Control of hypertension in the critically ill: a pathophysiological approach

Salgado, Diamantino Ribeiro; Silva, Eliezer; Vincent, Jean-Louis

doi:10.1186/2110-5820-3-17

Annals of Intensive Care

Table 4 Doses, pharmacokinetics, and pharmacodynamics of the intravenous antihypertensive agents most frequently used in intensive care units

From: Control of hypertension in the critically ill: a pathophysiological approach

Drugs	Intravenous dose	Onset/peak of action	Half-life/duration of action	Metabolism/excretion	Main side effects	Main clinical indications
Sympatholytic drugs
β-blockers
Propranolol (β₁- and β₂-receptor blocker)	1-3 mg every 2–5 min (over 1–30 min)	Onset: 5 min	Half-life: 3–5 h	Metabolism: hepatic CYP450	Hypotension, heart failure, heart block, dizziness, fatigue, confusion, depression, bronchospasm, Raynaud´s phenomenon, diarrhea, pruritus, rash	Cardiac ischemic syndromes with arterial hypertension and normal heart function. Avoid in pheochromocytoma crises
	Max dose: 5 mg		Duration: 6–12 h	Excretion: urine (96-99%)
	Infusion: not recommended
Metoprolol (selective β₁-receptor blocker)	5 mg every 3 min (over 1–30 min)	Onset: 5–10 min	Half-life: 3–7 h	Metabolism: hepatic CYP2D6	Hypotension, heart failure, heart block, dizziness, fatigue, depression, bronchospasm, diarrhea, pruritus, rash	Cardiac ischemic syndromes with arterial hypertension and normal heart function
	Max dose: 15 mg		Duration: 5–8 h	Excretion: urine (5-10% unchanged)
	Infusion: not recommended
Labetalol (α₁, β₁, and β₂-receptor blocker)	Bolus: 20–80 mg every 10 min. Max dose: 300 mg	Onset: 5–10 min	Half-life: 6 h	Metabolism: hepatic glucuronide conjugation	Nausea, scalp tingling, bronchospasm, dizziness, heart block, orthostatic hypotension	Most hypertensive emergencies, good for hypertension in neurocritically ill patients and pregnancy; caution in heart failure
Labetalol (α₁, β₁, and β₂-receptor blocker)	Infusion: 0.5-2.0 mg/min	Peak: 5–15 min	Duration: 3–18 h	Excretion: urine 50% (<5% unchanged), feces 50%
Esmolol (selective β₁-receptor blocker)	Bolus: 500 μ g/Kg (over 1 min)	Onset: 1–2 min	Half-life: 9 min	Metabolism: plasma esterases	Arterial hypotension, bronchospasm, heart block, heart failure	Hypertensive emergencies with normal or high cardiac output, and aortic dissection in particular. Contraindicated in pheochromocytoma crisis
	Max dose: 300 μg/Kg/min	Peak: 6–10 min	Duration: 10–30 min	Excretion: urine 70-90% (<1% unchanged)
	Infusion: 50–300 μg/Kg/min
α-Adrenergic antagonists
Phentolamine (peripheral α-receptor antagonist)	Bolus: 5–20 mg	Onset: 1–2 min	Half-life: 19 min	Metabolism: hepatic	Tachycardia, flushing, headache, orthostatic hypotension, dizziness, nasal congestion, pulmonary hypertension	Hypertensive emergencies associated with excessive catecholamine levels
	Max dose: 15 mg	Peak: 10–20 min	Duration: 15–30 min	Excretion: urine (10% unchanged)
	Infusion: not recommended
Urapidil (peripheral α₁-receptor antagonist and central serotonin antagonist)	Bolus: 12.5-25 mg	Onset: 3–5 min	Half-life: 2–4.8 h	Metabolism: hepatic	Headache, hypotension, dizziness	Hypertensive emergencies in postoperative and pregnant patients
	Max dose: 50 mg	Peak: 0.5-6 h	Duration: 4–6 h	Excretion: urine (15-20% unchanged), feces 10%
	Infusion: 5–40 mg/h
Centrally acting agents
Clonidine (central α₂ receptor agonist)	Bolus: not recommended	Onset: 5–10 min	Half-life: 12 h	Metabolism: Hepatic CYP450	Eye and mouth dryness, sedation, erectile dysfunction, orthostatic hypotension, bradycardia, drowsiness.	Hypertensive emergencies, particularly in the context of withdrawal syndrome and pain
	Max dose: 7.2 μg/min (or 450 μg/2 h)	Peak: 2–4 h	Duration: 6–10 h	Excretion: Urine (50% unchanged), feces/bile 20%
	Infusion: 1.2-7.2 μg/min
Methyldopa (central α₂ receptor agonist)	250-1000 mg every 6-8h	Onset: >1 h	Half-life: 2 h	Metabolism: Hepatic CYP450 and central adrenergic neurons	Peripheral edema, fever, depression, sedation, dry mouth, bradycardia, hepatitis, hemolytic anemia, lupus-like syndrome	Hypertensive emergencies, particularly in pregnant patients. Use limited by adverse effects
	Max dose: 1000 mg every 6h	Peak: 6–8 h	Duration: 12–24 h	Excretion: urine (85% metabolites), feces
	Infusion: not recommended
Dexmedetomidine (central α₂₋receptor agonist)	Bolus: 1 μg/Kg/min over 10 min (not necessary in sedated patients)	Onset: 6–15 min	Half-life: 2–2.5 h	Metabolism: hepatic	Hypotension, bradycardia, fever, nausea, vomiting, hypoxia, anemia	Hypertensive urgencies associated with hyperactive delirium or withdrawal syndrome
	Max dose: 1.5 μg/Kg/h	Peak: 1 h	Duration: 4 h	Excretion: urine (metabolites)
	Infusion: 0.2-0.7 μg/Kg/h
Calcium channel blockers
Nicardipine	Bolus: not recommended	Onset: 5–10 min	Half-life: 2–4 h	Metabolism: hepatic CYP3A4	Tachycardia, headache, flushing, peripheral edema, angina, nausea, AV block, dizziness	Most hypertensive emergencies; caution in heart failure
	Max dose: 30 mg/h	Peak: 30 min	Duration: 4–6 h	Excretion: urine 60% (<1% unchanged), feces 35%
	Infusion: 5–15 mg/h
Clevidipine	Bolus: not recommended	Onset: 1–2 min	Half-life: 1–15 min	Metabolism: plasma and tissue esterases	Atrial fibrillation, nausea, fever, insomnia, headache, acute renal failure	All hypertensive emergencies, particularly postoperative hypertension
	Max dose: 32 mg/h	Peak: 3 min	Duration: 5–15 min	Excretion: urine 63-74%, feces 7-22%
	Infusion: 1–2 mg/h
Diltiazem	Bolus: 0.25 mg/Kg (over 2 min)	Onset: 2–7 min	Half-life: 3.4 h	Metabolism: hepatic CYP3A4	Bradycardia, AV block, hypotension, cardiac failure, peripheral edema, headache, constipation, hepatic toxicity	Hypertensive emergencies associated with normal heart function and tachyarrhythmia
	Max dose: 15 mg/h	Peak: 7–10 min	Duration:30 min-10 h (median 7 h)	Excretion: bile, urine (2-4% unchanged)
	Infusion: 5–15 mg/h (≤24 h)
ACE inhibitor
Enalaprilat	Bolus: 1.25-5 mg every 6 h	Onset: 15–30 min	Half-life: 11 h	Metabolism: hepatic biotransformation	Hypotension, headache, worsening of renal function, hyperkalemia, angioedema, cough, agranulocytosis	Hypertensive emergencies associated with left ventricular dysfunction; caution in hypovolemia
	Max dose: 5 mg every 6 h	Peak: 3–4.5 h	Duration: 6–12 h	Excretion: urine (60-80%)
	Infusion: not recommended
Arterial vasodilators
Hydralazine (arteriolar vasodilator)	Bolus: 10–20 mg every 4–6 h	Onset: 5–20 min	Half-life: 2–8 h	Metabolism: Hepatic acetylation	Hypotension, tachycardia, headache, facial flushing, angina pectoris, vomiting, paradoxical hypertension, lupus-like syndrome	Hypertensive emergencies, especially severe hypertension in pregnancy
	Max dose: 40 mg per dose	Peak: 30–60 min	Duration: 1–8 h	Excretion: urine 52-90% (14% unchanged), feces 10%
	Infusion: not recommended
Fenoldopam (selective dopamine type 1-receptor agonist)	Bolus: not recommended	Onset: 5–10 min	Half-life: 5 min	Metabolism: Hepatic methylation	Hypotension, tachycardia, headache, nausea, facial flushing, angina, ST-T wave changes, elevated intraocular pressure	Hypertensive emergencies, especially severe hypertension in patients with acute renal failure
	Max dose: 1.6 μg/Kg/min	Peak: 15 min	Duration:30–60 min	Excretion: urine 90%, feces 10%.
	Infusion: 0.05-1.6 μg/Kg/min
Mixed arterial/venous vasodilators
Nitroprusside (nitric oxide donor)	Bolus: not recommended	Onset: 1–2 min	Half-life: <10 min (nitroprusside), 3 days (thiocyanate)	Metabolism: erythrocytes, hepatic methylation	Hypotension, tachycardia, headache, cyanide and thiocyanide intoxication, nausea, flushing, vomiting, muscle spasm, pulmonary shunt	Hypertensive emergencies, especially aortic dissection. Caution in renal and hepatic failure
	Max dose: 10 μg/Kg/min (<1 h)	Peak: 15 min		Excretion: urine
	Infusion: 0.25-4 μg/Kg/min		Duration: 1–10 min
Nitroglycerin (nitric oxide donor with predominant venular action)	Bolus: not recommended	Onset: 2–5 min	Half-life: 1–3 min	Metabolism: erythrocytes, hepatic, vessel wall	Hypotension, headache, dizziness, vomiting, tachyphylaxis, methemoglobinemia	Hypertensive emergencies, especially those associated with acute coronary syndrome, volume overload, or pulmonary edema
	Max dose: 300 μg/min	Peak: 5 min	Duration: 5–10 min	Excretion: urine
	Infusion: 5–300 μg/min
Diuretics
Furosemide (inhibits reabsorption of Na/Cl in the ascending loop of Henle)	Bolus: 20–40 mg	Onset: 5 min	Half-life: 30–60 min	Metabolism: hepatic	Hypokalemia, hypovolemia, hypotension, metabolic alkalosis, ototoxicity, thrombocytopenia, pancreatitis, interstitial nephritis, hyperglycemia, hyperuricemia	Hypertensive emergencies, especially those associated hypervolemia and/or heart failure
	Max dose: 200 mg/dose or 160 mg/h	Peak: 1–2 h	Duration: 2 h	Excretion: urine 88%, bile/feces 12%.
	Infusion: 10–40 mg/h
Bumetanide (inhibits reabsorption of Na/Cl in the ascending loop of Henle)	Bolus: 0.5-1 mg/dose up to 2 times/day	Onset: 2–3 min	Half-life: 1–1.5 h	Metabolism: hepatic	Hypokalemia, hypovolemia, hypotension, metabolic alkalosis, ototoxicity, thrombocytopenia, pancreatitis, interstitial nephritis, hyperglycemia, hyperuricemia	Hypertensive emergencies, especially those associated with hypervolemia and/or heart failure
	Max dose: 10 mg/day	Peak: 1–4 h	Duration:4–6 h	Excretion: urine 81%, bile 2%
	Infusion: 0.5-2 mg/h

ACE angiotensin-converting enzyme.

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