Vasopressors Used in the ICU
- Phenylephrine (Neosynephrine) at 10-200 μg/min: α1
- Norepinephrine (Levophed) at 4-12 μg/min: α1 (high), α2 (high), β1 (moderate)
- Epinephrine at > 0.1 μg/kg/min: α1 (high), α2 (high), β1 (high), β2 (high)
- Epinephrine at 0.005 – 0.02 μg/kg/min: β2 (high), β1 (moderate)
- Dobutamine at 2.5-10 μg/kg/min: β1 (high), β2 and α1 (low)
- Isoproterenol at 0.5-10 μg/min: : β1 (high), β2 (low)
- Dopamine at 3.0 – 7.5 μg/kg/min: β1, dopamine
PDE-III inhibition (synergism with β1 agonists, ex. epi)
- Milrinone 0.375 – 0.75 μg/kg/min
Vasopressor Agonism (primary systemic vascular resistance, relatively sparing the pulmonary vasculature)
- Vasopressin at 0.01– 0.04 units/min
- Dopamine at 0.5 – 3.0 μg/kg/min: dopamine
- Epinephrine at 0.02 – 0.1 μg/kg/min: α1 (low), β1 (high), β2 (high)
- Dopamine at > 7.5 μg/kg/min: α1, β1, dopamine
The cerebral vasculature in rats and pigs lacks significant α1 receptors [J Cereb Blood Flow Metab 1: 329, 1981], however human studies suggest otherwise – one study showed that norepinephrine-induced contractions in human cerebral vessels are mediated by α1 receptors [J Pharmacol Exp Ther 226: 861, 1993]. Another showed that alpha receptors are present but that inptraparenchmyal vessels lack significant muscarine receptors and choline acetyltransferase activity [J Cereb Blood Flow Metab 5: 458, 1985]
Norepinephrine (Levophed): does not affect CO except for a mild increase at low doses. First drug of choice in septic patients.
Phenylephrine (Neosynephrine) is a pure α1-agonist and is ideal in patients with hypotension and tachycardia. Avoid in SCI (use dopamine first line, even before fluids). May decrease cardiac output and renal perfusion. To maintain cerebral perfusion during systemic hypotension, it is common clinical practice to raise blood pressure using a vasopressor. Phenylephrine is probably the most frequent choice. Concerns were raised in the past about a possible direct cerebral vasoconstrictive effect, negating the potential benefits from increased systemic blood pressure. In the article,”A Decrease in Spatially Resolved Near-Infrared Spectroscopy-Determined Frontal Lobe Tissue Oxygenation by Phenylephrine Reflects Reduced Skin Blood Flow,” published in Anesthesia & Analgesia, it was shown possibly that the decrease in ScO2 during phenylephrine is a result of extracranial vasoconstriction.
Dopamine if first-line in spinal cord injury patients (Greenberg) and should be used prior to giving fluids.
Dobutamine is dangerous as it may exacerbate myocardial ischemia in 10%.
Anti-Hypertensives in the ICU
ANTI-HYPERTENSIVES (VASODILATORS) USED IN THE ICU
IV agents Action Onset Peak Duration Comments Labetalol α and β blocker 5 min 19 min 3-6 h No effects on ICP Esmolol β blocker Minimal bronchospasm Nicardipine CCB No effects on ICP Enalaprilat ACE inhibitor Avoid in pregnancy Hydralazine Arterial only 10 min 30 min 3-6 h Cerebral dysautoregulation? Nitroglycerin Venous >> arterial 1 min 1 min 1-3 min May raise ICP (Greenberg) Nitroprusside Arterial and venous seconds 1 min 1-3 min Raises ICP in patients with mass lesions Oral Agents Metoprolol β blocker Cardioselective when < 200 mg/day Clonidine α2-agonist 30 min 2 hr 3-8h Sedating, causes fluid retention Enalapril ACE inhibitor 15 min 60 min 4-6 h Avoid in pregnancy Nifedipine CCB 5 min 15 min 3-5 h May increase cardiac risk
Nicardipine is ideal as it effectively lowers blood pressure but does not raise ICP, does not require an arterial line, does not reduce heart rate, and may even be used in conjunction with a beta-blocker. Start at 5 mg/hr IV and titrate (can go as high as 15 mg/hr).
Labetalol also has no adverse effects on ICP. It does not affect cardiac output and minimally affects pulse rate. As compared to nitroprusside, labetalol lowers ICP and improves CPP [Crit Care Med 16: 765, 1998]
Nifedipine is short acting and can increase cardiac index but all short-acting CCBs may be associated with cardiac risk, so its use is rarely justified.
Nitroprusside may be used with caution – animal studies (cats) have suggested that it may adversely affect cerebral autoregulation, however a small study of anesthetized patients analyzed with Xenon studies refutes this [Eur J Clin Invest 12: 383, 1982]. A study of patients with intracranial mass lesions showed that nitroprusside, which dilates cerebral vessels, raises ICP and lowers CPP (p < 0.005) [J Neurosurgery 48: 329, 1978]. Andrews believes that it may also result in cerebral venous hypertension (data unavailable on PubMed). According to Greenberg, it may raise ICP.
Neurosurgical Concerns Regarding Blood Pressure Management:
- Norepinephrine (Levophed) raises BP with possible mild increases in CO
- Phenylephrine (Neosynephrine) raises BP, lowers HR, and may decrease CO
- In spinal cord injuries, avoid phenylephrine (use dopamine first-line, even before fluids)
- Nitroprusside should be avoided as it has been shown to raise ICP in patients with intracranial mass lesions [J Neurosurgery 48: 329, 1978]. Nitroglycerine may do the same.