The hormonal and metabolic response to stress in the neonate

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It is apparent that adult patients demonstrate a catabolic response to the stresses induced by operative or accidental trauma. It seems that the degree of this catabolic response may be quantitatively related to the extent of the trauma or the magnitude of associated complications such as infection. The host response to infection, traumatic injury, or major operative stress is characterized by such events as fever, pituitary and stress hormone elaboration, mineral redistribution, and increased acute-phase protein synthesis [21]. The beneficial effects of this stress response consist in providing alternate energy sources to meet metabolic demands and essential building blocks for synthetic activities occuring in the postoperative period. It has been suggested that the hyperglycemic response is essential for supplying the increased glucose requirements of injured tissue [81]. In addition, the proteolytic component of the stress response provides the necessary amino acid elements for reparative protein synthesis and production of acute-phase reactants by the liver. The changes in metabolic patterns induced by the stress response are satisfied in part by increased lipolysis and ketogenesis to provide an alternate source of metabolic fuel for tissues such as the brain and skeletal muscle. Additionally, the observed gluconeogenesis may aid in maintaining the glucose supply for vital organs principally dependent on glucose [52, 160]. This metabolic response has also been shown to potentiate many adverse conditions in the postoperative period and to further exacerbate the stress response. Examples include a hypermetabolic state with attendant increased VO2, increased energy requirements, increased temperature, elevated cardiac output, and altered or impaired inflammatory or immune-responsiveness. Numerous investigators have demonstrated that adult patients exposed to severe degrees of traumatic stress are subjected to greatly increased rates of complications such as cardiac or pulmonary insufficiency, myocardial infarction, impaired hepatic and/or renal function, gastric stress ulcers, and sepsis. Furthermore, evidence exists to suggest that this response may be life-threatening if the induced catabolic activity remains excessive or unchecked for a prolonged period. Moyer et al. were able to identify with a great degree of certainty the patients who were likely to die based on a single analysis of a variety of plasma-borne substrates obtained up to 9 days prior to death [103]. It is apparent that modulating or blunting the catabolic response induced by the stress state may have beneficial effects. In studies of postoperative pain management, improved pain control resulted in reduction of postoperative nitrogen loss and shortened periods of convalescence following operation [28, 88]. It is evident from this review that human newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin. The catecholamines may be the agents of primary importance in this response, and thus may modulate the remaining components of the hormonal response to stress as well as the metabolic changes, including inhibition of insulin release, marked hyperglycemia, and breakdown of the neonate's stores of nutrients (carbohydrate, protein, and fat). These reactions ultimately result in the release of glucose, NEFA, ketone bodies, and amino acids. Although these metabolic by-products are necessary to meet the body's altered energy needs in a time of increased metabolic demands, it is not difficult to imagine that a severe or prolonged response would be very detrimental to a previously ill neonate with limited reserves of nutrients and already high metabolic demands imposed by rapid growth, organ maturation, and adaptation to the postnatal environment. Preliminary investigations by Anand et al. outlined in this review indicate that alterations in anesthetic technique with the addition of agents such as halothane and fentanyl may be able to significantly blunt this catabolic response. In addition, it appears that modulation of the immune response may also greatly affect the postoperative catabolic response. It is hopeful that future developments and the acquisition of more detailed knowledge o the response will allow us to modify the stress response in neonates in order to further decrease their mortality and morbidity.