Effect of Continuous Hypertonic Saline Infusion on Clinical Outcomes in Patients with Traumatic Brain Injury: A Retrospective Causal Analysis

Abstract Purpose: Intracranial pressure (ICP) control has long been recognized as an important requirement for traumatic brain injury (TBI) patients. Nevertheless, the long-term effect of hypertonic saline (HTS) remains unknown. The aim of this study was to elucidate the effect on clinical outcomes in TBI patients admitted to intensive care unit (ICU) settings.Methods: We retrospectively identified moderate to severe TBI patients from two public databases named Medical Information Mart for the Intensive Care (MIMIC)-IV and eICU Collaborative Research Database (eICU-CRD). A marginal structural Cox model (MSCM) was used, with time-dependent variates designed to reflect exposure over time during the ICU stay. A trajectory modeling, based on intracranial pressure evolution pattern, allowed identification of subgroups. Results: Overall, in our cohort of 1955 eligible patients, 130 (6.65%) received HTS. MSCM indicated that the HTS was significantly associated with better Glasgow coma score [(GCS): hazard ratio (HR) 1.19, 95% confidence interval (95% CI) 1.01-1.40, p = 0.041], higher infection complications [eg. urinary tract infection (HR 1.88, 95% CI 1.26-2.81, p = 0.002)], and increased ICU LOS (HR 2.02, 95% CI 1.71-2.40, p < 0.001). A protective effect from GCS by the HTS was found in the subgroup with medium and low ICP. Conclusion: Our study revealed no significant difference in the all-cause mortality rates between patients receiving HTS or not. Increased occurrence rates of infection and electrolyte imbalance were inevitable outcomes caused by continuous HTS infusion. Although the study suggested the slight beneficial effects including better neurological outcome, the results warrant further validation.