Intensive Care Med (1989) 15:$44-$45 IntensiveCare Medicine © Springer-Verlag 1989 The ontogeny of the metabolic and endocrine stress response in the human fetus, neonate and child M. P. Ward Platt 1 K. J. S. Anand 2 and A. Aynsley-Green 1 1 Department of Child Health, University of Newcastle upon Tyne, The Medical School, Newcastle upon Tyne, UK, and 2Department of Anaesthesia, Children's Hospital Medical Centre, Boston, Massachusetts, USA Abstract. Evidence of an endocrine and metabolic response to stress is evident from the mid trimester of fetal life. The ontogeny of this response is seen in the different patterns of response evident in the fetus, neo- nate, infant and child. These data raise important issues concerning the management of pain and stress in early life. Key words: Stress - Analgesia - Metabolic - En- docrine - Ontogeny The metabolic and endocrine effects of injury [1], burns [2], and surgery [3] have been studied extensive- ly in adult subjects. Until recently few data were available on the metabolic and endocrine response to surgical stress in neonates and children, and even less was known about the human fetus. In the absence of such data, anaes- thetic practice has been empirical. Lippman wrote just over 10 years ago that in neonatal surgery for patent ductus arteriosus (PDA), "anaesthetic or analgesic agents ... in our experience, are unnecessary" [4]; our own literature review [5] encompassing a total of 1157 neonates undergoing PDA ligation confirmed that three quarters received no anaesthesia or minimal anaesthesia during surgery, and a recent survey cited by Gauntlett [6] indicated that "although 85% of these (anaesthetists) answering believed that newborn babies felt pain, only about 5% used narcotic analgesia in this group and few used local analgesic blocks regularly' Because all children have to meet the metabolic cost of growth and have a relatively larger glucose re- quirement per unit body weight than adults (because of their relatively larger brains), they are propor- tionately more vulnerable to metabolic instability. This situation is even more pronounced in the new- born, where with limited reserves of carbohydrate, protein and fat the baby has to contend with a lower temperature environment, organ maturation and par- ticularly rapid growth [7]. The effects of surgery would be expected to be most deleterious to the most vulnerable children, and indeed this has been shown to be the case [8]. Evidence for a classical endocrine stress response in fetal life comes from studies of amniotic fluid con- centrations of adrenocortical steroids [9]. These data imply that the fetus is capable of mounting an autono- mous adrenocortical response and that maternal opiate administration may reduce the magnitude of it. Acute fetal distress at birth is also accompanied by substantial increases in the circulating concentrations of gut hormones [i0]: the local action of motilin may thus provide a physiological explanation for the pas- sage of meconium that is associated with fetal distress [11]. Since the fetus can be both a producer and a con- sumer of glucose and lactate [12], it is possible that under conditions of acute stress the fetus might pro- duce a metabolic response such as hyperglycaemia. However, under conditions of chronic stress such as placental failure, Soothill et al. [13] have demonstrated that profound hypoglycaemia and marked hyperlac- tataemia accompany hypoxia in umbilical venous blood. It is now clear that term and preterm neonates can- not be considered as a homogenous group in the con- text of their stress responses [14]. Given the same anaesthetic for major surgery, term and preterm neo- nates showed substantial differences in their metabolic responses. Some babies developed a massive stress response, but in spite of this, glucose and lactate con- centrations returned to pre-operative values within 24 h post-operatively. Postoperative concentrations of