Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Lancet Respir Med. 2014 Sep;2(9):706-16. doi: 10.1016/S2213-2600(14)70144-4. Epub 2014 Jul 24.

Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial.

Author information

  • 1CHU Nantes, Pôle anesthésie réanimations, Service d'Anesthésie Réanimation chirurgicale, Nantes, France. Electronic address: karim.asehnoune@chu-nantes.fr.
  • 2CHU Rennes, Service d'anesthésie réanimation 1, Université de Rennes 1, Rennes, France.
  • 3Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Service d'Anesthésie Réanimation Chirurgicale, Beaujon, France.
  • 4Plateforme de Biométrie-Cellule de promotion à la recherche clinique, CHU Nantes, Nantes, France; EA 4275 SPHERE Biostatistics, Pharmacoepidemiology & Human Sciences Research, UFR de Pharmacie, Université de Nantes, Nantes, France.
  • 5CHU Angers, Service d'Anesthésie Réanimation, Angers, France.
  • 6Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Service d'Anesthésie Réanimation chirurgicale, Créteil, France.
  • 7CHU Brest, Service d'Anesthésie Réanimation, Brest, France.
  • 8CHU Clermont Ferrand, Service d'Anesthésie Réanimation, Clermont Ferrand, France.
  • 9Department of Anesthesiology and Intensive Care, University Hospital of Toulouse, Equipe d'accueil Modélisation de l'agression tissulaire et nociceptive, University Toulouse 3 Paul Sabatier, Toulouse, France.
  • 10Service des Réanimations, Division Anesthésie Réanimation Douleur Urgence, CHU Nimes, Nimes, France.
  • 11CHU Montpellier, Hôpital Gui de Chauliac, Service d'Anesthésie Réanimation, Montpellier, France.
  • 12CHU Caen, Service d'Anesthésie Réanimation, Caen, France.
  • 13Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Service d'Anesthésie Réanimation chirurgicale, Paris, France.
  • 14CHU Bordeaux, Service d'Anesthésie Réanimation, Bordeaux, France.
  • 15CHU Grenoble, Hôpital Michallon, Service d'Anesthésie Réanimation, Grenoble, France.
  • 16CHU Poitiers, Service d'Anesthésie Réanimation, Poitiers, France.
  • 17CHU Montpellier, Hôpital Lapeyronie, Service d'Anesthésie Réanimation, Montpellier, France.
  • 18CHU Nantes, Pôle anesthésie réanimations, Service d'Anesthésie Réanimation chirurgicale, Nantes, France.
  • 19CHU Nantes, Pôle Biologie Pharmacie, Service Pharmacie, Nantes, France.

Abstract

BACKGROUND:

Hospital-acquired pneumonia is common after traumatic brain injury, and might be partly a result of traumatic brain injury-induced adrenal insufficiency. We tested the efficacy of low-dose hydrocortisone with fludrocortisone for the prevention of hospital-acquired pneumonia.

METHODS:

We did this double-blind, phase 3, placebo-controlled trial in 19 intensive care units in France. We enrolled patients aged 15-65 years in the first 24 h after severe traumatic brain injury (Glasgow coma scale score ≤8 and trauma-associated lesion on brain CT scan). Patients were randomly assigned (1:1; fixed blocks of 12, stratified by centre and mechanism, Glasgow coma scale, age, and arterial pressure [MGAP] score) to receive either hydrocortisone (200 mg per day tapered) and fludrocortisone (50 μg tablet once per day) or matching placebo for 10 days. Before receiving study drug, adrenal function was assessed with a short corticotropin test. Treatment was stopped if patients had no adrenal insufficiency. The primary outcome was the occurrence of hospital-acquired pneumonia within 28 days after randomisation. We did an intention-to-treat analysis and a modified intention-to-treat analysis including only patients with adrenal insufficiency (adjusted for etomidate use). This study is registered with ClinicalTrials.gov, number NCT01093261.

FINDINGS:

From Sept 1, 2010, to Nov 29, 2012, we enrolled 336 patients (168 assigned to each group). Eight patients withdrew consent. At day 28, 74 of 165 patients (45%) in the steroid group and 87 of 163 (53%) in the placebo group had developed one or more episodes of hospital-acquired pneumonia (hazard ratio [HR] 0·75; 95% CI 0·55-1·03, p=0·07). In intention-to-treat analysis, we recorded 86 episodes of hospital-acquired pneumonia in the steroid group versus 110 in the placebo group (median 0, IQR 0-1 vs median 1, IQR 0-1 cases per patient, p=0·07). In modified intention-to-treat analyses, the HR for hospital-acquired pneumonia with steroids versus placebo was 0·80 (95% CI 0·56-1·14, p=0·22) in patients with adrenal insufficiency, and, in an exploratory preplanned analysis, 0·48 (0·23-1·01; p=0·05) in patients with normal adrenal function. We recorded no adverse events related to treatment.

INTERPRETATION:

Low-dose hydrocortisone with fludrocortisone did not improve the outcome of patients with traumatic brain injury. However, the study was underpowered because the proportion of patients with hospital-acquired pneumonia in the placebo group was lower than expected. The results were close to statistical significance for efficacy, meaning that further studies are therefore needed.

FUNDING:

Société Française d'Anesthésie Réanimation.

Copyright © 2014 Elsevier Ltd. All rights reserved.

PMID:
25066331
[PubMed - in process]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk