The Interaction of Vasopressin and Corticosteroids in Septic Shock: A Pilot Randomized Controlled Trial

TY - JOUR

T1 - The Interaction of Vasopressin and Corticosteroids in Septic Shock

T2 - A Pilot Randomized Controlled Trial

AU - Gordon, Anthony C.

AU - Mason, Alexina J.

AU - Perkins, Gavin D.

AU - Stotz, Martin

AU - Terblanche, Marius

AU - Ashby, Deborah

AU - Brett, Stephen J.

PY - 2014/6

Y1 - 2014/6

N2 - Objectives: Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock. Retrospective analyses have suggested that there may be an interaction between these drugs, with higher circulating vasopressin levels and improved outcomes in patients treated with both vasopressin and corticosteroids. We aimed to test for an interaction between vasopressin and corticosteroids in septic shock.Design: Prospective open-label randomized controlled pilot trial.Setting: Four adult ICUs in London teaching hospitals.Patients: Sixty-one adult patients who had septic shock.Interventions: Initial vasopressin IV infusion titrated up to 0.06 U/min and then IV hydrocortisone (50 mg 6 hourly) or placebo. Plasma vasopressin levels were measured at 6-12 and 24-36 hours after hydrocortisone/placebo administration.Measurements and Main Results: Thirty-one patients were allocated to vasopressin + hydrocortisone and 30 patients to vasopressin + placebo. The hydrocortisone group required a shorter duration of vasopressin therapy (3.1 d; 95% CI, 1.1-5.1; shorter in hydrocortisone group) and required a lower total dose of vasopressin (ratio, 0.47; 95% CI, 0.32-0.71) compared with the placebo group. Plasma vasopressin levels were not higher in the hydrocortisone group compared with the placebo group (64 pmol/L difference at 6- to 12-hour time point; 95% CI, -32 to 160 pmol/L). Early vasopressin use was well tolerated with only one serious adverse event possibly related to study drug administration reported. There were no differences in mortality rates (23% 28-day mortality in both groups) or organ failure assessments between the two treatment groups.Conclusions: Hydrocortisone spared vasopressin requirements, reduced duration, and reduced dose, when used together in the treatment of septic shock, but it did not alter plasma vasopressin levels. Further trials are needed to assess the clinical effectiveness of vasopressin as the initial vasopressor therapy with or without corticosteroids.

AB - Objectives: Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock. Retrospective analyses have suggested that there may be an interaction between these drugs, with higher circulating vasopressin levels and improved outcomes in patients treated with both vasopressin and corticosteroids. We aimed to test for an interaction between vasopressin and corticosteroids in septic shock.Design: Prospective open-label randomized controlled pilot trial.Setting: Four adult ICUs in London teaching hospitals.Patients: Sixty-one adult patients who had septic shock.Interventions: Initial vasopressin IV infusion titrated up to 0.06 U/min and then IV hydrocortisone (50 mg 6 hourly) or placebo. Plasma vasopressin levels were measured at 6-12 and 24-36 hours after hydrocortisone/placebo administration.Measurements and Main Results: Thirty-one patients were allocated to vasopressin + hydrocortisone and 30 patients to vasopressin + placebo. The hydrocortisone group required a shorter duration of vasopressin therapy (3.1 d; 95% CI, 1.1-5.1; shorter in hydrocortisone group) and required a lower total dose of vasopressin (ratio, 0.47; 95% CI, 0.32-0.71) compared with the placebo group. Plasma vasopressin levels were not higher in the hydrocortisone group compared with the placebo group (64 pmol/L difference at 6- to 12-hour time point; 95% CI, -32 to 160 pmol/L). Early vasopressin use was well tolerated with only one serious adverse event possibly related to study drug administration reported. There were no differences in mortality rates (23% 28-day mortality in both groups) or organ failure assessments between the two treatment groups.Conclusions: Hydrocortisone spared vasopressin requirements, reduced duration, and reduced dose, when used together in the treatment of septic shock, but it did not alter plasma vasopressin levels. Further trials are needed to assess the clinical effectiveness of vasopressin as the initial vasopressor therapy with or without corticosteroids.

KW - adrenal cortex hormones

KW - drug interactions

KW - intensive care

KW - multiple organ failure

KW - sepsis

KW - vasopressins

KW - ADVANCED VASODILATORY SHOCK

KW - ATRIAL-NATRIURETIC-PEPTIDE

KW - SURVIVING SEPSIS CAMPAIGN

KW - LOW-DOSE VASOPRESSIN

KW - ACUTE KIDNEY INJURY

KW - ARGININE-VASOPRESSIN

KW - ORGAN FAILURE

KW - INTERNATIONAL GUIDELINES

KW - CONSENSUS CONFERENCE

KW - NOREPINEPHRINE

UR - http://www.scopus.com/inward/record.url?scp=84901497746&partnerID=8YFLogxK

U2 - 10.1097/CCM.0000000000000212

DO - 10.1097/CCM.0000000000000212

M3 - Article

C2 - 24557425

SN - 0090-3493

VL - 42

SP - 1325

EP - 1333

JO - Critical Care Medicine

JF - Critical Care Medicine

IS - 6

ER -