Comparison of Extubation Delay After Prolonged Sedation With Inhaled Isoflurane Using the MIRUS® Device or Continuous Intravenous Midazolam in Patients With Septic Shock in Intensive Care
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- The delay between the first sedation stop and extubation
研究概览
简要总结
This monocentric, prospective, controlled, randomized, single-blind study will be conducted in surgical resuscitation at the Rouen University Hospital. The aim of our research project is to evaluate the extubation time after sedation with inhaled isoflurane compared to conventional intravenous sedation with midazolam, in patients who require prolonged sedation (3 to 28 days) in a context of septic shock. This population is particularly at risk of hypnotic accumulation due to the prolonged duration of use and the increased risk of developing renal or hepatic impairment in connection with septic shock.
Based on data from the literature on shorter durations of up to 96 hours of sedation, the investigators expect a decrease in the time to extubation in patients sedated with isoflurane as well as a better quality of awakening with a decrease in resuscitation delirium. This shortened duration of mechanical ventilation could have beneficial effects on the morbidity associated with prolonged sedation and ventilation: reduction of pneumopathies acquired under mechanical ventilation, reduction of the length of stay in resuscitation and hospitalization.
详细描述
In intensive care, sedation of patients is frequently used for their management. Combined with analgesia, it provides the comfort essential for the implementation of certain therapies such as mechanical ventilation.
Classically, sedation is based on the combination of a hypnotic and an injectable morphine, most often midazolam and sufentanil. Midazolam is a benzodiazepine with many advantages: few hemodynamic effects, no limited duration of use and good workability. However, its use presents several difficulties in resuscitation:
- Some patients have accelerated metabolism and resistance to benzodiazepines, either through chronic use of psychotropic or narcotic drugs. These patients develop tolerance phenomena due to enzyme induction. This tachyphylaxis leads to an increased need for midazolam to achieve the therapeutic goal.
- Some pathologies, such as ARDS, require deep sedation in the initial phase, which may last several days. After this phase, prolonged sedation may be necessary before achieving sufficient improvement to allow sedation to be stopped.
- The metabolism of midazolam is dependent on liver function and its elimination from renal function. Alteration of these functions, common in resuscitation, results in impaired elimination with accumulation of midazolam and 2 active metabolites, 1-hydroxy-midazolam and 1-hydroxy-midazolam-glucuronide.
These three difficulties may lead to an undesirable prolongation of the sedation period beyond the cessation of midazolam infusion, which is associated with an increase in morbidity such as neuromyopathies, ventilator-associated pneumopathies (VAPP), deliriums and withdrawal syndromes. These complications increase the length of stay and mortality in intensive care units.
For 30 years there has been a growing interest in the use of sedation in resuscitation with volatile halogenated agents (VHAs). These agents, administered by inhalation, have many advantages: short onset of action, good workability, effect not dependent on renal or hepatic function, almost exclusive and predictable respiratory elimination, absence of tachyphylaxis and metabolism not sensitive to enzyme induction. For these reasons, AVHs are widely used in anesthesia in the operating room. The hypnotic action of HVAs is closely correlated with the expired fraction of HVAs. Measured by gas analysers, it allows precise monitoring of the therapeutic effect. In contrast to resuscitation ventilators, all anesthesia ventilators are equipped with evaporation tanks and administration circuits, gas analyzers and associated facilities for their disposal. These technical constraints mean that, despite their many theoretical advantages, AVHs have not been used in resuscitation area.
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
- Single (Participant)
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
- •Major patients,
- •Sedated with midazolam and sufentanil for a maximum of 3 days and ventilated invasively,
- •Presenting a duration of sedation and invasive ventilation expected after inclusion between 3 days and 10 days,
- •Presenting septic shock according to the SEPSIS-3 definition with the following 4 criteria :
- •Clinical suspicion of infection or positive microbiological sample if applicable,
- •Organ Failure: SOFA (Sepsis-related Organ Failure Assessment) ≥ 2 (Annex n°5),
- •Need for vasoactive amines to maintain sufficient organ perfusion pressure,
- •Arterial lactate > 2mmol/l,
- •Stabilized septic shock without the need to increase noradrenaline doses over the last 6 hours,
- •For women, absence of current pregnancy: negative pregnancy test,
- •Subjects affiliated to a social security system.
- •If the patient is unable to sign the consent (emergency situation) the consent will be signed by his or her representative ((1) the trusted person, or failing that, (2) a family member, or (3) a relative of the person concerned). In this case, the patient will subsequently be asked for consent to continue the study.
排除标准
- •Refusal of the patient to continue the study after waking up,
- •Duration of sedation after randomization less than 3 days or more than 10 days.
研究组 & 干预措施
sedation by inhaled isoflurane
sedation by midazolam with the MIRUS device
干预措施: Prolonged sedation with isoflurane (Drug)
sedation with intravenous midazolam
continuation of sedation with intravenous midazolam
干预措施: Prolonged sedation with midazolam (Drug)
结局指标
主要结局
The delay between the first sedation stop and extubation
时间窗: 10 days
The delay between the first sedation stop and extubation. This time will be measured from the first interruption of sedation to the patient's extubation. If the patient needs to be resedated prior to extubation, the stop of sedation for the primary endpoint measurement will be the first stop of sedation.
次要结局
- Measurement of midazolam and 2 active metabolites, 1-OHM and 1-OHMG(24, 48 and 96 hours)
- A measure of overall survival at 90 days defined by the duration between the inclusion date and the date of death.(90 days)
- Total duration of intensive care and hospital stay(90 days)
- Security(90 days)
- Wake-up time(10 days)
- Total duration of sedation and mechanical ventilation(90 days)
- Measurement of wake-up time defined by the duration between the day of the first sedation stop and a RASS score of 0,(10 days)
- Doses of vasopressor, hypnotic and morphine amines administrated(3 days)
- Measurement of the number of days without mechanical ventilation(90 days)
- Costs of sedative treatments (midazolam and isoflurane) and the devices needed to administer them (syringes and tubing for midazolam, reflector and filter exchanger for isoflurane)(90 days)