Treatment The therapeutic approach of HAP/VAP must be patient- based and institution-speci \201 c. Empirical treatment choice must be guided by characteristics of patients, local pa ttern of antimicrobial resistance and direct staining of respiratory samples. Initial empir ic therapy for HAP/VAP according to time to onset and presence of risk factors Onset Pathogens Antibiotic therapy S. pneumoniae H. in \202 unzae MSSA Enterobacteriaceae GNB MDR P. aeruginosa K. pneumoniae Acinetobacter baumannii Early onset without risk factors Ceftriaxone or Quinolone or Ampi/sulbactam or Ertapenem Antipseudomonal cephalosporin or An tipseudomonal carbapenem or Piperacilin/tazobactam and quinolone or aminoglycoside \200 Late onset or with risk factors for MDR pathogen Further reading American Thoracic Society. Guidelines for the management of adults with hos pital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Cri t Care Med 2005; 171: 388 \200\223416. MRSA Linezolid or vancomycin Canadian Critical Care Trial Group. A randomized trial of diagnostic techniques for ventila tor-associated pneumonia. N Engl J Med 2006; 355: 2619 \200\22330. Key points \200 Empirical antibiotic choice driven by local micro- biological data Data demonstrate an impo rtant variability in pathogens in different centers and different ICUs. Prompt initiation o f appropriate antimicrobial treatment Appropriate initial antibiotic treatment is associate d with better outcomes in HAP/VAP patients. The shorter the delay in starting empirical tre atment, the better the impact on prognosis, LOS and cost. Appropriateness of antimicrobial treatment (dose, pharmacokinetics/dynamics considerations, tissue penetration) Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for v entilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588-98. Rello J, S -Borges M, Correa H, et al. Variations in etiology of ventilator-associated pne umonia across four treatment sites: implications for antimicrobial prescribing practices. A m J Respir Crit Care Med 1999; 160: 608 \200\22313. Rello J, Vidaur L, Sandiumenge A, et al. De-escalation therapy in ventilator-associated pne umonia. Crit Care Med 2004; 32:2183 \200\22390. Resar R, Pronovost P, Haraden C, et al. Using a bundle approach to improve ventilator care processes and reduce ventilator- associated pneumonia. Jt Comm J Qual Patient Saf 2005; 31: 243 \200\2238. 280 B MADDEN Pulmonary hypertension De \201 nition Pulmonary hypertension is said to occur when the mean pulmonary artery pres sure exceeds 25mm Hg at rest or 30mm Hg with exercise. The term pulmonary arterial hyperten sion (PAH) denotes a series of apparently unre- lated disorders which share the histopathol ogical entity of plexogenic pulmonary arteriopathy (PPA). Examples include idiopathic PAH, familial PAH and pulmonary hyper- tension associated with scleroderma, hepatic cirrhosis, H IV infection and Eisenmenger \200\231s syndrome. In addition, pulmo- nary hypertension can occur in association with cardiac diseases (left heart failure, mitral valve disease), resp iratory disorders (emphysema, pulmonary \201 brosis), pulmonary thromboembolic disease an d various miscellaneous conditions. Although these latter conditions are more common causes of pulmonary hypertension, the severity of pulmonary hypertension is usually less than tha t seen in PAH and the histopathology is not PPA in nature. Idiopathic PAH was typically des cribed in young females, although with increasing awareness the condition is now being diag nosed in patients beyond the 4th and 5th decades of life. The incidence and prevalence of t he condi- tion is estimated to be 4 per million and 10 per million of the population, respe ctively. The prevalence of PAH is estimated to be in the region of 100 per million of the p opulation. The incidence and prevalence of pulmonary hypertension in patients with cardiac and respiratory disorders are not precisely known, although they are believed to be conside rably higher than for PAH. 5 Miscellaneous \200 Histiocytosis Lymphangioleiomyomatosis PAH is associated with a poor survival and a poor quality of life. There is no cure, limite d treatment options and incomplete understanding of the disease. Pathology PPA occurs in a select group of disorders. The reason why this pathological entit y occurs is not clear, although it is possible that the lung only has a \201 nite number of responses to injury which feed into \201 nal common pathway mecha- nisms. This may exp lain why similarities occur in patients with conditions such as obliterative bronchiolitis following lung transplantation and those with obliterative bronchiolitis associated with rh eumatoid disease or respiratory syncytial virus infection in childhood. Likewise, although many condi- tions have been implicated as causing ARDS, the pathology is similar regardless of etiology. In PPA there is initial vasocon- striction and subsequent smooth muscle migra tion from the inner half of the media of muscular pulmonary arterioles into the lumen to be come myo \201 broblasts capable of laying down either smooth muscle or \201 brous tissue . The cells pro- liferate in a concentric fashion and ultimately obliterate the lumen. When sectioned, the vessels have the appearance of a cut onion, hence the term onion skin proli feration. As the radius gets progressively compromised, the resistance to \202 ow increas es. At points of weakness in the vessel (proxi- mally at branching areas) the vessel disten ds and ruptures. Hemorrhage occurs and primitive blood vessels grow into this area in a hap hazard or plexiform arrangement. The combination of concentric laminar intimal (onion skin) pro- liferation and plexiform lesions is referred to as PPA. Some authors believe that ple xiform lesions may represent a form of collateral irculation. Why these particular changes occur in diseases with such diverse etiology and clinical presentation is not under- stood. Immunoreactive cells in the lung for gastrin-releasing peptide and calcitonin may be impor tant factors in smooth muscle migration. There is extensive ongoing research into endotheli al dysfunction in patients with PAH. Pulmonary h9ypertension Diagnostic classi \201 cation (World Congress on Pulmonary Hyperte nsion Venice 2003) 1 Pulmonary arterial hypertension (PAH) \200 \200 Idiopathic PAH Familial PAH Related to \200 \200 \200 \200 \200 Pulmonary capilla ry haemangiosis Pulmonary veno-occlusive disease Others (e.g. glycogen storage disease, spl enectomy) Connective tissue diseases HIV Portal hypertension Anorexigens Congenital heart diseases Survival PAH carries a poor prognosis, and for those patients with class IV New York Heart Association (NYHA) status, the 5-yr actuarial survival is signi \201 cantly lower than tha t for patients with lung, breast, prostate, colon and gastric carcinoma. A median survival of 2.8yrs has been reported for untreated patients in class III or IV NYHA. Survival and qu ality of life have improved for selected patients treated with agents such as endothelin re ceptor antago- nists, prostacyclin analogs and PDE inhibitors. \200 \200 2 Associated with left heart disease Atrial or ventricular dysfunction Valvular disease \200 3 Associated with lung disease/hypoxaemia \200 \200 \200 \200 COPD Interstitial lung diseases Sleep-disordered breathing Developmental abnormalities Chro nic exposure to high altitude Prognostic factors The following factors are useful in predicting mortality in PAH: 1 Etiol ogy 2 Functional capacity (NYHA or PAH class) 3 Exercise capacity (unencouraged 6min walk t est) 4. Haemodynamics (severity of RV dysfunction) 5 Echo parameters (pericardial effusion carries worse 4 Associated with chronic thrombotic and/or embolic disease \200 \200 \200 Obstruction of proximal pulmonary artery Obstruction of distal pulmonary artery Non-thrombo tic pulmonary emboli prognosis). 281 CHAPTER 17.17 Pulmonary hypertension Quality of life Patients with PAH have similar quality of life scores when compared with th ose for patients with chronic obstructive lung disease and end-stage renal failure. Patients with NYHA functional class II and IV should be evaluated for bilateral lung transp lantation. Some patients with chronic thromboembolic pulmonary hypertension may be candidat es for pulmonary thromboendarterec- tomy. Atrial septostomy has been used to palliate patie nts with advanced PAH due to its potential to decompress the failing right ventricle and im prove cardiac index. Natural history Early on, patients with pulmonary hypertension may be asymptomatic or exhib it dyspnoea with exertion. In the early stages of the disease, the non-speci \201 c nature of the symptoms may lead to either failure of diagnosis or incorrect diagnosis. Many patie nts have had their symptoms attributed to depression. As the condition progresses, the PVR rises and the cardiac output falls. At this stage, patients may change from having relative ly few symptoms to experiencing dysp- noea, chest pain, palpitations or syncope with exerti on and subsequently at rest. As the condition progresses further, right heart failure and d eath occur. Median survival from diagnosis if NYHA functional class III or IV and untreated is 2.8yrs. Genetic aspects Disease-causing mutations in bone morphogenetic protein receptor II (BMPR2) may underlie familial PAH. Mutations have been detected in 55% of families, and show autos omal dominance with incomplete penetrance. Thus far up to 26% of sporadic cases (idiopathic PAH) have BMPR2 muta- tions. BMPs are a family of secreted growth factors. BMPR2 regulates cell proliferation in response to ligand binding. Mutations lead to a loss of the inhibito ry action of BMP on vascular smooth muscle cell growth. As a consequence, inappropriate cel lular proliferation can occur. Current theories on the pathophysiology of pulmonary hypertension Patients may have a genet ic predisposition (e.g BMPR2 mutation) or have a risk factor such as autoimmune disease or HIV, and this facilitates vascular injury. When vascular injury occurs, endothelial cell dy sfunction follows and can give rise to in \202 ammation and loss of local vasoreactivity, and facilitate thrombus formation. Smooth muscle cell dysfunction can also occur independen tly. As a consequence, disease progression and vascular remodeling ensue. Therapeutic targets Abnormalities in endothelial function with respect to vaso- reactivity, intimal proliferation and thrombus formation are believed important in the pathogenesis of this condition. Increasing attention has been given to endothelin 1 (which causes vasocons triction and cellular proliferation), NO (which via cGMP promotes vasodilatation and is ant iprolif- erative) and prostacyclin (which, acting via cAMP, also potentiates vasodilatation and is antiproliferative). NO or prostacyclin analogs are important in managing patients w ith this condition, as are endothelin receptor antagonists. Recently attention has focused on PDE type 5 inhibitors. Summary PAH is a progressive and lethal disease whose initial symp- toms can be non-speci \201 c. A comprehensive diagnostic approach is required to identify associated conditions a nd characterize haemodynamics and functional profiles. Although at present there is no cure for PAH, it is hoped that increasing awareness and understanding of disease mechanisms wil l facilitate the development of effective treatment modalities. Therapeutic options Current drugs available have improved quality of life and prolonged sur vival for some patients with PAH. Drug therapy can be given orally, e.g. Sildena \201 l (a PDE type 5 inhibitor) or Bosentan (endothelin A and B receptor antag- onist), by inhalatio n (prostacyclin), SC (prostacyclin ana- logues) and IV (prostacyclin). Other treatment opti ons include atrial septostomy and lung transplantation. A small number of patients (<10%) w ill respond to calcium channel blockers. These patients will have demonstrated a positive v ascular reactivity test at cardiac catheterization where the pulmonary artery pressure can be reduced to close to nor- mal values following administration of agents such as NO with a n increase in or unchanged cardiac output. Other therapeutic agents being considered includ e lipid-lowering drugs, anti-in \202 ammatory agents, monoclonal antibodies and antiplatel et agents. Further experience with these therapies is awaited. Further reading ACCP. Evidence-based clinical practice guidelines. Diagnosis and management of pulmonary arterial hypertension. Chest 2004; 126: S1 \200\22392 Madden BP, Sheth A, Wilde M, et al. Does Sildena \201 l produce a sustained benefit in pat ients with pulmonary hypertension associated with parenchymal lung and cardiac disease? Vas cul Pharmacol 2007; 47: 184 \200\2238. This page intentionally left blank 283 Chapter 18 Cardiovascular disorders Chapter contents Hypertension 284 Tachyarrhythmias 288 Bradyarrhythmias 290 Myocardial infarction: diagnosis 292 NSTEMI 294 STEMI 296 Acute heart failure: assessment 300 Acute heart failure: manageme nt 304 Bacterial endocarditis 308 284 T ANTONIOS Hypertension De \201 nition Hypertension is de \201 ned as sustained SBP \211 140mm Hg and/or DBP \211 90mm Hg (Table 18.1.1). In the UK, the prev- alence of hypertension is 32%. Of these, only 22% have controlled BP (<140/90mm Hg). Essential (primary) hyper- tension accounts fo r 80 \200\22390% of cases. Secondary causes of hypertension include renal and endocrine dis orders and drug-induced hypertension (Table 18.1.2). Treatment of uncomplicated essential hypertension First-line therapy Young non-black indivi duals tend to have higher activity of the renin \200\223angiotensin \200\223aldosterone sys tem (RAAS) as evi- denced by higher plasma renin activity (PRA). They respond well to angio tensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), wher eas those with a low PRA, i.e. the elderly and black individuals, respond better to either calcium channel blockers (CCBs) or diuretics (Fig. 18.1.1). Table 18.1.1 BHS de \201 nitions of hypertension SBP DBP Drug combinations BP control on monotherapy is rarely achieved. The most effective way to c ontrol BP is to combine 2 or more antihypertensive agents that lower BP by different mechan isms. ACE inhibitors and ARBs (A) combine well with CCB (C) and diuretics (D). This gives r ise to the A/CD rule for combining drugs, in which a drug from A group is added to another from either the C or D groups (Fig. 18.1.1). The next step is to add a drug from each group : A + C + D. Optimal BP <120 <80 Normal BP <130 <85 High \200\223normal blood pressure 130 \200\223139 85 \200\22389 Grade 1 hypertension (mild) 140 \200\223159 90 \200\22399 Grade 2 hypertension (moderate) 160 \200\223179 100 \200\223109 Grade 3 hypertension (severe) >180 >110 Table 18.1.2 Causes of secondary hypertension Management of hypertension in different patient groups The elderly Low-dose thiazide diuret ics are the preferred \201 rst-line treatment. Dihydropyridine CCBs are suitable alternat ives when thiazides are contraindicated or not tolerated. Renal Renovascular disease Atherosclerotic renal artery stenosis Fibromuscular dysplasia Renal parenchymal disease The very elderly No \201 rm evidence exists to guide treatment for patients above the age of 80yrs. If antihypertensive treatment has been started before the age of 80, they should be contin- ued. Acute and chronic glomerulonephritis Polycystic disease Diabetic nephropathy Collagen vascular disease Diabetes mellitus Type 2 diabetes ACE inhibitors and ARBs have an antiproteinuric effect an d delay progression from microalbuminuria to overt nephropathy. Combined use of ACE inhibit ors and ARBs is more effective in reducing albuminuria and to some extent BP. Renal transplantation Endocrine Adrenal cortex Conn \200\231s syndrome (primary aldosteronism) Cushing \200\231s syndrome Congenital adrenal hyperplasia Type 1 diabetes ACE inhibitors have a speci \201 c renoprotective action inde- pendent of the BP-lowering effect. ACE inhibitor therapy should be titrated to the maximum tolerated r ecom- mended dose. The target BP in type 1 diabetes with neph- ropathy is <130/80mm Hg or l ower, <125/75mm Hg, when there is proteinuria \211 1g/24h. Dexamethazone-responsive aldosteronism Adrenal medulla Pheochromocytoma Hyperparathyroidism Acromegaly Coarctation of aorta Ethnic groups Afro-Caribbean hypertensive subjects are more respon- sive to diuretics and C CBs. ACE inhibitors and ARBs in monotherapy may be less effective in blacks because the RAA S is frequently suppressed but when these drugs are combined with a diuretic or a CCB they are quite effec- tive. Drug induced Oral contraceptives Cyclosporin Steroids Carbenoxolone and liquorice Tyramine and MAOIs Hypertensive crises A hypertensive crisis is de \201 ned as severe hypertension with ongoi ng or impending target organ damage (TOD). The rate of the rise in BP in relation to the pr evious levels of BP is more important than the absolute BP level. Erythropoetin NSAIDs Pregnancy induced hypertension 285 CHAPTER 18.1 Hypertension The BHS/NICE recommendations for combining BP Lowering drugs Young (e.g. <55 yr) and non-black Old (e.g. \211 55 yr) or black Step 1 A C or D C or D A + Step 2 Step 3 A D C + + Step 4 Resistant Hypertension Add: another diuretic, -blocker, -Blocker, or refer to a hypertension specialist Fig. 18.1.1 The BHS/NICE recommendations for combining BP-lowering drugs. Aortic dissection Aortic dissection must be excluded in any patient present- ing with sever e hypertension and chest pain, back pain or abdominal pain. It is life-threatening, with ve ry poor prog- nosis if not treated (mortality is 1%/h). Aortic dissection is classi \201 e d as type A if it involves the ascending aorta or type B if it does not. Surgical treatment is usually required for type A dissection, whereas type B responds more favoura- bly to me dical treatment. Severe refractory hypertension is nearly omnipresent, especially in the ac ute phase even in patients without history of hypertension. Propagation of the dissection i s dependent not only on the elevation of the BP itself, but also on the velocity of LV ejec tion and the rate of increase of the aortic pulse wave. Therefore, the immediate reduction of BP and shear stress is of paramount importance to prevent the extension, hemorrhage and rupture of the dissection. BP should be reduced quickly (within 15 \200\22330min) to the lo west tolerated level that preserves adequate organ perfusion. The initial treatment of choi ce is a combination of IV B-blocker (e.g. esmolol or metoprolol) or a combined A \200\223B blocker (e.g. labetalol) and a vasodilator (e.g. SNP or dihydropyridine CCB). The recent CA F \211 trial, a substudy of the ASCOT trial, has shown that a combination of a dihydropyrid ine CCB and an ACE inhibitor was more effective in reducing central aortic pressure than a combination of a B-blocker and a diuretic. Therefore, the combination of a CCB and an ACE i nhibitor should be considered in the treatment. A hypertensive emergency is de \201 ned as a situation that requires immediate BP lowering (not necessarily to normal values) to prevent or limit TOD. Hypertensive urgency is a situ ation in which severely elevated BP is not accompa- nied by any evidence from history, phys ical examination or laboratory investigation of acute TOD. Individuals under this category could be: 1 Known hypertensive patients who are not compliant with their medication; prior therapy should be restarted (if there are no side effects). 2 For patients taking their medications regularly, therapy should be increased (either by i ncreasing the dose(s) of drugs or by adding new drugs). 3 For patients on no treatment, hypertension therapy should be started with oral agents (e. g. nifedipine SR or LA, or amlodipine) and a follow-up appointment arranged urgently with a hypertension clinic. Individuals with untreated severe or accelerated hyperten- sion have a dreadful long-term p rognosis. The most com- mon causes of death are renal failure, strokes and MI. Management of hypertensive emergencies The key to a successful outcome is the prompt recogn ition and initiation of treatment. Full medical history and physi- cal examination includin g palpation of all peripheral pulses and a fundoscopic examination is mandatory. Specific p oints in the patient \200\231s past medical history include patient \200\231s BP prior to p resentation and drug history (including pre- scription, over-the-counter and recreational d rugs). Initial investigations should include FBC, electrolytes, urea, creatinine, urine dip stick, CXR and ECG. These tests should be performed simultaneously with the initiation of a ntihypertensive therapy. The approach in treating hypertensive emergency is ini- tially to reduce BP by 15 \200\22325% with further reductions accomplished more gradually. The initi al reduction should be achieved over a period of 2 \200\2234h, with less rapid reduc- tion over the next 24h. Acute pulmonary oedema More than 90% of patients with heart failure have a history of hyper tension. The clinical syndrome of heart failure is usually characterized by signs and sympt oms of intravascu- lar and interstitial volume overload. IV GTN is the drug of choice in th e initial treatment, together with an IV loop diuretic (e.g. frusemide) and diamorphine. GT N reduces both preload and afterload while improving coronary blood \202 ow. There is ver y little clinical experience with the use of ACE inhibitors in patients with acute LV failu re, but a short-acting ACE inhibitor (e.g. captopril) may be added if necessary. It is impo rtant to stress here that patients with malignant hypertension who present with acute ( \202 ash) pulmonary Pathophysiology A sudden increase in PVR (e.g. secondary to non-compli- ance) triggers an i ncrease in circulating levels of vasocon- strictor substances such as angiotensin II and no radrenaline. 286 T ANTONIOS damage. The resulting renal ischaemia prompts massive release of renin and angiotensin II, triggering a vicious cycle. The rapid increase in BP enhances pressure natriuresis, which f urther stimulates the RAAS, resulting in secondary hyperaldosteronism, hypokalaemia and met abolic alkalosis. Malignant hypertension rarely occurs de novo, and is usually a consequenc e of untreated essential or secondary hyper- tension such as renal artery stenosis, phaeoch romocytoma or scleroderma. The incidence of malignant hypertension remains stable across th e UK and Europe, with 1 \200\2232 cases per 100 000 per year. Malignant hypertension has a very poor prognosis if untreated, with a mortality rate >90% within 1yr, but with proper t reatment 5yr survival is 60 \200\223 75%. Most patients who present with malignant hyperten sion have volume depletion secondary to pressure naturesis. Therefore, further diuresis may exacerbate the hyperten- sion and cause further deterioration in kidney function. oedema may not have volume overload. In fact, they may have volume depletion secondary to p ressure naturesis. Therefore, IV diuresis may exacerbate the hypertension and cause further clinical deterioration. The use of diuret- ics should be reserved for patients who are cli nically \202 uid overloaded and should not be prescribed routinely. STEMI and ACS Hypertension is very common in patients presenting with acute coronary syndro me (ACS). The overall prevalence of hypertension in US patients presenting with NSTEMI is 50% while in Europe the prevalence is 34%. IV GTN is the drug of choice for ACS and STEMI as it reduces PVR while improving coronary perfusion. B- Blockers attenuate the activity of the adrenergic system and the RAAS, and improve survival in post-MI patients. In ACS, B-bl ockers should be started IV then switched to oral when the patient is stable. When B-blocke rs are contraindicated, a non-dihydropyridine CCB (diltiazem or verapamil) can be used if t he patient does not have severe LV dysfunction. Short-acting dihydropyridine CCB should not be used in the treatment of hypertensive crisis when associated with ACS or acute STEMI. A CE inhibitors could be added if hyperten- sion persists, as they signi \201 cantly improve survival during STEMI. SNP, unlike GTN, increases heart rate and provokes ST segment eleva tion, and should not be used alone. Hypertensive encephalopathy Hypertensive encephalopathy is much less common these days with the use of modern antihypertensive drugs. It is believed to be due to cerebral oedema seco ndary to fail- ure of CBF autoregulation and rapid elevation of cerebral perfusion. Symptom s and signs include headache, nausea and vomiting, visual disturbances, altered level of co n- sciousness, confusion, disorientation, focal or generalized seizures and retinopathy inc luding papilloedema. Diagnosis may be dif \201 cult as it is one of exclusion requiring th at stroke, encephalitis, vasculitis, subarachnoid hemorrhage and mass lesions need to be ex cluded. The de \201 nite crite- rion to con \201 rm the diagnosis is a prompt improvement in the patient \200\231s clinical condition with the response to antihy- pertensive treatm ent. The goal of treatment is to reduce BP by 25% within the \201 rst hour or to a level of 160/100mm Hg, whichever value is higher. It must be emphasized that cerebral hypoperfus ion and neurological deterioration may result if more reductions in BP are achieved quickly . In this case, BP should be allowed to increase and further reductions should be attempted more slowly. Cocaine overdose Cocaine overdose is often associated with uncontrolled severe hypertension and coronary artery vasoconstriction leading to angina, MI and sudden death. These effects are mediated through A-adrenergic receptors and therefore B-blockers alone (i.e. without A -blockers) may exacerbate the hypertension and the clinical condition, and are there- fore contraindicated. A non-dihydropyridine CCB (e.g. diltiazem or verapamil) or a combined A \200\223B blocker, e.g. labetalol, may be used. Severe pre-eclampsia and eclampsia Pre-eclampsia is de \201 ned as hypertension (BP \211 140/90mm Hg) in the second half of pregnancy (i.e. after 20 weeks of gestation) associated with proteinuria and oedema. Eclampsia is the occurrence of seizures in a patient with pre- eclampsia. Treatment with antihypertensive drugs is not usually indicated for BP <160/100mm Hg. ACE inhibi- tors and ARBs are contraindicated in pregnancy because of the increase in fetal and neonatal morbidity and mortality. Methyldopa remains the mainstay of treatment fo r patients with moderate gestational hypertension because of its foe- tal and neonatal safe ty. The drug, however, has many adverse side effects. For pre-eclamptic patients with sever e hypertension, IV hydralazine or labetalol could be given. SNP can cause pro- found re \202 ex paradoxical bradycardia and hypotension, and should be avoided. Stroke Appropriate treatment of hypertension in the setting of acute stroke remains content ious. There is little scienti \201 c evidence and no clinically established bene \201 t f or rapid low- ering of BP among persons with acute ischaemic stroke. Aggressive lowering of BP may cause neurological worsen- ing. However, it is generally agreed that severe hyperte n- sion (BP >180/110mm Hg) may be an indication for treatment as higher BP levels is a cont raindication to IV thrombolysis. If thrombolysis is not considered, then emer- gency admini stration of antihypertensive drugs should be withheld unless the SBP is >220mm Hg and/or DB P is >120mm Hg. Treatment could be started with IV labetalol. A reasonable goal would be to lower BP by 25% within the \201 rst day. Previously hypertensive patients with mild to m oderate strokes who are not at high risk for increased ICP may have their usual pre-stroke antihypertensive med- ications restarted 24h after their stroke. Malignant hypertension Malignant (accelerated) hypertension is a syndrome char- acterized b y severely elevated BP accompanied by retin- opathy including papilloedema, nephropathy, en cephalopathy and microangiopathic haemolytic anemia. Pathologically it is characterized by \201 brinoid necrosis in arterioles, myointimal proliferation in small arteries, plate- l et and \201 brin deposition, and breakdown of normal vascu- lar autoregulation function. The resulting vasoconstriction induces severe elevation in BP and widespread endothelial Drugs for the treatment of hypertensive emergencies Sodium nitroprusside SNP dilates arteri olar resistance and venous capacitance vessels and decreases both the afterload and preload . It is 287 CHAPTER 18.1 Hypertension BP in patients with hypertensive crises, with onset of action within 5min and duration of a ction of 3 \200\2236h. The drug is contraindicated in patients with acute LV failure, heart block and COPD. a very potent agent with an immediate onset and short duration of action; plasma t1/2 is 2 \200\2233min. Continuous arte- rial BP monitoring is recommended to avoid overreduc- tion i n BP. The drug is light sensitive and should be shielded from light to prevent degradation. The usual dose is 0.3 \200\223 10mcg/kg/min. Cyanide poisoning may occur with pro- longed or high dose administration, especially in individuals with renal or hepatic insuf \201 ci ency. Manifestations of poi- soning include CNS depression, seizures and lactic acido- sis. Esmolol Esmolol is an ultrashort-acting B1-selective adrenergic blocking agent with an extr emely brief t1/2 of <10min. This agent is available for IV use both as a bolus and as an in fu- sion. The recommended loading dose is 0.5 \200\2231mg followed by an infusion of 50 \200\223200mcg/kg/min. GTN GTN dilates arteriolar resistance and venous capacitance vessels. It reduces preload an d afterload, improves LV func- tion and reduces myocardial oxygen demand. GTN dilates both epicardial coronary vessels with stenosis and collater- als, and increases blood supply to ischaemic areas. It is the drug of choice for reducing BP in individuals with STEMI, ACS an d acute pulmonary oedema. However, the BP-low- ering effect of GTN is not as predictable as with SNP, and higher doses (up to 300mcg/min) may be required to achieve an adequate respo nse. Onset of action is almost immediate, with a very short duration of action (t1/2 3 \200 \223 5min). The starting dose is 5 \200\22315mcg/min. Nitrate tolerance is a problem even w ithin the \201 rst 24h. Further reading Antonios TF, Cappuccio FP, Markandu ND, et al. A diuretic is more effective than a beta-blocker in hypertensive patients not controlled on amlodipine and lisinopril. Hypertension 1996; 27: 1325 \200\2238. Dahlof B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihype rtensive regimen of amlodipine adding perindopril as required versus atenolol adding bendro \202 umethi- azide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pr essure Lowering Arm (ASCOT-BPLA): a multicen- tre randomized controlled trial. Lancet 2005; 366: 895 \200\223906. Ravid M, Lang R, Rachmani R, et al. Long-term renoprotective effect of angiotensin-converti ng enzyme inhibition in non-insulin- dependent diabetes mellitus. A 7-year follow- up study . Arch Intern Med 1996; 156: 286 \200\2239. Labetalol Labetalol is a selective A1- and non-selective B-adrenergic receptor blocker. Its differential effects on A:B receptors are 1:3 after oral administration and 1:7 after IV a dministra- tion, respectively. The drug can be given IV as a 20 \200\22380mg mini-bolus inj ection (q 10min) or 2 \200\2234mg/min infusion. Labetalol produces a prompt and controlled reduction in Williams B, Lacy PS, Thom SM, et al. Differential impact of blood pressure-lowering drugs o n central aortic pressure and clinical outcomes: principal results of the Conduit Artery Fu nction Evaluation (CAFE) study. Circulation 2006; 113: 1213 \200\22325. Williams B, Poulter NR, Brown MJ, et al. Guidelines for manage- ment of hypertension: repor t of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hyper tens 2004; 18: 139 \200\22385. 288 T PRABHAHAR & S PRICE Tachyarrhythmias Excessive rapidity in the action of the heart, usually de \201 ned as a heart rate >100bpm , and associated with increased incidence of major cardiac events and length of ICU stay. T achyarrhythmias may arise from the atria or the ventricles. Management principles \200 Generally, as for AF \200 Digoxin may convert to AF (rate co ntrol easier) \200 Overdrive atrial pacing may be used to cardiovert (suc- cess rate of a pproximately <50%) Atrial \201 brillation (AF) Characterized by uncoordinated atrial activation. Main fea- t ures are described in Table 18,2,1. Multi-focal atrial tachycardia Multi-focal atrial tachycardia is an irregular cardiac rhyth m caused by at least 2 different sites of competing atrial activ- ity with the sinus node. The main features are described in Table 18.2.1. Management principles \200 \200 Correction/removal of potential cause(s) Restoration of sinus rhythm if possible (chemical/ electri- cal cardioversion) Prevention/exclusion of intracardiac thrombus (TOE) Rate contro l (amiodarone/B-blocker/calcium channel blockade) where cardioversion is not possible Antic oagulation may be required and should be tailored to the individual patient situation Management principles \200 Frequently transient. May spontaneously convert to sinus rhythm, AF or atrial \202 utter Treat any precipitating cause Antiarrhythmics (B-blockers, magnesium or verapamil) may be u sed Electrical cardioversion is not generally effective \200 \200 Prophylaxis and maintenance of sinus rhythm \200 Pre-excitation syndromes Characterized by intermittent tachycardia (narrow or broad complex ) associated with an accessory AV connec- tion where a re-entry circuit between atria and v entricles occurs. Includes the Wolf \200\223Parkinson \200\223White (WPW) syn- drome. Note that pre-excitation (delta wave) is seen in only 3/1000 ECGs. Risk of post-cardiothoracic surgery AF is reduced by amiodarone, B-blockade or dltiazem. Di goxin should not be used. In post-operative AF, rhythm control should be the initial option . If antiarrhythmics are required to maintain sinus rhythm, B-blockade/amiodarone may be co nsidered Management principles \200 \200 Atrial \202 utter Atrial flutter is the expression of rapid and regular atrial excitation . The main features are described in Table 18.2.1. AF is potentially life-threatening (may degenerate to VF) In 50% of patients with WPW, card iac arrest is the \201 rst manifestation Adenosine should be avoided Table 18.2.1 Rhythm Substrate ECG features Incidence Risk factors 4 \200\2235% general ICU; 25 \200\223 40% cardiac ICU Age, diabetes, hypertension, structural and ischaemic heart disease, cardiac failure, chang es in intravascular volume, increased sympathetic activity, inotropic agents, intracardiac lines, electrolyte imbalance, lung disease, SIRS, hyperthyroidism Absent P waves; \201 brillatory waves and irregular ventricular response (intact AV condu ction) AF Following 4 \200\2236 re-entry circuit wavelets in the atria near anatomical/ functional ba rriers 5.2% general ICU As AF, plus pericarditis AFl Multiple re-entrant/ ectopic atrial waves Regular \200\230saw-tooth \200\231 atrial de \202 exion waves best seen in leads II, III and aVF COPD, hypoxaemia, PE, congestive heart failure and electrolyte imbalance. 0.05 \200\2230.32% in-patients. ICU incidence not known \200\224probably underdiagnosed Atrial rate >100bpm and >3 morphologically distinct P waves. P \200\223P intervals are irre gular and there is an isoelectric baseline between P waves MAT ?Triggered activity due to intracellular calcium overload or delayed \200\230afterdepolari zation \200\231 41% general ICU Cardiac disease, electrolyte imbalance, hypoxaemia, acidaemia, drugs Wide QRS complexes (>140ms), negative precordial, independent atrial activity, capture and fusion beats VT Originates from one or more ventricular ectopic foci, rate >100bpm Not known Risk factors: drugs electrolyte imbalance, subarachnoid hemorrhage, QTc prolongation and in secticide poisoning Characteristic paroxysms of 5 \200\22320 beats at heart rate >200bpm and alternating electr ical axis in 10 \200\22312 beats TdP Cycles of alternating electrical polarity with electrical axis rotating around the baseline . AF = atrial \201 brillation; A \202 , atrial \202 utter; MAT = multi-focal atrial tach ycardia; VT = ventricular tachycardia; TdP = Torsade de pointes. 289 CHAPTER 18.2 Tachyarrhythmias causes, IV magnesium. Consider overdrive pacing or iso- proterenol Early consultation with an electrophysiologist is advised for the ICU patient with a pre-ex citation syndrome Electrical cardioversion should be used in emergency Key points \200 Ventricular tachycardia Characterized by a regular broad-complex tachycardia. The main feat ures are described in Table 18.2.1. Treatment of all tachyarrhythmias on the ICU should include correction/removal of potential causes. Restoration of sinus rhythm is the main goal. Where standard pharmacological or el ectrical therapy fails, expert advice should be sought from an electro- physiologist as spe cialist intervention may be required. \200 Management principles \200 \200 In all cases: correction/removal of potential cause(s) Non-sustained VT with haemodynamic c ompromise: consider lignocaine/amiodarone infusion or ventricular pacing Sustained VT with no haemodynamic compromise: ligno- caine/amiodarone and, if no myocardial ischaemia, con- s ider procainamide. If drug treatment fails, cardioversion Sustained VT with haemodynamic co mpromise: cardio- version Polymorphic VT with normal QT interval: may be associ- ated with myocardial ischaemia; therefore, electrical car- dioversion is recommended with a plan for revascularization where possible Torsade de pointes: the main features described in Table 1 8.2.1. In addition to correction/removal of potential Further reading Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/ AHA/ESC guidelin es for the management of patients with supraventricular arrythmias. J Am Coll Cardiol 2003; 42: 1493 \200\223531. Grant AO. Recent advances in the treatment of arrhythmias. Circ J 2003; 67: 651 \200\2235. National Collaborating Center for Chronic Conditions. Atrial \201 bril- lation; national clinical guideline for management in primary and secondary care. London: Royal College of P hysicians, 2006. Trappe HJ, Brandt B, Weismuller P, et al. Arrhythmias in the inten- sive care patient. Curr Opin Crit Care 2003; 9: 345 \200\22355. Trohman RG. Supraventricular tachycardia: Implication for the intensivist. Crit Care Med 2000; 28 (Suppl.): N129 \200\22335. 290 A IGUCHI & S PRICE Bradyarrhythmias A slow ventricular rate, usually de \201 ned as <60bpm, but may be absolute (<40bpm) or re lative (excessively slow for the patient \200\231s clinical status). Bradyarrhythmias are d ue to either sinus node dysfunction or AV conduction distur- bances.