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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Anesthesiology. Author manuscript; available in PMC 2010 November 1.
Published in final edited form as:
PMCID: PMC2770091
NIHMSID: NIHMS149301

Lung Water: What You See (With Computed Tomography) and What You Get (With a Bedside Device)

Eduardo LV Costa, M.D., Ph.D.* and Marcos F Vidal Melo, M.D., Ph.D.*

Newspaper headlines have greeted with circumspection the report from the Government Accountability Office on the United States Food and Drug Administration (FDA) processes to regulate medical devices. They used sentences such as “Left to the FDA’s own devices” 1 and “Is That Device Safe?” 2. Such headlines bring attention to the fact that FDA requirements for approval and clearance of medical devices are markedly different from those for drugs3, 4. Most new devices are cleared, not approved, through the premarket notification (510(k)) pathway. This is a FDA process based on the assumption that the majority of new devices are essentially equivalent to those already approved. Physiological monitors are usually among these, and frequently enter the market due to their substantial equivalence to previous models, with limited scrutiny of efficacy 3, 4. Thus, as new monitors are introduced, it is crucial for good clinical practice to understand their principles, advantages and limitations. In this issue of Anesthesiology, Easley et al.5 apply functional lung imaging techniques to study measurements of extravascular lung water (EVLW) using the single indicator (iced saline) transpulmonary thermodilution method. The device was recently cleared by the FDA (PiCCO, Pulsion Medical Systems, Munich, Germany).

Measurement of EVLW has been of clinical and research interest for decades. The expectation is that it would be superior to blood oxygenation and chest radiography for assessment of pulmonary edema. Recently, availability of the transpulmonary thermodilution technology, which facilitated bedside measurements, revived the interest for that measurement6. Many studies reinforced the concept that EVLW could be a useful clinical and research tool. EVLW was suggested as a predictor of mortality in patients with severe sepsis 7 and acute lung injury (ALI)8, 9, as a diagnostic tool in detecting early pulmonary edema10, and evaluating the effect of ventilatory modes during esophagectomy11. The measurement has also been proposed to guide fluid therapy in acute respiratory distress syndrome 12, and subarachnoid hemorrhage13, and to assess the effect of steroids during cardiac surgery14. EVLW was the primary outcome variable in clinical trials to study the efficacy of salbutamol to resolve pulmonary edema in patients with ALI/acute respiratory distress syndrome (The beta-agonist lung injury trial)15 and lung resection16.

Assessment of EVLW following an intravenous central injection of iced saline involves considerable and at times conflicting assumptions17, 18. The measurement premises include that the thermal indicator reaches and equilibrates equally in all lung regions, and that the central circulation volumes between the injection and temperature measurement site can be described as a small number of individual well-mixed compartments, each showing a monoexponential decay of temperature with time. Certainly, these and other assumptions do not apply to all conditions and may significantly compromise the measurement18. However, the relevant point is: are those premises acceptable in specific clinical conditions to allow for reliable measurements?

Pulmonary perfusion is heterogeneously distributed in the normal19 and diseased20 lung. Regional pulmonary perfusion is also altered by several factors such as hypoxic pulmonary vasoconstriction21, endogenous nitric oxide production22, pulmonary embolism23, inspired oxygen fraction24, positive end-expiratory pressure 25, body position19, and inhaled nitric oxide26. Redistribution of lung aeration with perfusion clearly alter the arterial kinetics of centrally injected tracers27. As a consequence, assumption of a homogeneous exposure of lung tissue to a thermoindicator and of a monoexponential behavior in the washout of that indicator may not be warranted.

Easley et al.5 bring novel direct quantitative information on the topic in a dog model of ALI with saline lavage. The authors used high-resolution computed tomography (CT) techniques to assess total lung tissue and perfusion and show that, in the presence of transpulmonary thermodilution EVLW in the 20–30 mL/kg range, acute changes in regional perfusion due to intravenous endotoxin resulted in an average increase of 6 mL/kg in EVLW. Such increase occurred while CT measured tissue volume was unchanged and pulmonary perfusion increased to regions of poor aeration. The findings indicate that redistribution of perfusion towards thermally silent regions can increase the measurement of EVLW without a real increase in lung water content.

This study highlights the importance of using a large animal in experiments to insure results that are more relevant to patients. In fact, the used animal model produced a heterogeneous distribution of lung aeration and perfusion during ALI comparable to that observed in humans. Also, use of non-invasive imaging techniques allowed the authors to investigate in-vivo and in detail perfusion redistribution in a clinical-like condition, in contrast to previous invasive methods such as caval balloon-occlusion 28. Whole lung CT quantification of lung tissue, a well established method, is another strength of the paper for accurate measurements in short intervals.

The results of Easley et al. imply that in conditions where significant pulmonary edema develops, considerable differences in EVLW measurements could be caused by redistribution of lung perfusion. The observed differences were larger than those seen in the beta-agonist lung injury trial between treatment and control groups15. Accordingly, modifications in regional lung perfusion, similar to those that occur during sepsis or thromboembolism, could produce misleading EVLW measurements. This implies that the expected reliability of transpulmonary thermodilution EVLW to follow trends28 cannot be taken for granted. It requires interpretation in light of potential simultaneous changes in regional perfusion. Such results are consistent with the influence of the type of ALI on the accuracy of EVLW measurements2931. The results in this investigation are also similar to the results found in sepsis28 and ALI29 animal studies comparing gravimetric measurements of lung water, the gold standard of EVLW measurement but too invasive for human studies, to EVLW measurements utilizing thermodilution or double indicator methodology. Redistribution of pulmonary perfusion during human ALI may be smaller than that observed in animals20 and this may reduce variability of EVLW measurements in humans. However, early and recent evidence of thromboembolic disease in acute respiratory distress syndrome 32, 33 suggest that significant changes in perfusion could occur. Unfortunately, there is limited information on the topographical distribution of lung perfusion in humans, particularly during ALI.

There are also limitations in the study. CT measurement of lung tissue represents radiologic density and does not differentiate between pulmonary edema, blood, and tissue. Assessment of regional lung perfusion with CT has not been comprehensively compared to more established methods in the setting of ALI, and was done using a single slice. Furthermore, endotoxin is known to produce a rapid recruitment of inflammatory cells to the lungs. These cells are composed mostly of water, constitute additional thermal volume in close contact with the indicator, and could be an additional factor modifying EVLW measurements. Given the non-significant changes in the CT estimates of lung tissue, the short time between measurements of lung tissue and perfusion before and after endotoxin, and the increasing experience with measurements of perfusion with CT, it is unlikely that such limitations alter the fundamental message of the study.

Topographical heterogeneity and mismatch of individual properties are essential characteristics of normal lung function and these properties become exaggerated in disease states. Therefore, any global measurement of EVLW will be inherently problematic in all conditions where lung perfusion is significantly altered, including sepsis, ALI, and thromboembolism. The approach of Easley et al. in studying a global parameter with a clinically relevant model and using sophisticated noninvasive imaging methods is a welcome contribution. It provides us with quantitative data to ponder the balance between complex physiologic information and practicality. Bedside measurements of EVLW can be an important instrument for human research and, potentially, clinical decision making. Easley et al. remind us that the application of transpulmonary thermodilution methodology is only helpful when lung physiology is understood and the benefit of this technology in clinical practice needs further investigation.

Acknowledgments

Supported by the National Heart, Lung, and Blood Institute grant No. HL086827 from the National Institutes of Health, Bethesda, Maryland.

Footnotes

Conflict of Interest: Dr. Vidal Melo was lent a PiCCO device and given 8 catheters by Pulsion Medical Systems (Munich, Germany) for experiments in his laboratory.

RE: Easley RB, Mulreany DG, Lancaster CT, Custer JW, Fernandez-Bustamante A, Colantuoni E, Simon BA: Redistribution of Pulmonary Blood Flow Impacts Thermodilution-based Extravascular Lung Water Measurements in a Model of Acute Lung Injury

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