Feasibility and Safety of an Analgesia-first Strategy Without Hypnotic Sedatives in Adult Patients Admitted to the Intensive Care Unit After Neurosurgical Craniotomy: a Single-arm, Single-centre Exploratory Prospective Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- The rate of successful protocol management during the first 24 hours after initiation of the analgesia-first strategy
研究概览
简要总结
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.
详细描述
This is a single-centre, single-arm, open-label, exploratory prospective clinical study conducted in the Department of Critical Care Medicine, Beijng Tiantan Hospital, Capital Medical University, China, a major neurosurgical centre. The ICU mainly receives patients after neurosurgical procedures. The study is reported according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) reporting guidelines.
All patients admitted to the ICU after neurosurgical craniotomy will be screened. Written informed consent will be obtained preoperatively whenever feasible for patients undergoing planned craniotomy. For patients who lack decision-making capacity postoperatively, consent may be obtained from a legally authorized representative according to IRB-approved procedures and local regulations. Capacity will be assessed by the treating clinician and research team before consent. Patients who regain capacity after representative consent will be informed about the study and asked to confirm continued participation. Deferred consent will not be used unless specifically permitted by the IRB. Patients or legally authorized representatives may withdraw from the study at any time without affecting clinical care.
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 . The intervention sequence is summarized in Table 2. 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/kg/min to a maximum of 0.20 µg/kg/min to target RASS -2 to +1 and CPOT 0-1 . Continuous SpO2, respiratory rate, heart rate, and non-invasive or invasive blood pressure monitoring will be required during continuous remifentanil infusion. For non-ventilated patients, continuous pulse oximetry and respiratory rate monitoring are mandatory; capnography will be used when available or when clinically indicated. For mechanically ventilated patients, ventilator synchrony and apnea alarms will also be monitored.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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;
- •Investigator judgment that inclusion is inappropriate because of a specific safety concern that is documented in the screening record.
研究组 & 干预措施
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.
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
干预措施: analgesia-first strategy without hypnotic sedatives (Drug)
结局指标
主要结局
The rate of successful protocol management during the first 24 hours after initiation of the analgesia-first strategy
时间窗: from enrollment to the discharge of ICU, 28 days or death, whichever came first
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.
The incidence rate of adverse events
时间窗: from enrollment to the discharge of ICU, 28 days or death, whichever came first
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.
次要结局
- 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)
- hospital length of stay(from enrollment to the discharge of ICU, 28 days or death, whichever came first)
研究者
Guangzhi Shi
Director of the department of critical care unit
Beijing Tiantan Hospital