Opioid-free Sedation in Patients with Severe Traumatic Brain Injury. A Feasibility Study

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and hospitalisations worldwide, marked by primary and secondary injuries. Sedation plays a crucial role in the comprehensive management of patients with severe TBI.(1) It serves as a preventive treatment to avoid secondary brain insults and facilitates the implementation of other interventions like mechanical ventilation. Propofol and opioids are one of the most commonly used drugs for sedation in TBI. However, the use of opioids is associated with an array of side effects.(2) Current literature suggest that ketamine & dexmedetomidine can be used in TBI patients.(3,4) OBJECTIVE: This study evaluates the efficacy and safety of an opioid-free sedation regimen using ketamine-dexmedetomidine (Group KD) compared to the standard propofol-fentanyl combination (Group PO) in patients with severe TBI admitted to trauma intensive care unit. The study aims to identify a sedation strategy that ensures effective sedation and analgesia while reducing the opioid-related side effect burden. The primary objective was to find out the “percentage of time spent in goal Richmond Agitation Sedation (RASS) score, i.e., RASS score of -3 to -4” in two groups. Secondary objectives were to note the incidence of hemodynamic alterations, side effects of drugs, decrease in serum cortisol level at 48 hours & FOUR score at ICU discharge. METHODOLOGY: This study is a prospective, randomised trial conducted in the trauma ICU of Level 1 Trauma Centre. Thirty patients with severe traumatic brain injury requiring intubation and mechanical ventilation were enrolled in the study, 15 in each group. Ketamine and Dexmedetomidine were given as sedation in Group KD, and Propofol and fentanyl in Group PO. Sedation was initiated and titrated to achieve a target RASS score of -3 to -4, checked every 15 minutes initially and hourly after that for 48 hours. Hemodynamic alterations, incidence of agitation (RASS>+1), VAP, withdrawal symptoms, decrease in serum cortisol level at the end of 48 hrs, FOUR score and any neuro worsening were noted. RESULTS: Thirty patients were enrolled, with comparable demographics in both groups. Patients in both groups maintained target RASS scores for similar durations (94.4% in Group KD vs. 98% in Group PO, p = 0.279). Serum cortisol reduction was significantly greater in Group KD (38% vs. 13.8%, p = 0.0002). The incidence of bradycardia was higher in group KD (p=0.002), whereas more patients in Group PO had withdrawal symptoms (p = 0.0002) and constipation (p = 0.0078). Agitation and VAP rates were similar. Three patients in group KD and one patient in group PO got extubated with FOUR score of 16 on discharge from the ICU. The four score on discharge from the ICU ranged from 8 to 16 with similar frequency across different scores between the groups (all scores had p-value >0.05). There was one case of neuro worsening in group KD. CONCLUSION: Ketamine-Dexmedetomidine sedation for conservative management of severe TBI patients is as effective as the more practiced propofol-fentanyl sedation while avoiding the significant side effects of opioid use. This study highlights non-opioid drug combinations as a promising alternative for regular analgosedative in the management of TBI patients.