Inhalational (Sevoflurane) Versus Intravenous (Propofol) Sedation in Adults With a Moderate Form of ARDS: A Multicentral Randomized Pilot Trial
试验速览
- 阶段
- 3 期
- 状态
- 暂停
- 发起方
- 入组人数
- 310
- 试验地点
- 1
- 主要终点
- P/F ratio
研究概览
简要总结
The American European Consensus Conference (AECC) 1994 defined acute respiratory distress syndrome (ARDS) as an acute inflammatory syndrome manifesting as diffuse pulmonary edema and respiratory failure that cannot be explained by, but may co-exist with, left-sided heart failure. During the sequel Conference of the European Society of Intensive Care Medicine, in 2012 minor changes were made, and since that so-called Berlin definition of ARDS is used worldwide for the description of this severe disease. Three grades of severity were proposed to distinguish ARDS according to the level of hypoxemia with a mortality of 24% in patients with mild ARDS, rising to 48% in those with severe ones.
Systemic inflammation is considered to be the main reason of ARDS. Activated neutrophils interact with the alveolar-capillary membrane causing the increasing permeability with the sequence lung edema's development. Inflammatory exudate inactivates surfactant leading to collapse and consolidation of distal airspaces with progressive loss of the lung's gas exchange surface area. Unfortunately, systemic inflammatory response syndrome (SIRS) simultaneously inhibits the mechanism of active pulmonary vasoconstriction and allows deoxygenated blood to pass through unventilated areas of the lung boosting the right-to-left shunt. Both mechanisms lead to hypoxemia, which is the main and obligatory feature of ARDS.
Actually, endothelial dysfunction and transcapillary leakage seem to be one of the main steps in the development of respiratory failure during ARDS. Last decades it was found out that glycocalyx is also participating in this process too.
Thus, it became clear that substances preserving endothelium and glycocalyx from SIRS-causing damage may have a beneficial effect in ARDS treatment. It seems to be crucially important so as the majority of drugs failed to demonstrate any positive effects in terms of ARDS treatment.
To the moment we have some evidence, which came from experimental studies, that halogenated anesthetics can preserve glycocalyx against ischemia-reperfusion injury.
The primary objective for the multicentral INVERSE Trial will be to determine the effects of inhalational (sevoflurane) versus intravenous (propofol) sedation on P/F ratio on the second day, hospital mortality and ICU (intensive care unit), and in-hospital length of stay in adults with a moderate form of ARDS.
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
- •Age > 18
- •Endotracheal intubation or tracheostomy
- •Timing: Acute onset of new or worsening of chronic respiratory symptoms within 72 hours before the randomization
- •Chest imaging: Bilateral opacities-not fully explained by effusions, lobar/lung collapse, or nodules
- •Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload
- •Oxygenation: 100 mm Hg < PaO2/FiO2 ≤ 200 mm Hg with PEEP ≥ 5 cm H2O
排除标准
- •History or family history of malignant hyperthermia
- •History of propofol infusion syndrome
- •Documented or suspected increased intracranial pressure
- •Chronic restrictive pulmonary disease
- •Chronic obstructive pulmonary disease
- •Neuromuscular disease
- •Chest wall disorder
- •Pulmonary vascular disease
- •NYHA class ≥ 3
- •Severe pulmonary hypertension (mean pulmonary artery pressure > 40 mmHg)
- •Documented ongoing COVID-19 infection
- •Ongoing immunosuppressive therapy
- •Previous randomization in this trial
- •Post randomization exclusion criterion: Documented ongoing COVID-19 infection during the first 48 hours after the randomization
研究组 & 干预措施
Inhalational sedation
干预措施: Sevoflurane (Drug)
Intravenous sedation
干预措施: Propofol (Drug)
结局指标
主要结局
P/F ratio
时间窗: day 2 after the randomization
PaO2 divided on FiO2
次要结局
- Ventilator free days in ICU(1 year)
- Ventilator free days during hospitalization(1 year)
- 28-days mortality(28 day)
- 6-months mortality(6 months)
- 1-year mortality(1 year)
- Length of stay in the intensive care unit(1 year)
- Length of hospitalization(1 year)
研究者
Valery Likhvantsev, MD
Head of the Research V. Negovsky Reanimatology Research Institute
Negovsky Reanimatology Research Institute