a lowering of blood  pressure often associated with bradycardia. This agent is also associated with  depression.   Drug combinations using agents that act by different mechanisms have an additive  effect. Most clinicians recommend initiating therapy with a single agent and advancing  to the low-dose combination therapy. Some patients will require multiple medications  to achieve their blood pressure targets and will benefit from drug combinations. Drug  combination therapy may also help to improve patient compliance.   Metoprolol/hydrochlorothiazide is a combination of metoprolol, a beta-blocker, and  hydrochlorothiazide, a thiazide diuretic. Metoprolol is a betal -selective blocker at low  doses; at higher doses, it also inhibits beta2-adrenoreceptors. Hydrochlorothiazide  inhibits sodium reabsorption in distal renal tubules, resulting in increased excretion of  water, sodium, potassium, and hydrogen ions.   Valsartan/hydrochlorothiazide is a combination of valsartan, an angiotensin receptor  blocker, and hydrochlorothiazide, a diuretic. Valsartan is a prodrug that produces direct  antagonism of angiotensin II receptors. It displaces angiotensin II from ATI receptor  and may lower blood pressure by antagonizing ATI -induced vasoconstriction,  aldosterone release, catecholamine release, arginine vasopressin release, water  intake, and hypertrophic responses. Hydrochlorothiazide inhibits sodium and chloride  reabsorption in distal renal tubules, resulting in increased excretion of water, sodium,  potassium, and hydrogen ions.   Valsartan/amlodipine/hydrochlorothiazide is a combination of amlodipine, a  dihydropyridine calcium channel blocker, valsartan, an angiotensin receptor blocker,   and hydrochlorothiazide, a diuretic. Amlodipine exhibits antianginal and  antihypertensive effects by inhibiting the influx of calcium in cardiac and smooth  muscle cells of the coronary and peripheral vasculature, resulting in dilatation of  coronary and peripheral arteries. Valsartan is a prodrug that produces direct  antagonism of angiotensin II receptors. It displaces angiotensin II from the ATI  receptor and may lower blood pressure by antagonizing ATI -induced vasoconstriction,  aldosterone release, catecholamine release, arginine vasopressin release, water  intake, and hypertrophic responses. Hydrochlorothiazide inhibits sodium and chloride  reabsorption in distal renal tubules, resulting in increased excretion of water, sodium,  potassium, and hydrogen ions.   Enalapril/hydrochlorothiazide is a combination of enalapril, an ACE inhibitor, and  hydrochlorothiazide, a diuretic. Hydrochlorothiazide inhibits sodium reabsorption in  distal renal tubules, resulting in increased excretion of water, sodium, potassium, and  hydrogen ions. Enalapril prevents the conversion of angiotensin I to angiotensin II, a  potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in  aldosterone secretion. It helps control blood pressure and proteinuria.   Malignant hypertension and accelerated hypertension are both hypertensive  emergencies, with similar outcomes and therapies. Malignant hypertension may or  may not be associated with clinical conditions present in hypertensive urgency. A  patient with malignant hypertension always has retinal papilledema (as seen in the  image below), as well as flame-shaped hemorrhages and exudates. Other clinical  features of malignant hypertension may include encephalopathy, confusion, left  ventricular failure, intravascular coagulation, and impaired renal function, with  hematuria and weight loss.   The pathologic hallmark of malignant hypertension is fibrinoid necrosis of the  arterioles, which occurs systemically, but specifically in the kidneys. These patients  develop fatal complications if untreated, and more than 90% will not survive beyond 1-  2 years..   Papilledema. Note the swelling of the optic disc, with blurred margins   Approximately 3-45% of adult patients have at least one incident of increased BP  during their stay in the emergency department (ED). The fundamental principle in  determining the necessary ED care of the hypertensive patient is the presence or  absence of end-organ dysfunction. Many patients present to the ED with elevated BPs;  however, only a small proportion of patients will require emergency treatment. An  important point to remember in the management of the patient with any degree of BP  elevation is to "treat the patient and not the number."   The primary goal of the emergency physician is to determine which patients with acute  hypertension are exhibiting symptoms of end-organ damage and require immediate  intravenous (IV) parenteral therapy. In contrast, patients presenting with acutely  elevated BP (systolic BP [SBP] >200 mm Hg or diastolic BP [DBP] >120 mm Hg)  without symptoms that are sustained throughout the ED stay and whose BP stays  significantly elevated to this level on discharge should have initiation of medical  therapy and close follow-up in the outpatient setting.   Thus, optimal control of hypertensive situations balances the benefits of immediate  decreases in BP against the risk of a significant decrease in target organ perfusion.   The emergency physician must be capable of appropriately evaluating patients with an  elevated BP, correctly classifying the hypertension, determining the aggressiveness  and timing of therapeutic interventions, and making disposition decisions.   Acutely lowering BP in the ED for clinical situations other than those listed below is  controversial and generally should be avoided.   An important point to remember in the management of the patient with any degree of  BP elevation is to "treat the patient and not the number." In patients presenting with  hypertensive emergencies, antihypertensive drug therapy has been shown to be  effective in acutely decreasing blood pressure.   Sodium nitroprusside is a commonly used medication. It is a short-acting agent, and  the BP response can be titrated from minute to minute. However, patients must have  constant monitoring in an intensive care unit. The potential exists for thiocyanate  and cyanide toxicity with prolonged use or if the patient has renal or hepatic failure .   Diazoxide may also be used in hypertensive crisis. Small boluses of 100 mg are  administered every 5 minutes, as indicated. Diazoxide is not preferred with  concomitant congestive heart failure or low cardiac output.   Labetalol, an alpha- and beta-blocking agent, has proven to be quite beneficial in the  treatment of patients with hypertensive emergencies. Labetalol is particularly preferred  in patients with acute dissection. Boluses of 10-20 mg may be administered, or the  drug may be infused at 1 mg/min until the desired BP is obtained. Once an adequate  BP level is obtained, oral hypertensive therapy should be initiated, and patients are  gradually weaned from parenteral agents.   As the BP approaches its goal, increase the clevidipine dose by less than double, and  lengthen the time between dose adjustments to every 5-10 minutes. An approximately  1-2 mg/h increase produces an additional 2-4 mm Hg decrease in SBP. Typically, the   therapeutic response is achieved with 4-6 mg/h, although severe hypertension may  require higher doses. Most patients have received maximum doses of 16 mg/h or less;  experience is limited with short-term dosing as high as 32 mg/h. Because of lipid load  restrictions, do not exceed 1 000 ml_ or an average of 21 mg/h within a 24-hour period;  experience is limited with use beyond 72 hours.   Rapid BP reduction is indicated in neurologic emergencies, such as hypertensive  encephalopathy, acute ischemic stroke, acute intracerebral hemorrhage,   In hypertensive encephalopathy, the treatment guidelines are to reduce the MAP 25%  over 8 hours. Labetalol, nicardipine, esmolol are the preferred medications; however,  nitroprusside and hydralazine should be avoided.   For acute ischemic stroke, the preferred medications are labetalol and nicardipine.  Withhold antihypertensive medications unless the SBP is >220 mm Hg or the DBP is  >120 mm Hg, UNLESS the patient is receiving IV or intra-arterial (IA) fibrinolysis; then,  the goal BP is an SBP of < 1 85 mm Hg and DBP <110 mm Hg. After treatment with  fibrinolysis, the SBP should be maintained < 180 mm Hg and the DBP at < 105 mm Hg  for 24 hours.   For acute intracerebral hemorrhage, the preferred medications are labetalol,  nicardipine, and esmolol; avoid nitroprusside and hydralazine. The treatment is based  on clinical/radiographic evidence of increased intracranial pressure (ICP). If there are  signs of increased ICP, maintain the MAP just below 130 mm Hg (or SBP < 180 mm  Hg) for the first 24 hours after onset. In patients without increased ICP, maintain the  MAP <110 mm Hg (or SBP < 1 60 mm Hg) for the first 24 hours after symptom onset.   Recent evidence shows that in cases of acute intracerebral hemorrhage, early  intensive BP control is well tolerated and can reduce hematoma growth in patients  treated within 6 hours after the onset of intracerebral hemorrhage. The target systolic  pressure for these studies was 140 mm Hg and routine IV medications were used. The  target SBP was maintained over 7 days.   In subarachnoid hemorrhage, nicardipine, labetalol, and esmolol are also the preferred  agents; again, nitroprusside and hydralazine should be avoided. Maintain the SBP <  160 mm Hg until the aneurysm is treated or cerebral vasospasm occurs. Although oral  nimodipine is used to prevent delayed ischemic neurologic deficits, it is NOT indicated  for treating acute hypertension.   Rapid BP reduction is also indicated in cardiovascular emergencies, such as aortic  dissection, acute coronary syndrome, and acute heart failure.   In aortic dissection, the preferred medications are labetalol, nicardipine, nitroprusside  (with beta-blocker), esmolol, and morphine sulfate. However, avoid beta-blockers if  there is aortic valvular regurgitation or suspected cardiac tamponade. Maintain the  SBP at < 1 10 mm Hg, unless signs of end-organ hypoperfusion are present. The   preferred treatment includes a combination of narcotic analgesics (morphine sulfate),  beta blockers (labetalol, esmolol), and vasodilators (nicardipine, nitroprusside).   Calcium channel blockers (verapamil, diltiazem) are an alternative to beta blockers.   For acute coronary syndrome, beta blockers and nitroglycerin are the preferred drugs.  Treatment is indicated if the SBP is >1 60 mm Hg and/or the DBP is >1 00 mm Hg.  Reduce the BP by 20-30% of baseline. Note that thrombolytics are contraindicated if  the BP is >185/100 mm Hg.   In acute heart failure, the preferred medications are IV or sublingual nitroglycerin and  IV enalaprilat. Treat with vasodilators (in addition to diuretics) for a SBP >140 mm Hg.   Diazepam, phentolamine, and nitroglycerin/nitroprusside are the preferred drugs.  However, avoid beta-adrenergic antagonists before administering phentolamine.   Hypertension and tachycardia from cocaine toxicity rarely require specific treatment.  Alpha-adrenergic antagonists (phentolamine) are the preferred agents for cocaine-  associated acute coronary syndromes. Pheochromocytoma treatment guidelines are  similar to that of cocaine toxicity. Only after alpha blockade can beta blockers be  added for BP control.   The preferred medications are hydralazine, labetalol, and nifedipine. Avoid -  Nitroprusside, angiotensin-converting enzyme inhibitors, esmolol. In women with  eclampsia or preeclampsia, the SBP should be < 160 mm Hg and the DBP should be <  110 mm Hg in the antepartum and intrapartum periods. If the platelet count is less than  100,000 cells mm 3 , the BP should be maintained below 150/100 mm Hg. Patients with  eclampsia or preeclampsia should also be treated with IV magnesium sulfate to avoid  seizures.   Nitroprusside, nitroglycerin, and esmolol are preferred. Target the perioperative BP to  within 20% of the patient's baseline pressure, except if there is the potential for life-  threatening arterial bleeding. Perioperative beta blockers are the first choice in patients  undergoing vascular procedures or in patients with an intermediate or high risk of  cardiac complications.    18.100 THE INFLUENCE OF COMORBIDITY ON THE CHOICE OF ANTIHYPERTENSIVE  DRUG THERAPY    Left ventricular  dysfunction, post-  myocardial infarction or  established coronary heart  disease Type 1 diabetic  nephropathy Secondary  stroke prevention 4   ACE inhibitor intolerance  Type 2 diabetic  nephropathy Hypertension  with left ventricular  hypertrophy Heart failure in  ACE-intolerant patients,  after myocardial infarction   Left ventricular  dysfunction after  myocardial infarction  Intolerance of other  antihypertensrve drugs  Proteinuric renal  disease, chronic renal   Insidious increased thirst (ie, polydipsia) and urination (ie, polyuria) are the most  common early symptoms of diabetic ketoacidosis (DKA). Malaise, generalized  weakness, and fatigability also can present as symptoms of DKA.   Nausea and vomiting usually occur and may be associated with diffuse abdominal  pain, decreased appetite, and anorexia. A history of rapid weight loss is a symptom in  patients who are newly diagnosed with type 1 diabetes.   Patients may present with a history of failure to comply with insulin therapy or missed  insulin injections due to vomiting or psychological reasons. Decreased perspiration is  another possible symptom of DKA.   Altered consciousness in the form of mild disorientation or confusion can occur.  Although frank coma is uncommon, it may occur when the condition is neglected or if  dehydration or acidosis is severe.   Effects on vital signs that are related to DKA may include the following:   The physical examination should also include detection of the signs of possible  intercurrent illnesses such as myocardial infarction, urinary tract infection, pneumonia,  and perinephric abscess. Search for signs of infection is mandatory in all cases.   Noticing that the body temperature may be within the reference range or low, even in  the presence of intercurrent infection, is particularly important.   Symptoms of hyperglycemia associated with diabetic ketoacidosis may include  thirst, polyuria, polydipsia, and nocturia.   Signs of acidosis may include shallow rapid breathing or air hunger (Kussmaul or  sighing respiration), abdominal tenderness, and disturbance of consciousness.   Although these signs are not usual in all cases of diabetic ketoacidosis (DKA), their  presence signifies a severe form of DKA.   Signs of dehydration include a weak and rapid pulse, dry tongue and skin,  hypotension, and increased capillary refill time.   Complications associated with DKA include sepsis and diffuse ischemic processes.  Other associated complications include the following:   • CVT - Myocardial infarction - DVT - Acute gastric dilatation   • Heavy use of concentrated carbohydrate beverages (eg, sodas, sports drinks)   Managing diabetic ketoacidosis (DKA) in an intensive care unit during the first 24-48  hours always is advisable. When treating patients with DKA, the following points must  be considered and closely monitored:   It is essential to maintain extreme vigilance for any concomitant process, such as  infection, cerebrovascular accident, myocardial infarction, sepsis, or deep venous  thrombosis .   It is important to pay close attention to the correction of fluid and electrolyte loss during  the first hour of treatment. This always should be followed by gradual correction of  hyperglycemia and acidosis. Correction of fluid loss makes the clinical picture clearer  and may be sufficient to correct acidosis. The presence of even mild signs of  dehydration indicates that at least 3 L of fluid has already been lost.   Patients usually are not discharged from the hospital unless they have been able to  switch back to their daily insulin regimen without a recurrence of ketosis. When the  condition is stable, pH exceeds 7.3, and bicarbonate is greater than 18 mEq/L, the  patient is allowed to eat a meal preceded by a subcutaneous (SC) dose of regular  insulin.   Insulin infusion can be discontinued 30 minutes later. If the patient is still nauseated  and cannot eat, dextrose infusion should be continued and regular or ultra-short-acting  insulin should be administered SC every 4 hours, according to blood glucose level,  while trying to maintain blood glucose values at 100-180 mg/dL.   Fluid resuscitation is a critical part of treating patients with DKA. Intravenous solutions  replace extravascular and intravascular fluids and electrolyte losses. They also dilute  both the glucose level and the levels of circulating counterregulatory hormones. Insulin  is needed to help switch from a catabolic state to an anabolic state, with uptake of  glucose in tissues and the reduction of gluconeogenesis as well as free fatty acid and  ketone production.   Initial correction of fluid loss is either by isotonic sodium chloride solution or by lactated  Ringer solution. The recommended schedule for restoring fluids is as follows:   Administer 1 L every 4 hours, depending on the degree of dehydration and central  venous pressure readings   When the patient becomes euvolemic, the physician may switch to half the isotonic  sodium chloride solution, particularly if hypernatremia exists. Isotonic saline should be  administered at a rate appropriate to maintain adequate blood pressure and pulse,  urinary output, and mental status.   If a patient is severely dehydrated and significant fluid resuscitation is needed,  switching to a balanced electrolyte solution (eg, Normosol-R, in which some of the  chloride in isotonic saline is replaced with acetate) may help to avoid the development   When blood sugar decreases to less than 180 mg/dl_, isotonic sodium chloride solution  is replaced with 5-10% dextrose with half isotonic sodium chloride solution.   After initial stabilization with isotonic saline, switch to half-normal saline at 200-1000  mL/h (half-normal saline matches losses due to osmotic diuresis).   Insulin should be started about an hour after IV fluid replacement is started to allow for  checking potassium levels and because insulin may be more dangerous and less  effective before some fluid replacement has been obtained.   Although the incidence of life-threatening hypokalemia due to aggressive insulin  administration is very low, there is little to no advantage in starting insulin prior to  rehydration and evaluation of serum potassium levels. Initial bolus of insulin does not  change overall management of DKA.   Pediatric protocols to minimize the risk of cerebral edema by reducing the rate of fluid  repletion vary. The International Society for Pediatric and Adolescent Diabetes  (ISPAD) Clinical Practice Consensus Guidelines suggest initial fluid repletion in  pediatric patients should be 10-20 mL/kg of normal saline (0.9%) solution during the  first 1-2 hours without initial bolus, and then, after 1-2 hours, insulin should be started  to avoid pediatric cerebral edema.   ISPAD provides detailed fluid administration guidelines. Total volume over the first 4  hours should not exceed 40-50 mL/kg. Fluid administration is as vital in children as in  adults.   When insulin treatment is started in patients with DKA, several points must be  considered. A low-dose insulin regimen has the advantage of not inducing the severe  hypoglycemia or hypokalemia that may be observed with a high-dose insulin regimen.   Only short-acting insulin is used for correction of hyperglycemia. Subcutaneous  absorption of insulin is reduced in DKA because of dehydration; therefore, using  intravenous or intramuscular routes is traditionally preferable.   SC use of the fast-acting insulin analog (lispro) has been tried in pediatric DKA (0.15  U/kg q2h). The results were shown to be comparable to IV insulin, but ketosis took 6  additional hours to resolve. Such technically simplified methods may be cost-effective  and may preclude admissions to intensive care units in patients with mild cases.   The initial insulin dose is a continuous IV insulin infusion using an infusion pump, if  available, at a rate of 0.1 U/kg/h. A mix of 24 units of regular insulin in 60 mL of  isotonic sodium chloride solution usually is infused at a rate of 15 mL/h (6 U/h) until the  blood glucose level drops to less than 180 mg/dL; the rate of infusion then decreases  to 5-7.5 mL/h (2-3 U/h) until the ketoacidotic state abates.   Larger volumes of an insulin and isotonic sodium chloride solution mixture can be  used, providing that the infusion dose of insulin is similar. Larger volumes may be  easier in the absence of an IV infusion pump (eg, 60 U of insulin in 500 mL of isotonic  sodium chloride solution at a rate of 50 mL/h).   The optimal rate of glucose decline is 100 mg/dL/h. Do not allow the blood glucose  level to fall below 200 mg/dL during the first 4-5 hours of treatment. Hypoglycemia may  develop rapidly with correction of ketoacidosis.   Allowing blood glucose to drop to hypoglycemic levels is a common mistake that  usually results in a rebound ketosis derived by counter-regulatory hormones. Rebound  ketosis necessitates a longer duration of treatment. The other hazard is that rapid  correction of hyperglycemia and hyperosmolarity may shift water rapidly to the  hyperosmolar intracellular space and may induce cerebral edema.   Although DKA was a common problem in patients with diabetes who were treated with  continuous subcutaneous insulin infusion through insulin infusion pumps, the incidence  of DKA was reduced with the introduction of pumps equipped with sensitive electronic  alarm systems that alert users when the infusion catheter is blocked.   If the potassium level is greater than 6 mEq/L, do not administer potassium  supplement. If the potassium level is 4.5-6 mEq/L, administer 10 mEq/h of potassium  chloride. If the potassium level is 3-4.5 mEq/L, administer 20 mEq/h of potassium  chloride.   Monitor serum potassium levels hourly, and the infusion must be stopped if the  potassium level is greater than 5 mEq/L. The monitoring of serum potassium must  continue even after potassium infusion is stopped in the case of (expected) recurrence  of hypokalemia.   In severe hypokalemia, not starting insulin therapy is advisable unless potassium  replacement is under way; this is to avert potentially serious cardiac dysrhythmia that  may result from hypokalemia.   Potassium replacement should be started with initial fluid replacement if potassium  levels are normal or low. Add 20-40 mEq/L of potassium chloride to each liter of fluid  once the potassium level is less than 5.5 mEq/L. Potassium can be given as follows:  two thirds as KCI, one third as KP04.   Sodium bicarbonate only is infused if decompensated acidosis starts to threaten the  patient's life, especially when associated with either sepsis or lactic acidosis. If sodium  bicarbonate is indicated, 100-150 mL of 1.4% concentration is infused initially. This  may be repeated every half hour if necessary. Rapid and early correction of acidosis  with sodium bicarbonate may worsen hypokalemia and cause paradoxical cellular  acidosis.   Bicarbonate typically is not replaced as acidosis will improve with the above treatments  alone. Administration of bicarbonate has been correlated with cerebral edema in  children.   In the presence of infection, the administration of proper antibiotics is guided by the  results of culture and sensitivity studies. Starting empiric antibiotics on suspicion of  infection until culture results are available may be advisable.   Cerebral edema is a serious, major complication that may evolve at any time during  treatment of DKA and primarily affects children. It is the leading cause of DKA mortality  in children.   Be extremely cautious to avoid cerebral edema during initiation of therapy.   Deterioration of the level of consciousness in spite of improved metabolic state usually  indicates the occurrence of cerebral edema. MRI usually is used to confirm the  diagnosis.   Cerebral edema that occurs at initiation of therapy tends to worsen during the course  of treatment. Mannitol or hypertonic saline should be available if cerebral edema is  suspected.   According to Wolfsdorf et al, 0.5-1 g/kg intravenous mannitol may be given over the  course of 20 minutes and repeated if no response is seen in 30-120 minutes. Also, if   no response to mannitol occurs, hypertonic saline (3%) may be given at 5-10 mg/kg  over the course of 30 minutes.   Clinical cerebral edema is rare and carries the highest mortality rate. Although  mannitol (0.25-1 g/kg IV) and dexamethasone (2-4 mg q6-12h) frequently are used in  this situation, no specific medication has proven useful in such instances.   Muir et al have identified diagnostic criteria for cerebral edema that include abnormal  response to pain, decorticate and decerebrate posturing, cranial nerve palsies,   abnormal central nervous system respiratory patterns, fluctuating level of  consciousness, sustained heart rate deceleration, incontinence, and more nonspecific   criteria such as vomiting, headache, lethargy, and elevated diastolic blood pressure   Cerebral edema begins with mental status changes and is believed to be due partially  to idiogenic osmoles, which have stabilized brain cells from shrinking while the diabetic  ketoacidosis was developing.   Cardiac dysrhythmia may occur secondary to severe hypokalemia and/or acidosis  either initially or as a result of therapy in patients with DKA. Usually, correction of the  cause is sufficient to treat cardiac dysrhythmia, but if it persists, consultation with a  cardiologist is mandatory. Performing cardiac monitoring on patients with DKA during  correction of electrolytes always is advisable.   Pulmonary edema may occur for the same reasons as cerebral edema in patients with  diabetic ketoacidosis. Be cautious of possible overcorrection of fluid loss, though it  occurs only rarely.   Although initial aggressive fluid replacement is necessary in all patients, particular care  must be taken in those with comorbidities such as renal failure or congestive heart  failure . Diuretics and oxygen therapy often suffice for the management of pulmonary  edema.   Nonspecific myocardial injury may occur in severe DKA, which is associated with  minute elevations of myocardial biomarkers (troponin T and CK-MB) and initial ECG  changes compatible with myocardial infarction (Ml).   Acidosis and very high levels of free fatty acids could cause membrane instability and  biomarker leakage. Coronary arteriography usually is normal, and patients tend to  recover fully without further evidence of ischemic heart disease. Regardless of the  pathogenesis, the presence of minute biomarker elevations and ECG changes do not  necessarily signify Ml in DKA.   In patients with diabetic ketoacidosis, hypoglycemia may result from inadequate  monitoring of glucose levels during insulin therapy.   Hypokalemia is a complication that is precipitated by failing to rapidly address the total  body potassium deficit brought out by rehydration and insulin treatment, which not only  reduces acidosis but directly facilitates potassium reentry into the cell.   An endocrinologist also may be consulted to assist with management after the patient  has been stabilized adequately.   Any mental status change in pediatric patients suggests the possibility of cerebral  edema, and when this occurs, a pediatric endocrinologist or pediatric intensivist should  be consulted as soon as possible. Psychological counseling of young children and  adolescents usually is helpful.   Frequent blood glucose monitoring at home makes DKA less likely, as this allows them  to promptly search for possible reasons for unexpectedly high blood glucose values  before the condition progresses to DKA.   In a study of 127 patients with DKA who were admitted to a pediatric intensive care  unit, Bradley and Tobias concluded that multiple weaknesses existed in the prehospital  care of these patients.^These included lack of appropriate laboratory evaluation,  excessive insulin dosing (both bolus doses and infusion rates), lack of fluid  resuscitation, use of inappropriate fluids for resuscitation, and the use of sodium  bicarbonate.   Patients with urinary calculi may report pain, infection, or hematuria . The passage of stones into  the ureter with subsequent acute obstruction, proximal urinary tract dilation, and spasm is associated  with classic renal colic.   Acute onset of severe flank pain radiating to the groin, gross or microscopic hematuria,   nausea, and vomiting not associated with an acute abdomen are symptoms that most likely   indicate renal colic caused by an acute ureteral or renal pelvic obstruction from a calculus. Renal  colic pain rarely, if ever, occurs without obstruction.   Patients with large renal stones known as staghorn calculi (see the image below) are often relatively  asymptomatic. The term "staghorn" refers to the presence of a branched kidney stone occupying the  renal pelvis and at least one calyceal system. Such calculi usually manifest as infection and  hematuria rather than as acute pain.   Complete staghorn calculus that fills the collecting system of the kidney (no intravenous  contrast material in this patient). Although many staghorn calculi are struvite (related to  infection with urease-splitting bacteria), the density of this stone suggests that it may be  metabolic in origin and is likely composed of calcium oxalate. Percutaneous  nephrostolithotomy or perhaps even open surgical nephrolithotomy is required to  remove this stone.    . Location and quality of pain are related to position of the stone within the urinary tract.  Severity of pain is related to the degree of obstruction, presence of ureteral spasm,  and presence of any associated infection.   Stones obstructing the ureteropelvic j unction may present with mild-to-severe deep  flank pain without radiation to the groin, due to distention of the renal capsule. Stones  impacted within the ureter cause abrupt, severe, colicky pain in the flank and ipsilateral  lower abdomen with radiation to the testicles or the vulvar area. Intense nausea, with  or without vomiting, usually is present.   Pain from upper ureteral stones tends to radiate to the flank and lumbar areas. On the  right side, this can be confused with cholecystitis or cholelithiasis; on the left, the  differential diagnoses include acute pancreatitis, peptic ulcer disease, and gastritis.   Midureteral calculi cause pain that radiates anteriorly and caudally. This  midureteral pain in particular can easily mimic appendicitis on the right or acute  diverticulitis on the left.    Distal ureteral stones cause pain that tends to radiate into the groin or testicle in the  male or labia majora in the female because the pain is referred from the ilioinguinal or  genitofemoral nerves.   Stones lodged at the ureterovesical junction also may cause irritative voiding  symptoms, such as urinary frequency and dysuria. If a stone is lodged in the intramural  ureter , symptoms may appear similar to cystitis or urethritis. These symptoms include   suprapubic pain, urinary frequency, urgency, dysuria, stranguria, pain at the tip of the  penis, and sometimes various bowel symptoms, such as diarrhea and tenesmus.  These symptoms can be confused with pelvic inflammatory disease, ovarian cyst  rupture, or torsion and menstrual pain in women.   Calculi that have entered the bladder are usually asymptomatic and are passed  relatively easily during urination.   The first phase is the acute or onset phase. The typical attack starts early in the  morning or at night , waking the patient from sleep. When it begins during the day, it  tends to start slowly and insidiously. The pain is usually steady, increasingly severe,  and continuous, sometimes punctuated by intermittent paroxysms of even more  excruciating pain.   The second phase is the constant phase. Once the pain reaches maximum intensity,  it tends to remain constant until it is either treated or allowed to diminish  spontaneously. The period of sustained maximal pain is called the constant phase of  the renal colic attack. This phase usually lasts 1-4 hours but can persist longer than 12  hours in some cases. Most patients arrive in the ED during this phase of the attack.   The third phase is the abatement or relief phase. During this final phase, the pain  diminishes fairly quickly, and patients finally feel relief.   Nausea and vomiting occur in at least 50% of patients with acute renal colic. Nausea is  caused by the common innervation pathway of the renal pelvis, stomach, and   intestines through the celiac axis and vagal nerve afferents. . Nonsteroidal anti-  inflammatory drugs (NSAIDs) can often cause gastric irritation and Gl upset.   The presence of a renal or ureteral calculus is not a guarantee that the patient does  not have some other, unrelated medical problem causing the Gl symptoms.   In some cases, a stone may pass before the definitive imaging procedure has been  completed. In these cases, residual inflammation and edema still may cause some  transient or diminishing obstruction and pain even without any stone being positively  identified.   The classic presentation for a patient with acute renal colic is the sudden onset  of severe pain originating in the flank and radiating interiorly and anteriorly. The  pain is usually, but not always, associated with microscopic hematuria, nausea,  and vomiting.   Dramatic costovertebral angle tenderness is common; this pain can move to the  upper or lower abdominal quadrant as a ureteral stone migrates distally.   Abdominal examination usually is unremarkable. Bowel sounds may be hypoactive, a  reflection of mild ileus, which is not uncommon in patients with severe, acute pain.   Peritoneal signs are usually absent — an important consideration in distinguishing renal  colic from other sources of flank or abdominal pain. Testicles may be painful but  should not be very tender and should appear normal.   Unlike patients with an acute abdomen, who usually try to lie absolutely still, patients  with renal colic tend to move constantly, seeking a more comfortable position.   (However, patients with pyonephrosis also tend to remain motionless.) The classic  patient with renal colic is writhing in pain, pacing about, and unable to lie still, in  contrast to a patient with peritoneal irritation, who remains motionless to minimize  discomfort.   Lack of hematuria alone does not exclude the diagnosis of acute renal colic.  Tachycardia and hypertension are relatively common in these cases , even in patients  with no prior personal history of abnormal cardiac or blood pressure problems.   Fever is not part of the presentation of uncomplicated nephrolithiasis. The presence of  pyuria, fever, leukocytosis, or bacteriuria suggests the possibility of a urinary infection  and the potential for an infected obstructed renal unit or pyonephrosis. Such a   condition is potentially life threatening and should be treated as a surgical emergency.   In patients older than 60 years presenting with severe abdominal pain and with  no prior history of renal stones, look carefully for physical signs of abdominal  aortic aneurysm (AAA)   Abscess formation - Serious infection of the kidney that diminishes renal  function   Infected hydronephrosis is the most deadly complication because the presence  of infection adjacent to the highly vascular renal parenchyma places the patient  at risk for rapidly progressive sepsis and death.   A ureteral stone associated with obstruction and upper UTI is a true urologic  emergency.   Complete ureteral obstruction may occur in patients with tightly impacted stones. This  is best diagnosed via IVP and is not discernible on noncontrast CT scan. Patients with  2 healthy kidneys can tolerate several days of complete unilateral ureteral obstruction  without long-term effects on the obstructed kidney. If a patient with complete  obstruction is well hydrated and pain and vomiting are well controlled, the patient can   be discharged from the ED with urologic follow-up within 1-2 days.   Acute renal colic with resultant flank pain is a common and sometimes complex clinical  problem. Whereas noncontrast abdominopelvic computed tomography (CT) scans  have become the imaging modality of choice, in some situations, renal  ultrasonography or a contrast study such as intravenous pyelography (IVP) may be  preferred.   A kidneys-ureters-bladder (KUB) radiograph, in addition to the renal colic CT scan,  facilitates the review and follow-up of stone patients. Alternatively, the “CT scout” (a  digital reconstruction from the CT that has an appearance similar to a KUB) is almost  as sensitive as a KUB and is a good substitute at the initial assessment if the stone  seen on the CT scan is visible on the CT scout   Initial stones in elderly people and in children are relatively uncommon; however,  consider kidney stones whenever acute back or flank pain is encountered, regardless  of patient age. When stones occur in persons in these uncommon age groups, a  metabolic workup consisting of a 24-hour urine collection and appropriate serum  laboratory testing is recommended.   laboratory tests in all patients with an acute stone episode :   Urinary sediment/dipstick test for demonstration of blood cells, with a test for  bacteriuria (nitrite) and urine culture in case of a positive reaction  Serum creatinine level, as a measure of renal function   In addition, patients with fever warrant a complete blood cell count. Patients with  vomiting should have serum or plasma sodium and potassium levels measured.   Microscopic examination of the urine for evidence of hematuria and infection is a  critical part of the evaluation of a patient thought to have renal colic. Gross or   microscopic hematuria is only present in approximately 85% of patients with urinary  calculi. The lack of microscopic hematuria does not eliminate renal colic as a potential  diagnosis.   Attention should also be paid to the presence or absence of leukocytes, crystals, and  bacteria and to the urinary pH. In general, if the number of white blood cells (WBCs) in  the urine is greater than 1 0 cells per high-power field or greater than the number of  RBCs, suspect a UTI. Pyuria (>5 WBCs/hpf on a centrifuged specimen) in a patient  with ureterolithiasis should prompt a careful search for signs of infected   Urinary crystals of calcium oxalate, uric acid, or cystine may occasionally be found  upon urinalysis. When present, these crystals are very good clues to the underlying  type and nature of any obstructing calculus.   Determining urinary pH also helps. A urine pH greater than 7 suggests presence  of urea-splitting organisms, such as Proteus, Pseudomonas, or Klebsiella species,  and struvite stones. A urine pH less than 5 suggests uric acid stones.   Whereas mild leukocytosis often accompanies a renal colic attack, a high index of  suspicion for a possible renal or systemic infection should accompany any serum WBC  count of 15,000/pL or higher in a patient presenting with an apparent acute kidney  stone attack, even if afebrile. A depressed RBC count suggests a chronic disease  state or severe ongoing hematuria.   A high serum uric acid level may indicate gouty diathesis or hyperuricosuria . while  hypercalcemia suggests either renal-leak hypercalciuria (with secondary  hyperparathyroidism) or primary hyperparathyroidism. If the serum calcium level is  elevated, serum PTH levels should be obtained.   To identify urinary risk factors, a 24-hour urine profile, including appropriate serum  tests of renal function, uric acid, and calcium, is needed.   The most common findings on 24-hour urine studies include  hypercalciuria, hyperoxaluria , hyperuricosuria , hypocitraturia , and low urinary volume.  Other factors, such as high urinary sodium and low urinary magnesium concentrations,  may also play a role. A finding of hypercalcemia should prompt follow-up with an intact  parathyroid hormone study to evaluate for primary and secondary  hyperparathyroidism.   Another clinical approach to hypercalciuria, when hyperparathyroidism has been  excluded with appropriate blood tests, is avoidance of excessive dietary calcium (usual  recommendation, 600-800 mg/d), modest limitation of oxalate intake, and thiazide  therapy..   Hyperoxaluria may be primary (a rare genetic disease), enteric. Oxalate restriction  and vitamin B-6 supplementation are somewhat helpful in patients with idiopathic   hyperoxaluria . Enteric hyperoxaluria is the type that is most amenable to treatment;  dietary calcium supplementation often produces dramatic results.   Calcium citrate is the recommended supplement because it tends to further  reduce stone formation. Calcium carbonate supplementation is less expensive but  lacks citrate’s added benefit. Calcium works as an oxalate binder, reducing oxalate  absorption from the Gl tract. It should be administered with meals, especially those  that contain high-oxalate foods. The supplement should not contain added vitamin D,  because this increases calcium absorption, leaving less calcium in the Gl tract to bind  to oxalate. The optimal 24-hour urine oxalate level is 20 mg/d or less.   Hyperuricosuria predisposes to the formation of calcium-containing calculi because  sodium urate can produce malabsorption of macromolecular inhibitors or can serve as  a nidus for the heterogeneous growth of calcium oxalate crystals. Gouty diathesis, a  condition of increased stone production associated with high serum uric acid levels, is  also possible.   Therapy involves potassium citrate supplementation, allopurinol, or both. In general,  patients with pure uric acid stones and hyperuricemia are treated with allopurinol, and   The optimal 24-hour urine uric acid level is 600 mq/d or less.   Excess sodium excretion can contribute to hypercalciuria by a phenomenon known as  solute drag. Elevated urinary sodium levels are almost always associated with dietary  indiscretions. Decreasing the oral sodium intake can decrease calcium excretion,  thereby decreasing calcium saturation.   An elevated phosphorus level is useful as a marker for a subtype of absorptive  hypercalciuria known as renal phosphate leak (absorptive hypercalciuria type III).   Renal phosphate leak is identified by high urinary phosphate levels, low serum  phosphate levels, high serum 1,25 vitamin D-3 (calcitriol) levels, and hypercalciuria.  This type of hypercalciuria is uncommon and does not respond well to standard  therapies.   Magnesium and, especially, citrate are important chemical inhibitors of stone  formation. Hypocitraturia is one of the most common metabolic defects that predispose  to stone formation, and some authorities have recommended citrate therapy as  primary or adjunctive therapy to almost all patients who have formed recurrent   Lemon juice is an excellent source of citrate; alternatively, large quantities of lemonade   can be ingested, and this, of course, has the added benefit of providing increased fluid   Magnesium is a more recently recognized inhibitor of stone formation, and the clinical   role of magnesium replacement therapy is less well defined than that of citrate.   Some stones, such as those composed of uric acid or cystine, are pH-dependent,  meaning that they can form only in acidic conditions. Calcium phosphate and struvite  only form when the urine pH is alkaline. Although the other parameters in the 24-hour  urine usually identify patients at risk of forming these stones, pH studies can be  important in monitoring these patients, in optimizing therapy with citrate  supplementation, and in identifying occult stone disease in some patients.   Plain abdominal radiography (also referred to as flat plate or KUB radiography) is  useful for assessing total stone burden, as well as the size, shape, composition, and  location of urinary calculi in some patients. Calcium-containing stones (approximately  85% of all upper urinary tract calculi) are radiopaque, but pure uric acid, indinavir-  induced, and cystine calculi are relatively radiolucent on plain radiography.   When used with other imaging studies, such as a renal ultrasonography or,  particularly, CT scanning, the plain film helps provide a better understanding of the  characteristics of urinary stones revealed with these other imaging studies. This may  also be helpful in planning surgical therapy.   If a stone is not visible on a flat plate radiograph, it could be a radiolucent uric acid   stone that can be dissolved with alkalinizing medication . Such a stone is more likely if  the urine pH indicates very acidic urine. In practice, any patient with symptoms of  acute renal colic who demonstrates a urine pH lower than 6.0 should be  considered at risk for a possible uric acid stone. If a stone of adequate size is  visible on a CT scan but not visible on KUB, then uric stones should be considered.   The flat plate radiograph is inexpensive, quick, and usually helpful even if no specific  stone is observed. It is extremely useful in following the progress of previously  documented radiopaque calculi and checking the position of any indwelling double-J  stents   Renal ultrasonography by itself is frequently adequate to determine the presence of a  renal stone. The study is mainly used alone in pregnancy or in combination with plain  abdominal radiography to determine hydronephrosis or ureteral dilation associated  with an abnormal radiographic density believed to be a urinary tract calculus. A stone  easily identified with renal ultrasonography but not visible on the plain  radiograph may be a uric acid or cystine stone, which is potentially dissolvable   In addition, ultrasonography is not reliable for small stones (ie, those smaller than 5  mm) and does not help in the evaluation of kidney function.   Renal ultrasonography works best in the setting of relatively large stones within the  renal pelvis or kidney and sometimes at the UPJ. Whether the stones are radiolucent   or radio-opaque does not matter because an ultrasound image is based strictly on  density, not on calcium content. Ultrasonography is a good way to monitor known  stones after medical or surgical therapy if the stones are large enough to be detected  by this modality and are in a suitable position.   The combination of renal ultrasonography with KUB radiography has been proposed  as a reasonable initial evaluation protocol when a CT scan cannot be performed or is  unavailable. When combined with KUB radiography, ultrasonography can quickly and  inexpensively provide substantial information about the urinary tract without the risk of  contrast nephrotoxicity or hypersensitivity. IVP can then be limited to those patients for  whom additional information is required for a diagnosis or for whom the etiology of the  pain remains unclear.   Future studies may utilize 2-dimensional ultrasonography in combination with color  Doppler analysis of the ureteral jets to enhance sensitivity of ultrasonography in  patients with ureteral colic.   Before the advent of helical CT, IVP, also known as intravenous urography (IVU), was  the test of choice in diagnosing ureterolithiasis. IVP is widely available and fairly  inexpensive but less sensitive than noncontrast helical CT. CT scanning with delayed  contrast series and thin slices has reduced the need for IVP in the evaluation of  problematic ureteral stones.   The main advantage of IVP is the clear outline of the entire urinary system that it  provides, making visualization of even mild hydronephrosis relatively easy. IVP is  helpful in identifying the specific problematic stone among numerous pelvic  calcifications, as well as in demonstrating renal function and establishing that the other  kidney is functional. These determinations are particularly helpful if the degree of  hydronephrosis is mild and the noncontrast CT scan findings are not definitive. IVP can  also show nonopaque stones as filling defects.   Disadvantages include the need for IV contrast material, which may provoke an  allergic response or renal failure, and the need for multiple delayed films, which can  take up to 6 hours. Obtaining the IVP is also a relative labor-intensive process. In  addition, IVP may fail to reveal alternative pathology if a stone is not discovered,  delaying the final diagnosis. False-negative results usually occur with stones located at  the ureterovesical junction.   KUB radiographs are obtained immediately before contrast administration and at 1 , 5,  10, and 15 minutes afterwards or until visible contrast material fills both ureters (see  the image below). Prone films are sometimes obtained to enhance visualization of the  ureters. When the bladder is full of contrast and the distal ureters contain sufficient  contrast for visualization, the patient is asked to void; then a postvoid film is taken.  Sometimes, oblique views are needed when bone or bowel contents overlie the area of  interest.    Intravenous pyelogram (IVP) demonstrating dilation of the right renal  collecting system and right ureter consistent with right ureterovesical stone.    Look for direct visualization of stone within the ureter, unilateral ureteral dilation,  delayed appearance of the nephrogram phase, lack of normal peristalsis pattern of the  ureter, or perirenal contrast extravasation. Degree of obstruction is graded based on  delay in appearance of the nephrogram.   Typically, an IVP positive for a ureteral stone is one that shows a delayed nephrogram  effect and columnization. The ureter is peristaltic, so the entire ureter is not usually  visualized on a single film except when an obstruction is present, such as from a  stone. Even without observing any specific stone, the presence of a nephrogram effect  in one kidney with normal function of the opposite kidney is highly suggestive, but not  diagnostic, of ureteral obstruction.   Extravasation of contrast around the collecting system may be a sign of a ruptured  fornix, while pyelolymphatic backflow indicates that contrast has entered into the renal  lymphatic drainage system. Both are considered signs of a more severe ureteric  obstruction.   However, no published study has indicated that the clinical course, treatment outcome,  or residual renal damage is altered in any way in these patients. In fact, this  information about the radiological assessment of the relative severity of the obstruction  rarely affects clinical treatment decisions, except perhaps in persons with solitary  kidneys.    Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal  failure. A serum creatinine level of more than 2 mg/dL is a relative contraindication to the use of IV  contrast agents.   At most institutions that offer this examination, CT scanning has replaced IVP, the  historic criterion standard, for the assessment of urinary tract stone disease, especially  for acute renal colic. CT scans are readily available in most hospitals and can be  performed and read in just a few minutes. Numerous studies have demonstrated that  CT has a sensitivity of 95-100% and superior specificity and accuracy when compared  with IVP.    A renal colic study consists of a noncontrast or unenhanced CT scan of the abdomen  and pelvis, including very narrow cuts taken through the kidneys and bladder areas,  where symptomatic stones are most likely to be encountered.   Noncontrast helical CT scan of the abdomen demonstrating a stone at the right ureterovesical junction.   An abdominal flat plate or KUB radiograph is sometimes automatically included in a  renal colic study, depending on the institution and the preferences of the medical staff.   It can reveal other pathology (eg, AAAs, appendicitis , pancreatitis, cholecystis,  ovarian disorders, diverticular disease, renal carcinoma). If the patient’s true  underlying pathology is something other than a kidney stone, the CT scan is more  clinically useful than an IVP for examining the possibilities.   The density of the stone can assist in predicting stone composition and response to  shockwave lithotripsy.   It exposes the patient to a relatively high radiation dose (and thus should not be  performed on pregnant women).   The most precise imaging method for determining the anatomy of the ureter and renal pelvis and for  making a definitive diagnosis of any ureteral calculus is not IVP or renal colic CT scanning but  retrograde pyelography.   A nuclear renal scan can be used to objectively measure differential renal function, especially in a  dilated system for which the degree of obstruction is in question. This is also a reasonable study in  pregnant patients, in whom radiation exposure must be limited.   Magnetic resonance imaging (MRI) has virtually no role in the current evaluation of acute renal colic  in the typical patient. Direct detection of most stones is not possible with MRI, and MRI should not be  used for that purpose in most instances. MRIs are generally more expensive than other studies, such  as CT scans, which reveal stones much better.   Treatment of nephrolithiasis involves emergency management of renal (ureteral) colic,  including surgical interventions where indicated, and medical therapy for stone  disease.   In emergency settings where concern exists about possible renal failure, the focus of  treatment should be on correcting dehydration, treating urinary infections.   reducing risks of acute renal failure from contrast nephrotoxicity , particularly in  patients with preexisting azotemia (creatinine >2 mg/dL), diabetes, dehydration, or  multiple myeloma. Adequate intravenous (IV) hydration is essential to minimize the  nephrotoxic effects of IV contrast agents . Choosing imaging studies that do not require  IV contrast (eg, ultrasonography, plain abdominal flat plate radiographs, noncontrast  computed tomography [CT] scans) is wise, especially in patients at increased risk for  developing renal failure.   Most small stones with relatively mild hydronephrosis can be treated with observation   and acetaminophen . More serious cases with intractable pain may require drainage  with a stent or percutaneous nephrostomy. The internal ureteral stent is usually  preferred in these situations because of decreased morbidity.   A stone chemical composition analysis should be performed whenever possible, and  information should be provided to motivated patients about possible 24-hour urine  testing for long-term nephrolithiasis prophylaxis   The size of the stone is an important predictor of spontaneous passage. A stone less  than 4 mm in diameter has an 80% chance of spontaneous passage; this falls to  20% for stones larger than 8 mm in diameter. However, stone passage also  depends on the exact shape and location of the stone and the specific anatomy  of the upper urinary tract in the particular individual. For example, the presence of  a ureteropelvic junction (UPJ) obstruction or a ureteral stricture could make passing  even very small stones difficult or impossible. Most experienced emergency  department (ED) physicians and urologists have observed very large stones passing  and some very small stones that do not move.   Aggressive medical therapy has shown promise in increasing the spontaneous stone  passage rate and relieving discomfort while minimizing narcotic usage. Aggressive  treatment of any proximal urinary infection is important to avoid potentially   dangerous pyonephrosis and urosepsis. In these cases, consider percutaneous  nephrostomy drainage rather than retrograde endoscopy, especially in very ill patients.   Medical therapy for stone disease takes both short- and long-term forms. The former  includes measures to dissolve the stone (possible only with noncalcium stones)   or to facilitate stone passage, and the latter includes treatment to prevent further stone  formation. Stone prevention should be considered most strongly in patients who have  risk factors for increased stone activity, including stone formation before age 30 years,  family history of stones, multiple stones at presentation, and residual stones after  surgical treatment.   The decision to hospitalize a patient with a stone is usually made based on clinical  grounds rather than on any specific finding on a radiograph. Generally, hospitalization  for an acute renal colic attack is now officially termed an observation because most   patients recover sufficiently to go home within 24 hours. Admission rate for patients  with acute renal colic is approximately 20%.    Hospital admission is clearly necessary when any of the following is present:   Ureteral obstruction from a stone occurs in a solitary or transplanted kidney.   Ureteral obstruction from a stone occurs in the presence of a urinary tract infection  (UTI), fever, sepsis, or pyonephrosis.   Infected hydronephrosis, defined as UTI proximal to an obstructing stone, mandates  hospital admission for antibiotics and prompt drainage. Midstream urine culture and  sensitivity was a poor predictor of infected hydronephrosis in one series, being positive  in only 30% of cases. ^   The clinical presentation of infected hydronephrosis is variable. Pyuria (>5 white  blood cells [WBCs] per high-power field [hpf]) is almost always present but is  not diagnostic of proximal infection   Proteus, and Klebsiella species. In another small study of 38 patients with  hydronephrosis, 16 had infected hydronephrosis and 22 had sterile hydronephrosis.  Ultrasonography alone detected 6 of 16 cases of pyonephrosis, a sensitivity of 38%.  Using a cutoff value of 3 mg/dl_ for C-reactive protein and 100 mm/h for erythrocyte  sedimentation rate, the diagnostic accuracy of detecting infected hydronephrosis and  pyonephrosis increased to 97%.   Relative indications to consider for a possible admission include comorbid conditions  (eg, diabetes), dehydration requiring prolonged intravenous (IV) fluid therapy, renal  failure, or any immunocompromised state. Patients with complete obstruction,  perinephric urine extravasation, a solitary kidney, or pregnancy, and those with a poor  social support system, also should be considered for admission, especially if rapid  urologic follow-up is not reliably available.   Larger stones (ie, > 7 mm) that are unlikely to pass spontaneously require some type  of surgical procedure. In some cases, hospitalizing a patient with a large stone to  facilitate surgical stone intervention is reasonable. However, most patients with acute  renal colic can be treated on an ambulatory basis.   About 15-20% of patients require invasive intervention due to stone size, continued  obstruction, infection, or intractable pain. Several techniques are available to the  urologist when the stone fails to pass spontaneously, including extracorporeal shock  wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy.   Initial treatment of a renal colic patient in the ED starts with obtaining IV access to  allow fluid, analgesic, and antiemetic medications to be administered . Many of  these patients are dehydrated from poor oral intake and vomiting. Although the role of  supranormal hydration in the management of renal (ureteral) colic is controversial (see   below), patients who are dehydrated or ill need adequate restoration of circulating  volume.   After diagnosing renal (ureteral) colic, determine the presence or absence of  obstruction or infection . Obstruction in the absence of infection can be initially  managed with analgesics and with other medical measures to facilitate passage of the  stone. Infection in the absence of obstruction can be initially managed with  antimicrobial therapy. In either case, promptly refer the patient to a urologist.   If neither obstruction nor infection is present, analgesics and other medical measures  to facilitate passage of the stone (see below) can be initiated with the expectation that  the stone will likely pass from the upper urinary tract if its diameter is smaller than 5-6  mm (larger stones are more likely to require surgical measures).   If both obstruction and infection are present, emergency decompression of the upper  urinary collecting system is required (see Surgical Care). In addition, immediately  consult with a urologist for patients whose pain fails to respond to ED management.   The cornerstone of ureteral colic management is analgesia, which can be achieved  most expediently with parenteral narcotics or nonsteroidal anti-inflammatory drugs  (NSAIDs).   Parenteral narcotics are the mainstay of analgesia for patients with acute renal colic.  They work primarily on the central nervous system (CNS) to reduce the perception of  pain. They are inexpensive and quite effective. When considering a medication and  dosage range, remember that acute renal colic is probably the most painful  malady to affect humans. Adverse effects of narcotic analgesics include respiratory  depression, sedation, constipation, a potential for addiction, nausea, and vomiting.   Morphine is a potent narcotic analgesic that controls severe pain primarily through a  CNS mechanism via specific receptor site interactions.   Adverse effects of morphine include respiratory depression, drowsiness, mood  changes, nausea, vomiting, increases in the cerebrospinal fluid pressure, and cough  reflex depression. The most bothersome is respiratory depression caused by a direct  effect on the brain stem respiratory center. This effect is most severe in patients who  are elderly, debilitated, or both.   Naloxone (0.4 mg or 1 ml.) is a specific narcotic antagonist for both meperidine and  morphine sulfate that can be administered to counteract inadvertent narcotic  overdosage or unusual opioid sensitivity. Naloxone has no analgesic properties.   Of the NSAIDs, the only one approved by the US Food and Drug Administration  (FDA) for parenteral use is ketorolac. Ketorolac works at the peripheral site of  pain production rather than on the CNS. It has been proven in multiple studies to be  as effective as opioid analgesics, with fewer adverse effects. The dosage is 30-60 mg  IM or 30 mg IV initially followed by 30 mg IV or IM every 6-8 hours. A dose of 15 mg is   Some practitioners use parenteral ketorolac in the hospital but recommend either  ibuprofen or oral cyclooxygenase-2 inhibitors (eg, celecoxib or meloxicam) for pain  management in outpatients.   Chemically, ketorolac is similar to aspirin and may increase the prothrombin time when  administered with anticoagulants. Ketorolac can increase methotrexate toxicity and  phenytoin levels. It is potentiated by probenecid and should be avoided in patients with  peptic ulcer disease, renal failure, or recent gastrointestinal (Gl) bleeding.   Metoclopramide is the only antiemetic that has been specifically studied in the  treatment of renal colic. In 2 double-blinded studies, it apparently provided pain relief  equivalent to narcotic analgesics in addition to relieving nausea. Its antiemetic effect  stems from its dopaminergic receptor blockage in the CNS. It has no anxiolytic activity  and is less sedating than other centrally acting dopamine antagonists. The effect of  metoclopramide begins within 3 minutes of an IV injection, but it may not take effect for  as long as 15 minutes if administered IM.   The usual dose in adults is 10 mg IV or IM every 4-6 hours as needed.   Several studies have now demonstrated that desmopressin (DDAVP), a potent  antidiuretic that is essentially an antidiuretic hormone, can dramatically reduce the pain  of acute renal colic in many patients. It acts quickly, has no apparent adverse effects,  reduces the need for supplemental analgesic medications, and may be the only  immediate therapy necessary for some patients. It is available as a nasal spray (usual  dose of 40 meg, with 10 meg per spray) and as an IV injection (4 mcg/mL, with 1 ml_  the usual dose). Generally, only 1 dose is administered.   Although desmopressin is thought to work by reducing the intraureteral pressure, it  may also have some direct relaxing effect on the renal pelvic and ureteral musculature.   While some of the human studies lack adequate controls and further studies must be  conducted, desmopressin therapy currently appears to be a promising alternative or  adjunct to analgesic medications in patients with acute renal colic, especially in  patients in whom narcotics cannot be used or in whom the pain is unusually resistant  to standard medical treatment.   Use antibiotics if a kidney stone or ureteral obstruction has been diagnosed and the  patient has clinical evidence of a UTI. Evidence of a possible UTI includes an  abnormal finding upon microscopic urinalysis, showing pyuria of 10 WBCs/hpf (or more  WBCs than RBCs), bacteriuria, fever, or unexplained leukocytosis. Perform a urine  culture in these cases because a culture cannot be performed reliably later should the  infection prove resistant to the prescribed antibiotic.   The traditional outpatient treatment approach detailed above has recently been  improved with the application of a more aggressive treatment approach known as  active medical expulsive therapy (MET). Many randomized trials have confirmed the  efficacy of MET in reducing the pain of stone passage, increasing the frequency of  stone passage, and reducing the need for surgery.   MET should be considered in any patient with a reasonable probability of stone  passage. Given that stones smaller than 3 mm are already associated with an 85%  chance of spontaneous passage, MET is probably most useful for stones 3-1 0 mm in  size. Overall, MET is associated with a 65% greater likelihood of stone passage.   The original rationale for MET was based on the possible causes of failure to  spontaneously pass a stone, including ureteral stricture, muscle spasm, local  edema, inflammation, and infection. Various common drugs were considered that  would potentially benefit these problems, improve spontaneous stone passage, and  alleviate renal colic discomfort.   Although NSAIDs have ureteral-relaxing effects and, as such, can be considered a  form of MET, patient outcomes have been significantly improved only with the use of  more potent (off-label) medications. The initially popularized regimens for MET  included corticosteroids such as prednisone, as in the following example:   Ketorolac at 1 0 mg orally every 6 hours for 5 days  Nifedipine XL at 30 mg/d PO for 7 days  Prednisone 20 mg PO twice a day for 5 days  Trimethoprim/sulfamethoxazole DS once a day for 7 days  Acetaminophen 2 tablets 4 times a day for 7 days   An oral opioid pain medication (oxycodone-acetaminophen) as needed for  breakthrough pain   Prochlorperazine suppository as needed for control of nausea  Although corticosteroids are effective, concerns about their side effects (admittedly not  supported by randomized data) limited the acceptance of MET. More recently,  randomized studies have demonstrated great efficacy of the following individual  agents, sparing the corticosteroid component.   The calcium channel blocker nifedipine is indicated for angina, migraine headaches,  Raynaud disease, and hypertension, but it can also reduce muscle spasms in the  ureter, which helps reduce pain and facilitate stone passage. Ureteral smooth muscle  uses an active calcium pump to produce contractions, so a calcium channel blocker  such as nifedipine would be expected to relax ureteral muscle spasms.   The alpha-blockers, such as terazosin, and the alpha-1 selective blockers, such as  tamsulosin, also relax the musculature of the ureter and lower urinary tract, markedly  facilitating passage of ureteral stones. Some literature suggests that the alpha-  blockers are more effective in this setting than the calcium channel blockers, and most  practitioners currently use alpha-blockers preferentially over calcium channel blockers.   Multiple prospective randomized controlled studies in the urology literature have  demonstrated that patients treated with oral alpha-blockers have an increased rate of  spontaneous stone passage and a decreased time to stone passage. The best  studied of these is tamsulosin, 0.4 mg administered daily.   A systematic review by Singh et al found that MET using either alpha antagonists or  calcium channel blockers augmented the stone expulsion rate for moderately sized  distal ureteral stones. Adverse effects were noted in 4% of those taking alpha  antagonists and in 15.2% of those taking calcium channel blockers.   MET with calcium channel blockers and alpha-blockers also appears to improve the  results of ESWL (see Surgical Care) inasmuch as the stone fragments resulting from  treatment appear to clear the system more effectively.   • A typical regimen for this aggressive therapy is as follows:   • 1-2 oral acetaminophen tablets every 4 hours as needed for pain   MET with 30 mg nifedipine extended-release tablet once daily. 0.4 mg tamsulosin once   Limit MET to a 10- to 14-day course, as most stones that pass during this  regimen do so in that time frame. If outpatient treatment fails, promptly consult a  urologist.   IV hydration in the setting of acute renal colic is controversial. Whereas some  authorities believe that IV fluids hasten passage of the stone through the urogenital  system, others express concern that additional hydrostatic pressure exacerbates the  pain of renal colic. One small study of 43 ED patients found no difference in pain score  or rate of stone passage in patients who received 2 L of saline over 2 hours versus  those who received 20 mL of saline per hour.   IV hydration should be given to patients with clinical signs of dehydration or to those  with a borderline serum creatinine level who must undergo intravenous pyelography  (IVP).   Collecting any passed kidney stones is extremely important in the evaluation of a  patient with nephrolithiasis for stone-preventive therapy. Yet, in a busy ED, the simple  instruction to strain all the urine for stones can be easily overlooked.   In general , stones that are 4 mm in diameter or smaller will probably pass  spontaneously , and stones that are larger than 8 mm are unlikely to pass without  surgical intervention .   With MET, stones 5-8 mm in size often pass, especially if located in the distal ureter.  The larger the stone, the lower the possibility of spontaneous passage (and thus the   greater the possibility that surgery will be required), although many other factors  determine what happens with a particular stone.   The primary indications for surgical treatment include pain, infection, and  obstruction. Infection combined with urinary tract obstruction is an extremely  dangerous situation, with significant risk of urosepsis and death, and must be treated  emergency in virtually all cases. Additionally, certain occupational and health-related  reasons exist.   Specific contraindications may apply to a given treatment modality. For example, do  not perform SWL if a ureteral obstruction is distal to the calculus or in pregnancy.   For an obstructed and infected collecting system secondary to stone disease, virtually  no contraindications exist for emergency surgical relief either by ureteral stent  placement (a small tube placed endoscopically into the entire length of the ureter from  the kidney to the bladder) or by percutaneous nephrostomy (a small tube placed  through the skin of the flank directly into the kidney).   Many urologists have a preference for one technique or the other, but, in general,  patients who are acutely ill, who have significant medical comorbidities, or who harbor  stones that probably cannot be bypassed with ureteral stents undergo percutaneous  nephrostomy, while others receive ureteral stent placement.   The vast majority of symptomatic urinary tract calculi are now treated with noninvasive  or minimally invasive techniques, while open surgical excision of a stone from the  urinary tract is now limited to isolated atypical cases.   Guidelines are now available to assist the urologist in selecting surgical treatments.   The 2005 American Urological Association (AUA) staghorn calculus guidelines  recommend percutaneous nephrostolithotomv as the cornerstone of management .ln  the ureteral stone guidelines produced by a joint effort of the AUA and the European  Association of Urology, SWL and ureteroscopy are both recognized as first-line  treatments for ureteral stones   Internal ureteral stents form a coil at either end when the stiffening insertion guide wire  is removed. One coil forms in the renal pelvis and the other in the bladder.   The major drawback of stents, however, is that they are often quite uncomfortable for  patients due to direct bladder irritation, spasm, and reflux. This discomfort can be  alleviated to some extent by pain medications, anticholinergics (eg, oxybutynin,  tolterodine), alpha-blockers, and topical analgesics (eg, phenazopyridine).    In some cases, drainage of an obstructed kidney is necessary and stent placement is  inadvisable or impossible. In particular, such cases include patients with pyonephrosis  who have a UTI or urosepsis exacerbated by an obstructing calculus. In these patients,  retrograde endourological procedures like retrograde pyelography and stent placement  may exacerbate infection by pushing infected urinary material into the obstructed renal  unit. Percutaneous nephrostomy is useful in such situations.   ESWL, the least invasive of the surgical methods of stone removal, utilizes an  underwater energy wave focused on the stone to shatter it into passable fragments.   It is especially suitable for stones that are smaller than 2 cm and lodged in the   It is contraindicated in pregnancy, untreatable bleeding disorders, tightly impacted  stones, or in cases of ureteral obstruction distal to the stone. In addition, the  effectiveness is limited for very hard stones (which tend to be dense on CT scan),  cystine stones, and in very large patients.   The patient, under varying degrees of anesthesia (depending on the type of lithotriptor  used), is placed on a table or in a gantry that is then brought into contact with the  shock head. The deeper the anesthesia (general endotracheal), the better the results.   SWL is limited somewhat by the size and location of the calculus. A stone larger than  1 .5 cm in diameter or one located in the lower section of the kidney is treated less  successfully. Fragmentation still occurs, but the large volume of fragments or their  location in a dependent section of the kidney precludes complete passage.    Along with SWL, ureteroscopic manipulation of a stone (see the image below) is a  commonly applied method of stone removal. A small endoscope, which may be rigid,  semirigid, or flexible, is passed into the bladder and up the ureter to directly visualize  the stone.   Two calculi in a dependent calyx of the kidney (lower pole) visualized  through a flexible fiberoptic ureteroscope. In another location, these  calculi might have been treated with extracorporeal shockwave  lithotripsy (ESWL), but, after being counseled regarding the lower  success rate of ESWL for stones in a dependent location, the patient  elected ureteroscopy. Note that the image provided by fiberoptics,  although still acceptable, is inferior to that provided by the rod-lens  optics of the rigid ureteroscope in the previous picture.    Ureteroscopy is especially suitable for removal of stones that are 1-2 cm, lodged   in the lower calyx or below, cystine stones, and high attenuation ("hard") stones.   The typical patient has acute symptoms caused by a distal ureteral stone, usually  measuring 5-8 mm. Stones smaller than 5 mm in diameter generally are retrieved   using a stone basket, whereas tightly impacted stones or those larger than 5 mm are  manipulated proximally for SWL or are fragmented using an endoscopic direct-contact  fragmentation device.   Often, a ureteral stent must be placed after ureteroscopy in order to prevent   obstruction from ureteral spasm and edema . Since a ureteral stent is often  uncomfortable, many urologists eschew stent placement following ureteroscopy in  selected patients.   Percutaneous nephrostolithotomy allows fragmentation and removal of large calculi  from the kidney and ureter. Percutaneous nephrostolithotomy is especially useful for  stones larger than 2 cm in diameter.   In some cases, a combination of SWL and a percutaneous technique is necessary to  completely remove all stone material from a kidney. This technique, called sandwich  therapy, is reserved for staghorn or other complicated stone cases. In such cases,  experience has shown that the final procedure should be percutaneous  nephrostolithotomy.   Urinary calculi composed predominantly of calcium cannot be dissolved with current  medical therapy; however, medical therapy is important in the long-term  chemoprophylaxis of further calculus growth or formation.   Uric acid and cystine calculi can be dissolved with medical therapy. Patients with uric  acid stones who do not require urgent surgical intervention for reasons of pain,  obstruction, or infection can often have their stones dissolved with alkalization of the  urine. Sodium bicarbonate can be used as the alkalizing agent, but potassium citrate  is usually preferred because of the availability of slow-release tablets and the  avoidance of a high sodium load.   The dosage of the alkalizing agent should be adjusted to maintain the urinary pH  between 6.5 and 7.0. Urinary pH of more than 7.5 should be avoided because of the  potential deposition of calcium phosphate around the uric acid calculus, which would  make it undissolvable. Both uric acid and cystine calculi form in acidic environments.   Even very large uric acid calculi can be dissolved in patients who comply with therapy.  Roughly 1 cm per month dissolution can be achieved. Practical ability to alkalinize the  urine significantly limits the ability to dissolve cystine calculi.   Prophylactic therapy might include limitation of dietary components, addition of stone-  formation inhibitors or intestinal calcium binders, and, most importantly, augmentation   Besides advising patients to avoid excessive salt and protein intake and to increase  fluid intake, base medical therapy for long-term chemoprophylaxis of urinary calculi on  the results of a 24-hour urinalysis for chemical constituents.   Chemoprophylaxis of uric acid and cystine calculi consists primarily of long-term  alkalinization of urine. If hyperuricosuria or hyperuricemia is documented in patients  with pure uric acid stones (present in only a relative minority), allopurinol (300 mg qd)  is recommended because it reduces uric acid excretion.   Pharmaceuticals that can bind free cystine in the urine (eg, D-penicillamine, 2-alpha-  mercaptopropionyl-glycine) help reduce stone formation in cystinuria. Therapy should  also include long-term urinary alkalinization and aggressive fluid intake. Captopril has  been shown to be effective in some trials, although, again, strong data are lacking.   Routine use should be avoided but can be added in patients who have difficulty in  dissolving and preventing cystine stones.   In almost all patients in whom stones form, an increase in fluid intake and, therefore,  an increase in urine output is recommended. This is likely the single most important  aspect of stone prophylaxis. Patients with recurrent nephrolithiasis traditionally have  been instructed to drink 8 glasses of fluid daily to maintain adequate hydration  and decrease chance of urinary supersaturation with stone-forming salts. The  goal is a total urine volume in 24 hours in excess of 2 liters.   The only other general dietary guidelines are to avoid excessive salt and protein  intake. Moderation of calcium and oxalate intake is also reasonable.   Dietary calcium should not be restricted beyond normal unless specifically indicated  based on 24-hour urinalysis findings. Urinary calcium levels are normal in many  patients with calcium stones. Reducing dietary calcium in these patients may  actually worsen their stone disease, because more oxalate is absorbed from the  Gl tract in the absence of sufficient intestinal calcium to bind with it. This results  in a net increase in oxalate absorption and hyperoxaluria, which tends to increase  new kidney stone formation in patients with calcium oxalate calculi.   As a rule, dietary calcium should be restricted to 600-800 mg/d in patients with diet-  responsive hypercalciuria who form calcium stones. This is roughly equivalent to a  single high-calcium or dairy meal per day.   The most common causes of kidney stones are hypercalciuria, hyperuricosuria,  hyperoxaluria, hypocitraturia, and low urinary volume. Each of these major factors can  be measured easily with a 24-hour urine sample using one of several commercial   laboratory packages now available. Kidney stone preventive therapy consists of dietary  adjustments, nutritional supplements, medications, or combinations of these.   Strongly encourage patients who have a stone at a young age (ie, < 25 y), multiple  recurrences, a solitary functioning kidney, or a history of prior kidney stone surgery to  obtain a 24-hour urine collection for stone prevention analysis, especially if they are  motivated to comply with a long-term stone prevention program. These 24-hour urine  collection kits can be obtained from a number of commercial medical laboratories.   Patients with primary hyperoxaluria usually present with a urinary oxalate level in  excess of 100 mg/d. Early medical treatment is required to decrease the oxalate level  and to prevent deterioration of renal function.   Dietary oxalate restrictions are of no substantial benefit in this type of hyperoxaluric  disease. Several medications have been useful.   New and future treatment modalities under investigation include probiotic  supplementation, chaperones and hepatocyte cell transplantation, and recombinant  gene therapy to replace the enzyme.   Pyridoxine deficiency is known to increase urinary oxalate excretion. High-dose  pyridoxine may reduce the production of oxalate by enhancing the conversion of  glyoxylate to glycine, thereby reducing the substrate available for metabolism to  oxalate. A daily dose of 150-500 mg may be required to sufficiently reduce the oxalate  level. A normal urinary oxalate level (< 40 mg/d) can be achieved in some patients.   Supplementation with magnesium in the form of magnesium hydroxide and  magnesium oxide has been used. Magnesium can complex with oxalate in the  intestinal tract, reducing the level of available free oxalate and urinary calcium oxalate  supersaturation. It does not directly affect the increased endogenous production of  oxalate   When used in combination with pyridoxine, significant reductions in urinary oxalate  levels have been noted.   It is essential to increase urinary volume. Optimal 24-hour urinary volumes of 3-4 L/d  may be needed to ameliorate the effects of severe hyperoxaluria. Increasing urine  volume usually requires multiple nightly disruptions of sleep for extra water  consumption.   Thiazides have been shown to decrease urinary oxalate excretion somewhat, possibly   Other factors that can contribute to stone formation, such as urinary citrate and uric  acid, need to be optimized.   Small-bowel obstruction (SBO) leads to proximal dilatation of the intestine due to  accumulation of Gl secretions and swallowed air. This bowel dilatation stimulates cell  secretory activity, resulting in more fluid accumulation. This leads to increased  peristalsis above and below the obstruction, with frequent loose stools and flatus early  in its course.   Vomiting occurs if the level of obstruction is proximal. Increasing small-bowel  distention leads to increased intraluminal pressures. This can cause compression of  mucosal lymphatics, leading to bowel wall lymphedema.   With even higher intraluminal hydrostatic pressures, increased hydrostatic pressure in  the capillary beds results in massive third spacing of fluid, electrolytes, and proteins  into the intestinal lumen. The fluid loss and dehydration that ensue may be severe  and contribute to increased morbidity and mortality.   Bacteria in the gut proliferate proximal to the obstruction. Microvascular changes in the  bowel wall allow translocation to the mesenteric lymph nodes. This is associated with  an increase in the incidence of bacteremia due to Escherichia coli, but the clinical  significance is unclear.   The most common cause of small-bowel obstruction (SBO) is postsurqical adhesions   Prevention of SBO may be essentially limited to decreasing the risk of adhesion  formation by decreasing the number of intra-abdominal procedures (ie, laparotomies)  and resultant scar formation.   Another commonly identified cause of SBO is an incarcerated groin hernia. Other  etiologies include malignant tumor (20%), hernia (10%), inflammatory bowel disease  (5%), volvulus (3%), and miscellaneous causes (2%). The causes of SBO in pediatric  patients include congenital atresia, pyloric stenosis, and intussusception.   Obstruction can be characterized as either partial or complete versus simple or  strangulated. No accurate clinical picture exists to detect early strangulation of  obstruction.   Abdominal pain, often described as crampy and intermittent, is more prevalent in  simple obstruction. Often, the presentation may provide clues to the approximate  location and nature of the obstruction.   Usually, pain that occurs for a shorter duration of time and is colicky and accompanied  by bilious vomiting may be more proximal. Pain that lasts as long as several days, is  progressive in nature, and is accompanied by abdominal distention may be typical of a  more distal obstruction.   Changes in the character of the pain may indicate the development of a more serious  complication (ie, constant pain of a strangulated or ischemic bowel).   Vomiting - Associated more with proximal obstructions  Diarrhea - An early finding   Constipation - A late finding, as evidenced by the absence of flatus or bowel  movements   Fever and tachycardia - Occur late and may be associated with strangulation  Previous abdominal or pelvic surgery, previous radiation therapy, or both - May be  part of the patient's medical history   Abdominal distention is present. The duodenal or proximal small bowel has less  distention when obstructed than the distal bowel has when obstructed . Hyperactive  bowel sounds occur early as Gl contents attempt to overcome the obstruction:   Exclude incarcerated hernias of the groin, femoral triangle, and obturator  foramina. Proper genitourinary and pelvic examinations are essential.   Gross or occult blood, which suggests late strangulation or malignancy  Masses, which suggest obturator hernia   Check for symptoms commonly believed to be more diagnostic of intestinal   No reliable way exists to differentiate simple from early strangulated obstruction on  physical examination. Serial abdominal examinations are important and may detect  changes early.   The following conditions should be considered in the differential diagnosis  - Esophageal rupture or tear - Gl foreign body - Gastroenteritis   If the diagnosis is unclear, admission and observation are warranted to detect early  obstructions. Essential laboratory tests are needed; these include the following:    Blood urea nitrogen (BUN) level - If the BUN level is increased, this may indicate  decreased volume state (eg, dehydration)   Creatinine level - Creatinine level elevations may indicate dehydration  Complete blood count (CBC) - The white blood cell (WBC) count may be elevated  with a left shift in simple or strangulated obstructions; increased hematocrit is an  indicator of volume state (ie, dehydration)   Laboratory tests to exclude biliary or hepatic disease are also needed; they include   Plain radiographs are diagnostically more accurate in cases of simple obstruction.  However, diagnostic failure rates of as much as 30% have been reported.   In one small study, the sensitivity of plain radiography was reported to be 75%, and  specificity was reported to be 53%; similar findings were reported in a second study. In  another study, plain films were more accurate in the detection of acute SBO and the  accuracy was higher if interpreted by more-experienced radiologists.   Dilated small-bowel loops with air-fluid levels indicate SBO, as does absent or minimal  colonic gas. SBO is demonstrated in the radiographs below.   Computed tomography (CT) scanning is the study of choice if the patient has fever,  tachycardia, localized abdominal pain, and/or leukocytosis.   CT scanning is useful in making an early diagnosis of strangulated obstruction and in  delineating the myriad other causes of acute abdominal pain, particularly when clinical  and radiographic findings are inconclusive. It also has proved useful in distinguishing  the etiologies of small-bowel obstruction (SBO), that is, in distinguishing extrinsic  causes (such as adhesions and hernia) from intrinsic causes (such as neoplasms and  Crohn disease). In addition, CT scanning differentiates the above from intraluminal  causes, such as bezoars. The modality may be less useful in the evaluation of small  bowel ischemia associated with obstruction.   CT scanning is capable of revealing abscess, inflammatory process, extraluminal  pathology resulting in obstruction, and mesenteric ischemia and enables the clinician  to distinguish between ileus and mechanical small bowel obstruction in postoperative  patients.   The modality does not require oral contrast for the diagnosis of SBO. because the    The accuracy of magnetic resonance imaging (MRI) almost approaches that of CT  scanning for the detection of obstructions. MRI is also effective in defining the location  and etiology of obstruction.   Ultrasonography is less costly and invasive than CT scanning and may reliably exclude  SBO in as many as 89% of patients; specificity is reportedly 1 00%.   Initial emergency department (ED) treatment consists of aggressive fluid  resuscitation .   clinically, early surgical consultation, and administration of antibiotics.  (Antibiotics are used to cover against gram-negative and anaerobic organisms.)   Initial decompression can be performed by placement of a nasogastric (NG) tube for  suctioning Gl contents and preventing aspiration . Monitor airway, breathing, and  circulation (ABCs).   Blood pressure monitoring, as well as cardiac monitoring in selected patients  (especially elderly patients or those with comorbid conditions), is important.   Continued NG suction provides symptomatic relief, decreases the need for  intraoperative decompression, and benefits all patients. No clinical advantage to using  a long tube (nasointestinal) instead of a short tube (NG) has been observed.   A nonoperative trial of as many as 3 days is warranted for partial or simple obstruction.  Provide adequate fluid resuscitation and NG suctioning. Resolution of obstruction  occurs in virtually all patients with these lesions within 72 hours.   Malignant tumor - Obstruction by tumor is usually caused by metastasis; initial  treatment should be nonoperative (surgical resection is recommended when feasible)  Inflammatory bowel disease - To reduce the inflammatory process, treatment  generally is nonoperative in combination with high-dose steroids; consider parenteral  treatment for prolonged periods of bowel rest, and undertake surgical treatment,  bowel resection, and/or stricturoplasty if nonoperative treatment fails.   Intra-abdominal abscess - CT scan-guided drainage is usually sufficient to relieve  obstruction   Radiation enteritis - If obstruction follows radiation therapy acutely, nonoperative  treatment accompanied by steroids is usually sufficient; if the obstruction is a chronic  sequela of radiation therapy, surgical treatment is indicated  Incarcerated hernia - Initially use manual reduction and observation; advise elective  hernia repair as soon as possible after reduction   Acute postoperative obstruction - This is difficult to diagnose, because symptoms  often are attributed to incisional pain and postoperative ileus; treatment should be  nonoperative   Adhesions - Decreasing intraoperative trauma to the peritoneal surfaces can prevent  adhesion formation   A strangulated obstruction is a surgical emergency. In patients with a complete small-  bowel obstruction (SBO), the risk of strangulation is high and early surgical intervention  is warranted. Patients with simple complete obstructions in whom nonoperative trials  fail also need surgical treatment but experience no apparent disadvantage to delayed  surgery.   Laparoscopy has been shown to be safe and effective in selected cases of SBO. A  review of retrospective clinical trials showed that laparoscopy showed better results in  terms of hospital stay and mortality reduction versus open surgery, but prospective,  randomized, controlled trials to assess all outcomes are still needed.   Oxygen and appropriate monitoring are also required. Antibiotics are used to cover  gram-negative and anaerobic organisms. In addition, analgesia and antiemetic are   administered as indicated clinically. As previously mentioned, a nonoperative trial of as  many as 3 days is warranted for partial or simple obstruction. Resolution of obstruction  occurs in virtually all patients with these lesions within 72 hours.   Appendicitis is defined as an inflammation of the inner lining of the vermiform appendix  that spreads to its other parts   In fact, despite diagnostic and therapeutic advancement in medicine, appendicitis  remains a clinical emergency and is one of the more common causes of acute  abdominal pain.   No single sign, symptom, or diagnostic test accurately confirms the diagnosis of   appendiceal inflammation in all cases, and the classic history of anorexia and   periumbilical pain followed by nausea, right lower quadrant (RLQ) pain, and vomiting   Appendicitis may occur for several reasons, such as an infection of the appendix, but  the most important factor is the obstruction of the appendiceal lumen . Left untreated,  appendicitis has the potential for severe complications, including perforation or sepsis,  and may even cause death (see Prognosis and Complications). However, the  differential diagnosis of appendicitis is often a clinical challenge because appendicitis  can mimic several abdominal conditions   The appendix is a wormlike extension of the cecum and, for this reason, has been  called the vermiform appendix. The average length of the appendix is 8-10 cm (ranging  from 2-20 cm). The appendix appears during the fifth month of gestation, and several  lymphoid follicles are scattered in its mucosa. Such follicles increase in number when  individuals are aged 8-20 years. A normal appendix is seen below.    The appendix is contained within the visceral peritoneum that forms the serosa, and its  exterior layer is longitudinal and derived from the taenia coli; the deeper, interior  muscle layer is circular. Beneath these layers lies the submucosal layer, which  contains lymphoepithelial tissue.   Taenia coli converge on the posteromedial area of the cecum, which is the site  of the appendiceal base. The appendix runs into a serosal sheet of the peritoneum  called the mesoappendix, within which courses the appendicular artery , which is  derived from the ileocolic artery. Sometimes, an accessory appendicular artery  (deriving from the posterior cecal artery) may be found.   The vasculature of the appendix must be addressed to avoid intraoperative  hemorrhages. The appendicular artery is contained within the mesenteric fold that  arises from a peritoneal extension from the terminal ileum to the medial aspect of the  cecum and appendix; it is a terminal branch of the ileocolic artery and runs adjacent to  the appendicular wall. Venous drainage is via the ileocolic veins and the right colic vein  into the portal vein; lymphatic drainage occurs via the ileocolic nodes along the course  of the superior mesenteric artery to the celiac nodes and cisterna chyli.   The appendix has no fixed position. It originates 1 .7-2.5 cm below the terminal ileum,  either in a dorsomedial location (most common) from the cecal fundus, directly beside  the ileal orifice, or as a funnel-shaped opening (2-3% of patients). The appendix has a  retroperitoneal location in 65% of patients and may descend into the iliac fossa in 31%.   In fact, many individuals may have an appendix located in the retroperitoneal space;  in the pelvis; or behind the terminal ileum, cecum, ascending colon, or liver. Thus, the  course of the appendix, the position of its tip, and the difference in appendiceal  position considerably changes clinical findings, accounting for the nonspecific signs  and symptoms of appendicitis.   Reportedly, appendicitis is caused by obstruction of the appendiceal lumen from a  variety of causes (see Etiology). Independent of the etiology, obstruction is believed to  cause an increase in pressure within the lumen. Such an increase is related to  continuous secretion of fluids and mucus from the mucosa and the stagnation of this  material. At the same time, intestinal bacteria within the appendix multiply, leading to  the recruitment of white blood cells (see the image below) and the formation of pus  and subsequent higher intraluminal pressure.   Technetium-99m radionuclide scan of the abdomen shows focal uptake of  labeled WBCs in the right lower quadrant consistent with acute appendicitis,  v y   If appendiceal obstruction persists, intraluminal pressure rises ultimately above that of  the appendiceal veins, leading to venous outflow obstruction. As a consequence,  appendiceal wall ischemia begins, resulting in a loss of epithelial integrity and allowing  bacterial invasion of the appendiceal wall.   Within a few hours, this localized condition may worsen because of thrombosis of the  appendicular artery and veins, leading to perforation and gangrene of the appendix. As  this process continues, a periappendicular abscess or peritonitis may occur.   Appendicitis is caused by obstruction of the appendiceal lumen. The most common  causes of luminal obstruction include lymphoid hyperplasia secondary to inflammatory  bowel disease (IBP) or infections (more common during childhood and in young  adults), fecal stasis and fecaliths (more common in elderly patients), parasites  (especially in Eastern countries), or, more rarely, foreign bodies and neoplasms.   Variations in the position of the appendix, age of the patient, and degree of inflammation make  the clinical presentation of appendicitis notoriously inconsistent. Statistics report that 1 of 5  cases of appendicitis is misdiagnosed; however, a normal appendix is found in 15-40% of  patients who have an emergency appendectomy.    Niwa et al reported an interesting case of a young woman with recurrent pain in who was  referred for appendicitis, treated with antibiotics, and was found to have an appendiceal  diverticulitis associated with a rare pelvic pseudocyst at laparotomy after 12 months. Her  condition was probably due to diverticular perforation of the pseudocyst.   The classic history of anorexia and periumbilical pain followed by nausea, right lower quadrant   Nausea is present in 61-92% of patients; anorexia is present in 74-78% of patients.   In addition, when vomiting occurs, it nearly always follows the onset of pain .   Vomiting that precedes pain is suggestive of intestinal obstruction , and the diagnosis of  appendicitis should be reconsidered. Diarrhea or constipation is noted in as many as 18% of  patients and should not be used to discard the possibility of appendicitis.   Typically, symptoms begin as periumbilical or epigastric pain migrating to the right lower  quadrant (RLQ) of the abdomen. This pain migration is the most discriminating feature of  the patient's history, .   Patients usually lie down, flex their hips, and draw their knees up to reduce movements and to  avoid worsening their pain. Later, a worsening progressive pain along with vomiting, nausea,  and anorexia are described by the patient. Usually, a fever is not present at this stage.   In addition to recording the history of the abdominal pain, obtain a complete summary of the  recent personal history surrounding gastroenterologic, genitourinary, and pneumologic  conditions, as well as consider gynecologic history in female patients.   An inflamed appendix near the urinary bladder or ureter can cause irritative voiding   Consider the possibility of an inflamed pelvic appendix in male patients with apparent cystitis.   Also consider the possibility of appendicitis in pediatric or adult patients who present   It is important to remember that the position of the appendix is variable, the base of the  appendix was located at the McBurney point in only 4% of patients; in 36%, the base was  within 3 cm of the point; in 28%, it was 3-5 cm from that point; and, in 36% of patients, the  base of the appendix was more than 5 cm from the McBurney point.   The most specific physical findings in appendicitis are rebound tenderness , pain on  percussion, rigidity, and guarding . Although RLQ tenderness is present in 96% of patients,  this is a nonspecific finding. Rarely, left lower quadrant (LLQ) tenderness has been the major  manifestation in patients with situs inversus or in patients with a lengthy appendix that extends  into the LLQ. Tenderness on palpation in the RLQ over the McBurney point is the most  important sign in these patients.   A careful physical examination, not limited to the abdomen, must be performed in any patient  with suspected appendicitis. Gastrointestinal (GI), genitourinary, and pulmonary systems must  be studied. Male infants and children occasionally present with an inflamed hemiscrotum due to  migration of an inflamed appendix or pus through a patent processus vaginalis. This is often  initially misdiagnosed as acute testicular torsion.   In addition, perform a rectal examination in any patient with an unclear clinical picture, and  perform a pelvic examination in all women with abdominal pain.   According to the American College of Emergency Physicians (ACEP) 2010 clinical policy  update, clinical signs and symptoms should be used to stratify patient risk and to choose next  steps for testing and management.   In a minority of patients with acute appendicitis, some other signs may be noted. However,  their absence never should be used to rule out appendiceal inflammation.   The Rovsing sign (RLQ pain with palpation of the LLQ) suggests peritoneal irritation in the   The obturator sign (RLQ pain with internal and external rotation of the flexed right hip)   suggests that the inflamed appendix is located deep in the right hemipelvis.   The psoas sign (RLQ pain with extension of the right hip or with flexion of the right hip   against resistance) suggests that an inflamed appendix is located along the course of the right   The Dunphy sign (sharp pain in the RLQ elicited by a voluntary cough) may be helpful in    Similarly, RLQ pain in response to percussion of a remote quadrant of the abdomen, or to firm  percussion of the patient's heel, suggests peritoneal inflammation.   The Markle sign, pain elicited in a certain area of the abdomen when the standing patient drops   from standing on toes to the heels with a jarring landing.   There is no evidence in the medical literature that the digital rectal examination (DRE) provides  useful information in the evaluation of patients with suspected appendicitis; however, failure to  perform a rectal examination is frequently cited in successful malpractice claims. In 2008,  Sedlak et al studied 577 patients who underwent DRE as part of an evaluation for suspected  appendicitis and found no value as a means of distinguishing patients with and without  appendicitis.   The incidence of appendicitis is unchanged in pregnancy relative to the general population, but  the clinical presentation is more variable than at other times.   During pregnancy, the appendix migrates in a counterclockwise direction toward the right  kidney, rising above the iliac crest at about 4.5 months' gestation. RLQ pain and tenderness  dominate in the first trimester, but in the latter half of pregnancy, right upper quadrant  (RUQ) or right flank pain must be considered a possible sign of appendiceal  inflammation.   Nausea, vomiting, and anorexia are common in uncomplicated first trimester pregnancies, but  their reappearance later in gestation should be viewed with suspicion.   Several investigators have created diagnostic scoring systems to predict the likelihood of acute  appendicitis. In these systems, a finite number of clinical variables is elicited from the patient  and each is given a numeric value; then, the sum of these values is used.   The best known of these scoring systems is the MANTRELS score, which tabulates migration  of pain, anorexia, nausea and/or vomiting, tenderness in the RLQ, rebound tenderness, elevated  temperature, leukocytosis, and shift to the left (see Table 1). Table 1. MANTRELS Score    Clinical scoring systems are attractive because of their simplicity; however, none has been  shown prospectively to improve on the clinician's judgment in the subset of patients evaluated  in the emergency department (ED) for abdominal pain suggestive of appendicitis. The  MANTRELS score, in fact, was based on a population of patients hospitalized for suspected  appendicitis, which differs markedly from the population seen in the ED.   Computer-aided diagnosis consists of using retrospective data of clinical features of patients  with appendicitis and other causes of abdominal pain and then prospectively assessing the risk  of appendicitis. Computer-aided diagnosis can achieve a sensitivity greater than 90% while  reducing rates of perforation and negative laparotomy by as much as 50%.    However, the principle disadvantages to this method are that each institution must generate its  own database to reflect characteristics of its local population, and specialized equipment and  significant initiation time are required. In addition, computer-aided diagnosis is not widely  available in US EDs.   The stages of appendicitis can be divided into early, suppurative, gangrenous, perforated,  phlegmonous, spontaneous resolving, recurrent, and chronic.   In the early stage of appendicitis, obstruction of the appendiceal lumen leads to  mucosal edema, mucosal ulceration, bacterial diapedesis, appendiceal distention due  to accumulated fluid, and increasing intraluminal pressure. The visceral afferent nerve  fibers are stimulated, and the patient perceives mild visceral periumbilical or epigastric  pain, which usually lasts 4-6 hours.   Increasing intraluminal pressures eventually exceed capillary perfusion pressure,  which is associated with obstructed lymphatic and venous drainage and allows  bacterial and inflammatory fluid invasion of the tense appendiceal wall. Transmural  spread of bacteria causes acute suppurative appendicitis. When the inflamed serosa of  the appendix comes in contact with the parietal peritoneum, patients typically  experience the classic shift of pain from the periumbilicus to the right lower abdominal  quadrant (RLQ), which is continuous and more severe than the early visceral pain.   Persisting tissue ischemia results in appendiceal infarction and perforation. Perforation  can cause localized or generalized peritonitis.   An inflamed or perforated appendix can be walled off by the adjacent greater omentum  or small-bowel loops, resulting in phlegmonous appendicitis or focal abscess.   If the obstruction of the appendiceal lumen is relieved, acute appendicitis may resolve  spontaneously. This occurs if the cause of the symptoms is lymphoid hyperplasia or  when a fecalith is expelled from the lumen.    The incidence of recurrent appendicitis is 10%. The diagnosis is accepted as such if  the patient underwent similar occurrences of RLQ pain at different times that, after  appendectomy, were histopathologically proven to be the result of an inflamed  appendix.    Chronic appendicitis occurs with an incidence of 1% and is defined by the following: (1)  the patient has a history of RLQ pain of at least 3 weeks’ duration without an  alternative diagnosis; (2) after appendectomy, the patient experiences complete relief  of symptoms; (3) histopathologically, the symptoms were proven to be the result of  chronic active inflammation of the appendiceal wall or fibrosis of the appendix.   The classic history of anorexia and periumbilical pain followed by nausea, right lower  quadrant (RLQ) pain, and vomiting occurs in only 50% of cases. Vomiting that  precedes pain is suggestive of intestinal obstruction, and the diagnosis of appendicitis  should be reconsidered.    The differential diagnosis of appendicitis is often a clinical challenge because  appendicitis can mimic several abdominal conditions (see Differentials). Patients with  many other disorders present with symptoms similar to those of appendicitis, such as  the following:   Other problems that should be considered in a patient with suspected appendicitis  include appendiceal stump appendicitis, typhlitis, epiploic appendagitis, psoas  abscess, and yersiniosis.   Appendicitis is misdiagnosed in 33% of nonpregnant women of childbearing age. The  most frequent misdiagnoses are PIP, followed by gastroenteritis and urinary tract  infection .   In distinguishing appendiceal pain from that of PID, anorexia and onset of pain more  than 14 days after menses suggests appendicitis.   Previous PID, vaginal discharge, or urinary symptoms indicates PIP . On physical  examination, tenderness outside the RLQ, cervical motion tenderness, vaginal  discharge, and positive urinalysis support the diagnosis of PID.   Although negative appendectomy does not appear to adversely affect maternal or fetal  health, diagnostic delay with perforation does increase fetal and maternal morbidity.  Therefore, aggressive evaluation of the appendix is warranted in pregnant women.   The level of urinary beta-human chorionic gonadotropin (beta-hCG) is useful in  differentiating appendicitis from early ectopic pregnancy. However, with regard to the  WBC count, physiologic leukocytosis during pregnancy makes this study less useful in  the diagnosis than at other times, and no reliable distinguishing WBC parameters are  cited in the literature.   Appendicitis is misdiagnosed in 25-30% of children, and the rate of initial misdiagnosis  is inversely related to the age of the patient. The most common misdiagnosis is  gastroenteritis, followed by upper respiratory infection and lower respiratory infection.   Children with misdiagnosed appendicitis are more likely than their counterparts to have  vomiting before pain onset, diarrhea, constipation, dvsuria. signs and symptoms of   upper respiratory infection, and lethargy or irritability . Physical findings less likely to be  documented in children with a misdiagnosis than in others include bowel sounds;  peritoneal signs; rectal findings; and ear, nose, and throat findings.   Abdominal Abscess  Cholecystitis and Biliary Colic  Constipation  Crohn Disease  Diverticular Disease   Patients with appendicitis may not have the reported classic clinical picture 37-45% of  the time, especially when the appendix is located in an unusual place .   In such cases, imaging studies may be important but not always available. However,  patients with appendicitis usually have accessory signs that may be helpful for .For  example, the obturator sign is present when the internal rotation of the thigh elicits pain  (ie, pelvic appendicitis), and the psoas sign is present when the extension of the right  thigh elicits pain (ie, retroperitoneal or retrocecal appendicitis).   Laboratory tests are not specific for appendicitis, but they may be helpful to confirm  diagnosis in patients with an atypical presentation.   Studies consistently show that 80-85% of adults with appendicitis have a white blood  cell (WBC) count greater than 1 0,500 cells/pL. Neutrophilia greater than 75% occurs in  78% of patients. Less than 4% of patients with appendicitis have a WBC count less  than 10,500 cells/pL and neutrophilia less than 75%.   CBC tests are inexpensive, rapid, and widely available; however, the findings are  nonspecific. In infants and elderly patients, a WBC count is especially unreliable  because these patients may not mount a normal response to infection. In pregnant  women, the physiologic leukocytosis renders the CBC count useless for the diagnosis   C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver in  response to infection or inflammation and rapidly increases within the first 12 hours.  CRP has been reported to be useful in the diagnosis of appendicitis; however, it lacks  specificity and cannot be used to distinguish between sites of infection.   CRP levels of greater than 1 mg/dL are commonly reported in patients with  appendicitis, but very high levels of CRP in patients with appendicitis indicate  gangrenous evolution of the disease, especially if it is associated with leukocytosis and  neutrophilia. However, CRP normalization occurs 12 hours after onset of symptoms.  Several prospective studies have shown that, in adults who have had symptoms for  longer than 24 hours, a normal CRP level has a negative predictive value of 97-100%  for appendicitis. Thimsen et al noted that a normal CRP level after 12 hours of  symptoms was 100% predictive of benign, self-limited illness.   Multiple studies have examined the sensitivity of CRP level alone for the diagnosis of  appendicitis in patients selected to undergo appendectomy   Investigators have also studied the ability of combinations of WBC count and CRP to reliably rule out  the diagnosis of appendicitis.   Mohammed et al prospectively studied 216 children admitted for suspected  appendicitis and found a triple screen sensitivity of 86% and a negative predictive  value of 81 . However, Yang et al found that only 6 of 740 patients with appendicitis had  a WBC count less than 10,500 cells/p L AND neutrophilia that was less than 75%,   AND a normal CRP level, yielding a sensitivity of 99.2% for the "triple screen."   Liver and pancreatic function tests (eg, transaminases, bilirubin, alkaline phosphatase,  serum lipase, amylase) may be helpful to determine the diagnosis in patients with an  unclear presentation.   Urinalysis may be useful in differentiating appendicitis from urinary tract conditions .   Mild pyuria may occur in patients with appendicitis because of the relationship of the   appendix with the right ureter . Severe pyuria is a more common finding in urinary tract  infections (UTIs). Proteinuria and hematuria suggest genitourinary diseases or  hemocoagulative disorders.   One study of 500 patients with acute appendicitis revealed that approximately one third  reported urinary symptoms, most commonly dysuria or right flank pain. One in 7  patients had pyuria greater than 1 0 WBCs per high power field (hpf), and 1 in 6  patients had greater than 3 red blood cells (RBCs) per hpf. Thus, the diagnosis of  appendicitis should not be dismissed due to the presence of urologic symptoms or  abnormal urinalysis.   For women of childbearing age, the level of urinary beta-human chorionic gonadotropin  (beta-hCG) is useful in differentiating appendicitis from early ectopic pregnancy.   According to a report by Bolandparvaz et al, measurement of the urinary 5-  hydroxyindoleacetic acid (U-5-HIAA) levels could be an early marker of  appendicitis. The rationale of such measurement is related to the large amount of  serotonin-secreting cells in the appendix . The investigators noted that U-5-HIAA levels  increased significantly in acute appendicitis, decreasing when the inflammation shifted    to necrosis of the appendix. Therefore, such decrease could be an early warning sign  of perforation of the appendix.   Computed tomography (CT) scanning with oral contrast medium or rectal Gastrografin  enema has become the most important imaging study in the evaluation of patients with  atypical presentations of appendicitis. Intravenous contrast is usually not necessary.    Studies have found a decrease in negative laparotomy rate and appendiceal  perforation rate when pelvic CT imaging was used in selected patients with suspected  appendicitis. An enlarged appendix is shown in the CT below.   CT scan reveals an enlarged appendix with thickened walls, which do    The use of CT has dramatically increased since the introduction of multidetector CT  (MDCT) scanners. A large, single center study found that MDCT has a high rate of  sensitivity and specificity (98.5% and 98%, respectively) for diagnosing acute  appendicitis.   In adults with appendicitis, the diagnostic performance of CT scans with intravenous  contrast alone is comparable to that of scans with both intravenous and oral contrast,  and patients who receive CT scans with intravenous contrast alone are discharged  more quickly from the emergency department.   . Ultrasonography may offer a safer alternative as a primary diagnostic tool for   appendicitis, with CT scanning used in those cases in which ultrasonograms are   Because of concerns about patient exposure to radiation during CT scans,  ultrasonography has been suggested as a safer primary diagnostic modality for  appendicitis, with CT scanning used secondarily when ultrasonograms are negative or  inconclusive.   In pediatric patients, the ACEP 2010 clinical policy update recommends using  ultrasonography for confirmation, but not exclusion, of acute appendicitis. To  definitively exclude acute appendicitis, CT is recommended.   A healthy appendix usually cannot be viewed with ultrasonography. When appendicitis  occurs, the ultrasonogram typically demonstrates a noncompressible tubular structure  of 7-9 mm in diameter (see the images below).   Sagittal graded compression transabdominal sonogram shows an  acutely inflamed appendix. The tubular structure is noncompressible,  lacks peristalsis, and measures greater than 6 mm in diameter. A thin  rim of periappendiceal fluid is present.    Transverse graded compression transabdominal sonogram of an acutely  inflamed appendix. Note the targetlike appearance due to thickened wall  and surrounding loculated fluid collection.    Vaginal ultrasonography alone or in combination with transabdominal scan may be  useful to determine the diagnosis in women of childbearing age. One study of 22  pregnant women in the first and second trimesters showed that graded compression  ultrasonography had a sensitivity of 66% and specificity of 95%.   The kidneys-ureters-bladder (KUB) radiographic view is typically used to visualize an  appendicolith in a patient with symptoms consistent with appendicitis (see the following  image). This finding is highly suggestive of appendicitis, but appendicoliths also occur  in fewer than 1 0% of cases. The consensus in the literature is that plain radiographs  are insensitive, nonspecific, and not cost-effective.    Kidneys-ureters-bladder (KUB) radiograph shows an appendicolith in  the right lower quadrant. An appendicolith is seen in fewer than 10%  of patients with appendicitis, but, when present, it is essentially  pathognomonic.   Whole blood is withdrawn for radionuclide scanning. Neutrophils and macrophages are labeled with  technetium Tc 99m ( 99m Tc) albumin and administered intravenously. Then, images of the abdomen   and pelvis are obtained serially over 4 hours. Localized uptake of tracer in the RLQ suggests  appendiceal inflammation; this is shown in the images below.   Technetium-99m radionuclide scan of the abdomen shows focal  uptake of labeled WBCs in the right lower quadrant consistent with  acute appendicitis.   Magnetic resonance imaging (MRI) plays a relatively limited role in the evaluation of  appendicitis because of its high cost, long scan times, and limited availability.   However, the lack of ionizing radiation makes it an attractive modality in pregnant  patients . In fact, Cobben et al showed that MRI is far superior to transabdominal  ultrasonography in evaluating pregnant patients with suspected appendicitis.   If ultrasonography demonstrates an inflamed appendix, the patient should undergo  appendectomy. If graded compression ultrasonography is nondiagnostic, the patient  should undergo MRI of the abdomen and pelvis.   Appendectomy remains the only curative treatment of appendicitis, but  management of patients with an appendiceal mass can usually be divided into the  following 3 treatment categories:   Patients with a phlegmon or a small abscess: After intravenous (IV) antibiotic therapy, an  interval appendectomy can be performed 4-6 weeks later.   Patients with a larger well-defined abscess: After percutaneous drainage with IV antibiotics is  performed, the patient can be discharged with the catheter in place. Interval appendectomy  can be performed after the fistula is closed.   Patients with a multicompartmental abscess: These patients require early surgical drainage.  Although many controversies exist over the nonoperative management of acute  appendicitis, antibiotics have an important role in the treatment of patients with this  condition. Antibiotics considered for patients with appendicitis must offer full  aerobic and anaerobic coverage. The duration of the administration is closely  related to the stage of appendicitis at the time of the diagnosis, considering either  intraoperative findings or postoperative evolution. According to several studies,  antibiotic prophylaxis should be administered before every appendectomy. When  the patient becomes afebrile and the white blood cell (WBC) count normalizes,   antibiotic treatment may be stopped. Cefotetan and cefoxitin seem to be the best  choices of antibiotics. (See Medications).   The emergency department (ED) clinician must evaluate the larger group of  patients who present to the ED with abdominal pain of all etiologies with the goal  of approaching 100% sensitivity for the diagnosis in a time-, cost-, and  consultation-efficient manner.   The administration of analgesics to patients with acute undifferentiated abdominal  pain has historically been discouraged and criticized because of concerns that they  render the physical findings less reliable.    However, at least 8 randomized controlled studies have demonstrated that  administering opioid analgesic medications to adult and pediatric patients with  acute undifferentiated abdominal pain is safe; no study has shown that analgesics  adversely affect the accuracy of physical examination. V jSl Ea   Consider ectopic pregnancy in women of childbearing age, and obtain a  qualitative beta-human chorionic gonadotropin (beta-hCG) measurement in  all cases.   Administer intravenous antibiotics to those with signs of septicemia and to those  who are to proceed to laparotomy.   Nonsurgical treatment may be useful when appendectomy is not accessible or when  it is temporarily a high-risk procedure. Anecdotal reports describe the success of IV  antibiotics in treating acute appendicitis in patients without access to surgical  intervention (eg, submariners, individuals on ships at sea).   In a prospective study of 20 patients with ultrasonography-proven appendicitis,  symptoms resolved in 95% of patients receiving antibiotics alone, but 37% of these  patients had recurrent appendicitis within 14 months.   Preoperative antibiotics have demonstrated efficacy in decreasing postoperative  wound infection rates in numerous prospective controlled studies, and they should  be administered in conjunction with the surgical consultant. Broad-spectrum gram-  negative and anaerobic coverage is indicated (see Medications).   Penicillin-allergic patients should avoid beta-lactamase type antibiotics and  cephalosporins. Carbapenems are a good option in these patients.   A retrospective study suggested that the risk of appendiceal rupture is minimal in  patients with less than 24-36 hours of untreated symptoms, -and another  retrospective study suggested that appendectomy within 12-24 hours of  presentation is not associated with an increase in hospital length of stay, operative  time, advanced stages of appendicitis, or complications compared with  appendectomy performed within 12 hours of presentation.   Additional studies are needed to demonstrate whether initiation of antibiotic  therapy followed by urgent appendectomy is as effective as emergent  appendectomy for patients with unperforated appendicitis.   Initially performed in 1987, laparoscopic appendectomy has been performed in  thousands of patients and is successful in 90-94% of attempts. It has also been  demonstrated that laparoscopic appendectomy is successful in approximately 90%  of cases of perforated appendicitis. However, this procedure is contraindicated in  patients with significant intra-abdominal adhesions.   The 2010 SAGES guideline lists the following conditions as suitable for  laparoscopic appendectomy:   Uncomplicated appendicitis  Appendicitis in pediatric patients  Suspected appendicitis in pregnant women  According to the SAGES guideline, laparoscopic appendectomy may be the  preferred approach in the following cases:   The SAGES guideline states that the laparoscopic approach should be preferred in  women of childbearing age with presumed appendicitis.   Diagnostic laparoscopy may be useful in selected cases (eg, infants, elderly  patients, female patients) to confirm the diagnosis of appendicitis. This procedure  has been suggested for pregnant patients in the first trimester with suspected   If findings are positive, such procedures should be followed by definitive surgical  treatment at the time of laparoscopy. Although negative appendectomy does not  appear to adversely affect maternal or fetal health, diagnostic delay with perforation  does increase fetal and maternal morbidity. Therefore, aggressive evaluation of the  appendix is warranted in this group.   Advantages of laparoscopic appendectomy include increased cosmetic satisfaction  and a decrease in the postoperative wound-infection rate. Some studies show that  laparoscopic appendectomy shortens the hospital stay and convalescent period  compared with open appendectomy.   Disadvantages of laparoscopic appendectomy are increased cost and an operating  time approximately 20 minutes longer than that of an open appendectomy;  however, the latter may resolve with increasing experience with laparoscopic  technique. The SAGES guideline recommends practicing a consistent operative  method to reduce cost, operating time, and complications.   Complications of appendicitis may include wound infection, dehiscence, bowel  obstruction, abdominal/pelvic abscess, and, rarely, death. Stump appendicitis also  occurs rarely; however, at least 36 reported cases of appendicitis in the surgical  stump after previous appendectomy exist.   The goals of therapy are to eradicate the infection and to prevent complications. Thus,  antibiotics have an important role in the treatment of appendicitis, and all such. Agents  under consideration must offer full aerobic and anaerobic coverage. The duration of  the administration is closely related to the stage of appendicitis at the time of the  diagnosis.   Antibiotic agents are effective in decreasing the rate of postoperative wound infection  and in improving outcome in patients with appendiceal abscess or septicemia. The  Surgical Infection Society recommends starting prophylactic antibiotics before surgery,  using appropriate spectrum agents for less than 24 hours for nonperforated  appendicitis and for less than 5 days for perforated appendicitis. Regimens are of  approximately equal efficacy, so consideration should be given to features such as  medication allergy, pregnancy category (if applicable), toxicity, and cost.   The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate  concentrations and inhibit the biosynthesis of cell wall mucopeptide.   This agent is a drug combination of beta-lactamase inhibitor with ampicillin. It is used as a single  agent and interferes with bacterial cell wall synthesis during active replication, causing bactericidal  activity against susceptible organisms. Ampicillin/sulbactam also has activity against some gram-  positive organisms, gram-negative organisms (nonpseudomonal species), and anaerobic bacteria.   Cephalosporins are structurally and pharmacologically related to penicillins. They inhibit bacterial cell  wall synthesis, resulting in bactericidal activity.    This drug is also a second-generation cephalosporin that is indicated as single agent for the  management of infections caused by susceptible gram-positive cocci and gram-negative rods. It has  a half-life of 0.8 hours.   Cefepime is a fourth-generation cephalosporin. It has gram-negative coverage comparable to  ceftazidime but has better gram-positive coverage. Cefepime is a zwitter ion that rapidly penetrates  gram-negative cells.   Aminoglycosides have concentration-dependent bactericidal activity. These agents work by binding  to the 30S ribosome, inhibiting bacterial protein synthesis.   Gentamicin is an aminoglycoside antibiotic used for gram-negative coverage, as well as in  combination with an agent against gram-positive organisms and another one against anaerobes.  Gentamicin is not the drug of choice, but consider using this drug if penicillins or other less toxic  drugs are contraindicated, when it is clinically indicated, and in mixed infections caused by  susceptible staphylococci and gram-negative organisms. This agent may be administered  intravenously or ntramuscularly and has numerous regimens; the dose must be adjusted for  creatinine clearance and changes in volume of distribution.   Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. It  is used as a single agent and is effective against most gram-positive and gram-negative bacteria.   These agents can be used to relieve acute undifferentiated abdominal pain in patients   Ciprofloxacin is a fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by  inhibiting DNA gyrase and topoisomerase, which are required for replication, transcription, and  translation of genetic material. Quinolones have broad activity against gram-positive and gram-  negative aerobic organisms.    Levofloxacin is used for infections caused by various gram-negative organisms, antipseudomonal  infections due to multidrug resistant gram-negative organisms.   Anti-infectives such as metronidazole and tigecycline are effective against many types of bacteria  that have become resistant to other antibiotics.   Metronidazole has broad gram-negative and anaerobic coverage and is used in combination with  aminoglycosides (eg, gentamicin). This agent appears to be absorbed into cells; intermediate  metabolized compounds bind DNA and inhibit protein synthesis, causing cell death.   These agents can be used to relieve acute undifferentiated abdominal pain in patients presenting to  the ED.   Morphine sulfate is the drug of choice for analgesia because of its reliable and predictable effects,  safety profile, and ease of reversibility with naloxone. Various intravenous doses are used; morphine  sulfate is commonly titrated to the desired effect.   Carbon monoxide (CO) is a colorless, odorless gas produced by incomplete  combustion of carbonaceous material. Commonly overlooked or misdiagnosed, CO  intoxication often presents a significant challenge, as treatment protocols, especially  for hyperbaric oxygen therapy, remain controversial because of a paucity of definitive  clinical studies.   CO is formed as a by-product of burning organic compounds. Although most fatalities  result from fires, stoves, portable heaters, and automobile exhaust cause  approximately one third of deaths. These often are associated with malfunctioning or  obstructed exhaust systems and suicide attempts. Cigarette smoke is a significant  source of CO. Natural gas contains no CO, but improperly vented gas water heaters,  kerosene space heaters, charcoal grills, hibachis, and Sterno stoves all emit CO. Other  sources of CO exposure include propane-fueled forklifts, gas-powered concrete saws,  inhaling spray paint, indoor tractor pulls, and swimming behind a motorboat.   Children riding in the back of enclosed pickup trucks seem to be at particularly high  risk. Industrial workers at pulp mills, steel foundries, and plants producing  formaldehyde or coke are at risk for exposure, as are personnel at fire scenes and  individuals working indoors with combustion engines or combustible gases.   CO toxicity causes impaired oxygen delivery and utilization at the cellular level. CO affects  several different sites within the body but has its most profound impact on the organs (eg, brain,  heart) with the highest oxygen requirement.    Toxicity primarily results from cellular hypoxia caused by impedance of oxygen delivery. CO  reversibly binds hemoglobin, resulting in relative functional anemia. Because it binds  hemoglobin 230-270 times more avidly than oxygen, even small concentrations can result in  significant levels of carboxyhemoglobin (HbCO).   CO binds to cardiac myoglobin with an even greater affinity than to hemoglobin; the resulting  myocardial depression and hypotension exacerbates the tissue hypoxia. Decrease in oxygen  delivery is insufficient, however, to explain the extent of the CO toxicity. Clinical status often  does not correlate well with HbCO level, leading some to postulate an additional impairment of  cellular respiration.   HbCO levels often do not reflect the clinical picture, yet symptoms typically begin with  headaches at levels around 10%. Levels of 50-70% may result in seizure, coma, and fatality.   CO is eliminated through the lungs. Half-life of CO at room air temperature is 3-4 hours. One  hundred percent oxygen reduces the half-life to 30-90 minutes; hyperbaric oxygen at 2.5 atm   Misdiagnosis commonly occurs because of the vagueness and broad spectrum of complaints;  symptoms often are attributed to a viral illness .   Any of the following should alert suspicion in the winter months, especially in  relation to the previously named sources and when more than one patient in a  group or household presents with similar complaints.   Symptoms may not correlate well with HbCO levels. For nonfatal nonintentional non -  fire-related exposures , the most common symptom was headache (37%) followed by  dizziness (18%) and nausea (17%).   - Bizarre neurologic symptoms, coma  Chronic exposures also present with the above symptoms; however, they may  present with loss of dentition, gradual-onset neuropsychiatric symptoms, or, simply,  recent impairment of cognitive ability.   Physical examination is of limited value. Inhalation injury or burns should always alert  the clinician to the possibility of CO exposure.   - Marked tachypnea (rare; severe intoxication often associated with mild or no  tachypnea)   Skin: Classic cherry red skin is rare (ie, "When you're cherry red, you're dead"); pallor  is present more often.   - Flame-shaped retinal hemorrhages - Bright red retinal veins (a sensitive early  sign)   - Patients display memory disturbance (most common), including retrograde and  anterograde amnesia with amnestic confabulatory states.   - Patients may experience emotional lability, impaired judgment, and decreased  cognitive ability.   - Other signs include stupor, coma, gait disturbance, movement disorders, and  rigidity.   - Patients display brisk reflexes, apraxia, agnosia, tic disorders, hearing and  vestibular dysfunction, blindness, and psychosis.   Long-term exposures or severe acute exposures frequently result in long-term  neuropsychiatric sequelae. Additionally   - After recovery from the initial incident, patients present several days to weeks later  with neuropsychiatric symptoms such as those just described. Two thirds of patients  eventually recover completely.   - MRI changes may remain long after clinical recovery. Predicting and preventing  long-term complications and delayed encephalopathy have been the object of recent  studies, many of which focus on the role of hyperbaric oxygen therapy.   Most unintentional fatalities occur in stationary vehicles from preventable causes such  as malfunctioning exhaust systems, inadequately ventilated passenger compartments,  operation in an enclosed space, and utilization of auxiliary fuel-burning heaters inside a  car or camper.   Most unintentional automobile-related CO deaths in garages have occurred despite  open garage doors or windows, demonstrating the inadequacy of passive ventilation in  such situations.   In the setting of structure fires, CO presents greater risk to firefighters and victims than  thermal injury or oxygen deprivation.   Most developing countries utilize unvented cookstoves, burning wood, charcoal,  animal dung, or agricultural waste. Studies have shown a concurrent rise in  HbCO with these types of exposure in developing countries.   Acute Respiratory Distress Syndrome - Altitude Illness - Cerebral Syndromes  Depression and Suicide - Diabetic Ketoacidosis    HbCO analysis requires direct spectrophotometric measurement in specific blood gas  analyzers. Bedside pulse CO-oximetry is now available but requires a special unit and  is not a component of routine pulse oximetry.   Perform intubation for the comatose patient or, if necessary, for airway protection, and  provide 1 00% oxygen therapy.   Institute cardiac monitoring. Pulse oximetry, although not useful in detecting HbCO, is  still important because a low saturation causes an even greater apprehension in this  setting.   Give notification for comatose or unstable patients because rapid or direct transfer to a  hyperbaric center may be indicated.   If possible, obtain ambient CO measurements from fire department or utility company  personnel, when present.   Early blood samples may provide much more accurate correlation between HbCO and  clinical status; however, do not delay oxygen administration to acquire them.   Cardiac monitor: Sudden death has occurred in patients with severe arteriosclerotic  disease at HbCO levels of only 20%.   Pulse oximetry: HbCO absorbs light almost identically to that of oxyhemoglobin.  Although a linear drop in oxyhemoglobin occurs as HbCO level rises, pulse oximetry  will not reflect it. Pulse oximetry gap, the difference between the saturation as  measured by pulse oximetry and one measured directly, is equal to the HbCO level.  However, new pulse CO-oximetry units are available which can screen for CO toxicity  at the bedside.   Continue 100% oxygen therapy until the patient is asymptomatic and HbCO  levels are below 10%. In patients with cardiovascular or pulmonary compromise, lower  thresholds of 2% have been suggested.   Calculate a gross estimate of the necessary duration of therapy using the initial level  and half-life of 30-90 minutes at 100% oxygen. Complicated issues of treatment of  fetomaternal poisoning are discussed in Special Concerns.   In uncomplicated intoxications, venous HbCO levels and oxygen therapy are likely  sufficient. Evaluate patients with significant cardiovascular disease and initial HbCO  levels above 15% for myocardial ischemia and infarction.   Consider immediate transfer of patients with levels above 40% or cardiovascular or  neurologic impairment to a hyperbaric facility, if feasible. Persistent impairment after 4  hours of normobaric oxygen therapy necessitates transfer to a hyperbaric center.  Pregnant patients with lower carboxyhemoglobin levels (above 15%) should be  considered for hyperbaric treatment.   Serial neurologic examinations, including funduscopy, CT scans, and, possibly, MRI,  are important in detecting the development of cerebral edema. Cerebral edema  requires intracranial pressure (ICP) and invasive blood pressure monitoring to further  guide therapy. Head elevation, mannitol, and moderate hyperventilation to 28-30 mm  Hg PC0 2 are indicated in the initial absence of ICP monitoring. Glucocorticoids have  not been proven efficacious, yet the negative aspects of their use in severe cases are  limited.   Do not aggressively treat acidosis with a pH above 7.15 because it results in a  rightward shift in the oxyhemoglobin dissociation curve, increasing tissue oxygen  availability. Acidosis generally improves with oxygen therapy.   In patients who fail to improve clinically, consider other toxic inhalants or thermal  inhalation injury. Be aware that the nitrites used in cyanide kits  cause methemoglobinemia , shifting the dissociation curve leftward and further  inhibiting oxygen delivery at the tissue level. Combined intoxications of cyanide and  CO may be treated with sodium thiosulfate 12.5 g intravenously to prevent the  leftward shift.   Admit patients to a monitored setting and evaluate acid-base status if HbCO levels  are 30-40% or above 25% with associated symptoms.   Hyperbaric oxygen therapy (HBO) currently rests at the center of controversy  surrounding management of CO poisoning. Increased elimination of HbCO clearly  occurs. Certain studies proclaim major reductions in delayed neurologic sequelae,  cerebral edema, pathologic central nervous system (CNS) changes, and reduced  cytochrome oxidase impairment. Despite these individual claims, systematic reviews  have not revealed a clear benefit of HBO, so no clear guidelines for its use have been  determined.   HBO at 3 atm raises the amount of oxygen dissolved in the serum to 6.8%, enough to  sustain cerebral metabolism. Elimination half-life is reduced to 15-23 minutes.  Elimination half-life of CO from methylene chloride intoxication of 13 hours at room air  temperature is reduced to 5.8 hours. Chambers are small monoplace hulls, allowing  space for a single patient in a supine position who can be viewed through a window  at the head, or they are acrylic walled and allow full visualization. Many of these  monoplace chambers allow for care of critically ill patients, including intravenous  lines, arterial lines, and ventilator. Others are large multiplace chambers that permit  ventilation equipment and allow medical teams to accompany the patient. A  monoplace chamber is shown below.    Treatment regimens usually involve 100% oxygen at 2.4-3 atm for 90-120 minutes.  Re-treatment, although controversial, may be performed for acutely and chronically  persistent symptoms. One study suggests that degree of acidosis can predict the  need for re-treatment.   Complications of therapy include decompression sickness, sinus and middle ear  barotrauma, seizure, progression of pneumothorax to tension pneumothorax, gas  embolism, reversible visual refractive changes, and complications related to transport  of unstable patients.   For treatment of complications from therapy, decongestants are useful, prophylactic  myringotomy is common and a requirement for intubated patients, and chest tube  placement is mandatory with pneumothorax. Exercise caution in patients who have  experienced chest compressions, central venous catheterization, intubation, and  positive pressure ventilation. Seizures are most often secondary to oxygen toxicity  and do not mandate anticonvulsant therapy or discontinuation of HBO therapy.   Febrile seizures are the most common type of seizures observed in the pediatric age  group.   The National Institutes of Health described a febrile seizure as, "An event in infancy or  childhood usually occurring between three months and five years of age, associated   with fever, but without evidence of intracranial infection or defined cause. £***&! u* 4M*  Jt> ijjiis ljjST it does not exclude children with prior neurological impairment  and neither provides specific temperature criteria nor defines a "seizure."   Febrile seizures occur in young children at a time in their development when the  seizure threshold is low. This is a time when young children are susceptible to frequent  childhood infections such as upper respiratory infection, otitis media , viral syndrome,  and they respond with comparably higher temperatures.   Febrile seizures are divided into 2 types: simple febrile seizures (which are  generalized, last < 1 5 min and do not recur within 24 h) and complex febrile seizures  (which are prolonged, recur more than once in 24 h, or are focal). Complex febrile  seizures may indicate a more serious disease process, such as meningitis, abscess,   Febrile seizures tend to occur in families . In a child with febrile seizure, the risk of  febrile seizure is 10% for the sibling and almost 50% for the sibling if a parent has  febrile seizures as well. Although clear evidence exists for a genetic basis of febrile  seizures, the mode of inheritance is unclear.   The type of seizure (generalized or focal) and its duration should be described to help  differentiate between simple and complex febrile seizures.   Focus on the history of fever, duration of fever, and potential exposures to illness.   A history of the cause of fever (eg, viral illnesses, gastroenteritis ) should be elucidated.  Recent antibiotic use is particularly important because partially treated meningitis must  be considered.   A history of seizures, neurologic problems, developmental delay, or other potential  causes of seizure (eg, trauma, ingestion) should be sought.   A careful physical examination often reveals otitis media , pharyngitis , or a viral  exanthem.   Check for meningeal signs as well as for signs of trauma or toxic ingestion.   Risk factors for developing febrile seizures  Family history of febrile seizures - High temperature - Parental report of  developmental delay   Maternal alcohol intake and smoking during pregnancy has a 2-fold increased risk.  Interestingly, no data support the theory that a rapid rise in temperature is a cause of   About one third of all children with a first febrile seizure experience recurrent seizures.   . Family history of a febrile seizure in a first-degree relative  . Brief duration between fever onset and initial seizure   Patients with all 4 risk factors have greater than 70% chance of recurrence. Patients  with no risk factors have less than a 20% chance of recurrence.   Epidural and Subdural Infections - Epidural Hematoma - Meningitis - Pediatrics,  Bacteremia and Sepsis   Patients with active seizures should be treated with airway management, high-flow  oxygen, supportive care, and anticonvulsants as necessary.   Acute treatment such as rectal diazepam (0.5 mq/kq) and buccal 0.4-0. 5 mg/kg) or  intranasal (0.2 mg/kg) are effective and can be given at home for a seizure lasting  longer than 5 minutes.   Patients who are postictal should receive supportive care and antipyretics as   Patients presenting with status epilepticus should be treated with airway management  and anticonvulsants as necessary.   Patients presenting with history and physical examination findings consistent with a  simple febrile seizure should have frequent neurologic examinations to monitor mental  status.   The cause of the febrile illness should be sought and treated.   Antipyretics should be considered. Acetaminophen (Tylenol) and ibuprofen (Motrin) are  often used.   Parental anxiety and fear that their child may die or will develop brain damage needs  to be addressed with reassurance and education.   Patients presenting in status epilepticus can be treated with routine seizure  medications, including benzodiazepines, phenytoin, and phenobarbital.   Antipyretics should be used in patients who appear uncomfortable secondary to fever. Antipyretics do  not appear to prevent recurrence of febrile seizures.   Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body  heat via vasodilation and sweating.    One of the few NSAIDs indicated for reduction of fever. Inhibits the formation of prostaglandins.   Prophylactic treatment with an anticonvulsant agent may be considered for subsequent fever episodes.   Can decrease number of subsequent febrile seizures when given with each febrile episode. Modulates  postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. Appears to act  on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. Also has been found  to be an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.   Rapidly distributes to other body fat stores. Twenty minutes after initial IV infusion, serum concentration drops  to 20% of C max -   Individualize dosage and increase cautiously to avoid adverse effects. Available as IV, PO, and PR dosage  forms.   Sedative hypnotic with short onset of effects and relatively long half-life.   By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in  the brain, may depress all levels of CNS, including limbic and reticular formation.    Important to monitor patient's blood pressure after administering dose. Adjust as necessary.   A transient ischemic attack (TIA) is an acute episode of temporary neurologic dysfunction   resulting from focal cerebral ischemia not associated with permanent cerebral infarction.   The clinical symptoms of TIA typically last less than an hour, but prolonged episodes can  occur. While the classical definition of TIA included symptoms lasting as long as 24 hours,  advances in neuroimaging have suggested that many such cases represent minor strokes with  resolved symptoms rather than true TIAs.   A group of cerebrovascular experts proposed a shift from the arbitrary time-based definition of  TIA to a tissue-based definition in 2002 with a new definition for TIA as "a brief episode of  neurological dysfunction caused by focal brain or retinal ischemia, with clinical symptoms  typically lasting less than one hour, and without evidence of acute infarction." This proposed  new definition was well received and endorsed by many clinicians. The American Heart  Association and American Stroke Association (AHA/ASA) 2009 Guidelines endorsed this new  definition, modifying it with the omission of the phrase "typically less than one hour," as there  is no time cutoff that reliably distinguishes whether a symptomatic ischemic event will result in  tissue infarction.   The AHA/ASA-endorsed definition of TIA is as follows: Transient ischemic attack (TIA) is a   transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal   Ruling out metabolic or drug-induced etiologies for symptoms consistent with a TIA is  important.   Most importantly, a fingerstick blood glucose should be checked for hypoglycemia. Serum  electrolytes should be sent to investigate for electrolyte derangements. The following tests are  considered emergent: serum chemistry profile, including creatinine; coagulation studies; and  complete blood count.   Initial assessment is aimed at excluding emergent conditions that can mimic a TIA, such as  hypoglycemia, seizure, or intracranial hemorrhage. Laboratory studies, including CBC,  coagulation studies, and electrolyte levels, should be obtained. Antithrombotic therapy should  be initiated as soon as intracranial hemorrhage has been ruled out   The transient ischemic attack (TIA) is characterized by a temporary reduction or cessation of cerebral  blood flow in a specific neurovascular distribution that is due to low flow through a partially occluded  vessel, an acute thromboembolic event, or stenosis of a small penetrating vessel.   The transient ischemic attack (TIA) workup is focused on emergent/urgent risk stratification and  management.    Numerous potential underlying causes can be readily identified, including the following:   • Embolic sources - Valvular disease, ventricular thrombus, and thrombus formation due to atrial  fibrillation   • Arteritis - Inflammation of the arteries occurring primarily in elderly persons, especially women;  noninfectious necrotizing vasculitis (primary cause); drugs; irradiation; local trauma   • Mass lesions (eg, tumors, subdural hematomas) - Less frequently cause transient symptoms and  more often result in progressive persistent symptoms   TIA etiologies in children, which can differ from those in adults, include the following:   - Drug abuse (eg, cocaine) - Clotting disorders - Central nervous system  infection   Patients with TIAs have an increased risk of stroke and death from coronary artery disease  (depending on risk factors in the study group, approximately 6-10% per year).   The probability that a person will have a stroke in the 5 years following a TIA is reported to be 24-  29%.   It is essential that patients who are being discharged from the hospital first receive clear instruction to  ensure understanding of the need for a complete and rapid workup through close follow-up care. The  patient who has had a TIA needs to be educated about lifestyle modification and cardiovascular  risk factors .   Also essential for patients is education on stroke symptoms, the need to call emergency services  immediately if any of these symptoms occur, and the contact number for emergency services (91 1 in  the United States).   Additionally, despite program efforts in public education, many patients still do not seek medical  attention after experiencing TIA symptoms. A recent population-based study of patients suffering TIA  or minor stroke found that 31% of all patients who experienced a recurrent stroke within 90 days of  their first TIA or minor stroke did not seek medical attention after the initial event.Public health  professionals and physicians need to do more, such as promoting and participating in medical  screening fairs and public outreach programs.   A transient ischemic attack (TIA) may last only minutes, and symptoms often resolve  before the patient presents to a clinician. Thus, historical questions should be  addressed not just to the patient but also to family members, witnesses, and  emergency medical services (EMS) personnel. Witnesses often perceive abnormalities  that the patient cannot, such as changes in behavior, speech, gait, memory, and  movement.   Significant medical history questions to elicit any risk factors for relevant underlying  disease include questions about the following:   - Recent surgery (eg, carotid, cardiac) - Previous strokes - Seizures - CNS  infections   - Use of illicit drugs - Complete medication regimen - Known   irradiationThromboembolic risk factors such as carotid artery stenosis, venous or  arterial thromboembolism, patent foramen ovale, atrial fibrillation, prior myocardial  infarction, or left ventricular dysfunction   Carefully investigate onset, duration, fluctuation, and intensity of symptoms. Reviewing  the patient's medical record is extremely important for identifying deficits from previous  strokes, seizures, or cardiac events. The primary care physician can be a reliable  resource for insights into previous episodes and workup.   If a patient has a history of associated trauma or cardiac symptoms, the differential  diagnosis widens. Pertinent negative items (eg, lack of headache, lack of chest pain,  lack of eye pain) in the review of systems also are important.   Carotid or vertebral dissection can occur in association with both major and minor  trauma. The patient may provide a history of blunt or torsion injury to the neck.  Controversy exists regarding whether chiropractic manipulation or massage therapy  increases the risk of arterial dissection.   The goal of the physical examination is to carefully uncover any neurologic deficits,  evaluate for underlying cardiovascular risk factors, and seek any potential thrombotic  or embolic source of the event.   A stroke scale prompts the examiner to be thorough and allows different examiners to  reliably repeat the examination during subsequent phases of the evaluation. Any  neurologic abnormalities should suggest the diagnosis of stroke (or ongoing neurologic  event) rather than TIA.   mastoiditis, meningitis) and vasculidities. Carotid arteries can be examined for pulse   Funduscopy can identify retinal plaques, retinal pigmentation, and optic disc margins.  Pupil reaction to direct and consensual light exposure can be assessed.   In addition to performing standard auscultation, examine the chest for the presence  of surgical scars, for the presence of a pacemaker/automatic implantable cardioverter  defibrillator (AICD), or for other clues that the patient may have a cardiac disorder and  increased risk of a cardioembolic phenomenon.   Cardioembolic events are significant causes of TIAs. Identify the rhythm for irregularity  or other unusual rhythms and rates, murmurs, or rubs that might suggest valvular  disease, atrioseptal defects, or ventricular aneurysm (a source of mural thrombi).   - Asymmetrical mouth retraction - Loss of the nasolabial crease  difficulty   The cerebellar system can be tested by assessing ocular movement, gait, and finqer-  to-nose and heel-to-knee movements, looking for signs of past-pointing and dvstaxia,   The speech and language system can be tested to assess for both aphasia and  dysarthria.   A neurologic examination is the foundation of the TIA evaluation and should focus in  particular on the neurovascular distribution suggested by the patient’s symptoms.  Subsets of the neurologic examination include the following:   - Speech and language testing - Cerebellar system (be sure to see the patient walk)   Mental status can be assessed formally (Mini-Mental Status Examination, Quick  Confusion Scale) or as part of the patient's overall response to questions and  interactions with the examiner.   Test muscle stretch reflexes of the biceps, triceps, brachioradialis, patellar, and  Achilles. In addition, inspect posture and the presence of tremors.   Test the strength of the shoulder girdle, upper extremities, abdominal muscles, and  lower extremities, and test passive movement of major joints to look for spasticity,  clonus, and rigidity.   The National Institutes of Health Stroke Scale (NIHSS) (see Table 1, below) is used  mostly by stroke teams for quantifying neurological impairment. It enables the  consultant to rapidly determine the severity and possible location of the stroke.   A patient's score on the NIHSS is strongly associated with outcome, and it can help to  identify those patients who are likely to benefit from thrombolytic therapy and those  who are at higher risk of developing hemorrhagic complications of thrombolytic use.   This scale is easily used and focuses on the following 6 major areas of the neurologic  examination:   The NIHSS is a 42-point scale, with minor strokes usually being considered to have a  score less than 5. An NIHSS score greater than 1 0 correlates with an 80% likelihood of  visual flow deficits on angiography. Yet, discretion must be used in assessing the  magnitude of the clinical deficit; for instance, if a patient's only deficit is being mute, the  NIHSS score will be 3. Additionally, the scale does not measure some deficits  associated with posterior circulation strokes (ie, vertigo, ataxia).   The examiner should assess the patient's overall health and appearance, making an  assessment of the following:   - Attentiveness - Ability to interact with the examiner - Language and  memory skills   It has been suggested that transient ischemic attacks (TIAs) are a subset of a larger  category termed transient neurological attacks (TNAs).   TNAs are defined as episodes of sudden onset of neurological symptoms that  completely resolve within 24 hours and have no clear diagnosis. When a TNA is  associated with focal symptoms attributed to an arterial territory of the brain, it is  consistent with a stroke or TIA and is termed a focal TNA.   In contrast, a nonfocal TNA is a temporary event of diffuse, nonlocalizing, cerebral  symptoms that set in suddenly and resolve quickly. Symptoms of nonfocal TNAs may  include altered consciousness, nonrotatory dizziness, positive visual phenomena,  paresthesias, bilateral weakness, or generalized feelings of unwell with a clinical  suspicion for neurological disease. When symptoms are both focal and nonfocal, the  term “mixed TNA” would apply.   Nonfocal TNAs have long been considered to be benign. A recent study showed,  however, that patients who had suffered a prior nonfocal TNA were at higher risk of  stroke and dementia, especially vascular dementia, compared with patients who did  not have a history of prior TNA. Although more research is required, this study  challenges the idea that nonfocal TNAs are benign events. Further workup should be  considered in patients suffering nonfocal TNAs to elucidate the underlying cause of  their transient symptoms and to risk stratify them further.   Ruling out metabolic or drug-induced etiologies for symptoms consistent with a  transient ischemic attack (TIA) is important. Most importantly, a fingerstick blood  glucose should be performed for hypoglycemia. Serum electrolytes should be  measured for electrolyte derangements.   Serum chemistry profile, including creatinine - Coagulation studies - Complete  blood cell count   The following tests typically are helpful and often can be performed on an urgent basis:   Screening for hypercoagulable states (particularly in younger patients with no known  vascular risk factors) include the following:   Protein C, protein S, antithrombin III activities  Activated protein C resistance/Factor V Leiden   National recommendations for urgent evaluation of the patient with a transient  ischemic attack (TIA) include imaging of the brain within 24 hours of symptom onset,  preferably MRI with diffusion-weighted imaging (DWI), but if this is not available, then a  CT scan should be obtained. The cerebral vasculature should be imaged urgently,  preferably at the same time as the brain. Brain imaging can identify an area of  ischemia in up to 25% of patients, and TIA mimics may be identified as well. Vessel  imaging can identify a stenosis or occlusion that requires early intervention.   The noncontrast cranial CT scan is widely and rapidly available and often serves as  the initial imaging evaluation. It can aid in diagnosing the following:   A new area of ischemia or infarction  Old areas of ischemia  Intracranial mass such as tumor   MRI is more sensitive than CT for acute ischemia, infarction, previous intracranial  bleeding, and other underlying lesions. MRI is less widely available on an acute basis  than CT scan, however. The presence of ischemic lesions on an MRI appears to  increase the short-term risk of stroke, highlighting its value in acute risk stratification. In  addition, a negative DWI image in concert with low-risk clinical features can mark  those at minimal short-term stroke risk. Recent data suggest that patients with DWI  abnormalities, despite low ABCD2 scores, are at just as high a risk for stroke as  patients with high ABCD2 scores but no DWI abnormalities.   Vascular imaging for TIA includes Doppler ultrasound, computed tomographic angiography (CTA),  and MRA.   Carotid Doppler ultrasonography of the neck can be used to identify patients in need of  urgent surgical or endovascular therapy. Transcranial Doppler can be a  complementary examination evaluating patency of cerebral vessels and collateral  circulation.   Computed tomographic angiography (CTA) is of increasing value in identifying  occlusive disease in the cerebrovascular circulation. Magnetic resonance angiography  (MRA) is another alternative for imaging vessels in both the brain and neck.  Conventional angiography can be performed when the other modalities are unavailable  or yield discordant results.   Transthoracic or transesophageal echocardiography (TTE/TEE) can evaluate for a  cardioembolic source or for risk factors such as patent foramen ovale.   Twelve-lead electrocardiography should be performed as soon as possible after  transient ischemic attack (TIA) and can evaluate for dysrhythmias such as atrial  fibrillation.   Cardiac monitoring (inpatient telemetry or Holter monitor) is recommended as "useful"  in patients without a clear diagnosis after initial brain imaging and electrocardiography.   Lumbar puncture (LP) may be indicated if subarachnoid hemorrhage, infectious etiology, or  demyelinating disease is to be excluded.   Rapid transport is essential to evaluate the patient who may have fleeting or stuttering  symptoms. Fingerstick glucose can quickly rule out hypoglycemia. Intravenous (IV)   access can be established, although transport should not be delayed for this. Collect  all the patient's prescription bottles.   The family or witnesses should be instructed to go to the ED, or contact information for  these individuals should be obtained. Some communities may have EMS preferentially  transfer patients with high-risk stroke symptoms to centers with specific stroke  expertise.   Global CNS depression and airway or cardiac compromise are not typically features of  a transient ischemic attack (TIA). In fact, the level of consciousness and neurologic  examination are expected to be at the patient's baseline. Initial assessment is aimed at  excluding emergent conditions that can mimic a TIA, such as hypoglycemia, seizure,  or intracranial hemorrhage.   Laboratory studies, including CBC, coagulation studies, and electrolyte levels, should  be obtained. Obtain an electrocardiogram (ECG) and evaluate for symptomatic  rhythms or evidence of ischemia. Brain imaging is recommended within 24 hours of  symptom onset. While MRI with diffusion-weighted imaging (DWI) is preferred, a  noncontrast head CT is a reasonable first choice when MRI is not readily available.   Although controversy exists regarding the need for admission, there is no controversy  regarding the need for urgent evaluation, risk stratification, and initiation of stroke  prevention therapy.   The availability of local resources determines whether this urgent evaluation should  occur as an inpatient, in an ED observation unit, or in rapid follow-up. To determine  appropriate disposition, the emergency physician should decide on the necessary  workup, then discuss with the neurologist or primary care physician how best to ensure  that this occurs promptly. In addition to the rapidity of the risk stratification workup, the  emergency physician should consider the potential benefit of decreased time to  thrombolysis in hospitalized patients diagnosed with TIA who develop a new stroke in  the first 24-48 hours after diagnosis.   One randomized controlled trial of an ED diagnostic protocol found that they could  reduce cost, length of stay, and provide appropriate risk stratification by performing this  workup in an ED observation unit (with neurology consultation) rather than in an  inpatient unit.   Vital signs must be obtained promptly and addressed as indicated. Cardiac monitoring  can capture a relevant dysrhythmia. Pulse oximetry can evaluate for hypoxia.   Intravenous access (if not already established by EMS) should be obtained. Obtain a  fingerstick glucose level, and treat the patient accordingly.   Patients may be significantly hypertensive. Unless there is specific concern for end-  organ damage from a hypertensive emergency, blood pressure should be managed  conservatively while ischemic stroke is being ruled out.   For acute ischemic stroke, the American Heart Association recommends initiating  antihypertensive therapy only if blood pressure is higher than 220/120 mm Hq or if   mean arterial pressure is greater than 130 mm Hq . Unless there is a concerning  comorbid cardiac or other condition requiring blood pressure lowering, allowing the  patient's blood pressure to autoregulate at a higher level (during the acute phase) may  help maximize cerebral perfusion pressure.   Medical management is aimed at reducing both short- and long-term risk of stroke.  Antithrombotic therapy should be initiated as soon as intracranial hemorrhage has  been ruled out, given the high short-term risk of stroke following TIA. The AHA/ASA  guidelines for the prevention of stroke in patients with stroke or transient ischemic  attack, issued in 2006 and updated in 2010, are summarized below.   Antiplatelet agents are recommended rather than oral anticoagulation as initial therapy.  Aspirin (50-325 mg/d), combination aspirin/extended-release dipyridamole, and  clopidogrel are all reasonable first-line options (class I recommendation).   Combination aspirin/extended-release dipyridamole (Aggrenox) may be superior to  aspirin alone (class lla recommendation)and can be started within 7 days of the event.   Clopidogrel may be considered instead of aspirin alone (class lib recommendation).  Aspirin in combination with clopidogrel increases the risk of hemorrhage and is not  routinely recommended for patients with TIA (class III recommendation).   In patients with atrial fibrillation after TIA, long-term anticoagulation with warfarin (goal  INR, 2-3) is typically recommended. Aspirin, 325 mg/d, is recommended for those  unable to take oral anticoagulants. The 2010 AHA/ASA guidelines on stroke prevention  after TIA or stroke state that clopidogrel should not be used in combination with aspirin  therapy, as the bleeding risk of clopidogrel plus aspirin is similar to that of warfarin.   The 201 0 AHA/ASA guidelines also state that it is reasonable for patients with atrial  fibrillation who require temporary interruption of oral anticoagulation, but are at high  risk for stroke, to be given low molecular weight heparin subcutaneously as bridging  therapy.   In acute Ml with left ventricular thrombus, oral anticoagulation with warfarin (goal INR  2-3) is reasonable. Aspirin up to 162 mg/d should be used concurrently for ischemic  coronary artery disease.   Either oral anticoagulation with warfarin (goal INR 2-3) or antiplatelet therapy may be  considered in dilated cardiomyopathy. In rheumatic mitral valve disease, oral  anticoagulation with warfarin (goal INR 2-3) is reasonable. Antiplatelet agents would  not normally be added to warfarin unless patients experience recurrent embolism  despite a therapeutic INR.   According to the 201 0 AHA/ASA guidelines, the benefit of warfarin after stroke or TIA  in patients with sinus rhythm and cardiomyopathy characterized by systolic dysfunction  has not been established.   In mitral valve prolapse, long-term antiplatelet therapy is reasonable. In mitral annular  calcification, antiplatelet therapy can be considered. Those with mitral regurgitation can  be considered for warfarin or antiplatelet therapy.   In aortic valve disease, antiplatelet therapy may be considered. For mechanical  prosthetic valves, oral anticoagulation with warfarin (goal INR 2. 5-3. 5) is  recommended. For those with TIAs despite therapeutic INR, aspirin, 75-100 mg/d, can  be added to the regimen. For bioprosthetic valves, patients with TIA and no other  source of thromboembolism can be considered for oral anticoagulation with warfarin  (goal INR 2-3).   The 201 0 AFIA/ASA guidelines state the following for patients with stroke or TIA due to  50-99% stenosis of a major intracranial artery:   Maintenance of blood pressure of less than 140/90 mm Fig and total cholesterol less  than 200 mg/dL is recommended.   Patients with TIA and ipsilateral carotid artery stenosis may be candidates for urgent (<  2 wk) carotid endarterectomy. In certain patients, carotid artery stenting is a  reasonable alternative. This can be discussed acutely or rapid follow-up arranged.   Patients with symptoms attributable to extracranial vertebral stenosis may be  candidates for endovascular treatment, and again, this should be arranged expediently  if available.   According to the AFIA/ASA 2010 guidelines, optimal medical treatment for these  patients includes antiplatelet and statin therapies as well as risk factor modification.  This is also optimal medical treatment for patients with symptomatic extracranial  carotid disease.   Patients selected for outpatient care should have a clear follow-up plan and stroke  prevention initiated as above, including antiplatelet medication and risk-factor  modification. Antiplatelet agents typically should be initiated as soon as intracranial  bleeding is ruled out. As above, the agent to be used varies with the patient and the  specific indication.   The following should be included in any long-term monitoring of TIA patients:   A smoking-cessation strategy, which may include medication, should be initiated.  Heavy drinkers should eliminate or reduce alcohol consumption.   Medical management is aimed at reducing both short- and long-term risk of stroke. Antithrombotic  therapy should be initiated as soon as intracranial hemorrhage has been ruled out, given the high  short-term risk of stroke following TIA.   These agents inhibit platelet function by blocking cyclooxygenase and subsequent aggregation.   Aspirin blocks prostaglandin synthetase action, which, in turn, inhibits prostaglandin synthesis and  prevents formation of platelet-aggregating thromboxane A2.   This combination may be superior to aspirin alone in preventing cardiovascular events following TIAs.  Aspirin irreversibly inhibits formation of cyclooxygenase, thus preventing formation of thromboxane  A2, a platelet aggregator and vasoconstrictor. Platelet inhibition lasts for the life of a cell  (approximately 10 d). Dipyridamole is a platelet adhesion inhibitor that possibly inhibits RBC uptake  of adenosine, itself an inhibitor of platelet reactivity.   In addition, it may inhibit phosphodiesterase activity leading to increased cyclic-3',5'-adenosine  monophosphate within platelets and formation of the potent platelet activator thromboxane A2. Each  capsule contains 25 mg aspirin and 200 mg dipyridamole, for a total of 50 mg aspirin and 400 mg  dipyridamole to be given per day.   Clopidogrel selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated  activation of glycoprotein GPIIb/llla complex, thereby inhibiting platelet aggregation.   Dipyridamole is administered to complement usual warfarin therapy. It inhibits platelet adhesion,  which may inhibit adenosine uptake by RBCs. It may increase cyclic-3',5'-AMP within platelets and  formation of the potent platelet activator thromboxane A2. In addition, it may reduce the risk of stroke  when used as monotherapy instead of aspirin.    Ticlopidine is a second-line antiplatelet therapy for patients who cannot tolerate or do not respond to  aspirin therapy. In some circumstances, it can be an alternative to clopidogrel.    Warfarin interferes with hepatic synthesis of vitamin K-dependent coagulation factors. It is used for  prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic  disorders.   Though often considered a benign disease, acute gastroenteritis remains a major  cause of morbidity and mortality in children around the world, accounting for 1 .87  million deaths annually in children younger than 5 years, or roughly 19% of all child  deaths. Because the disease severity depends on the degree of fluid loss, accurately  assessing dehydration status remains a crucial step in preventing mortality. Luckily,  most cases of dehydration in children can be accurately diagnosed by a careful clinical  examination and treated with simple, cost-effective measures.   Adequate fluid balance in humans depends on the secretion and reabsorption of fluid  and electrolytes in the intestinal tract; diarrhea occurs when intestinal fluid output  overwhelms the absorptive capacity of the gastrointestinal tract. The 2 primary  mechanisms responsible for acute gastroenteritis are (1) damage to the villous   brush border of the intestine, causing malabsorption of intestinal contents and   leading to an osmotic diarrhea, and (2) the release of toxins that bind to specific   enterocvte receptors and cause the release of chloride ions into the intestinal   However, even in severe diarrhea, various sodium-coupled solute co-transport  mechanisms remain intact, allowing for the efficient reabsorption of salt and water. By  providing a 1 :1 proportion of sodium to glucose, classic oral rehydration solution (ORS)  takes advantage of a specific sodium-glucose transporter (SGLT-1 ) to increase the  reabsorption of sodium, which leads to the passive reabsorption of water. Rice- and  cereal-based ORS may also take advantage of sodium-amino acid transporters to  increase reabsorption of fluid and electrolytes.   (1) differentiating gastroenteritis from other causes of vomiting and diarrhea in children   In some cases, the history and physical examination can also aid in determining the  type of pathogen responsible for the gastroenteritis, though only rarely will this affect  management.   Diarrhea: Duration of diarrhea, the frequency and amount of stools , the time since  last episode of diarrhea, and the quality of stools.   Frequent, watery stools are more consistent with viral gastroenteritis , whereas stools  with blood or mucus are indicative of a bacterial pathogen . Similarly, a long duration  of diarrhea (>14 d) is more consistent with a parasitic or noninfectious cause of  diarrhea.   Vomiting: Duration of vomiting, the amount and quality of vomitus (eg, food contents,  blood, bile), and time since the last episode of vomiting. When symptoms of vomiting  predominate, one should consider other diseases such as gastroesophageal reflux  disease (GERD), diabetic ketoacidosis, pyloric stenosis, acute abdomen, or urinary   Urination: Increase or decrease in frequency of urination measured by number of  wet diapers, time since last urination, color and concentration of urine, and presence  of dysuria. Urine output may be difficult to determine with frequent watery stools.  Abdominal pain: Location, quality, radiation, severity, and timing of pain, per report  of parents and/or child. In general, pain that precedes vomiting and diarrhea is more  likely to be due to abdominal pathology other than gastroenteritis.   Signs of infection: Presence of fever, chills, myalgias, rash, rhinorrhea, sore throat,  cough. These may indicate evidence of systemic infection or sepsis.   Appearance and behavior: Weight loss, quality of feeding, amount and frequency of  feeding, level of thirst, level of alertness, increased malaise, lethargy, or irritability,  quality of crying, and presence or absence of tears with crying.   Antibiotics: History of recent antibiotic use increases the likelihood of Clostridium  difficile.   Travel: History of travel to endemic areas may make prompt consideration of  organisms that are relatively rare in the United States, such as parasitic diseases or  cholera.   General: Weight, ill appearance, level of alertness, lethargy, irritability as depicted in  the video below.   Head, ears, eyes, nose, and throat (HEENT): Presence or absence of tears, dry or  moist mucous membranes, and whether the eyes appear  Cardiovascular: Heart rate and quality of pulses   Respiratory: Rate and quality of respirations (The presence of deep, acidotic  breathing suggests severe dehydration   Abdomen: Abdominal tenderness, guarding, and rebound, bowel sounds. Abdominal  tenderness on examination, with or without guarding, should prompt consideration of  diseases other than gastroenteritis.   Rectal: Quality and color of stool, presence of gross blood or mucus  Extremities: Capillary refill time, warm or cool extremities   Skin: Abdominal rash may indicate typhoid fever (infection with Salmonella typhi),  whereas jaundice might make viral or toxic hepatitis more likely. The slow return of  abdominal skin pinch suggests decreased skin turgor and dehydration , while a doughy  feel to the skin may indicate hypernatremia .   Identifying the specific etiologic agent responsible for the acute gastroenteritis rarely  changes management. However, it may be helpful to differentiate between viral,  bacterial, parasitic, and noninfectious causes of diarrhea.   By far, viruses remain the most common cause of acute gastroenteritis in children,  both in the developed and developing world. Rotavirus represents the most important  viral pathogen worldwide, responsible for 29% of all diarrhea-related deaths. Rotavirus  infection follows seasonal variation, with an increased incidence in winter and  decreased incidence in summer.   Viral gastroenteritis typically presents with low-grade fever and vomiting followed  by copious watery diarrhea (up to 1 0-20 bowel movements per day), with symptoms  persisting for 3-8 days.   In developed countries, bacterial pathogens account for a small portion, perhaps 2-  1 0%, of all cases of pediatric gastroenteritis.   Relative to viral gastroenteritis, bacterial disease is more likely to be associated with  high fevers, shaking chills, bloody bowel movements (dysentery), abdominal cramping,  and fecal leukocytes.   In developing countries, enterotoxigenic Escherichia coli (ETEC) remains the most  important bacterial cause of acute gastroenteritis in children, followed  by Campylobacter, Salmonella , and Shigella species, while also causing the majority of  traveler's diarrhea cases in all age groups. Unlike other bacterial causes of  gastroenteritis, ETEC is unlikely to cause dysentery.   Clostridium difficile has emerged as an important cause of antibiotic-associated  diarrhea in children. Any antibiotic can trigger infection with C difficile, though  penicillins, cephalosporins, and clindamycin are the most likely causes. Since 50% of  neonates and young infants are colonized with C difficile, symptomatic disease is   Parasites remain yet another source of gastroenteritis in young children,  with G/arcf/a and Cryptosporidium the most common causes in the United States.  Parasitic gastroenteritis generally present with watery stools but can be  differentiated from viral gastroenteritis by a protracted course or history of travel to  endemic areas.    The vast majority of children presenting with acute gastroenteritis do not require serum  or urine tests, as they are unlikely to be helpful in determining the degree of  dehydration. In a meta-analysis of 6 studies, only serum bicarbonate (< 17) had  statistically significant positive and negative likelihood ratios for detecting moderate  dehydration.    Clinically significant electrolyte abnormalities are rare in children with moderate  dehydration. However, any child being treated with intravenous fluids for severe  dehydration should have baseline electrolytes , bicarbonate, and urea/creatinine drawn.  Laboratory tests are also indicated in patients with moderate dehydration whose  history and physical examination are inconsistent with straightforward gastroenteritis.   Fecal leukocytes and stool culture may be helpful in children presenting with  dysentery. Children older than 12 months of age with a recent history of antibiotic use  should have stool tested for C difficile toxins. Those with a history of prolonged watery  diarrhea (>1 4 d) or travel to an endemic area should have stool sent for ova and  parasites.   Any child with evidence of systemic infection should have a complete workup,  including CBC and blood cultures. If indicated, urine cultures, chest radiography,  and/or lumbar puncture should be performed.   Abdominal films are not indicated in the management of acute gastroenteritis. If the  clinician suspects a diagnosis other than acute gastroenteritis based on history and  physical examination findings, appropriate imaging modalities should be pursued.   Table 2. Assessment of Dehydration According to the World Health Organization*   Not enough of the above signs to classify as some or severe dehydration    Children with acute gastroenteritis rarely require intravenous access. In those  presenting with circulatory collapse due to severe dehydration or sepsis, intravenous  access should be obtained and followed by an immediate 20 mL/kg bolus of  normal saline.   The American Academy of Pediatrics, the European Society of Pediatric  Gastroenterology and Nutrition (ESPGAN), and the World Health Organization all   recommend oral rehvdration solution (ORS) as the treatment of choice for   countries , based on the results of dozens of randomized, controlled trials and several  large meta-analyses.   Initial care in the emergency department should focus on correction of dehydration.  The type and amount of fluid given should reflect the degree of dehydration in the  child.   If the child is breastfed, the mother should be encouraged to breastfeed more  frequently than usual and for longer at each feed.   If the child is not exclusively breastfed, then oral maintenance fluids (including  clean water, soup, rice water, yogurt drink, or other culturally appropriate fluid)  should be given at a rate of approximately 500 mL/day for children younger than  2 years, 1000 mL/day for children aged 2-10 years, and 2000 mL/day for children  older than 10 years.   In addition, ongoing fluid losses should be replaced with 10 mL/kg body weight of  additional ORS for each loose stool and 2 mL/kg body weight of additional ORS for  each episode of emesis (both for breastfed and nonbreastfed children).   Children should be given 50-100 mL/kg of ORS over a 2- to 4-hour period to replace  their estimated fluid deficit, with additional ORS given to replace ongoing losses (10   mL/kg body weight for each stool and 2 mL/kg body weight for each episode of  emesis).   After the initial rehydration phase, patients may be transitioned to maintenance fluids  as described above.   ORS should be given slowly by the caregiver or parent using a teaspoon, syringe, or  medicine dropper at a rate of 5 ml_ every 1-2 minutes. If tolerated by the patient, the  rate of ORS delivery can be increased slowly over time.   For patients who do not tolerate ORS by mouth, nasogastric (NG) feeding is a safe  and effective alternative.   Multiple clinical trials have found NG rehydration to be as efficacious as intravenous  rehydration, but more cost-effective and with fewer adverse events.   Patients should be reassessed frequently by the clinician to ensure adequacy of oral  intake and resolution of the various signs and symptoms of dehydration.   Severe dehydration constitutes a medical emergency requiring immediate resuscitation  with intravenous fluids. Intravenous access should be obtained,   And patients should be administered a bolus of 20-30 mL/kg lactated Ringer's (LR)  or normal saline (NS).   If pulse, perfusion, and/or mental status do not improve, a second bolus should be  administered.   After this, the patient should be given an infusion of 70 mL/kg LR or NS over 5  hours (children <12 months) or 2.5 hours (older children). If no peripheral veins  are available, an intraosseous line should be placed. Serum electrolytes, bicarbonate,  urea/creatinine, and glucose levels should be sent.   Once resuscitation is complete and mental status returns to normal, rehydration should  continue with ORS as described above, as it has been shown to decrease the rate of  hyponatremia and hypernatremia when compared with intravenous rehydration.   A large CochraneDatabase of Systematic Reviews meta-analysis confirmed several  earlier studies showing that reduced osmolarity ORS (osmolarity < 250 mmol/L) is  associated with fewer treatment failures, lower stool output, and less frequent vomiting  compared with standard osmolarity ORS for patients with noncholera  gastroenteritis. However, patients with cholera appear to have higher rates of  hyponatremia with reduced osmolarity ORS compared with standard osmolarity ORS,  without any of the added benefits seen in patients with noncholera gastroenteritis.   In developing countries, clinicians can use WHO ORS sachets or a homemade   solution of 3 q (1 tsp) salt and 18 q (6 tsp) sugar added to 1 liter of clean   New research suggests that polymer-based ORS, made from complex carbohydrates  such as rice, wheat, or maize, may reduce stool output and length of diarrhea  compared with glucose-based ORS. With these solutions, carbohydrates are slowly  digested in the small intestine, releasing glucose to facilitate sodium uptake without  adding a significant osmotic load to bowel contents   In general, children with gastroenteritis should be returned to a normal diet as  rapidly as possible. Early feeding reduces illness duration and improves  nutritional outcome.   Breastfed infants should continue breastfeeding throughout the rehydration and  maintenance phases of acute gastroenteritis. Formula fed infants should restart  feeding at full strength as soon as the rehydration phase is complete (ideally in 2-4 h).  Weaned children should restart their normal fluids and solids as soon as the  rehydration phase is complete. Fatty foods and foods high in simple sugars should  be avoided.   For most infants, clinical trials have found no benefit of lactose-free formulas over  lactose-containing formulas. Similarly, highly specific diets, such as the BRAT  (bananas, rice, applesauce, and toast) diet, have not been shown to improve  outcomes and may provide suboptimal nutrition for the patient.   The goals of pharmacotherapy are to reduce morbidity, to prevent complications, and  for prophylaxis. Antidiarrheal (ie, kaolin-pectin) and antimotility agents (ie, loperamide)  are contraindicated in the treatment of acute gastroenteritis in children because of their  lack of benefit and increased risk of side effects, including ileus, drowsiness, and  nausea.jj4' j ^ ji&i cy* j i^a ya t _ s ic.   Probiotics are live microbial feeding supplements commonly used in the treatment  and prevention of acute diarrhea. Possible mechanisms of action include synthesis of  antimicrobial substances, competition with pathogens for nutrients, modification of   toxins, and stimulation of nonspecific immune responses to pathogens . Two large  systematic reviews have found probiotics (especially Lactobacillus GG) to be effective  in reducing the duration of diarrhea in children presenting with acute  gastroenteritis. Because probiotic preparations vary widely, estimating the  effectiveness of any single preparation is difficult. o^iLi ^ .. ^ ^   One meta-analysis, including 18 published studies, all conducted in developing  countries, found zinc supplementation to be effective in reducing the duration and  severity of diarrhea in children with acute gastroenteritis. The WHO recommends zinc  supplementation (10-20 mg/d for 10-14 d) for all children younger than 5 years  with acute gastroenteritis, though little data exist to support this  recommendation for children in developed countries. u* oVi un»    Clinical trials reported that the vaccines prevented 74-78% of all rotavirus  gastroenteritis cases, nearly all severe rotavirus gastroenteritis cases, and nearly all  hospitalizations due to rotavirus.   Because most cases of acute gastroenteritis in developed and developing countries  are due to viruses, antibiotics are generally not indicated.   Even in cases (eg, dysentery) where a bacterial pathogen is suspected, antibiotics  may prolong the carrier state ( Salmonella ) or may increase the risk of hemolytic uremic  syndrome (enterohemorrhagic E coli).   In patients with positive stool assays or high clinical suspicion for C difficile, the  offending antibiotic should be stopped immediately. Metronidazole (30 mg/kg/d  divided qid for 7 d) can be used as a first-line agent, with oral vancomycin reserved for  resistant infections.   Though generally not recommended for children younger than 8 years, tetracycline (50  mg/kg/d divided qid for 3 d) and doxycycline (6 mg/kg single dose) remain the  treatment of choice for cholera. Alternative treatments with good efficacy include  erythromycin and ciprofloxacin.   For patients with ova and parasites confirming infection with Giardia, metronidazole  (35-50 mg/kg/d divided q8h) remains the drug of choice . Nitazoxanide oral  suspension (aged 1 -3 y: 1 00 mg ql 2h for 3 d, aged 4-1 1 y: 200 mg ql 2h for 3 d) is as  effective as metronidazole and has the added benefit of treating other intestinal  parasites, such as Cryptosporidium.   Recommended as the treatment of choice for mild-to-moderate cases of C  difficilecoWWs. Provides effective therapy, with reported response rates from 95-1 00%.   .Metronidazole IV may be administered to those patients who cannot tolerate PO  medications because of its potential to accumulate in the inflamed colon. IV route is  not as effective as PO.   Inhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites.   Elicits antiprotozoal activity by interference with the pyruvate: ferredoxin  oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is  essential to anaerobic energy metabolism   Inpatient admission should be considered for all children with acute gastroenteritis in  the following situations:   Caregivers are unable to manage oral rehydration or provide adequate care at home.  Substantial difficulties exist in administering ORS, such as intractable vomiting or  inadequate ORS intake.   Failure of treatment occurs, such as worsening diarrhea or dehydration, despite  adequate ORS intake.   Factors are present necessitating closer observation, such as young age, decreased  mental status, or uncertainty of diagnosis.   Children with mild-moderate dehydration, age < 6 months, or high frequency of  stools/vomits should be monitored in the emergency department for a minimum of 4-6  hours before discharge.   Parents should be instructed to continue providing maintenance ORS fluids at home as  needed. Breastfeeding and formula feeding should be continued for infants, and  children should be encouraged to return to a regular diet as rapidly as possible.   Parents should be instructed to look for the various signs of dehydration outlined  above, such as change in mental status, decreased urine output, sunken eyes,  absence of tears, dry mucous membranes, and slow return of abdominal skin pinch.  Parents should seek medical attention if dehydration returns, oral intake is inadequate,  or if their child develops worsening abdominal pain, fever >1 01 °F, or prolonged  diarrhea lasting longer than 14 days.   In 1983, Warren (a biologist) and Marshall (a clinician) described Helicobacter pylori  (HP) . At first, they named the bacterium Campylobacter pyloridis. Later, it was  named Campylobacter pylori. Since then, a large number of reports have been  produced on H pylori and its pathogenetic potential.   In fact, although peptic ulcer disease is the most studied disease related to H  pylori infection, this bacterium is seemingly involved in the pathogenesis of several  extragastric diseases, such as mucosa-associated lymphoid tissue lymphomas  (MALTomas) . coronaritis, gastroesophageal reflux disease (GERD) . iron deficiency  anemia , skin disease, and rheumatologic conditions. Flowever, at present, many of   these associations remain largely uncertain, and the debate to confirm or refute  causality related to these associations is still open.   H pylori infection occurs more frequently in developing countries than in industrialized  countries. H pylori strains differ in their potential to cause diseases. Although anyone  can develop a microscopic gastritis, only a minority of infected persons develop ulcers  or other diseases.   The most common route of H pylori infection is either oral-to-oral (stomach contents  are transmitted from mouth to mouth) or fecal-to-oral (from stool to mouth) contact.  Parents and siblings seem to play a primary role in transmission.   In the authors' opinion, no significant differences in the presence and frequency of  symptoms, such as nausea, vomiting, pain, heartburn, or diarrhea, occur in patients  who are infected with H pylori and patients who are not. No definite evidence  demonstrates a clear relationship between the symptoms of the H pylori- associated  gastritis and abdominal pain or dyspeptic symptoms from other conditions. Of patients,  30-35% have no symptoms.   No specific clinical signs have been described in patients with H pylori infection.   • Patients may feel dyspepsia or abdominal discomfort, such as during gastritis or with  epigastric pain (eg, duodenal ulcers).   • In some cases, patients may feel hungry in the morning and may have halitosis.   H pylori infection causes atrophic and even metaplastic changes in the stomach.   The bacterial adhesion appears to result in tyrosine phosphorylation and is specific for  gastric cells.   The adhesion of H pylori to the gastric cells causes a direct decrease in mucosal levels  of glutathione, a fundamental molecule in the maintenance of the cellular redox status  and in the molecular regulation of host immune responses.   However, the LPS of H pylori may induce the production of autoantibodies that are  able to worsen atrophy in the corpus mucosa and cause a concomitant increase in  parietal cell antibodies. Such events are accompanied by a decrease in anti-H  pylori immunoglobulin titers. This process leads to a scenario of severe atrophy without  bacterial colonization combined with high levels of autoantibodies against gastric  parietal cells.   A number of reports show the close association between H pylori infection and low-  grade gastric MALTomas.   Giannakis and colleagues demonstrated that H pylori may adapt to gastric stem cells,  influencing their biology and contributing to tumorigenesis of the stomach.   - Duodenal Ulcers - Gastric Cancer - Gastric Ulcers - Gastrinoma  Gastritis. Acute   Gastritis, Atrophic - Gastritis, Chronic - Gastritis, Stress-Induced  Gastroesophageal Reflux Disease   This novel rapid test is based on monoclonal antibody immunochromatography of  stool samples. The test has been reported to be very specific (98%) and sensitive  (94%).   The results are positive in the initial stages of infection and can be used to detect  eradication after treatment.   Although the H pylori fecal antigen test is an interesting tool, information about the  cost of the test is pending.   The carbon 13 urea breath test (UBT) is based on the detection of the products  created when urea is split by the organism.   Patients are asked to drink urea (usually with a beverage) labeled with a carbon  isotope (carbon 13 or carbon 14). After a certain duration, the concentration of the  labeled carbon is measured in the breath. The concentration is high only when  urease is present in the stomach. Because the human stomach does not produce  urease, such a reaction is possible only with H pylori infection.   The breath test is expensive but is becoming increasingly more available.   Other problems include false-negative results due to infection with coccoid forms of H  pylori that do not produce as much urease or intake of antibiotics, bismuth, histamine  2 (H2) blockers, or proton pump inhibitors.   The serology test has a high (>90%) specificity and sensitivity. It is currently based  on the quantitation of immunoglobulin G antibodies against/-/ pylori by the means of  an enzyme-linked immunosorbent assay.   It is useful for detecting a newly infected patient, but it is not a good test for follow-up  of treated patients because the results do not indicate present infection with H pylori.  The antibody titer may remain elevated for a long time after H pylori eradication. The  number of false-positive results is age related and increases with age.   Only treat patients who have a test result positive for H pylori infection. Carefully  educate patients regarding the importance of completing the prescription and about the  potential adverse effects of the medication. Importantly, consider possible antibiotic  resistance when selecting the treatment regimen.   The US Food and Drug Administration has approved some regimens, which are now  accepted internationally, for the treatment of H pylori infection in patients with peptic  ulcer disease, both gastric and duodenal. These regimens are also known as triple  therapies and have reported cure rates from 85-90%.   Administer triple therapies for 10-14 days. The treatment regimens are omeprazole,  amoxicillin, and clarithromycin (OAC) for 10 days;   and lansoprazole, amoxicillin, and clarithromycin (LAC) , which has been approved  for either 1 0 days or 1 4 days of treatment.   H pylori eradication rates were higher for a 7-day antibiotic regimen containing  lansoprazole, amoxicillin, and clarithromycin (LAC), when used as first-line therapy  compared with levofloxacin, amoxicillin, and lansoprazole (LAL) .Additionally, LAC did  not achieve a higher rate of eradication than LAL as second-line therapy; thus,  consideration of the sequence of administering antibiotic regimens for H pylori is  important.   All the eradication treatments have a high incidence of certain adverse effects (eg,   nausea, metallic taste). If skin rash, vomiting, or diarrhea occurs, discontinue   Surgery is not required for patients with H pylori infection, but it may be considered in  patients with severe complications, such as cancer.   The goals of pharmacotherapy are to eradicate the microorganism, to prevent  complications, and to reduce morbidity. Triple therapies are used. Worldwide,  accepted treatment regimens are BMT, LAC, and OAC. BMT regimen is based on the  administration of bismuth subsalicylate, metronidazole, and tetracycline. Add an H2-  receptor antagonist for an additional 4 weeks. LAC regimen is based on the  administration of lansoprazole, amoxicillin, and clarithromycin. OAC regimen is based  on the administration of omeprazole, amoxicillin, and clarithromycin.   Increasing resistance to antibiotics has made alternative treatments necessary. In a  phase 3 trial conducted by Malfertheiner et al, quadruple therapy (omeprazole plus a  single 3-in-1 capsule containing bismuth subcitrate potassium, metronidazole, and  tetracycline) was tested against standard therapy in adults with recorded H  pylori infection. This study suggests quadruple therapy provides superior eradication  with similar safety and tolerability to standard therapy.   The approved antidiarrheal for this infection is bismuth subsalicylate. It has both antisecretory and  antimicrobial activity.   Has cytoprotective effect on Gl mucosa, probably due to stimulation of prostaglandin production and  modulation of immune response. In addition, has been demonstrated that some deposits (probably  bismuth salts) appear on both surfaces of the cell wall of H pylori after < 1 h. Such deposits induce  distortion and vacuolization of the bacterial cell and loss of adherence of H pylori from antral  epithelium.    Reduced to its active form intracellularly only by anaerobic organisms, then disrupts helical structure  of DNA and inhibits bacterial nucleic acid synthesis.   Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing  RNA-dependent protein synthesis to arrest.   Inhibits final stage of bacterial cell wall synthesis due to binding to specific PBPs on inner part of  bacterial wall, leading to bacterial lysis.   Bind to proton pump of parietal cell, inhibiting secretion of hydrogen ions into gastric lumen. Relieve  pain and heal peptic ulcers more rapidly than H2 antagonists.    Works by inhibiting the H7K + -ATPase enzyme system of gastric parietal cells.    Decreases gastric acid secretion by inhibiting parietal cell H7K + -ATP pump.   Reversible competitive blockers of histamine at H2 receptors, particularly those in gastric parietal  cells, wherein they inhibit acid secretion. H2 antagonists are highly selective, do not affect the HI  receptors, and are not anticholinergic agents. Proton pump inhibitors are usually preferred.   Reduces basal and nocturnal gastric acid secretion by competitive inhibition of binding of histamine  to receptors (H2 receptor) on gastric parietal cells. Although not effective as single agents for the  eradication of H pylori, appears to increase systemic absorption of bismuth subsalicylate.   Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric  acid secretion, gastric volume, and hydrogen ion concentrations.   Gout and pseudogout are the 2 most common crystal-induced arthropathies. They are  debilitating illnesses in which recurrent episodes of pain and joint inflammation are  caused by the formation of crystals within the joint space and deposition of crystals in  soft tissue. If untreated, these disorders can lead to joint destruction and renal  damage. Rarely, gout can produce significant ocular findings. The incidence of age-  related macular degeneration (ARMD) is higher in patients with gout.   Gout is inflammation caused by monosodium urate monohydrate (MSU) crystals.  Pseudogout is inflammation caused by calcium pyrophosphate (CPP) crystals and is  sometimes referred to as calcium pyrophosphate disease (CPPD).   Although gout is associated with hyperuricemia, the level of uric acid does not itself  precipitate gout; rather, acute changes in the level of uric acid cause gout. Most  individuals with hyperuricemia do not have gout, but if high uric acid levels go  untreated, 90% of patients develop gout within 30 years.   Hyperuricemia is found in 90% of individuals with gout, but it is also found in patients  taking diuretics and even in those taking low doses of aspirin.   Primary gout is related to underexcretion or overproduction of uric acid. Secondary  gout is related to myeloproliferative diseases or their treatment, therapeutic regimens  producing hyperuricemia, renal failure, renal tubular disorders, lead poisoning,  hyperproliferative skin disorders, enzymatic defects (eg, deficient hypoxanthine-  guanine phosphoribosyl transferase, and glycogen storage diseases).   Gout is definitively diagnosed based on the demonstration of urate crystals in  aspirated synovial fluid. Classic radiographic findings may also be diagnostic. (See  Workup).   Improvements in early diagnosis and the availability of definitive treatment have  significantly improved the prognosis of gout, as evidenced by the declining incidence of  disabling chronic tophaceous gout. However, tophaceous gout may still develop  because of misdiagnosis, poor management, medication intolerances, and/or poor  patient compliance.   Treatment of gout is important to relieve pain, prevent disease progression, and  prevent tissue deposition of uric acid (eg, in the kidneys) that may produce kidney  stones or urate nephropathy.   Treatment of the acute phase of pseudogout is identical to that of gout. Unlike gout,  however, no specific therapeutic regimen exists to treat the underlying cause of  pseudogout, but colchicine and hydroxychloroquine are effective for prophylaxis.   Gout is one of the oldest diseases in the medical literature. Since the time of the  Greeks, many authors have written about gout as the result of personal excess; its  association with a diet rich in meat and alcohol gained it the sobriquet, “the king of  diseases and the disease of kings”. However, among the abstinent was John Milton,  who lived a life of rigorous self-discipline and yet, to his anger and despair, suffered  from what commonly was regarded as just punishment of the dissolute.   Gout can be considered a disorder of metabolism that allows uric acid/urate to  accumulate in blood and tissues. When tissues become supersaturated, the urate salts  precipitate, forming crystals. In addition, the crystals also are less soluble under acid  conditions, so any condition predisposing to acidosis also precipitates urate crystals.   Urate initially precipitates in the form of needlelike crystals. The light-retarding (phase-  shifting) characteristics of urate crystals allow them to be recognized by polarizing  microscopy.   Many conditions and drugs have been associated with an increase in plasma (and  subsequent synovial) urate levels. A genetic predisposition for the disease exists.   Gout develops in the setting of excessive stores of uric acid in the form of monosodium  urate. Uric acid is an end-stage by-product of purine metabolism. Humans remove uric  acid primarily by renal excretion.   When excretion is insufficient to maintain serum urate levels below the saturation level  of 6.8 mg/dL (with some variability depending on temperature and pH), hyperuricemia  may develop, and urate can crystallize and deposit in soft tissues.   Ninety percent of patients with gout develop excess urate stores due to an inability to  excrete sufficient amounts of normally produced uric acid in the urine (underexcretion).  The remaining patients either overconsume purines or produce excessive amounts of  uric acid endogenously (overproduction).   Overproduction of uric acid may also occur in disorders that cause high cell turnover  with release of purines, which are present in high concentration in cell nuclei. These  disorders include myeloproliferative and lymphoproliferative disorders, psoriasis,  hemolytic anemias, pernicious anemia, and ineffective erythropoiesis (as in B-12  deficiency). Cell lysis from chemotherapy for malignancies, especially those of the  hematopoietic or lymphatic systems, can raise uric acid levels, as can excessive  exercise and obesity.   Common causes of secondary gout due to underexcretion of uric acid include renal  insufficiency, lead nephropathy (saturnine gout), starvation or dehydration,  hypothyroidism, hyperparathyroidism, drugs, and chronic ethanol (especially beer and  hard liquor) abuse. These disorders should be identified and corrected, if possible.   Comorbidities, including hypertension, diabetes, renal insufficiency,  hypertriglyceridemia, hypercholesterolemia, diabetes, obesity, and early menopause,  are associated with a higher incidence of gout.    Foods that are rich in purines include anchovies, sardines, sweetbread, kidney, liver,  and meat extracts. Consumption of fructose-rich foods and beverages (eg, those  sweetened with high-fructose corn syrup) are associated with an increased risk of gout  in both men and women.   Individual gout flares are often triggered by acute increases or decreases in urate  levels that may lead to the production, exposure, or shedding of crystals that are not  coated with apo B or apo E. This can result from acute alcohol ingestion, acute  overindulgence in foods high in purines, rapid weight loss, starvation, trauma,  emotional stress, or hemorrhage.   Similarly, flares can be precipitated by additions of or changes in dosage of  medications that raise or lower uric acid levels, such as loop or thiazide  diuretics, aspirin, allopurinol, or uricosurics.   Medications that increase uric acid levels via effects on renal tubular transport include  loop and thiazide diuretics, low-dose aspirin, and cyclosporine A. Agents that lower  levels of uric acid include radiocontrast dyes, xanthine oxidase inhibitors (eg,  allopurinol, febuxostat), and uricosurics (eg, probenecid, sulfinpyrazone).   Although the pathophysiology, clinical presentation, and acute-phase treatment of gout  and pseudogout are very similar, the underlying causes of the 2 diseases are very  different. Many cases of pseudogout are idiopathic, but pseudogout has also been  associated with aging, trauma, and many different metabolic abnormalities, the most  common of which are hyperparathyroidism and hemochromatosis. Pseudogout attacks  have been reportedly induced by etidronate disodium therapy and angiography.   Although patients with gout often have other risk factors for renal disease, including  hypertension and diabetes, chronic urate nephropathy can contribute to renal  insufficiency. Chronic urate nephropathy in patients with chronic tophaceous gout can  result from the deposition of urate crystals in the medullary interstitium and pyramids,  resulting in an inflammatory reaction that can lead to fibrotic changes. This process is  characterized by hyperuricemia that is disproportional to the degree of renal  impairment and is associated with a benign urinary sediment.   Gout is associated with considerable morbidity, with acute episodes often causing  incapacitation. However, gout that is treated early and properly carries an excellent  prognosis if patient compliance is good.   With early treatment, gout should be totally controlled. If attacks recur, successful uric  acid adjustment (requiring lifelong use of uricosuric or allopurinol medication) usually  suppresses further activity. During the first 6-24 months of uricosuric or allopurinol  therapy, acute attacks of gout may occur.   Chronic injury to intra-articular cartilage leaves the joints more susceptible to  subsequent joint infections.   Draining tophi can become secondarily infected. Untreated chronic tophaceous gout  can lead to severe joint destruction and renal impairment. Deposition of MSU crystals  in the kidney can result in inflammation and fibrosis, leading to reduced renal function  or chronic nephropathy.   Acute attacks of pseudogout usually resolve within 1 0 days. Prognosis for resolutions  of acute attacks is excellent. Some patients experience progressive joint damage with  functional limitation.   Hyperuricemia and gout are associated with an increased overall likelihood of  mortality. Whether this is directly attributable to hyperuricemia or gout or to gout-  associated diseases (eg, insulin resistance, type 2 diabetes mellitus, abdominal  obesity, hypercholesterolemia, hypertension) has been much debated.   Although no evidence has shown that gout or hyperuricemia causes any of these  disorders, elevated urate levels have been shown to correlate with blood pressure in   adolescents. Among middle-aged men, hyperuricemia with gout was a significant  independent risk for death due to cardiovascular disease.   Patients with severe hyperuricemia should avoid food with high purine content.  Moderation in food and alcohol is advised. Early recognition of acute attacks is critical,  as intervention with medication is much more effective earlier in the attack.   The spontaneous onset of pain, edema, and inflammation in the metatarsal-phalangeal  joint of the great toe (podagra) is highly suggestive of acute crystal-induced arthritis.  Podagra is the initial joint manifestation in 50% of gout cases. Eventually, it is involved  in 90% of cases.   Podagra is not synonymous with gout, however. Podagra may be observed in patients  with pseudogout, sarcoidosis, gonococcal arthritis, psoriatic arthritis, and reactive  arthritis.   Other than the great toe, the most common sites of gouty arthritis are the ankle, wrist,  and knee. In early gout, only 1 or 2 joints are usually involved. Consider the diagnosis  in any patient with acute monarticular arthritis of any peripheral joint except the  glenohumeral joint of the shoulder, in which a crystal-induced arthritis is more likely to  be due to pseudogout.   In addition to the shoulder, the most common sites of pseudogout arthritis are the knee  and wrist. Case reports have documented carpal tunnel syndrome as an initial  presentation of pseudogout.   Case reports of pseudogout forming masses in the spinal ligamentum flavum have  been documented.These have led to both single and multi-level myelopathy.   Although crystal-induced arthritis is most commonly monarticular, polyarticular acute  flares are not rare, and many different joints may be involved simultaneously or in rapid  succession. Multiple joints in the same limb often are involved, as when inflammation  begins in the great toe and then progresses to involve the midfoot and ankle.   Gout attacks begin abruptly and reach maximum intensity within 8-12 hours. The joints  are red, hot, and exquisitely tender; even a bed sheet on the swollen joint is  uncomfortable. The onset of symptoms in pseudogout is usually more insidious and  may occur over several days.   Untreated, the first attacks resolve spontaneously in less than 2 weeks. A history of  intermittent inflammatory arthritis, in which the joints return to normal between attacks,   is typically caused by crystalline disorders and is characteristic of gouty arthritis early  in its course.   Gout initially presents as polyarticular arthritis in 10% of patients. Elderly women,  particularly women with renal insufficiency who are taking a thiazide diuretic, can  develop polyarticular arthritis as the first manifestation of gout. These attacks may  occur in coexisting Heberden and Bouchard nodes. Such patients may also develop  tophi more quickly, occasionally without prior episodes of acute gouty arthritis.   The pattern of symptoms in untreated gout changes over time. The attacks become  more polyarticular. Although more joints may become involved, inflammation in a given  joint may become less intense. More proximal and upper-extremity joints become  involved. Attacks occur more frequently and last longer.   Eventually, patients may develop chronic polyarticular arthritis, sometimes nearly  symmetrical, that can resemble rheumatoid arthritis. Indeed, chronic polyarticular  arthritis that began as an intermittent arthritis should prompt consideration of a  crystalline disorder in the differential diagnoses.   Acute flares of gout can result from situations that lead to increased levels of serum  uric acid, such as the consumption of beer or liquor, overconsumption of foods with  high purine content, trauma, hemorrhage, dehydration, or the use of medications that  elevate levels of uric acid. Acute flares of gout also can result from situations that lead  to decreased levels of serum uric acid, such as the use of radiocontrast dye or  medications that lower the levels of uric acid, including allopurinol and uricosurics.   Patients with gout are profoundly more likely to develop renal stones than are healthy  individuals (by a factor of 1000); therefore, they may have a history of renal colic and  of hematuria. Indeed, renal stones may precede the onset of gout in 40% of affected  patients. While 80% of these patients may have stones composed entirely of uric acid,  20% may develop calcium oxalate or calcium phosphate stones with a uric acid core.   Because gout is frequently present in patients with the metabolic syndrome (eg, insulin  resistance or diabetes, hypertension, hypertriglyceridemia, and low levels of high-  density lipoproteins) and because the presence of these associated disorders can lead  to coronary artery disease, these problems should be sought and treated in patients  diagnosed with gout.   Fever, chills, and malaise do not distinguish cellulitis or septic arthritis from crystal-  induced arthritis because all 3 illnesses can produce these signs and symptoms. A  careful history may uncover risk factors for cellulitis or septic arthritis, such as possible  exposure to gonorrhea, a recent puncture wound over the joint, or systemic signs of  disseminated infection.   Patients with an acute attack of gout or pseudogout most often present with  involvement of a single joint. However, examine all joints to determine if the patient's  arthritis is monoarticular or polyarticular. Involved joints have all the signs of  inflammation: swelling, warmth, erythema, and tenderness.   The erythema over the joint may resemble cellulitis; the skin may desquamate as the  attack subsides. The joint capsule becomes quickly swollen, resulting in a loss of  range of motion of the involved joint.   During an acute gout attack, patients may be febrile, particularly if it is an attack of  polyarticular gout.   However, look for sites of infection that may have seeded the joint and caused an  infectious arthritis that can resemble or coexist with acute gouty arthritis.   Migratory polyarthritis is a rare presentation. Polyarticular gout commonly involves the  small joints of the fingers and toes, as well as the knees. An inflammatory synovial  effusion may be present. Uncommonly, acute gout may present as carpal tunnel  syndrome.   Chronic arthritis with tenderness and swelling, with or without redness, warmth, or joint  damage, may be present.   Posterior interosseous nerve syndrome has been reported because of elbow  inflammation causing compression of the nerve. In patients presenting with a swollen  elbow and inability to extend the fingers actively, this should be considered. Treatment  with intra-articular steroids has led to resolution of the nerve palsy in a case report.   Although gout typically causes joint inflammation, it can also cause inflammation in  other synovial-based structures such as bursae and tendons. Tophi are collections of  urate crystals in the soft tissues. They tend to develop after about a decade in  untreated patients who develop chronic gouty arthritis. Tophi tend to develop earlier in  women, particularly those receiving diuretics. 
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