Preventing ventilator-induce lung injury (VILI): Optimizing PEEP titration in ARDS

While necessary, mechanical ventilation can lead to ventilator-induced lung injury (VILI) in critically ill patients with acute respiratory failure, particularly those with concomitant acute respiratory distress syndrome (ARDS). Mechanisms of VILI include, 1) alveolar overdistention caused by excessive transpulmonary pressure, 2) atelectrauma caused by cyclic opening and closing of alveoli, 3) biotrauma induced by release of inflammatory mediators from injured lung, and 4) local stress and strain occurring at the boundary between collapsed and expanded alveoli. By limiting tidal volume and plateau pressure, lung-protective ventilation not only mitigates alveolar overdistention, but also reduces mortality in patients with ARDS. The application of PEEP further stabilizes the lung by preventing alveolar collapse during expiration, thereby reducing cyclic atelectasis. However, the optimal approach to PEEP titration to minimize VILI has not been delineated. 


Numerous methods have been utilized to adjust PEEP in ARDS. One approach has been to titrate the PEEP level to optimize oxygenation; however, this method fails to identify excessive recruitment and derecruitment that leads to dynamic strain. The use of lung mechanics, specifically titrating PEEP to best lung compliance (V/P), has been utilized for over 40 years and has been shown to be predictive of mortality. In ARDS, the presence of dependent lung water reduces the size of aerated lung, giving rise to the concept of the “baby lung.” Amato et al. studied the relationship between respiratory system compliance (CRS) and functional lung size. Rather than simply using predicted tidal volume based on ideal body weight, the authors assessed driving pressure to estimate the size of the functional (or baby) lung. Driving pressure can be calculated by subtracting PEEP from the plateau pressure (DP = Pplat – PEEP), or can be expressed as the ratio of tidal volume to respiratory system compliance (P = Vt/CRS). The authors found that adjusting PEEP to minimize driving pressure was associated with mortality reduction. While driving pressure is connected mathematically to respiratory system compliance and tidal volume, driving pressure was the only ventilatory variable to independently predict survival in this landmark study. Moreover, higher PEEP was protective only when associated with decreased driving pressure.  


One limitation of strictly using lung mechanics to titrate PEEP is that respiratory system compliance comprises not only the compliance of the lung parenchyma, but also the chest wall and abdomen. A reduced chest wall compliance, as seen in obesity or increased intra-abdominal pressure, can lead to underdosing PEEP when pleural pressure is not incorporated. In order to avoid alveolar overdistention or underdistention, both the pressure inside the alveolus (i.e. airway circuit pressure measured by the ventilator) and outside the alveolus (pleural pressure) must be known. When an esophageal pressure monitor is used to estimate esophageal pressure (Pes) as a surrogate for pleural pressure, the transpulmonary pressure (TPP), or the alveolar distending pressure, can be calculated by subtracting the pleural pressure (Ppl) from the airway circuit pressure (Paw). 


TPP = Airway circuit pressure (Paw) – pleural pressure (Ppl)

While this approach is physiologically sound, a recent randomized controlled trial among patients with moderate to severe ARDS failed to show an outcome benefit using the invasive approach of Pes-guided PEEP. To prevent alveolar collapse in this study, the authors set the PEEP level to maintain a positive transpulmonary pressure during expiration (0 to 6 cm H20) and limited inspiratory TPP to less than 30 cm H20 (ideally < 20 cm H20). This trial demonstrated no significant difference in death or days free from mechanical ventilation utilizing transpulmonary pressure to guide PEEP as compared with empiric high PEEP. 


The question remains, should oxygenation, lung compliance, driving pressure or transpulmonary pressure guide adjustment of positive-end expiratory pressure (PEEP)? The most convincing data demonstrates that increases in PEEP are associated with improved outcome only when driving pressure is lowered. Functional lung size in ARDS is dynamic. By scaling tidal volume to respiratory system compliance, driving pressure can be used as a proxy for lung strain. While there may be a role for invasively monitoring transpulmonary pressure to titrate PEEP in morbidly obese patients, this was not born out in a recent randomized control trial. 


While the ideal method for PEEP titration remains elusive, I would advocate for titrating PEEP to the lowest driving pressure, while maintaining a lung-protective tidal volume ≤ 6 cc/kg ideal body weight and plateau pressure < 30 cm H20.



Amato BP, et al. Driving pressure and survival in the acute respiratory distress syndrome. New Engl J Med2015;372(8):747-755. 


Beitler JR, et al. Effect of titrating PEEP with an esophageal-pressure guided strategy vs an empirical high PEEP-FiO2 strategy on death and days free from MV among patients with ARDS: a randomized clinical trial. JAMA2019;321(9):846-857. 


ARDSnet. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. New Engl J Med. 2000;342(18):1301-1308. 


Gattinoni L et al. The “baby lung” became an adult. Int Care Med 2016;42:663-673


Nieman GF, et al. Personalizing mechanical ventilation according to physiologic parameters to stabilize alveoli and minimize ventilator-induced lung injury (VILI). Int Care Med Exp. 2017;5(8):1-21.