Gastric mucosal end-tidal PCO2 difference as a continuous indicator of splanchnic perfusion

A. Uusaro*, P. Lahtinen, I. Parviainen and J. Takala1

Critical Care Research Program, Department of Anesthesiology and Intensive Care, Division of Critical Care, Kuopio University Hospital, Kuopio, Finland 1Present address: Department of Intensive Care Medicine, University Hospital of Bern (Inselspital), Bern, Switzerland

Accepted for publication: May 20, 2000


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Gastric mucosal and arterial blood PCO2 must be known to assess mucosal perfusion by means of gastric tonometry. As end-tidal PCO2 (PE'CO2) is a function of arterial PCO2, the gradient between PE'CO2 and gastric mucosal PCO2 may reflect mucosal perfusion. We studied the agreement between two methods to monitor gut perfusion. We measured the difference between gastric mucosal PCO2 (air tonometry) and PE'CO2 (=DPCO2gas) and the difference between gastric mucosal PCO2 (saline tonometry) and arterial blood PCO2 (=DPCO2sal) in 20 patients with or without lung injury. DPCO2gas was greater than DPCO2sal but changes in DPCO2gas reflected changes in DPCO2sal. The bias between DPCO2gas and DPCO2sal was 0.85 kPa and precision 1.25 kPa. The disagreement between DPCO2gas and DPCO2sal increased with increasing dead space. We propose that the disagreement between the two methods studied may not be clinically important and that DPCO2gas may be a method for continuous estimation of splanchnic perfusion.

Br J Anaesth 2000; 85: 563–9

Keywords: gastrointestinal tract, mucosal perfusion; monitoring, splanchnic perfusion


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Gastrointestinal hypoperfusion may lead to organ dysfunction, increased mortality and increased cost of care of critically ill patients.13 However, we do not have a practical method for assessment of gut mucosal perfusion.46 Gastrointestinal saline tonometry is still controversial and not routinely used in critical care, for several reasons. Originally the gastric tonometer was designed to measure gastric mucosal PCO2 which was then used to calculate gastric mucosal pH (pHi).7 8 Gastric mucosal pH was assumed to reflect splanchnic perfusion and oxygenation. However, the calculation of pHi necessitates both taking arterial blood sample to measure bicarbonate concentration and the use of a cumbersome formula. In addition, experimental and clinical studies have shown that the calculation of pHi using arterial blood bicarbonate concentration may be incorrect, the use of pHi alone ignores the effects of systemic acid–base status on gastric mucosal pH and there is also a potential bias from the measurement of saline PCO2 with different blood gas analysers.911

The measurement of gastric mucosal PCO2 has become more popular in experimental and clinical studies and avoids the potential problems of pHi. An automated gas tonometer was developed to measure gastric mucosal PCO2, so that repeated analysis of saline samples for PCO2 and the potential errors of analysis are eliminated and the measurements are now easier.10 12 13 Clinical and experimental studies have validated gas tonometry using conventional saline tonometry as a reference.1416 However, the gradient between systemic PCO2 and gastric mucosal PCO2 is the variable of interest that reflects mucosal perfusion.4 17 Repeated arterial blood samples are needed to measure blood PCO2 which may not be feasible in clinical practice and may make clinicians unwilling to use gastric tonometry. On the other hand, without continuous or semi-continuous measurements important episodes of splanchnic hypoperfusion may not be noticed.

The partial pressure of carbon dioxide (CO2) of end expiratory gas (end tidal CO2, PE'CO2) can be used to estimate arterial PCO2.18 PE'CO2 is routinely monitored in intubated patients although PE'CO2 does not necessarily accurately represent arterial CO2 if the proportion of dead space ventilation is increased as in patients with lung injury.19 However, the difference between PE'CO2 and gastric mucosal CO2 (measured by gas tonometry) could reflect gastric mucosal perfusion continuously or semi-continuously without a need for laboratory testing. We hypothesized that this would be the case even in patients with increased physiologic dead space, providing that the dead space remains relatively constant. To our knowledge this possibility has not been tested. We designed our study to investigate if the gradient between gastric mucosal PCO2 and end-tidal CO2 can be used to monitor gastric mucosal perfusion.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The study was approved by the Ethics Committee of the Kuopio University Hospital and a written informed consent was obtained either from the patient (patients recovering from cardiac surgery), or from the relatives (patients with acute lung injury, ALI). We studied 10 patients who were recovering from cardiac surgery (and who did not have lung injury) and 10 patients who had ALI. We defined ALI as PaO2/FIO2 less than 200 mm Hg (26.7 kPa). We studied patients with ALI because increased dead space ventilation increases the difference between arterial CO2 and PE'CO2 and this may reduce the accuracy of gastric-mucosal end-tidal PCO2 difference to indicate gastric-mucosal arterial PCO2 difference (gastric-mucosal end-tidal PCO2 tends to be higher than gastric-mucosal arterial PCO2 difference). All patients were intubated, mechanically ventilated (Servo 900C, Siemens AB, Solna, Sweden) and sedated as clinically appropriate during the measurements.

Two gastric tonometers, a gas and a saline tonometer, were inserted in each patient via mouth. The correct positions of the tips of the tonometers were confirmed by x-ray. We used continuous gastric suctioning but H2-blockers were not given to any patient.20 21 Gas tonometer (Tonocap®, Datex/Instrumentarium, Helsinki, Finland) was used to measure gastric mucosal partial pressure of carbon dioxide (PrCO2) in 15 min intervals during the 8 h study period. In Tonocap® the device fills the tonometer TRIP-catheter (Tonometrics, Datex/Instrumentarium, Finland) with 5 ml gas (air) and a sample of this gas is drawn after an equilibration period. The PCO2 of this sample is measured by Tonocap® using the same standard infra-red method that is used to measure the partial pressure of end-tidal CO2 (PE'CO2). A time dependent correction factor of 1.12 (for incomplete equilibration time of 15 min) for the mucosal PCO2 (PrCO2) was used. The Tonocap® was calibrated before the measurements according to the manufacturer’s recommendation using calibration gas (5±0.03% CO2 in 95% oxygen, Datex/Instrumentarium, Helsinki, Finland). The mean value of PrCO2 was calculated each hour to allow comparison between gas and saline tonometers. End-tidal CO2 was measured from the expired air immediately distal to the intubation tube using an AS3 monitor (Datex/Instrumentarium, Helsinki, Finland). The gastric-mucosal end-tidal PCO2 difference (DPCO2gas) was calculated by subtracting end tidal PCO2 from gastric mucosal PCO2 (as measured by Tonocap®).

We measured PrCO2 using conventional saline tonometry and arterial PCO2 each hour throughout the study. With the saline tonometry PrCO2 was measured using 2.5 ml of sodium chloride in the tonometer balloon. Both the saline and arterial blood samples were analysed within 2 min of withdrawal using a blood–gas analyser (ABL-520, Radiometer, Copenhagen, Denmark). We did not take into account the potential bias related to blood gas analyser.10 A time dependent correction factor of 1.13 (for incomplete equilibration time of 60 min) for the PrCO2 was used with saline tonometry and the measurements were carried out according to the manufacturer’s recommendations. Gastric-mucosal arterial PCO2 difference (DPCO2sal) was calculated by subtracting arterial PCO2 from gastric mucosal PCO2 (as measured by saline tonometry). We regarded this difference (DPCO2sal) as the reference to represent true systemic-gastric mucosal PCO2. In addition to the comparison between DPCO2sal and DPCO2gas, we also compared the differences between gastric mucosal PCO2 (measured using gas tonometry) and arterial blood PCO2 or end-tidal PCO2. This was done to eliminate potential errors in the saline technique, such as those related to blood–gas analyser bias, inappropriate equilibration factors and tonometer catheter dead space effects.

Arterial end-tidal PCO2 difference was calculated by subtracting end-tidal PCO2 from arterial blood PCO2. This gradient was calculated to indirectly estimate dead space ventilation of the lung. The higher the gradient between arterial (PaCO2) end-tidal PCO2 (PE'CO2), the higher is the dead space ventilation of the lung. The fraction (%) of dead space ventilation (VD/VT) was estimated using the following equation: VD/VT = (PaCO2PE'CO2)/PaCO2.

Statistical analysis
Our main interest in the analysis was to study the agreement between DPCO2gas and DPCO2sal. We studied this agreement using the method described by Bland and Altman.22 In addition to graphical display we also calculated bias (the mean difference between the two measurements) and precision (SD of the bias) for this comparison. Because we repeated measurements, the effect of time, and particularly time by group (DPCO2gas or DPCO2sal) interaction, was analysed using general linear model with repeated measures option (statistical package SPSS for Windows, version 7.5). This analysis was carried out to test whether changes in gastric-mucosal systemic PCO2 difference during the study were similar for DPCO2gas and DPCO2sal. We used regression analysis to study the correlation between two variables and t-test when appropriate. A P-value of <0.05 was considered statistically significant. Results are given as mean (SD).


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The fraction of dead space ventilation was 11 (7)% (mean (SD)) in CABG patients and 25 (12)% in patients with ALI (P<0.001). The mean values and standard deviations of gastric mucosal end tidal PCO2 difference (DPCO2gas) and gastric mucosal arterial PCO2 difference (DPCO2sal) for each hour during the whole study period are shown in Figure 1. When all patients were analysed together there was a significant effect of time (P<0.01) but no time by group interaction (P=0.33) indicating that the changes of gastric mucosal-systemic PCO2 difference were similar for DPCO2sal and DPCO2gas. Also in this analysis the group effect was not significant (P=0.084). DPCO2gas tended to be greater that DPCO2sal both in patients with ALI and in patients recovering from cardiac surgery. However, the difference between the two methods was greater in patients with ALI. Figure 2 shows that the agreement between the two methods to reflect gastric mucosal systemic PCO2 is reasonably good, except for higher mean gastric mucosal systemic PCO2 differences. With greater mean gastric mucosal-systemic PCO2 differences, DPCO2gas tends to overestimate DPCO2sal (Fig. 2). The bias and the precision of this comparison are 0.85 and 1.25 kPa, respectively. The comparison between gastric mucosal PCO2 (measured by gas tonometry) and arterial blood PCO2 or end-tidal CO2 is shown in Figure 3. The difference between gastric mucosal PCO2 (gas tonometry) and end-tidal CO2 was higher (P=0.022, ‘group’ effect) than the difference between gastric mucosal PCO2 (gas tonometry) and arterial blood PCO2. In addition, the effect of time was significant (P<0.001) but there was no time by group interaction (P=0.9). In Bland and Altman analysis the bias and the precision of this comparison are 1.08 and 0.85 kPa, respectively (figure not shown).



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Fig 1 Gastric mucosal end tidal PCO2 difference (DPCO2gas) and gastric mucosal-arterial PCO2 difference (DPCO2sal) (mean (SD)) during the 8 h study period. (Top) Patients with ALI; (middle) patients recovering from cardiac surgery; (bottom) all patients combined. When all patients were analysed together (bottom) using general linear model there was a significant effect of time (P<0.01) but no time by group (DPCO2gas or DPCO2sal) interaction (P=0.33).

 


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Fig 2 The agreement between DPCO2gas and DPCO2sal analysed using the method by Bland and Altman.20 DPCO2air=gastric mucosal end-tidal PCO2 difference when mucosal PCO2 was measured using gas tonometry. DPCO2sal=gastric mucosal arterial PCO2 difference when mucosal PCO2 was measured using saline tonometry. Solid line indicates bias of this comparison and dotted lines indicate ±2 SD of the bias.

 


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Fig 3 Gastric mucosal-systemic PCO2 difference (mean (SD)) during the 8 h study period. Gastric mucosal PCO2 was measured using Tonocap®. Open symbols = gastric mucosal-arterial blood PCO2, closed symbols = gastric mucosal-end-tidal PCO2. (Top) Patients with ALI; (middle) patients recovering from cardiac surgery; (bottom) all patients combined. When all patients were analysed together (bottom) using general linear model there was a significant effect of time (P<0.001) and group (P=0.02) but no time by group (arterial blood PCO2 or end-tidal PCO2) interaction (P=0.9).

 
As expected, the difference between DPCO2gas and DPCO2sal increased with increasing arterial end-tidal PCO2 difference (Fig. 4). Figure 5 shows a reasonable correlation between the maximum change from baseline in DPCO2sal and the corresponding change in DPCO2gas. The correlation in gastric mucosal PCO2, when it was measured both by saline and by gas tonometry, is shown in Figure 6 and the Bland–Altman plot for the same comparison in Figure 7. The bias in this Bland–Altman analysis was –0.26 kPa and the precision 0.81 kPa. Finally, the correlation showing the mean gastric mucosal PCO2 (measured by air and saline tonometry) for each patient during the whole study period is shown in Figure 8.



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Fig 4 Correlation between arterial end-tidal PCO2 difference (=arterial–PE'CO2) and DPCO2gas–DPCO2sal difference. DPCO2gas=gastric mucosal PCO2-end-tidal PCO2 when gastric mucosal PCO2 is measured using gas tonometry. DPCO2sal=gastric mucosal PCO2–arterial PCO2 when gastric mucosal PCO2 is measured using saline tonometry.

 


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Fig 5 The maximum change from baseline in DPCO2sal and the corresponding change in DPCO2gas. DPCO2gas=gastric mucosal PCO2–end-tidal PCO2 when gastric mucosal PCO2 is measured using gas tonometry. DPCO2sal=gastric mucosal PCO2–arterial PCO2 when gastric mucosal PCO2 is measured using saline tonometry.

 


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Fig 6 Correlation between paired gastric mucosal PCO2 measurements when PCO2 was measured simultaneously using both saline and gas tonometry.

 


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Fig 7 The agreement between simultaneous gastric mucosal PCO2 measurements when both air (Tonocap®) and saline tonometry were used. Mean PCO2=(Tonocap® PCO2+saline tonometry PCO2)/2. Analysis was done using the method by Bland and Altman.20 Solid line indicates bias of this comparison and dotted lines indicate ±2 SD of the bias.

 


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Fig 8 Correlation between the mean gastric mucosal PCO2 values calculated for each patient during the 8 h study period. Measurements were done simultaneously both by air and saline tonometry.

 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
We found that the difference between gastric mucosal PCO2 (measured by gas tonometry) and end-tidal PCO2 (DPCO2gas) reflects the difference between gastric mucosal PCO2 (measured by saline tonometry) and arterial PCO2 (DPCO2sal). We also found that PCO2gas systematically overestimated DPCO2sal and that DPCO2gas has some obvious limitations. However, the agreement between the two methods is acceptable and allows DPCO2gas to be used in clinical practice as a semi-continous indicator of the adequacy of splanchnic perfusion.

The advantage of DPCO2gas is that it reflects the adequacy of gastric mucosal perfusion continuously. A monitor is a warning device that reveals progressive change, e.g. perfusion abnormalities, promptly, and continuous monitoring is the best option in clinical practice. The gastric mucosal systemic PCO2 (arterial blood) gradient best reflects mucosal perfusion. Also, gut perfusion decreases early in shock, often when systemic haemodynamics are stable.23 Saline tonometry, and gas tonometry, both need repeated samples for arterial blood or saline PCO2. It is not feasible in clinical practice to draw and analyse arterial blood and gastric tonometer saline samples at frequent, e.g. 10–15 min intervals, if patients are clinically stable. However, because splanchnic perfusion deteriorates early in shock, this clinically stable phase of critical illness would be ideal to monitor gastrointestinal perfusion. The measurement of gastric mucosal-end-tidal CO2 is a convenient method to continuously monitor gastric mucosal perfusion without a need to repeatedly analyse saline or arterial blood samples. Because no laboratory work is needed, several potential errors and problems related with sample handling and analysis are avoided. We used a separate monitor to analyse end-tidal CO2 but a newer version of Tonocap® automatically analyses and displays both gastric mucosal and end-tidal PCO2. Tonocap® (both mucosal PCO2 and end-tidal PCO2) has to be calibrated once every 2 months with a gas of known PCO2. There is no need for recalibration after ventilatory adjustments and also temperature has no effect on the measurements. The potential problem of water evaporation in the tubing of capnograph is avoided because Tonocap® includes a water separation system which is based on a hydrophilic membrane.

We are not aware of any studies that have evaluated the gastric-mucosal end-tidal PCO2 difference to assess splanchnic perfusion. There are several studies that examined the agreement between gastric mucosal PCO2 measured by saline and gas tonometry.1416 In our study the correlation between gastric mucosal PCO2 measured by saline and gas tonometry was not as good as has been reported elsewhere. We do not have a clear explanation for this discrepancy. Also, we do not know why gas tonometry systematically gave higher values than saline tonometry (Figs 6 and 8). We did not use H2-blockers in our patients but this should not affect the agreement between the two methods. It is not clear if H2-blockers are needed in critically ill patients to improve the performance of gastric tonometry.20 21 24 25 In patients with cardiogenic shock, a systematic disagreement between saline and gas tonometry was found.26 Under-correction of saline samples may be responsible although correction was done according to manufacturer’s recommendations. We regarded saline technique as a gold standard but this may not necessarily be true.27 28 In vivo, gas tonometry gave a closer agreement with the PCO2 of the test solution.27 Also, the bias between gas and saline tonometry was reduced by replacing saline by buffered electrolyte solutions.27 We used saline with our conventional tonometry and this may have contributed to the differences in our study. The degree of clinically important disagreement between different methods to estimate mucosal perfusion is more important than the disagreement per se.

The normal gastric mucosal systemic PCO2 difference is not known and more importantly we do not know how large a difference is clinically important in critically ill patients. In our previous study with healthy volunteers, the gastric mucosal arterial PCO2 gap varied between 1.4 and 3 kPa depending on whether nasogastric suction or H2-blockers were used.20 A more recent study in healthy volunteers suggested a normal threshold value of <1.1 kPa for a gastric mucosal arterial PCO2 difference.29 Gastric mucosal PCO2 depends on several factors such as aerobic and anaerobic production of CO2 and also on perfusion of the gastric mucosa,17 and it is not clear to what extent increased gastric mucosal PCO2 indicates tissue hypoxia or decreased mucosal perfusion. A recent experimental study suggested that gastric mucosal PCO2 has to increase to >13 kPa to indicate tissue hypoxia.30 In our study the bias and the precision of the agreement between DPCO2gas and DPCO2sal were 0.85 and 1.25 kPa, respectively. Therefore, we propose, that the small disagreement between these methods may not be clinically important.

One obvious problem with the use of the gastric mucosal end-tidal PCO2 difference is that in patients with impaired gas exchange, end-tidal CO2 does not represent arterial (and hence systemic) PCO2.19 In patients who do not have ALI this is not a large problem but in patients who have lung injury, end-tidal CO2 may underestimate systemic PCO2. We found that in patients who have ALI, DPCO2gas overestimated DPCO2sal more than in patients who do not have ALI. Figure 3 also shows that the disagreement between DPCO2gas and DPCO2sal increases as the arterial end-tidal PCO2 difference increases (indicating increased dead space ventilation). However, for at least two reasons the potential overestimation of the gastric mucosal systemic PCO2 difference is not a major clinical problem. First, it is physiologically obvious and easily recognizable. A significant difference between arterial blood PCO2 and end-tidal CO2, can be easily measured and used to interpret DPCO2gas. Secondly, an overestimate of the gastric mucosal systemic PCO2 difference using DPCO2gas means that truly increased PCO2 differences will not be left undetected. We found that changes in DPCO2gas reflected changes in DPCO2sal during our study period, but the time period for our study was relatively short and probably was during steady state CO2 production, lung function and dead space ventilation. Therefore, we cannot address the potential impact of changes in these variables during the progression of critical illness.

The difference between gastric mucosal end tidal PCO2 is a potentially useful method for continuous monitoring of splanchnic perfusion. It is easy to use and it does not require much additional work from staff, and the limits of the method are easy to assess and they do not jeopardize patient care. Studies of clinical outcome, based on interventions using this information are needed.


    Footnotes
 
* Corresponding author: Department of Anesthesiology and Intensive Care, Division of Critical Care, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland Back


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
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