Effect of therapeutic hypothermia on renal and myocardial function in asphyxiated (near) term neonates: A systematic review and meta-analysis

Abstract

Background: Therapeutic hypothermia (TH) is a well-established neuroprotective therapy applied in (near) term asphyxiated infants. However, little is known regarding the effects of TH on renal and/or myocardial function.

Objectives: To describe the short- and long-term effects of TH on renal and myocardial function in asphyxiated (near) term neonates.

Methods: An electronic search strategy incorporating MeSH terms and keywords was performed in October 2019 and updated in June 2020 using PubMed and Cochrane databases. Inclusion criteria consisted of a RCT or observational cohort design, intervention with TH in a setting of perinatal asphyxia and available long-term results on renal and myocardial function. We performed a meta-analysis and heterogeneity and sensitivity analyses using a random effects model. Subgroup analysis was performed on the method of cooling.

Results: Of the 107 studies identified on renal function, 9 were included. None of the studies investigated the effects of TH on long-term renal function after perinatal asphyxia. The nine included studies described the effect of TH on the incidence of acute kidney injury (AKI) after perinatal asphyxia. Meta-analysis showed a significant difference between the incidence of AKI in neonates treated with TH compared to the control group (RR = 0.81; 95% CI 0.67-0.98; p = 0.03). No studies were found investigating the long-term effects of TH on myocardial function after neonatal asphyxia. Possible short-term beneficial effects were presented in 4 out of 5 identified studies, as observed by significant reductions in cardiac biomarkers and less findings of myocardial dysfunction on ECG and cardiac ultrasound.

Conclusions: TH in asphyxiated neonates reduces the incidence of AKI, an important risk factor for chronic kidney damage, and thus is potentially renoprotective. No studies were found on the long-term effects of TH on myocardial function. Short-term outcome studies suggest a cardioprotective effect.

Fig 1. PRISMA chart of the identification and selection of studies regarding short-term renal and myocardial function.

Fig 2. Risk of bias assessed in the included randomized controlled trials.

Plus-sign represents ‘low risk’, minus-sign represents ‘high risk’, empty represents ‘unclear risk’.

Fig 3. Forest plot of the effect of hypothermia on the incidence of AKI in asphyxiated neonates, expressed in risk ratios.

Subgroup selective head cooling with mild systemic hypothermia: there is no significant difference between cooled and non-cooled neonates. Subgroup whole body cooling: there is a significant difference between cooled and non-cooled neonates.