Eero J Pesonen1, Pertti K Suominen, Juho Keski-Nisula, Ilkka P Mattila, Paula Rautiainen, Timo Jahnukainen. 1. 1Department of Anesthesiology and Intensive Care Medicine, Peijas Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 2Department of Anesthesiology and Intensive Care Medicine, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 3Department onf Pediatric Cardiac and Transplantation Surgery, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 4Department of Pediatric Nephrology and Transplantation, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Abstract
OBJECTIVES: Plasma neutrophil gelatinase-associated lipocalin is a kidney injury marker used in pediatric heart surgery. Neutrophil gelatinase-associated lipocalin is also a constituent of specific granules of neutrophils. Corticosteroids are widely used in pediatric heart surgery. Methylprednisolone inhibits degranulation of neutrophil-specific granules. Use of corticosteroids has not been taken into account in studies of neutrophil gelatinase-associated lipocalin in pediatric heart surgery. We studied the influence of systemically administered methylprednisolone on plasma neutrophil gelatinase-associated lipocalin concentrations in pediatric heart surgery. DESIGN: Two separate double-blinded randomized trials. SETTING: PICU at a university-affiliated hospital. PATIENTS: Forty neonates undergoing open-heart surgery and 45 children undergoing ventricular and atrioventricular septal defect correction. INTERVENTIONS: First trial (neonate trial), 40 neonates undergoingopen-heart surgery received either 30 mg/kg IV methylprednisolone (n = 20) or placebo (n = 20). Second trial (ventricular septal defect trial), 45 children undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg ofmethylprednisolone IV after anesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15). MEASUREMENTS AND MAIN RESULTS:Plasma neutrophilgelatinase-associated lipocalin and creatinine were measured in both series. Lactoferrin levels were measured as a marker of neutrophil-specific granules in the ventricular septal defect trial only. No differences in creatinine levels occurred between the groups of either trial. Preoperative, neutrophil gelatinase-associated lipocalin did not differ between the study groups of either trial. Preoperatively administered methylprednisolone in the neonate trial reduced neutrophil gelatinase-associated lipocalin by 41% at 6 hours postoperatively (p = 0.002). Preoperatively administered methylprednisolone in the ventricular septal defect trial reduced neutrophil gelatinase-associated lipocalin by 47% (p = 0.010) and lactoferrin by 52% (p = 0.013) 6 hours postoperatively. Lactoferrin levels in the ventricular septal defect trial correlated with neutrophil gelatinase-associated lipocalin (R = 0.492; p = 0.001) preoperatively and after weaning from cardiopulmonary bypass (R = 0.471; p = 0.001). CONCLUSIONS: Preoperatively administered methylprednisolone profoundly decreases plasma neutrophil gelatinase-associated lipocalin levels. Neutrophil gelatinase-associated lipocalin seems to originate to a significant extent from activated neutrophils. Preoperative methylprednisolone is a confounding factor when interpreting plasma neutrophil gelatinase-associated lipocalin levels as a kidney injury marker in pediatric heart surgery.
RCT Entities:
OBJECTIVES: Plasma neutrophil gelatinase-associated lipocalin is a kidney injury marker used in pediatric heart surgery. Neutrophil gelatinase-associated lipocalin is also a constituent of specific granules of neutrophils. Corticosteroids are widely used in pediatric heart surgery. Methylprednisolone inhibits degranulation of neutrophil-specific granules. Use of corticosteroids has not been taken into account in studies of neutrophil gelatinase-associated lipocalin in pediatric heart surgery. We studied the influence of systemically administered methylprednisolone on plasma neutrophil gelatinase-associated lipocalin concentrations in pediatric heart surgery. DESIGN: Two separate double-blinded randomized trials. SETTING: PICU at a university-affiliated hospital. PATIENTS: Forty neonates undergoing open-heart surgery and 45 children undergoing ventricular and atrioventricular septal defect correction. INTERVENTIONS: First trial (neonate trial), 40 neonates undergoing open-heart surgery received either 30 mg/kg IV methylprednisolone (n = 20) or placebo (n = 20). Second trial (ventricular septal defect trial), 45 children undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone IV after anesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15). MEASUREMENTS AND MAIN RESULTS: Plasma neutrophil gelatinase-associated lipocalin and creatinine were measured in both series. Lactoferrin levels were measured as a marker of neutrophil-specific granules in the ventricular septal defect trial only. No differences in creatinine levels occurred between the groups of either trial. Preoperative, neutrophil gelatinase-associated lipocalin did not differ between the study groups of either trial. Preoperatively administered methylprednisolone in the neonate trial reduced neutrophil gelatinase-associated lipocalin by 41% at 6 hours postoperatively (p = 0.002). Preoperatively administered methylprednisolone in the ventricular septal defect trial reduced neutrophil gelatinase-associated lipocalin by 47% (p = 0.010) and lactoferrin by 52% (p = 0.013) 6 hours postoperatively. Lactoferrin levels in the ventricular septal defect trial correlated with neutrophil gelatinase-associated lipocalin (R = 0.492; p = 0.001) preoperatively and after weaning from cardiopulmonary bypass (R = 0.471; p = 0.001). CONCLUSIONS: Preoperatively administered methylprednisolone profoundly decreases plasma neutrophil gelatinase-associated lipocalin levels. Neutrophil gelatinase-associated lipocalin seems to originate to a significant extent from activated neutrophils. Preoperative methylprednisolone is a confounding factor when interpreting plasma neutrophil gelatinase-associated lipocalin levels as a kidney injury marker in pediatric heart surgery.
Authors: Luke W Schroeder; Jason R Buckley; Robert E Stroud; Renee H Martin; Elizabeth K Nadeau; Ryan Barrs; Eric M Graham Journal: Pediatr Crit Care Med Date: 2019-10 Impact factor: 3.624
Authors: Jef Van den Eynde; Nicolas Cloet; Robin Van Lerberghe; Michel Pompeu B O Sá; Dirk Vlasselaers; Jaan Toelen; Jan Y Verbakel; Werner Budts; Marc Gewillig; Shelby Kutty; Hans Pottel; Djalila Mekahli Journal: Clin J Am Soc Nephrol Date: 2021-10 Impact factor: 10.614