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Vasopressors and inotropes

Vasopressor and inotropic drugs in adults from receptor pharmacology, kinetics, and trial evidence through selection by shock phenotype, infusion calculation, complications, weaning, and bridge and palliative inotrope therapy.

Definitions and classes of vasoactive drugs

Vasoactive drugs are agents given by continuous intravenous infusion to change arterial pressure, cardiac output, or both. A vasopressor raises systemic vascular resistance (SVR) and arterial pressure by constricting arterioles and, to a lesser extent, veins. An inotrope raises myocardial contractility and therefore stroke volume at a given preload and afterload. Many drugs do both, and the balance depends on dose, receptor density, acid-base status, and the state of the circulation. An inodilator (milrinone, levosimendan) combines inotropy with arterial and venous dilation, so it raises cardiac output while lowering SVR, pulmonary vascular resistance (PVR), and filling pressures. A chronotrope (isoproterenol, and dopamine and epinephrine at some doses) raises heart rate, which matters in bradycardia-dependent low output and in the denervated transplanted heart.

The distinction is pharmacologic, and the clinical decision follows the hemodynamic problem. Hypotension with a low SVR and a preserved or high cardiac output is a vasopressor problem. A low cardiac output with high filling pressures and a high SVR is an inotrope or unloading problem. Most patients in cardiogenic shock have both a pressure problem and an output problem, and the sequence of drugs reflects which threatens organ perfusion first.

Mean arterial pressure (MAP) equals cardiac output multiplied by SVR, plus central venous pressure. A vasopressor that raises SVR without supporting the heart raises MAP only if the ventricle can maintain its stroke volume against the higher afterload. A normal heart does so; a failing left ventricle, whose stroke volume is highly afterload sensitive, often does not. An inotrope that raises output while lowering SVR may leave MAP unchanged or lower it. These two relationships explain most of the clinical behavior of these drugs.

Classes of vasoactive drugs used in adult shock and advanced heart failure. Digoxin is an oral inotrope used for rate control and symptom reduction in chronic heart failure and has no role in shock.

Receptor pharmacology: adrenergic, dopaminergic, vasopressin, angiotensin, and phosphodiesterase pathways

Alpha-1 adrenergic receptors are coupled to the Gq protein. In vascular smooth muscle, activation of phospholipase C generates inositol trisphosphate, which releases calcium from the sarcoplasmic reticulum, and diacylglycerol, which activates protein kinase C. Calcium-calmodulin activates myosin light-chain kinase, and the muscle contracts. Arterioles constrict, which raises SVR, and capacitance veins constrict, which shifts unstressed blood volume into stressed volume and raises venous return. Myocardial alpha-1 receptors contribute a modest positive inotropic effect. Alpha-2 receptors on presynaptic sympathetic terminals inhibit norepinephrine release, and postsynaptic vascular alpha-2 receptors add to vasoconstriction.

Beta-1 adrenergic receptors are coupled to the Gs protein. Adenylyl cyclase raises cyclic adenosine monophosphate (cAMP), which activates protein kinase A. Protein kinase A phosphorylates L-type calcium channels (more calcium entry with each beat), phospholamban (faster calcium reuptake by the sarcoplasmic reticulum calcium ATPase), the ryanodine receptor, and troponin I (faster relaxation). The results are positive inotropy, chronotropy, dromotropy, and lusitropy. Each of these actions raises myocardial oxygen consumption, and the higher cytosolic calcium load lowers the threshold for triggered activity and arrhythmia.

Beta-2 adrenergic receptors relax vascular and bronchial smooth muscle through the same cAMP pathway and lower SVR. In skeletal muscle and the liver they stimulate glycogenolysis, glycolysis, and the sodium-potassium ATPase, which explains the hyperglycemia and hypokalemia seen with epinephrine. The failing human ventricle contains a higher proportion of beta-2 receptors because beta-1 receptors are selectively downregulated.

Dopamine receptors. D1 receptors (Gs-coupled) dilate renal, mesenteric, coronary, and cerebral arterioles and promote natriuresis. Presynaptic D2 receptors inhibit norepinephrine release. Dopamine also acts on alpha and beta receptors and releases norepinephrine from nerve terminals, so part of its effect depends on intact neuronal norepinephrine stores.

Vasopressin receptors. V1a receptors on vascular smooth muscle are Gq-coupled and constrict arterioles through the same calcium pathway as alpha-1 receptors but independently of adrenergic signaling. V2 receptors in the renal collecting duct mediate water reabsorption through aquaporin-2. V1b (V3) receptors in the anterior pituitary stimulate corticotropin release. Vasopressin also closes ATP-sensitive potassium channels in vascular smooth muscle, which are opened in septic vasodilation, and it potentiates the response to catecholamines. Some vascular beds, including the pulmonary circulation, respond with nitric oxide–mediated dilation, which is the basis for its relatively neutral effect on PVR.

Angiotensin II type 1 (AT1) receptors are Gq-coupled and constrict arterioles; they also stimulate aldosterone and vasopressin release. In septic shock, endothelial injury reduces the activity of angiotensin-converting enzyme, so angiotensin I accumulates and angiotensin II falls. Exogenous angiotensin II bypasses that defect.

Phosphodiesterase-3 hydrolyzes cAMP in cardiomyocytes and vascular smooth muscle. Its inhibition raises cAMP without receptor stimulation, so milrinone's inotropic effect persists when beta receptors are blocked or downregulated. In vascular smooth muscle, higher cAMP causes relaxation, which produces the systemic and pulmonary vasodilation that distinguishes the inodilators.

Calcium sensitization. Levosimendan binds troponin C in a calcium-dependent manner and stabilizes the calcium-bound conformation, which increases force without raising the cytosolic calcium transient. It also opens ATP-sensitive potassium channels in vascular smooth muscle and mitochondria, producing vasodilation.

Receptor targets of vasoactive drugs. cAMP, cyclic adenosine monophosphate.

Hemodynamic determinants: pressure, flow, resistance, and oxygen delivery

Organ perfusion depends on the perfusion pressure across each vascular bed and on the flow the heart delivers. Perfusion pressure is MAP minus the downstream pressure. That pressure is central venous pressure for the kidney and liver, intracranial pressure for the brain, and left ventricular end-diastolic pressure (approximated by wedge pressure) for the subendocardium. Subendocardial perfusion pressure is therefore aortic diastolic pressure minus left ventricular end-diastolic pressure. Within its autoregulatory range, each organ keeps flow constant despite changes in pressure; below the lower limit, flow falls with pressure. In chronic hypertension the autoregulatory curve shifts to the right, which is the physiologic basis for higher MAP targets in some hypertensive patients.

Oxygen delivery is cardiac output multiplied by arterial oxygen content. A vasopressor raises pressure, and in the presence of a responsive heart it raises output through venoconstriction and a higher venous return. An inotrope raises output by increasing contractility. Neither drug raises oxygen content, and neither corrects anemia, hypoxemia, or a mechanical lesion.

The ventricle and the arterial tree are coupled. A failing left ventricle operates on a flat contractility (end-systolic pressure-volume) relationship, so each increase in afterload produces a large fall in stroke volume. The right ventricle is even more sensitive to its afterload, the pulmonary arterial impedance. A healthy right ventricle tolerates acute pulmonary hypertension poorly, and right ventricular perfusion depends on the difference between aortic pressure and right ventricular pressure throughout the cardiac cycle. This explains why systemic vasopressors support the failing right ventricle (they restore right coronary perfusion pressure) while drugs that raise PVR harm it.

Heart rate contributes to cardiac output, but tachycardia shortens diastole, which reduces ventricular filling and coronary perfusion time. Catecholamine-induced tachycardia therefore raises myocardial oxygen demand and lowers oxygen supply at the same time, which matters most in ischemic heart disease, aortic stenosis, hypertrophic cardiomyopathy, and mitral stenosis.

Drug effects on the pressure-volume loop

The pressure-volume loop of the left ventricle shows each drug's action as a shift in one boundary. The end-systolic pressure-volume relationship (ESPVR) describes contractility; its slope is end-systolic elastance. The effective arterial elastance (Ea, approximately end-systolic pressure ÷ stroke volume) describes afterload. It appears as a line from end-diastolic volume on the volume axis to the end-systolic corner of the loop. The end-diastolic pressure-volume relationship describes compliance. Stroke volume is the width of the loop, and the point where the arterial elastance line meets the ESPVR sets end-systolic volume.

In cardiogenic shock, the ESPVR is flat and shifted to the right. A vasopressor steepens the arterial elastance line: end-systolic pressure rises, and because the contractility line is flat, end-systolic volume moves right and stroke volume narrows. The loop moves up and to the right, filling pressure rises, and wall stress and oxygen demand increase. This cost is accepted when it restores coronary and organ perfusion pressure, because the left ventricle cannot recover while its own coronary supply is inadequate. Once pressure is adequate, further vasopressor escalation adds afterload without benefit.

An inotrope steepens the ESPVR. With afterload unchanged, end-systolic volume falls and stroke volume widens, at the cost of higher pressure-volume area and oxygen consumption. Dobutamine and milrinone also flatten the arterial elastance line through vasodilation, which widens the loop further and lowers end-diastolic pressure. If the ventricle is underfilled or the vasculature already dilated, the fall in pressure can outweigh the rise in flow. A pure vasoconstrictor such as phenylephrine steepens the arterial elastance line without changing the ESPVR, so in a failing ventricle it narrows the loop, raises filling pressure, and lowers output. Diuretics and venodilators move the loop to the left along the diastolic curve. They lower end-diastolic pressure and widen the coronary perfusion gradient (aortic diastolic pressure minus left ventricular end-diastolic pressure) until preload falls below what the ventricle needs.

Mechanical devices act on the same diagram: a microaxial pump removes blood from the ventricle throughout the cycle and converts the loop to a triangle with lower volumes and pressures, while venoarterial extracorporeal support raises afterload and can widen and shift the loop to the right unless the ventricle is unloaded. Each drug and device can therefore be described by the boundary it moves and by the oxygen cost of the move.

Hemodynamic targets: mean arterial pressure, cardiac index, and perfusion markers

Mean arterial pressure. In septic shock, the initial MAP target of the 2026 Surviving Sepsis Campaign (SSC) guideline is 65 mm Hg. In SEPSISPAM, 776 patients with septic shock were randomized to a MAP target of 80 to 85 or 65 to 70 mm Hg. Mortality did not differ at 28 days (36.6% and 34.0%) or at 90 days. New atrial fibrillation was more frequent with the higher target. In the prespecified subgroup with chronic hypertension, the higher target reduced the need for renal replacement therapy without a mortality difference. In the 65 trial, 2,600 patients aged 65 years or older with vasodilatory hypotension were randomized to permissive hypotension (MAP 60 to 65 mm Hg) or usual care. Vasopressor exposure fell, and 90-day mortality was 41.0% and 43.8% (P = 0.15), with an adjusted odds ratio of 0.82.

In cardiogenic shock, a MAP above 60 to 65 mm Hg is a reasonable initial target in the 2025 American College of Cardiology (ACC) concise clinical guidance. Higher targets raise afterload and myocardial oxygen demand without proven benefit. Patients with right ventricular failure, raised central venous pressure, or raised intracranial or intra-abdominal pressure may need a higher MAP to achieve the same organ perfusion pressure.

Cardiac output and cardiac index. The 2022 American Heart Association (AHA), ACC, and Heart Failure Society of America (HFSA) heart failure guideline lists suggested hemodynamic criteria for cardiogenic shock: systolic pressure below 90 mm Hg or mean pressure below 60 mm Hg, cardiac index below 2.2 L/min/m², wedge pressure above 15 mm Hg, and cardiac power output below 0.6 W. Inotropes are titrated to perfusion end points, and a cardiac index above 2.2 L/min/m² with a cardiac power output above 0.6 W is a common working goal. Cardiac power output (MAP × cardiac output ÷ 451) integrates pressure and flow and was the strongest hemodynamic correlate of in-hospital mortality in the SHOCK registry. Its calculation and thresholds are set out on the cardiogenic shock page.

Perfusion markers. Lactate, urine output, mentation, skin perfusion and capillary refill, and central (ScvO2) or mixed (SvO2) venous oxygen saturation measure whether pressure and flow are adequate. The 2026 SSC guideline suggests capillary refill time and serial lactate measurements to guide resuscitation (both conditional, low certainty). Impaired hepatic clearance prolongs lactate elevation after perfusion has recovered. A low SvO2 (below about 60%) in a patient with adequate hemoglobin and oxygenation indicates inadequate oxygen delivery, and a normal or high value can occur with sepsis, shunting, or impaired oxygen extraction.

Hemodynamic and perfusion targets during vasoactive therapy. Targets are individualized for chronic hypertension, raised venous or intracranial pressure, and goals of care. SvO2, mixed venous oxygen saturation; ScvO2, central venous oxygen saturation.

Preload, fluid responsiveness, and the order of resuscitation

Vasoactive drugs act on a circulation whose volume state determines their effect. In hypovolemia, a vasopressor raises pressure by constricting already constricted beds and worsens tissue perfusion; the norepinephrine and dopamine labels both direct correction of hypovolemia before or during infusion, and the norepinephrine label warns that pressure can appear normal while organ flow falls. In septic shock, fluid and a vasopressor are started together when hypotension is severe. In CENSER, 310 adults with sepsis and hypotension were randomized to early low-dose norepinephrine or standard care. Shock control at 6 hours was 76.1% and 48.4%. Mortality at 28 days did not differ significantly (15.5% and 21.9%), and cardiogenic pulmonary edema and new arrhythmia were less frequent with early norepinephrine.

In cardiogenic shock, most patients are congested and fluid is harmful; a small fluid challenge is given only when examination, echocardiography, or catheter measurements show underfilling, as after overdiuresis or in right ventricular infarction with low filling pressures. Dynamic indices predict whether stroke volume will rise with fluid: the change in stroke volume or velocity-time integral during a passive leg raise, and pulse pressure or stroke volume variation in patients on controlled ventilation in sinus rhythm with adequate tidal volumes. Static measures such as central venous pressure or inferior vena cava size predict fluid responsiveness poorly and are distorted by positive-pressure ventilation, tricuspid regurgitation, pulmonary hypertension, and raised intra-abdominal pressure.

The response to the first vasoactive drug is itself diagnostic. A patient whose pressure rises on norepinephrine but whose lactate, urine output, and venous saturation do not improve has an output problem, not a pressure problem. A patient who becomes hypotensive on dobutamine is underfilled or vasodilated. A patient whose wedge pressure rises sharply on a vasopressor has a ventricle near the limit of its afterload tolerance.

Monitoring during vasoactive therapy

Continuous electrocardiographic monitoring and frequent blood pressure measurement are required for every vasoactive infusion; the norepinephrine label specifies blood pressure every 2 minutes until the target is reached and every 5 minutes thereafter. An arterial catheter gives beat-to-beat pressure, allows frequent blood sampling, and avoids the inaccuracy of cuff measurements in vasoconstricted or arrhythmic patients. Radial arterial pressure can differ from central aortic pressure during intense vasoconstriction, and a femoral catheter is placed when the radial reading is implausibly low.

Perfusion is reassessed after each change: mentation, skin temperature and mottling, capillary refill, urine output, serial lactate during active resuscitation, and venous oxygen saturation when a central or pulmonary artery catheter is present. Echocardiography is repeated when the response is unexpected, to identify new outflow obstruction, tamponade, a mechanical complication, or a change in ventricular function. Electrolytes (potassium, magnesium, ionized calcium), glucose, and kidney function are followed closely because catecholamines and inotropes shift potassium and glucose. Peripheral infusion sites and the extremities are inspected for extravasation and ischemia.

Pharmacokinetics of vasoactive drugs

Catecholamines are cleared within minutes by neuronal reuptake, catechol-O-methyltransferase, and monoamine oxidase, so doses are titrated every few minutes, and interruption of an infusion (a line change, an empty syringe, a flush of a carrier line) produces hypotension within minutes. Kidney and liver failure do not require dose changes, because response is titrated to effect.

Phenylephrine is not a catechol, and its metabolism by monoamine oxidase and sulfotransferase is slower than that of the catecholamines, so its terminal half-life is hours although its effective half-life is minutes.

Milrinone is cleared more slowly. Its terminal elimination half-life in heart failure is about 2.3 to 2.4 hours, and it is excreted largely unchanged by the kidney (83% of an oral dose appears in urine as milrinone). Without a loading dose, steady state takes several half-lives. Levosimendan's own half-life is about 1 hour, but its active metabolite OR-1896 has a half-life of roughly 70 to 80 hours, so hemodynamic effects persist for days after a 24-hour infusion.

Pharmacokinetics from the US prescribing information for each drug (norepinephrine, epinephrine, dopamine, dobutamine, milrinone, vasopressin, angiotensin II, phenylephrine) and published levosimendan pharmacology. COMT, catechol-O-methyltransferase; MAO, monoamine oxidase; ACE2, angiotensin-converting enzyme 2.

Vasoactive drug reference: receptor activity, hemodynamic effect, doses, and adverse effects

Doses from the US prescribing information, the 2025 ACC concise clinical guidance on cardiogenic shock (Table 2), the 2022 AHA/ACC/HFSA heart failure guideline, and the 2018 ACC/AHA/Heart Rhythm Society (HRS) bradycardia guideline. Weight-based doses use actual body weight unless local protocols specify otherwise. CO, cardiac output; HR, heart rate; SVR, systemic vascular resistance; PVR, pulmonary vascular resistance; LV, left ventricular.

Norepinephrine: first-line vasopressor in septic and cardiogenic shock

Pharmacology. Norepinephrine is a potent alpha-1 agonist with moderate beta-1 and minimal beta-2 activity. It raises SVR and MAP, constricts venous capacitance vessels and raises venous return, and supports cardiac output through beta-1 inotropy. The rise in afterload triggers a baroreflex slowing of the heart, so heart rate usually changes little. Cardiac output rises, stays the same, or falls depending on ventricular function: it rises in vasodilatory shock with a normal heart and in right ventricular failure (where coronary perfusion pressure is restored), and can fall in severe left ventricular failure with high afterload sensitivity. Coronary blood flow increases through a higher perfusion pressure and metabolic coronary vasodilation.

Evidence and place in therapy. Norepinephrine is the first-line vasopressor in septic shock. The 2026 SSC guideline recommends it over the other vasopressors (strength and certainty are listed in the septic shock table). The preference over dopamine rests on SOAP II, in which norepinephrine caused half as many arrhythmias and dopamine was associated with higher mortality in the cardiogenic subgroup. In cardiogenic shock, norepinephrine is the usual first vasopressor when hypotension threatens perfusion; the evidence is indirect and comes from SOAP II and OptimaCC. The 2025 ACC concise guidance describes it as a reasonable first choice, and the 2017 AHA scientific statement on cardiogenic shock also favored norepinephrine.

Dosing. The US label expresses dosing as a fixed rate: 8 to 12 mcg/min initially, adjusted to effect, with a typical maintenance dose of 2 to 4 mcg/min. Intensive care practice uses weight-based dosing, usually starting at 0.05 to 0.1 mcg/kg/min and titrating every few minutes. The 2025 ACC guidance lists 0.05 to 1 mcg/kg/min in cardiogenic shock. The 2021 SSC guideline tied doses of 0.25 mcg/kg/min or more to the addition of vasopressin and, after 4 hours, corticosteroids in septic shock. The label preparation is 4 mg in 1,000 mL of dextrose-containing solution (4 mcg/mL); concentrated preparations of 16 to 64 mcg/mL are used for fluid restriction. Dextrose protects against oxidation, and the label does not recommend administration in saline alone.

Adverse effects. Excess vasoconstriction causes digital, cutaneous, and splanchnic ischemia, particularly in hypovolemia, peripheral arterial disease, or high-dose prolonged infusion. The label cautions against infusion into leg veins in older patients and in those with occlusive vascular disease. Extravasation causes necrosis and is treated with phentolamine. Tachyarrhythmia is less frequent than with dopamine or epinephrine. Abrupt cessation causes marked hypotension, so the infusion is reduced gradually. The product contains sodium metabisulfite.

Epinephrine: metabolic effects, shock, anaphylaxis, and cardiac arrest

Pharmacology. Epinephrine stimulates beta-1, beta-2, and alpha receptors. At low infusion rates, beta effects predominate: contractility, heart rate, and cardiac output rise, and beta-2 vasodilation may lower diastolic pressure. As the dose rises, alpha-1 vasoconstriction dominates and SVR increases. Epinephrine is the most potent catecholamine inotrope, and it raises myocardial oxygen consumption and the double product more than norepinephrine at equipressor doses.

Metabolic effects. Beta-2 stimulation of skeletal muscle glycolysis and the sodium-potassium pump raises lactate (aerobic hyperlactatemia, independent of tissue hypoxia), glucose, and potassium uptake into cells. The rise in lactate confounds the principal biochemical marker of perfusion. A falling lactate after epinephrine is stopped, or a lactate that rises while other perfusion markers improve, is consistent with a drug effect, whereas a rising lactate with worsening mentation, urine output, and SvO2 indicates hypoperfusion.

Evidence in cardiogenic shock. OptimaCC randomized 57 patients with infarct-related cardiogenic shock to epinephrine or norepinephrine. Cardiac index and arterial pressure responses were similar, but refractory shock developed in 37% of patients given epinephrine and 7% of those given norepinephrine (P = 0.008), and the trial stopped early. Epinephrine raised heart rate, the double product, and lactate. An individual patient data meta-analysis of 2,583 patients with cardiogenic shock from 16 cohorts found that epinephrine exposure was associated with higher short-term mortality (odds ratio 3.3; 4.2 after propensity matching). These are observational data in which epinephrine is often the last drug added to the sickest patients, so confounding by severity is likely. The combined evidence places epinephrine after norepinephrine and dobutamine or milrinone in cardiogenic shock, except during cardiac arrest and in shock with severe bradycardia.

Evidence in septic shock. CATS randomized 330 patients with septic shock to epinephrine alone or norepinephrine plus dobutamine as needed. Mortality did not differ at 28 days (40% and 34%) or at 90 days, nor did time to hemodynamic success. The 2026 SSC recommendations on adding epinephrine are listed in the septic shock table.

Anaphylaxis and cardiac arrest. Epinephrine is first-line treatment of anaphylaxis: 0.3 to 0.5 mg intramuscularly into the anterolateral thigh in adults, repeated every 5 to 10 minutes as necessary (label). A continuous intravenous infusion is used for anaphylactic shock that persists despite intramuscular doses and fluid. In cardiac arrest, epinephrine 1 mg intravenously or intraosseously every 3 to 5 minutes raises aortic diastolic and coronary perfusion pressure. In PARAMEDIC2, 8,014 patients with out-of-hospital arrest were randomized to epinephrine or placebo. Survival at 30 days was 3.2% and 2.4% (odds ratio 1.39), but survival with a favorable neurologic outcome did not differ (2.2% and 1.9%), and severe neurologic impairment was more common among survivors who received epinephrine.

Dopamine and the SOAP II trial

Pharmacology. Dopamine is the metabolic precursor of norepinephrine. Its receptor profile is dose dependent but overlaps widely between patients. At about 1 to 5 mcg/kg/min, D1 stimulation dilates renal and mesenteric arterioles and promotes natriuresis. At about 5 to 10 mcg/kg/min, beta-1 stimulation raises contractility and heart rate. Above about 10 mcg/kg/min, alpha-1 vasoconstriction predominates. Part of its action is indirect, through release of neuronal norepinephrine, so the response is blunted when catecholamine stores are depleted in advanced heart failure or prolonged shock. Dopamine also suppresses prolactin, thyrotropin, and growth hormone secretion from the anterior pituitary.

SOAP II. SOAP II randomized 1,679 patients with shock of any cause to dopamine or norepinephrine as first-line vasopressor. Open-label norepinephrine, epinephrine, or vasopressin was added when blood pressure could not be maintained with 20 mcg/kg/min of dopamine or 0.19 mcg/kg/min of norepinephrine. Mortality at 28 days was 52.5% with dopamine and 48.5% with norepinephrine (odds ratio 1.17; 95% CI 0.97 to 1.42; P = 0.10). Arrhythmic events occurred in 24.1% and 12.4% (P < 0.001). In the prespecified subgroup of 280 patients with cardiogenic shock, dopamine was associated with higher 28-day mortality (P = 0.03 in Kaplan-Meier analysis); the 1,044 patients with septic shock and 263 with hypovolemic shock showed no significant difference. The subgroup finding is the main evidence against dopamine in cardiogenic shock and was not a separately powered comparison.

Low-dose ("renal-dose") dopamine. Low-dose dopamine increases urine output but does not protect the kidney. In the Australian and New Zealand Intensive Care Society trial, 328 critically ill patients with early renal dysfunction were randomized to dopamine 2 mcg/kg/min or placebo; peak creatinine, the need for renal replacement therapy, and length of stay did not differ. In ROSE-AHF, 360 patients with acute heart failure and an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m² received low-dose dopamine, low-dose nesiritide, or placebo with diuretics; dopamine did not increase 72-hour urine volume or change cystatin C.

Current role. Dopamine is a second-line chronotrope and pressor for symptomatic bradycardia unresponsive to atropine, at 5 to 20 mcg/kg/min (2018 ACC/AHA/HRS bradycardia guideline, Class 2b for beta-agonist drugs in patients at low likelihood of ischemia), while transcutaneous or transvenous pacing is arranged. Patients treated with monoamine oxidase inhibitors in the preceding 2 to 3 weeks receive an initial dose no greater than one-tenth of the usual dose (label). Dopamine is inactivated in alkaline solutions.

Vasopressin: VASST, VANISH, and catecholamine-sparing use

Physiology and pharmacology. Endogenous vasopressin rises early in shock and then falls to inappropriately low concentrations in established septic shock, a relative deficiency that is the rationale for low-dose replacement. Exogenous vasopressin at 0.03 to 0.04 units/min raises SVR through V1a receptors, restores sensitivity to catecholamines, and allows the norepinephrine dose to fall. It has no direct inotropic or chronotropic effect. Heart rate falls slightly, and cardiac output is unchanged or falls, more so in patients with impaired left ventricular function; the label warns that cardiac index may decrease. Its relative sparing of the pulmonary circulation makes it attractive in right ventricular failure and pulmonary hypertension, where it raises systemic pressure with little change in PVR.

VASST. VASST randomized 778 patients with septic shock receiving at least 5 mcg/min of norepinephrine to low-dose vasopressin (0.01 to 0.03 units/min) or additional norepinephrine (5 to 15 mcg/min), each added to open-label vasopressors. Mortality at 28 days was 35.4% and 39.3% (P = 0.26), and at 90 days 43.9% and 49.6% (P = 0.11). In the prespecified stratum of less severe shock (norepinephrine 5 to 14 mcg/min at randomization), 28-day mortality was 26.5% with vasopressin and 35.7% with norepinephrine (P = 0.05); in more severe shock it was 44.0% and 42.5%. The test for heterogeneity was not significant.

VANISH. VANISH randomized 409 patients with early septic shock in a 2 × 2 factorial design to vasopressin (titrated up to 0.06 units/min) or norepinephrine, and to hydrocortisone or placebo. Kidney failure–free days did not differ. Renal replacement therapy was used less often with vasopressin (25.4% and 35.3%; difference −9.9 percentage points), a secondary finding, and mortality did not differ.

Guideline position. The 2026 SSC guideline (recommendation table) does not specify a norepinephrine dose at which to add vasopressin. The 2021 SSC guideline noted that vasopressin was usually started when norepinephrine reached 0.25 to 0.5 mcg/kg/min, and that range remains common practice. In cardiogenic shock, vasopressin is a catecholamine-sparing adjunct in mixed shock and in right ventricular failure, used at a fixed dose; no trial has tested it as a primary agent.

Dosing and administration. The label specifies 0.01 to 0.07 units/min for septic shock (start 0.01 units/min) and 0.03 to 0.1 units/min for postcardiotomy shock (start 0.03 units/min), titrated by 0.005 units/min every 10 to 15 minutes. After the target pressure has been maintained for 8 hours without catecholamines, the label describes tapering by 0.005 units/min every hour. Many units give 0.03 or 0.04 units/min as a fixed dose. Higher doses are associated with digital, mesenteric, and coronary ischemia. Vasopressin is diluted to 0.1 or 1 unit/mL.

Adverse effects and interactions. Digital and skin necrosis, mesenteric ischemia, reduced cardiac output, bradycardia, hyponatremia (through V2 activity), and thrombocytopenia are reported. Drugs that cause the syndrome of inappropriate antidiuresis (for example, selective serotonin reuptake inhibitors, tricyclic antidepressants, haloperidol, chlorpropamide, vincristine, and cyclophosphamide) can enhance the pressor response, and drugs that cause diabetes insipidus (lithium, demeclocycline) can blunt it. Vasopressin and catecholamines have additive pressor effects.

Terlipressin. Terlipressin is a longer-acting vasopressin analogue with greater V1 selectivity. It is approved in the United States for hepatorenal syndrome, not for shock.

Angiotensin II: ATHOS-3 and use in refractory vasodilatory shock

Pharmacology and rationale. Synthetic human angiotensin II constricts arterioles through AT1 receptors and stimulates aldosterone and vasopressin release. It acts independently of adrenergic and vasopressin receptors, which makes it a third mechanism in catecholamine-refractory vasodilatory shock. Patients with high circulating angiotensin I relative to angiotensin II, a sign of reduced angiotensin-converting enzyme activity, have been proposed as the group most likely to respond.

ATHOS-3. ATHOS-3 randomized 344 patients with vasodilatory shock to angiotensin II or placebo. All were receiving more than 0.2 mcg/kg/min of norepinephrine or equivalent, and 321 received a study drug. The primary end point, a MAP response at 3 hours (a rise of at least 10 mm Hg or to at least 75 mm Hg without an increase in background vasopressors), occurred in 69.9% with angiotensin II and 23.4% with placebo (odds ratio 7.95). The cardiovascular component of the Sequential Organ Failure Assessment score improved more at 48 hours. Mortality at 28 days was 46% and 54% (hazard ratio 0.78; 95% CI 0.57 to 1.07; P = 0.12). The trial was not powered for mortality.

Dosing and safety. The label starts angiotensin II at 20 ng/kg/min, titrated as often as every 5 minutes by up to 15 ng/kg/min, with a maximum of 80 ng/kg/min in the first 3 hours and 40 ng/kg/min for maintenance; doses as low as 1.25 ng/kg/min may be used. Central venous administration is recommended in the label, and the drug is diluted to 5,000 or 10,000 ng/mL. Arterial and venous thrombotic events occurred in 12.9% of patients given angiotensin II and 5.1% given placebo in ATHOS-3, mainly deep venous thrombosis (4.3% and 0%), so concurrent venous thromboembolism prophylaxis is required. Angiotensin-converting enzyme inhibitors may increase the response and angiotensin receptor blockers may reduce it. Angiotensin II is used as an adjunct in refractory vasodilatory shock. It has not been studied in cardiogenic shock, and the raised afterload it produces is undesirable in a failing left ventricle.

Phenylephrine and its role in dynamic left ventricular outflow obstruction

Pharmacology. Phenylephrine is a selective alpha-1 agonist. It raises SVR and MAP, constricts veins (raising preload), and slows the heart through the baroreflex. It has no inotropic action. In a normal heart, cardiac output is maintained or falls slightly; in left ventricular dysfunction, the rise in afterload without inotropic support reduces stroke volume, and output falls. The label dose for hypotension during anesthesia is a 40 to 100 mcg intravenous bolus, repeated up to 200 mcg every 1 to 2 minutes as needed, or an infusion of 10 to 35 mcg/min, not to exceed 200 mcg/min. Acidosis reduces its effect.

Dynamic outflow obstruction. In obstructive hypertrophic cardiomyopathy, systolic anterior motion of the mitral valve and the outflow gradient increase when preload falls, afterload falls, or contractility rises. Hypotension in this setting is worsened by inotropes, vasodilators, and diuretics. A larger end-systolic cavity relieves the obstruction. The 2024 AHA/ACC hypertrophic cardiomyopathy guideline recommends intravenous phenylephrine or another vasoconstrictor without inotropic activity, alone or with a beta blocker, for acute hypotension that does not respond to fluid (Class 1). The same physiology applies to takotsubo syndrome with basal hyperkinesis and systolic anterior motion, and to hypovolemia with a hypertrophied ventricle. It also applies to a small hyperdynamic ventricle after aortic valve replacement for aortic stenosis or after mitral repair. Echocardiography establishes the mechanism before the drug is chosen. Management of obstructive physiology is described on the hypertrophic cardiomyopathy page.

Other uses and limits. Phenylephrine is widely used to correct anesthesia-induced vasodilation, to raise blood pressure when tachyarrhythmia limits beta-agonists (for example, septic shock with rapid atrial fibrillation), and in aortic stenosis, where a pure vasoconstrictor restores coronary perfusion pressure without tachycardia. The 2025 ACC cardiogenic shock guidance strongly discourages phenylephrine as a single first-line infusion in cardiogenic shock, because it lowers output in left ventricular failure. No randomized trial supports phenylephrine as a primary agent in septic shock.

Dobutamine: dosing, beta-blocker interaction, tolerance, and adverse effects

Pharmacology. Dobutamine is a synthetic catecholamine given as a racemic mixture. The (+) isomer is a beta-1 and beta-2 agonist and an alpha-1 antagonist; the (−) isomer is an alpha-1 agonist. The net effect is strong beta-1 inotropy with modest chronotropy, mild beta-2 vasodilation, and little net alpha effect. Stroke volume and cardiac output rise, SVR and filling pressures fall, and blood pressure rises, stays the same, or falls depending on whether the rise in output outweighs the fall in resistance. Dobutamine does not act on dopamine receptors and does not release norepinephrine. It facilitates atrioventricular nodal conduction, so atrial fibrillation can develop a rapid ventricular response.

Dosing. The label starts dobutamine at 0.5 to 1 mcg/kg/min and titrates every few minutes to response, usually 2 to 20 mcg/kg/min; rates up to 40 mcg/kg/min have rarely been required. In cardiogenic shock and advanced heart failure, 2.5 to 5 mcg/kg/min is a common starting range, and the 2022 AHA/ACC/HFSA guideline lists 2.5 to 20 mcg/kg/min. Low doses provide most of the hemodynamic benefit with less tachycardia. Premixed bags contain 500 to 4,000 mcg/mL.

Beta-blocker interaction. Dobutamine competes with beta blockers at the receptor. In patients on chronic beta blockade, higher doses are needed for the same inotropic effect, and the blunting is greatest with carvedilol, which also blocks alpha-1 receptors. In a hemodynamic study of 29 patients before and after 9 to 12 months of beta blockade, chronic carvedilol abolished the rise in heart rate, stroke volume, and cardiac index during dobutamine infusion. It also produced a rise in pulmonary and wedge pressures and in systemic and pulmonary vascular resistance. Metoprolol blunted the response to a lesser degree. The phosphodiesterase inhibitor response was preserved or enhanced with either beta blocker. The label notes that dobutamine may be ineffective after recent beta blockade and that peripheral resistance may increase. In patients on high-dose beta blockade, milrinone is the more reliable inotrope.

Tolerance and long-term use. Beta-receptor downregulation reduces the hemodynamic effect over days of continuous infusion. In the limited label data, cardiac output stayed elevated in some patients at 72 hours and returned toward baseline in others. The 2022 heart failure guideline acknowledges tachyphylaxis and notes that the agent may need to be changed during longer support.

Adverse effects. Reported effects include tachycardia (a rise of 30 beats/min or more in about 10% of adults in label studies), a rise in systolic pressure of 50 mm Hg or more in about 7.5%, ventricular ectopy, rapid atrial fibrillation, myocardial ischemia, and hypotension in underfilled or vasodilated patients. Hypersensitivity reactions include fever, rash, bronchospasm, and peripheral eosinophilia; eosinophilic (hypersensitivity) myocarditis was found in explanted hearts of transplant candidates on prolonged infusions and regressed in some after dobutamine was tapered. The diagnosis is suspected when cardiac function deteriorates with eosinophilia on long-term dobutamine. Premixed preparations may contain sulfites. Dobutamine provides no benefit across a fixed mechanical obstruction such as severe aortic stenosis, and it increases the gradient in dynamic outflow obstruction.

Milrinone in kidney dysfunction, pulmonary hypertension, and right ventricular failure

Pharmacology. Milrinone inhibits phosphodiesterase-3 in the myocardium and vascular smooth muscle. It raises contractility and lusitropy, dilates systemic and pulmonary arterioles and veins, and lowers wedge pressure, right atrial pressure, SVR, and PVR. Heart rate rises less than with dobutamine at a comparable increase in output. Because its action does not require beta receptors, it is effective during beta blockade and in the downregulated receptor state of advanced heart failure, and it is additive with beta agonists.

Dosing. The label specifies an optional loading dose of 50 mcg/kg over 10 minutes and a maintenance infusion of 0.375 to 0.75 mcg/kg/min (standard 0.5 mcg/kg/min), not to exceed 1.13 mg/kg/day. In practice the loading dose is usually omitted because it causes hypotension. Infusions start at 0.125 to 0.25 mcg/kg/min, the lower end of the 0.125 to 0.75 mcg/kg/min range in the 2022 AHA/ACC/HFSA heart failure guideline (0.125 to 0.5 mcg/kg/min in the 2025 ACC guidance). Without a load, the full effect develops over several hours. The standard premixed concentration is 200 mcg/mL.

Kidney dysfunction. Milrinone is cleared by the kidney, and its terminal half-life rises substantially in severe kidney impairment. The label reduces the infusion rate according to creatinine clearance. Accumulation produces delayed hypotension and arrhythmia hours after the dose was last changed, and the effect persists after the infusion is stopped. In fluctuating acute kidney injury, dobutamine, which has no renal clearance, is easier to titrate.

Maintenance infusion rates in kidney impairment from the US prescribing information for milrinone lactate. The standard rate with normal kidney function is 0.5 mcg/kg/min. Patients receiving renal replacement therapy are dosed at the lowest rates and titrated to effect.

Pulmonary hypertension and right ventricular failure. Milrinone lowers PVR while raising right ventricular contractility, which suits right ventricular failure from pulmonary hypertension, after cardiac surgery or heart transplantation, and after left ventricular assist device implantation. Its systemic vasodilation, however, lowers aortic pressure and with it right coronary perfusion, so it is commonly paired with norepinephrine or vasopressin. Inhaled milrinone, used in some cardiac surgical units for selective pulmonary vasodilation, is an off-label route. Acute right ventricular failure in pulmonary hypertension is managed as described on the pulmonary hypertension page.

Evidence outside shock. In OPTIME-CHF, 949 patients hospitalized with exacerbation of systolic heart failure who did not require inotropes were randomized to a 48-hour milrinone infusion (0.5 mcg/kg/min) or placebo. Days hospitalized for cardiovascular causes within 60 days did not differ (median 6 and 7). Sustained hypotension requiring intervention (10.7% and 3.2%) and new atrial arrhythmias (4.6% and 1.5%) were more frequent with milrinone, and in-hospital and 60-day mortality did not differ significantly. In PROMISE, oral milrinone 40 mg daily in 1,088 patients with class III or IV heart failure increased all-cause mortality by 28% and cardiovascular mortality by 34%, with the largest excess (53%) in class IV. These trials are the basis for avoiding inotropes in heart failure without hypoperfusion and for the label warning that long-term intravenous use has not been shown to be safe.

Adverse effects. Reported effects include hypotension, atrial and ventricular arrhythmias (ventricular arrhythmias in 12.1% of patients in the label's phase II and III trials, most of them ectopy or nonsustained ventricular tachycardia), headache, hypokalemia, and, uncommonly, thrombocytopenia. Like dobutamine, milrinone does not overcome severe fixed valvular obstruction.

Dobutamine versus milrinone: DOREMI and the choice of inotrope

DOREMI randomized 192 patients with cardiogenic shock (Society for Cardiovascular Angiography and Interventions [SCAI] stages B to E) to milrinone or dobutamine in a double-blind design, with doses escalated in four stages. The primary composite of in-hospital death, resuscitated cardiac arrest, transplantation or mechanical support, nonfatal infarction, stroke or transient ischemic attack, or renal replacement therapy occurred in 49% with milrinone and 54% with dobutamine (relative risk 0.90; 95% CI 0.69 to 1.19; P = 0.47). In-hospital death occurred in 37% and 43% (relative risk 0.85; 95% CI 0.60 to 1.21), and the rates of resuscitated arrest, mechanical support, and renal replacement therapy did not differ. The trial was powered for a large effect, and its confidence intervals are compatible with a moderate advantage for either drug. No trial has compared an inotrope with placebo in cardiogenic shock with adequate power.

Because outcome does not differ, the choice rests on pharmacology. The 2022 heart failure guideline states that the choice of inotrope is guided by blood pressure, concurrent arrhythmias, and availability.

Pharmacologic comparison of the two inotropes in US use. DOREMI found no difference in clinical outcomes between them in cardiogenic shock.

Levosimendan: calcium sensitization and trial evidence

Pharmacology. Levosimendan sensitizes troponin C to calcium and opens ATP-sensitive potassium channels. Contractility rises without a large rise in cytosolic calcium or myocardial oxygen consumption, and systemic, pulmonary, and coronary vessels dilate. Its long-lived active metabolite OR-1896 sustains hemodynamic effects for about a week after a 24-hour infusion. It is approved in many European, Latin American, and Asian countries and is not approved in the United States.

Evidence. In LIDO, 203 patients with severe low-output heart failure received levosimendan (24 mcg/kg load, then 0.1 mcg/kg/min for 24 hours) or dobutamine (5 mcg/kg/min). The hemodynamic end point (a 30% rise in cardiac output and a 25% fall in wedge pressure) was met in 28% and 15%, and 180-day mortality was 26% and 38%. The larger SURVIVE trial randomized 1,327 patients with acute decompensated heart failure requiring inotropes and found no difference in 180-day mortality (26% and 28%; hazard ratio 0.91; P = 0.40), with more atrial fibrillation, hypokalemia, and headache with levosimendan. In LeoPARDS, 516 adults with sepsis received levosimendan or placebo; organ dysfunction and 28-day mortality (34.5% and 30.9%) did not differ, supraventricular tachyarrhythmia was more frequent (3.1% and 0.4%), and weaning from ventilation was less successful. In LEVO-CTS, prophylactic levosimendan before cardiac surgery in 882 patients with an ejection fraction of 35% or less did not reduce death, renal replacement therapy, perioperative infarction, or mechanical support.

Place in practice. European practice uses levosimendan for low-output states on beta blockade, for weaning from temporary mechanical support, and as intermittent infusions in advanced heart failure. US practice uses milrinone for the same physiologic indications.

Isoproterenol and chronotropic support

Isoproterenol is a nonselective beta agonist without alpha activity. It raises heart rate and contractility and dilates skeletal muscle and pulmonary vessels, so systolic pressure rises, diastolic pressure falls, and coronary perfusion pressure may fall. Its uses are chronotropic: symptomatic bradycardia and atrioventricular block while pacing is arranged, bradycardia-dependent torsades de pointes (where a faster rate shortens repolarization), bradycardia in the denervated transplanted heart (which responds to direct beta agonism but not to atropine), and electrophysiologic testing. The label dose for shock is 0.5 to 5 mcg/min initially, and the 2018 ACC/AHA/HRS bradycardia guideline lists 1 to 20 mcg/min by infusion (or 20 to 60 mcg boluses). It is avoided in ischemic heart disease, hypertrophic cardiomyopathy with obstruction, and long QT syndromes in which adrenergic stimulation triggers arrhythmia, such as congenital long QT syndrome type 1. The bradycardia page sets out the acute drug and pacing sequence.

Rescue agents for refractory vasoplegia: methylene blue, hydroxocobalamin, and corticosteroids

Vasoplegia is vasodilatory shock with a low SVR and preserved or high cardiac output that persists despite adequate volume and escalating vasopressors. Its common causes are septic shock, cardiopulmonary bypass (postcardiotomy vasoplegia, more frequent with preoperative angiotensin-converting enzyme inhibitors, long bypass times, and heart failure), left ventricular assist device implantation, anaphylaxis, and drug toxicity (calcium channel blockers, beta blockers, and metformin-associated lactic acidosis). Inducible nitric oxide synthase, ATP-sensitive potassium channel opening, relative vasopressin and corticosteroid deficiency, and reduced angiotensin II generation contribute. Each rescue drug targets one of these mechanisms.

Methylene blue. Methylene blue inhibits nitric oxide synthase and soluble guanylate cyclase, which reduces cyclic guanosine monophosphate–mediated vasodilation. Typical doses are 1 to 2 mg/kg intravenously over 10 to 30 minutes, sometimes followed by an infusion; the labeled indication is acquired methemoglobinemia at 1 mg/kg over 5 to 30 minutes. In a single-center trial of 91 patients with septic shock, methylene blue started within 24 hours shortened time to vasopressor discontinuation (69 and 94 hours) and added one vasopressor-free day, without a difference in mortality. Methylene blue carries a boxed warning for serotonin syndrome with selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and opioids. It causes hemolysis in glucose-6-phosphate dehydrogenase deficiency, interferes with pulse oximetry (falsely low saturation), can raise PVR, and turns the urine blue-green.

Hydroxocobalamin. Hydroxocobalamin binds nitric oxide and hydrogen sulfide. The 5 g dose labeled for cyanide poisoning raises blood pressure (substantial increases are a labeled warning), and it is used off-label for postcardiotomy and septic vasoplegia, particularly when serotonergic drugs make methylene blue unsafe. Evidence is limited to case series and retrospective cohorts. It colors skin and urine red, interferes with colorimetric laboratory assays, triggers blood-leak alarms on hemodialysis machines, and has been associated with oxalate nephropathy and acute kidney injury.

Corticosteroids. Critical illness–related corticosteroid insufficiency and reduced adrenergic receptor responsiveness contribute to vasopressor dependence. In ADRENAL, hydrocortisone 200 mg/day in 3,800 ventilated patients with septic shock did not reduce 90-day mortality (27.9% and 28.8%) but resolved shock faster (median 3 and 4 days). In APROCCHSS, hydrocortisone plus fludrocortisone in 1,241 patients reduced 90-day mortality from 49.1% to 43.0% and increased vasopressor-free days. The 2021 SSC guideline specified hydrocortisone 200 mg/day (50 mg every 6 hours or a continuous infusion), started when norepinephrine or epinephrine of 0.25 mcg/kg/min or more has been required for at least 4 hours. Corticosteroids have no established role in cardiogenic shock without adrenal insufficiency.

Oral and bolus agents: midodrine, droxidopa, and ephedrine

Midodrine is an oral prodrug converted to desglymidodrine, an alpha-1 agonist. It is approved for symptomatic orthostatic hypotension at 10 mg three times daily and carries a boxed warning for supine hypertension. It has been used to hasten liberation from intravenous vasopressors. In MIDAS, 132 patients requiring a single intravenous vasopressor for at least 24 hours received midodrine 20 mg every 8 hours or placebo; time to vasopressor discontinuation did not differ (23.5 and 22.5 hours), and bradycardia was more frequent with midodrine (7.6% and 0%).

Droxidopa is an oral norepinephrine prodrug converted by aromatic L-amino acid decarboxylase. It is approved for symptomatic neurogenic orthostatic hypotension (Parkinson disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy), starting at 100 mg three times daily and titrated to a maximum of 600 mg three times daily, with a boxed warning for supine hypertension. It has no established role in shock.

Ephedrine is a direct alpha and beta agonist and an indirect agent that releases neuronal norepinephrine. It is given in intravenous boluses of 5 to 10 mg, not to exceed 50 mg (label), for hypotension during anesthesia, where it raises pressure and heart rate. Repeated doses produce tachyphylaxis as norepinephrine stores are depleted.

Randomized evidence for vasoactive drugs

Randomized trials that define current vasoactive practice. RR, relative risk.

Choosing agents by shock phenotype and hemodynamics

The drug follows the hemodynamic lesion. Three questions define it: whether perfusion pressure is adequate, whether cardiac output is adequate for the metabolic demand, and which ventricle (or which vascular bed) has failed. Echocardiography answers the third question and often the second, and invasive hemodynamics answer all three when the clinical picture is mixed or the response to the first drug is unexpected. The phenotype changes during treatment. Prolonged cardiogenic shock develops a vasodilatory component, and sepsis unmasks or causes myocardial depression.

Vasoactive selection by shock phenotype. RAP, right atrial pressure; PAPi, pulmonary artery pulsatility index; SAM, systolic anterior motion; LVOT, left ventricular outflow tract.

Vasoactive drugs within the cardiogenic shock pathway

The diagnosis, SCAI stages, revascularization, temporary mechanical circulatory support, and shock-team care of cardiogenic shock are covered on the cardiogenic shock page; this section summarizes where the drugs fit. No vasoactive drug has reduced mortality in a randomized trial of cardiogenic shock, and drugs support perfusion while the cause is treated.

The 2022 AHA/ACC/HFSA heart failure guideline recommends intravenous inotropic support in cardiogenic shock to maintain systemic perfusion and preserve end-organ performance (Class 1, level B-NR). It also states that temporary mechanical support is reasonable when end-organ function cannot be maintained by pharmacologic means (Class 2a). The 2025 ACC concise guidance advises the lowest dose that supports adequate perfusion for the shortest possible duration. It describes norepinephrine as a reasonable first choice for most hypotensive patients, strongly discourages phenylephrine as a single first-line infusion, and states that inodilators or vasodilators may be considered in normotensive cardiogenic shock, especially when systemic vascular resistance is raised. The 2017 AHA scientific statement on contemporary management of cardiogenic shock reached similar conclusions and emphasized hemodynamic phenotyping. The 2021 European Society of Cardiology (ESC) heart failure guideline grades both an inotrope and a vasopressor (preferably norepinephrine) as Class IIb in cardiogenic shock and advises against routine inotrope use without hypoperfusion.

The SCAI SHOCK classification uses the intensity of drug support as a staging criterion. Stage C (classic shock) requires one pharmacologic or mechanical intervention beyond volume. Stage D (deteriorating) is failure of the initial strategy, including escalation of vasoactive doses or the addition of a second drug. Stage E (extremis) includes bolus vasopressors and resuscitation. Escalating doses of two or more vasoactive drugs signal that the strategy is failing, because rising catecholamine doses increase myocardial oxygen demand, arrhythmia, and peripheral ischemia without restoring perfusion. At that point the cause, the phenotype, and the case for mechanical support or transfer are reassessed. The vasoactive-inotropic score quantifies this escalation and is described in the section on the score and norepinephrine equivalents.

The drug sequence differs with the cause. In infarct-related shock, norepinephrine supports perfusion pressure during emergency revascularization of the culprit artery. In acute-on-chronic heart failure shock, patients are often on beta blockers, are more congested, and depend on output more than pressure, which favors milrinone or dobutamine with diuresis. Fulminant myocarditis, postpartum cardiomyopathy, and post-transplant graft dysfunction are supported with inotropes while recovery or definitive therapy is awaited. Takotsubo syndrome with outflow obstruction is treated as dynamic obstruction, and catecholamine inotropes are used sparingly in takotsubo syndrome without obstruction because catecholamine excess is part of its mechanism. Acute severe mitral or aortic regurgitation and ventricular septal rupture are supported with afterload reduction as a bridge to surgery: nitroprusside when blood pressure allows, or a balloon pump for mitral regurgitation and septal rupture. Norepinephrine is reserved for hypotension.

Right ventricular failure and pulmonary hypertension

The failing right ventricle depends on its coronary perfusion pressure, its afterload, ventricular interdependence, and atrioventricular synchrony. Systemic hypotension reduces right coronary flow in a dilated, pressure-loaded right ventricle and starts a spiral of ischemia and further dilation. Norepinephrine restores aortic pressure and right ventricular perfusion; its effect on PVR is small at usual doses. Vasopressin raises systemic pressure with less effect on PVR and is used as an adjunct or alternative. Phenylephrine raises PVR along with SVR and is a poor choice. Dobutamine at low doses and milrinone raise right ventricular contractility, and milrinone lowers PVR, at the cost of systemic hypotension that often needs a vasopressor.

Inhaled pulmonary vasodilators (nitric oxide, epoprostenol) lower PVR without systemic hypotension, and correction of hypoxemia, hypercapnia, and acidosis lowers PVR further. Excess volume dilates the right ventricle, shifts the septum, impairs left ventricular filling, and worsens tricuspid regurgitation, so fluids are given only when the right ventricle is underfilled. In right ventricular infarction, restoration of right coronary flow is the definitive treatment; nitrates and diuretics are avoided in the preload-dependent phase, and atrioventricular synchrony is maintained by pacing when needed. The ST-elevation myocardial infarction page covers right ventricular infarction, and the pulmonary embolism page covers right ventricular failure from acute embolism, where norepinephrine is the usual vasopressor and reperfusion is the definitive therapy.

Septic shock and mixed septic and cardiogenic shock

Septic shock is defined by a vasopressor requirement to maintain a MAP of 65 mm Hg or more and a lactate above 2 mmol/L despite adequate volume. The 2026 SSC guideline, developed by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine, sets the current approach.

Vasoactive recommendations of the 2026 Surviving Sepsis Campaign adult guideline, as listed by the Society of Critical Care Medicine.

Mixed shock. A patient may have cardiogenic shock that acquires a vasodilatory component (prolonged shock, infection, cardiopulmonary bypass, sedation), or septic shock with sepsis-induced cardiomyopathy. A low SVR (below about 800 dyn·s·cm⁻⁵) with an inadequate cardiac output and high filling pressures identifies the combination. Norepinephrine is the base, vasopressin spares catecholamines without adding tachycardia, and an inotrope is added only for a low output confirmed by echocardiography or catheter measurements. Milrinone without pressor support is poorly tolerated, because its vasodilation adds to the low SVR. Sepsis-induced cardiomyopathy is often reversible within days, and inotrope support is withdrawn as the ejection fraction recovers.

Hemorrhagic, anaphylactic, neurogenic, postcardiotomy, and obstructive shock

Hemorrhagic and hypovolemic shock. Vasoconstriction is already maximal, and vasopressors without volume worsen tissue hypoperfusion. Treatment is hemorrhage control, balanced blood product resuscitation, and correction of coagulopathy. The sixth European guideline on major bleeding after trauma recommends a restricted volume strategy (systolic pressure 80 to 90 mm Hg until bleeding is controlled, in patients without brain injury). It recommends norepinephrine in addition to fluids when that strategy does not achieve the target pressure (Grade 1C), with dobutamine for myocardial dysfunction. In SOAP II, the 263 patients with hypovolemic shock showed no mortality difference between dopamine and norepinephrine.

Anaphylactic shock. Intramuscular epinephrine is first-line and is repeated every 5 to 10 minutes as needed. Refractory hypotension is treated with large-volume crystalloid and an intravenous epinephrine infusion, with norepinephrine or vasopressin added for persistent vasodilation. Patients taking beta blockers may respond poorly to epinephrine, and glucagon, which raises cAMP independently of beta receptors, is used in that setting.

Neurogenic shock. High cervical or thoracic spinal cord injury interrupts sympathetic outflow, producing vasodilation and, above about T6, bradycardia from unopposed vagal tone. Norepinephrine provides alpha and beta support; phenylephrine alone worsens bradycardia. Neurosurgical guidelines recommend avoiding systolic pressure below 90 mm Hg and maintaining MAP at 85 to 90 mm Hg for the first 7 days after acute spinal cord injury.

Postcardiotomy vasoplegia and low output. After cardiopulmonary bypass, vasoplegia is treated with norepinephrine and vasopressin (the label for vasopressin includes postcardiotomy shock at 0.03 to 0.1 units/min), and methylene blue or hydroxocobalamin is used for refractory cases. Low cardiac output after surgery is treated with inotropes (epinephrine, dobutamine, or milrinone), pacing, correction of tamponade and graft or valve problems, and mechanical support when drugs fail.

Obstructive shock. Tamponade, tension pneumothorax, and massive pulmonary embolism are treated by relieving the obstruction. Vasopressors maintain coronary and cerebral perfusion until then; in tamponade, they are a temporizing measure before pericardiocentesis.

Acute decompensated heart failure without hypoperfusion

Most patients hospitalized with heart failure are congested and adequately perfused, and inotropes in this group cause harm without benefit. In the ADHERE registry of 15,230 treated episodes, patients who received nitroglycerin or nesiritide had lower adjusted in-hospital mortality than those who received milrinone or dobutamine (risk-adjusted odds ratios 0.46 to 0.69), an observational finding that is consistent with the trial data. The 2022 guideline lists the need for intravenous inotropes as a clinical indicator of advanced heart failure and recommends short-term inotropes only for severe systolic dysfunction with low blood pressure and a significantly low cardiac index, to maintain perfusion and end-organ function. Diuretics and vasodilators remain the treatment of congestion, as set out on the heart failure with reduced ejection fraction page.

Vasoactive drugs in valvular heart disease and other fixed or dynamic lesions

Severe aortic stenosis. Cardiac output across a fixed stenosis depends on preload, a slow enough heart rate for ejection and coronary filling, and a coronary perfusion pressure high enough to perfuse a hypertrophied ventricle. Hypotension reduces coronary flow and starts a cycle of ischemia and falling output, and tachycardia from beta-agonists is poorly tolerated. A vasoconstrictor with little or no chronotropic effect (phenylephrine, a pure alpha-1 agonist, or norepinephrine, whose modest beta-1 activity adds little tachycardia) is therefore the usual first drug for hypotension. Inotropes cannot overcome severe fixed obstruction, as the dobutamine and milrinone labels state. In patients with severe aortic stenosis, left ventricular systolic dysfunction, and a low cardiac index without hypotension, nitroprusside lowered systemic resistance and raised the cardiac index from 1.60 to 2.22 L/min/m² at 6 hours and 2.52 L/min/m² at 24 hours in a series of 25 patients monitored invasively. The drug is used only with an arterial line and adequate MAP, as a bridge to valve replacement or balloon valvuloplasty. Low-dose dobutamine has a separate diagnostic role in low-flow, low-gradient aortic stenosis, where it distinguishes true severe from pseudosevere stenosis, as described on the aortic stenosis page.

Acute aortic regurgitation. Bradycardia lengthens diastole and increases regurgitant volume, and vasoconstriction raises the regurgitant fraction. Inotropes and chronotropes (dobutamine) and vasodilators (nitroprusside) support forward output until surgery. A balloon pump is contraindicated with more than mild aortic regurgitation because diastolic inflation increases regurgitation.

Acute mitral regurgitation and ventricular septal rupture. Afterload reduction directs flow forward. Nitroprusside, with an inotrope when output is low, and a balloon pump support the patient until surgical or transcatheter repair. Vasopressors increase the regurgitant fraction or the left-to-right shunt and are used only to restore a perfusing pressure.

Mitral stenosis. Tachycardia shortens diastolic filling across the stenotic valve and raises left atrial pressure. Beta-agonist inotropes are poorly tolerated, and phenylephrine or vasopressin with rate control is used for hypotension, together with treatment of atrial fibrillation.

Pulmonary vascular disease and Eisenmenger physiology. Systemic vasodilation increases right-to-left shunting and cyanosis in patients with an intracardiac shunt and fixed pulmonary hypertension, so systemic vasoconstriction with a drug that spares the pulmonary circulation (vasopressin or norepinephrine) is preferred when hypotension develops.

Bolus vasopressors during intubation, procedures, and transport

Transient hypotension from anesthetic induction, sedation, positive-pressure ventilation, or neuraxial anesthesia is treated with intravenous boluses while the cause resolves or an infusion is prepared. The labeled bolus doses are phenylephrine 40 to 100 mcg, repeated up to 200 mcg every 1 to 2 minutes, and ephedrine 5 to 10 mg, not to exceed 50 mg in total. Phenylephrine raises pressure without tachycardia and is suited to vasodilation with a normal or fast heart rate; ephedrine raises both pressure and rate and is suited to vasodilation with bradycardia. Small boluses of dilute epinephrine are used off-label in emergency and critical care settings, and dilution errors in preparing them have been reported to cause severe hypertension and arrhythmia.

Bolus therapy does not replace an infusion in sustained shock. In patients with cardiogenic or right ventricular shock, induction of anesthesia and the transition to positive pressure are high-risk moments: sympathetic tone falls, venous return falls, and right ventricular afterload rises. A vasopressor infusion is therefore running before induction in these patients, and the induction drugs and doses are chosen for hemodynamic stability. During interfacility transport, infusions are consolidated onto pumps loaded with enough drug for the full transport, concentrated solutions limit fluid, and a bolus plan is prepared for transfer between monitors and beds.

Pulmonary artery catheter profiles and the expected effect of each drug

The pulmonary artery catheter measures the variables that each drug changes: right atrial pressure, wedge pressure, cardiac output, SVR, PVR, and SvO2. Its measurement technique, normal values, and calculated indices are covered on the right heart catheterization and hemodynamics page. The 2022 heart failure guideline states that a pulmonary artery catheter may be considered in cardiogenic shock to define hemodynamic subsets and appropriate management (Class 2b). Serial measurements after each drug change show whether the change produced the intended effect.

Expected direction of change in pulmonary artery catheter measurements after starting each drug in a patient with left ventricular dysfunction. Effects vary with volume status, dose, and baseline physiology. RAP, right atrial pressure.

The response pattern guides the next step. A MAP that rises while cardiac output and SvO2 fall after norepinephrine indicates afterload-sensitive left ventricular failure and the need for an inotrope or mechanical unloading. Hypotension after milrinone with a fall in SVR and a rise in output indicates that output is no longer the limiting variable and that a vasopressor is needed.

Vasoactive drugs with temporary mechanical circulatory support

Temporary mechanical support (intra-aortic balloon pump, microaxial flow pump, venoarterial extracorporeal membrane oxygenation [ECMO], and right-sided devices) is used when drugs cannot maintain perfusion or when the drug doses required cause unacceptable ischemia or arrhythmia. Device selection, evidence, and complications are covered on the cardiogenic shock page. Drugs continue during support for specific purposes. Vasopressors maintain MAP when a vasodilatory component persists on a microaxial pump or ECMO. Inotropes maintain right ventricular function when a left-sided device increases venous return to the right heart, and they promote aortic valve opening and left ventricular ejection on venoarterial ECMO. There, retrograde flow raises left ventricular afterload, and a nonejecting ventricle distends and forms thrombus. During weaning from a device, low-dose inotropes are often started or continued to test and support native function, and the vasoactive-inotropic score is tracked as flow is reduced.

Infusion calculations and standard concentrations

Weight-based infusion rates follow one equation: rate (mL/h) = dose (per kg per min) × weight (kg) × 60 ÷ concentration (per mL). For drugs dosed per minute without weight (vasopressin in units/min, phenylephrine and isoproterenol in mcg/min), weight drops out: rate (mL/h) = dose per min × 60 ÷ concentration. The reverse calculation, from a pump rate to the delivered dose, is dose = rate × concentration ÷ (weight × 60), or rate × concentration ÷ 60 when weight does not enter. Units must match: a norepinephrine concentration of 16 mcg/mL with a dose in mcg/kg/min, an angiotensin II concentration of 10,000 ng/mL with a dose in ng/kg/min, and a vasopressin concentration of 0.1 unit/mL with a dose in units/min.

Rate (mL/h) = dose × weight × 60 ÷ concentration for weight-based drugs, and dose × 60 ÷ concentration for drugs dosed per minute. Each drug opens with an example concentration that can be changed to match the bag in use. Ranges are those in the US prescribing information and the cited guidance; individual targets are set by the hemodynamic response.

Example preparations. Concentrations differ between institutions, and concentrated solutions (norepinephrine 32–64 mcg/mL, vasopressin 1 unit/mL, angiotensin II 5,000 or 10,000 ng/mL depending on fluid restriction) are used to limit volume. Each rate in the right-hand column is calculated from the equation above.

Vasoactive-inotropic score and norepinephrine equivalents

Patients often receive several drugs at once, and two scales combine them. The vasoactive-inotropic score (VIS) was derived in infants after cardiac surgery and weights each drug by approximate potency: dopamine + dobutamine + 100 × epinephrine + 10 × milrinone + 100 × norepinephrine (all in mcg/kg/min) + 10,000 × vasopressin (units/kg/min). In the derivation cohort of 174 infants, a high maximum score in the first 48 hours was associated with an adjusted odds ratio of 8.1 for a poor outcome. In 493 adults with cardiogenic shock, in-hospital mortality rose across quintiles of VIS from 8.2% (score 1 to 10) to 65.7% (score above 85), and scores of 39 to 85 and above 85 remained independent predictors (adjusted odds ratios 3.85 and 10.83). The cardiogenic shock page places the score among other risk models.

The norepinephrine equivalent (NEE) expresses total vasopressor intensity in mcg/kg/min of norepinephrine and is used in septic shock trials and to compare vasopressor exposure between patients. An updated formula (2023) is: norepinephrine + epinephrine + dopamine ÷ 100 + 0.06 × phenylephrine (all mcg/kg/min) + 2.5 × vasopressin (units/min) + 0.0025 × angiotensin II (ng/kg/min). Inotropes without vasoconstrictor activity (dobutamine, milrinone) are not included. A rising VIS or NEE indicates escalation, and the change over time carries more information than any single value.

Phenylephrine and angiotensin II are not part of the vasoactive-inotropic score and enter only the norepinephrine equivalent; vasopressin enters the score in units/kg/min and the norepinephrine equivalent in units/min. Mortality bands are those of a single-center cardiogenic shock cohort and describe the first 48 hours of support.

Central versus peripheral administration

Vasopressors were traditionally given only through central venous catheters because extravasation from a peripheral vein can cause necrosis. Delay in starting a vasopressor while central access is obtained prolongs hypotension. The 2026 SSC guideline suggests starting vasopressors peripherally without waiting for central access (recommendation table); the 2021 version added that peripheral infusion is for a short period and in a vein in or proximal to the antecubital fossa. In a meta-analysis of 11 adult studies with 16,055 patients, local adverse events with peripheral vasopressor infusion occurred in 1.8% (95% CI 0.1% to 4.8%). In a systematic review of 1,382 patients, extravasation occurred in 3.4%, with no reported tissue necrosis or limb ischemia, and all events were managed conservatively or with vasodilators.

Institutional protocols for peripheral infusion specify a large-bore catheter (often 20 gauge or larger) in a large proximal vein, preferably placed with ultrasound and confirmed by blood return. They also specify avoidance of the hand, wrist, and antecubital crease, dilute concentrations, a maximum dose and duration before central access, and site checks every 1 to 2 hours. Norepinephrine, phenylephrine, vasopressin, dopamine, and epinephrine have all been infused peripherally. Angiotensin II is labeled for central administration. Inotropes such as dobutamine and milrinone are less vesicant and are commonly given peripherally, and long-term home inotropes are given through a peripherally inserted central catheter or tunneled line.

Central venous access remains preferred for high or escalating doses, multiple concurrent vasoactive drugs, prolonged infusions, and patients with poor peripheral veins. A dedicated lumen avoids bolus delivery when other infusions are flushed. Changing infusion syringes or bags with overlap ("double pumping") avoids interruption of short half-life drugs.

Extravasation: recognition and phentolamine

Extravasation of a vasoconstrictor causes local ischemia: blanching, coolness, pain, and swelling at and beyond the catheter tip, followed by dusky discoloration, blistering, and necrosis. Infusion is stopped immediately, the catheter is left in place to aspirate residual drug and then removed, and the limb is elevated.

The label for norepinephrine directs infiltration of the area as soon as possible with 5 to 10 mg of phentolamine mesylate in 10 to 15 mL of 0.9% sodium chloride, using a fine hypodermic needle. Phentolamine is a competitive alpha-adrenergic antagonist; it reverses vasoconstriction from norepinephrine, epinephrine, phenylephrine, and dopamine, and blanching that resolves after infiltration confirms the response. It does not antagonize vasoconstriction from vasopressin or angiotensin II. Topical nitroglycerin and subcutaneous terbutaline have been used as alternatives when phentolamine is unavailable, with less supporting evidence. The site is marked and photographed, and plastic surgery is consulted for progressive ischemia or necrosis.

Arrhythmia with vasoactive drugs

Beta-1 stimulation raises cytosolic calcium, shortens refractoriness, increases automaticity, and promotes triggered activity, and phosphodiesterase inhibition does the same through cAMP. Hypokalemia and hypomagnesemia from beta-2 stimulation and diuretics, acidosis, myocardial ischemia, central venous catheters, and the underlying cardiomyopathy add to the risk. Atrial fibrillation is the most common arrhythmia; ventricular ectopy, ventricular tachycardia, and, rarely, ventricular fibrillation occur.

Arrhythmia risk differs between drugs. Dopamine doubled arrhythmic events compared with norepinephrine in SOAP II. In SEPSISPAM, the higher MAP target, achieved with more norepinephrine, increased new atrial fibrillation. Dobutamine facilitates atrioventricular conduction and can turn atrial fibrillation into a rapid ventricular response. Milrinone was associated with ventricular arrhythmias in 12.1% of patients in the label's trials. Levosimendan increased atrial fibrillation in SURVIVE and supraventricular tachyarrhythmia in LeoPARDS. Vasopressin and angiotensin II have no direct chronotropic action, and vasopressin's catecholamine-sparing effect is part of its rationale in patients with tachyarrhythmia.

Management begins with dose reduction or substitution: norepinephrine for dopamine, vasopressin added to lower the catecholamine dose, milrinone for dobutamine when the problem is tachycardia from beta stimulation, or the reverse when the problem is hypotension. Potassium and magnesium are replaced. Amiodarone is the usual drug for atrial fibrillation with rapid response or recurrent ventricular arrhythmia in shock, because beta blockers and nondihydropyridine calcium channel blockers depress contractility and lower pressure. Unstable tachyarrhythmias are cardioverted.

Myocardial ischemia, oxygen demand, and organ toxicity

Every inotrope that raises contractility and heart rate raises myocardial oxygen consumption. In a ventricle with ischemic but viable myocardium, inotropes can extend ischemia and infarct size; the dobutamine label notes this concern after acute infarction. Tachycardia shortens diastole and reduces coronary perfusion time. Epinephrine raises the double product most. Calcium sensitization (levosimendan) and phosphodiesterase inhibition raise oxygen demand less per unit of inotropy, but neither has improved outcomes in ischemic shock. Norepinephrine raises coronary perfusion pressure, which can improve subendocardial perfusion in hypotensive patients, at the cost of a higher afterload. Mechanical unloading lowers oxygen demand while supporting output, which is one rationale for devices when drug doses escalate.

Excessive vasoconstriction causes digital ischemia and gangrene (more often with high-dose norepinephrine, vasopressin, and angiotensin II, particularly with peripheral arterial disease or low-output states), mesenteric ischemia, and acute kidney injury when renal perfusion pressure falls with venous congestion. Catecholamines raise glucose and lactate, and beta-2 agonists lower potassium. Catecholamine excess can itself produce stress (takotsubo-like) cardiomyopathy. Prolonged high-dose catecholamines are associated with immunosuppression, ileus, and hypermetabolism. Vasopressin causes hyponatremia and, at higher doses, coronary vasoconstriction and reduced cardiac output.

Drug interactions: monoamine oxidase inhibitors, tricyclics, beta blockers, and others

Drug interactions from the US prescribing information for norepinephrine, dopamine, phenylephrine, vasopressin, angiotensin II, and methylene blue, and from hemodynamic studies of beta blockade.

Tachyphylaxis and catecholamine resistance

Catecholamine resistance is a failure of MAP to respond to escalating adrenergic doses. Its causes are partly reversible. Prolonged agonist exposure uncouples and internalizes beta receptors and reduces their number, a process that limits dobutamine over days. Severe acidosis impairs adrenergic receptor coupling and reduces the response to catecholamines and to phenylephrine. Inducible nitric oxide synthase and ATP-sensitive potassium channel opening in septic shock and after cardiopulmonary bypass cause vasodilation that adrenergic agonists cannot overcome. Relative vasopressin deficiency, critical illness–related corticosteroid insufficiency, and reduced angiotensin II generation remove the noncatecholamine supports of vascular tone. Hypocalcemia, hypothyroidism, and hypovolemia blunt the response.

The response follows the mechanism. Correctable factors (hypovolemia, ionized calcium, severe acidosis, adrenal insufficiency, an unrecognized bleed, pneumothorax, tamponade, or abdominal compartment syndrome) are sought first. Drugs with nonadrenergic mechanisms are then added: vasopressin, corticosteroids in septic shock, angiotensin II, and methylene blue or hydroxocobalamin for vasoplegia. In cardiogenic shock, escalating catecholamines are a sign that mechanical support or a change in the plan is needed.

Weaning vasoactive support

Vasoactive drugs are reduced when the cause is controlled and perfusion has been adequate for several hours: lactate falling or normal, urine output and mentation restored, and filling pressures acceptable. Vasopressors are reduced in small steps to keep MAP at the target, because the short half-lives of catecholamines produce hypotension within minutes of a large reduction or interruption. The norepinephrine label specifies gradual reduction and avoidance of abrupt withdrawal.

When several vasopressors are running, the order of withdrawal is guided by the indication and side effects. Observational studies conflict on whether stopping vasopressin or norepinephrine first produces less hypotension. Many units withdraw the drug with the most harmful side effects first (epinephrine, then high-dose norepinephrine). Hydrocortisone is continued while vasopressors are needed and then tapered or stopped.

Inotropes are reduced in small steps while cardiac output, SvO2, urine output, kidney function, and symptoms are monitored. A failed wean (falling SvO2, rising lactate or creatinine, oliguria, or recurrent congestion) at low doses identifies inotrope dependence. In heart failure, guideline-directed medical therapy is restarted as perfusion allows; beta blockers are restarted last and at low doses after inotropes are off. Patients who cannot be weaned are evaluated for durable left ventricular assist device or transplantation, or for palliative inotrope therapy.

Bridge inotropes before left ventricular assist device or transplantation

The 2022 AHA/ACC/HFSA guideline addresses patients with advanced (stage D) heart failure that is refractory to guideline-directed medical therapy and device therapy. For those eligible for and awaiting mechanical circulatory support or cardiac transplantation, continuous intravenous inotropic support is reasonable as bridge therapy (Class 2a, level B-NR). Inotropes maintain perfusion and end-organ function, which preserves eligibility for surgery, and they can reverse pulmonary hypertension that would otherwise preclude transplantation. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles 2 (progressive decline despite inotropes) and 3 (stable but inotrope dependent) define the acuity of these patients.

In a single-center series of 197 patients discharged on inotropes, 60 were bridged to transplantation or left ventricular assist device, and 55 of them were maintained on inotropes until the procedure. Across the series, milrinone was used in 84.8% and dobutamine in 15.2%. Bridge inotropes are given through a peripherally inserted central catheter or tunneled line, and patients are followed closely by the advanced heart failure team. The advanced heart failure evaluation and the choice between devices and transplantation are summarized on the heart failure with reduced ejection fraction page.

Palliative and home inotrope therapy

Guideline position. The 2022 guideline addresses patients with stage D heart failure who are ineligible for both mechanical support and transplantation despite optimal guideline-directed and device therapy. In select patients, continuous intravenous inotropic support may be considered as palliative therapy for symptom control and improvement in functional status (Class 2b, level B-NR). In patients with heart failure, long-term use of continuous or intermittent intravenous inotropes for reasons other than palliative care or a bridge to advanced therapies is potentially harmful (Class 3: Harm, level B-R). The harm recommendation rests on the excess mortality with long-term inotropes in PROMISE and related trials. The guideline notes that lower doses are preferred and that the ongoing need for inotropes is reassessed.

Outcomes. Palliative inotropes improve symptoms, functional class, and time out of hospital in selected patients, at the cost of line infection, arrhythmia, and the burden of continuous infusion. In the single-center series above, patients who received inotropes for palliation or who preferred inotropes to a left ventricular assist device had a median survival of 9.0 months, with 1-year survival of 47.6% and 2-year survival of 38.4%. These figures come from a selected population and describe the trajectory of the underlying disease as much as the drug.

Practice. Home inotropes require a stable dose established in hospital (often a low dose of milrinone or dobutamine), a dedicated central line, a portable pump, a home infusion service, and a plan for line care. The defibrillator is discussed at the start: shocks are distressing at the end of life, and deactivation of tachyarrhythmia therapy is part of the goals-of-care conversation when the aim is comfort. Discussions cover what the infusion can and cannot achieve, what happens if the line becomes infected, and whether the infusion continues in hospice. The 2022 guideline recommends palliative and supportive care, including goals-of-care discussion and symptom management, for all patients with heart failure (Class 1). Palliative care consultation is reasonable for patients with advanced heart failure, including those receiving inotropic support (Class 2a). Intermittent outpatient infusions (for example, levosimendan in European practice) are an alternative strategy outside the United States. In US guidance, intermittent inotropes for reasons other than palliation fall under the Class 3: Harm recommendation.

Special populations: pregnancy, older adults, kidney and liver disease, obesity, and children

Pregnancy and delivery. Vasoactive drugs are given when maternal shock requires them, because maternal perfusion determines fetal perfusion. Phenylephrine and norepinephrine are used for hypotension after spinal anesthesia at cesarean delivery. Vasopressin clearance increases up to fivefold at term because of placental vasopressinase. Peripartum cardiomyopathy with shock is supported with inotropes and early mechanical support in a center with advanced heart failure care. Postpartum hemorrhage is treated with blood products and uterotonics before vasopressors.

Older adults. Older patients have stiffer arteries, a higher prevalence of coronary disease, peripheral arterial disease, and atrial fibrillation, and are more susceptible to digital and mesenteric ischemia from vasoconstrictors. MAP targets at age 65 years or older and in chronic hypertension are set out in the targets section.

Kidney and liver disease. Catecholamines, vasopressin, and angiotensin II are titrated to effect regardless of renal or hepatic function. In cirrhosis, vasodilation and relative adrenal insufficiency increase vasopressor requirements, lactate clearance is slow, and terlipressin (with albumin) is used for hepatorenal syndrome, not for shock.

Obesity. Weight-based doses are usually calculated on actual body weight in practice, and some institutions use ideal or adjusted weight for norepinephrine in severe obesity. Because doses are titrated to effect, the weight used matters most when a fixed weight-based threshold triggers another intervention (vasopressin, corticosteroids, trial eligibility), and the weight basis is documented.

Children. Vasoactive drugs in children are dosed by weight with different pharmacokinetics. The vasoactive-inotropic score was derived in infants after cardiac surgery, and pediatric shock follows a separate Surviving Sepsis Campaign pediatric guideline.

Sources of error in vasoactive therapy

• Treating a blood pressure number without assessing output and perfusion, so that a rising MAP on escalating norepinephrine is accepted while cardiac output, SvO2, and urine output fall.
• Starting milrinone or another inotrope in a hypotensive patient without vasopressor support, or giving a milrinone loading dose in hypotension.
• Using phenylephrine as the sole agent in left ventricular cardiogenic shock, or in right ventricular failure with high PVR.
• Choosing dopamine as first-line therapy in cardiogenic or septic shock, or using low-dose dopamine for renal protection.
• Escalating catecholamines in refractory cardiogenic shock without reassessing the cause, the phenotype, and the case for mechanical support.
• Using vasopressors as a substitute for volume and blood in hemorrhagic shock.
• Making concentration and unit errors: mg against mcg, per hour against per minute, pounds against kilograms, and unrecognized concentration changes between bags.
• Interrupting a catecholamine infusion during line or bag changes, or flushing a line that carries a vasopressor.
• Delaying vasopressors in septic shock while waiting for central access.
• Missing early extravasation, applying heat, or using phentolamine for vasopressin or angiotensin II extravasation.
• Giving methylene blue to a patient taking serotonergic drugs.
• Omitting venous thromboembolism prophylaxis with angiotensin II.
• Continuing intravenous inotropes long term for reasons other than palliation or a bridge to advanced therapies, or starting palliative inotropes without a discussion of goals and defibrillator settings.

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