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

Educational Objective
To learn about fluid therapy for patients with moderate to severe traumatic brain injury.
1 Credit CME
Key Points

Question  What is the effect of continuous infusion of hypertonic saline solution in patients with traumatic brain injury?

Findings  In this randomized clinical trial that included 370 adults with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline vs standard care resulted in an odds ratio for better neurological outcomes (based on the Extended Glasgow Outcome Scale) of 1.02 after 6 months; this was not statistically significant.

Meaning  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.

Abstract

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

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Article Information

Corresponding Author: Antoine Roquilly, MD, PhD, CHU de Nantes, Service d’anesthésie réanimation chirurgicale, Hôtel Dieu-HME, 5 allée de l’ile Gloriette, Nantes 4400, France (antoine.roquilly@chu-nantes.fr).

Accepted for Publication: March 25, 2021.

Author Contributions: Dr Roquilly had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Roquilly, Demeure dit Latte, Mahe, Vourc’h, Flet, Feuillet, Asehnoune.

Acquisition, analysis, or interpretation of data: Roquilly, Moyer, Huet, Lasocki, Cohen, Dahyot-Fizelier, Chalard, Seguin, Jeantrelle, Vermeersch, Gaillard, Cinotti, Demeure dit Latte, Vourc’h, Martin, Chopin, Lerebourg, Chiffoleau, Feuillet.

Drafting of the manuscript: Roquilly, Chalard, Vermeersch, Cinotti, Vourc’h, Feuillet, Asehnoune.

Critical revision of the manuscript for important intellectual content: Moyer, Huet, Lasocki, Cohen, Dahyot-Fizelier, Seguin, Jeantrelle, Gaillard, Demeure dit latte, Mahe, Vourc’h, Martin, Chopin, Lerebourg, Flet, Chiffoleau, Asehnoune.

Statistical analysis: Feuillet.

Obtained funding: Roquilly.

Administrative, technical, or material support: Vermeersch, Cinotti, Demeure dit Latte, Vourc’h, Martin, Chopin, Lerebourg, Flet, Chiffoleau.

Supervision: Roquilly, Asehnoune.

Conflict of Interest Disclosures: Dr Roquilly reported receiving grants and consulting fees from Merck and bioMérieux. Dr Cinotti reported receiving personal fees from Paion. Dr Asehnoune reported receiving lecture fees from Baxter, Fisher & Paykel, and LFB and consulting fees from Edwards Lifesciences and LFB. No other disclosures were reported.

Funding/Support: This study was supported by a grant from the French Ministry of Health Programme Hospitalier de Recherche Clinique Inter-regional 2016 (PHRCI 2016, RC16_0474). The Nantes University Hospital acted as the sponsor of the study.

Role of the Funder/Sponsor: The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3.

Group Information: The members of the Atlanrea Study Group and the Société Française d’Anesthésie Réanimation (SFAR) Research Network appear in Supplement 4.

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