Lack of agreement between tonometric and gastric juice partial carbon dioxide tension

INTRODUCTION: In recent years there has been growing interest in tonometric estimation of gastric intramucosal pH (pHi). More recently, attention has focused on the gradient between intraluminal and arterial PCO(2). pHi appears to be a useful diagnostic and prognostic tool in critically ill patients, and may also be used as a therapeutic guide. However, intraluminal PCO(2) is the parameter measured to calculate pHi, and it is assumed as equivalent to the PCO(2) of the upper layers of the gastric mucosa. Direct measurement of PCO(2) in gastric juice might offer advantages over tonometry. Tonometer costs could be saved, and equilibration time would no longer be necessary. Additionally, preanalytic factors that account for poor reproducibility, such as inadequate volume of saline in the tonometer, errors in the dwell time of the sample or in the technique used to aspirate saline, mixing of the sample with tonometer dead space and delay in analysis, could be prevented. Nevertheless, to our knowledge few experimental or clinical studies have examined PCO(2) in gastric juice. Moreover, no comparison with simultaneous tonometric samples has been performed. Our goal was to compare simultaneous measurement of PCO(2) in gastric juice and in saline samples from a tonometer. Data from the present study show that gastric juice PCO(2) is systematically higher. Furthermore, differences widen at high PCO(2) values, and data dispersion becomes even more striking. Therefore, tonometric PCO(2) and gastric juice PCO(2) are not interchangeable. PATIENTS AND METHODS: The present study was approved by the local ethics committee, and informed consent was obtained from the next of kin of each patient. We studied 15 consecutive mechanically ventilated patients from a medical/surgical intensive care unit, in whom tonometric monitoring was indicated by attending physicians. All patients were receiving 50 mg intravenous ranitidine every 8 h. Gastric tonometers were filled with saline, which was extracted after 90 min of equilibration time. At the same time, gastric juice was anaerobically extracted from the aspiration port of the tonometer. The initial 20 ml was discarded. PCO(2) in both samples was measured using a blood gas analyzer (AVL 945; AVL List GMBH, Gratz, Austria). These measurements were taken at various time points in each patient, and under various haemodynamic and oxygen transport conditions, All measurements were performed with the patient fasted. Correlation between the two measurements was examined using the Bland-Altman technique. We also performed an in vitro study to quantify the precision and bias for the AVL 945. For this purpose, a stable PCO(2) in saline solution was achieved by bubbling 5% carbon dioxide calibration gas. RESULTS: We performed 112 pairs of measurements in 15 patients. Table 1 shows clinical data and the first values of arterial, tonometered and gastric juice PCO(2) for each patient. Regression analysis demonstrated a significant correlation between both methods of measuring PCO(2) (r( 2) =0.43; gastric juice PCO(2) = -28.79 + [2.55 × tonometric PCO(2)]; P < 0.0001; Fig. 1). However, the bias calculated as the mean difference of gastric juice and tonometric PCO(2) was 51 mmHg. The 95% limits of agreement were 315 mmHg (Fig. 2). For mean PCO(2) values lesser than 100 mmHg, the bias and the 95% limits of agreement were 19 and 102 mmHg, respectively. As mean PCO(2) increased, the scattering of differences widened (r( 2) =0.71; P < 0.0001). In an effort to prevent the bias related to multiple measurements per patient, we performed Bland-Altman analysis with the first measurement of each patient. After this the results remained similar (bias 55 mmHg, 95% limits of agreement 216 mmHg). The AVL 945 blood gas analyzer showed a negative bias of 0.97 mmHg and a precision of 2.13 mmHg. This bias was considered negligible, so no further correction was made to saline tonometric values. DISCUSSION: The results of the present study show that tonometric PCO(2) and gastric juice PCO(2) are not interchangeable. Gastric juice PCO(2) is systematically higher. At high PCO(2) values the differences widen, and data dispersion becomes even more marked. There is no clear cause for these observations. A possible explanation might be that tonometric PCO(2) is generated over a time interval, whereas gastric juice PCO(2) might reflect rapid changes in mucosal metabolism. Different equilibrium time could also account for data dispersion, but not for the positive bias for gastric juice. Rapid changes should occur in both directions. Another potential confounding factor is the ability of blood gas analyzers to measure PCO(2) in gastric juice. Measurement of PCO(2) in 0.9% saline is an important source of error in the estimation of pHi. Variation in PCO(2) values may occur with different PCO(2) equilibration solutions. For example, bias is -66.5% when the Nova Stat Profile 7 blood gas analyzer (Nova Biomedical, Waltham, MA, USA) measures concentration of 1.95% of CO(2) equilibrated in normal saline. However, bias changes to +45.4% when 1.95% CO(2) is equilibrated in human albumin solution 4.5%. It would not be surprising if gastric juice components such as proteins, mucopolisaccharides and others interfere with CO(2) solubility and its subsequent measurement by blood gas analyzers. In this way, intersubject and intrasubject variation in gastric juice composition could also account for data dispersion. Fiddian-Green et al [1] measured PCO(2) in gastric contents of anaesthetized dogs. They isolated the stomach from the oesophagus and the duodenum with ligatures, and washed it through a catheter with saline. Then, they instilled 250 ml 0.9% saline and took samples to measure PCO(2) and to estimate pHi. Simultaneously, mucosa pH was recorded with a microglass probe. They found a statistically significant correlation between both methods. However, data dispersion in the graph was considerable. We were able to exclude analyzer underestimation of PCO(2) in saline as the cause for the present results. In vitro performance of the AVL 945 in blood was good. It showed a negative bias less than 1 mmHg and a precision of about 2 mmHg. We cannot infer from the present data the technique that should be the gold standard for measuring PCO(2) in gastric mucosa. However, the studies that have established the normal values for pHi, prognostic changes and its uses as a therapeutic index have been performed with tonometry. Hence, more data are needed for the routine measurement of PCO(2) in gastric juice.