Background
Paediatric patients undergoing surgery for congenital heart disease (CHD) are at risk for postoperative low cardiac output syndrome (LCOS) and mortality. LCOS affects up to 25% of children after heart surgery. It consists of reduced myocardial function and increases postoperative morbidity, prolongs mechanical ventilation, and lengthens the duration of intensive care unit (ICU) stay. Pharmacological prophylaxis involves inotropes, including catecholamines, phosphodiesterase III inhibitors, or calcium sensitisers, to enhance myocardial contractility. It is unclear whether they are effective in preventing LCOS or death in this vulnerable population.
Objectives
1. To evaluate the relative benefits and harms of inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD.
2. To generate a clinically useful ranking of prophylactic inotropes for the prevention of LCOS and mortality in paediatric patients undergoing surgery for CHD according to benefits and harms.
Search methods
We searched CENTRAL, MEDLINE, Embase, Web of Science, and clinical trial registries, most recently in December 2023 and April 2024. We also checked reference lists from identified studies and review articles. We did not apply any language restrictions.
Selection criteria
We included randomised controlled trials comparing inotropes from one drug class (catecholamines, phosphodiesterase type III inhibitors, calcium sensitisers) to another (either alone or in combination) or placebo, in paediatric patients (birth to 18 years of age) undergoing surgery for CHD.
Data collection and analysis
Two review authors independently selected studies, extracted data, assessed risk of bias, and rated the certainty of evidence using the CINeMA framework. We performed random‐effects network and pairwise meta‐analyses comparing the relative effects of each possible pair of medications with each other or placebo. Where meta‐analysis was not possible, we provided a narrative description of the results. We ranked the prophylactic medications according to their effects relative to each other. The primary outcomes were all‐cause mortality within 30 days, time to death, and LCOS incidence; secondary outcomes were length of ICU stay, length of hospital stay, duration of mechanical ventilation, inotrope score, mechanical circulatory support, and adverse events.
Main results
We included 13 studies with 937 participants. All except two multicentre studies were conducted at single tertiary care hospitals. Participants comprised children from birth to 14 years of age undergoing surgery for different types of CHD on cardiopulmonary bypass. Five studies compared levosimendan versus milrinone; two compared levosimendan versus placebo; two compared milrinone versus placebo (one comparing two different doses); one compared levosimendan versu...
