ALICANTE, SPAIN—For almost 30 years, Light’s criteria have been the basis by which transudative and exudative pleural effusions are differentiated. New evidence suggests, though, that the serum– pleural fluid gradients for total protein and albumin may be better for that purpose in some patients, such as those with congestive heart failure.[1] The reason: The gradients are not greatly affected by diuresis.

It has been known for decades that diuresis raises pleural fluid concentrates of protein and lactate dehydrogenase (LDH), which increases the likelihood that a transudative effusion will be misidentified as exudative. Until recently, however, it has been unclear what other markers could be used to help accurately distinguish the type of effusion present in patients undergoing diuresis.

GRADIENTS VERSUS RATIOS

Romero-Candeira et al prospectively enrolled 21 adults with transudative pleural effusions from congestive heart failure. None of the patients had been given diuretics before the study. All patients underwent diuresis during the study (most often, 40 to 80 mg/d of furosemide). Pleural fluid and serum samples were taken just before the start of diuresis and then about every 48 hours for as long as the effusion was radiographically evident. The pleural fluid was obtained by thoracentesis.

In each sample, concentrations of a number of biochemical markers, including total protein, albumin, and LDH, were measured. For each component, the serum–pleural fluid gradient was calculated by subtracting the pleural fluid concentration from the serum concentration. The pleural fluid:serum ratio was also determined by dividing the pleural fluid concentration by the serum concentration. Because it is thought that repeated thoracentesis may alter pleural fluid biochemical characteristics, the study also included 31 controls with congestive heart failure who underwent thoracentesis only once, after diuresis. These patients most often received 40 to 120 mg/d of furosemide.

On average, the subjects underwent diuresis for five days; median weight loss was 3 kg. In comparison with the samples obtained before treatment had started, those acquired on the last day of diuresis had significantly higher pleural fluid total protein, albumin, and LDH concentrations. Serum total protein and albumin levels also rose markedly during diuresis. As a result, the pleural fluid:serum ratios for protein and albumin rose substantially, and the LDH ratio dropped dramatically. However, the serum–pleural fluid gradients for total protein and albumin changed only slightly.

Overall, the pleural fluid concentrations of total protein and albumin each increased by almost 50% during diuresis, the pleural fluid:serum ratios for those variables rose by 38% and 27%, respectively; and the serum–pleural fluid gradients changed by only about 10%.

Fifteen patients underwent thoracentesis at least three times. Repeated samples from these patients showed that the impact of diuresis on pleural fluid concentrations was immediate; total protein, albumin, and LDH levels had all risen significantly by the time the first posttreatment sample was obtained. However, these levels continued to rise markedly thereafter.

According to the investigators, two thirds of the effusions in patients who underwent at least three thoracenteses would have been misclassified as exudative had Light’s criteria been used. In contrast, only three (20%) effusions would have been misdiagnosed had the serum–pleural fluid total protein or albumin gradient been used.

Even among the controls, who underwent thoracentesis only once, 12 (39%) effusions would have been misclassified as exudates by Light’s criteria, the investigators reported. The protein gradient would have correctly identified all but three (10%) of these effusions; the albumin gradient would have accurately diagnosed all but five (16%).

IMPLICATIONS FOR PRACTICE

In an interview with PULMONARY REVIEWS, V. Courtney Broaddus, MD, put these findings in context. “Although transudates can change to exudates with diuresis, this is uncommon and usually associated with chemistry results that are only slightly abnormal,” she noted. However, the possibility of misclassification increases when multiple thoracenteses are performed, said Dr. Broaddus, an Associate Professor in the Lung Biology Center at the University of California, San Francisco. In an editorial accompanying the paper by Romero-Candeira et al, Dr. Broaddus noted that other studies have shown that the albumin gradient may be preferable to the total protein gradient.[2] Thus, for now, she recommended that physicians use the albumin gradient if the protein and LDH concentration ratios are slightly exudative in a patient with heart failure who has undergone diuresis. However, no test result should take the place of clinical judgment, Dr. Broaddus added.

—Timothy Begany

References
1. Romero-Candeira S, Fernández C, Martín C, et al. Influence of diuretics on the concentration of proteins and other components of pleural transudates in patients with heart failure. Am J Med. 2001;110:681-686.
2. Broaddus VC. Diuresis and transudative effusions—changing the rules of the game. Am J Med. 2001;110:732-735.

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