The β-Agonist Lung Injury Trial (BALTI) and the Measurement of Extravascular Lung Water

Abstract

Abundant experimental evidence has been reported indicatingthe possible value of -adrenergic agents in accelerating reab-sorption of fluid from edematous lungs following various formsof injury in animals (1, 2). However, clinical studies have yetto document the usefulness of these agents in humans. It wastherefore gratifying to see a report by Perkins and colleaguesthat evaluated the efficacy of intravenous salbutamol over a 7-dperiod in a group of 40 patients with acute lung injury/acuterespiratory distress syndrome (3). This study indicated a signifi-cant decrease in lung water in treated patients relative to thosewho received placebo. In an accompanying editorial, Matthayand Abraham indicated that though the study appeared encour-aging, the thermal procedure used to make these measurementsneeded “validation,” and they were concerned that reductions inlung water were not matched by improvements in gas exchangeor mortality (4).The thermodilution approach can be traced to early studiesof Chinard and coworkers in which labeled water was injectedinto a systemic vein with dye, and arterial blood was collectedto estimate the amount of water in the lungs (5). Labeled waterwas subsequently replaced with a thermal signal, which can bereadily measured on line and is more diffusible than labeledwater. Although transpulmonary thermodilution represents aseductive extension of washout techniques long used by pulmo-nologists for measuring gas volumes in the lungs, there is reasonto believe that it will inevitably yield equivocal and potentiallymisleading information regarding lung water and should there-fore be abandoned (6). There are two unavoidable problemsassociated with the approach. First, a decrease in calculatedwatervolumescanreflectreducedperfusionofsomeareasofthelungs ratherthan a reduction inlung water. Thiscould representworsening ratherthan resolutionoflung injury.Second,becausethe thermal signal can recirculate to the lungs before washoutiscomplete,itisimpossibletodeterminetheoutflowpatternwithany degree of certainty. A predictable (e.g., monoexponential)washout pattern is assumed, but this would not be expectedin a lung with variable regions of edema and perfusion. Thesefundamental concerns led to the failure of comparable ap-proaches to gain widespread acceptance over the past four de-cades. Critical decisions regarding extension of clinical studiesof -adrenergic agents for treatment of lung injury should bebased on animal, clinical, and radiologic criteria, rather thanthermal dilution data.