Comparative Effectiveness of Midazolam-Based Sedation on the Need for Intracranial Pressure Lowering Therapies in Traumatic Brain Injury

Sedatives play an important role in the management of patients with severe traumatic brain injury (sTBI) in the intensive care unit (ICU). Benzodiazepines are common for sedation (midazolam-based) but have been discouraged for non-brain-injured patients in the ICU. This study aimed to investigate the effect of midazolam-based sedation versus non-midazolam-based sedation on the need for intracranial pressure (ICP) lowering therapies in patients with sTBI in the ICU. We studied patients with sTBI (Glasgow Coma Sale ≤8) from 14 ICUs in Europe and Australia, who received ICP monitoring and continuous instrumental variable (IV) sedation for at least 24 h. We analyzed the association between sedation strategy and the need for ICP lowering therapies during the first 7 ICU days using a multivariable logistic regression model, adjusted for clinical markers of injury severity. We also analyzed the center as an IV in a random effects model to address potentially unmeasured confounding. Among 227 patients with sTBI, 152 (67%) received midazolam-based sedation. These patients had a lower age and higher median Glasgow Coma Scale on admission compared with 75 patients in the non-midazolam-sedated group. In logistic regression analyses, patients with midazolam-based sedation had higher odds of receiving hyperosmolar therapy (odds ratio [OR]: 3.4, 95% confidence intervals [CI]: 1.6-7.7). This effect could not be confirmed in the instrumental variable analysis (hyperosmolar therapy: OR: 1.3, 95% CI: 0.1-13.1). The mean ICU length of stay was significantly longer in the midazolam-based sedation group compared with the non-midazolam-based sedation group (19 vs. 13 days, hazards ratio 0.6, 95% CI: 0.4-0.8). Midazolam-based sedation was common for patients with sTBI without a significantly increased need for ICP therapies but an association with longer ICU stay. Larger prospective comparative effectiveness studies are needed regarding sedation strategies in critically ill patients with TBI.