Comparison of Pleural Fluid ph Values Obtained Using Blood Gas Machine, ph Meter, and ph Indicator Strip*
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1 Comparison of Pleural Fluid ph Values Obtained Using Blood Gas Machine, ph Meter, and ph Indicator Strip* Dong-sheng Cheng, MD; R. Michael Rodriguez, MD; Jeffrey Rogers, RRT; Marvin Wagster; DanielL. Starnes, MD; and Richard W. Light, MD, FCCP Study purpose: The purpose of this study was to compare the pleural fluid ph values obtained with a blood gas machine (phhg), with a ph meter (phmet), and with a ph indicator strip (phstrip), to determine if the pleural fluid ph measured by a ph meter or a ph indicator strip was sufficiently accurate for clinical decisions. Methods: The pleural fluid ph was determined, within 20 min after being collected anaerobically, by a blood gas machine (CIBA-Corning model 288), ph meter (Corning ph meter 610A), and ph indicator strip (Baxter Diagnostic) following routine laboratory procedures in 50 pleural fluids. Pleural fluid ph was determined in seven additional samples with the blood gas machine and a ph meter at 25 and 37 C respectively, initially, and after 30 min. Results: The mean phhg (7.42 ± 0.01) was significantly less than the mean phmet (7.58 ± 0.02) or the mean phstrip (8.23 ± 0.06). There were significant differences between the phhg and the phmet (p < 0.001), and between the phhg and the phstrip (p < 0.001). Analysis of the additional seven samples demonstrated that when the blood gas machine was set at 25 C, the phbg (phbg = 7.54 ± 0.02) and the phmet (7.53 ± 0.01) were almost identical. Conclusion: When the pleural fluid ph is going to he used for decision making, only the ph values provided by the blood gas machine are sufficiently accurate. (CHEST 1998; 114: ) Key words: blood gas machine; empyema; ph; ph meter; pleural fluid Abbreviations: phbg = pleural fluid ph measured by blood gas machine; ph met = pleural fluid ph measured by ph meter; phstrip = pleural fluid ph measured by indicator strip he measurement of pleural fluid ph is useful in T the diagnosis and management of patients with pleural effusion. 1 2 The first article that suggested that a ph < 7.20 was useful in identifying complicated parapneumonic effusions used a blood gas machine to measure the ph (phbg). 2 Subsequent articles concerning the utility of pleural fluid ph measurements also have used blood gas machines. 3-6 With this method, the samples are collected anaerobically directly into a hepalinized syringe, kept in ice, immediately transferred to the laboratory, and the ph is determined with a blood gas machine. 3 However, it has been our observation that the methods by which the pleural fluid ph is measured vary markedly from laboratory to laboratmy. Many laboratories are hesitant to measure the pleural fluid ph *From the Departments of Medicine, Radiology, and Pathology, Saint Thomas Hospital and Vanderbilt University, Nashville, TN. Supported b y Saint Thomas Foundation, Nashville, TN. Correspondence to: Richard W. Light, MD, FCCP, Director of Pulmonan1 Disease Program, Saint Thomas Hospital, PO Box 380, 4220 Harding Rd, Nashville, TN 37202; rlight@ stthomas. org via the blood gas machine and alternatively measure the pleural fluid ph via a ph meter (phmet) or ph indicator strip (phstrip). The purpose of the present study was to determine if the pleural fluid ph, as determined by a ph meter or a ph indicator strip, was sufficiently accurate. We hypothesized that sufficiently accurate pleural fluid ph measurements could be obtained only via a blood gas machine. MATERIALS AND METHODS Between September 1, 1997, and November 30, 1997, we prospectively studied 50 pleural fluid specimens from 45 consecutive patients who underwent thoracentesis under ultrasound guidance in the Department of Radiology (5 patients had bilateral pleural effusions ). The study was approved by the Institutional Review Board of Saint Thomas Hospital and prior to the study all patients signed an informed consent. The pleural fluid was obtained using ultrasonic guidance and a 17 -gauge plastic catheter. The pleural fluid was collected directly into a heparinized blood gas syringe and was maintained anaerobically. The syringe containing the pleural fluid was immediately placed in ice for transfer to the Laboratory Service. The pleural fluid ph was measured via the three different methods within 20 min of the thoracentesis. 1368
2 The pleural fluid ph was determined by the following three methods: (1) via blood gas machine (CIBA-Corning Model 288; Coming Glass Works; Norwood, MA) (phbg) at body temperature (37 C); (2) via ph meter (Corning ph meter 610A; Corning Glass Works) (phmet) at room temperature (25 C); and (3) via ph indicator strip (Baxter Diagnostic; Deerfield, IL) (phstrip) at room temperature (25 C). The pleural fluid Pco 2 was also determined by the same blood gas machine a t the same time. A filter (Clot Catcher, CIBA Corning) to capture debris was inserted between the syringe and the blood gas machine. Before each measurement, the blood gas machine was calibrated automatically with the standard solution and the ph meter was calibrated vvith a standard ph solution (ph = 7.00). The stated accuracy for measuring ph via the three different methods is for the blood gas machine, 0.01 for the ph meter, and 1.0 for the ph indicator strip. After the first 50 specimens were analyzed, we intensively studied 7 additional specimens in an attempt to determine why the ph readings with the blood gas machine and the ph readings with the ph meter did not agree more closely. For each of the seven specimens, we measured the ph via the blood gas machine at 25 and 37 C. We also measured the ph via the ph meter at 25 C initially and at 10-min intervals thereafter for a total of 30 min. After the last measurement was made with the ph meter, the s pecimen was taken from the cuvette of the ph meter and analyzed via the blood gas machine. Statistical Methoru The data are reported as the mean ::':: SEM unless othervvise noted. The usefulness of the ph values obtained with the ph meter and with the ph indicator strip were assessed by calculating the bias and precision of the phmet and the phsttip relative to the phbg. The bias is the mean difference between the phbg and the ph met or the phstrip. The precision is the SD of the bias. The correlations for three methods of determining ph were analyzed with linear regression. Alpha was set at The analysis was performed with specific software (Sigma stat V3.0 program; Jande! Scientific; San Rafael, CA). RESULTS Fifty samples were collected from 45 different patients (5 patients had bilateral pleural effusions). The diagnoses in the 45 patients included 19 effusions postcoronary artery bypass surgery, 10 congestive heart failure, 9 malignant pleural effusions, 5 parapneumonic effusions, and 2 miscellaneous effusions. Thirty-five pleural fluid samples were exudates and 15 were transudates by the criteria of Light et ap Both the ph meter and the indicator strip provided mean ph values that were significantly higher (p < 0.001) than the ph from the blood gas machine. The mean phbg was 7.42 with a SE of 0.01 and a range of 7.17 to The mean phmet was 7.58 ± 0.02, and the mean phstrip was 8.23 ± Although there was a significant correlation (r = 0.56, p < ) between the ph measured with the blood gas machine and the ph measured with the ph meter (Fig 1), the ph meter gave consistently higher ph values than did the blood gas machine. The bias for pleural fluid ph measured with the ph meter as compared with the pleural fluid ph measured with the blood gas machine was 0.15 witl1 the ph meter providing a higher ph value. The precision for measuring the pleural fluid ph with the ph meter as compared with the pleural fluid ph measured with the blood gas machine was The degree of inaccuracy was comparable in all subgroups. The ph indicator strip was less accurate than the blood gas machine or the ph meter in measuring the phbg _.-. - n=50 r-0.56 p<0.001 'Line of identity Linear regression ~ , , , , PH met FIGURE l. phbg vs phmet for all pleural fluid specimens. The solid line is the line determined by linear regression analysis. The dotted line is the line of identity. CHEST I 114 I 5 I NOVEMBER,
3 pleural fluid ph (Fig 2). Although there is a significant relationship (r = 0.32, p = 0.02) between the ph as measured by the indicator strip and the blood gas machine, the indicator strip was not accurate in measuring the pleural fluid ph. The bias for the pleural fluid ph measured with the indicator strip as compared with the blood gas machine was 0.81, with the indicator strip providing a higher ph value. The precision for measuring pleural fluid ph with the indicator strip was 0.40 (Table 1). The pleural fluid phbg was significantly correlated (r = 0.63, p < 0.001) vvith the pleural fluid Pco 2. The pleural fluid Pco 2 values ranged from 30 to 80 mm Hg and were in the range that one would expect for arterial ph values. There was not a significant relationship between the difference in the phbg and the phmet and either the pleural fluid HC0 3 - (r = 0.002, p = 0.99) or the pleural fluid Pco 2 (r = 0.18, p = 0.21 ). When the seven additional samples were studied in more depth, the explanation for the discrepancy between the phbg and the ph met became apparent. If both the blood gas machine and the ph meter were set at 37 C, the mean phbg was much lower than the mean phmet (Table 2). However, if both of the machines were set at a temperature of 25 C, the mean phbg (7.54) was almost identical to the mean phmet (7.53) (Table 2). In none of the seven cases did the phbg differ from the phmet by > 0.03 when they were measured at 25 C. The mean phbg measured at 25 C (7.54) was higher than the mean phbg measured at 37 C (7.36) because the mean Table l-the Bias and Precision Between phbg and phmet or phstrip ph met- phbg phstrip - phbg Bias Precision (SD of Bias) Pco 2 was lower at 25 C (31.8 mm Hg) than it was at 37 C (53.8 mm Hg) (Table 2). When the pleural fluid was maintained in the cuvette of the ph meter for 30 min, the phmet became progressively higher (Table 2) because the Pco 2 decreased with time (Table 2). The mean phmet increased from 7.54 to 7.71 while the mean Pco 2 decreased from 31.8 to 17.6 mm Hg. When the fluid from the cuvette was reanalyzed by the blood gas machine, the phbg at 25 C had increased from 7.53 to The phbg a t 25 C after 30 min was within 0.07 units of the phmet at 25 C after 30 min in all cases. When the incubated fluid was measured with the blood gas machine at 37 C, the ph was significantly higher than it had been at zero time (Table 2). The Pco 2 measured at 37 C had decreased from 53.8 to 29.9 mm Hg. DISCUSSION The results of the present study demonstrate that the ph values obtained with either the ph meter or phbg 7.7 i ~ Line of identity n=50 r= p= '\ PHstrip Linear regression FIGURE 2. phbg vs phstrip for all pleural fluid specimens. The solid line is the line determined by linear regression analysis. The dotted!me IS the!me of 1dentJty. 1370
4 lr)..-<ocj'1"<.co>t-o> a 6 t r. i o o < D o : i.. r ~...tc'ic")-.:::f"c")c'ic')c't O':lOOC'lQ)t-l()l()<;.O 0 ~ 0 0 c i c 0 6 t... = rl...-trlc'ic\lrlc'lrl c-lo><.co>oc'lcoo..... ; r : C! ) a. > ~ ~ c r )..... ; C')C')c-lC'JC'lc-lc-lC'l COOOl!)"f...-triOO o ; j ~ l f ) r - : t - = r l a ) C ' ) l() <:.0 ~ <.0 l() ~ ~ 11) ffio-10-loomrl'-.::t'...-t t--gl!)l()c.oooc.ot ~ r - : r - : r - : t - = r - : t - = t - = O>OCJC'-lc-1'1"'1"lr)C'l <. C <. C ~ ' 1 " ~ <. C ~ l r ) r-:r-:r-:r-:r-:r-:r-:r-: CMO)C()C"),..."'<::'tt >lr)lr)<.COCJ<.Ctr-: t...: r-: r-: r-: r-: r-: r-..: t- c.o 0 0 C'l C'-l C"),..., OOOCJ<.C<.C<.COO<.Ct- 1--._:.-: r-: r-: r-:.-: r-: r-: C " ' ) C \ J C " ) Q ) C ' l r l ~ C ' ) l() }!") l(') ~ l() o:..c: lj') lj') ~ r - : r - : r - : r - : r - : r - : r - : H")l()C'IO:...-tellf)"i"' H") l() lf) ~ lf) C.O lf) l() r--.:r-:r-:r-:r-:r-:r-:r-: C ' l N ~ O > c - l C ~ C ' l l r ) l r ) l r ) ~ l r ) <. C l r ) l r ) r-:.-...:.-...: r-: r-: r-: r-: r-: t - t - " " ' " r l C ' ) ~ o ;,! ) (. Q C " ) C " ) C ' ) C ' ) C ' ) ~ C " " ) C ' ) r-:r-:r-:r-:r-:r-:r-:r-: the ph indicator strip are not sufficiently accurate to guide therapeutic decisions. The mean values of the pleural fluid ph measured with the ph meter (7.58 :±: 0.02) and ph indicator strip (8.23 :±: 0.06) were higher than the mean ph with the blood gas machine (7.42 :±: 0.01) (p < 0.001, respectively). There are two separate explanations for the ph meter providing higher ph values. First, the ph meter measures the ph at 25 C rather than at 37 C. If the blood gas machine is set to measure the ph at 25 C, the ph values on the two different machines are nearly identical (Table 2) if the samples are measured simultaneously. Second, if the sample in the ph meter cuvette is allowed to stand for even a few minutes, the measured ph will increase because the Pco 2 in the fluid decreases. The level of the pleural fluid ph is frequently used to assist in making decisions regarding patients with pleural effusions. In the differential diagnosis of pleural effusions, the presence of a low pleural fluid ph ( < 7.20) limits the diagnostic possibilities.l 2 In the treatment of patients with parapneumonic effusion, the pleural fluid ph is useful in identifying those patients who will need tube thoracostomy for the resolution of their effusion In the treatment of patients with malignant pleural effusion, the presence of a low pleural fluid ph indicates that pleurodesis is less likely to be successful. 2 6 In addition, the prognosis of patients with malignant pleural effusion is poorer if the pleural fluid ph is low. 2 9 The present study demonstrates that the ph meter (Coming ph meter model 610A) is not sufficiently accurate to measure pleural fluid ph. The precision for this ph meter using the phbg as a gold standard was This indicates that the 95% confidence interval for the phbg is the phmet :±: This accuracy is inadequate for clinical use. To our knowledge there have been no other articles assessing the accuracy of this ph meter or any other ph meter in measuring the pleural fluid ph. The present study also demonstrates why the ph meter (Corning) does not accurately reflect the pleural fluid ph. The ph meter measures the ph at 25 C rather than at 37 C. Therefore, the Pco 2 is lower and the ph is higher with the ph meter than with the blood gas machine. However, as demonstrated in Table 2, if the blood gas machine is set at a temperature of 25 C, the ph values measured on the two different machines are nearly identical if they are measured simultaneously. We attempted to set this ph meter at 37 C rather than 25 C and found that the ph values at the setting of 37 C were not much different than those when it was set at 25 C. The present study also demonstrates that the pleural fluid ph, as measured by this ph meter, increases if the sample is allowed to stand for more CHEST /114/5/ NOVEMBER,
5 than a couple minutes before the measurement is performed. The ph increases in this situation because the Pco 2 decreases, presumably due to carbon dioxide escaping into the air. Can a ph meter rather than a blood gas machine ever be used for the accurate measurement of the pleural fluid ph? Our study demonstrates that the phmet at 25 C is very close to the phbg at 25 C if the ph is measured immediately after the fluid is placed in the cuvette of the ph meter. Using the ph determined by the ph meter, one could obtain a close estimate of the ph that would have been obtained with a blood gas machine if they would extrapolate the ph back to 37 C. Unfortunately, one would expect errors to be frequent with such manipulations. Alternatively, it is possible that a ph meter could be developed that would measure the ph accurately at 37 C. To our knowledge, such a device is not available. In conclusion, the routine measurement of the pleural fluid ph via a ph meter is not sufficiently accurate for clinical decision making. The ph meter provides ph values that are too high because it measures the ph at 25 C rather than at 37 C. Accordingly, the Pco 2 is lower and the ph is higher. The inaccuracy of the ph meter is further increased due to the fact that carbon dioxide escapes from the cuvette during its measurement. If clinical decisions are going to be based on pleural fluid ph measurements, pleural fluid should be withdrawn anaerobically into a heparinized syringe and taken immediately to the laboratory for measurement of the ph with a blood gas machine at 37 C. If the laboratory is fearful that particulate matter in the pleural fluid will damage the membranes of the machine, a filter can be placed between the syringe containing the pleural fluid and the blood gas machine as was done in the present study. It should also be noted the ph as measured by indicator strip is not sufficiently accurate as shown in this and previous reports. 10 REFERENCES 1 Light RW. Pleural diseases. 3rd ed. Baltimore, MD: William & Wilkins, Sahn SA. The pleura. Am Rev Respir Dis 1988; 138: Light RW, MacGregor MI, Ball WC, et al. Diagnostic significance of pleural fluid ph and l,aco 2. Chest 1973; 64: Light RW, Girrard WM, Jenkinson SG, et al. Parapneumonia effusion. Am J Med 1980; 69: Potts DE, Levin DC, Sahn SA. Pleural fluid ph in parapnemonic effusions. Chest 1976; 70: Rodriguez-Panadero F, Mejias JL. Low glucose and ph levels in malignant pleural effusion: diagnostic significance and prognostic value in respect to pleurodesis. Am Rev Respir Dis 1989; 139: Light RW, MacGregor MI, Luchsinger PC, et a!. Pleural effusions: the diagnostic separation of transudates and exudates. Ann Intern Med 1972; 77: Heffner JE, Brown LK, Barbieri C, et al. Pleural fluid chemical analysis in parapneumonic effusions: a meta-analysis. Am J Respir Crit Care Med 1995; 151: Rodriguez-Panadero F, Mejias JL. Survival time of patients with pleural metastatic carcinoma predicted by glucose and ph studies. Chest 1989; 95: Lesho EP, Roth BJ. Is ph paper an acceptable, low-cost alternative to the blood gas analyzer for determining pleural fluid ph? Chest 1997; 112:
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