Positive End-expiratory Pressure and Lung Recruitment
Since the first description of ARDS by Ashbaugh and colleagues, PEEP has been integral to the management of hypoxemia in ARDS.[47,48] More recently, the use of higher PEEP has been studied as a possible strategy to avoid lung injury. While several strategies for optimizing PEEP have been tested, none have yet shown a mortality benefit and one strategy was even associated with harm in ARDS patients. Consequently, PEEP titration remains a controversial area of ventilator management and great care must be taken when applying PEEP at the bedside.
Physiological Basis for Titrating PEEP
Applied at the correct level, PEEP might mitigate the risk of ventilator-induced lung injury (VILI). By preventing end-expiratory collapse of alveoli and small airways during tidal ventilation, PEEP prevents the shear stresses resulting from cyclic opening and closing of alveolar units—"atelectrauma."[49,50] PEEP effectively reduces intrapulmonary shunt and improves oxygenation by opening collapsed lung units to participate in gas exchange. Increasing the number of aerated lung units participating in ventilation reduces the dynamic tidal strain and stress applied to the lung[52,53] (Figure 2). Finally, lung recruitment by PEEP results in more homogeneous inflation of the lung; this can significantly reduce mechanical stress resulting from local inhomogeneities in the lung, which act as stress multipliers.
The effect of PEEP on dynamic strain depends on recruitability of the lungs. In the top panel, applying PEEP to the lung increases lung volume but because no additional alveoli are recruited, tidal ventilation is applied to the single alveolar unit and this unit experiences all of the dynamic strain. The amount of strain applied to the lung is determined by the ratio of tidal volume to end-expiratory lung volume (VT/EELV) at a given PEEP and FRC. In this theoretical (and simplified) representation, dynamic strain is approximately one-third in the nonrecruitable lung. In the bottom panel, applying PEEP to the lung increases lung volume and recruits an additional previously collapsed alveolus to participate in tidal ventilation. The same tidal volume is now distributed between two alveolar units, hence decreasing the dynamic strain experienced by each individual unit. This is the mechanism by which lung recruitment from PEEP is thought to decrease dynamic stress and strain. EELV, end-expiratory lung volume; FRC, functional residual capacity; PEEP, positive end-expiratory pressure.
At the same time, PEEP has important cardiorespiratory interactions which can limit the aforementioned physiological benefit. Depending on the underlying left ventricular function PEEP may improve cardiac output by a relative reduction in afterload. At higher levels of PEEP, however, the increased intrathoracic pressure can be deleterious by elevating right atrial pressure, decreasing the gradient for venous return,[55,56] and reducing left ventricular preload—ultimately reducing cardiac output.[56,57] PEEP may also influence right ventricular performance indirectly by increasing pulmonary vascular resistance. This occurs as elevated pressures occlude the alveolar septal vasculature, thereby increasing right ventricular afterload and reducing cardiac output.[58,59]
From a pulmonary parenchymal perspective, PEEP may contribute to VILI by over-distending aerated lung units. Given that the ARDS lung is functionally a "baby lung," applied PEEP that fails to open collapsed alveoli will injuriously overinflate residual lung units propagating lung inflammation and injury, similar to the effects of excess tidal volume. Therefore, the benefit and harm of PEEP on the patient's overall physiological condition will depend on how much lung can be recruited and on hemodynamic conditions.
Recruitment Maneuvers and the Open Lung Approach
In view of concerns about the injurious effects of atelectasis and potential benefits of PEEP, the "open lung approach" gained favor. Opening pressures in alveolar units often exceed 35 cm H2O (the accepted safe upper limit of plateau pressure) while the PEEP required to maintain patency after opening is lower. Thus, various "recruitment" maneuvers for maximally inflating the lung to optimize lung recruitment have been studied. A recruitment maneuver is a sustained increase in airway pressure with the goal to open collapsed alveoli, after which sufficient PEEP is applied to keep the lungs open. A sustained inflation is the most commonly employed maneuver: the ventilator is set to continuous positive airway pressure (CPAP) mode and pressures are increased to 30 to 40 cm H2O for 30 to 40 seconds. An alternate approach is the "staircase" maneuver involving progressive increases in PEEP while maintaining a constant airway driving pressure until a maximum peak pressure of 50 to 60 cm H2O is achieved. The physiological effects of recruitment maneuvers are transient and depend on the concomitant PEEP strategy. The effects of a recruitment maneuver on lung injury are unclear, and hemodynamic instability (hypotension and/or bradycardia) can occur during maneuvers. The benefits of lung recruitment depend on lung recruitability, but these maneuvers can be used as a diagnostic test to assess for recruitability.
Clinical Evidence Guiding the Delivery of PEEP
In patients with ARDS, no clinical trial has definitively concluded whether a high or low PEEP strategy is associated with improved outcomes. The ALVEOLI, LOVS, EXPRESS, and ART trials provide the highest quality evidence to answer the high versus low PEEP question. The LOVS and ALVEOLI trials were both randomized controlled clinical trials that compared high to low PEEP/FiO2 tables in the ventilation management of patients with ARDS. In both of these trials, the higher PEEP arms resulted in increased mean arterial oxygen tensions[66,67] but neither trial was able to demonstrate a mortality benefit of a particular strategy. The French EXPRESS trial, though designed with a plateau pressure limit of 28 to 30 cm H2O, also failed to show a mortality benefit.
The recently published ART trial was a multicenter randomized controlled trial (RCT) including just over 1,000 patients with moderate-to-severe ARDS randomized to a lower PEEP or higher PEEP arm with aggressive lung recruitment maneuvers. Surprisingly, and different from previous trials, the 28-day mortality rate was significantly higher in the higher PEEP plus recruitment maneuver group compared with the control arm (55 vs. 49%, respectively). Several methodological criticisms were raised about this trial. One major concern was that the duration and amplitude of the lung recruitment maneuver in the experimental arm were excessive, increasing the risk of respiratory acidosis and barotrauma. Peak recruitment pressures of 60 cm H2O and a recruitment time process of 24 minutes without ensuring adequate volume resuscitation might have explained in part the three cardiac arrests and seven pneumothoraces documented during recruitment. A high proportion of patient–ventilator asynchrony in the experimental arm raised further concerns for significant VILI during controlled ventilation.[70,71] Some of these issues may explain this trial's disappointing result. Of note, a recent pilot RCT which also involved recruitment maneuvers and a decremental PEEP trial identifying the PEEP level associated with the maximum dynamic compliance demonstrated that an open lung approach improved oxygenation and respiratory system mechanics without detrimental effects on 60-day mortality, ventilator-free days, or barotrauma and set the stage for a larger trial.
It is important to note that none of the trials to date have explicitly considered lung recruitability as a criterion for enrolment or as a prespecified factor for stratifying analysis of the primary end-point. Given the foregoing physiological considerations, lung recruitability is likely a key determinant of benefit or harm from PEEP. The importance of considering recruitability is supported by the observations that the oxygenation response to increased PEEP predicts mortality and that the effect of PEEP on mortality appears to be mediated by its effect on driving pressure (since both favorable oxygenation responses and mechanical responses will reflect lung recruitment).
Optimal PEEP Management
In the contemporary management of patients with ARDS, the optimal approach to titrating PEEP remains unclear. It is clear that no strategy should attempt to apply a "one-size-fits-all" approach and individual variation in lung recruitability must be considered. The biological phenotype of ARDS may also be a crucially important consideration. A variety of strategies for titrating PEEP are under investigation such as oxygen response to PEEP, computed tomography, driving pressure, pressure–volume loops, stress index, esophageal manometry, and electrical impedance tomography. After 20 years of investigation, PEEP remains a challenging and important area of clinical investigation.
Semin Respir Crit Care Med. 2019;40(1):81-93. © 2019 Thieme Medical Publishers