Phase 1/Phase 2, Single-Center, Controlled Study of the Effectiveness of Combined High Frequency Oscillation and Tracheal Gas Insufflation in Improving the Clinical Course of Patients With Severe Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Physiological variables (i.e. ventilation pressures and oxygenation) during the first 7-10 days following randomization
研究概览
简要总结
In the past five years, there is a growing body of published evidence on the feasibility, and oxygenation and lung protection benefits of high frequency oscillation (HFO) in the acute respiratory distress syndrome (ARDS). The investigators have recently demonstrated the short term feasibility and additional benefits with respect to oxygenation of HFO combined with tracheal gas insufflation (TGI). In the present clinical trial, the investigators intend to test the hypothesis that HFO-TGI may result in improved respiratory physiology and clinical course compared to low tidal volume conventional mechanical ventilation in patients with severe ARDS.
详细描述
OBJECTIVES AND UNDERLYING HYPOTHESIS
High frequency oscillation (HFO) has beneficial physiological effects in acute respiratory distress syndrome (ARDS) [1-4]. A recent randomized controlled trial of HFO versus conventional mechanical ventilation (CMV) with traditional tidal volumes (10.1± 2.8 mL•kg-1 predicted body weight) reported a trend toward reduced 30-day mortality in the HFO arm (37% versus 52% in the CMV group; P = 0.10) [3]. To-date, HFO has not been compared to CMV with low tidal volumes (6.2 ± 1.1 mL•kg-1 predicted body weight) in ARDS [5], with respect to respiratory physiology and clinical course.
The main mechanisms of gas exchange during CMV are bulk convection and diffusion. [4, 6]. Tracheal gas insufflation (TGI) promotes CO2 elimination during CMV [7-9]. During HFO, additional gas exchange mechanisms comprise asymmetric velocity profiles, Taylor dispersion/turbulence, cardiogenic mixing, pendelluft effect, and collateral ventilation [4, 6].
We have recently shown that in patients with moderate-to-severe, primary ARDS, HFO combined with TGI (HFO-TGI) substantially improves oxygenation relative to both standard HFO and CMV according to the ARDS network protocol [5, 10]. Mean airway pressure (mPaw) was set at 1 cm H2O above the point of maximal curvature (PMC) of the expiratory pressure volume curve. During HFO-TGI, it is probably feasible to reduce mPaw, while still achieving PaO2 and peripheral oxygen saturation (SaO2) targets similar to those set by the ARDS network protocol [5]. This may result in reduced and non-traumatic ventilation pressures during HFO-TGI. Furthermore, if HFO-TGI-related gas exchange benefits are maintained during post-HFO-TGI CMV [10], then a reduction of ventilation pressures relative to the pre-HFO-TGI CMV may be feasible as well. However, the use of reduced ventilation pressures may minimize ventilator associated lung injury. In this study, we will test the hypothesis that HFO-TGI may improve the respiratory physiology and clinical course of patients with severe ARDS.
METHODS Patients
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Early Acute Respiratory Distress Syndrome
- •PaO2/FiO2 < 150 mm Hg at PEEP ≥ 8 cm H2O
- •Age 18-75 years
- •Body weight > 40 kg
排除标准
- •More than 1 chest tube/hemithorax with persistent airleak for > 72 h)
- •Systolic pressure < 90 mm Hg with fluids/norepinephrine at ≥ 0.5 μg/kg/min
- •Heart disease (defined in Detailed Description)
- •Chronic obstructive pulmonary disease (defined in Detailed Description)
- •Intracranial abnormalities (any cause of intracranial pressure > 20 mm Hg)
- •Chronic interstitial lung disease
- •Lung biopsy or resection on current admission
- •Previous lung or bone marrow transplant or immunosuppression
- •Pregnancy or morbid obesity
- •Inability to wean from prone positioning or inhaled nitric oxide
- •Enrollment in another interventional study
研究组 & 干预措施
HFO-TGI
Patients with severe Acute Respiratory Distress Syndrome receiving sessions of high frequency oscillation and tracheal gas insufflation according to the study protocol
干预措施: High Frequency Oscillation and Tracheal Gas Insufflation (Other)
CMV
Patients with severe Acute Respiratory Distress Syndrome receiving only conventional mechanical ventilation according to the study protocol
结局指标
主要结局
Physiological variables (i.e. ventilation pressures and oxygenation) during the first 7-10 days following randomization
时间窗: 8-10 days post-randomization
Survival to days 28 and 60 post-randomization and to Hospital Discharge
时间窗: 28 days to more than 60 days post-randomization
次要结局
- Ventilator free days(28 days and 60 days)
- Number of Organ or system failure free days(28 days and 60 days)
- Occurence of Barotraumas/airway injury(28 days and 60 days)
研究者
Spyros D. Mentzelopoulos
Assistant Professor of Intensive Care Medicine
University of Athens