Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve

Abstract

Aims: To investigate the relationship between adrenal gland function and pressor response to noradrenaline in septic shock.

Methods: Basal cortisol level, noradrenaline--mean arterial pressure dose-response curve and cortisol response to intravenous corticotrophin bolus were obtained in nine patients fulfilling usual criteria for septic shock and in six normal volunteers. In patients with septic shock, dose-response curve to noradrenaline was determined a second time 60 min after a 50 mg intravenous hydrocortisone bolus.

Results: As compared with controls, patients with septic shock had increased basal cortisol levels (mean+/-s.d.: 1564+/-818 vs 378+/-104 nmol l(-1) , P=0.002, 95% confidence interval for difference in means: [452, 1920]) and a blunted cortisol response to corticotrophin (403+/-461 vs 1132+/-195 nmol l(-1), P=0.008, [-1163, -2951). Five patients had impaired adrenal function reserve. As compared with controls, septic patients displayed a moderate and non significant decrease in pressor sensitivity to noradrenaline (P=0.112). As compared with patients with adequate adrenal response, patients with impaired adrenal function reserve showed a significant decrease in pressor sensitivity to noradrenaline (P=0.038). In septic patients, hydrocortisone improved pressor response to noradrenaline (P=0.032). This effect was more marked in patients with impaired adrenal function reserve so that, as compared with patients with adequate response, the difference was no longer significant (P=0.123).

Conclusions: In septic shock, impaired adrenal function reserve may partly be accounted for by the depressed pressor sensitivity to noradrenaline. The latter may be substantially improved by physiological doses of hydrocortisone.

Figure 1

Patients (n = 9; squares) and controls (n = 6; circles) cortisol response to corticotrophin (i.e., difference between basal concentration and the highest of the 30 and 60 min concentrations after a 0.25 mg tetracosactrin intravenous bolus) as a function of individual values of basal plasma cortisol levels.

Figure 2

Increase in mean systemic arterial pressure in response to a stepwise infusion of noradrenaline in septic shock patients (n = 9; squares) and controls (n = 6; circles). Data are means±s.e. mean.

Figure 3

Increase in mean systemic arterial pressure in response to a stepwise infusion of noradrenaline in septic shock patients with impaired adrenal function reserve (n = 5; squares) and adequate adrenal response (n = 4; circles). Data are means±s.e. mean.

Figure 4

Maximum increase in mean systemic arterial pressure as a function of peak adrenal response after corticotrophin (i.e. highest value of plasma cortisol between 30 and 60 min after a 0.25 mg tetracosactrin intravenous bolus), in septic shock patients. Spearman correlation coefficient = 0.783 and P = 0.013.

Figure 5

Increase in mean systemic arterial pressure in response to a stepwise infusion of noradrenaline in septic shock patients at baseline (n = 9; squares) and 1 h after a 50 mg hydrocortisone intravenous bolus (n = 9; circles). Data are means±s.e. mean.

Figure 6

Increase in mean systemic arterial pressure in response to a stepwise infusion of noradrenaline 1 h after a 50 mg hydrocortisone intravenous bolus in septic shock patients with impaired adrenal function reserve (n = 5; squares) and adequate adrenal response (n = 4; circles). Data are means s.e. mean.