Opioid-free Analgesia in Intensive Care Unit: a Prospective, Monocentric, Randomized, Double Blind, Feasability Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Daily remifentanil consumption (after randomisation)
研究概览
简要总结
ICU patients experience moderate to severe pain. Studies and guidelines point out the benefits of multimodal analgesia on pain control, opioid spare and on lowering its adverse effects. However, no recommendation about drugs or protocol has been formulated. In our study, investigators studied the feasibility and the impact on Remifentanil spare of a standardized protocol using multimodal analgesia (Paracetamol, Nefopam, Tramadol, Ketamine, Remifentanil) compared to the standard-of-care strategy using Paracetamol and Remifentanil. The investigators conducted a prospective, ''proof of concept'', randomized, double-blind, parallel group, placebo-controlled trial. The investigators studied multimodal analgesia versus standard-of-care in ICU patients requiring sedation-analgesia for invasive mechanical ventilation.The investigators hypothesized that Remifentanil consumption decrease by 15% with the use of a standardized multimodal analgesia strategy
详细描述
ICU patients requiring sedation-analgesia for mechanical ventilation for at least 48 hours are randomized in 2 parallel groups : control arm using ''standard of care'' analgesia (Paracetamol and Remifentanil), and interventional arm using multimodal analgesia at different level according to pain accessed by BPS (Step 1 : Paracetamol, Nefopam, Tramadol, Step 2 : Ketamine, Step 3 : Remifentanil). Sedation drugs are standard of care (Propofol and Midazolam if Propofol isn't enough) to obtain prescribed sedation accessed by RASS. Double-bling is kept for 72 hours until the primary outcome is obtained.
The investigators hypothesize a 15% reduction of Remifentanil consumption in the interventional group.
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
- Triple (Participant, 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
- •Patient hospitalized in ICU and requiring sedation-analgesia for mechanical ventilation.
- •Patient undergoing mechanical ventilation for more than 2 hours and less than 24 hours.
- •Informed consent signed by the patient or his trusted person, legal representative, family member, curator or tutor, or emergency consent procedure.
- •Patient affiliated to the French Government Public Health Insurance.
- •Patient over 18 years old.
排除标准
- •Patient already involved in a trial that might influence our primary endpoint.
- •Patient in exclusion-period determined by another trial or study.
- •Patient who is likely to be requiring less than 48 hours of mechanical ventilation.
- •Patient with contraindication or allergies to at least one of the following medication : paracetamol, nefopam, tramadol, ketamine, remifentanil.
- •Patient with hepatic insufficiency (defined as PT < 50%).
- •Parturient or breast-feeding patient.
- •Patient suffering from moderate to severe Acute Respiratory Distress Syndrome (ARDS), with decreased PaO2/FiO2 ratio under 150mmHg after respiratory optimization (courant volume 6mL/kg and PEEP > 5mbar).
- •Patient requiring curare treatment.
- •Patients with an indication for locoregional analgesia prior to extubation (perineural sealing, epidural analgesia).
研究组 & 干预措施
OFA Group
A fixed combination of nefopam and tramadol will be initiated at daily doses. An initial dose of 50mg tramadol and 20mg nefopam IV over 30 min. will be administered. Reassessment of analgesia will be performed every 30 min. for two hour and then every 2 hours.
- If BPS is > 4, administration of ketamine with an initial bolus of 0.15mg/kg followed by continuous administration at a dose of 0.15mg/kg/hour.
- If the BPS is < 4, remifentanil is introduced at the minimum effective dose, in a stepwise fashion according to the theoretical ideal weight
- In the event of maximum pain requiring the full range of therapies in the algorithm the total dose of tramadol will be 450mg/day and nefopam 120mg/day, in accordance with summaries of product characteristics.
- If the BPS < or = 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped, according to the following scheme: remifentanil, ketamine, tramadol and then nefopam.
干预措施: OFA multimodal analgesia (Drug)
Control group
Analgesia combines paracetamol (1g every 6 to 8 hours according to age and weight recommendations) and remifentanil, adapted according to a tiered administration system depending on the Behavior Pain Scale (BPS) and the theoretical ideal weight. Remifentanil doses are adjusted so that the patient has a BPS score of 4 or less. Reassessment of analgesia will be carried out every 30 minutes until analgesic adaptation is complete, then every 2 hours as is usually done in our department.
If the BPS is less than or equal to 4, the therapeutic de-escalation will be done with a reverse algorithm until the analgesic drugs are stopped.
After the sedation balance phase, the patient's BPS will be assessed every 2 hours.
干预措施: Standard multimodal analgesia (Drug)
结局指标
主要结局
Daily remifentanil consumption (after randomisation)
时间窗: 48th hour after randomisation
daily consumption of remifentanil between the 24th hour and the 48th hour after randomisation of patients admitted to the ICU and requiring at least 48 hours of mechanical ventilation
次要结局
- Impact of a non-opioid analgesia strategy on mental confusion(Day 28)
- Impact of a non-opioid analgesia strategy on fluid intake(Day 28)
- Impact of a non-opioid analgesia strategy on the occurrence of morphine-related adverse events(Day 28)
- Impact of a non-opioid analgesia strategy onICU and hospital length of stay(Day 90)
- Impact of a non-opioid analgesia strategy on morphine savings at D7(Day 28)
- Impact of a non-opioid analgesia strategy on organ failure at D28(Day 28)
- Impact of a non-opioid analgesia strategy on extubation failure rates(48 hours after extubation)
- Impact of the non-opioid analgesia strategy on vital prognosis at D28 and D90.(Day 90)
- Impact of a non-opioid analgesia strategy on the duration of mechanical ventilation(Day 28)
- Impact of an opioid-free analgesia strategy on norepinephrine(Day 28)
- Impact of a non-opioid analgesia strategy on the incidence of ventilator-associated pneumonia(Day 28)
- Impact of a non-opioid analgesia strategy on morphine dependence at D90(Day 90)
- Impact of an opioid-free analgesia strategy on sedative consumption(Day 28)