Early inhaled isoflurane sedation in neurocritical patients with invasive intracranial pressure monitoring: the NEURO-CONDA randomized pilot trial

PURPOSE: Evidence on inhaled sedation in neurocritically ill patients remains limited, mainly due to concerns about potential increases in intracranial pressure (ICP). We aimed to evaluate the efficacy and safety of early isoflurane sedation compared with propofol in invasively monitored neurocritical patients without intracranial hypertension. METHODS: NEURO-CONDA is a phase IV, randomized, open-label, parallel-group pilot trial conducted in a tertiary ICU (May 2024-October 2025). Adult neurocritical patients requiring ICP monitoring and without intracranial hypertension were randomized to receive either propofol or isoflurane. The primary endpoints were efficacy (assessed with RASS and BIS™) and safety, defined as the occurrence of serious adverse drug reactions (ADRs), including sustained ICP elevation or cerebral perfusion pressure (CPP) < 60 mmHg requiring increased vasopressor support. Nociception (NOL®) and other systemic parameters were recorded for up to 72 h. Analyses were performed according to the intention-to-treat principle. RESULTS: Thirty patients were included (15 per group), and baseline characteristics were comparable; 19 had traumatic brain injury. Sedation efficacy was 100% in both groups throughout the study period. No serious ADRs occurred. ICP and CPP remained stable throughout the study period without requiring higher doses of vasopressors in the isoflurane sedated group. CONCLUSIONS: In this randomized pilot trial, early sedation with isoflurane was feasible and achieved reliable deep sedation without compromising intracranial or cerebral perfusion parameters in invasively monitored neurocritical patients without intracranial hypertension. Larger randomized studies are warranted to confirm these findings and assess long-term neurological outcomes.