EM guidemap - Hypertensive emergencies Click on any of the headings or subheadings to rapidly navigate to the relevant section of the guidemap
Summary of drug choice in the treament of hypertensive emergencies
Appendix
Introduction Hypertensive emergency = Rapid decompensation of vital organ function secondary to an inappropriately elevated blood pressure, or life-threatening conditions that are critically aggravated by the presence of an elevated blood pressure
- the actual height of the blood pressure is not the most critical factor determining the existence of a hypertensive emergency
- it is the emergent need to expeditiously reduce the blood pressure so as to limit/avoid life-threatening complications that specifically defines an entity as a hypertensive emergency eg. any degree of hypertension is dangerous in a patient with an acute aortic dissection and the hypertension therefore requires expeditious treatment
- patients with a hypertensive emergency should have their blood pressure reduced significantly within < 1 hour of ED presentation
- the amount by which the blood pressure should be reduced depends on the particular hypertensive emergency
*Hypertensive urgency = Significantly elevated blood pressure in a patient with evidence of acute-on-chronic end organ damage, but no evidence of life-threatening target organ dysfunction
* (note that my definition of a hypertensive urgency differs from many standard definitions - because I do not regard asymptomatic high blood pressure in a patient with no evidence of acute-on-chronic hypertensive pathology as a true hypertensive urgency)
- patients with a definite hypertensive urgency are hypertensive patients with i) accelerated hypertension (grade 3 hypertensive retinopathy) without evidence of a hypertensive encephalopathy, ii) hypertensive patients with acute-on-chronic renal insufficiency (proteinuria, hematuria, rapidly increasing BUN/creatinine), iii) hypertensive patients with mild CHF
- those hypertensive patients have a hypertensive urgency and they should be promptly admitted to hospital for monitored treatment of the hypertension => the blood pressure should be decreased slowly over a 12 - 24 hour time period
- hypertensive patients with chronic end-organ damage + no evidence of acute decompensation (chronic renal insufficiency and/or long-standing LVH) should have their blood pressure decreased even more slowly (over a 24 - 72 hour time period), and those patients do not necessarily require admission to hospital if dependable follow-up care can be arranged
- a markedly elevated blood pressure (eg. > 220/120) in a patient with no evidence of any acute target organ dysfunction is not a hypertensive urgency, and a simple decision has to made whether to institute long-term outpatient treatment of the asymptomatic hypertension, or whether to simply arrange outpatient referral within 24 - 48 hours
- the blood pressure should be decreased very gradually over > 24 - 72 hours if a decision is made to initiate outpatient treatment of the asymptomatic hypertensive patient in the ED
- the choice of outpatient anti-hypertensive agent should be based on the individual patient's age, race, and associated pathology; and the choice of an anti-hypertensive drug should also preferably be influenced by the "habitual" anti-hypertensive drug preferences of the patient's family doctor => it is important to avoid choosing a drug that will be discontinued by the patient's family doctor within the next few days - a short-term change in anti-hypertensive drug treatment is not cost-effective and it unnecessarily delays effective control of the patient's high blood pressure
- the chosen anti-hypertensive drug should be used at the correct starting dose and prompt follow-up should be ensured (see the appendix for further details on "how to choose an anti-hypertensive drug for outpatient use")
- the use of a single po dose of an anti-hypertensive drug, that could rapidly lower the blood pressure to unpredictable levels, is highly discouraged - because of the risk of too rapid and too great a decrease in the blood pressure => iatrogenic cardiac and/or cerebral ischemia (especially in the elderly); and because of the rebound hypertension that could occur when the anti-hypertensive effect of the oral agent inevitably wears-off
- nifedipine sl or po is absolutely contra-indicated, because it is associated with overshoot of the blood pressure and secondary cardiac and cerebral ischemia; while clonidine is contra-indicated because it is very sedating and causes rebound hypertension if it is discontinued after the patient leaves the ED
(patients with chronically elevated blood pressure have a shift in their cerebral blood pressure/blood flow auto-regulatory curve so that the lower limit of cerebral auto-regulation occurs at a higher blood pressure => lowering the blood pressure below this lower limit will produce cerebral ischemia)
Medical decision-making and treatment - patients usually present with neuro-visual complaints (blurred vision, double vision, headache, vomiting, confusion or impaired cognitive function, drowsiness, seizures, coma, scattered non-anatomical focal neurological signs, cortical blindness) and they often have clinical evidence of malignant hypertension (grade 3 or 4 hypertensive retinopathy)
- the encephalopathy is usually due to a sudden rise in the blood pressure and the symptoms are due to the breakdown in cerebral auto-regulation and the subsequent development of secondary cerebral edema, punctate hemorrhages and cerebral micro-infarctions
- evidence of other organ damage can be present - acute renal failure, cardiac ischemia, cardiac failure or microangiopathic hemolytic anemia
- the blood pressure should be decreased by < 20% in the first hour of treatment (or to a diastolic blood pressure of 110mmHg) with a maximum total decrease of ~ 30% over the next 48 - 72 hours - using an infusion of nitroprusside
(failure of improvement in the abnormal neurological signs could signify a CVA, and over-zealous treatment of the hypertension can induce/aggravate cerebral ischemia)
Cerebrovascular ischemia or intra-cerebral hemorrhage
- there is no definite evidence to suggest that emergent treatment of the hypertension will improve the neurological outcome
(hypertension could be a secondary phenomenon in ICH and sponataneously improve after a few hours)
- there is no definite evidence that hypertension causes enlargement of an ICH or the risk of re-bleeding
- vasospasm and decreased cerebral perfusion is common in areas adjacent to an ICH and decreasing the MAP can aggravate the cerebral ischemia
- cerebral edema is a secondary phenomenon that occurs in patients with an ICH, and there is no direct causal relationship to the presence or height of the high blood pressure
- acute neurological deterioration is common in the first few hours after an ICH, but there is no known causal link to a concomitantly raised blood pressure
- although there is no definite evidence to suggest that treatment of hypertension alters the course of the disease, cautious treatment of a persistently elevated blood pressure (> 220/120) is acceptable if done very gradually over 24 - 48 hours
- very high blood pressure ( > 140 diastolic) should be modestly decreased by a maximum of 20 - 25% over 12 - 24 hours (excessive or too rapid a blood pressure reduction => may aggravate the neurological deficit)
- nitroprusside is often used as the drug-of-choice - however nitroprusside can increase the ICP and therefore decrease cerebral blood flow in areas with "fixed" cerebral artery narrowing => will cause a cerebral 'steal' phenomenon and secondary focal cerebral ischemia
- IV labetalol or IV nicardipine could be a better choice, because they are less likely to impair cerebral blood flow
Cardiac ischemia or acute cardiac failure
- any associated hypertension should be aggressively treated in the presence of acute cardiac ischemia or acute pulmonary edema
- the blood pressure should be reduced to normal or near-normotensive levels
- IV nitroglycerine is the drug-of-choice and it should be rapidly titrated to effect
- beta blockers are also indicated in patients with cardiac ischemia, but they are contra-indicated in cardiac failure
- IV nitroprusside can be used as a supplementary drug if the blood pressure cannot be effectively decreased with maximal IV nitroglycerin therapy
(nitroprusside can produce a degree of coronary 'steal' and aggravate cardiac ischemia in certain areas of the myocardium where "fixed" stenotic coronary blood vessels cannot dilate in response to a decreasing blood pressure)
- ACEI's (sl captopril or IV enalprilat) have been used to treat hypertension associated with 'flash' pulmonary edema, but they can cause overshoot of the blood pressure in patients with high renin levels and they cannot easily be titrated
(ACEI's are contra-indicated in patients with bilateral renal artery stenosis or renal insufficiency, or in volume depleted or hyperkalemic patients)
- the blood pressure should be reduced to normal or to just-below-normal levels (systolic bp = 100 -120 mmHg) as soon as possible
- shear stresses on the vessel wall should also be decreased by choosing drugs that reduce the dp/dt ratio
- trimethaphan has traditionally been the drug-of-choice, but it also causes many autonomic side-effects and suffers from rapid tachyphylaxis => fallen into disfavor and very infrequently used
- a combination of sodium nitroprusside + beta blocker is probably the best choice
- it is imperative that beta blockade be established before nitroprusside is infused, and the heart rate should be kept between 60 - 80 bpm
(esmolol has an advantage over propanolol - the traditional choice - in that it is readily titratable with a very short half-life lasting only a few minutes, which is useful if there are relative contra-indications to using a beta blocker)
- labetalol is a suitable single agent choice (it has both beta and alpha blocking effects)
- drugs that stimulate reflex sympathetic activity (eg.hydralazine) are absolutely contra-indicated
Adrenergic crises (drug-induced or secondary to a pheochromocytoma)
- it is important to use anti-hypertensive agents that cause direct vasodilation or alpha blockade, because use of beta blockers alone can cause a paradoxical aggravation of the hypertension
- the drug-of-choice is phentolamine or a combination of sodium nitroprusside + beta blocker
(nitroprusside should be infused before administering the beta blocker)
- labetalol alone is relatively contra-indicated because it causes relatively greater beta blockade => a paradoxical increase in the blood pressure may occur secondary to the unopposed alpha effects of adrenaline (or other sympathomimetic eg. cocaine, amphetamines, tyramine in patients taking a MAOI)
- presenting symptoms include epigastric pain, headache, anxiety, visual disturbances, edema and hypereflexia
- the diastolic blood pressure should be decreased to a target range of 80 - 100mmHg
- hydralazine is the drug-of-choice for the treatment of the hypertension, while labetalol is an alternative first-line drug
- magnesium sulfate is usually given concurrently with the anti-hypertensive agent
(see the "eclampsia" guidemap for further details)
- sodium nitroprusside is relatively contra-indicated during pregnancy and ACEI's are absolutely contra-indicated during pregnancy
Summary of drug choice in the treatment of hypertensive emergencies
Type of emergency |
Drug of choice |
Alternative or second-line drugs |
Hypertensive encephalopthy |
Nitroprusside |
Labetalol or nicardipine |
CVA |
Labetalol |
Nitroprusside, nicardipine |
Acute pulmonary edema |
Nitroglycerin |
Nitroprusside +/- ACEI |
Cardiac ischemia |
Nitroglycerin +/- beta blockers |
Nitroprusside |
Aortic dissection |
Trimethaphan |
Labetalol |
Adrenergic crises |
Phentolamine |
Labetalol |
Eclampsia |
Hydralazine |
Labetalol |
Drug profiles - first-line agent for the majority of hypertensive emergencies
- rate of onset is very rapid (seconds) and its duration of action is very short (few minutes)
- very potent => patient's blood pressure requires very frequent monitoring
- is administered as an IV infusion, preferably in an ICU-setting with intra-arterial line monitoring
- light-sensitive, so the IV bag requires shielding against the light
- direct vasodilator and venodilator and also increases cerebral blood flow and ICP
- may cause a regional decrease in coronary flow - "coronary steal" - which is of uncertain significance
- metabolized to thiocyanate in the liver and excreted slowly by the kidneys (thiocyanate toxicity can occur in the presence of renal failure or during prolonged infusion - presents with weakness, nausea, tinnitus, muscle spasm, hyperreflexia, disorientation, psychosis)
- cyanide toxicity can occur in patients with hepatic impairment => metabolic acidosis
- extravasation can cause local tissue necrosis
- relatively contra-indicated during pregnancy
- dose = 0.5mcg/kg/min => increase dose in increments of 0.5mcg/kg/min q 5 - 10 minutes to maximum of 10mcg/kg/min
- both an alpha and beta blocker (in the ratio of 1:3 - 1:7)
- causes marked orthostatic effects, so the patient should be kept supine during therapy
- causes less increase in ICP than nitroprusside => may be a drug-of-choice in stroke patients
- contra-indicated in CHF, heart block and COPD/asthma
- blood pressure falls within 5 - 10 minutes with peak effect in 30 minutes, therefore usually given by repeat IV boluses q 10 - 15 minutes
- duration of action is 3 - 6 hours
- dose = 10 - 20 mg (0.25 - 0.5mg/kg) over two minutes IV => repeat or double dose q 10 minutes if insufficient effect to a maximum dose of 300mg
- can also be given by IV infusion = 0.5 - 2 mg/min
- does not have a predictable IV dose-response relationship
- smooth transition to oral therapy with labetalol possible
- direct arterial vasodilator
- significant reflex sympathetic stimulation is a common side-effect, and trimethaphan is therefore contra-indicated in acute aortic dissection and angina
- effect occurs within 15 minutes and lasts several hours
- given IV by slow bolus injection over 5 minutes, and repeated q 20 - 30 mins
- dose = 5 - 10mg IV q 20 mins
- duration of effect = 4 - 6 hours => can be dosed q 4h when blood pressure under control
- drug-of-choice for eclampsia because of its safety profile in pregnancy
- causes reflex tachycardia, severe flushing, salt and water retention and also increases ICP => therefore emerency use limited to the treatment of eclampsia
- competitive, non-selective alpha blocker
- drug-of-choice only for "hypercatecholamine states"
- given by IV bolus with onset of action in 1 - 2 minutes, and with variable duration of 30 - 120 minutes
- dose = 2 - 10mg IV q 5 - 15 mins
- can be given by infusion at 5 - 10mcg/kg/min
- dihyropyridine calcium channel antagonist, which has been traditionally used for the control of peri-operative hypertension in cardiac surgery patients
- does not depress LV function, but reflex sympathetic response could occur
- does not adversely increase ICP and may therefore be an acceptable choice in stroke patients
- given by IV infusion and effects seen within 15 minutes
- can have prolonged effect after 12 hours of infusion and is not as easily titratable as nitroprusside
- contra-indicated in heart block, recent AMI, renal failure
- dose = start at 2 - 4 mg/h => increase infusion by 1 - 2mg/h q 15 mins to maximum dose of 15mg/h
- selective post-synaptic dopaminergic receptor agonist, which is expensive and not readily available
- new drug, which has not been extensively studied in hypertensive emergencies
- potent arterial vasodilatory action and could be as effective as nitroprusside
- onset of action within 5 mins and lasts 10 mins
- target blood pressure usually achieved in 45 - 90 mins
- increases renal blood flow and has a powerful natriuretic effect, which could be beneficial in sodium overloaded patients or in patients with impaired renal perfusion
(nitroprusside deceases creatinine clearance)
- initial dose = 0.1mcg/kg/min => increase dose in increments of 0.1mcg/kg/min q 15 minutes to a maximum of 1.6mcg/kg/min
- could produce a smoother decrease in blood pressure than nitroprusside with less risk of blood pressure overshoot
- similar to nitroprusside in that it does not cause rebound hypertension and can either be tapered or stopped abruptly
- mild adverse effects and it could be better tolerated than nitroprusside because it does not cause cyanide toxicity and it is not light-sensitive - however, it does increase IOP (although the clinical significance is unknown)
- beta-1 selective blocker with no intrinsic sympathomimetic activity
- effect within 5 mins and lasts < 30 mins when discontinued
- dose = load 500 mcg/kg over 1 minute and start infusion at 50 - 100 mcg/kg/min => repeat bolus dose of 500 mcg/kg if no effect within 5 minutes and increase dose by 50 mcg/kg/min => repeat cycle q 5 mins until maximum infusion dose of 300 mcg/kg/min
- contra-indicated in cocaine toxicity (if used alone) and LVF and COPD/asthma and high-grade heart block
- causes phlebothrombophlebitis => therefore use large vein's also causes local necrosis if extravasation occurs
- produces ganglionic blockade and inhibits both sympathetic and parasympathetic activity
- rapid onset (1 - 5 minutes) and brief duration of action (5 - 10 minutes)
- starting dose = 0.5 - 1.0 mg/min => increase the dose every 15 minutes
- was the traditional drug-of-choice for aortic dissection because it did not result in a secondary increase in heart rate or cardiac output => however the effect on heart rate is variable and depends on the severity of parasympathetic blockade
- ganglionic blockade side effects (dry mouth, paralytic ileus, gastric and urinary retention, blurred vision, exacerbation of glaucoma) limit its usefulness
- it has also rarely been associated with respiratory depression and paralysis => respiratory arrest
- tachyphylaxis is common after 24 - 48 hours
- because of the frequency of side-effects and the availability of more effective agents => infrequently used
Appendix - an ED physician has to decide whether to initiate treatment of an asymptomatic patient's uncontrolled hypertension with an anti-hypertensive drug
- the decision is based on a personal perception of the risk:benefit ratio of starting the patient on long-term anti-hypertensive treatment compared to the policy of non-treatment + timely referral to the patient's family doctor
(there are no studies comparing these two strategies - it remains an unresolved dilemma)
- there are a large number of anti-hypertensive drugs available for the long-term (outpatient) management of hypertension => difficult for the inexperienced ED physician to make a rational choice
- first-line drugs include diuretics, beta blockers, calcium channel antagonists, ACEI's, angiotensin-receptor antagonists and alpha adrenergic antagonists
- initial drug choice should be affected by co-existent factors - age, race and associated pathology eg. angina, CHF, renal insufficiency, LVH, obesity, hyperlipidemia, gout and bronchospastic disease
- previous long-term trials have shown a decreased cardiovascular and cerebrovascular mortality in hypertensive patients treated with the combination of thiazide diuretics + beta blockers => favoring these drugs in the absence of contra-indications to their use (hyperlipidemia, glucose intolerance, elevated uric acid, severe CHF, bronchospastic disease)
- the young hypertensive patient (< 35 years) usually has increased sympathetic tone and elevated plasma renin levels => beta blockers may be effective but they cause sexual dysfunction, they may also impede athletic performance by limiting cardiac output and they may also adversely affect HDL => other drugs may be better choices
- the hypertensive patient with CAD is at risk of unstable angina and AMI and would benefit from beta blockers (ACEI's are associated with a better outcome in the post-AMI patient with systolic dysfunction, and non-dihydropyridine calcium antagonists are useful for diastolic dysfunction)
- the hypertensive patient with CHF is at risk of LV dilatation and sudden death and ACEI's are associated with decreased mortality, decreased risk of recurrent AMI and decreased recurrent hospitalizations for CHF
- the hypertensive type 1 diabetic patient with diabetic nephropathy will also benefit from ACEI's
Individualized anti-hypertensive drug therapy based on co-existing conditions
Co-existing condition Diuretic Beta blocker Alpha blocker Calcium channel
blockerACEI Older age ++ +/- + + + Black race ++ +/- + + +/- Angina +/- ++ + ++ + Post AMI + ++ + +/- ++ CHF ++ ? + - ++ CVA + + +/- ++ + Renal insufficiency ++ +/- + ++ ++ Diabetes - - ++ + ++ Dyslipidemia - - ++ + + BPH ++
Some commonly-used anti-hypertensive drugs
Drug Initial dose Usual dose range
Beta blockers
Atenolol 50mg qd 25 - 100mg Metoprolol 50mg bid 50 - 450 mg Nadolol 40 mg qd 20 - 240mg Propanolol 40mg bid 40 - 240mg Proponolol LA 80mg qd 60 - 240 mg Labetalol 100mg bid 200 - 1200 mg Cardevidol
6.25 mg bid 12.5 - 50 mg Calcium channel blockers
Diltiazem 5 mg qd 2.5 - 10 mg Diltiazem SR 60 - 120 mg bid 120 - 360 mg Diltiazem CD 180 mg bid 180 - 360 mg Diltiazem XR 80 mg qd 180 - 480 mg Nicardipine 20mg tid 60 - 120 mg Nicardipine SR 30 mg bid 60 - 120 mg Nifedipine XL 30 mg qd 30 - 90 mg Verapamil SR 120 - 140 mg qd 120 - 480 mg
Angiotensin-converting enzyme inhibitors
Captopril 25 mg bid 50 - 450 mg Enalapril 5 mg qd 2.5 - 40 mg Fosinopril 10 mg qd 10 - 40 mg Lisinopril 10 mg qd 5 - 40 mg
Diuretics
Chlorthiazide 500mg qd 125 - 1000 mg Hydrochlorthiazide 25 mg qd 12.5 - 50 mg Indapamide 1.25 mg qd 2.5 - 5 mg Metolazone 2.5 mg qd 1.25 - 5 mg Bumetanide 0.5 mg qd 0.5 - 5 mg Furosemide 20 mg qd 20 - 320 mg Torsemide 5 mg qd 5 - 10 mg