© 2002 American Thoracic Society
Controversies around Lung Protective Mechanical VentilationCritical Care Medicine Programme Mount Sinai Hospital and University Health Network University of Toronto Toronto, Canada In this issue of AJRCCM (pp. 1510–1514), Eichacker and coworkers (1) present an analysis of five recent randomized controlled trials (2–6) evaluating strategies for lung protective mechanical ventilation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). They make three points that are worth discussing: (1) In the two "beneficial" trials (2, 3), the differences in mortality appear attributable to increased mortality in the control arms as opposed to benefit in the low tidal volume arms; (2) the control arms of the "beneficial" trials (2, 3) did not reflect the standard of care, and thus applicability of the studies is limited; and (3) very low tidal volumes, often recommended, may be harmful. Before I give my opinion on these points, I would like to point out potential concerns with the analysis by Eichacker and coworkers (1), which the authors allude to. It is an oversimplification to view the pooled studies (2–6) simply as low tidal volume approaches. Each study contained detailed protocols regarding end-expiratory pressure, pH control, peak and plateau pressure limits, ventilator mode, weaning and extubation, and ventilatory-adjuncts such as recruitment maneuvers, nitric oxide, pressure–volume curves, and so on. Moreover, there are problems in drawing definitive conclusions from analyses such as that of Eichacker and coworkers (1), given, among many other factors, the varying patient populations and the small number of studies and patients pooled (7). Furthermore, the primary variables used in their analysis were tidal volumes and plateau pressures, and because the investigators of each study measured (and in some cases did not specify how they measured) these variables differently, the results are of questionable value. Finally, plateau pressures without appreciation for the stiffness of the lung and chest wall can be misleading. Despite these limitations, the authors make some interesting points (1), which have already stimulated intense discussion because of their immediate implications for patient management and clinical trials in critical care (8). At the time the pooled trials (2–6) were designed, the opinion of experts was that plateau pressures of 35 cm H2O or higher were of concern and that this issue required further investigation in the setting of randomized trials (9). Eichacker and coworkers point out that the mean values for the control arms of the two "beneficial" trials (2, 3) push that limit (1). This information, combined with very recent observational data (10), makes it hard for me not to concur that high plateau pressures in the control arms likely contributed to the observed differences in mortality—an opinion I could not draw before the ARDSNet trial (2). As a result, I believe an approach that limits airway pressures (for example, no higher than 30–35 cm H2O) is safe, applicable to most patients, and easily implemented. That said, this approach requires formal testing. In addition, pressures measured at the airway opening may be high for reasons other than lung overdistention (such as a stiff abdomen), and in such a setting, higher airway pressures may be acceptable. Eichacker and coworkers (1) demonstrate that in the two "beneficial" trials the mean values of tidal volume and plateau pressure in the control arms after randomization were higher than the values before randomization. As a result, they conclude the control arms did not reflect the standard of care. On this point I disagree. It is true that experts recommended that tidal volumes be reduced to avoid overdistention (9). The recommendation, however, also included a call for conclusive data (9). The pooled trials are a result of this call (2–6). Expert recommendations likely led to practice modifications; given the lack of proof, however, this should hardly be considered the standard of care. In my opinion, the standard of care in this setting is better reflected in the approach before practice changes evolved. I also would like to point out that even the "nonbeneficial" studies allowed for control tidal volumes as high as 15 ml/kg (regardless of whether the mean value reflected this) (4–6). When there are no strict guidelines, it is difficult to definitively define a standard of care. Given that all the trials (including our own [4]) went through several peer-reviews, investigator (clinical experts) discussions, multiple research ethics and data/safety monitoring boards, and given the consistency in permitted tidal volumes in the control arms among trials, I cannot agree that the control arms were not a reasonable standard of care. In addition, I do not believe that the approach clinicians take in academic centers necessarily reflects care in most intensive care units, because most units are in nonacademic centers where many clinicians lack formal critical care training (11). If the "beneficial" trials (2, 3) had not been conducted we would lack conclusive evidence that adjustments to pressures and volumes can save lives. In fact, we would be left only with the results of the "nonbeneficial" studies, which suggest that restrictions of tidal volume and airway pressure are not important. As a result, unacceptable behaviors such as pressure/volume adjustments based purely on carbon dioxide level would have been allowed to persist to the detriment of patients. Finally, in many (perhaps most) clinical issues in critical care there is lack of consensus on the "standard of care," and frequently there are two camps of opinion. Although I think the comments on standard of care by Eichacker and coworkers (1) are worth discussing, I hope they will be used to improve future trial designs and not slow our ability to answer important questions. Low volume ventilation may lead to harm in a number of ways, with injury associated with the repeated opening and closing of airways being of primary concern (12). An approach that utilizes high end-expiratory pressures, however, might mitigate this injury (12). It is worth noting in the two "beneficial" trials (2, 3) some patients in the low-volume arms had high end-expiratory pressures either by design or inadvertently (13). This, coupled with the low mortality (especially in the ARDSnet study [2]) and the inherent problems in drawing definitive conclusions from a pooled analysis such as that of Eichacker and coworkers (1), prevents me from concluding that any of the low-volume approaches tested to date are harmful. I believe the ARDSnet study (2) is one of the most important critical care studies that has been published to date and should prompt clinicians to evaluate and, in most cases, modify their practice. I also believe it is the intervention against which future ventilator strategies should be tested. REFERENCES
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
