An evidence-based review of the use of vasoactive and inotropic medications in post-operative paediatric patients after cardiac surgery with cardiopulmonary bypass from 2000 to 2020

Abstract

Background: Infants with moderate-to-severe CHD frequently undergo cardiopulmonary bypass surgery in childhood. Morbidity and mortality are highest in those who develop post-operative low cardiac output syndrome. Vasoactive and inotropic medications are mainstays of treatment for these children, despite limited evidence supporting their use. Methods: To help inform clinical practice, as well as the conduct of future trials, we performed a systematic review of existing literature on inotropes and vasoactives in children after cardiac surgery using the PubMed and EMBASE databases. We included studies from 2000 to 2020, and the patient population was defined as birth – 18 years of age. Two reviewers independently reviewed studies to determine final eligibility. Results: The final analysis included 37 papers. Collectively, selected studies reported on 12 different vasoactive and inotropic medications in 2856 children. Overall evidence supporting the use of these drugs in children after cardiopulmonary bypass was limited. The majority of studies were small with 30/37 (81%) enrolling less than 100 patients, 29/37 (78%) were not randomised, and safety and efficacy endpoints differed widely, limiting the ability to combine data for meta-analyses. Conclusion: Vasoactive and inotropic support remain critical parts of post-operative care for children after cardiopulmonary bypass surgery. There is a paucity of data for the selection and dosing of vasoactives and inotropes for these patients. Despite the knowledge gaps that remain, numerous recent innovations create opportunities to rethink the conduct of clinical trials in this high-risk population.

A systematic review of clinical study evidence for pulmonary vasodilator therapy following surgery with cardiopulmonary bypass in children with CHD

“…Similar to previously described, PubMed and EMBASE were searched to identify studies investigating the use of pulmonary vasodilator medications in children following cardiac surgery with cardiopulmonary bypass. [17][18][19] Studies from 2000 through 2020 were included to assess medication use in current clinical practice. Children were defined as from birth to age 18 years.…”

“…65,66 Milrinone is the most used intravenous vasoactive medication for children with pulmonary hypertensive crises and may reduce pulmonary arterial pressures in children with pulmonary hypertension. 17,67 Nevertheless, its use in the paediatric population remains off-label. 15 Additionally, milrinone has a relatively long half-life compared to other inotropes and is primarily renally cleared, so both optimal dosing and timing of therapy in critically ill children at risk for acute kidney injury are important to define.…”

A systematic review of the evidence supporting post-operative antithrombotic use following cardiopulmonary bypass in children with CHD

“…We searched PubMed and EMBASE to identify studies investigating the use of antithrombotic medications in children after cardiac surgery with cardiopulmonary bypass, similarly to research previously described. 16 Studies from 2000 to 2020 were included to reflect medication use in the context of current clinical practice. We defined children as those from birth to age 18 years.…”

A systematic review of the evidence supporting post-operative diuretic use following cardiopulmonary bypass in children with Congenital Heart Disease

“…PubMed and EMBASE were searched to identify studies investigating the use of diuretics in children after cardiac surgery with cardiopulmonary bypass, similarly to research previously described. 17 Studies from 2000 to 2020 were included to reflect medication use in the context of current clinical practice. Children were defined as birth to age 18 years.…”