title: A comparison of three dose timings of methylprednisolone in infant cardiopulmonary bypass.
abstract: Although commonly used in pediatric cardiopulmonary bypass (CPB) optimal dose and timing of steroid administration is unclear. We hypothesized that early administration of a commonly used dose of methylprednisolone given the evening before surgery (ultra-early) would be more effective in decreasing CPB-related inflammatory response than when given at induction of anesthesia (early) or in pump prime (standard). This was a triple-arm, parallel, active control, superiority RCT including 54 infants <2 years old who were randomised to receive 30 mg/kg methylprednisolone at one of the 3 time points. Outcomes included alveolar-arterial oxygen gradient (AaDO2) during, 24, 48 and 72 hours post-CPB, IL-6, IL-8 and reduced (GSH) to oxidized (GSSG) glutathione ratio (pre-ultrafiltration on CPB, end-CPB and 24 hours), PICU length of stay (LOS) and ventilator days. Data were analysed using descriptive statistics and a random effects regression model. The ultra-early group had higher Risk Adjusted Congenital Heart Surgery Score, lower age and longer CPB times than the other groups. No significant differences in AaDO2, IL-8, PICU LOS and ventilator days were observed between groups. Compared to the ultra-early group, the overall rise in IL-6 in the early and standard groups was lower, -27.8 pg/ml (95% CI -52.7,-2.9) and -35.3 pg/ml (95% CI -64.3,-6.34), respectively. GSH:GSSG was significantly lower in the standard group (-35.9; 95% CI -63.31,-8.5) at 24 hours post-CPB. Ultra-early administration of methylprednisolone does not improve AaDO2 post-CPB, nor diminish cytokine release. Lower GSH:GSSG in the standard group suggests less oxidative stress. However despite statistical adjustments conclusions are limited by the unbalanced randomisation of the groups.
authors.affiliation: Department of Pediatric Anesthesia, McGill University Health Center/Montreal Children's Hospital, 2300 Tupper Street, Room C-1118, Montreal, Quebec Canada ; Department of Pediatrics, McGill University Health Center/Montreal Children's Hospital, Montreal, Canada.
authors.forename: Davinia E
authors.initials: DE
authors.lastname: Withington
authors.affiliation: Department of Pediatrics, McGill University Health Center/Montreal Children's Hospital, Montreal, Canada ; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University Montreal, Montreal, Canada.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Fontela
authors.affiliation: Department of Critical Care, Centre Hospitalier Universitaire Ste Justine, Montreal, Canada.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Harrington
authors.affiliation: Division of Pediatric Cardiothoracic Surgery, McGill University Health Center/Montreal Children's Hospital, Montreal, Canada.
authors.forename: Christo
authors.initials: C
authors.lastname: Tchervenkov
authors.affiliation: Department of Pediatrics, McGill University Health Center/Montreal Children's Hospital, Montreal, Canada.
authors.forename: Larry C
authors.initials: LC
authors.lastname: Lands
keywords: Cardiopulmonary bypass; Inflammatory response; Leukotrienes; Methylprednisolone; Oxidative stress; Oxygenation; Pediatric