Strategies to Prevent Acute Kidney Injury after Pediatric Cardiac Surgery: A Network Meta-Analysis

Abstract

Background and objectives: AKI is a common complication after pediatric cardiac surgery and has been associated with higher morbidity and mortality. We aimed to compare the efficacy of available pharmacologic and nonpharmacologic strategies to prevent AKI after pediatric cardiac surgery.

Design, setting, participants, & measurements: PubMed/MEDLINE, Embase, Cochrane Controlled Trials Register, and reference lists of relevant articles were searched for randomized controlled trials from inception until August 2020. Random effects traditional pairwise, Bayesian network meta-analyses, and trial sequential analyses were performed.

Results: Twenty randomized controlled trials including 2339 patients and 11 preventive strategies met the eligibility criteria. No overall significant differences were observed compared with control for corticosteroids, fenoldopam, hydroxyethyl starch, or remote ischemic preconditioning in traditional pairwise meta-analysis. In contrast, trial sequential analysis suggested a 80% relative risk reduction with dexmedetomidine and evidence of <57% relative risk reduction with remote ischemic preconditioning. Nonetheless, the network meta-analysis was unable to demonstrate any significant differences among the examined treatments, including also acetaminophen, aminophylline, levosimendan, milrinone, and normothermic cardiopulmonary bypass. Surface under the cumulative ranking curve probabilities showed that milrinone (76%) was most likely to result in the lowest risk of AKI, followed by dexmedetomidine (70%), levosimendan (70%), aminophylline (59%), normothermic cardiopulmonary bypass (57%), and remote ischemic preconditioning (55%), although all showing important overlap.

Conclusions: Current evidence from randomized controlled trials does not support the efficacy of most strategies to prevent AKI in the pediatric population, apart from limited evidence for dexmedetomidine and remote ischemic preconditioning.

Keywords: acute kidney injury; acute renal failure; cardiac surgical procedures; children; congenital heart disease; heart; network meta-analysis; specialties; surgical.

Graphical abstract

Figure 1.

Flow diagram of the literature search depicting the number of included and excluded studies throughout the process. CENTRAL/CCTR, Cochrane Controlled Trials Register.

Figure 2.

Direct pairwise meta-analysis. Forest plots showing no effects of either (A) corticosteroids, (B) fenoldopam, (C) hydroxyethyl starch (HES), or (D) remote ischemic preconditioning (RIPC) on AKI after pediatric cardiac surgery. Pooled odds ratio and conclusions plots. 95% CI, 95% confidence interval; df, degrees of freedom; DL, DerSimonian-Lairds.

Figure 3.

Network meta-analysis. (A) Network plot showing the preventive strategies that have been tested in randomized controlled trials for their efficacy in preventing AKI. Circles are weighted according to the number of studies including the intervention, and lines are weighted according to the number of studies comparing the two connected interventions. (B) Forest plots showing that none of the strategies could effectively prevent AKI. The relative effects of preventive strategies compared with control, as estimated from both direct and indirect estimates in the network, are shown. (C) League heat plot showing no differences in the comparative efficacy of preventive strategies included in the network meta-analysis. The estimate (odds ratio; 95% confidence interval) is located at the intersection of the row defining index treatment and the column defining comparison treatment. CPB, cardiopulmonary bypass; CrI, credible interval; HES, hydroxyethyl starch; RIPC, remote ischemic preconditioning.

Figure 4.

Surface under the cumulative ranking curve (SUCRA) plot showing that milrinone had the highest probability of being ranked first, although showing important overlap with the other preventive strategies. For each preventive strategy, the cumulative probability of being ranked 1st through 11th is displayed. The more the curve for a certain strategy is located toward the upper left corner, the higher its SUCRA value and the greater its performance.