Lung protective ventilation: targeting tidal volume and plateau pressure vs. driving pressure

The acute respiratory distress syndrome (ARDS) constitutes 23.4% of mechanically ventilated patients (1). Prevention of ventilator-induced lung injury has typically revolved around the use of tidal volumes of 5–8 ml/kg of predicted body weight and limitation of plateau pressures to 30 cm H₂O. However, the lung available for ventilation is significantly reduced and highly variable in patients with ARDS. Hence, the use of tidal volumes based on the predicted body weight leads to variable lung stress, proportionate to the extent of lung involvement. 

What is driving pressure?

The airway driving pressure represents the stress applied to the lungs. It is measured at the bedside as the difference between the plateau pressure (Pplat) and the positive end-expiratory pressure (PEEP). It effectively denotes the tidal volume tailored to lung compliance. 

Driving pressure = Pplat – PEEP

Compliance = tidal volume/Pplat – PEEP

Thus, Pplat – PEEP (driving pressure) = tidal volume/compliance 

Hence, targeting the driving pressure effectively titrates tidal volume based on lung compliance in contrast to the predicted body weight. Considering the relatively small size of the functional lung in ARDS, tidal volumes titrated to the lung available for ventilation, represented by compliance, maybe physiologically more appropriate. The driving pressure is expected to be high in a poorly recruited lung at low levels of PEEP; it will also rise if the applied PEEP is too high, with overdistension of the lungs. In other words, there is an optimal level of PEEP at which the driving pressure is lowest for a given tidal volume, wherein the lung compliance is optimal. The application of an ideal level of PEEP may be expected to result in optimal lung recruitment, and thus, reduce driving pressures. 

Driving pressure and clinical outcomes

Studies on animal models have shown that tissue damage may be more dependent on the amplitude of cyclical stretch in contrast to the level of maximal stretch (2). Lung tissue may withstand sustained stretching without injury. Driving pressures of less than 20 cm H₂O  was employed as part of a lung-protective strategy that resulted in a significantly lower 28-d mortality in an early randomized controlled trial (3). 

Amato et al. retrospectively analyzed data from 3562 patients from nine randomized controlled trials using multilevel mediation analysis. In this study, the driving pressure was the strongest predictor of survival. The important findings of this study were: 1. For similar PEEP levels, mortality was higher with increasing driving pressures. 2. When the driving pressure remained constant, an increase in the PEEP level did not result in higher mortality, despite higher plateau pressures. 3. Importantly, at similar plateau pressure levels, the mortality decreased with lower driving pressures. This was probably because increasing PEEP levels improved lung recruitment and compliance, thereby allowing lower driving pressures for similar tidal volumes (4). 

A meta-analysis of four studies, including 3,252 patients, revealed significantly higher mortality with higher driving pressures. The median (IQR) upper limit of driving pressure in this meta-analysis was 15 (14–16) cm H₂O. A sensitivity analysis of three studies that used similar driving pressure limits (13–15 cm H2O) also revealed a similar effect on mortality (5).  A hospital-based registry study analyzed patients who underwent non-cardiothoracic surgery under general anesthesia with endotracheal intubation. On multivariable regression analysis, lung-protective ventilation was associated with a reduced risk of respiratory complications in the postoperative period. Driving pressure had a dose-dependent association with postoperative pulmonary complications in this study (6).  

Transpulmonary driving pressure

The transpulmonary driving pressure is the difference between the end-inspiratory and end-expiratory transpulmonary pressures. The transpulmonary driving pressure directly correlates with stress on the lung alone; it removes the variable impact of chest-wall compliance. 

Transpulmonary driving pressure = (Pplat – PEEP) – (end-inspiratory – end-expiratory esophageal pressure) 

Estimation of pleural pressure is required to measure transpulmonary pressure, which requires the measurement of esophageal pressure. The airway driving pressure is relatively simple to measure, based on readily available ventilation parameters and correlates with the transpulmonary driving pressure. 

Future perspectives

In a retrospective observational study of patients ventilated using a tidal volume-based protocol, 60% of patients received a driving pressure exceeding the suggested upper limit of 15 cm of H₂O at the time of commencement of ventilator support (7). Targeting driving pressure is based on a strong physiological rationale and supported by clinical evidence. However, the safe range of driving pressures is currently unclear. Besides, the impact of driving pressure in the presence of spontaneous breathing efforts is also unknown. Controlled studies are required in the future to compare the conventional tidal volume and Pplat based strategies with a driving pressure-based strategy. 

The bottom line 

• Optimization of ventilatory support is important to prevent ventilation-induced lung injury; the use of a low tidal volume strategy with limitation of plateau pressures has been conventionally considered to be the most effective strategy.

• Considering the limited and highly variable volume of the ventilatable lung in patients with ARDS, the use of tidal volumes based on predicted body weight may not be optimal.

• The driving pressure is based on a sound physiological rationale and targets tidal volumes based on lung compliance, in contrast to predicted body weight. 

• A driving pressure of 15 cm of H₂O has been suggested as a reasonable target, with an upper Pplat limit of 40 cm of H₂O, largely based on observational studies (4). 

• The transpulmonary driving pressure may more precisely represent lung stress; however, the airway driving pressure is easier to measure by the bedside and maybe a reasonable surrogate.

• Controlled studies are required to confirm the beneficial effect of a driving pressure-based ventilator strategy in patients with ARDS. 

References

1.         Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788–800.

2.         Tschumperlin DJ, Oswari J, Margulies AS. Deformation-induced injury of alveolar epithelial cells. Effect of frequency, duration, and amplitude. Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):357–62.

3.         Passos AMB, Valente BCS, Machado MD, Borges MR, Paula SG, Geraldo L-F, et al. Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. N Engl J Med. 1998;8. 

4.         Amato MBP, Meade MO, Slutsky AS, Brochard L, Costa ELV, Schoenfeld DA, et al. Driving Pressure and Survival in the Acute Respiratory Distress Syndrome. N Engl J Med. 2015 Feb 19;372(8):747–55.

5.         Aoyama H, Pettenuzzo T, Aoyama K, Pinto R, Englesakis M, Fan E. Association of Driving Pressure With Mortality Among Ventilated Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis*. Crit Care Med. 2018 Feb;46(2):300–6. 

6.         Ladha K, Vidal Melo MF, McLean DJ, Wanderer JP, Grabitz SD, Kurth T, et al. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study. BMJ. 2015 Jul 14;351:h3646. 

7.         Baldomero AK, Skarda PK, Marini JJ. Driving Pressure: Defining the Range. Respir Care. 2019 Aug;64(8):883–9.