Induced hypothermia in severe bacterial meningitis: a randomized clinical trial.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mourvillier Bruno, Tubach Florence, van de Beek Diederik, Garot Denis, Pichon Nicolas, Georges Hugues, Lefevre Laurent Martin, Bollaert Pierre-Edouard, Boulain Thierry, Luis David, Cariou Alain, Girardie Patrick, Chelha Riad, Megarbane Bruno, Delahaye Arnaud, Chalumeau-Lemoine Ludivine, Legriel Stéphane, Beuret Pascal, Brivet François, Bruel Cédric, Camou Fabrice, Chatellier Delphine, Chillet Patrick, Clair Bernard, Constantin Jean-Michel, Duguet Alexandre, Galliot Richard, Bayle Frédérique, Hyvernat Hervé, Ouchenir Kader, Plantefeve Gaetan, Quenot Jean-Pierre, Richecoeur Jack, Schwebel Carole, Sirodot Michel, Esposito-Farèse Marina, Le Tulzo Yves, Wolff Michel
Аннотация
OBJECTIVE: To test the hypothesis that induced hypothermia improves outcome in patients with severe bacterial meningitis.
DESIGN, SETTING, AND PATIENTS: An open-label, multicenter, randomized clinical trial in 49 intensive care units in France, February 2009-November 2011. In total, 130 patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale [GCS] score of ≤8 for <12 hours) with community-acquired bacterial meningitis were randomized.
INTERVENTIONS: Hypothermia group received a loading dose of 4°C cold saline and were cooled to 32°C to 34°C for 48 hours. The rewarming phase was passive. Controls received standard care.
MAIN OUTCOMES AND MEASURES: Primary outcome measure was the Glasgow Outcome Scale score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4 [unfavorable outcome]). All patients received appropriate antimicrobial therapy and vital support. Analyses were performed on an intention-to-treat basis. The data and safety monitoring board (DSMB) reviewed severe adverse events and mortality rate every 50 enrolled patients.
RESULTS: After inclusion of 98 comatose patients, the trial was stopped early at the request of the DSMB because of concerns over excess mortality in the hypothermia group (25 of 49 patients [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99; 95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3°C (0.9°C) and 37.0°C (0.9°C) in the hypothermia and control group, respectively. At 3 months, 86% in the hypothermia group compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78-6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the presence of septic shock at inclusion, mortality remained higher, although not significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar results. Post hoc analysis showed a low probability to reach statistically significant difference in favor of hypothermia at the end of the 3 planned sequential analyses (probability to conclude in favor of futility, 0.977).
CONCLUSIONS AND RELEVANCE: Moderate hypothermia did not improve outcome in patients with severe bacterial meningitis and may even be harmful. Careful evaluation of safety issues in future trials on hypothermia are needed and may have important implications in patients presenting with septic shock or stroke.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00774631.