Adjuvant Continuous Infusion of Nefopam Versus Standard of Care in Mechanically Ventilated Critically Ill Patients: Randomized Double-blind Controlled Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Cumulative dose of fentanyl
研究概览
简要总结
The aim of this prospective, randomized, active control, double blinded study is to assess the effect and safety of continuous infusion nefopam in mechanically ventilated ICU patients compared to standard of care. It is being hypothesized that continuous infusion nefopam will reduce opioid use with acceptable safety profile compared to standard of care.
详细描述
Pain is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage". Critically ill patients experience pain at rest and during standard caring procedures. Arterial catheter insertion, chest tube removal, wound drain removal, wound care, and turning are associated with the greatest increased pain intensity. Pain have short and long-term sequelae on critically ill patients. Short-term sequelae include impaired tissue oxygenation, impaired wound healing, and impaired immune functions. Long-term sequelae include chronic pain, Post-traumatic stress disorder (PTSD) symptoms, and a lower health-related quality of life.
The gold standard for pain assessment is patient's self-report of pain. For critically ill able to self-report pain the 0-10 numeric rating scale in a visual format (NRS-V) is the best to use. Unfortunately, a lot of critically ill patients are unable to communicate and self-report pain. So, using behavioral pain scales are suitable in this type of patients, Critical care pain observation tool (CPOT) demonstrates validity and reliability for monitoring pain in critical ill adult patient who are unable to self-report pain and in whom behaviors are observable. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption (PADIS) guideline panel suggests "using an assessment-driven, protocol-based, stepwise approach for pain and sedation management in critically ill adults" and state as a good practice statement "critically ill adults should be regularly assessed for delirium using a valid tool".
Opioids are a cornerstone in the management of pain in critically ill patient, but have a lot of negative consequences including constipation, urinary retention, bronchospasm, over-sedation, respiratory depression, hypotension, nausea, truncal rigidity, delirium, and immunosuppression. Also, they contribute to vasodilatation and hypotension which lead to increased resuscitation fluids volume in critically ill patient.
"Multi-modal analgesia" also known as "balanced analgesia" approach via using non-opioids adjuvant or in replacement of opioids to target different pain pathways leads to optimizing analgesia and reducing opioids consumption. In France, the second most prescribed non-opioids in mechanically ventilated intensive care unit (ICU) patient is nefopam. Nefopam is a non-opioid, non-steroidal centrally acting analgesic, although the exact mechanism of action poorly understood, analgesic activity is thought to be via inhibiting dopamine, norepinephrine, serotonin reuptake. Nefopam was non-inferior to fentanyl for pain control in patients undergoing elective cardiac surgery without increase in adverse effects. Nefopam has a fentanyl sparing effect up to 50% in patients underwent laparoscopic total hysterectomy.
The 2018 PADIS guideline panel made a conditional recommendation for using "nefopam (if feasible) either as an adjunct or replacement for an opioid to reduce opioid use and their safety concerns for pain management in critically ill adults".
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients >18 years on mechanical ventilation and expected to need ventilatory support for the next 24 hours.
- •Candidate for sedation and analgesia protocol
排除标准
- •Pregnant and/or lactating woman.
- •Has been intubated for duration longer than 12 hours in an intensive care unit.
- •Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury.
- •Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness.
- •Admission as a consequence of a suspected or proven drug overdose
- •Mean arterial pressure (MAP) < 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomization.
- •Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment.
- •Patients with severe hepatic impairment (Child-Pugh class C) or end stage renal disease (ESRD) (creatinine clearance < 30 ml/min or on chronic hemodialysis) due to altered pharmacokinetics [20].
- •Need for deep sedation such as administration of neuromuscular blockers.
- •Convulsions or previous history of convulsions.
- •Risk of urinary retention linked to uretroprostatic disorders.
- •Risk of acute angle glaucoma.
- •Known intolerance of or hypersensitivity to study medications or constituents.
研究组 & 干预措施
Nefopam group
Adjunct continuous infusion of nefopam plus standard of care in ICU for assessment and management of pain, sedation, and delirium.
Nefopam will be administered as an initial dose of 20 mg IV dose infused over 15 minutes then, as continuous infusion of 5 mg/hr for 24 hours.
干预措施: Nefopam (Drug)
Nefopam group
Adjunct continuous infusion of nefopam plus standard of care in ICU for assessment and management of pain, sedation, and delirium.
Nefopam will be administered as an initial dose of 20 mg IV dose infused over 15 minutes then, as continuous infusion of 5 mg/hr for 24 hours.
干预措施: Standard of care in the ICU for assessment and management of pain, sedation, and delirium. (Drug)
Control group
Standard of care in the ICU for assessment and management of pain, sedation, and delirium.
干预措施: Standard of care in the ICU for assessment and management of pain, sedation, and delirium. (Drug)
结局指标
主要结局
Cumulative dose of fentanyl
时间窗: First 24 hour after randomization.
To compare the cumulative dose of fentanyl
次要结局
- Re-intubation(28 days post-randomization)
- Incidence of delirium(24 hour after randomization)
- Richmond Agitation and Sedation Score (RASS)(First 24 hours after randomization.)
- pain score(First 24 hours after randomization.)
- Duration of mechanical ventilation (MV)(The number of calendar days from intubation date to extubation date, until ICU discharge, death, or 28 days post-randomization, whichever comes first.)
- vasopressor requirements(First 24 hours after randomization.)
- Hemodynamics(First 24 hours after randomization.)
- ICU length of stay (LOS)(From randomization to ICU discharge date)
- Tracheostomy(28 days post-randomization)
- Unplanned extubation (self-extubation)(28 days post-randomization)
- Use of antipsychotics(24 hour after randomization)
- Use of physical restraint(24 hour after randomization)
- Mortality rate at the time of hospital discharge or 28 days after randomization, whichever comes first.(28 days after randomization)
研究者
Mohammed Gamal Abdelraouf Amer
Clinical Reseacher
Cairo University