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A new simple tool for tonometric determination of the PCO2 in the gastrointestinal tract: in vitroandin vivovalidation studies

Boda, D.*; Kaszaki, J.; Tálosi, G.*

European Journal of Anaesthesiology (EJA): August 2006 - Volume 23 - Issue 8 - p 680-685
doi: 10.1017/S026502150600055X
Original Article

Background and objective: Following the discovery of the feasibility of assessing the adequacy of the splanchnic perfusion by means of gastrotonometry, this technique became extensively used in clinical practice and in research. At present, high-technology instruments are available for the purpose. However, there is still a need for a simple, cheap tool that is easily applicable for patients of all ages. The present article describes such a tool and presents the results of in vitro and in vivo validation measurements with it.

Methods: Balloon-free tonometric probes consisting of silicone rubber tubes were developed. In vitro measurements of the uptake of CO2 inside the probes and for comparison in a conventional ballooned intestinal tonometer were made in a closed container maintained at 37°C. In in vivo studies in anaesthetized dogs, the tonometric PCO2 values were determined with a tonometric probe and catheter introduced simultaneously into the ileum of the animals and the results were analysed by the Bland–Altman method.

Results: The in vitro equilibration studies revealed that the filling media inside the probes equilibrated rapidly with the PCO2 content of the chamber. The data obtained from the in vivo investigations with the two different methods demonstrated a statistically significant linear association (correlation coefficient: 0.778, significance: P < 0.001).

Conclusion: The new simple tonometric probe described appears to be a reliable tool with certain advantages for gastric tonometry. However, further studies are warranted before its general clinical use.

* University of Szeged, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Department of Paediatrics, Hungary

University of Szeged, Albert Szent-Györgyi Medical and Pharmaceutical Centre, Department of Surgical Research, Hungary

Correspondence to: D. Boda, Department of Paediatrics, University of Szeged, P. O. Box 471, H-6701, Szeged, Hungary. E-mail:; Tel: +36 62 545338; Fax: +36 62 545329

Accepted for publication 8 February 2006

First published online 4 April 2006

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Following the first description of gastrotonometry [1] for measurement of the partial pressure of carbon dioxide (PgCO2) in the gastrointestinal tract and the demonstration of the feasibility of the assessment of the adequacy of the splanchnic perfusion with this technique [2], it became extensively used in clinical practice, mainly to monitor the condition of patients in critical states, but also in research [3–6]. At present, high-technology instruments are available for the purpose [7–11].

Nevertheless, there is still a need for a simple, cheap tool that provides results in a short time and is easily applicable for patients in various conditions of awakeness, causing them the minimum discomfort.

We have found that these requirements can be fulfilled by a probe made entirely from silicone rubber. This article describes such a tool and presents the results of in vitro and in vivo measurements with it.

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Material and methods

Description of the new tonometric probe

The new probe consists entirely of highly permeable silicone rubber tubing. The lumen of the initial segment A is larger than that of the later segment B (Fig. 1). During measurements, the segments are held together by a 4–5 mm wide silicone rubber ring C. Segments A and B are sealed together so as to communicate with each other. Sealing is achieved at room temperature with a vulcanizing flowable silicone rubber which hardens in some minutes, creating strong adherence. The silicone rubber components used for manufacturing the probes were obtained from PeMu Plastic Industry Corporation, Solymar, Hungary, under the description Wacker R-401/80, DCL BP-50 PSI, F.BS ‘for medical purposes’.

Figure 1.

Figure 1.

Segment A is connected to a 50–70 cm long polyethylene line which serves to transfer the filling medium into the probe. After equilibrium has been attained between the CO2 content of the medium into which the probe has been inserted and the CO2 content of the filling medium (by gaseous diffusion through the permeable silicone rubber tubing), the filling medium is transferred from segment B to a CO2 monitoring device. Either room air or saline-bicarbonate solution (containing 145 mmol NaCl + 25 mmol NaHCO3) was used as filling medium. With room air as filling medium, a Sidestream Microcap Handheld Capnograph, (Oridion Medical Ltd, Jerusalem, Israel) was used as monitoring device. With saline-bicarbonate solution as filling medium, an ABL 700 Radiometer (Copenhagen, Denmark) served as monitoring device.

Probes were produced in two lengths (the distance between the fastening ring and the tip of the probe): 70 cm for adults and 30 cm for infants and children, with lumen diameters of 2 mm and 1.5 mm respectively, for segment A, both with wall thicknesses of 0.5 mm. The lumen diameter of segment B was 0.8 mm and its wall thickness was 0.2 mm. The results of the equilibrium measurements with the silicone rubber probes and room air as filling medium were compared with those obtained with the conventional ballooned intestinal tonometer (TRIP Tonometrics Inc., Worcester, MA).

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In vitro investigations

Air tonometry.

For measurements of the in vitro uptake of CO2 into the probes, a glass container was used as an equilibration chamber. The probes or intestinal tonometer were inserted into this up to fastening ring C; the balloon part of the intestinal tonometer was closed in an airtight manner. The glass container was perfused with air containing CO2 at 5.32 kPa, provided from gas cylinders at a flow rate of 5 L min−1 and maintained at 37°C. Room air was used as filling medium. In the examination with the TRIP catheter, the balloon was inflated with 2.5 mL air. Validation of the in vitro uptake of CO2 by the filling medium was performed for 1, 2, 3, 5, 7 and 10 min for both probes and the conventional balloon catheter and also for 30, 60 and 90 min for the catheter. At each time point, four parallel measurements were made. The PCO2 value of the container was checked every 30 min. This value was used as the reference for the measurement data. After the defined time intervals, a portion of the filling medium was aspirated to the monitor at a flow rate of 60 mL min−1 and the result was displayed by the capnograph.

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Saline tonometry.

In the measurements of the in vitro uptake of CO2 by saline-bicarbonate solution as filling medium, the probe was filled at time 0 up to ring C, and after the predetermined time was evacuated by manual aspiration with a syringe. The fluid was collected according to the manufacturer’s instructions, inside ‘clinitube’ capillary sampling tubes positioned after segment B, the tubes were tightly capped, and the contents were analysed for PCO2 as usual. All in vitro measurement data obtained after the given equilibration times were expressed as percentages of the reference value.

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In vivo investigations

These experiments were approved by the Animal Investigation Committee of the University of Szeged. 25 dogs (12–16 kg bodyweight) were anaesthetized with intravenous pentobarbital and endotracheally intubated, but breathed spontaneously. Body temperatures of the animals were monitored throughout the experiments. After a median laparotomy, the root of the superior mesenteric artery (SMA) was dissected free. An ultrasonic flow-probe (Transonic Systems Inc., Ithaca, NY, USA) was placed around the exposed SMA to measure the mesenteric blood flow. A branch of a tributary of the ileal vein supplying the terminal part of the ileum was cannulated with 2-F polyethylene catheter to take blood sample and measure mesenteric venous pressure. The peripheral arterial and mesenteric venous pressures (Pressure transducer, mode P23 Db; Statham Instruments, Los Angeles, California), SMA blood flow were monitored and registered with a computerized data-acquisition system (Haemosys 1.17 Experimetria Ltd, Budapest, Hungary). Mesenteric vascular resistance (MVR) was calculated from standard formula.

A TRIP catheter and a tonometric probe (with 1.5 mm lumen diameter) were introduced simultaneously into the cavity of the terminal part of the ileum. The TRIP catheter was filled with 2.5 mL of normal saline solution, and capped. The tonometer probe was filled with saline-bicarbonate solution. After equilibration for 30 min, the TRIP catheter was evacuated according to the manufacturer’s directions. After removal and discarding of a 1 mL deadspace volume, the saline was aspirated and analysed for PCO2. The adjusted PCO2 value was obtained by multiplying the measured PCO2 by the correction factor provided by the catheter manufacturer for saline tonometry, given for an equilibration time of 30 min. Saline-bicarbonate solution samples from the tonometer probes were collected at the same time as the filling medium from the TRIP catheters into the Radiometer ‘clinitube’ capillary sampling tubes and were analysed for PCO2 without adjustment. In a pilot study five dogs were tested with 90, 60 and 30 min equilibration times. After the correction of the PCO2 values of the TRIP catheter, calculated with the help of the manufacturer’s correction factor, no significant difference was found either between the tests with various equilibration times or between the values of the two catheters. According to this, and also because of practical reasons we chose the shorter, 30-min-long equilibration period. (The results of these animal experiments served as base-line data for further comprehensive hypoxic-reperfusion studies, which will be reported elsewhere.)

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Statistical analysis

The in vitro CO2 uptake data measured after various equilibration times with the different tonometers and filling media were calculated as mean and standard deviation of the results of the four parallel measurements. The bias (the mean difference between the measured in vivo values), as a marker of the accuracy, and the standard deviation (calculated from bias data), as a marker of the precision, were calculated as described by Bland and Altman [12]. The data obtained with the probe and TRIP catheter was analysed via Pearson’s coefficient of correlation and its significance. During the in vivo pilot studies and the haemodynamic stability measurements, one way repeated measures analysis of variance was performed within the groups, while one way analysis of variance was calculated between the parallel measurement results of the two different tonometric catheters.

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Experimental in vitro CO2 uptake data after given equilibration times for the probe with a lumen diameter of 1.5 mm and the TRIP catheter are depicted in Figure 2. In vitro CO2 uptake results expressed as percentages of the reference data under the various experimental conditions are presented in Table 1.

Figure 2.

Figure 2.

Table 1

Table 1

The data reveal that the time required for the in vitro uptake of CO2 from the closed equilibration chamber into the tonometric probes was very short. Equilibrium was virtually fully achieved within 10 min for both the 1.5 mm and 2 mm lumen diameter probes with either room air or saline-bicarbonate solution as filling medium. However, as previously observed under different experimental conditions [13], the time required for equilibrium to be attained was significantly longer when the solution was applied as filling medium. The equilibrium with room air within the conventional catheter was fairly fast, similarly as published earlier [13,14], as 91.4% of the equilibrium level being attained after 20 min and the full equilibrium was achieved at 90 min.

Bias and precision data obtained by Bland and Altman analysis of the results of the in vivo studies involving simultaneous measurements with the tonometric probe and TRIP catheter are depicted in Figure 3. In the majority of measurements the tonometric PCO2 values obtained with the TRIP catheter were definitely lower than those obtained with the tonometric probe (mean difference = −0.416 kPa, and SD = 0.617) and the correlation coefficient (R = 0.778) between these data indicated a statistically significant linear association (P < 0.001). During the 30-min-long equilibration period the mesenteric circulation of the animals was stable. There was not any significant change regarding either the SMA blood flow values (from 264.941 ± 110.599 to 251.328 ± 111.863 mLmin−1; mean ± standard deviation) or MVR values (from 0.579 ± 0.283 to 0.610 ± 0.319 mmHg mL−1 min−1; mean ± standard deviation).

Figure 3.

Figure 3.

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Both the production and the use of this new tonometric probe are very simple. The probes used in the present research were produced under laboratory circumstances by a technician, but they are also suitable for serial industrial manufacturing. One of the advantages of the tool is the short time necessary for equilibration between the CO2 contents of the gastrointestinal tract and the filling medium. This is due to the very high permeability of the silicone rubber for gases, but not for other substances. The gaseous exchange is carried out over the total length of the wall of the inserted segment of the probe. The comparatively low volume of the filling medium, determined by the small dimensions of the probes, is an additional factor in the rapidity of the gaseous equilibration process. A further advantage of the presented method is the simplicity of the measuring process. This is particularly so for measurements with room air as filling medium, the use the Microcap Capnograph furnishing excellent accuracy and reproducibility in the monitoring of the gaseous content of the probe. Saline-bicarbonate solution may be preferable as filling medium in those units where only blood–gas analysis equipment is available for monitoring. However, a liquid filling medium is necessary also in cases where extremely high gastric PCO2 levels are expected, because the maximum level of measurement of capnometers is generally 100 mmHg CO2. Equilibration inside a probe containing a liquid filling medium is definitely slower than for a gaseous one. The bicarbonate content of the liquid filling medium prolongs the equilibration, but solutions containing bicarbonate are more stable as concerns the dissolved CO2 content [14,15]. As measurements with saline involve a larger standard deviation, parallel measurements are advisable. These disadvantages are compensated by the circumstance that the collection of the equilibrated material by our proposed method is simple, without loss of the CO2 content of the sample. Since, as we mentioned, in the case of saline as a filling material, the equilibration time is longer, than in the case of air [9,13,14], for a correct comparison of the new tonometric probe and the TRIP catheter we chose to test the TRIP catheter with air, the medium of quicker equilibrium properties and good accuracy. The in vitro uptake of CO2 by the TRIP catheter with room air as filling medium inside an equilibration chamber was fairly fast in our in vitro experimental circumstances, partly because 2.5 mL air was applied instead of the generally used 5.0 mL.

The data obtained by the two methods in the in vivo validation study indicated appropriate parallelism. However, the values determined with the TRIP were consistently lower than those with the tonometric probe. This may be a consequence of incomplete equilibration inside the balloon of the catheter, or of some change in the correction factor under the given circumstances [13].

The objection may be raised that the new method does not measure exclusively the gastric PCO2. This is true because during the measurement the probe is only partially inside the stomach. However, a number of studies have proved that measurements in other parts of the gastrointestinal tract, in the oesophagus and in the mouth yield values identical to the gastric PCO2 [8,10,16]. Accordingly, we consider that the presented method furnishes data characteristic of the gastrointestinal tract.

In further examinations currently in progress, we have applied the method in humans, the results demonstrating that use of the new tonometric probe meets the given aims. Naturally, further wide-ranging clinical and experimental studies are needed before the method can be recommended for use in general clinical practice.

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We would like to thank Tamás Juhász for his kind assistance during the animal experiments and Ilona Szécsi for her technical assistance. We are also indebted to the chairman of the Department of Paediatrics, Sándor Túri MD, PhD, DSc for his kind help and the financial support of the Foundation for the Research and Education of the Department of Paediatrics, University of Szeged. The animal experiments were supported by a grant from the Hungarian Research Found (OTKA T035275).

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© 2006 European Society of Anaesthesiology