Lichtarowicz-Krynska, Ewa Jadwiga; (2004) The endocrine and metabolic stress responses in critical illness in childhood. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Critical illness in childhood is of immense clinical significance, since 1 : 1000 paediatric hospital admissions requires intensive care for a mean duration of 4 days with a mortality rate of 6.4%. The stress of critical illness induces a coordinated response in multiple organ systems, including the neuroendocrine, metabolic and immune systems, in order to enhance the probability of survival. The aims of the present study were to describe the magnitude and nature of the metabolic and endocrine response (MER) over the first few days of critical illness in children, to relate it to illness severity, patient age and diagnosis. Interactions between different hormones and metabolites were examined with particular emphasis on the GH axis, lipid metabolism and adrenocortical responses. 60 children admitted to PICU were studied (31 with meningococcal sepsis). Blood levels of lactate, pyruvate, acetoacetate, ?-hydroxybutyrate, free fatty acids, glucagon, insulin, GH, IGF-1, IGFBP-3, IGFBP-1, T4, TSH, cortisol, aldosterone, renin and catecholamines were measured by microassays. Collectively, all children showed evidence of endocrine stress, however there appeared to be little correlation between the MER at presentation and classical measurements of critical illness severity (PROM). Plasma lactate levels, however, correlated better with many of the metabolites and hormones. The MER may describe aspects of illness severity not addressed by the current scoring systems. Significant differences were observed between the different diagnostic categories and the MER at presentation. Plasma aldosterone levels were significantly lower in the patients with meningococcal disease. These were dissociated from appropriately elevated plasma renin levels. Hyperreninaemic hypoaldosteronism has not been reported previously in critically ill children. Plasma cortisol levels were elevated in the meningococcal sepsis category, they fell faster than in other critically ill children. Plasma cortisol levels were lower in the meningococcal patients with higher inotrope requirement. Plasma levels of aldosterone correlated with elements of the IGF-1 axis, again a feature not previously described. The retrospective assessment of initial design of the study and areas of future research are also addressed.

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