1025-99 Relationship Between Low Cortisol Response to Corticotropin and Reduced Vessels Contractility in Human Septic Shock

The relationship between the cortisol response to corticotropin and vessels α-adrenoreceptor sensitivity to dopamine is assessed in 20 patients fulfilling Bone's criteria for septic shock, by drawing dose-response curves for mean arterial pressure (MAP, mmHg, beat-to-beat recording of finger blood pressure, Finapress) during stepwise incremental doses of dopamine (D, μ g/kg/min, 0–2.5–5–7.5–10–12.5–15–20–25–30). Just before D administration all patients undergo a short corticotropin stimulation test (Synacthen, Ciba) consisting of a 0.25 mg IV bolus of tetracosactrin (plasma cortisol levels, ng/ml, are assessed immediately before the test and 30 and 60 minutes afterwards). The cortisol response to corticotropin is defined as the greater difference between baseline and 30 and 60 minutes plasma cortisol levels (D max Cort, ng/ml). Dose response curve fitting parameters are estimated in individual subjects using a multiple dose non linear regression program (SYSTAT, Inc software). The relationship between curve fitting parameters and D max Cort is studied by using the Spearman correlation test. The mean values of curve fitting parameters are Emax = 81 ± 23 (mmHg) and EC50 = 6.3 ± 2.5 (D titration giving 50% of Emax μ g/kg/min). Basal cortisol concentrations and D max Cort are respectively 439 ± 284 and 111 ± 192 (ng/ml). Emax correlated positively and strongly with D max Cort (p = 0.007). No relationship is found between D max Cort and EC50, plasma norepinephrine levels, and arterial lactates. We conclude that the weaker the cortisol response to corticotropin the more hypereactive the vessels in human septic shock. This result underlines the key role of endogenous steroids in vascular tone regulation during sepsis, and raises again the usefulness of physiological doses of steroids rather than high doses for the management of septic shock.