2.3 Vasoactive & Inotropic Pharmacology

Matching the Drug to the Hemodynamic Problem

Vasoactive drugs are chosen by the receptor they stimulate and the hemodynamic deficit you must correct. Four receptor families drive the exam answers:

• Alpha-1 (a1): arterial vasoconstriction, raising SVR and MAP.
• Beta-1 (b1): increased contractility (inotropy) and heart rate (chronotropy), raising cardiac output.
• Beta-2 (b2): vasodilation and bronchodilation.
• Dopaminergic and V1 (vasopressin) receptors: dose-dependent and non-catecholamine vasoconstriction.

A vasopressor primarily raises SVR/MAP (fixing vasodilation); an inotrope primarily raises contractility and output (fixing pump failure). Many agents do both, and the key exam skill is knowing which effect dominates.

Vasopressors

Norepinephrine (Levophed) — strong a1 with modest b1. It raises SVR and MAP with less tachyarrhythmia than dopamine, which is why the Surviving Sepsis Campaign names it the first-line vasopressor for septic and most distributive shock. Typical infusion 0.01-3 mcg/kg/min (about 2-20 mcg/min), titrated to MAP.

Epinephrine — a1, b1, and b2. At low doses beta effects dominate (inotropy, chronotropy, bronchodilation); at high doses alpha vasoconstriction predominates. It is the second-line add-on in septic shock, the drug for anaphylaxis (IM 0.3-0.5 mg of 1:1000), and the code drug for cardiac arrest (1 mg IV of 1:10,000). Infusion 0.01-0.5 mcg/kg/min. Watch for tachycardia, hyperglycemia, and lactate elevation.

Vasopressin — a non-catecholamine acting on V1 receptors to vasoconstrict independent of adrenergic tone. Given at a fixed 0.03 units/min as an adjunct to norepinephrine in septic shock to raise MAP and spare catecholamine dose. It is not titrated; higher doses risk digital, mesenteric, and cardiac ischemia.

Phenylephrine (Neo-Synephrine) — a pure a1 agonist. It raises SVR/MAP but triggers reflex bradycardia and can lower cardiac output. Useful when tachyarrhythmias make norepinephrine risky, or briefly for neurogenic hypotension. Dose about 40-180 mcg/min.

Dopamine — dose-dependent: low (1-3 mcg/kg/min) dopaminergic (renal, no proven clinical benefit), moderate (3-10) b1 inotropy, high (>10) a1 vasoconstriction. It causes more tachyarrhythmias than norepinephrine and is now reserved for select bradycardic patients (an ACLS alternative to atropine/pacing) rather than routine shock.

Inotropes

Dobutamine — predominant b1 with some b2. It raises contractility and cardiac output while mildly lowering SVR (afterload reduction), making it the inotrope of choice in cardiogenic shock and low-output heart failure once perfusion pressure is supported. Dose 2-20 mcg/kg/min. It can cause hypotension (from b2 vasodilation) and tachycardia, so a vasopressor may be needed alongside.

Milrinone — a phosphodiesterase-3 (PDE-3) inhibitor, an "inodilator" that raises contractility while dilating both systemic and pulmonary vessels. Because it works independent of beta-receptors, it is valuable in patients on chronic beta-blockers and in right-ventricular failure with pulmonary hypertension. Dose 0.125-0.75 mcg/kg/min. It is renally cleared (accumulates and causes prolonged hypotension in renal failure) and commonly causes hypotension and ventricular arrhythmias.

Vasoactive & Inotropic Agents

Titration and Safety

Titrate every vasoactive to an explicit hemodynamic goal, most often MAP >= 65 mmHg, adjusting in small increments while watching heart rate, rhythm, and perfusion (urine output, lactate, capillary refill). Best practice tested on the CCRN: infuse through a central line whenever possible; never bolus a continuous vasopressor; double-check pump concentration and rate; and wean gradually to prevent rebound hypotension. If norepinephrine or another potent vasoconstrictor extravasates, stop the infusion and infiltrate the site with phentolamine to reverse local ischemia. Finally, remember the treatment sequence in shock: restore volume and perfusion pressure first (vasopressor to a MAP goal), then add an inotrope for persistent low output — giving an inotrope to a hypovolemic, vasodilated patient without a pressor will worsen hypotension.

Choosing an Agent by Hemodynamic Profile

Match the drug to the deficit shown by the numbers. Low SVR with adequate output (distributive shock) calls for a vasoconstrictor: norepinephrine first, then vasopressin. Low cardiac output with high SVR and high filling pressures (cardiogenic shock) calls for an inotrope once MAP is supported: dobutamine, or milrinone when the patient is on beta-blockers or has right-ventricular failure with pulmonary hypertension. Persistent hypotension despite volume and a first pressor is "refractory" shock, prompting a second agent (epinephrine or vasopressin) and a search for adrenal insufficiency, acidosis, or missed source control.

Titration Worked Example

A septic patient on norepinephrine at 8 mcg/min has a MAP of 60 mmHg. You increase to 12 mcg/min and the MAP rises to 68 — at goal. Rather than pushing the norepinephrine higher (and risking arrhythmia and digital ischemia), the evidence-based next step for a rising catecholamine requirement is to add fixed-dose vasopressin 0.03 units/min to spare the norepinephrine dose. If the cardiac index then remains low with a high lactate despite an adequate MAP, add dobutamine for inotropy.

High-Yield Pharmacology Traps

• Vasopressin is never titrated — it runs at a fixed 0.03 units/min.
• Dobutamine and milrinone can cause hypotension through vasodilation; they are inotropes, not resuscitation pressors.
• Milrinone accumulates in renal failure, causing prolonged hypotension.
• Phenylephrine causes reflex bradycardia and can drop cardiac output despite raising blood pressure.
• Dopamine causes more tachyarrhythmias than norepinephrine and is no longer a routine shock pressor.