Background: Milrinone is widely used following repair of Tetralogy of Fallot (TOF) to improve myocardial contractility, reduce pulmonary vascular resistance and support right ventricular function. However, evidence supporting its routine use remains limited and largely derives from infants undergoing early repair in high-income settings. In many low- and middle-income countries (LMICs), children frequently undergo repair later in childhood after prolonged cyanosis and right ventricular pressure overload, resulting in a distinct postoperative physiology that may alter both the indications for and response to milrinone therapy.

Objective: To review the physiological rationale and current clinical evidence for milrinone use after late TOF repair and explore how postoperative haemodynamic support may be better guided by individual physiological characteristics.

Methods: A comprehensive narrative review of experimental, physiological and clinical studies evaluating milrinone following TOF repair was undertaken. Evidence was synthesised with current understanding of postoperative right ventricular dysfunction, restrictive physiology, pulmonary vascular interactions and low cardiac output syndrome, with particular consideration of children undergoing delayed repair in LMICs.

Results: Current evidence demonstrates considerable variation in milrinone dosing strategies and timing of administration, with limited high-quality evidence supporting routine prophylactic use. Late TOF repair represents a distinct postoperative physiological phenotype characterised by chronic cyanotic adaptation, right ventricular remodelling, restrictive physiology and altered pulmonary vascular function, suggesting that postoperative vasoactive strategies should not simply be extrapolated from infant TOF repair. These physiological differences are likely to influence both haemodynamic response and clinical benefit from milrinone. Existing studies rarely account for this heterogeneity, highlighting an important knowledge gap. These observations support consideration of a physiology-guided approach in which milrinone use is individualised according to the patient's postoperative haemodynamic profile rather than administered routinely.

Conclusion: Current evidence is insufficient to support routine prophylactic milrinone administration following late TOF repair. A physiology-guided approach to postoperative haemodynamic support may better account for the heterogeneity of postoperative right ventricular physiology than uniform treatment protocols. Prospective studies are needed to determine which patients derive the greatest benefit from milrinone and to optimise postoperative management in both high-income and resource-limited settings.

To be updated