Feasibility and safety of an analgesia-first strategy without hypnotic sedatives in adult patients admitted to the intensive care unit after neurosurgical craniotomy: a protocol for a single-arm, single-center exploratory prospective study.

Introduction: Postoperative neurosurgical patients often require pain management and agitation control while still being assessed for consciousness and focal neurological signs. General ICU trials suggest that minimizing the use of hypnotic sedatives may be feasible for selected mechanically ventilated patients; however, neurocritical care patients may have different safety requirements. This study aims to explore the feasibility and safety of an analgesia-first strategy, without the routine use of hypnotic sedatives, in adult patients admitted to the ICU after neurosurgical craniotomy. Methods and analysis: This is a single-center, single-arm, open-label, exploratory prospective study. A total of 65 adult patients after neurosurgical craniotomy with an anticipated ICU stay of more than 24 h and Richmond Agitation-Sedation Scale (RASS) score ≥ + 1 will be enrolled, provided that they do not require deep sedation. Eligible patients will receive protocolized nonpharmacological measures and remifentanil-based analgesia titrated from 0.1 to 0.2 μg/kg/min every 10-15 min to achieve a target RASS score of -2 to +1 and Critical-Care Pain Observation Tool (CPOT) score of 0-1. Rescue sedation with midazolam or propofol is permitted when clinically required for safety. The primary endpoint is successful protocol management during the first 24 h after initiation, defined as absence of protocol failure caused by rescue hypnotic sedative use, sustained RASS scores outside the target range, a serious safety event requiring protocol discontinuation, or clinical deterioration. Key safety endpoints include significant agitation, accidental extubation, accidental catheter or drain removal, respiratory depression, severe hypotension or bradycardia, delirium, opioid-induced rigidity, neurological deterioration, seizures, emergent neurosurgical intervention, and urgent unplanned computed tomography (CT) or magnetic resonance imaging (MRI) for suspected neurological worsening. Secondary endpoints include analgesic and sedative exposure, nursing workload, bispectral index (BIS) values, duration of intubation, ventilator-free days through day 28, ICU and hospital length of stay, ICU costs, pneumonia, and in-hospital mortality. Clinical trial registration: ClinicalTrials.gov, identifier NCT06727435.