Growth hormone secretion in critical illness: effect of dopamine

The catabolic state is a major contributor to the morbidity and mortality of critical illness. The underlying mechanism is poorly understood. We examined the endogenous secretion of an anabolic protein, GH, and studied the effect exerted on its secretion by dopamine, a catecholamine that is frequently administered for cardiovascular purposes in critical care. In a randomized controlled study of critically ill adult polytrauma patients (n = 11), we evaluated the effect of prolonged (83- to 296-h) dopamine infusion (5 micrograms/kg.min, iv) on the dynamics of GH secretion and on serum insulin-like growth factor-I, cortisol, and insulin concentrations. The effect of brief (15- to 21-h) dopamine administration was documented in an additional randomized controlled cross-over study involving nine patients. The GH profiles, obtained by blood sampling every 20 min for 9 h during 2 consecutive nights, were examined by deconvolution analysis. GH release was found to be exclusively pulsatile in all patients. Prolonged and brief dopamine infusions appeared to have similar effects. Twenty-four hours before initiation or after withdrawal of dopamine infusion, mean serum GH concentrations, mean secretion rate, amount of GH per secretory burst, and secretory burst amplitude were low, but, respectively, a median of 17% (P = 0.028), 36% (P = 0.046), 40% (P = 0.008), and 94% (P = 0.002) higher than those during dopamine infusion. After dopamine withdrawal, increased GH secretion was detectable within 3 h. Dopamine's effect on GH release was specific, as this agent had no discernable effect on the elevated serum cortisol and insulin concentrations or the low plasma insulin-like growth factor-I levels within 24 h. In conclusion, the present data suggest that pulsatile GH secretion is low during critical illness and that dopamine infusion further attenuates GH secretion through amplitude modulation, possibly as a result of a direct inhibitory action on the somatotropes. The latter iatrogenic effect might further aggravate the catabolic state of critical illness.