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The -Agonist Lung Injury Trial (BALTI)

Abundant experimental evidence has been reported indicating the possible value of -adrenergic agents in accelerating reabsorption of fluid from edematous lungs following various forms of injury in animals (1, 2). However, clinical studies have yet to document the usefulness of these agents in humans. It was therefore gratifying to see a report by Perkins and colleagues that evaluated the efficacy of intravenous salbutamol over a 7-d period in a group of 40 patients with acute lung injury/acute respiratory distress syndrome (3). This study indicated a significant decrease in lung water in treated patients relative to those who received placebo. In an accompanying editorial, Matthay and Abraham indicated that though the study appeared encouraging, the thermal procedure used to make these measurements needed "validation," and they were concerned that reductions in lung water were not matched by improvements in gas exchange or mortality (4).

The thermodilution approach can be traced to early studies of Chinard and coworkers in which labeled water was injected into a systemic vein with dye, and arterial blood was collected to estimate the amount of water in the lungs (5). Labeled water was subsequently replaced with a thermal signal, which can be readily measured on line and is more diffusible than labeled water. Although transpulmonary thermodilution represents a seductive extension of washout techniques long used by pulmonologists for measuring gas volumes in the lungs, there is reason to believe that it will inevitably yield equivocal and potentially misleading information regarding lung water and should therefore be abandoned (6). There are two unavoidable problems associated with the approach. First, a decrease in calculated water volumes can reflect reduced perfusion of some areas of the lungs rather than a reduction in lung water. This could represent worsening rather than resolution of lung injury. Second, because the thermal signal can recirculate to the lungs before washout is complete, it is impossible to determine the outflow pattern with any degree of certainty. A predictable (e.g., monoexponential) washout pattern is assumed, but this would not be expected in a lung with variable regions of edema and perfusion. These fundamental concerns led to the failure of comparable approaches to gain widespread acceptance over the past four decades. Critical decisions regarding extension of clinical studies of -adrenergic agents for treatment of lung injury should be based on animal, clinical, and radiologic criteria, rather than thermal dilution data.

Richard M. Effros

Harbor-UCLA Medical Center, Torrance, California

FOOTNOTES

Conflict of Interest Statement: R.M.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev 2002;82:569–600.[Abstract/Free Full Text]
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3. Perkins GD, McAuley DF, Thickett DR, Gao F. The -agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial. Am J Respir Crit Care Med 2006;173:281–287.[Abstract/Free Full Text]
4. Matthay MA, Abraham E. -adrenergic agonist therapy as a potential treatment for acute lung injury. Am J Respir Crit Care Med 2006;173:254–255.[Free Full Text]
5. Chinard FP, Enns T, Nolan MF. Pulmonary extravascular water volumes from transit time and slope data. J Appl Physiol 1962;17:179–183.[Abstract/Free Full Text]
6. Effros RM. Lung water measurements with the mean transit time approach. J Appl Physiol 1985;59:673–683.[Abstract/Free Full Text]

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