MechanismDecreases coronary vasospasm, increases coronary blood flow. Induces vessel dilatation, decreasing cardiac workload. Dose5–20 µg/min IV infusion Also referenced as0.25–5 mcg/kg/min IV Onset / Duration2–5 min onset · 3–5 min duration after discontinuation Adverse EffectsHeadache, tachycardia, nausea, vomiting, flushing, methaemoglobinaemia, hypotension, bradycardia PrecautionsRequires special delivery system due to drug binding to plastic tubing. Tolerance may develop. Useful primarily with myocardial ischaemia. Do not give to patients who have taken phosphodiesterase inhibitors within 24 hours (48 hours for tadalafil).

ActionCalcium channel blocker Dose5 mg/h IV; may increase by 1–2.5 mg/h every 15 minutes to 15 mg/h Onset / Duration1–5 min onset · 3–6 hours duration Adverse EffectsHypotension, tachycardia, headache CommentsMay precipitate myocardial ischaemia

ActionCalcium channel blocker Dose1–2 mg/h IV initially; double rate every 90 seconds until near goal, then by smaller amounts every 5–10 minutes to a maximum of 32 mg/h Onset / Duration2–4 min onset · 5–15 min duration Adverse EffectsHeadache, nausea, vomiting PrecautionsLipid emulsion — contraindicated in patients with allergy to soy or egg

ActionAlpha, β1, β2 blocker Dose20 mg IV bolus over 10 minutes, then 1–2 mg/min IV infusion; up to 300 mg total Also referenced as20–40 mg IV every 10 minutes to 300 mg; 2 mg/min infusion Onset / Duration5–10 min onset · 3–6 hours / 15–30 min after discontinuation Adverse EffectsBronchoconstriction, heart block, orthostatic hypotension, GI, bradycardia PrecautionsAvoid in acute LV systolic dysfunction, asthma. May be continued orally. Respiratory distress in COPD, asthma patients — test dose of esmolol recommended, switch to diltiazem if esmolol intolerant.

ActionUltra-short-acting β-adrenergic blocker Dose500 µg/kg IV bolus or 25–100 µg/kg/min infusion; may repeat bolus after 5 min or increase infusion rate to 300 µg/kg/min Also referenced asLoading dose 500 mcg/kg IV over 1 minute; maintenance 25–200 mcg/kg/min Onset / Duration1–5 min onset · 10–30 min duration / 15–30 min after discontinuation Adverse EffectsFirst-degree heart block, congestive heart failure, asthma, bradycardia, nausea PrecautionsAvoid in acute LV systolic dysfunction, asthma. Weak antihypertensive.

ActionVasodilator Dose0.25–10 mcg/kg/min IV Onset / DurationSeconds onset · 3–5 min duration Adverse EffectsGI, CNS; thiocyanate and cyanide toxicity especially with renal and hepatic insufficiency; hypotension; coronary steal; decreased cerebral blood flow; increased intracranial pressure PrecautionsNo longer the first-line agent. Always use β-blocker prior to vasodilators. Cyanide and thiocyanate toxicity — avoid with reduced renal function or therapy > 24–48 hours.

ActionVasodilator — direct vasodilation of arterioles, decreases systemic resistance Dose5–20 mg IV bolus; may repeat after 20 minutes; 5–10 mg IV bolus repeat every 4–6 hours Onset / Duration10–30 min onset · 2–6 hours duration / > 1 hour after discontinuation Adverse EffectsTachycardia, headache, vomiting, aggravation of angina pectoris, GI PrecautionsAvoid in coronary artery disease, dissection. Rarely used except in pregnancy.

ActionDopamine receptor agonist Dose0.1–1.6 mcg/kg/min IV Onset / Duration4–5 min onset · < 10 min duration Adverse EffectsReflex tachycardia, hypotension, increased intraocular pressure CommentsMay protect kidney function

ActionACE inhibitor Dose1.25 mg IV every 6 hours Onset / Duration15 min onset · 6 hours or more duration Adverse EffectsExcessive hypotension CommentsAdditive with diuretics. May be continued orally. Enalaprilat may cause sustained hypotension — use with caution.

ActionDiuretic Dose10–80 mg orally Onset / Duration15 min onset · 4 hours duration Adverse EffectsHypokalaemia, hypotension CommentsAdjunct to vasodilator

ActionAlpha-adrenergic blocker UseSympathetic crisis, cocaine toxicity, phaeochromocytoma RouteIV or IM PrecautionsMust be given before β-blockers in catecholamine excess — giving β-blockers first may cause paradoxical hypertension

Preferred Agents

• Nicardipine IV continuous infusion PRIMARY
• Labetalol IV continuous infusion PRIMARY
• Fenoldopam IV continuous infusion
• Clevidipine IV continuous infusion
• Esmolol, Enalaprilat (alternatives)

tPA Candidate — BP > 185/110 mmHg

• Labetalol 10–20 mg IV over 1–2 minutes, may repeat 1 time
• Other agents (hydralazine, enalaprilat) may be considered when appropriate
• If BP is not maintained at or below 185/110 mmHg — do NOT administer rtPA

During and After rtPA — maintain BP ≤ 180/105 mmHg

• Monitor BP every 15 min for 2 hours from start of rtPA, then every 30 min for 6 hours, then every hour for 16 hours
• If SBP 180–230 mmHg or DBP 105–120 mmHg: Labetalol 10 mg IV followed by continuous IV infusion 2–8 mg/min
• If BP not controlled or DBP > 140 mmHg — consider IV sodium nitroprusside
• After fibrinolysis: maintain SBP < 180 mmHg and DBP < 105 mmHg for 24 hours

tPA Candidate — BP > 185/110 (Nicardipine Protocol)

• Nicardipine IV 5 mg/h; titrate up by 2.5 mg/h every 5–15 min; maximum 15 mg/h; adjust when desired BP is reached
• Nitroprusside may be used if BP not controlled with above agents or DBP > 140 mmHg

Hypertension Excludes tPA — BP > 185/110 on 3rd measurement

• Treat if > 220/120 mmHg on third of three measurements, spaced 15 min apart
• Labetalol 10 mg IV bolus followed by IV continuous infusion 2–8 mg/min
• Nicardipine IV 5 mg/h; titrate up by 2.5 mg/h every 5–15 min; max 15 mg/h
• Do not lower SBP by > 10–15% in first 24 hours

No Fibrinolysis — SBP > 220 or DBP > 120

• Reasonable goal: lower BP by 15% during first 24 hours after stroke onset
• Be careful with BP control in patients taking oral β-blockers or clonidine — antihypertensive withdrawal syndrome may occur

If SBP > 200 or MAP > 150 mmHg

• Consider aggressive management with IV infusion, or IV boluses while maintaining CPP ≥ 60 mmHg

If SBP 180–200 or MAP 130–150 mmHg

• Use infusions or IV boluses while maintaining CPP ≥ 60 mmHg

If SBP 180–200 or MAP 130–150 — No elevated ICP

• Goal MAP: 110 mmHg (160/90 mmHg)

With Signs of Increased ICP

• Maintain MAP just below 130 mmHg (or SBP < 180 mmHg) for first 24 hours after onset

Without Increased ICP

• Maintain MAP < 110 mmHg (or SBP < 160 mmHg) for first 24 hours after symptom onset

Controlled lowering with IV Labetalol

• Recommended only when SBP > 200 mmHg or DBP > 110 mmHg (in absence of bradycardia)
• Labetalol IV bolus 10–20 mg, may repeat one time; or IV continuous infusion

Preferred Agents

• Nicardipine IV continuous infusion
• Labetalol IV bolus or continuous infusion
• Esmolol IV bolus, then continuous infusion
• Clevidipine IV continuous infusion

Nimodipine

• Used to prevent delayed ischaemic neurological deficits
• NOT indicated for treating acute hypertension
• Nimodipine decreases mortality — BP control is not its primary goal; some decrease in BP may be seen
• Clazosentan is used with success in lieu of nimodipine and has similar hypotensive effects

Preferred Agents

• Nicardipine IV continuous infusion
• Labetalol IV bolus 10–20 mg, or continuous infusion
• Esmolol IV bolus, then continuous infusion
• Clevidipine IV continuous infusion

Preferred Treatment — Combination of:

• a) Narcotic analgesics (morphine sulphate)
• b) β-blockers: Labetalol or Esmolol — OR — calcium channel blockers (verapamil, diltiazem if β-blocker intolerant)
• c) Vasodilators: Nicardipine, Nitroprusside, Nitroglycerin

Labetalol

• 20 mg IV bolus over 10 min then continuous infusion
• Always use β-blocker prior to vasodilators

Nicardipine

• IV continuous infusion (after β-blocker)

Nitroprusside

• IV continuous infusion (after β-blocker)
• Nitroprusside alone increases wall stress from reflex tachycardia — always use β-blocker first

Avoid β-blockers if:

• Aortic valvular regurgitation AVOID β-BLOCKERS
• Suspected cardiac tamponade AVOID β-BLOCKERS

Primary / SecondaryPrimary: Esmolol + sodium nitroprusside · Secondary: Labetalol · Alternative: Esmolol + (clevidipine or nicardipine), diltiazem, verapamil

Preferred Medications

• β-blockers (Metoprolol or Labetalol IV) PREFERRED
• Nitroglycerin (SL, topical, or IV continuous infusion) PREFERRED
• Esmolol, Nicardipine (alternatives)

Precautions

• Do not give nitrates to patients who have taken phosphodiesterase inhibitors ≤ 24h (48h for tadalafil)
• Do not give β-blockers in CHF, low-output states, or other contraindications
• Monitor for hypotension — consider RV infarct and volume depletion
• Routine use of IV β-blocker therapy is controversial

Indication-SpecificPrimary: Nitroglycerin · Secondary: Metoprolol, Labetalol · Alternative: Esmolol, Nicardipine

Preferred Agent

• IV or sublingual Nitroglycerin FIRST LINE
• Furosemide (diuresis through vasodilation; symptomatic relief)
• Enalaprilat IV SECONDARY

AlternativesClevidipine, Nicardipine, Sodium Nitroprusside, Nesiritide Precautions

• Intubation or noninvasive ventilatory support decreases preload and may drop BP
• Enalaprilat may cause sustained hypotension — although FDA-approved, use of nesiritide is controversial
• Nicardipine — use with caution; some patients experience a negative inotropic effect
• Nitroprusside — cyanide and thiocyanate toxicity with reduced renal function or therapy > 24–48 h
• Nesiritide — mixed outcomes; most recent ASCEND-HF trial showing no difference in dyspnoea and mortality

Preferred Agents

• Nitroprusside
• Clevidipine
• Nicardipine

NoteAvoid β-blockers — β-blockade prolongs diastole and worsens regurgitation

Preferred Medications

• Hydralazine PRIMARY
• Labetalol SECONDARY
• Nifedipine (oral)
• Nicardipine (alternative)

Medications to AVOID

• Nitroprusside AVOID
• ACE inhibitors (angiotensin-converting enzyme inhibitors) AVOID
• Esmolol AVOID

Seizure Prophylaxis

• IV Magnesium sulphate — treat all patients with eclampsia or preeclampsia to avoid seizures
• Preeclampsia/eclampsia: IV Magnesium 6g initially administered in all cases
• Emergent caesarean section is definitive treatment for eclampsia

Preferred Medications

• Benzodiazepines (Diazepam) — 1st line for cocaine-associated ACS and sympathomimetic drug overdose FIRST LINE
• Phentolamine IV or IM PRIMARY
• Nitroglycerin / Nitroprusside

Phaeochromocytoma Specifics

• Primary: Phentolamine, Nitroprusside, Nicardipine
• β-blockers can be added for BP control ONLY after α-blockade
• Alternative: Fenoldopam, Clevidipine, Nicardipine, Sodium Nitroprusside

Medications to AVOID

• β-adrenergic antagonists prior to phentolamine administration AVOID
• Beta-blocker monotherapy including labetalol — contraindicated for sympathetic crisis AVOID
• Labetalol controversial — if given, administer along with a nitrate

Preferred Agents

• Clevidipine IV continuous infusion PREFERRED
• Nicardipine IV continuous infusion PREFERRED
• Fenoldopam IV continuous infusion (may protect kidney function)
• Labetalol, Sodium Nitroprusside (alternatives)

Avoid

• Nitroprusside — results in cyanide and thiocyanate toxicity AVOID
• ACE inhibitors acutely (some authors contradict this) AVOID
• Angiotensin-converting enzyme inhibitors and diuretics should be avoided (acute kidney injury)

Preferred Treatment

• PO ACE inhibitor (e.g. Captopril) PRIMARY
• IV antihypertensives (e.g. Nicardipine, Nitroprusside)

Preferred

• Nitroglycerin SL, topical, or IV continuous infusion — IV nitrates dilate capacitance vessels at low doses; higher doses dilate arterioles
• Enalaprilat IV — ACE inhibitor (avoid hypotension)
• Nicardipine IV continuous infusion — use with caution; some patients experience a negative inotropic effect
• Nitroprusside IV — cyanide/thiocyanate toxicity with reduced renal function or therapy > 24–48 h
• Loop diuretics

Goals of TreatmentDiminish cardiac workload and improve coronary artery perfusion Optimal AgentsPrimary: Nitroglycerin · Secondary: Metoprolol, Labetalol AlternativesEsmolol, Nicardipine CaveatsRoutine use of intravenous beta blocker therapy is controversial

Goals of TreatmentReduce impedance to forward flow and diminish cardiac workload Optimal AgentsPrimary: Nitroglycerin, Furosemide · Secondary: Enalaprilat AlternativesClevidipine, Nicardipine, Sodium Nitroprusside CaveatsIntubation or noninvasive ventilatory support decreases preload and may drop BP. Enalaprilat may cause sustained hypotension. Although FDA-approved, use of nesiritide is controversial.

Goals of TreatmentReduce shear force and dP/dt Optimal AgentsPrimary: Esmolol + Sodium Nitroprusside · Secondary: Labetalol AlternativesEsmolol + (Clevidipine or Nicardipine), Diltiazem, Verapamil CaveatsAvoid beta blockers if aortic regurgitation is present

Goals of TreatmentReduce haemorrhagic conversion and oedema while avoiding regional hypoperfusion Optimal AgentsPrimary: Nicardipine · Secondary: Labetalol AlternativesEsmolol CaveatsAcute BP reduction is indicated only with planned fibrinolytic administration or when secondary target organ dysfunction is involved. Nitric oxide donors and hydralazine should be avoided.

Goals of TreatmentReduce haematoma expansion and perihaematomal oedema Optimal AgentsPrimary: Nicardipine · Secondary: Labetalol AlternativesEsmolol CaveatsBP may decrease with pain management alone. Clevidipine is currently under investigation. Nitric oxide donors and hydralazine should be avoided.

Goals of TreatmentDecrease brain oedema, reduce intracranial pressure, improve autoregulatory control Optimal AgentsPrimary: Nicardipine · Secondary: Labetalol AlternativesEsmolol, Enalaprilat CaveatsOther causes of altered mental status should be considered in the evaluation. Nitric oxide donors and hydralazine should be avoided.

Goals of TreatmentDecrease pressure in renal parenchyma and glomerular apparatus Optimal AgentsPrimary/Secondary: Clevidipine, Nicardipine AlternativesLabetalol, Sodium Nitroprusside CaveatsAngiotensin-converting enzyme inhibitors and diuretics should be avoided

Goals of TreatmentDecrease intracranial pressure while maintaining placental perfusion Optimal AgentsPrimary: Hydralazine · Secondary: Labetalol AlternativesNicardipine CaveatsIntravenous magnesium (6g initially) is administered in all cases. Emergent caesarean section is definitive treatment.

Goals of TreatmentReduce alpha₁-adrenergic receptor-mediated vasoconstriction Optimal AgentsPrimary: Phentolamine · Secondary: Nitroglycerin AlternativesFenoldopam, Clevidipine, Nicardipine, Sodium Nitroprusside CaveatsBenzodiazepines are first-line therapy when sympathetic crisis is caused by cocaine or amphetamines. Beta blocker monotherapy (including labetalol) is contraindicated.