Renal function (including urinalysis) Infection-related antiphospholipid antibodies Special cultures for Coxiella, Bartonella and mycoplasma if initial cultures are negative Pre-operative MRSA screen Common sites of infection \200 \200 Prosthetic valves Left-sided structures (>85%) Aortic lesions (55 \200\22360%) \200 Mitra l lesions (25 \200\22330%) \200 Mitral + aortic lesions (15%) \200 Right-sided structur es (10 \200\22315%) Clinical features The clinical features of bacterial endocarditis will depend on a number o f factors including the nature of the underly- ing lesion and the virulence of the infectin g organism. Acute bacterial endocarditis presents as a sudden illness charac- terized by hi gh temperatures, rigors, exhaustion, weakness and collapse. Patients are frequently very un well. Subacute endocarditis tends to present in a more insidious non-spe- ci \201 c manner with symptoms of anorexia, weight loss, fever, myalgia, arthralgia or fatigue. The clinica l features of IE are due to: \200 Treatment IE causes signi \201 cant morbidity and mortality. Prevention is a priority, alt hough early diagnosis and appropriate therapy are essential. Once the diagnosis is establis hed, treatment should be commenced according to local guidance or directed by microbiologic al advice. Treatment should be initiated once blood cultures have been taken, and subsequen tly adjusted once the results are known. Early involvement of cardiolo- gists, microbiologi sts and cardiac surgeons is advisable. The majority of endocarditis is caused by streptococ cal organisms (50 \200\22370%) with S. viridans accounting for half of these; staphylococca l organisms account for 25%, although in IV drug abusers this increases to 60%, with assoc iated increases in fungal and anaerobic organisms, and entero- cocci (10%). Empirical treat ment depends on the likely organism. \200 Bacteraemia/septicaemia \200\224fever, rigors, chills, malaise, anorexia, confusion, arthra lgia. Tissue destruction \200\224valvular incompetence, root and myocardial abscess (20 \200\22340%), prosthetic valve dehis- cence, heart block, cardiac failure. Embolic phenomen a \200\224occur in 50% cases of infective endocarditis resulting in: cerebrovascular accide nt (CVA), acute peripheral limb ischaemia, MI, TIAs, spleen and kidney infarction, PE and m ycotic aneurysms (2 \200\223 15%). Immunological phenomena \200\224splinter hemorrhages (5 \200\223 15%), Osler \200\231s nodes (5 \200\22310%) (tender nodes in pulp of \201 ngerti ps), Janeway lesions (10 \200\22320%) (macules on palms or wrists), vasculitis rash, Roth s pots ( \202 ame-shaped hemorrhages in the retina), arthralgia, nephritis, splenomegaly (30 \200\22350%). Acute onset (often staphylococcal organisms) \200\224flu- cloxacillin (8 \200\22312g IV dai ly in 4 \200\2236 divided doses) plus gen- tamicin (1mg/kg body weight IV 8 hourly, modifie d according to renal function). Gradual presentation (often A-haemolytic streptococcal orga nisms) \200\224penicillin (7.2g IV daily in six divided doses) or ampicillin/amoxicillin (2 g IV 6 hourly) plus gentamicin (1mg/kg body weight 8 hourly IV, modi \201 ed according to renal function). Patients with penicillin allergy, intracardiac prosthesis or suspected MRS A \200\224vancomycin (1g 12 hourly IV, modi \201 ed according to renal function) plus rifa mpicin Table 18.9.1 outlines commonly useful investigations. The diagnosis of IE is based on the c ombination of clinical, microbiological and echocardiographic \201 ndings. De \201 nite IE is diagnosed on (1) pathological criteria where microorganisms are found by culture or h istology in an embolized vegetation, an intracardiac abscess or (2) clinical 309 CHAPTER 18.9 Bacterial endocarditis shock due to valvular heart disease, or those with pros- thetic valve endocarditis. Early i ntervention may be associ- ated with improved outcome. Antibiotic therapy should be continu ed for 4 \200\2236 weeks. Response to treatment should be carefully monitored with repeated evaluation of clinical state and laboratory investi- gations. Table 18.9.2 The Duke classi \201 cation. Major criteria Positive blood culture of organisms known to cause IE from 2 separate blood cultures. Persistently positive blood cultures In 2 blood cultures drawn >12h apart Mortality Overall mortality remains at 20%. Prosthetic valve endo- carditis carries an eve n higher mortality rate (26 \200\22370%). Right-sided endocarditis is usually related to IV drug abuse and carries a more favorable mortality risk at 4 \200\2235%. IE with staphyloco ccal organisms or with fungi have a high associated mortality (50%) when compared with ente ro- cocci (25%) or streptococci (15%). In all of 3 or majority of 4 separate blood cultures with the \201 rst and last drawn ove r 1h apart Evidence of endocardial involvement Positive echocardiographic \201 ndings Mobile intracardiac mass on valve or supporting structures or in the path of a regurgitant jet, or on implanted material. Prophylaxis People with predisposing factors for bacterial endocarditis include those with prosthetic heart valves, previous bacte- rial endocarditis, acquired valvular heart disease with ste- nosis or regurgitation, structural congitential heart disease (excluding fully r epaired atrial and venticular septal defects and patent ductus arteriosous), and hypertroph ic cardio- myopathy. At present antibiotic prophylaxis against infec- tive endocarditis is not recommended for people undergoing dental procedures and other invasive clincial procedu res involving the respiratory, genitourinary (includ- ing urological, gynecological, obstet ric procedures, and childbirth), and the upper and lower gastrointestinal tracts. Recommend ations may change, and it is wise to consult a national formulary. Episodes of infection in those at risk of infective endocardi- tis should be investigated and treated promptly to r educe the risk of endocarditis developing. If a person at risk of infective endocarditis is receiving antimicrobial therapy because they are undergoing a procedure at a site where th ere is a suspected infection, the person should receive an antibiotic that covers organisms that cause infective endo- carditis. Abscess New dehiscence of prosthetic valve or new valve regurgitation Clinical evidence of new valvular regurgitation Positive serology e.g. Q fever, Bartonella spp, Chlamydia Spp Positive identi \201 cation of a microorganism Using molecular biology methods Minor criteria Predisposition Predisposing heart lesion or IV drug abuse Fever Temperature >38.0 C Vascular phenomena Arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conj unctival hemorrhage, Janeway lesions, new \201 nger clubbing, splinter hemorrhages, splen omegaly Immunological phenomena Glomerulonephritis, Osler \200\231s nodes, Roth spots, +ve rheumatoid factor, raised ESR (> 1.5 \227 normal) raised CRP (>100mg/dl) Further reading NICE clinical guideline 64. Prophylaxis against infective endocardi- tis: a ntimicrobial prophylaxis against infective endocarditis in adults and children undergoing i nterventional procedures. March 2008. Microbiological evidence Positive blood cultures but not meeting major criteria (300 \200\223600mg 12 hourly by mouth) plus gentamicin (1mg/ kg body weight 8 hourly IV, mo di \201 ed according to renal function). Surgery is indicated in up to 25 \200\22330% of infections. These tend to be in those with life-threatening congestive HFor This page intentionally left blank 311 Chapter 19 Renal disorders Chapter contents Prevention of acute renal failure 312 Diagnosis of acute renal failure 314 312 M JOANNIDIS Prevention of acute renal failure large RCTs of both non-oliguric and oliguric acute tubular necrosis. A recent study applyin g low-dose BNP (neseritide) conferred preservation of renal function in patients with chron ic kidney disease stage 3 undergoing cardiopulmo- nary bypass surgery. Currently the most p romising preliminary reports exist for the adenosine antagonist theophylline for CIN as wel l as some forms of nephrotoxic AKI such as cisplatin-associ- ated renal dysfunction. A rand omized placebo-controlled trial in neonates with perinatal asphyxia showed a signi \201 - cant increase in creatinine clearance after a single dose of theophylline within the \201 rst hour of birth. Acute kidney injury (AKI) often complicates the course of critical illness and was previous ly considered as a marker rather than a cause of adverse outcomes, it is independ- ently as sociated with an increase in both morbidity and mortality. The major causes of AKI in the I CU include hypoperfusion, sepsis and direct nephrotoxicity, with the common etiology believ ed to be a change in intrarenal haemodynamics with resultant acute tubular dysfunction and oxidant stress. Treatment of established acute renal failure in the ICU entails the use of RRT by means of various modalities, although this therapy itself carries an inher- ent morb idity and risk. Therefore, preventing or minimizing renal injury should confer a benefit to patients. Consequently, several pharmacological interventions have been tried to treat AKI . These interventions can be sepa- rated into measures in \202 uencing renal perfusion and meas- ures modulating intrarenal pathophysiology. Modulation of renal physiology Renal metabolism, tubular obstruction Loop diuretics have be en extensively investigated. They reduce oxygen consumption in the medulla in both animals and healthy volunteers. An RCT performed in established renal failure could not demonstrate improvement in out- come. Application of very high doses of frusemide, on the other hand, significantly increases the risk of serious adverse events such as hearing loss. Optimizing renal perfusion Volume expansion, inotropes, vasopressors Improvement of renal f unction associated with hypovolae- mia may be demonstrated by correcting volume status. The bene \201 cial effect of prophylactic volume expansion has repeatedly been demonstrated f or contrast-induced nephropathy (CIN), with normal saline showing some superiority over hal f-normal saline. Recent investigations indicate additional protection against CIN using iso tonic bicarbonate solutions (i.e. 150mmol/l sodium bicarbonate) compared with normal saline . In addition to the conventional inotropes dobutamine and dopexamine, the use of the new P DE inhibitor with myocardial calcium sensitizer activity, levosimendan, may improve renal f unction in patients with acute decompen- sated HF. Moreover, application of vasopressors in the setting of sepsis-associated AKI has shown some bene \201 t, although studies investi gating this aspect are small and mostly uncontrolled. Oxygen radical damage Several roles have been proposed for reactive oxygen spe- cies under both normal and pathological conditions, with the NAD(P)H oxidase system believed to be piv otal in their formation and instrumental in the development of certain pathophysiological c onditions in the kidney. Under certain circumstances there may be a role for antioxidant su pplementation with agents such as NAC, the antioxidant vitamin E ( -tocopherol), vitamin C (ascorbic acid) and selenium. NAC has been investigated in multiple trials, especially in the setting of CIN. Despite several reports showing prevention of CIN when evaluating this substance, meta- analysis has been inconclusive. Furthermore, NAC was ineffective in other settings of AKI such as major cardiovas- cular surgery or sepsis. Finally, studies of IV NA C in both human volunteers and patients receiving contrast media showed a decrease in serum creatinine which was not re \202 ected by concomitant changes of cystatin C which is cons idered the more sensi- tive marker of early changes in GFR than serum creatinine. Mannitol, an osmotic diuretic with oxygen radical-scaveng- ing properties, has been investigated in randomized trials for the prevention of CIN but proved to be of no bene \201 t compared wi th general measures such as volume expan- sion. Some authors favor mannitol for treatment o f AKI following crush injuries, but there have been no RCTs to substantiate this use of man nitol. Selenium is another antioxidant showing free radical scav- enger properties. Seleniu m supplementation reduces oxi- dative stress, intranuclear factor-B translocation and cytok ine formation, as well as tissue damage, and normal- izes all known selenoenzymes including intracellular glu- tathione peroxidase and thioredoxin reductase. It was thought that sele nium supplementation decreased the requirement for renal rescue therapy, but this \201 nd ing has not been reproduced in a prospective RCT in septic shock. (Selective) renal vasodilators Renal or low dose dopamine, though previously widely used, i s now known to be ineffective in improving renal function though it may cause a diuresis in itially, and in fact may worsen renal perfusion in patients with acute renal failure as det ermined by renal resistive indexes. Despite showing promising results in pilot studies of c ontrast neph- ropathy and sepsis-associated AKI, selective dopamine A1 agonists such as fen oldopam have failed to provide signi \201 - cant nephroprotection in larger studies of eit her early acute tubular necrosis or CIN. Prostaglandins (PGs) have been investigated mainly in the setting of contrast nephropathy. Both PGE and PGI (Iloprost) administered IV result ed in an attenuated rise of serum creatinine after application of contrast media. Major adv erse events such as hypotension as well as \202 ush and nausea at higher doses limit the extensive use of these substances. Natriuretic peptides improve renal blood \202 ow by ca using afferent glomerular dilatation resulting in increased GFR and urinary sodium excretio n. BNPs additionally inhibit aldosterone. Atrial natriuretic peptide (ANP) has been used in small human studies and shown to attenuate the rise in serum creatinine in ischaemic renal failure or in AKI after liver transplantation, but it has been ineffective in 313 CHAPTER 19.1 Prevention of acute renal failure basis of current evidence they can only have a weak recommendation. Adequate haemodynamic m anagement by volume expansion and vasopressors/inotropes and some renal vasodilators such a s theophylline are all rea- sonable interventions that may be employed in the preven- tion of AKI. Cocktails of antioxidants have been investigated in several small studies showing con \202 icting results. In one rand- omized trial in patients undergoing elective aortic aneu- rys m repair, use of an antioxidant cocktail resulted in an increased creatinine clearance on t he second post- operative day, but the incidence of renal failure was very low. Ascorbic ac id given orally 2h pre-contrast in a single-center trial appeared to protect against the de velopment of CIN. Further reading Abassi ZA, Hoffman A, Better OS. Acute renal failure complicating muscle crush injury. Semin Nephrol 1998; 18: 558/ Renal regeneration and repair Since the duration of AKI may be signi \201 cantly in \202 uenced by the time renal (tubular epithelial) cells need for regen- eration, several growth hormones including insulin-like growth factor (IGF-1), hepatocyte growth factor (HGF) and endothelial growth factor (EGF) have been investi- gated with limited success in animal exp eriments. However, investigations in established renal failure in humans did not demonstrat e a signi \201 cant improvement in renal recovery. Also a multi-center PRCT in 72 patients with acute renal failure similarly failed to show an effect of IGF-1 on renal recovery. Er ythropoietin (EPO) not only stimulates erythroid pro- genitor cells but it is also a tissue -protective cytokine that mediates local antiapoptosis and differentiation-inducing effects in response to injury. Animal data do suggest a renoprotective effect of EPO in both ischa emic and toxic acute renal failure, and human studies are currently being undertaken. Angstwurm MW, Engelmann L, Zimmermann T, et al. Selenium in Intensive Care (SIC): results o f a prospective randomized, pla- cebo-controlled, multiple-center study in patients with se vere systemic in \202 ammatory response syndrome, sepsis, and septic shock. Crit Care Med 2007; 35: 118 \200\22326. Bagshaw SM, Ghali WA. Theophylline for prevention of contrast- induced nephropathy: a syste matic review and meta-analysis. Arch Intern Med 2005; 165: 1087 \200\22393/ Briguori C, Airoldi F, D \200\231Andrea D, et al. Renal insuf \201 ciency following contra st media administration trial (REMEDIAL): a randomized comparison of 3 preventive strategie s. Circulation 2007; 115: 1211 \200\2237. Spargias K, Alexopoulos E, Kyrzopoulos S, et al. Ascorbic acid prevents contrast-mediated n ephropathy in patients with renal dysfunction undergoing coronary angiography or interventi on. Circulation 2004; 110: 2837 \200\22342. Wijnen MH, Vader HL, Van Den Wall Bake AW, et al. Can renal dysfunction after infra-renal a ortic aneurysm repair be modi \201 ed by multi-antioxidant supplementation? J Cardiovasc S urg 2002; 43: 483 \200\2238. Conclusion Pharmacologicalo prevention and treatment of AKI have been shown to have very li mited success, and on the 314 M JOANNIDIS Diagnosis of acute renal failure Acute renal failure is characterized by an abrupt deteriora- tion in renal function usually manifested as a drop in GFR and/or urine output. More than 30 de \201 nitions of acute re nal failure do exist, and most of them relate to absolute or relative changes in serum crea tinine. However, acute renal failure should be rather regarded as the end-point of a contin uum of dete- riorating renal function called AKI. In 2004, the RIFLE crite- ria were establ ished by the Acute Dialysis Quality Initiative (ADQI). On the basis of either increase of s erum creati- nine or reduction in urine output as a sensitive marker of renal dysfunction, acute renal injury is classi \201 ed into risk, injury and failure, with two additional cl asses loss and ESKD (end-stage kidney disease) defined by the requirement for RRT for >4 we eks and >3 months, res- pectively (Table 19.2.1). RIFLE relies on prior knowledge of the ba seline creatinine. The requirement for RRT has not been explicitly de \201 ned, although i t was discussed in the original ADQI document. The major problem with RIFLE is lack of a de \201 ned time fame in which an increase in serum creatinine should occur to be classi \201 ed as \200\230acute \200\231. To overcome this problem, a modi \201 ed RIFLE classi \201 cation was proposed in 2007, where determination of at least 2 serum creatinine value s within an observation period of 48h was suggested. An increase in serum creatinine of >0. 3 mg/dl or of at least 150% was required for diagnosis of AKI (resulting in RIFLE risk or s tage 1, respectively). Further classi \201 cation was performed according to relative incr ease in serum creatinine (Table 19.2.1). Finally, the requirement for RRT was considered to be classified as RIFLE failure (or AKI stage 3). Although initially not designed as an out come predictor, several studies valid- ated RIFLE with respect to severity of AKI and impai red survival. Characterization of acute renal failure into pre-renal azotaemia, renal failure and post-re nal obstruction is not explicitly discussed in current acute renal failure/AKI clas- si \201 cation systems. It appears that in critically ill patients especially, the discriminat ion between pre-renal azotemia and so called acute tubular necrosis (ATN) appears to be nei ther represented by histological \201 ndings nor relevant in terms of pathophysiology. Ne vertheless, exclusion of post- renal obstruction as a \201 rst step and discrimination be tween volume-responsive AKI and volume-unresponsive AKI is still of clinical relevance in d aily practice and should be continued. Parameters of glomerular function Serum creatinine Loss in GFR is re \202 ected by an incr ease in serum creatinine. Cystatin C Cystatin C is a small (13kDa) molecule produced by nucle- ated cells and freely \201 ltered by the glomerulus. Due to its small volume of distribution, small chages in G FR are re \202 ected by an increase in cystatin C. Cystatin has been evaluated in patients , in whom reduced muscle mass results in a falsely low serum creatinine value, e.g. patient s with liver cirrhosis. Urine analyzes Urinary sediment Urinary analysis is only of limited value for diagnosis of acute renal failure in critically ill patients. However, urinary sediment is still helpful in the differential diagnosis of renal impairmentn discriminating acute renal failure from other acute glomerular diseases (e.g. rapidly progressive glomer- ulonephtis, acute interst itial nephritis; see Table 19.2.2). \200\230Muddy brown casts \200\231 or tubular cells ma y be indicative of acute renal failure (so-called acute tubular necrosis); how- ever, a ben ign sediment does not exclude ARF. Leucocyturia, especially eosinophiluria is usually attri buted to acute interstitial nephritis. Table 19.2.1 Modi \201 ed RIFLE according to AKI stage. Stage Creatinine criteria Urine output criteria Table 19.2.2 Urinary analysis for AKI/acute renal failure. <0.5ml/kg/h for >6h Serum creatinine >0.3mg/dl (>26.4 mol/l) or increase to \211 150 \200\223 200% (1.5- to 2 -fold) from baseline AKI stage 1 (modi \201 ed RIFLE risk) Pre-renal azotaemia Acute renal failure (ATN) Glomerular disease (e.g. GN) Urinary sediment Benign \200\230Muddy brown \200\231 casts Tubular epithelial cells Nephritic (erythrocyte casts) <0.5ml/kg/h for >12 h AKI stage 2 (modi \201 ed RIFLE injury) Increase serum creatinine to >200 \200\223 300% (>2- to 3-fold) from baseline Urinary osmolality >500 <350 ? <0.3ml/kg/h x24 h or anuria x12h Increase serum creatinine to >300% (>3- fold) from baseline (or serum creatinine \211 4.0m g/dl ( \211 354 mol/l with an acute rise of at least 0.5mg/dl (44 mol/l) AKI stage 3 (modi \201 ed RIFLE failure)* Urinary sodium <10mmol/l >20mmol/l ?/low >40 <20 ? Urine/S- creatinine ratio >40:1 20 \200\22330:1 <40:1 S-urea/ creatinine ratio FENa FEUrea <1% >2% ? Individuals requiring RRT are considered to be classi \201 ed as stage 3 (modi \201 ed RI FLE failure). <35% \211 35% ? ATN = acute tubular necrosis; FE = fractional excretion; GN = glomerulonephritis 315 CHAPTER 19.2 Diagnosis of acute renal failure NHE-3 (sodium/hydrogen exchanger Isoform 3), a mem- brane-bound protein is also found in th e urine in ischaemic acute renal failure. Finally IL-18 was found to predict mortality in p atients with ARDS and acute renal failure. Urinary electrolytes Reduced urinary sodium and urea excretion may be diag- nostic of renal hypoperfusion. The calculation of fractional sodium excretion (FENa) or FEUrea (see below) is recom- mended, with values <1% and <35%, respectively, being considered as indicative f or renal hypoperfusion. Whereas FENa is increased despite hypoperfusion when using diuret- ics, FEUrea is not in \202 uenced by medical natriuresis. Neither of these parameters, how ever, can be considered reliable in sepsis. Neither decreased FENa nor FEUrea can be used t o rule out acute renal failure reliably. Fractional sodium/urea excretion Ultrasound Renal ultrasound is helpful in excluding post-renal obstruc- tion. Furthermore, it helps to discriminate acute damage from chronic damage kidneys. Acute renal failure typi cally is associated with bilaterally enlarged kidneys showing moderately enhanced parenchym al density. Chronically damaged kidneys are small, with clearly increased paren- chymal den sity. Acute renal failure is furtter characterized by increased resis- tive indices as dete rmined by Doppler- \202 ow measurements. UNa* PCr PNa* UCr FENa (%)* = 100 For FEUrea, use urea values instead of sodium. FENa: pre-renal if <1% FEUrea: pre-renal if <35% Further reading Abosaif NY, Tolba YA, Heap M, et al. The outcome of acute re- nal failure i n the intensive care unit according to RIFLE: model application, sensitivity, and predictab ility. Am J Kidney Dis 2005; 46: 1038 \200\22348. Biomarkers Several biomarkers have been investigated in terms of their usefulness to predic t acute renal failure earlier than stand- ard parameters. These are either enzyme activitie s of enzymes released by tubular cells or surface proteins only present in renal tubular ce lls: The release of (large molecular) proteins from renal epi- thelial damage has been used for early diagnosis of renal tubular damage for decades. The ost widely applied enzyme was N-acetylglucosaminidase (NAG) also successfully investigated in critically ill patients. D etermination, how- ever, is costly and mostly not automated. Neutrophil gelatinase-associat ed lipocalin (NGAL) is a 25kDa protein which is released in the kidney after ischae- mia. I n cardiac surgery in children and adults it can predict acute renal failure 24h earlier tha n creatinine . KIM-1 is a surface protein expressed in proximal tubular cells in ischaemia. In humans it has been shown to be secreted in ischaemic renal failure. Both KIM-1 and NAG may be predictors for requirement for RRT. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure \200\224 de \201 nition, outcome measures, animal models, \202 uid therapy and information technology needs: the Second I nternational Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Cr it Care 2004; 8: R204 \200\22312. Herget-Rosenthal S, Marggraf G, Husing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int 2004; 66: 1115 \200\22322. Kellum JA, Levin N, Bouman C, et al. Developing a consensus classi \201 cation system for acute renal failure. Curr Opin Crit Care 2002; 8: 509 \200\22314. Uchino S, Bellomo R, Goldsmith D, et al. An assessment of the RIFLE criteria for acute rena l failure in hospitalized patients. Crit Care Med 2006; 34: 1913 \200\2237. Parikh CR, Abraham E, Ancukiewicz M, et al. Urine IL-18 is an early diagnostic marker for a cute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol 2005 ; 16: 3046 \200\22352. This page intentionally left blank 317 Chapter 20 Gastrointestinal disorders Chapter contents Vomiting and gastric stasis/gastroparesis 318 Gastric erosions 320 Diarrhea 322 Upper gastr ointestinal hemorrhage (non-variceal) 324 Bleeding varices 326 Intestinal perforation 328 I ntestinal obstruction 330 Lower gastrointestinal bleeding 332 Colitis 334 Intra-abdominal s epsis 336 Pancreatitis 338 Acute acalculous cholecystitis 340 Splanchnic ischaemia 342 Abdo minal hypertension (IAH) and abdominal compartment syndrome 344 318 M BOOTH Vomiting and gastric stasis/gastroparesis Clinical features Nausea usually precedes vomiting, and is generally associ- ated with impa ired gastric motility. Retching follows \200\224the glottis remains closed and abdominal mu scles and the dia- phragm contract. Finally, the cardia relaxes and sustained contraction o f the abdominal muscles produces vomiting. In surgical abdominal complaints, pain usually p recedes vomiting, whereas the opposite is often the case with med- ical causes. (80% females), but risk factors for secondary gastroparesis include: \200 \200 type 1 diabetes abdominal surgery (vagotomy, fundoplication, bariatric surgery, heart/lung transplantation) hypothyroidism rheumatological disorders (e.g. scleroderma, SLE, amy- loid osis) \200 Evaluation \200 Causes These are legion, but include: \200 Gastric scintigraphy: gold standard for diagnosis. Performed after ingestion of a radiolabe lled meal (usu- ally 99mTc sulfur colloid cooked into test meal). Percentage radiolabel ret ention at 2 \200\2234h is compared with norms. Prokinetic agents, opiates and anticholiner- gics should be discontinued 48 \200\22372h prior to test, although serotonin receptor anta gonists (e.g. ondanset- ron) can be continued. Despite widespread use, correla- tion with s ymptoms (both pre- and post-treatment) is poor. Any GI disorder, including intestinal obstruction (chronic vomiting without other abdominal symptoms is unlikely to be due to GI disease). Acute viral infections, e.g. in \202 uenza , Epstein \200\223Barr virus, cytomegalovirus. Neurological disorders, e.g. raised ICP, men ingitis, migraine, vestibular disturbances. Metabolic disorders, e.g. uraemia (although unl ikely to be cause if blood urea <30mmol/l), hypercalcaemia, dia- betic ketoacidosis. Drugs, e.g. opiates, cytotoxics, digoxin toxicity Pregnancy Psychogenic Post-surgery, especially gastric. Alcohol excess. Other means of evaluation are not widely available, but include:- \200 \200 \200 \200 \200 Antroduodenal manometry: performed using nasogas- troduodenal manometry probes in the fasti ng and post- prandial periods. Typically there is a loss of antral contractility. Fasting m igratory motor complexes are seen to originate from the small intestine, rather than from t he stomach. Electrogastrography: cutaneous electrodes on the abdominal wall record gastric myoelectrical activity. Normal gastric slow wave frequency is 3 counts/min. Deemed abnorma l if dysrhythmias occur >30% of recording time, or solid meal ingestion fails to increase w ave amplitude. Ultrasound: antral cross-sectional area used to assess gastric emptying. Non -invasive, but highly operator dependent. Evaluation \200 History: important to differentiate vomiting from other, apparently similar entities, such as regurgitation, rumina- tion, bulimia. Careful examination of patient (and drug chart). F luid balance: signs of dehydration. Electrolyte/acid \200\223base status: vomiting can caus e hyponat- raemia (excessive sodium losses in vomitus) or hypernat- raemia (unreplaced loss es of hypotonic GI \202 uids). Loss of H+ and Cl \200\223 produces hypochloraemic alkalos is. K+ loss in the urine in exchange for H+ exacerbates hypokalae- mia. Treatment usually r equires IV normal saline with potassium supplements to correct chloride and potas- sium de \201 cits. \200 \200 Management The management of gastroparesis is often disappointing and ineffective, but the following can be tried: 1 Dietary manipulation: frequent, small meals. Replace solids with soups (liquid emptying phase often pre- served), low fat/ \201 bre foods. Investigations \200 \200 \200 \200 \200 2 Optimize glycaemic control: hyperglycaemia alone can cause delayed gastric emptying in di abetic patients (although no long term studies to con \201 rm symptom improvement with enh anced glycaemic control). Routine bloods (including amylase, calcium) Arterial blood gasses Pregnancy test Plain \201 lms: exclude intestinal obstruction. Oesophagogastroduodenoscopy: exclude peptic ulcer disease, malignancy. Barium series: exclude obstruction, superior mesenteric artery syndro me. Biliary ultrasound 3 Antiemetics: Antidopaminergics, e.g. prochlorperazine. Act cen- trally on medulla oblongata (CTZ). Can b e given in suppository/injectable form as well as orally. Antihistamines, e.g. diphenhydram ine. Act centrally on vestibular apparatus, and more often used for motion sickness. Antich olinergics, e.g. hyoscine. Serotonin (5-HT3) receptor antagonists, e.g. ondanset- ron. Act centrally and on peripheral vagal afferents. Generally used as prophylaxis for chemotherapy /radi- otherapy0induced vomiting, and post-operative symp- toms. Role in gastroparesis less clear. Gastroparesis De \201 ned as a symptomatic, chronic disorder characterized by delayed gast ric emptying and the absence of mechanical obstruction. Symptoms include early satiety, nau sea, vomit- ing, bloating and upper abdominal discomfort. Gastric food retention can lead t o bezoar formation. May be idiopathic \200 319 CHAPTER 20.1 Vomiting and gastric stasis/gastroparesis 4 Prokinetics: of medication, provided small bowel motility is pre- served. A trial period of NJ feeding i s sensible prior to jejunostomy placement. Gastrostomy tubes can assist in symptom control by allowing venting and draining of the stomach. Again the results of initial nasogastric d ecom- pression can help predict outcome. Metoclopramide: has prokinetic effects on proximal gut via 5-HT4 agonist and weak 5-HT3 ant agonist action. Also central dopamine receptor antagonist, giv- ing antiemetic effect. Loss of effectiveness with time and high incidence of CNS side effects (dystonias, drowsiness, Parkinsonism) limit use to the short term. Domperidone: peripheral D2 receptor antagonist w ith similar prokinetic effects to metoclopramide, but less able to cross blood \200\223brai n barrier, therefore fewer CNS side effects. Improvements in gastric emptying may be transi tory, with continued symptomatic relief being due to additional antiemetic properties. Eryt hromycin: macrolide antibiotic that acts via gas- troduodenal motilin receptors, enhancing antral con- tractility. Most effective when given IV in severe refractory gastroparesis. GI side effects (nausea/vom- iting/abdominal pain) can limit clinical effectiveness. Tegasero d: partial 5-HT4 agonist. Enhances gastric emptying in healthy volunteers, but little evide nce for effectiveness in gastroparesis. Cisapride: 5-HT4 agonist with proven long-term effe c- tiveness in increasing gastric emptying and improving symptoms. Withdrawn from market, h owever, due to action on cardiac potassium channels, leading to case reports of prolonged Q T interval, cardiac arrhythmias and sudden death. Can still be prescribed on a named patien t basis, provided there is no history of conduc- tion defects or concurrent medications kno wn to affect the QT interval. 2 Pyloric botulinum toxin: the increased pyloric tone seen in diabetic gastroparesis can be reduced (for a number of months) by pyloric botulinum toxin injection, but there are few s tudies as yet to support clinical effectiveness. 3 Gastric stimulation: electrodes are attached to the stomach at laparoscopy/laparotomy, an d connected to a subcutaneous electrical stimulator. Gastric pacing uses stimulation at a r ate slightly higher than the intrinsic slow wave frequency ( 3 contractions/min) thus entra in- ing gastric slow waves and accelerating gastric emptying. High frequency stimulation (1 2 contractions/min) has no effect on gastric emptying, but does appear to improve symptoms of nausea and vomiting. Currently the most effective combinations of stimulation parame- te rs remain unde \201 ned. Promising symptomatic improve- ments have been reported, mainly i n diabetic and idiopathic gastroparesis, but more experience is required. Further reading Lin Z, Forster J, Sarosiek I, McCallum RW. Treatment of gastropare- sis with electrical stimulation. Dig Dis Sci 2003; 48: 837 \200\22348. Parkman HP, Hasler WL, Fisher RS; American Gastroenterological Association. American Gastro enterological Association technical review on the diagnosis and treatment of gastroparesis. Gastroenterology 2004; 127: 1592 \200\223622. For those patients with symptoms refractory to dietary manipulation, antiemetics and prokin etics, the following can be considered: 1 Enteral feeds/gastrostomy: placing a jejunostomy can be effective, both for nutrition and for the administration 320 I RECHNER Gastric erosions 2 H+/pepsin/bile seep in and damage intracellular compo- De \201 nition Varies from mild erosions to ulcerations of the gastric mucosa. nents 3 Mucosal necrosis leads to ulcer formation Pepsin is still active unless pH >7 1 pH 5 \200\2237: pepsin still dissolves clot 2 pH <5. 4: pepsin prevents clot formation NB: alkaline gastric contents are not necessary for preve n- tion, and there is no evidence that hypersecretion of pep- sin per se is responsible for erosions Epidemiology Found in patients with a critical illness, which can effect all ages and occur in acute and chronic disease states. Incidence The incidence quoted in the 1980s is below. The true inci- dence now is dif \201 cult to determine, but the perception is that it is very much less than it used to be. 1 E rosions 40 \200\22350% 2 Ulcers 5% 3 Macroscopic/clinically relevant bleeding <2% Intracellular pH is probably more important than intragastric pH Prostaglandins result in 1 Increased blood \202 ow 2 Increased mucus production, and possibly mucus secretion 3 Dec reased ulcer incidence and promotion of healing Risk factors 1 Previous ulcer disease 2 Coagulopathy 3 Mechanical ventilation >48h 4 Previo us factors (now questioned): head injury, multiple trauma, severe burns, sepsis/SIRS, hypot ension, hypovol- aemia, renal failure, hepatic failure Bile salt Causes disruption of the mucosal barrier to occur, and pre- vention of duodenal r e \202 ux is associated with signi \201 cant reduction in gastric ulceration. Prevention Prophylaxis Gastric pH control, cytoprotective drugs, nutrition. Acid/pepsin production reduced by Mucosal resistance increased by Enteral feeds Enteral feeds Reduced incidence is also probably due to: 1 Better ICU management 2 Better oxygen and \202 uid management 3 Early NG feeding 4 Improved analgesia 5 Treatment of coagulopathy Prostaglandins ?Prostaglandins Antacids Sucralfate H2 blockers Pathology The site is usually the fundus and body, rarely in the antrum, duodenum or esopha gus 1 Mucosal ulceration: super \201 cial, eroding through to the muscularis mucosae only, little bleeding and heals rapidly. 2 Acute peptic ulceration: deep, through the muscular l ayer where the larger arteries reside, greater bleeding and slower to heal. Treat stress factors \200 \200 \200 Improve gut oxygen delivery Normovolaemia, adequate oxygenation and ventilation Maximize ca rdiac output and GI pressure Nasogastric feeds as soon as possible Especially high risk groups \200 \200 \200 \200 Head injury, major trauma, burns Prolonged IPPV Renal failure, hepatic failure Sepsis Factors which in \202 uence the risk of hemorrhage 1 Aspirin, NSAIDs, steroids 2 Alcohol 3 Anticoagulants and dextrans 4 Vitamin K de \201 ciency and platelet defects 5 Vasoconstri ctors Sucralfate or H2 blocker where \200 \200 NG aspiration of blood/ \200\230coffee ground \200\231 Previous peptic ulcer disease Omeprazole \200 \200 Local defense mechanisms include 1 The mucus barrier 2 Surfactants AND HCO3 secreted by muc osa 3 H+ reabsorbed by the mucosa is neutralized by blood- Clinical bleed on H2 blockers Endoscopically proven ulceration not healing with H2 blockers derived HCO3 Shock states result in 1 Mucosal ischaemia Treatment: mild bleed Maximize coagulation status/remove precipitants 1 Vitamin K 2 Stop he parin, NSAIDs other anticoagulants 3 Blood transfusion, FFP, platelets or other procoagulan ts TNF causes thrombosis within the gastric mucosal vessels Sympathetic redistribution of bloo d \202 ow away from the splanchnic bed Antacids Get pH >3.5 (ideally >7). 321 CHAPTER 20.2 Gastric erosions