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

Gordon, Anthony C. MD, FRCA, FFICM1,2; Mason, Alexina J. PhD3; Perkins, Gavin D. MD, FRCP, FFICM4,5; Stotz, Martin MD, AFICM2; Terblanche, Marius MSc, FRCA, FFICM6,7; Ashby, Deborah PhD, FMedSci3; Brett, Stephen J. MD, FRCA, FFICM2

doi: 10.1097/CCM.0000000000000212
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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.

1Section of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, London, United Kingdom.

2Centre for Perioperative Medicine and Critical Care Research, Imperial College Healthcare NHS Trust, London, United Kingdom.

3Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.

4Department of Critical Care, Warwick Clinical Trials Unit, University of Warwick, Coventry, United Kingdom.

5Heart of England NHS Foundation Trust, Birmingham, United Kingdom.

6Division of Asthma, Allergy & Lung Biology, King’s College London, London, United Kingdom.

7Critical Care Medicine, Guys & St Thomas’ NHS Foundation Trust, London, United Kingdom.

* See also p. 1531.

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Supported, in part, by the UK Intensive Care Foundation, the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centres based at Imperial College Healthcare NHS Trust and Imperial College London, and Guys and St Thomas’ NHS Foundation Trust and Kings College London. This article presents independent research part funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

Dr. Gordon is funded by a National Institute for Health Research (NIHR) Clinician Scientist Fellowship and has an NIHR trial grant to further investigate vasopressin. He has stock options with Sirius Genomics (which has submitted a patent, owned by the University of British Columbia [UBC] and licensed to Sirius Genomics, that is related to the genetics of vasopressin) and received support for article research from NIHR. His institution received grant support from NIHR (Clinician Scientist award and New vasopressin trial grant) and the Intensive Care Foundation (funded this trial) and has a patent (UBC has submitted a patent related to the use of vasopressin in septic shock, and he is named as an inventor on this patent). Dr. Ashby received support for article research from NIHR and is a NIHR Senior Investigator. Her institution received grant support from NIHR. Dr. Brett serves as the Chair of the Intensive Care Foundation. His institution received grant support from NIHR and Intensive Care Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: anthony.gordon@imperial.ac.uk

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins