Effect of Prone Positioning and Thoracoabdominal Binding on Lung and Muscle Protection in ARDS Patients With ICU-acquired Weakness Transitioning From Controlled to Spontaneous Breathing
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- (Randomized Crossover Trial Phase) Pendelluft Magnitude
研究概览
简要总结
Ventilator-induced diaphragmatic dysfunction and intensive care unit (ICU)-acquired weakness are two consequences of prolonged mechanical ventilation and critical illness in patients with acute respiratory distress syndrome (ARDS). Both complicate the process of withdrawing mechanical ventilation, increase hospital mortality and cause chronic disability in survivors. During transition from controlled to spontaneous breathing, these complications of critical illness favor an abnormal respiratory pattern and recruit accessory respiratory muscles which may promote additional lung and muscle injury. The type of ventilatory support and positioning may affect the muscle dysfunction and patient-self-inflicted lung injury at spontaneous breathing onset. In that regard, ARDS patients with ventilator-induced diaphragmatic dysfunction and ICU-acquired weakness who are transitioning from controlled to partial ventilatory support probably present an abnormal respiratory pattern which exacerbates lung and muscle injury. Physiological-oriented ventilatory approaches based on prone positioning or semi recumbent positioning with abdominal binding at spontaneous breathing onset, could decrease lung and muscle injury by favoring a better neuromuscular efficiency, and preventing intense inspiratory efforts and high transpulmonary driving pressures, as well as high-magnitude pendelluft. In the current project, in addition to perform a multimodal description of the severity of ventilator-induced diaphragmatic dysfunction and ICU-acquired weakness in prolonged mechanically ventilated ARDS patients, prone positioning and supine plus thoracoabdominal binding at spontaneous breathing onset will be evaluated.
详细描述
The study was designed in three phases: a multimodal physiological description, a randomized crossover trial, and a pilot randomized trial. The multimodal physiological description and the randomized crossover trial were conducted in the same cohort. The pilot randomized trial was not conducted.
Multimodal Physiological Description Phase: a multimodal physiological description was performed to characterize ICU acquired weakness and ventilator-induced diaphragm dysfunction in prolonged mechanically ventilated ARDS patients at spontaneous breathing onset, in pressure support ventilation mode. The assessments included conventional electromyography (cEMG); electrical activity of the diaphragm; respiratory muscle ultrasound; respiratory flow; tidal volume; airway, esophageal and gastric pressures; and hemodynamic and electrical impedance tomography monitoring. Diaphragm ultrasound and cEMG were performed after the crossover trial, to avoid reducing PEEP and PS to the standardized low values required for diaphragm ultrasound (PEEP and PS of 6 cmH2O) before the crossover conditions, which could alter respiratory mechanics at protocol entry; cEMG findings were not expected to change over this timeframe (amendment approved by IRB No. 45/2024; May 15, 2024).
Randomized Crossover Trial Phase: Patients were asigened in random order to three 60-minute conditions on pressure support ventilation mode: A.- Control group: semi-recumbent position at 45º (previously described as supine at 45º), B.- Thoracoabdominal binding: semi-recumbent position at 45º plus thoracoabdominal binding, C.- Prone positioning (without thoracoabdominal binding). These strategies were performed under individualized PEEP (obtained at the lowest combination of collapse and overdistension according to electrical impedance tomography), with 15-minute washout periods of in assisted/controlled ventilation between conditions.
Pilot Randomized Trial Phase: This phase was designed to randomize patients to one of the three strategies under standard PEEP (ARDSNet strategy), with PET/CT imaging and biomarker analysis. The originally registered enrollment (n = 36) corresponded to this phase. A protocol amendment approved by the local ethics committee in May 2024 established that patients enrolled in this phase were not required to have completed the multimodal description and crossover phases, and reduced the planned sample size to 12 patients due to budgetary and logistical constraints. The phase was ultimately not conducted; the decision not to conduct it was reported to the local ethics committee and approved by the national funding agency.
Enrollment: The target enrollment for the crossover phase (24 patients) was established in the May 2024 protocol amendment. Recruitment was closed after 14 patients had been enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Supportive Care
- 盲法
- None
盲法说明
Masking of participants, care providers and investigators was not feasible due to the nature of the interventions (body positioning and thoracoabdominal binding). In the multimodal physiological description, diaphragm ultrasound and conventional electromyography were performed by assessors unaware of the results of the other physiological assessments.
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 ARDS patients with moderate-severe ARDS on controlled protective mechanical ventilation for more than 2 days (modified from "more than 3 days" by the protocol amendment approved in May 2024)
- •Stable hemodynamics
- •Level of consciousness enough to initiate spontaneous breathing
排除标准
- •Unstable hemodynamics
- •Tracheostomy
- •Abnormal level of consciousness
- •Central nervous system injury
- •Esophageal varices
- •Pregnancy
- •Contraindications for installation of electrical impedance tomography or nasogastric catheter placement
- •Contraindications for prone positioning and thoracoabdominal binding
- •Chronic neuromuscular disorders
- •Obstructive lung disease; intrinsic positive end-expiratory pressure (PEEP) ≥3 cmH₂O (measured without inspiratory effort);
- •Recent-onset sepsis and moderate-to-severe metabolic acidosis;
- •Multi-organ failure with high short-term mortality risk
- •Clinical evidence of respiratory or hemodynamic instability
研究组 & 干预措施
Control Group
ARDS patients at spontaneous breathing onset on pressure support ventilation mode in semi-recumbent position at 45º degrees, performed under individualized PEEP applied in random order.
干预措施: Control (Procedure)
Prone Positioning
ARDS patients at spontaneous breathing onset on pressure support ventilation mode in prone position, performed under individualized PEEP applied in random order.
干预措施: Prone Positioning (Procedure)
Thoracoabdominal Binding
ARDS patients at spontaneous breathing onset on pressure support ventilation mode in semi-recumbent position at 45º degrees using thoracoabdominal binding with the binder's upper edge above the costal margin, performed under individualized PEEP applied in random order.
干预措施: Thoracoabdominal Binding (Procedure)
结局指标
主要结局
(Randomized Crossover Trial Phase) Pendelluft Magnitude
时间窗: One hour on each ventilatory strategy
Pendelluft magnitude monitored by electrical impedance tomography, analyzed as a continuous variable. Title corrected in September 2026 from "High-Magnitude Pendelluft", as no threshold was prespecified and the sample size calculation was based on a continuous outcome, according to the protocol amendment approved in May 2024.
(Randomized Crossover Trial Phase) Neuromechanical Coupling of the Diaphragm
时间窗: One hour on each ventilatory strategy
Ratio between transdiaphragmatic pressure and electrical activity of the diaphragm, measured by an esophageal/gastric catheter. Co-primary outcome with pendelluft magnitude. Prespecified as primary in the ethics-approved protocol and described in the Brief Summary and as a secondary outcome of the Pilot Randomized Trial Phase, but omitted in error from the Crossover Phase outcomes in the original registration. Added in September 2026.
(Second Phase) High-Magnitude Pendelluft
时间窗: Two hours on each ventilatory strategy during phase 2
Frequency of high-magnitude pendelluft monitored by electrical impedance tomography
(Third Phase) Change in Regional Lung Inflammation
时间窗: At baseline and after 24 hours of each ventilatory strategy during phase 3
Regional lung inflammation will be evaluated with dynamic positron emission tomography/computed tomography of fluoro-2-deoxy-D-glucose (18F-FDG) net uptake rate
(Third Phase) Change in Fast-Twitch Skeletal Muscle Troponin I Measured by ELISA
时间窗: At baseline and after 24 hours of each ventilatory strategy during phase 3
ELISA-based detection of fast-twitch skeletal muscle troponin I measured in plasma
(Third Phase) Change in Inflammatory Biomarkers Measured by ELISA (IL-6, IL-8, TNF-α, IFN-γ, IL-18, IL-1β, Caspase-1, RAGE, Angiopoietin-1 and 2) and change in oxidative stress related biomarkers (F2 isoprostane)
时间窗: At baseline and after 24 hours of each ventilatory strategy during phase 3
ELISA-based detection of inflammatory biomarkers (absolute and ratios) and oxidative stress related biomarkers (absolute and ratios) measured in plasma and in exhaled breath condensate
次要结局
- (Randomized Crossover Trial Phase) Respiratory Mechanics Variables(One hour on each ventilatory strategy)
- (Third Phase) Change in Neuromechanical Coupling of Diaphragm(At baseline and after 24 hours of each ventilatory strategy during phase 3)
- (Third Phase) Change in High-Magnitude Pendelluft(At baseline and after 24 hours of each ventilatory strategy during phase 3)
- (Third Phase) Change in Respiratory Mechanics Variables(At baseline and after 24 hours of each ventilatory strategy during phase 3)
- (Second Phase) Respiratory Mechanics Variables(Two hours on each ventilatory strategy during phase 2)
研究者
Rodrigo Cornejo
Full Professor
University of Chile