Network meta-analysis of indomethacin versus ibuprofen versus placebo for PDA in preterm infants.

OBJECTIVES: To evaluate the effects of indomethacin or ibuprofen compared with placebo on closure, morbidity and mortality in preterm infants <37 weeks' gestation with echocardiographically and/or clinically important patent ductus arteriosus (PDA) at >24 h of life. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL, Cochrane Library, clinicaltrials.gov, controlled-trials.com, American Pediatric and European Paediatric Research Societies and Effective Care of the Newborn Infant. REVIEW METHODS: Systematic review with network meta-analysis of randomised studies comparing intravenous indomethacin, ibuprofen or placebo for PDA in preterm infants at >24 h of life. RESULTS: Ten trials compared intravenous indomethacin versus intravenous ibuprofen, nine intravenous indomethacin versus placebo and one intravenous ibuprofen versus placebo. Both intravenous indomethacin (pooled RR 2.39 (95% CI 2.05 to 2.78)) and intravenous ibuprofen (RR 2.40 (95% CI 2.03 to 2.84)) closed a PDA more effectively than placebo. Intravenous ibuprofen was associated with approximately 30% greater risk of chronic lung disease than intravenous indomethacin (RR 1.28 (95% CI 1.03 to 1.60)) or placebo (RR 1.29 (95% CI 0.99 to 1.70)). Differences in risk or benefit were not significant between any combination of intravenous indomethacin, intravenous ibuprofen or placebo groups for intraventricular haemorrhage, necrotising enterocolitis and death. Reporting on neurological outcomes was insufficient for pooling. CONCLUSIONS: Intravenous indomethacin or ibuprofen administered to preterm infants for PDA at >24 h of life promoted ductal closure, but other short-term benefits were not seen. Treatment with intravenous ibuprofen may increase the risk of chronic lung disease. Good-quality evidence of treatment effect on morbidity, mortality and improved neurodevelopment is urgently needed.

Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy.

BACKGROUND: With improvements in neonatal intensive care, more premature infants are surviving the neonatal period. With this increase, more are presenting for surgery in early infancy. Of predominance in this period is the repair of inguinal herniae, appearing in 38% of infants whose birth weight is between 751g and 1000g. Most postoperative studies show that approximately 20% to 30% of otherwise healthy former preterm infants having inguinal herniorrhaphy under general anaesthesia have one or more apnoeas in the postoperative period. Regional anaesthesia might reduce postoperative apnoea in this population. OBJECTIVES: To determine if regional anaesthesia, in preterm infants undergoing inguinal herniorrhaphy, reduces post-operative apnoea, bradycardia, and the use of assisted ventilation, in comparison to those infants undergoing inguinal herniorrhaphy with general anaesthesia. SEARCH STRATEGY: Randomised controlled trials were identified by searching MEDLINE (1966-Nov 2002), EMBASE (1982-Nov 2002), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2002), reference lists of published trials and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of spinal versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two reviewers. Authors of each eligible study were contacted for missing data. Studies were analysed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 4.1. When possible meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI). MAIN RESULTS: Four small trials comparing spinal with general anaesthesia in the repair of inguinal hernia were identified. One trial was excluded due to inadequate information. There was no statistically significant difference in the proportions of infants having postoperative apnoea/bradycardia, typical RR 0.69 (0.40, 1.21) or postoperative oxygen desaturations, RR 0.91 (0.61, 1.37). If infants having preoperative sedatives were excluded, then the meta-analysis supported a reduction in postoperative apnoea in the spinal anaesthetic group, typical RR 0.39 (0.19, 0.81). There was a reduction of borderline statistical significance in the use of postoperative assisted ventilation with spinal anaesthesia. There was an increase of borderline statistical significance in anaesthetic placement failure when spinal anaesthesia was attempted. REVIEWER'S CONCLUSIONS: There is no reliable evidence from the trials reviewed concerning the effect of spinal as compared to general anaesthesia on the incidence of post-operative apnoea, bradycardia, or oxygen desaturation in ex-preterm infants undergoing herniorrhaphy. The estimates of effect in this review are based on a total population of only 108 patients or fewer.A large well designed randomised controlled trial is needed to determine if spinal anaesthesia reduces post-operative apnoea in ex-preterm infants not pretreated with sedatives. Adequate blinding, follow up and intention to treat analysis are required.