LACTOLOGY FOUNDATION

Cardiotonic drugs are used to increase the force of myocardial contraction, and from a lactation perspective most are either avoided or used with great caution because of narrow therapeutic index and limited data on breastfed infants.

Cardiotonic drugs overview

Cardiotonic drugs increase the force of cardiac contraction (positive inotropic effect) and are mainly used in heart failure and selected arrhythmias.
The most important group are cardiac glycosides, but several non‑glycoside inotropes are used in specific acute care settings, often as short infusions in intensive care.

Cardiac glycosides

Representatives: Digoxin is the most frequently used agent, while digitoxin has a longer half‑life, and strophanthin (ouabain) is rarely used because of its rapid onset and very short duration of action.
In modern practice, digoxin remains the main representative in chronic heart failure with reduced ejection fraction and in rate control for atrial fibrillation, whereas digitoxin and ouabain are largely historical or reserved for special indications.

Mechanism of action

Cardiac glycosides inhibit the Na⁺/K⁺‑ATPase pump in cardiomyocytes, which increases intracellular sodium concentration.
The elevated intracellular sodium reduces the activity of the Na⁺/Ca²⁺ exchanger, leading to accumulation of intracellular calcium and thereby enhancing myocardial contractility.

Additional electrophysiological effects

These drugs reduce the automaticity of the sinoatrial node (negative chronotropic effect), which slows heart rate.
They also prolong the refractory period of the atrioventricular (AV) node, a property that can be exploited to control ventricular response in supraventricular tachyarrhythmias such as atrial tachycardia or fibrillation.

Pharmacokinetics

Digoxin is well absorbed orally, undergoes hepatic metabolism to a limited extent and is eliminated predominantly by the kidneys, with a half‑life of about 36 hours, which necessitates dose adjustment in renal impairment.
Digitoxin has a longer half‑life and is eliminated mainly via hepatic metabolism, which may be advantageous in patients with severe renal dysfunction but increases the risk of accumulation in hepatic disease.

Clinical indications

Cardiac glycosides are used in chronic heart failure, where they can improve symptoms and exercise tolerance in selected patients.
They are also employed in atrial fibrillation or flutter to help control ventricular rate by slowing AV conduction, particularly in sedentary or elderly patients.

Adverse effects

Cardiac adverse effects include various arrhythmias such as ventricular extrasystoles and different degrees of AV block, reflecting their narrow therapeutic index.
Extra‑cardiac adverse effects may involve gastrointestinal disturbances, headaches and characteristic visual disturbances described as “yellow‑green halos” around objects.

Toxicity and management

The risk of toxicity increases in the presence of hypokalaemia, hypomagnesaemia and renal insufficiency, so electrolyte disturbances and renal function must be carefully monitored.
Management of digoxin toxicity includes correction of electrolytes (potassium and magnesium), supportive care and, in severe or life‑threatening cases, administration of digoxin‑specific antibody fragments (Digibind).

Lactation considerations for glycosides

Digoxin passes into breast milk in low concentrations, and available clinical data suggest that infant exposure is well below therapeutic levels, but the drug’s narrow therapeutic index mandates cautious use and monitoring of the breastfed infant for bradycardia, lethargy or poor feeding.
In lactating women, individualized risk–benefit assessment is essential, with preference for the lowest effective dose, regular monitoring of maternal serum levels, and coordination with a paediatrician when long‑term maternal digoxin therapy is required.

Phosphodiesterase III inhibitors

Representatives: Milrinone and enoximone are short‑term inotropes used primarily in acute decompensated heart failure.
They are not suitable for chronic oral therapy because of increased mortality and are reserved for monitored settings such as intensive care units.

Mechanism and effects

These agents inhibit phosphodiesterase III (PDE‑III), leading to increased intracellular cyclic AMP, increased calcium influx into cardiomyocytes and enhanced contractility.
PDE‑III inhibition also causes peripheral vasodilation, thereby reducing afterload and further improving cardiac output at the cost of potential hypotension.

Indications and adverse reactions

Milrinone and enoximone are used for short‑term treatment of severe heart failure, often when other inotropes or vasodilators are insufficient.
Adverse effects include tachycardia, hypotension and pro‑arrhythmic events, so continuous haemodynamic and ECG monitoring is standard during therapy.

Lactation considerations for PDE‑III inhibitors

Because milrinone and enoximone are administered as short intravenous infusions in critically ill patients, and there are virtually no data on excretion into human milk, breastfeeding is usually interrupted or postponed during treatment and for an appropriate washout period.
In practice, these drugs are seldom a chronic issue in lactation counselling, but when used peripartum or postpartum in the mother, temporary milk expression and discard with subsequent re‑lactation planning may be advisable in collaboration with cardiology and neonatology teams.

β1‑adrenergic agonists

Representatives: Dobutamine and dopamine are β1‑adrenergic agonists used as potent inotropes in acute settings such as cardiogenic shock.
They are typically administered intravenously under strict monitoring because of their strong haemodynamic effects and potential for arrhythmias.

Mechanism and clinical use

By stimulating β1‑adrenergic receptors, these drugs increase cyclic AMP and exert positive inotropic and chronotropic effects, thereby raising cardiac output.
Clinical indications include acute heart failure and cardiogenic shock, often as bridge therapy while definitive measures (revascularisation, surgery, mechanical support) are arranged.

Adverse effects and tolerance

Adverse effects comprise tachycardia, arrhythmias and, in the case of dopamine, dose‑dependent peripheral vasoconstriction or vasodilation; tolerance can develop with prolonged infusions.
Their use demands frequent reassessment, dose titration and limiting duration to the shortest possible period compatible with haemodynamic stability.

Lactation considerations for β1‑agonists

Dobutamine and dopamine have very short half‑lives and are used as continuous infusions in critical care; thus, ongoing breastfeeding during high‑dose infusion is rarely feasible or prioritised.
Given the absence of robust data on milk transfer and potential cardiovascular effects in the infant, breastfeeding is generally deferred during infusion and resumed when the mother is haemodynamically stable and the drugs have been discontinued, with consideration of pumping to maintain supply during the acute phase.

Calcium sensitiser: Levosimendan

Levosimendan is a representative of drugs that enhance myocardial sensitivity to calcium rather than increasing intracellular calcium concentration.
It is used in acute decompensated heart failure, often when conventional inotropes are inadequate or poorly tolerated.

Mechanism and clinical application

Levosimendan increases the sensitivity of troponin C to calcium, resulting in stronger myocardial contraction without a proportional rise in oxygen consumption.
This mechanism, combined with vasodilatory effects via opening of ATP‑sensitive potassium channels, can improve haemodynamics while theoretically limiting additional myocardial oxygen demand.

Lactation considerations for levosimendan

Data on levosimendan excretion into breast milk are extremely limited, and given its long‑acting metabolites and potent cardiovascular effects, conservative practice is to avoid breastfeeding during and shortly after infusion.
In mothers receiving levosimendan for acute decompensated heart failure, individualized lactation plans—often involving temporary milk expression, discarding expressed milk during therapy and careful timing of breastfeeding resumption—should be developed with input from cardiology and lactation specialists.

Summary from a lactation perspective

Across all cardiotonic classes, the primary concerns in breastfeeding are the narrow therapeutic index of many agents, limited pharmacokinetic data in milk and the vulnerability of neonates and young infants to bradycardia, arrhythmias and haemodynamic instability.
For chronic therapies such as digoxin, breastfeeding may be compatible with appropriate monitoring, whereas for acute intravenous inotropes (PDE‑III inhibitors, β1‑agonists, levosimendan) breastfeeding is usually paused during treatment, with a focus on maintaining lactation and safely resuming once the mother is stable and drug exposure has waned.