Effect of hydrocortisone on phenylephrine– mean arterial pressure dose‐response relationship in septic shock

Background Septic shock is characterized by decreased responsiveness to catecholamines. Because endogenous steroids are known to play a role in the modulation of vasomotor tone, the purpose of our study was to investigate the phenylephrine–mean arterial pressure dose‐response relationship in patients with septic shock and the effect of a physiological dose of hydrocortisone on it. Methods Twelve patients meeting usual criteria for septic shock and 12 age‐matched control subjects were investigated before and 1 hour after receiving 50 mg intravenous hydrocortisone. Sixteen incremental doses of phenylephrine (μg/kg/min) were infused, and the effects on mean arterial pressure (mm Hg) were recorded. A sigmoid model, E = E 0 + [E max · Dγ/(ED 50 γ + Dγ)], was fitted to individual data. In this model, E is the predicted effect and D is the dose of phenylephrine infused. E 0 represents the basal value of effect (ie, the value of mean arterial pressure without drug), E max is the maximum theoretical effect, ED 50 is the dose of phenylephrine for which an effect of 50% of E max is observed, and γ is the Hill coefficient which accounts for the sigmoidicity of the curve. Results As compared with in control subjects, in patients, E 0 was decreased before (58 ± 8 versus 73 ± 7 mm Hg) and after (64 ± 12 versus 82 ± 10 mm Hg) administration of hydrocortisone (P = .0001 for group), E max was reduced before (39 ± 17 versus 84 ± 18 mm Hg) and after (77 ± 26 versus 106 ± 21 mm Hg) administration of hydrocortisone (P = .0001 for group), ED 50 was not modified, and γ was increased before (3.5 ± 1.8 versus 1.3 ± 0.3) and after (1.9 ± 1.1 versus 1.3 ± 0.3) administration of hydrocortisone (P = .0010 for group). Hydrocortisone similarly increased E 0 in both groups (P = .0003 for sequence, P = .2883 for interaction), increased more E max in patients than in control subjects (P < .0001 for sequence; P = .0280 for interaction), did not change ED 50 , and decreased γ in patients but not in control subjects (P = .0025 for sequence, P = .0025 for interaction). Conclusions In patients with septic shock, the E max of phenylephrine is decreased, whereas its ED 50 is not modified, both before and after administration of hydrocortisone. A physiological dose of hydrocortisone tends to normalize the relationship. Clinical Pharmacology & Therapeutics (2000) 68 , 293–303; doi: 10.1067/mcp.2000.109354