Metabolic and endocrine effects of surgery and anaesthesia in the human newborn infant
This project was designed to investigate the ability of newborn infants to respond to surgical stress and to consider alternative methods of anaesthetic management in view of their hormonal and metabolic response. Concentrations of blood metabolites (glucose, lactate, pyruvate, alanine, acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids, triglycerides) and plasma hormones (insulin, glucagon, noradrenaline, adrenaline, aldosterone, corticosterone, cortisol, 11-deoxycorticosterone, 11-deoxycortisol, progesterone, 17-hydroxyprogesterone, cortisone) were measured in blood samples drawn before and after surgery, at 6, 12 and 24 hours postoperatively. Urinary total nitrogen and 3-methylhistidine/ creatinine ratios were measured for 3 days postoperatively. Peri-operative management was standardised and severity of surgical stress was assessed by a scoring method. In a preliminary study of 29 neonates, substantial hormonal and metabolic changes demonstrated the ability of neonates to mount a stress response to surgery. Compared to adult responses, the magnitude of these changes was greater but their duration was remarkably short-lived. Significant differences were found between preterm and term neonates, and between neonates given different anaesthetic management. Randomised controlled trials were designed for studying the effects of : (1) halothane anaesthesia in 36 neonates undergoing general surgical procedures, (2) fentanyl anaesthesia in 16 preterm neonates undergoing ligation of patent ductus arteriosus, (3) high-dose fentanyl anaesthesia in 13 neonates undergoing cardiac surgery. On comparing the responses of neonates within each trial, the stress response of neonates given halothane or fentanyl anaesthesia was diminished; their : (a) catecholamine responses were decreased or abolished, (b) glucocorticoid responses were suppressed, (c) changes in blood glucose and gluconeogenic precursors were decreased, (d) postoperative analgesic requirements were reduced, and (e) their clinical condition after surgery was more stable. The neonatal response was related to the severity of surgical stress, as assessed by the scoring method. Thus, hormonal and metabolic changes following surgery in preterm and term neonates are distinctly different from those of adult patients; the lack of adequate anaesthesia may cause an accentuation of the stress response.