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

Background: Septic shock is characterized by decreased responsiveness to ca techolamines. Because endogenous steroids are known to play a role in the m odulation of vasomotor tone, the purpose of our study was to investigate th e phenylephrine-mean arterial pressure dose-response relationship in patien ts with septic shock and the effect of a physiological dose of hydrocortiso ne on it. Methods: Twelve patients meeting usual criteria for septic shock and 12 age -matched control subjects were investigated before and 1 hour after receivi ng 50 mg intravenous hydrocortisone. Sixteen incremental doses of phenyleph rine (mu g/kg/min) were infused, and the effects on mean arterial pressure (mm Hg) were recorded. A sigmoid model, E = E-0 + [E-max . D-gamma/(ED(50)g amma + D-gamma)], was fitted to individual data. In this model, E is the pr edicted effect and D is the dose of phenylephrine infused. E-0 represents t he basal value of effect (ie, the value of mean arterial pressure without d rug), E-max is the maximum theoretical effect, ED50 is the dose of phenylep hrine for which an effect of 50% of E-max is observed, and gamma is the Hil l coefficient which accounts for the sigmoidicity of the curve. Results: As compared with in control subjects, in patients, E-0 was decreas ed 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 gr oup), ED50 was not modified, and gamma was increased before (3.5 +/- 1.8 ve rsus 1.3 +/- 0.3) and after (1.9 +/- 1.1 versus 1.3 +/- 0.3) administration of hydrocortisone (P = .0010 for group). Hydrocortisone similarly increase d E-0 in both groups (P = .0003 for sequence, P = .2883 for interaction), i ncreased more E-max in patients than in control subjects (P < .0001 for seq uence; P = .0280 for interaction), did not change ED50, and decreased gamma 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 d ecreased, whereas its ED50 is not modified, both before and after administr ation of hydrocortisone. A physiological dose of hydrocortisone tends to no rmalize the relationship.