Variable Ventilation During Acute Respiratory Failure

Acute respiratory failure requiring support with mechanical ventilation occurs with an incidence of 77-100 per 100,000 person-years and accounts for half of all patients admitted to the intensive care unit. Major causes of acute respiratory failure include pneumonia, asthma, emphysema, and acute lung injury. These causes of acute respiratory failure may result in partial lung collapse (atelectasis), and airway narrowing (bronchoconstriction)that result in decreased oxygen levels requiring support with the ventilator. The prolonged inactivity in the supine position associated with mechanical ventilation can further result in atelectasis requiring increased oxygen supplementation through the ventilator.

The current standard of care in acute respiratory failure is a strategy of mechanical ventilation using a single lung volume delivered repeatedly. However, the current standard mechanical ventilation strategy is not consistent with the variability in respiration of healthy humans and has been shown to contribute to increased lung injury in some studies. The mortality associated with acute respiratory failure is high, 30-40%. Thus, improvements in mechanical ventilation strategies that improve oxygen levels and potentially decrease further lung injury delivered by the ventilator are warranted.

Recent studies by BU Professor Bela Suki and others in humans and animals with acute lung injury, bronchoconstriction, and atelectasis have shown that varying the lung volumes delivered by a ventilator significantly decreases biomarkers of lung injury, improves lung mechanics, and increases oxygenation when compared to identical mean volumes of conventional, monotonous low lung volume ventilation.

Therefore, we propose a first-in-human, Phase I study to evaluate the safety of this novel mode of ventilation, Variable Ventilation, during acute respiratory failure