an Analgesia-first Strategy Without Hypnotic Sedatives in Adult Patients Admitted to the Intensive Care Unit After Neurosurgical Craniotomy

Summary

Analgesia and sedation are core components of intensive care unit (ICU) care. They are used to relieve pain and anxiety, prevent harmful physiological stress responses, improve tolerance of invasive devices and mechanical ventilation, and reduce noxious stimulation. Contemporary ICU practice has moved away from deep continuous sedation toward analgesia-first care, lighter sedation targets, delirium prevention, early mobilization, and patient-centred comfort strategies.

Patients admitted to the ICU after neurosurgical craniotomy pose a specific challenge. Postoperative agitation after intracranial surgery may lead to unplanned extubation, catheter or drain removal, injury, hypertension, coughing, increased sympathetic activation, and potentially adverse neurological consequences. The incidence of agitation after elective intracranial operations was 29%, which was higher than that previously observed in other surgical populations. Neurosurgical patients may be more vulnerable to stress caused by agitation, due to longer anesthesia duration, delayed extubation and pain and post-craniotomy frontal pneumocephalus. Brain lesions and intracranial manipulations in neurosurgical patients might affect the brain regions which involves cognition and emotion, and are assumed to influence postoperative cognition. At the same time, excessive hypnotic sedation may obscure level of consciousness, pupillary and focal neurological examinations, early seizures, intracranial hypertension, or surgical complications. Previous neurosurgical studies have reported postoperative agitation and delirium after craniotomy were not rare, and risk factors including longer anesthesia duration, delayed extubation, pain, and postoperative pneumocephalus have been reported.

However, the investigations of analgesia and sedation in neurosurgical populations have been inadequate. Most of the researches about analgesia and sedation in general ICU were excluded the neurosurgical patients. These patients are special for its cruciality of evaluating the consciousness and neurological signs examination. The analgesia and sedation management is difficult and complex. Several general ICU studies support interest in minimizing routine hypnotic sedation. In a single-centre randomized trial, a protocol of no sedation with morphine boluses increased ventilator-free days and shortened ICU and hospital stay compared with sedation and daily interruption, although agitated delirium was more frequent. In the larger multicentre NONSEDA trial, mortality at 90 days did not differ significantly between nonsedation and light sedation with daily interruption, and many patients in the nonsedation group still required sedatives during ICU stay, most commonly because of delirium. Related NONSEDA substudies have also emphasized that the effects of nonsedation on physical function and cognition require dedicated evaluation.

These findings cannot be directly transferred to post-craniotomy neurocritical care. Reviews, consensus statements and observational studies in neurocritical care emphasize with brain-injured patients have unique sedation indications, including control of intracranial pressure, seizures, cerebral oxygen consumption, ventilator synchrony, and severe agitation. Observational data from brain-injury ICUs show wide variation in sedative and analgesic practice and support structured use of sedation and pain scales. Expert consensus also supports administering analgesics before sedatives when clinically appropriate, but acknowledges the limited high-quality evidence in this population. Therefore, an analgesia-first strategy without routine hypnotic sedatives should be evaluated cautiously with explicit neurological safety monitoring and rescue criteria.

Remifentanil is a short-acting opioid with rapid onset and offset because it is metabolized by non-specific blood and tissue esterases. These pharmacological features make it suitable for titrated analgesia when repeated neurological assessment is needed. We therefore designed this single-arm exploratory study to estimate the feasibility and safety of a remifentanil-based analgesia-first strategy without routine hypnotic sedatives in selected adult patients admitted to ICU after neurosurgical craniotomy.

Conditions

• Craniotomy
• Neurosurgical Patients

Interventions

DRUG

analgesia-first strategy without hypnotic sedatives

The study intervention is an analgesia-first strategy without routine hypnotic sedatives. The strategy does not imply absence of all sedative effect; remifentanil may influence arousal, and the RASS target includes light sedation. Routine hypnotic sedatives are avoided unless rescue sedation is clinically required. RASS and CPOT will be assessed routinely, with target RASS -2 to +1 and CPOT 0-1 . Reversible causes of discomfort will first be evaluated and treated, including hypoxia, airway obstruction, ventilator dyssynchrony, pain, urinary retention, nausea, tube irritation, environmental stressors, and neurological deterioration. Non-pharmacological measures such as reassurance, communication, family support when appropriate, sleep protection, and mobilization when safe will be used before pharmacological escalation.

Sponsors & Collaborators

• Beijing Tiantan Hospital

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2028-04-30

Completion

2028-08-31

Countries

• China

Study Locations