title: The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective open-label randomized controlled pilot trial.
  
  
  METHODS
  Four adult ICUs in London teaching hospitals.
  
  
  METHODS
  Sixty-one adult patients who had septic shock.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Gordon
authors.forename: Alexina J
authors.initials: AJ
authors.lastname: Mason
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.forename: Martin
authors.initials: M
authors.lastname: Stotz
authors.forename: Marius
authors.initials: M
authors.lastname: Terblanche
authors.forename: Deborah
authors.initials: D
authors.lastname: Ashby
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Brett
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D063305:Organ Dysfunction Scores; D010865:Pilot Projects; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy*; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014667:Vasopressins / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D006854:Hydrocortisone