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Pleural pH, survival and outcome of pleurodesis
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FRANCISCO RODRIGUEZ-PANADERO, Chief of Respiratory Endoscopy Section HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO
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frpanad{at}intercom.es FRANCISCO RODRIGUEZ-PANADERO
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Pleural fluid pH, survival and outcome of pleurodesis in malignant pleural effusions. To the editor: I have read with a real interest the three articles on pleural pH that appeared recently in CHEST , , . Two of them referred to the relation between pH and survival, and the third one concerned with the ability of pleural fluid pH to predict outcome of pleurodesis in malignant pleural effusions (MPE). Since our Group has been deeply involved in this issue, and actually our papers which had been published previously on this topic , , were repeatedly mentioned in all of the three articles, I would like to make some comments that could throw some light on this controversy. Regarding the paper from Burrows and coworkers1, I readily agree with them in that clinical parameters, and especially Karnofsky index, are very useful in evaluating patients with MPE, and in that they should be taken into consideration when dealing with these patients. Although that index was not specifically addressed in our papers, a clinical evaluation was certainly done in every patient, and actually it had a very important weight at the moment of taking decisions regarding pleurodesis. However, our belief was -and still is- that pH determination was useful in giving us a clue on the fate of the patients in the forthcoming few months, especially if the pH level was below 7.20. Having said that, I have some criticisms and comments to make regarding the Burrows and coworkers paper1: i) First, I wonder if their data are right in every respect. For example, the range of pH in their patients goes from 7.00 to ¡¡8.50!! (Table 1). The authors fail to mention this detail and to explain this finding in their article. I have never seen a pleural pH this high in more than 500 determinations made in patients with MPE at our institution, nor found a single case of MPE with this figure in the literature. Therefore, I guess that there were some errors in their data regarding pH, either due to a delay in testing or to a methodological error. I specifically guess that some of their pleural fluid samples were not submitted to the laboratory in anaerobic conditions, and that they were therefore contaminated with ambient air, with the subsequent and dramatic rise in pH values that commonly occurs in this circumstance . ii) If my previous assumptions were right, the immediate consequence would be that the pH quartiles shown in Table 2 are wrong. I suspect this is the case, since there is an unexpected short median survival quoted in the first quartile (3.1 months in those patients with the lowest hydrogen ion concentrations, which means those with the highest pH), while the remainder shows a clear association between pH and survival. Therefore, I guess that the lack of correlation between pH and survival in their series was likely related to this error. This correlation was actually found in the large analysis done by Heffner and coworkers2, in which pH was an independent predictor of survival (p<0.0039). iii) Another controversial issue in the paper from Burrows and coworkers refers to the relation between the extent of pleural carcinomatosis (EPC) and pH/survival. I have to assume that they made the EPC correctly, according to our previously published work6; however, they seem to contradict themselves when they write that they "cannot comment on the reliability of the EPC score..." and then state that it "may not be an accurate measure of the extent of neoplastic pleural disease." How did they come to this conclusion in their study? Although I agree with them in that a better rating system might be developed in the future, it has been very useful to us in the management of our patients with malignant pleural effusion. Regarding the articles from Heffner and coworkers2,3, I would like to say that I was indeed very happy to know that a meta-analysis on this matter was under way, and eagerly collaborated with Dr. Heffner in submitting as many data as I could. Actually, we provided almost half of the cases in his study (see Table 3 in reference 3). After reading carefully their papers on pH and pleurodesis outcome/survival, I do believe that Heffner and coworkers made an important contribution to the management of patients with MPE through clarification of what we know, and what we do not, on this matter. Table 5 (in reference 3) is especially relevant to me, in order to improve the clinical application of pH in MPE. However, I have to point out that the impact of mesothelioma cases may have been underestimated in their study: the amount of mesotheliomas included in the Heffner series is rather confusing to me, since Table 1 in reference 2 quotes 29 and Table 2 in reference 3 quotes 36 patients with pleura as the (primary) tumor site. Anyway, we contributed with 29 mesotheliomas and 193 carcinomas to the whole series, and I have made myself a few calculations using our own data: First, I would like to stress that there were significant differences in survival between our patients with mesothelioma and those with metastatic carcinomas (6 vs. 2.8 months, respectively, p=0.004), and this fact was made clear by us in a work that was published a few years ago (and not well known so far, I guess). On the other hand, median pH values tend to be lower on the mesothelioma group (7.31 vs. 7.34), which is understandable with the help of the pathophysiologic mechanisms involved in pH levels within the pleural space. As mesothelioma provokes a marked diffuse thickening of the pleural membranes by itself, one can expect that an early fall of pleural pH occurs in this condition. Therefore, I believe that those mesothelioma patients may have provoked a double-way bias when studying the pH-survival relationship (they survive longer, and have an average lower pH than metastatic carcinomas too). This was one of the reasons why we made a report on survival in pleural metastatic carcinomas (only) in 1993 in CHEST6. This bias could also explain some of the controversial reports on low pH and prolonged survival, and that of Bilaceroglu and colleagues in particular (quoted both by Burrows and coworkers and by Heffner and coworkers). In the largest study reporting pleurodesis with C. parvum in the literature, these authors found no correlation between pH and both survival and pleurodesis outcome in Turkey. However, a large subset of patients with mesothelioma (as it usually occurs in that country) was included in their series of 131 cases with MPE, thus making problematic the comparison with other studies. Finally, and regarding pH and pleurodesis outcome, I would like to point out that different procedures for pleurodesis -with repeated applications of the sclerosant in many cases- makes results hardly comparable in a "pooled" study. In addition, the same abovementioned problem regarding low pH in mesotheliomas might apply here, despite the fact that those cases from Bilaceroglu and colleagues were excluded from the study in the articles from Heffner and coworkers. In summary, I do believe that pleural pH still keeps its role in the management of patients with malignant pleural effusion, especially those who present with low pH/glucose levels. Although I would not exclude a single patient for pleurodesis on the sole basis of his/her low pH, taking into consideration this parameter when treating patients with MPE - together with a careful clinical evaluation- makes things easier to us in clinical practice. Francisco Rodríguez-Panadero, M.D. Send correspondence to: Francisco Rodríguez-Panadero, MD El Mirador, P.13-1ºB 41940 Tomares (Sevilla) SPAIN e-mail: frpanad@intercom.es frodriguez@hvr.sas.cica.es Burrows CM, Mathews C, Colt HG. Predicting survival in patients with recurrent symptomatic malignant pleural effusions. An assessment on the prognostic values of physiologic, morphologic, and quality of life measures of extent of disease. Chest 2000; 117:73-78. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of survival for patients with malignant pleural effusions. Chest 2000; 117:79-86. Heffner JE, Nietert PJ, Barbieri C. Pleural fluid pH as a predictor of pleurodesis failure. Analysis of primary data. Chest 2000; 117: 87-95. Rodríguez-Panadero F, Lopez Mejias J. Low glucose and pH levels in malignant pleural effusions. Diagnostic significance and prognostic value in respect to pleurodesis. Am Rev Respir Dis 1989; 139:663-667. Rodriguez-Panadero F, Lopez Mejias J. Survival time of patients with pleural metastatic carcinoma predicted by glucose and pH studies. Chest 1989; 95:320-324. Sanchez Armengol A, Rodríguez-Panadero F. Survival and talc pleurodesis in metastatic pleural carcinoma, revisited. Report of 125 cases. Chest 1993; 104:1482-1485. Chandler TM, McCoskey EH, Byrd RP, Roy TM. Comparison of the use and accuracy of methods for determining pleural fluid pH. Southern Med J 1999; 92:214-217. Rodríguez-Panadero F, Del Rey Perez JJ. Survival of malignant pleural mesotheliomas as compared to metastatic carcinomas. Eur Respir Rev 1993; 3,11: 208-210. Bilaceroglu S, Cagirici U, Perim K, et al. Corynebacterium parvum pleurodesis and survival is not significantly influenced by pleural pH and glucose level. Monaldi Arch Chest Dis 1998; 53:14-22. |
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