336 Medicine Update

57 Hypertensive Emergencies

ATUL BHASIN, DG JAIN, RM CHHABRA, RK SINGAL

ARTERIAL the risk of serious morbidity and death. is often severely raised, diastolic >130 mmHg but is Arterial Hypertension is a medical condition where always a poor correlation between pressure and end- the blood pressure is chronically elevated1. Persistent organ damage. Seriousness of hypertension is one of the risk factors for , heart and approach to treatment is determined by end organ attack and , and is a leading cause of chronic damage. While at the same time hypertensive urgency renal failure. is characterized by a lack of end organ damage. Hyper- tensive emergencies are associated with the following: DEFINITION • Neurological deficits primarily presenting as TIA, Blood pressure is a continuous variable, and risks hypertensive encephalopathy, intracranial of various adverse outcomes rise with it. “Hypertension” hemorrhage and stroke. is usually diagnosed on finding blood pressure above • Cardiovascular complications such as pulmonary 140/90 mmHg measured on both arms on three edema, acute , adrenergic crisis, occasions over a few weeks. Recently, the JNC VII (The dissecting aortic aneurysm, and eclampsia. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of • Renal complications as hematuria and progressive High Blood Pressure)2 has defined blood pressure over renal dysfunction. 120/80 mmHg and below 140/90 mmHg as “pre- In these conditions, the blood pressure (BP) should hypertension”. “Prehypertension is not a be lowered aggressively over minutes to hours. category. Rather, it is a designation chosen to identify individuals at high risk of developing hypertension (JNC Hypertensive Urgency VII).” Normal blood pressure is 120/80 mmHg. In This is distinguished from hypertensive emergency, patients with mellitus or kidney disease, studies in which the BP is a potential risk but has not yet caused have shown that blood pressure over 130/80 mmHg acute end-organ damage. Hypertensive crisis is defined should be considered a risk factor and may warrant as having a diastolic BP greater than 120 mmHg that treatment. persists after a period of observation and has optic disk edema, progressive target organ complication, and HYPERTENSIVE EMERGENCIES severe perioperative hypertension. These patients Hypertensive Emergency, also called Hypertensive require BP control over several days to weeks. Crisis, is severe hypertension with acute impairment of Hypertensive urgencies are associated with the an organ system, e.g., central nervous system (CNS) following: malignant hypertension, left ventricular cardiovascular and/or renal, requiring substantial failure, unstable angina, perioperative hypertension and reduction of blood pressure within one hour to avoid pre-eclampsia. Hypertensive Emergencies 337

Severe Hypertension Renal System The third category, severe hypertension, is elevated The renal system is impaired when high BP leads to BP not yet leading to significant organ damage. In these arteriosclerosis, fibrinoid necrosis, and an overall patients, the hypertension does not necessarily require impairment of renal protective autoregulation mecha- treatment during the emergency visit but does require nisms. This may manifest as worsening renal function, close follow-up with a primary care physician for long- hematuria, red blood cell (RBC) cast formation, and/or term BP control. In these cases, beginning antihyper- proteinuria. tensive therapy in the emergency may be appropriate. Hypertensive emergencies and urgencies occur in less than 1% of the 60 million people with hypertension. Emergency Department Considerations Even though not many people with hypertension Optimal control of hypertensive situations balances experience hypertensive crisis, there are still a significant the benefits of immediate decrease in BP against the risk number of events since so many people have of significant decrease in end-organ perfusion. The hypertension. emergency physician must be capable of the following: Frequency • Appropriately evaluating patients with an elevated BP. • In the US: More than 60 million Americans, about • Correctly classifying the hypertension. 25 to 30% of the population, have hypertension. Of these individuals, 70% have mild disease, 20% • Determining the aggressiveness and timing of moderate, and 10% severe hypertension – diastolic therapeutic interventions. BP (DBP) >110 mmHg. Approximately 1-2% develop An important point to remember in the management a hypertensive emergency with end-organ damage. of the patient with any degree of BP elevation is to “treat the patient and not the number”. Morbidity/ Mortality

Pathophysiology Morbidity and mortality depend on the extent of end- organ damage on presentation and the degree to which The three major organ systems affected by high BP BP is controlled subsequently. BP control may prevent are the central nervous system, cardiovascular system, progression to end-organ impairment. and renal system. • One-year mortality rate for an untreated hyper- tensive emergency is greater than 90%. Central Nervous System • Five-year survival rate among all patients presenting The CNS is affected as the elevated BP overwhelms with a hypertensive crisis is 74%. the normal cerebral autoregulation. Under normal Race: African Americans have a higher incidence of circumstances, with an increase in BP, cerebral arterioles hypertensive emergencies than Caucasians3. vasoconstrict and cerebral blood flow (CBF) remains constant. During a hypertensive emergency, the elevated Sex: Males are at greater risk of hypertensive BP overwhelms arteriolar control over vasoconstriction emergencies than females. and autoregulation of CBF. This results in transudate Age: Hypertensive emergencies occur most leak across capillaries and continued arteriolar damage. commonly in middle-aged patients. The peak incidence Subsequent fibrinoid necrosis causes normal auto- occurs in those aged 40 to 50 years4. regulatory mechanisms to fail, leading to clinically apparent papilledema, the sine qua non of malignant Etiological Causes of Hypertensive Emergencies hypertension. The end result of loss of autoregulation is hypertensive encephalopathy. Renal Cardiovascular System Renal artery stenosis The cardiovascular system is affected as increased Glomerulonephritis cardiac workload leads to cardiac failure; this is accom- Vascular panied by pulmonary edema, myocardial ischemia, or Vasculitis (hemolytic uremic syndrome, thrombotic myocardial infarction. thrombocytopenic purpura) 338 Medicine Update

Pregnancy Related with an initial DBP >130 mm Hg had their DBP Preeclampsia fall below critical levels after relaxation without specific treatment6. Eclampsia — Consider the context of the elevated BP (e.g., Pharmacological severe pain often causes increase in BP). Sympathomimetics • Screen for end-organ damage Clonidine, beta blocker withdrawal — Use historical criteria, physical examination steps, Cocaine lab studies, and diagnostic tests to evaluate for Amphetamines cause of hypertension6. Endocrine — Patients with end-organ damage usually require Cushing syndrome admission and rapid lowering of BP using intra- venous (IV) medications. Suggested medication Conn’s syndrome depends on the affected organ system. Pheochromocytoma — Patients without evidence of end-organ effects Rennin secreting adenoma may be discharged with follow-up: Thyrotoxicosis  The misconception remains that a patient Neurologic never should be discharged from the ED with 9 Intracranial elevated BP . As a result of this belief, patients are given oral medicines, such as nifedipine, Autoimmune in an effort to lower BP rapidly before Scleroderma Renal Crisis. discharge. This is not indicated and may be dangerous10. Treatment  Attempts to temporarily lower BP by using IV vasodilator therapy to achieve a decrease in mean these medicines may result in a precipitous arterial pressure (MAP) of 20 to 25% or a decrease in and difficult-to-correct drop in BP. Should this diastolic blood pressure (DBP) to 100 mmHg to 110 occur, end-organ hypo-perfusion may result. mmHg in the first 2 hours is recommended5. Decreasing Furthermore, patients who present with high the MAP/DBP further should be done more slowly, as BP may have had this elevation for some time one risks decreasing perfusion of end-organs6. Several and may need chronic BP control but may not drugs have proved beneficial in achieving this goal. tolerate rapid return of BP to a “normal” level.  Acute lowering of BP in the narrow window Prehospital Care of the ED visit does not necessarily improve • Address the manifestations of a hypertensive long-term morbidity and mortality rates11. emergency, such as chest pain or heart failure. Rapid BP reduction is indicated in the follow- Reduction of BP may not be indicated in the pre- ing circumstances with IV medication12: 7 hospital setting . — Acute myocardial ischemia • Oxygen, frusemide and nitrates may be appropriate.  Nitroglycerin • Under most circumstances, attempting to treat  Beta-blockers hypertension directly in the prehospital setting is  unwise, as rapid lowering of BP can critically Angiotensin-converting enzyme (ACE) decrease end-organ perfusion8. inhibitors (if available). — CHF with pulmonary edema Emergency Department Care  Nitroglycerin The fundamental principle in determining the  Frusemide necessary emergency care of the hypertensive patient is  Morphine. the presence or absence of end-organ damage. — Acute aortic dissection • Initial considerations (if the patient is not in distress)  Nitroprusside IV plus beta-blockers — Patient in distress should be counseled after an initial interview. In one study, 27% of patients  Alternative-Trimethaphan plus beta-blockers. Hypertensive Emergencies 339

— Cerebral vascular accident: Lowering BP is • Dose is 5 to 100 µg/min as IV infusion Nitroglycerin indicated in cardiac or renal compromise, DBP IV infusion should be started 5 to 10 ug/min then >130 mmHg, hypertensive encephalopathy, or may be increased up to >200 ug/min especially in subarachnoid hemorrhage (may require BP patients where sodium nitroprusside is relatively control to prevent rebleeding even without other contraindicated and in patients with ischemic heart evidence of end-organ damage)13. disease, impaired renal or hepatic function.  Nitroprusside — Onset: immediate; Duration: 1 to 5 min.  Labetalol • May cause , tachycardia, vomiting,  Nimodipine. methemoglobinemia. • Reduce BP quickly (over minutes to hours) in the • Excellent for titrating blood pressure in setting of following settings14: coronary ischemia. — Pheochromocytoma Labetalol  Phentolamine • Mixed alpha/beta blocker, excellent for most  Nitroprusside hypertensive emergencies  Labetalol. • Dose is 20-80 mg IV bolus every 10 minutes or 0.5 to — Hypertensive encephalopathy 2 mg/min infusion IV Start 20 mg IV, then 20-80 mg  Nitroprusside q10 min prn, or start with 0.5 mg/min infusion, then  Trimethaphan 1 to 2 mg/min (may be up to 4 mg/min) IV infusion up to 300 mg/d max.  Beta-blockers. — Onset: 5 to 10 min; Duration: 3 to 6 hr. — Eclampsia — Adverse effects: hypotension, bradycardia,  Hydralazine dizziness, scalp tingling.  Labetalol • Avoid in patients with heart block, bradycardia,  Magnesium IV. CHF, severe asthma or bronchospasm. • First or second line for eclampsia; excellent in INTRAVENOUS DRUGS catecholamine surges. Sodium Nitroprusside Enalaprilat • Standard rapidly acting agent effective in many cases. • Intravenous formulation of enalapril (ACE inhibitor). • Dose is 0.25-8 µg/kg/minute as IV infusion, start • Dose is 1.25 to 5.0mg q6 hour IV (duration of action with 0.3-0.5 ug/kg/min (about 20 to 50 ug/min), ~6 hours). then 1 to 3 ug/kg/min IV (max:<10 ug/kg/min) • Onset of action in 15 to 30 minutes; Duration 6 hours (50 mg in 250 ml D5W). or more. • Onset: 0.5-1 min; Duration: 2 to 5 min. • Highly variable response; precipitous BP drop in • Adverse effects: hypotension, N and V, appre- high-renin states, rarely angioedema, hyperkalemia, hension, cyanide (thiocyanate level >10 mg/dl is or acute renal failure. toxic; >20 mg/dl may be fatal) toxicity convulsion, • May be most useful in acute cardiogenic pulmonary twitching, psychosis, dizziness, etc. edema. • Nitroprusside has decreased efficacy in renal failure. • Avoid in acute myocardial infarction. • Toxic levels of cyanide build up rapidly in patients Diltiazem with renal failure. • Nausea, vomiting, muscle twitching and sweating • Initial dose 0.25 mg/kg over 2 min, followed by can occur. infusion of 0.35 mg/kg at an initial rate of 10 mg/ hour Nitroglycerin • Onset: 3 to 30 min • Highly effective in setting of coronary ischemia, acute • Adverse effects: excessive hypotension, flushing; coronary syndromes rarely amblyopia. 340 Medicine Update

Hydralazine • Duration: 4 to 12 hours. • Indicated primarily for eclampsia. • Adverse effects: Sodium retention, hyperglycemia, tachycardia, palpitations, chest pains, sedation and • Dose is 10-50 mg IV or IM titrate to effect (onset <20 somnolence. minutes, duration 3 to 8 hours): — Onset: 10 to 20 min; Duration: 3 to 8 hours. Consultations — Adverse effects: tachycardia, flushing, 1. Consultations may be indicated for co morbid contraindicated in angina or aortic dissection. conditions especially renal and endocrinal • Can be given IM as well, 10 to 50 mg (onset 20 to for their definitive treatment15. 30 minutes). 2. Since hypertension is usually a chronic problem, • Tachycardia, flushing, headache, vomiting, increased access to a primary care physician and long-term angina may occur. follow-up are essential for all patients. 3. White-coat hypertension is a transitional condition Nicardipine to hypertension outside medical settings, suggesting • IV formulation available though not commonly used. that white-coat hypertension may carry a poor 16 • Dose is 5 to 15 mg/hr IV, onset 5 to 10 minutes, cardiovascular prognosis . duration 1 to 4 hours. 4. In patients having elevated blood pressure, despite • Do not use in acute CHF or with coronary ischemia. taking medications, with evidence of target-organ injury a careful assessment of adherence to therapy • May be most useful for hypertension in the setting is warranted. Since volume overload is common in of subarachnoid hemorrhage. refractory hypertension use of a diuretic is recommended. If interventions are ineffective, a Esmolol different class of drug could be added, and the • Very short half-life (2-4 minutes) non-selective patient could be screened for renovascular hyper- β-blockade. tension. Regular follow-up is warranted, with a goal

• Dose is 250 to 500µg/kg/min for 1 minute, then 50 of maintaining the blood pressure below 140/90 17 to 100 µg/kg for 4 minutes. mmHg . • Sequence may be repeated, and continuous drip may 5. Goal-oriented management in chronic hypertension

be maintained. revealed better control rates than what is reported. DBP control was easy to achieve, achieving SBP goal • Onset of action is 1 to 2 minutes; 10 to 20 minute still remained difficult. Employing goal-oriented duration. management can translate BP control results • Mainly for acute aortic dissection, perioperatively, achieved in clinical trials into outpatient practice18. acute coronary ischemia. • May be used with caution in acute MI with depressed Dangers of Rapid Reduction in Blood Pressure LV to modulate heart rate. Rapid reduction of BP in asymptomatic severe • Very close monitoring is required, and fluid load is hypertension or hypertensive urgency is best avoided. large with this agent. Oral or sublingual drugs with rapid onset of action can result in an uncontrolled drop in blood pressure leading Phentolamine to stroke, myocardial ischemia and even death. Several • Mainly for catecholamine surges (pure alpha- serious side effects have been reported with the adrenergic blockade) administration of sublingual fast-acting nifedipine10. • Dose is 5 to 15 mg IV; onset 1 to 2 minutes; duration Therefore, its routine use to lower blood pressure rapidly 3 to 10 minutes in the general adult population is to be discouraged. • Tachycardia, flushing and headache may occur. Hypertensive Emergencies in Children Diazoxide Like adults emergency management of Hypertension 300 mg IV bolus - ? obsolete requires clinical assessment before starting therapy. • Onset: 1 to 2 min. Multidisciplinary care is required to search for the Hypertensive Emergencies 341

specific cause as the prevalence of hypertension is about 6. Vidit DG. Emergency room management of hypertension 1%19. It is important to establish cause in children as urgencies and emergencies. J Clin Hypertens (Greenwich) 2001; 3: 158-64. secondary causes are more common. IV labetolol and 7. Michael K. Magill, Karen Gunning, Susan Saffel-Shrier, et al. nitroprusside are commonly used. Recently, IV University of Utah school of Medicine, Salt lake city. Am Fam Nicardipine has been used. Oral nifedepine has been Physician 2003; 68: 853-865-6, copyright 2003; American used, but its use is controversial as its effect is less Academy of Family Physicians. predictable20. 8. Opie LH, Schall R. Evidence based evaluation of calcium channel blockers for hypertension: equality of mortality and CONCLUSION cardiovascular risk relative to conventional therapy. J Am Coll Cardiol 2002; 39: 315-22. The dividing line between high normal and 9. Vaughan CJ, Delanty N. Dept of Med, Hypertensive Emer- abnormally high BP threatening a life is to some extent gencies: Lancet 2000;356(9227): 411-7. artificial. Some patients may require treatment at even 10. O Mallia J, Sander G, Giles. Nifedipine associated myocardial lower pressure with symptoms of target organ damage. ischaemia or infarction in the treatment of Hypertensive Emergencies. Ann Int Med 1987;107:185-86. However decision to treat hypertensive emergency should be based on individual symptoms rather than 11. Kaplan NM. Management of hypertension emergencies. Lancet 1994; 344:1335-8. defined BP levels. The ever-changing scenario of 12. Vidi DG. Management of hypertensive urgencies and cardiovascular, renal and neurological complications of emergencies, Hypertension Primer; the Essentials of High hypertensive disease advocates early therapy in all age Blood pressure, Chap 151, 1999;437-40. groups. The judicious lowering of blood pressure is 13. 2003 European Society of Hypertension-European Society of required under clinical assessment with parentral drugs. guidelines for the management of arterial Hypertensive emergencies have become less frequent hypertension. J Hypertens 2003; 21:1011-53. in recent years but they still require very aggressive and 14. Chambers JP, Arnolda LF. Lowering Blood Pressure in 2003. careful management. Medical Journal of Australia 2003;179(6):306-12. 15. Bakris GL, Williams M, et al. Preserving renal function in adults with hypertension and diabetes: A consensus approach. REFERENCES National Kidney Foundation Hypertension and diabetes 1. Ram CVS, Kaplan NM. Hypertensive emergencies. In: Executive Committes Working Group. Am J Kidney Dis 2000; Textbook of Critical Care: Shoemaker WC, Thompson WL, 36:646-61. Holbrok PR, (Eds): Philadelphia, WB Saunders 1984. 16. The Ohasama Study: White-Coat Hypertension as a Risk Factor for the Development of Home Hypertension. Takashi Ugajin, 2. Chobanian AR, Bakris GL, Black HR, et al. The Seventh report et al. Arch Intern Med 2005;165:1541-6. of the Joint National Committee On Prevention, Detection, Evaluation and Treatment of High Blood Pressure. The JNC 17. Marvin Moser, John F Setaro. Resistant or Difficult-to-Control VII report. JAMA 2003; 289: 2560-72. Hypertension. NEJM 2006;355:385-92. 3. Kaplan NM. Ethnic aspects of Hypertension. Lancet 1994; 344: 18. Singer GM, Izhar M, Black HR. Goal-oriented hypertension 450-2. management: translating clinical trials to practice. Hypertension 2002;40:464-9. 4. Lip GY, Beevers M, Beevers G. The failure of malignant hypertension to decline: a survey of 24 yrs experience in a 19. National High Blood Pressure Education Program Working multiracial population in England. J Hypertens 1994; 12: 1297- Group on Hypertension Control in Children and Adolescents. A working group report from National High Blood Pressure 1305. Education Program. Pediatrics 1996;98:649. 5. Benetos A, Thomas F, Bean K, Gautier S, et al. Prognostic value 20. Houtman P. Management of Hypertensive Emergencies in of systolic and diastolic blood pressure in treated hypertensive Children. Paediatric and Perinatal Drug Therapy 2003;5(3):107- men. Arch Intern Med 2002; 162: 577-81. 10.