Commentary

The main aim of this article is to review the concept of driving pressure in adult and mechanically ventilated patients with acute respiratory distress syndrome (ARDS).

Background

A recent global epidemiologic study reported that 10.4% of total ICU admissions and 23.4% of all intubated patients were diagnosed as having ARDS, and mortality remains high [1]. Over the last 50 years [2], research has led to advances in mechanical ventilation that has improved survival among patients with ARDS [3]. However, it is also acknowledged that mechanical ventilation can also lead to ventilator-induced lung injury (VILI) [4]. Therefore, the current evidence-based management goal is to deliver lung protective ventilation with lower tidal volumes (between 4 and 8 mL/kg predicted body weight [PBW]) and limited airway pressures (below 28–30 cmH2O) in order to mitigate VILI in patients with ARDS [5, 6].

Driving pressure (see Table 1 for related terminology)

In patients without spontaneous breathing efforts (i.e., sedated and/or paralyzed on controlled mechanical ventilation), the driving pressure of the respiratory system is defined as the difference between plateau pressure and positive end-expiratory pressure (Pplat-PEEP), and can also be expressed as the ratio of tidal volume to respiratory system compliance (Vt/Crs) [7]. The potential importance of driving pressure in patients with ARDS was first recognized in 1998 [8]. More recently, a secondary analysis of previous randomized controlled trials (RCTs) of mechanical ventilation in ARDS patients demonstrated that driving pressure is the variable that is most strongly associated with mortality [7]. This finding was later confirmed in a systematic review and meta-analysis of driving pressure in patients with ARDS [9]. Moreover, the results of the meta-analysis suggested targeting driving pressure below 13–15 cmH2O, although it remains unclear how to best reduce the driving pressure as part of a ventilatory strategy at the bedside [9].

Table 1 Box glossary of driving pressure and lung mechanics in ARDS
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Conversely, in the presence of spontaneous breathing efforts, the negative change in pleural pressure generated by spontaneous breathing becomes additive to the distending pressure; therefore, driving pressure may be underestimated without considering these efforts. In these circumstances, the plateau pressure should be measured using a brief inspiratory hold (i.e., when no flow on volume control mode) to calculate actual driving pressure [10]. Although a recent study demonstrated that the spontaneous breathing can be injurious for both the lungs and diaphragm [11], the effects of driving pressure on clinical outcomes in the context of spontaneous breathing remain uncertain.

Since driving pressure is a way of representing the tidal volume adjusted for the respiratory system compliance, one reason that lower driving pressure may be associated with lower mortality may be due to a resultant reduction in cyclic lung stretch/inflation during mechanical ventilation [12]. This hypothesis is supported by the strong correlation between cyclic stretch, VILI, driving pressure, and survival in patients with ARDS—with driving pressure having a stronger association than the unadjusted tidal volume [7]. Furthermore, Chiumello et al. reported that driving pressure was significantly associated with lung stress (transpulmonary pressure) [13]. Thus, driving pressure represents the stress applied to the lungs, and adjusting tidal volume according to driving pressure rather than to predicted body weight may lead to better outcomes for patients, especially those with severely injured lungs. Driving pressure may also be used as a tool to help set PEEP, where lung recruitment and reduced inhomogeneity of stress (applied force to lungs) and strain (change of lung volume) with higher levels of PEEP lead to improved lung compliance and reduced driving pressure. Finally, in the setting of marked lung inhomogeneity (e.g., severe ARDS) which may further exacerbate the risk of VILI (due to stress raisers), the potential benefit of lower driving pressure may be even greater [14].

Future research on driving pressure

The concept of driving pressure seems intuitive and clinically reasonable given the physiological link to the small volume of aerated lung available for ventilation (“baby lung”) [15, 16]. However, the studies to date are hypothesis-generating and there is currently insufficient data to support the routine clinical use of driving pressure. First, prospective studies are needed to compare the predictive validity of driving pressure as compared to other ventilatory valuables. In addition, transpulmonary driving pressure (the difference between end-inspiratory transpulmonary pressure and end-expiratory transpulmonary pressure) better represents the pressure that actually applied to the lungs and may more accurately reflect the potential influence for VILI especially among patients with severe ARDS. Thus, the use of esophageal manometry to compute transpulmonary pressure is worthy of consideration in future studies. Such studies need to ascertain the optimal target of driving pressure and the subgroup of ARDS patients who could benefit most from ventilatory strategies targeting driving pressure [9]. Second, pilot studies demonstrating the safety and feasibility of a driving pressure-targeted strategy are needed before larger, confirmatory RCTs are conducted. Specifically, we need a better understanding of how a protocol targeting driving pressure can be implemented by bedside clinicians through the adjustment of tidal volume or other ventilatory variables. Finally, well-designed RCTs will be required to evaluate the potential efficacy of a driving pressure-based ventilation strategy as compared to the current standard of care (i.e., lung protective ventilation) [5, 6, 9]. We believe that RCTs evaluating therapeutic interventions in patients with ARDS should have mortality as the primary outcome, but long-term outcomes (e.g., functional status, quality of life) should also be evaluated prospectively. To start, these studies should focus on patients with severe ARDS who typically would not have spontaneous breathing efforts due to deep sedation and paralysis, but subsequent investigations of the impact of driving pressure in the presence of spontaneous breathing efforts will be required. Specifically, initial studies of driving pressure during spontaneous breathing may focus on the physiological and biochemical effects on the lungs and diaphragm.

Ongoing trials

Currently, there are few clinical trials of driving pressure in ARDS patients listed in clinical trial registries and recruiting patients (Table 2). ClinicalTrials.gov , European Union registry, Japanese registries network, ISRCTN, and Australian New Zealand Clinical Trials Registry were searched with term “driving pressure” on July 1, 2018. The DRiving pressure for Optimization of Positive end-expiratory pressure [DROP – Trial ID: ACTRN12618000554268] is an uncontrolled clinical trial in France to determine the best PEEP based on oxygenation (i.e., PaO2/FIO2 ratio) or driving pressure in patients with ARDS. Patients receive a decremental PEEP trial as part of standard care—maximum PEEP is initially achieved for a plateau pressure < 30 cmH2O, then PEEP is set to 15, 10, and 5 cmH2O. Arterial blood gases and driving pressure are measured at each PEEP level. PEEP according to best oxygenation (PaO2/FIO2 ratio) and the lowest driving pressure will be recorded and compared. Another study is the Does Automated Closed-Loop Ventilation Reduce the Driving Pressure Levels in Patients With ARDS [AiRDRoP—Trial ID: NCT03211494], a randomized crossover trial comparing driving pressure during automated closed-loop ventilation with conventional lung protective ventilation in patients with moderate or severe ARDS. Automated closed-loop ventilation is an extension of closed-loop ventilation, where ventilation and oxygenation are automatically adjusted according to the patient’s work of breathing, end-tidal CO2, and the ARDS Network PEEP-FIO2 table [17]. Finally, the Driving Pressure Limited Ventilation for Patients With ARDS [ART-2—Trial ID: NCT02365038] is a multicenter pilot RCT investigating the feasibility of a driving pressure-limited ventilatory strategy in comparison with the ARDS Network strategy in patients with ARDS. In the intervention arm, the tidal volume will be adjusted between 3 and 8 mL/kg PBW to achieve a target driving pressure of 13 cmH2O, without a limit on the plateau pressure. The primary outcome is the mean driving pressure between day 1 and day 3 after randomization. This trial will provide more information about how driving pressure-targeted strategy can be carried out at the bedside through the adjustment of tidal volume. Although these trials are focused on physiological outcomes, the results will provide important insights on how to design and conduct future trials of driving pressure in patients with ARDS, evaluating its effect on patient-important outcomes.

Table 2 Summary for ongoing trials of driving pressure in ARDS patients
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Conclusion

Mechanical ventilation remains the cornerstone of supportive care for patients with ARDS. While we wait for RCTs confirming the benefit and the prognostic role of the driving pressure in ARDS, lung protective ventilation with lower tidal volumes and inspiratory pressures should be prioritized. Driving pressure can be considered as a complementary tool to adjust tidal volume or PEEP, particularly in patients with severe ARDS.