Serum Beta-Endorphin Response to Stress Before and After Operation Under Fentanyl Anesthesia in Neonates, Infants and Preschool Children[*]

Abstract

Introduction: The endogenous opioid beta-endorphin is a known indicator of stress and pain. Opioid anesthesia during operation may prevent postoperative beta-endorphin hypersecretion. We examine the effect on serum beta-endorphin of both preoperative stress and stress of operation under opioids in neonates, infants and preschool children. In order to eliminate the effect of hospitalization anxiety we compared with inpatients of similar age with non-surgical disease.

Material and Methods: We included 74 surgical patients (25 neonates, 24 infants, 25 preschool children), and 44 non-surgical inpatients (14 neonates, 12 infants, 18 preschool children). Anesthesia comprised propofol and fentanyl. In presence of pain after extubation, supplementary morphine was administered. Sera were taken preoperatively and 2 h postoperatively in surgical patients, and once in non-surgical patients. Beta-endorphin was tested using ELISA (ng/ml).

Results: In all surgical patients beta-endorphin did not increase significantly after surgery. Neonates showed significantly elevated beta-endorphin preoperatively (mean±SD: 2.02±0.76) and postoperatively (2.07±0.90) compared to neonates with a non-surgical disease (1.05±0.34; p<0.005). In contrast, infants (preoperative values: 1.75±1.32, postoperative values: 2.00±1.83) did not differ from respective non-surgical inpatients (1.49±0.70). Before and after surgery, beta-endorphin was significantly elevated in preschool children (7.19±1.85, 6.42±1.31), as compared with neonates and infants (p<0.0005), and with preschool children with non-surgical disease (1.01±0.27; p<0.0005).

Conclusions: Fentanyl/propofol anesthesia, supplemented by postoperative morphine where necessary, protects from surgical stress and postoperative pain, as denoted by no postoperative increase of beta-endorphin in all age groups. Preschool children, who exhibit increased emotional perception, have explicitly high serum beta-endorphin before and after surgery. Preoperative preparation programs might be worthy in this age group. Neonates show a moderate but still significantly high response of beta-endorphin to stress, retained after operation. In contrast, infants tolerated stress better (not increased beta-endorphin pre- and post-operatively).

Key words

fentanyl - beta-endorphin - surgical stress - children - infants - neonates

1 Presented at the BAPS 55^th Annual Congress, Salamanca, Spain, July 2–5, 2008.

References

• 1 Dubois M, Pickar D, Cohen MR. et al . Surgical stress in humans is accompanied by an increase in plasma beta-endorphin immunoreactivity.  Life Sci. 1981;  29 1249-1254
• 2 Le Blanc-Louvry I, Coquerel A, Koning E. et al . Operative stress response is reduced after laparoscopic compared to open cholecystectomy.  Dig Dis Sci. 2000;  45 710-720
• 3 Matejec R, Ruwoldt R, Boedeker RH. et al . Release of beta-endorphin immunoreactive material under perioperative conditions into blood or cerebrospinal fluid: significance for postoperative pain?.  Anesth Analg. 2003;  96 481-486
• 4 Corc RC, Hameroff SR, Weiss JL. Effects of halothane and fentanyl anesthesia on plasma beta-endorphin immunoreactivity during cardiac surgery.  Anesth Analg. 1985;  64 677-680
• 5 Anand KJ, Hansen DD, Hickey PR. Hormonal-metabolic stress responses in neonates undergoing cardiac surgery.  Anesthesiology. 1990;  73 661-670
• 6 Rosendahl W, Schulz U, Teufel T. et al . Surgical stress and neuroendocrine responses in infants and children.  J Pediatr Endocrinol Metab. 1995;  8 187-194
• 7 Castejon-Casado J, Moreno-Prieto M, Valladares-Mendias JC. et al . Hormonal response to surgical stress in schoolchildren.  Eur J Pediatr Surg. 2001;  11 44-47
• 8 Ivani G, Vaira M, Fossa S. et al . Efficacité protectrice de trois méthodes anesthésiques a l’égard du stress chirurgical chez l’enfant.  Cah Anesthesiol. 1996;  44 297-302
• 9 Merli C, Azzolini M, Cecchettin M. et al . Effetti del fentanyl sulle concentrazioni plasmatiche di beta-endorfina e ACTH in chirurgia pediatrica.  Minerva Anestesiol. 1984;  50 539-545
• 10 Berg S. Paediatric and neonatal anaesthesia. In: Allman K, Wilson I Oxford Handbook of Anaesthesia. Oxford: Oxford University Press 2006: 757-814
• 11 Petraglia F, Facchinetti F, Parrini D. et al . Simultaneous circadian variations of plasma ACTH, beta-lipotropin, beta-endorphin and cortisol.  Horm Res. 1983;  17 147-152
• 12 SPSS Base 15.0 User's Guide. Chicago: SPSS Inc; 2006
• 13 Saarenmaa E, Huttunen P, Leppaluoto J. et al . Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: A randomized trial.  J Pediatr. 1999;  134 144-150
• 14 Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery.  N Engl J Med. 1992;  236 1-9
• 15 Willis RJ. Caudal epidural blockade. In: Cousins MJ, Bridenbaugh PO. Neural Blockade in Clinical Anesthesia and Management of Pain. Philadelphia: Lippincott-Raven 1998: 323-344
• 16 McCann ME, Kain ZN. The management of preoperative anxiety in children: an update.  Anesth Analg. 2001;  93 98-105
• 17 Kain ZN, Mayes LC, Weisman SJ. et al . Social adaptability, cognitive abilities, and other predictors for children's reactions to surgery.  J Clin Anesth. 2000;  12 549-554
• 18 Matejec R, Schulz A, Muehling J. et al . Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain?.  Neuropeptides. 2006;  40 11-21
• 19 Wardlaw SL, Stark RI, Baxi L. et al . Plasma beta-endorphin and beta-lipotropin in the human fetus at delivery: correlation with arterial pH and pO₂.  J Clin Endocrinol Metab. 1979;  49 888-891
• 20 Anand KJ, Phil D, Hickey PR. Pain and its effects in the human neonate and fetus.  N Engl J Med. 1987;  21 1321-1329
• 21 Ramanathan S, Puig MM, Turndorf H. Plasma beta-endorphin levels in the umbilical cord blood of preterm human neonates.  Biol Neonate. 1989;  56 117-120
• 22 Leuschen MP, Willett LD, Bolam DL. et al . Plasma beta-endorphin in neonates: effect of prematurity, gender and respiratory status.  J Clin Endocrinol Metab. 1991;  73 1062-1066

1 Presented at the BAPS 55^th Annual Congress, Salamanca, Spain, July 2–5, 2008.

Correspondence