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

NCT06727435 | Not Yet Recruiting DMC

• 1 other identifier: analgesia-first strategy
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

neurosurgical patients; analgesia-first; remifentanil; analgesia and sedation; neurosurgical craniotomy

Outcome Measures

Primary Outcomes (2)

• The rate of successful protocol management during the first 24 hours after initiation of the analgesia-first strategy

  Successful protocol management requires no rescue hypnotic sedative use, no protocol discontinuation for safety, and adequate RASS control according to the following operational rule: at least 80% of scheduled RASS assessments during the first 24 hours must be within the target range of -2 to +1, with no sustained RASS \> +1 lasting more than 30 minutes despite protocolized treatment and no RASS +3 or +4 at any scheduled or clinically indicated assessment.

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

• The incidence rate of adverse events

  Adverse events include accidental extubation, accidental catheter or drain removal, significant agitation, delirium, severe hypotension, severe bradycardia, respiratory depression, vomiting or aspiration risk, opioid-induced rigidity, seizure, neurological deterioration, suspected or confirmed intracranial hypertension, emergent neurosurgical intervention, and urgent unplanned CT or MRI for suspected neurological worsening.

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

Secondary Outcomes (6)

• Dosage of remifentanil

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

• ICU length of stay

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

• ICU cost

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

• Dosage of sedative drugs

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

• bispectral index (BIS) values

  from enrollment to the discharge of ICU, 28 days or death, whichever came first

Study Arms (1)

an analgesia-first strategy without routine hypnotic sedatives

EXPERIMENTAL

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. If RASS remains ≥ +1 and pharmacological treatment is required, remifentanil will be initiated at 0.10-0.15 µg/kg/min. The dose will be titrated every 10-15 minutes by 0.025 µg/k

Drug: analgesia-first strategy without hypnotic sedatives

Interventions

analgesia-first strategy without hypnotic sedatives DRUG

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.

an analgesia-first strategy without routine hypnotic sedatives

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-85 years;
• Admission to the ICU after neurosurgical craniotomy;
• Anticipated ICU stay greater than 24 hours according to the treating team at ICU admission or screening;
• The Richmond Agitation-Sedation Scale (RASS) score ≥ +1, indicating restlessness or agitation requiring clinical management;
• RASS, the Critical Care Pain Observation Tool (CPOT), and neurological status can be assessed reliably enough for protocol monitoring.

You may not qualify if:

• Need for deep sedation or therapeutic coma, including (partial pressure of oxygen(PaO2)/fraction of inspired oxygen(FiO2): PaO2/FiO2≤100 mmHg, neuromuscular blockade requiring unconsciousness, status epilepticus, mandatory immobility for surgical or procedural safety, severe traumatic brain injury and intracranial hypertension, therapeutic hypothermia and any clinical condition requiring RASS \< -2) \[15, 16\];
• Medullary lesion, brainstem condition, or other disorder associated with impaired respiratory drive in which opioid analgesia is judged unsafe by the treating physician \[17\];
• Inability to assess the RASS score or neurological status because of coma, severe aphasia, status epilepticus, severe cognitive dysfunction, schizophrenia, mania, or aother psychiatric or neurological condition that precludes reliable assessment.;
• Use of sedatives or opioid analgesics ≥ 1 week before enrollment;
• Expected ICU stay time less than or equal to 24 hours;
• Delirium, alcohol withdrawal, active severe psychiatric illness, or ongoing antipsychotic therapy before enrolment;
• Severe hepatic dysfunction (Child-Pugh grade C);
• Renal failure requiring renal replacement therapy;
• Need for major surgery during the ICU stay, except short bedside or minor procedures, such as lumbar puncture or ventricular drainage, etc.);
• Known allergy or contraindication to remifentanil, morphine, midazolam, propofol, or other protocol medications;
• Pregnancy or lactation;
• Participation in another interventional clinical trial that could interfere with the study intervention or outcomes.;
• Patient or legally authorized representative unwilling to participate;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital, South 4th Ring West Road 119, Fengtai District, Beijing 100070, China.

Beijing, China

Location

MeSH Terms

Conditions

Agnosia

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Guangzhi Shi, Professor

CONTACT

86-13601110669; shiguangzhi@bjtth.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the department of critical care unit

Model Details: a single-arm, single-centre exploratory prospective study

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: December 10, 2024
• Study Start: August 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)