Ventilator-induced Right Ventricular Injury During Electrical Impedance Tomography-based Positive End-expiratory Pressure Titration in Patients With Acute Respiratory Distress Syndrome: a Pilot Physiological Study.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Right ventricle diameter 1
研究概览
简要总结
Right ventricular failure may be associated with mortality in patients with acute respiratory distress syndrome (ARDS). Mechanical ventilation may promote right ventricular failure by inducing alveolar overdistention and atelectasis. Electrical impedance tomography (EIT) is a bedside non-invasive technique assessing the regional distribution of lung ventilation, thus helping titrating positive end-expiratory pressure (PEEP) to target the minimum levels of alveolar overdistension and atelectasis. The aim of this physiologic randomized crossover trial is to assess right ventricular size and function with transthoracic echocardiography with different levels of PEEP in adult patients with moderate-to-severe ARDS undergoing controlled invasive mechanical ventilation: the level of PEEP determined according to the ARDS Network low PEEP-FiO2 table, the PEEP value that minimizes the risk of alveolar overdistension and atelectasis (as determined by EIT), the highest PEEP value minimizing the risk of alveolar overdistension (as determined by EIT), and the lowest PEEP level that minimizes the risk of alveolar atelectasis (as determined by EIT). Our findings may offer valuable insights into the level of PEEP favoring right ventricular protection during mechanical ventilation in patients with ARDS.
详细描述
Acute respiratory distress syndrome (ARDS) is a diffuse pulmonary inflammatory disease with multifactorial etiology that is very common in patients admitted to the intensive care unit (ICU) and is associated with unsatisfactory short- and long-term prognosis. Patients with ARDS can develop right ventricular (RV) failure, which occurs in 22-50% of patients despite lung protective ventilation and is associated with increased mortality. Despite being required to ensure survival of patients with ARDS, mechanical ventilation itself may have injurious effects on RV function. First, high transpulmonary pressure, secondary to the use of high tidal volume, plateau pressure or positive end-expiratory pressure (PEEP), can cause alveolar overdistension, especially in the aerated parenchymal regions, and collapse of alveolar vessels. The consequent increase in pulmonary arterial pressure may lead to excessively high RV afterload and reduced systolic function. Second, the development of parenchymal atelectasis potentially secondary to the application of low tidal volumes and/or PEEP may increase pulmonary vascular resistance because of extra-alveolar vascular collapse. Finally, mechanical ventilation can have indirect effects on pulmonary circulation and RV function, mediated by alveolar oxygenation, acidosis, and hypercapnia.
The application of PEEP can prevent cyclic opening and closing of the alveoli (i.e., atelectrauma) and improve oxygenation. Ideally, PEEP should maintain lung recruitment and optimize oxygenation and dead space, while at the same time avoiding alveolar overdistension and hemodynamic complications. However, the PEEP titration strategy in patients with ARDS is still widely debated, due to the variability of the effects of PEEP in different patients and different lung parenchymal regions in the same patient. Depending on the extent of potentially recruitable lung parenchyma and the distribution of lung damage, the application of PEEP can cause alveolar overdistension and promote RV failure and/or favor alveolar recruitment and improve RV function. Therefore, it is stil unclear what level of PEEP is associated with the optimization of RV function in patients with ARDS. We may hypothesize that the level of PEEP able to reduce alveolar collapse without increasing overdistension may improve RV function.
Several strategies have been suggested to assess lung recruitability and PEEP responsiveness in patients with ARDS. Electrical impedance tomography (EIT) is a bedside non-invasive technique that monitors the regional distribution of lung ventilation. The choice of the PEEP value that minimizes the extent of overdistension and atelectasis, as assessed with EIT, was associated with better respiratory mechanics and survival in patients with severe ARDS in some pilot studies.
The aim of this prospective pathophysiological interventional study is to evaluate the variation of RV size and function with transthoracic echocardiography in adult patients requiring invasive controlled mechanical ventilation for moderate-to-severe ARDS with four different PEEP values applied according to a randomized sequence in each patient:
- The level of PEEP determined according to the ARDS Network low PEEP-fraction of inspired oxygen (FiO2) table;
- The PEEP value that minimizes the risk of overdistension and atelectasis, as determined by EIT;
- The highest PEEP value that minimizes the risk of overdistension, as determined by EIT;
- The lowest PEEP level that minimizes the risk of atelectasis, as determined by EIT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Being sedated and paralyzed, included patients will not be aware of the study phase.
The investigators performing the echocardiographic exams will be blinded to the experimental setting because the PEEP level set at the ventilator will be covered.
The echocardiographic measurement will be performed offline with no information on the experimental settings.
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
- •Moderate to severe acute respiratory distress syndrome
- •Inclusion within 72 hours of acute respiratory distress syndrome diagnosis
- •Endotracheal intubation or tracheostomy
排除标准
- •Age lower than 18 years old
- •Absence of informed consent
- •Thoracic surgery or lung transplant during the admission
- •Contraindications to recruitment maneuvers (mean arterial pressure lower than 65 mmHg despite administration of fluids or vasopressors, active air leaks through a chest tube, pneumothorax or subcutaneous or mediastinal emphysema in absence of chest drainage)
- •Contraindications to electrical impedance tomography (contraindication to recruitment maneuvers, presence of pacemakers or other electronic devices in the chest, injuries or burns in the electrode placement area)
- •ACEP quality < 4
研究组 & 干预措施
PEEP level according to the low PEEP-FiO2 table
Positive end-expiratory pressure (PEEP) level selected based on patient's fraction of inspired oxygen (FiO2) according to the low PEEP-FiO2 table proposed by the Acute Respiratory Distress Syndrome Network Guidelines
干预措施: Positive end-expiratory pressure titration (Procedure)
PEEP minimizing the risk of overdistension and atelectasis
Positive end-expiratory pressure (PEEP) level selected based on the intersection between the curves of the cumulative percentages of compliance loss due to alveolar overdistension and atelectasis, respectively, as assessed with an electrical impedance tomography-based decremental PEEP trial
干预措施: Positive end-expiratory pressure titration (Procedure)
PEEP minimizing the risk of overdistension
Highest positive end-expiratory pressure (PEEP) level associated with no alveolar overdistention selected based on the curve of the cumulative percentage of compliance loss due to alveolar overdistension, as assessed with an electrical impedance tomography-based decremental PEEP trial
干预措施: Positive end-expiratory pressure titration (Procedure)
PEEP minimizing the risk of atelectasis
Lowest positive end-expiratory pressure (PEEP) level associated with no alveolar collapse selected based on the curve of the cumulative percentage of compliance loss due to alveolar collapse, as assessed with an electrical impedance tomography-based decremental PEEP trial
干预措施: Positive end-expiratory pressure titration (Procedure)
结局指标
主要结局
Right ventricle diameter 1
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Maximal transversal dimension in the basal one third of right ventricular inflow at end-diastole in the right ventricle-focused apical four-chamber view
Right ventricle diameter 2
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Transversal right ventricular diameter in the middle third of right ventricular inflow, approximately halfway between the maximal basal diameter and the apex, at the level of papillary muscles at end-diastole.
Tricuspid annular plane systolic excursion
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Tricuspid annular longitudinal excursion by M-mode, measured between end-diastole and peak systole in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Right ventricle stroke index
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio of right ventricular stroke volume, calculated as product between velocity-time integral at the level of pulmonary valve and transverse area of right ventricular outflow tract in the aortic valve-level parasternal short axis view during systole, and body surface area
Eccentricity index
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio between two left ventricular axes, one parallel to the interventricular septum and one perpendicular to this, in the mid-papillary parasternal short axis view
Right ventricle systolic pressure
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Calculated from the velocity of tricuspid regurgitation jet, measured in the view allowing the highest value, by applying simplified Bernoulli equation and adding right atrial pressure estimated from central venous pressure
Right ventricle fractional area change
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio of the difference between end-diastolic area and end-systolic area to end-diastolic area, which are determined after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus, along the interventricular septum at end-diastole and at end-systole, in the right ventricle-focused apical four-chamber view
Systolic velocity of the lateral tricuspid annulus derived from tissue Doppler imaging
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Peak systolic velocity of lateral tricuspid annulus by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Right ventricular index of myocardial performance
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
The ratio of the sum between isovolumic contraction and relaxation times to ejection time measured by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Myocardial isovolumic acceleration
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Ratio of lateral tricuspid annulus peak velocity during isovolumic contraction to acceleration time by pulsed-wave tissue Doppler imaging in the apical four-chamber view that achieves parallel alignment of Doppler beam with right ventricular free wall longitudinal excursion
Right ventricular free wall longitudinal strain
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Peak value of longitudinal speckle-tracking-derived strain, averaged over the three segments of the right ventricular free wall, after manual tracing of right ventricular endocardial border from the lateral tricuspid annulus along the free wall to the apex and back to medial tricuspid annulus in right ventricle-focused apical four-chamber view
Right ventricle stroke work index
时间窗: Measured after 20 minutes from the application of each of the four levels of PEEP
Product between right ventricle stroke index and right ventricle systolic pressure
次要结局
- Ventilator settings(Measured after 20 minutes from the application of each of the four levels of PEEP)
- Respiratory mechanics(Measured after 20 minutes from the application of each of the four levels of PEEP)
- Arterial blood gas analysis(Measured after 20 minutes from the application of each of the four levels of PEEP)
- Ultrasound image quality(Measured after 20 minutes from the application of the intervention)
- Shunt(Measured after 20 minutes from the application of the intervention)
- Pleural and lung ultrasound(Measured after 20 minutes from the application of the intervention)
- Renal ultrasound(Measured after 20 minutes from the application of the intervention)
- Dead space(Measured after 20 minutes from the application of each of the four levels of PEEP)
- Ventilatory ratio(Measured after 20 minutes from the application of each of the four levels of PEEP)
- Hemodynamics(Measured after 20 minutes from the application of the intervention)
研究者
Tommaso Pettenuzzo
MD
University of Padova