Modifiable risk factors and the role of driving pressure in acute respiratory distress syndrome

In the December 2016 issue of Intensive Care Medicine (1), Laffey et al. published their analysis of potentially modifiable risk factors of mortality in patients with acute respiratory distress syndrome (ARDS) enrolled in the LUNG SAFE prospective cohort study.

Laffey and colleagues included 2,377 patients in their analysis and stratified them based on the Berlin Criteria. The etiology of ARDS was also identified, dividing patients in to having a pulmonary etiology versus non-pulmonary etiology. The LUNG SAFE study has multiple strengths including use of the Berlin criteria to classify patients and the stratification of patients into pulmonary etiology ARDS and non-pulmonary etiologies. Given it is a prospective cohort study it allowed for retrospective comparison of patients based on treatment provided.

ARDS continues to be associated with significant inpatient mortality, ranging from 24–46% and occurs in approximately 10% of ICU patients hospitalized worldwide (2-4).

Multiple non-modifiable predictors of ARDS associated mortality including older age, active neoplasm, immunosuppression, and chronic liver failure were identified and correspond with previous studies. Additionally, lower pH, lower PaO₂/FiO₂ ratio, and higher non-pulmonary sequential failure assessment (SOFA) score were identified as predictors of mortality. Of note, in the LUNGSAFE cohort mortality did not differ between patients with pulmonary versus extra-pulmonary etiology of ARDS.

Given the multiple associated non-modifiable predictors of ARDS associated mortality, identifying modifiable factors related to outcome can help to develop new treatment strategies and to potentially decrease in-hospital mortality.

This study identified several modifiable factors associated with in-hospital mortality including lower PEEP (<12 mmHg), higher peak inspiratory pressure, higher plateau pressure, higher driving pressure, and increased respiratory rate (1). Driving pressure was defined as plateau pressure minus PEEP and calculated for patients with no evidence of spontaneous ventilation (N=742). Amato et al. demonstrated that driving pressure was strongly associated with survival and increased driving pressure was associated with mortality by using a multilevel mediation analysis to analyze individual data from 3,562 patients with ARDS enrolled in previous trials (5). Additionally, Amato et al. demonstrated that increases in PEEP or decreases in tidal volume dictated by randomization were only beneficial if there was an associated decrease in driving pressure. The concordance of these two studies concerning driving pressure is compelling. The finding of increased survival with lower driving pressure supports Amato et al.’s post hoc analysis and should lead to further investigation through randomized control trials aimed at decreasing driving pressure via ventilator management.

Mechanical ventilation strategies using lower end-inspiratory (plateau) airway pressures, lower tidal volumes, and higher PEEP, i.e., lung-protective strategies, have been previously associated with increased survival in randomized clinical trials (6,7). This study again demonstrated that lower plateau pressures, and higher PEEP were associated with survival in concordance with prior studies (8). However, risk of hospital mortality was similar in patients with lower tidal volume (<8 cmH₂O mL/kg predicted body weight) compared to those with higher tidal volume. This is likely secondary to widespread adoption of low tidal volume ventilation and should not negate the impact of low tidal volume ventilation on survival.

A lower respiratory rate (20.3 vs. 21.6 breaths/min, P≤0.001) was also associated with improved survival (1). This is a novel finding which would benefit from further study.

ARDS remains under-recognized and the rate of implementation of evidence-based ventilatory strategies is under-utilized by treating physicians. We strongly feel that continued investigation of targeting driving pressure and lower respiratory rate are indicated based on the findings of Laffey et al.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

References

1. Laffey JG, Bellani G, Pham T, et al. Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Med 2016;42:1865-76. [Crossref] [PubMed]
2. Baumann WR, Jung RC, Koss M, et al. Incidence and mortality of adult respiratory distress syndrome: a prospective analysis from a large metropolitan hospital. Crit Care Med 1986;14:1-4. [Crossref] [PubMed]
3. ARDS Definition Task Force., Ranieri VM, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012;307:2526-33. [PubMed]
4. Bellani G, Laffey JG, Pham T, et al. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA 2016;315:788-800. [Crossref] [PubMed]
5. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015;372:747-55. [Crossref] [PubMed]
6. Villar J, Kacmarek RM, Perez-Mendez L, et al. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 2006;34:1311-8. [Crossref] [PubMed]
7. Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: Systematic review and meta-analysis. JAMA 2010;303:865-73. [Crossref] [PubMed]
8. Kregenow DA, Rubenfeld GD, Hudson LD, et al. Hypercapnic acidosis and mortality in acute lung injury. Crit Care Med 2006;34:1-7. [Crossref] [PubMed]