Positive Inotropic Drugs

Positive inotropic drugs increase myocardial contractility and are used short term in acute low-output states. They relieve hypoperfusion in cardiogenic shock, acute heart failure with end-organ hypoperfusion and post-cardiac surgery low output, but they raise oxygen demand and arrhythmia risk, and long-term oral use increases mortality.

Classification. Beta-1 agonists: dobutamine, dopamine, adrenaline, isoprenaline. Phosphodiesterase 3 inhibitors: milrinone and enoximone. Calcium sensitiser: levosimendan. Cardiac glycosides: digoxin. Glucagon, which acts independently of beta receptors.

Mechanism. Raising cyclic AMP (beta-1 agonists, phosphodiesterase 3 inhibitors, glucagon) increases calcium entry and release. Glycosides raise intracellular calcium by pump inhibition. Levosimendan binds troponin C, increasing calcium sensitivity without raising calcium load.

Haemodynamic profile. Dobutamine increases output with mild vasodilation. Dopamine acts by dose range on dopamine, beta-1 and alpha-1 receptors. Phosphodiesterase 3 inhibitors and levosimendan also vasodilate and are covered with inodilators. Adrenaline adds vasoconstriction.

Pharmacokinetics. Catecholamines have half-lives of minutes and need infusion. Milrinone and levosimendan last hours to days.

• Dobutamine: first-line inotrope for low output with adequate blood pressure.
• Dopamine: inotrope and pressor; more arrhythmia and worse outcome in cardiogenic shock than noradrenaline.
• Adrenaline: inotrope and pressor for refractory shock and arrest.
• Milrinone, enoximone: effective in beta blocker-treated patients and pulmonary hypertension.
• Levosimendan: long-acting; available in many regions but not all.
• Glucagon: beta blocker overdose.
• Digoxin: chronic oral use only.

• Cardiogenic shock: noradrenaline for pressure, with dobutamine 2.5 to 20 micrograms/kg/minute added for low output once blood pressure is supported.
• Acute heart failure with hypoperfusion: dobutamine 2.5 to 20 micrograms/kg/minute, or milrinone 0.375 to 0.75 micrograms/kg/minute for beta blocker-treated patients, as a short infusion until perfusion recovers.
• Low output after cardiac surgery: dobutamine or milrinone, with levosimendan where available.
• Septic cardiomyopathy: dobutamine when low output persists after fluids and noradrenaline.
• Beta blocker overdose: glucagon 3 to 5 mg intravenously, then 1 to 5 mg/hour.
• Stress echocardiography: dobutamine in steps of 5 to 40 micrograms/kg/minute.
• Palliative: intermittent or continuous infusion in end-stage heart failure, for symptom relief when no other option exists.
• Selection: use the lowest dose for the shortest time, and wean as perfusion improves.

Contraindications. Hypertrophic obstructive cardiomyopathy, significant outflow obstruction, uncorrected hypovolaemia, and tachyarrhythmia (relative).

Adverse effects. Tachycardia, atrial and ventricular arrhythmia, myocardial ischaemia, hypotension (phosphodiesterase 3 inhibitors, levosimendan), hypokalaemia, tolerance with prolonged beta agonist infusion, extravasation injury, and higher mortality with chronic oral use.

Interactions. Beta blockers blunt dobutamine and dopamine. Monoamine oxidase inhibitors potentiate dopamine. Halogenated anaesthetics raise arrhythmia risk. Diuretics with hypokalaemia add arrhythmia.

Monitoring. Continuous electrocardiography, arterial pressure, lactate, central venous oxygen saturation, urine output, potassium and magnesium. Echocardiography and cardiac output where available.

Referral and escalation. Any inotrope infusion needs critical care or coronary care. Dependence on inotropes should prompt advanced heart failure referral.

Special groups. Renal impairment: reduce milrinone. Older adults: higher arrhythmia risk. Pregnancy: limited data. Children: weight-based dosing.