Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury: The COBI Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 325; no. 20; pp. 2056 - 2066
• Main Authors: Roquilly, Antoine, Moyer, Jean Denis, Huet, Olivier, Lasocki, Sigismond, Cohen, Benjamin, Dahyot-Fizelier, Claire, Chalard, Kevin, Seguin, Philippe, Jeantrelle, Caroline, Vermeersch, Véronique, Gaillard, Thomas, Cinotti, Raphael, Demeure dit Latte, Dominique, Mahe, Pierre Joachim, Vourc’h, Mickael, Martin, Florian Pierre, Chopin, Alice, Lerebourg, Celine, Flet, Laurent, Chiffoleau, Anne, Feuillet, Fanny, Asehnoune, Karim
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 25-05-2021
• Subjects: Adult; Brain; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - drug therapy; Brain Injuries, Traumatic - therapy; Clinical trials; Combined Modality Therapy; Confidence intervals; Female; Fluid Therapy; Glasgow Outcome Scale; Head injuries; Hospitals; Humans; Hypernatremia - etiology; Hypertension; Hypnotics and Sedatives - therapeutic use; Infusions, Intravenous; Intensive care units; Intervention; Intracranial Hypertension - etiology; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Original Investigation; Patients; Saline Solution, Hypertonic - administration & dosage; Saline Solution, Hypertonic - adverse effects; Saline Solution, Hypertonic - therapeutic use; Saline solutions; Statistical analysis; Traumatic brain injury
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2021.5561

IMPORTANCE: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. OBJECTIVE: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. INTERVENTIONS: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. MAIN OUTCOMES AND MEASURES: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. RESULTS: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, −2.6% [95% CI, −12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, −4.9% [95% CI, −12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). CONCLUSIONS AND RELEVANCE: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03143751