Effect of APRV vs. LTV on Right Heart Function in ARDS Patients: a Single-center Randomized Controlled Study

Acute Respiratory Distress Syndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Pulmonary vascular dysfunction includes acute vascular inflammation, pulmonary vascular edema, thrombosis and pulmonary vascular remodeling. Alveolar collapse and over distension can also lead to increased pulmonary vascular resistance, Preventing the development of acute cor pulmonale in patients with acute respiratory distress. ARDS patients with RVD have a worse prognosis and a significantly increased risk of death, which is an independent risk factor for death in ARDS patients. Therefore, implementing a right heart-protective mechanical ventilation strategy may reduce the incidence of RVD.

APRV is an inverse mechanical ventilation mode with transient pressure release under continuous positive airway pressure, which can effectively improve oxygenation and reduce ventilator-associated lung injury. However, its effect on right ventricular function is still controversial. Low tidal volume (LTV) is a mechanical ventilation strategy widely used in ARDS patients. Meta-analysis results showed that compared with LTV, APRV improved oxygenation more significantly, reduced the time of mechanical ventilation, and even had a tendency to improve the mortality of ARDS patients However, randomized controlled studies have shown that compared with LTV, APRV improves oxygenation more significantly and also increases the mean airway pressure. Therefore, some scholars speculate that APRV may increase the intrathoracic pressure, pulmonary circulatory resistance, and the risk of right heart dysfunction but this speculation is not supported by clinical research evidence. In addition, APRV may improve right ventricular function by correcting hypoxia and hypercapnia, promoting lung recruitment and reducing pulmonary circulation resistance. Therefore, it is very important to clarify this effect for whether APRV can be safely used and popularized in clinic.we aim to conduct a single-center randomized controlled study to further compare the effects of APRV and LTV on right ventricular function in patients with ARDS, pulmonary circulatory resistance (PVR) right ventricular-pulmonary artery coupling (RV-PA coupling), and pulmonary vascular resistance (PVR).

Acute Respiratory DistressSyndrome (ARDS) is often complicated by Right Ventricular Dysfunction (RVD), and the incidence can be as high as 64%. The mechanism includes pulmonary vascular dysfunction and right heart systolic dysfunction. Pulmonary vascular dysfunction includes acute vascular inflammation, pulmonary vascular edema, thrombosis and pulmonary vascular remodeling. Alveolar collapse and alveolar overdistension can also lead to increased pulmonary vascular resistance, Preventing the development of acute cor pulmonale in patients with acute respiratory distress. ARDS patients with RVD have a worse prognosis and a significantly increased risk of death, which is an independent risk factor for death in ARDS patients \[2-4\]. Therefore, implementing a right heart-protective mechanical ventilation strategy may reduce the incidence of RVD.

Mechanical ventilation is the main treatment for moderate to severe ARDS. Mechanical ventilation promotes lung recruitment and reduces mechanical compression of pulmonary vessels between alveoli and alveolar walls. In addition, mechanical ventilation corrected hypoxemia and hypercapnia, thereby reducing reactive pulmonary vasoconstriction. All of the above can reduce pulmonary circulation resistance and right ventricular afterload, thereby improving right ventricular function in patients with ARDS. However, if hyperventilation occurs, it will increase the mechanical compression of pulmonary vessels on the alveolar wall, increase the intrathoracic pressure, and increase the afterload of the right heart, which will adversely affect the function of the right heart. There are a variety of ventilation strategies for patients with ARDS in clinical practice, but which mechanical ventilation has the protective function of right heart or has little effect on right heart function, so far there is a lack of relevant research reports.

Airway pressure release ventilation (APRV) is an inverse mechanical ventilation mode with transient pressure release under continuous positive airway pressure, which can effectively improve oxygenation and reduce ventilator-associated lung injury. However, its effect on right ventricular function is still controversial, so its clinical application is not popular, and it is only used as one of the salvage treatments for ARDS patients. Low tidal volume (LTV) is a mechanical ventilation strategy widely used in ARDS patients, but it does not further reduce mortality in patients with moderate to severe ARDS. Meta-analysis results showed that compared with LTV, APRV improved oxygenation more significantly, reduced the time of mechanical ventilation, and even had a tendency to improve the mortality of ARDS patients \[7\]. However, randomized controlled studies have shown that compared with LTV, APRV improves oxygenation more significantly and also increases the mean airway pressure \[8\]. Therefore, some scholars speculate that APRV may increase the intrathoracic pressure, pulmonary circulatory resistance, and the risk of right heart dysfunction , but this speculation is not supported by clinical research evidence. In addition, the results of animal experiments suggest that APRV improves oxygenation, promotes lung recruitment, and improves the heterogeneity of lung lesions in ARDS, without causing lung hyperventilation, suggesting that APRV may not increase pulmonary circulatory resistance. In addition, APRV may improve right ventricular function by correcting hypoxia and hypercapnia, promoting lung recruitment and reducing pulmonary circulation resistance. Therefore, the impact of APRV on right ventricular function is still unclear, and it is very important to clarify this effect for whether APRV can be safely used and popularized in clinic. Therefore, our research group conducted a prospective observational study, "The effect of APRV on right ventricular function evaluated by Transthoracic Echocardiography, \[2022\] Lun Lun Zi (0075)". The study results suggested that APRV improved lung perfusion in ARDS patients while effectively improving oxygenation and promoting lung recruitment. The incidence of RVD was not increased, and there was no hemodynamic deterioration in ARDS patients. APRV is safe and effective for patients with ARDS. However, the results of a single-arm prospective observational study with a small sample size cannot provide strong evidence for clinical practice. In the previous studies, all the right ventricular function was assessed by transthoracic echocardiography. Due to the limitation of the sound window of transthoracic echocardiography, the right ventricular function of some ARDS patients could not be evaluated. Therefore, this study intends to use transesophageal echocardiography or transthoracic echocardiography to fully evaluate the right ventricular function of all enrolled patients as much as possible, and to conduct a single-center randomized controlled study to further compare the effects of APRV and LTV on right ventricular function in patients with ARDS, pulmonary circulatory resistance (PVR), right ventricular-pulmonary artery coupling (RV-PA coupling), and pulmonary vascular resistance (PVR).Whether there are different effects on hemodynamics and mortality. It is hoped that the results of this study will provide more evidence support for the clinical application of APRV and benefit more ARDS patients.

Eligibility Criteria:
Inclusion Criteria:

* 1. Patients who meet the 2012 Berlin ARDS diagnostic criteria and perform invasive mechanical ventilation 2, PEEP≥5cmH2O, oxygenation index ≤200mmHg 3. Tracheal intubation and mechanical ventilation were performed for less than 48h at the time of inclusion 4. Age ≥18 years and ≤80 years

Exclusion Criteria:

* 1.abdominal pressure≥20mmHg 2.BMI≥35kg/m2; 3. pregnant and lactating women 4.expected duration of invasive mechanical ventilation \< 72 hours 5. neuromuscular diseases known to require prolonged mechanical ventilation 6.severe chronic obstructive pulmonary disease, severe asthma, Interstitial lung disease 7.intracranial hypertension, 8.pulmonary bullae or pneumothorax, subcutaneous emphysema, or mediastinal emphysema, 9.extracorporeal membrane oxygenation or prone position ventilation on admission to the ICU 10. uncorrected shock of various types and refractory shock 11.pulmonary embolism 12.severe cardiac dysfunction (New York Heart Association class III or IV). Acute coronary syndrome or sustained ventricular tachyarrhythmia), right heart enlargement due to chronic cardiopulmonary diseases, cardiogenic shock or after major cardiac surgery 13.poor cardiac sound window, unable to obtain cardiac ultrasound images 14.no informed consent was signed