Hydrocortisone in Severe Community-Acquired Pneumonia

  • Dequin, Pierre-François M.D., Ph.D.
  • Meziani, Ferhat M.D., Ph.D.
  • Quenot, Jean-Pierre M.D., Ph.D.
  • Kamel, Toufik M.D.
  • Ricard, Jean-Damien M.D., Ph.D.
  • Badie, Julio M.D.
  • Reignier, Jean M.D., Ph.D.
  • Heming, Nicholas M.D., Ph.D.
  • Plantefève, Gaëtan M.D.
  • Souweine, Bertrand M.D., Ph.D.
  • Voiriot, Guillaume M.D., Ph.D.
  • Colin, Gwenhaël M.D.
  • Frat, Jean-Pierre M.D., Ph.D.
  • Mira, Jean-Paul M.D., Ph.D.
  • Barbarot, Nicolas M.D.
  • François, Bruno M.D.
  • Louis, Guillaume M.D.
  • Gibot, Sébastien M.D., Ph.D.
  • Guitton, Christophe M.D., Ph.D.
  • Giacardi, Christophe M.D.
  • Hraiech, Sami M.D., Ph.D.
  • Vimeux, Sylvie M.D.
  • L'Her, Erwan M.D., Ph.D.
  • Faure, Henri M.D.
  • Herbrecht, Jean-Etienne M.D.
  • Bouisse, Camille M.D.
  • Joret, Aurélie M.D.
  • Terzi, Nicolas M.D., Ph.D.
  • Gacouin, Arnaud M.D.
  • Quentin, Charlotte M.D.
  • Jourdain, Mercé M.D., Ph.D.
  • Leclerc, Marie M.Sc.
  • Coffre, Carine M.Sc.
  • Bourgoin, Hélène Pharm.D.
  • Lengellé, Céline Pharm.D.
  • Caille-Fénérol, Caroline M.Sc.
  • Giraudeau, Bruno Ph.D.
  • Le Gouge, Amélie M.Sc.

  • From Université de Tours, INSERM, Center for the Study of Respiratory Diseases Unité 1100, Médecine Intensive-Réanimation and INSERM Centre d'Investigation Clinique 1415, Centre Hospitalier Universitaire (CHU) (P.-F.D.), Délégation à la Recherche Clinique et à l'Innovation, CHU (M.L., C.C.), Pharmacie à Usage Interne, CHU (H.B.), Centre Régional de Pharmacovigilance et d'Information sur le Médicament, Service de Pharmacosurveillance, CHU (C.L.), Université de Tours, Université de Nantes, INSERM SPHERE Unité 1246 (B.G.), and INSERM Centre d'Investigation Clinique 1415, CHU (B.G., A.L.G.), Tours, INSERM, Unité Mixte de Recherche 1260, Regenerative Nanomedicine, Université de Strasbourg, Faculté de Médecine, and Médecine Intensive-Réanimation Nouvel Hôpital Civil (F.M.), Médecine Intensive Réanimation, Hôpital de Hautepierre (J.-E.H.), Hôpitaux Universitaires de Strasbourg, Strasbourg, the Lipness Team, INSERM Lipids, Nutrition, Cancer-Unité Mixte de Recherche 1231 and LabEx LipSTIC, INSERM Centre d'Investigation Clinique 1432, Clinical Epidemiology, Université de Bourgogne, and Médecine Intensive Réanimation, CHU (J.-P.Q.), Dijon, Médecine Intensive Réanimation, Hôpital de la Source, Orléans (T.K.), INSERM Infection, Antimicrobials, Modeling, and Evolution (IAME) Unité 1137, Université Paris Cité (J.-D.R.), Sorbonne Université, Centre de Recherche Saint-Antoine Unité Mixte de Recherche 938 INSERM, Médecine Intensive Réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Tenon (G.V.), and Université Paris Cité, Paris, Médecine Intensive Réanimation, AP-HP, Hôpital Cochin (J.-P.M.), Médecine Intensive Réanimation, DMU ESPRIT, Colombes (J.-D.R.), Réanimation Polyvalente, Hôpital Nord Franche-Comté, Trévenans (J.B.), Université de Nantes et Médecine Intensive-Réanimation, Hôtel-Dieu, Nantes (J.R.), Fédération Hospitalo Universitaire (FHU) SEPSIS, INSERM Unité 1173, Faculté de Médecine Simone Veil, Université Versailles Saint Quentin, Université de Paris Saclay, and Médecine Intensive-Réanimation, AP-HP, Hôpital Raymond Poincaré (N.H.), Garches, Réanimation Polyvalente, CH Victor Dupouy, Argenteuil (G.P.), Université Clermont Auvergne Unité Mixte de Recherche, French National Center for Scientific Research (CNRS) 6023, Laboratoire Microorganismes: Génome Environnement and Médecine Intensive Réanimation, CHU Clermont-Ferrand, Clermont-Ferrand (B.S.), Médecine Intensive Réanimation, Centre Hospitalier Départemental de Vendée, La Roche-Sur-Yon (G.C.), INSERM Centre d'Investigation Clinique 1402, Investigations of Sleep, Acute Lung Injury, and Ventilation, Université de Poitiers, Faculté de Médecine et de Pharmacie de Poitiers, and Médecine Intensive Réanimation, CHU (J.-P.F.), Poitiers, Réanimation, Centre Hospitalier, Saint Brieuc (N.B.), Unité Mixte de Recherche 1092, Université, Limoges, and INSERM Centre d'Investigation Clinique 1435 and Réanimation Polyvalente, CHU (B.F.), Limoges, Réanimation Polyvalente, Hôpital de Mercy, Centre Hospitalier Régional (CHR) Metz-Thionville, Metz (G.L.), Université de Lorraine, and Médecine Intensive Réanimation, Hôpital Central, CHU, Nancy (S.G.), Réanimation Médico-Chirurgicale, Hôpital, Le Mans (C. Guitton), Réanimation Polyvalente, Hôpital d'Instruction des Armées Clermont Tonnerre (C. Giacardi), Laboratoire de Traitement de l'Information Médicale INSERM Mixte de Recherche Unité 1101, Université de Bretagne Occidentale (E.L.), and Médecine Intensive Réanimation, CHU de la Cavale Blanche (E.L.), Brest, Aix-Marseille Université, Health Service Research and Quality of Life Center, the Department of Medical Information, Assistance Publique-Hopitaux de Marseille (AP-HM), Marseille, and Médecine Intensive-Réanimation, AP-HM, Hôpital Nord, Marseille (S.H.), Réanimation, Centre Hospitalier, Montauban (S.V.), Médecine Intensive Réanimation, Centre Hospitalier Intercommunal Robert Ballanger, Aulnay-Sous-Bois (H.F.), Réanimation, Centre Hospitalier, Bourg-en-Bresse (C.B.), Médecine Intensive Réanimation, CHU, Caen (A.J.), INSERM Unité 1042, HP-2, Université Grenoble-Alpes, and Médecine Intensive Réanimation, CHU Grenoble Alpes, Grenoble (N.T.), Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Rennes (A.G.), Réanimation, Centre Hospitalier, Saint-Malo (C.Q.), INSERM Unité 1190, Université de Lille, and the Département de Réanimation, Hôpital Roger Salengro, CHU, Lille (M.J.), and INSERM Centre d'Investigation Clinique 1435, CHU, Limoges (C.C.-F.) — all in France.

Dr. Dequin can be contacted at [email protected] or at Service de Médecine Intensive-Réanimation, Hôpital Bretonneau, 37 044 Tours Cedex 9, France.

*A list of the members of the CRICS-TriGGERSep Network is provided in the Supplementary Appendix, available at NEJM.org.

Supported by the French Ministry of Health (Programme Hospitalier de Recherche Clinique 2014).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on March 21, 2023, and updated on April 6, 2023, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

New England Journal of Medicine 388(21):p 1931-1941, May 25, 2023. | DOI: 10.1056/NEJMoa2215145

ABSTRACT

BACKGROUND

Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear.

METHODS

In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 8 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days.

RESULTS

A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, −5.6 percentage points; 95% CI, −9.6 to −1.7; P=0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment.

CONCLUSIONS

Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.)

Hydrocortisone in Severe Community-Acquired Pneumonia

  • Friedrich, Jan O. M.D., D.Phil.
  • Gouvêa Bogossian, Elisa M.D.
New England Journal of Medicine 389(7):p 670-671, August 17, 2023. | DOI: 10.1056/NEJMc2307400

Time to Treat Severe Community-Acquired Pneumonia with Steroids?

  • Metlay, Joshua P. M.D., Ph.D.
  • Waterer, Grant W. M.B., B.S., Ph.D.
New England Journal of Medicine 388(21):p 2001-2002, May 25, 2023. | DOI: 10.1056/NEJMe2302544
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