Affiliations: Atlanta, GA
Dr. Martin is affiliated with the Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine.
Correspondence to: Greg S. Martin, MD, MSc, Assistant Professor of Medicine, Emory University School of Medicine, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303; e-mail: Greg_Martin@emory.org
Acute lung injury (ALI) and ARDS are common and lethal conditions. The spectrum of lung injury represented by ALI/ARDS affects approximately 150,000 people each year in the United States,1although the number may be much higher.2The mortality rate associated with ALI/ARDS depends on the underlying cause, varying from < 20% for traumatically injured patients to > 60% for sepsis-induced ALI/ARDS. Crude estimates of the health-care costs associated with ALI/ARDS may exceed $5 billion per year in the United States alone.3Substantial efforts have been devoted to finding effective therapies and improving clinical outcomes, and to date we have had limited, if any, success.4–6
In this issue of CHEST (see page 525), Stapleton and colleagues provide an expanded report on ALI/ARDS patients at the University of Washington. From these subjects, they report that the fatality rates of patients with ALI/ARDS have declined over time, with sepsis-related complications being the most common cause of death at nearly 50% and respiratory failure being a relatively uncommon cause of death at < 20%. Importantly, the reductions in patient fatalities are most apparent in patients with trauma-related ALI/ARDS, while patients with sepsis-related lung injury continue to experience the highest fatality rates. The proportion of deaths that occur within the first 3 days after contracting ALI/ARDS compared to those occurring later has not changed, yet it appears that death may be occurring more swiftly for the growing percentage of patients who have life support measures withdrawn.
How does this fit with our current understanding of ALI/ARDS? While much of the data regarding outcomes in ALI/ARDS is from the same productive group of investigators, we have good evidence that patient fatality rates have been declining over the past 20 years.7–9 Early mortality with ALI/ARDS is primarily related to the inciting event, while mortality after the first 3 days often relates to an intervening complication, such as sepsis.10 Interestingly, prior studies examining changes in fatalities have found that improvements were most apparent in the younger population and in those patients with sepsis, compared to the current study in which the outcomes of patients with sepsis-related ALI/ARDS have not significantly changed.7 Another timely finding of this study is the observation that ALI/ARDS patients are increasingly more likely to have care withdrawn prior to death, which is a finding that is consistent with data gathered in other critically ill populations where the withdrawal of life support may precede up to 90% of ICU deaths.11–12 Thus, we understand that important clinical outcomes for ALI/ARDS patients are changing, both in providing end-of-life care and in improving overall survival.
Why is this incremental expansion of knowledge problematic in patients with such an important and lethal condition as ALI/ARDS? I find this disturbing for two reasons. First, and foremost, sepsis remains a significant contributor and complicating factor among patients with ALI/ARDS. Second, we have not yet defined the reasons why patient fatality rates may be declining in an important and often studied condition such as ALI/ARDS.
Sepsis is consistently the most common cause of ALI/ARDS and also the most common cause of death after patients develop ALI/ARDS. Furthermore, the static fatality rates for patients with sepsis-related ALI/ARDS come at a time of great advances in the knowledge of sepsis epidemiology,13pathophysiology14–15 and treatment.16–17 While some of these advances temporally overlap or extend beyond the findings in the current study, it is clear that mortality with sepsis has been declining over the past 2 decades.13,18
According to the current study, outcomes are improving only in patients with ALI/ARDS among those with non–sepsis-related causes of injury. This raises the question of whether sepsis-related ALI/ARDS involves a different initiating mechanism or whether the pathophysiology is substantially different, thus producing contrasting outcomes compared to other causes. The difference may not be as straightforward as distinguishing direct and indirect causes of injury to the lung, given that sepsis and trauma are more similar than dissimilar in this respect. While the final common pathways may be similar, the individual pathways that lead to ALI/ARDS may be substantially different, comparing overwhelming infection and inflammation with the “two-hit” hypothesis espoused in patients who undergo trauma. Furthermore, acquired patient-specific factors may also influence outcomes, as sepsis patients are older and have more chronic comorbid medical conditions compared to young, healthy trauma patients. A combination of clinical and basic science research (ie, translational research) is needed to more fully dissect these differences.
The second disturbing finding is that we have not clearly defined the reasons why patient fatality rates are declining among ALI/ARDS patients. This is particularly salient given that we have not developed any specific therapies for ALI/ARDS, and that any improvements in mechanical ventilation strategies evolved after the time period of this study. While we should not refuse a “gift” of improved outcomes, it is unfortunate that fatality rates for patients with ALI/ARDS may be falling because they are passively carried along like a boat with the ebbing tide. In other words, we are not improving the care of ALI/ARDS patients specifically, but rather improving the care of ICU patients in general. That likely possibility is both heartening for critical care physicians and disheartening for ALI/ARDS patients and investigators. This point is further emphasized by the realization that patients may not die of ALI/ARDS, yet they nearly universally die with ALI/ARDS. Presumably there are directly attributable consequences from ALI/ARDS for patients, and thus we cannot optimize outcomes for ALI/ARDS patients by depending on general improvements in intensive care.
At present, the treatment of patients with ALI/ARDS remains grounded in supportive care that incorporates mechanical ventilation using low tidal volumes. In order to deliver the optimum supportive care, we must apply “best-care” practices for all of the corelated conditions that may intervene and contribute to poor outcomes in ALI/ARDS patients. For instance, ventilator-associated pneumonia (VAP) is associated with a greater duration of mechanical ventilation and a prolonged stay in the ICU, and VAP may influence mortality independent of other factors involved in the underlying critical illness.19For ALI/ARDS patients in whom the duration of mechanical ventilation may be prolonged, applying evidence for the prevention of VAP may be paramount in improving overall outcomes. There is good evidence for VAP prevention based on stress ulcer prophylaxis regimens, patient positioning, and ventilator interfacing and connectivity.20–22 Barriers to the application of appropriate mechanical ventilation have been explored in ALI/ARDS patients,23 yet we need to identify the barriers to all ALI/ARDS interventions so that we may design strategies to put evidence into practice.
To move toward the optimal patient-centered outcomes, we need a prospective study of ALI/ARDS patients, ideally with a suitable control group for comparison and refined definitions for both the cause of ALI/ARDS and for the cause of death after contracting ALI/ARDS. This would allow for better identification of the factors responsible for changing fatality rates and the development of prediction models for both the development of ALI/ARDS and its ultimate clinical outcomes. Such a study could also provide valuable information regarding end-of-life care, the barriers to optimal care, the costs associated with the care of ALI/ARDS patients, and ultimately on the predictors of ALI/ARDS risk and outcome to complement the tremendous advances in other areas of critical care medicine.
This study was supported by grants HL K23–67739 from the National Institutes of Health.
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