Tissue capnometry may be suitable for the indirect evaluation of regional hypoperfusion. We tested the performance of a new sublingual capillary tonometer in experimental hemorrhage. Thirty-six anesthetized, ventilated mini pigs were divided into sham-operated (
Disturbances of the microcirculation are tightly linked to circulatory failure of different origin; thus evaluation of the microcirculatory status has gained increasing importance in the diagnosis and treatment of critically ill patients. It is recognized that in spite of the normal values of global oxygen delivery regional tissue hypoperfusion may exist, which cannot be detected by conventional monitoring tools [
The measurement of the partial pressure of carbon dioxide (PCO2) in tissues is a potentially feasible technique for the indirect evaluation of the microcirculation [
Different sites of the gastrointestinal tract are available for the purpose of tissue capnometry and the assessment of the adequacy of mucosal blood flow. As PCO2 results gained from the stomach and the sublingual regions proved to be interchangeable [
It is generally acknowledged that monitoring of the sublingual microcirculation, the only site of intravital microscopy (IVM) available at the point of care for most critically ill patients, is of particular prognostic value [
The new capillary tonometer. Illustration of the new sublingual tonometer applied during the examinations.
The main goal of the current study was to test this new sublingual probe in a porcine model of hemorrhagic shock and compare its performance to direct microcirculatory measurements with IVM using the orthogonal polarization spectral (OPS) imaging technique. Another aim was to investigate how the capnometry-derived values relate to global indicators of hemodynamic changes during hemorrhage and resuscitation. We also hypothesized that if the same diagnostic end points can be reached, sublingual capnometry could offer a technically simpler, alternative method to monitor sublingual microcirculatory changes noninvasively.
The experiments were carried out in strict adherence to the National Institute of Health guidelines for the use of experimental animals and the study was approved by the Ethics Committee and the Institutional Animal Care and Use Committee at the University of Szeged. The study was conducted in the research laboratory of the Institute of Surgical Research in a manner that does not inflict unnecessary pain or discomfort upon the animals.
Thirty-six Vietnamese mini pigs of both genders, weighing 16–25 kg, underwent a 24 hr fasting preoperatively with free access to water; the animals were randomly allocated into control (sham-operated,
For measurement of the sublingual PCO2 (PSLCO2) the new sublingual capillary tonometer (see below) was placed under the tongue, and a specially designed latex face mask was used to close the oral cavity. Capnography was performed with a Microcap handheld capnograph (Oridion Medical Ltd, Jerusalem, Israel). The sublingual mucosal-to-arterial PCO2 difference (PSLCO2 gap) was calculated by subtracting PSLCO2 from the simultaneously taken PaCO2 values.
For central venous access the left jugular vein was catheterized. A three-lumen central venous catheter (7 F, Edwards Lifesciences LLC, Irvine, USA) was introduced for blood sampling and fluid administration using aseptic surgical technique. The central venous pressure (CVP) was monitored continuously with a computerized data-acquisition system (SPELL Haemosys; Experimetria Ltd., Budapest, Hungary). For hemodynamic measurements a special thermodilution catheter (Pulsiocath, PULSION Medical Systems AG, Munich, Germany) was placed into the left femoral artery. The cardiac output was monitored by transpulmonary thermodilution and continuous pulse contour analysis (PiCCO method). The right carotid artery was also catheterised for bleeding (7 F, PE, Access Technologies, Illinois, USA). The blood gas measurements were carried out by taking arterial and central venous blood samples simultaneously according to the study protocol, which were then analyzed by cooximetry with a blood gas analyzer (Cobas b221, Roche, Austria). Simplified oxygen extraction rate (O2ER) was calculated according to the standard formula from arterial (SaO2) and central venous oxygen saturations (ScvO2):
For direct evaluation and noninvasive visualization of the sublingual microcirculation the intravital OPS imaging technique (Cytoscan A/R, Cytometrics, Philadelphia, PA, USA) was used. A 10x objective was placed onto the sublingual mucosa, and microscopic images were recorded with an S-VHS video recorder (Panasonic AG-TL 700, Matsushita Electric Ind. Co. Ltd, Osaka, Japan). Quantitative assessment of the microcirculatory parameters was performed offline by frame-to-frame analysis of the videotaped images. Red blood cell velocity (RBCV;
The new sublingual capillary tonometer (Mediszintech Ltd, Budapest, Hungary) is a specially coiled silicone rubber tube (ID: 1.5 mm, OD: 2.0 mm, and length: 640 mm) with high permeability for gases, which is formed into a multiple V-shape by using a mould and is glued along five lines (Figure
The preparation period was followed by a 30 min resting period. After baseline measurements at 0 min (
Experimental protocol. Flow diagram representing the experimental protocol in both groups of animals. MAP is mean arterial pressure,
Animals in the control group were not submitted to bleeding. They underwent the same operation procedure and received the same instrumentation and monitoring. In this group 0.9% sodium chloride was infused at a rate of 10 mL kg−1 h−1 during the experiment. Hemodynamic, blood gas analysis and microcirculatory measurements were performed at the same time points.
The statistical software package SigmaStat for Windows (Jandel Scientific, Erkrath, Germany) was applied for data analysis. After testing for normality parametric methods were used. Two-way repeated measures analysis of variance (ANOVA) was applied for statistical analysis. For the analysis of differences between the sham-operated and the hemorrhagic shock groups, the time dependent differences from the baseline (
Severe shock state was achieved in the animals of the shock group as indicated by marked and significant changes in macrohemodynamics during the first 60 minutes: MAP decreased, heart rate (HR) increased, and cardiac index (CI) and global end-diastolic volume index (GEDVI) decreased significantly (Figures
Macrohemodynamic parameters. Changes of macrohemodynamic parameters, mean arterial pressure (a), heart rate (b), cardiac index (c), and global end-diastolic volume index (d).
Sublingual capnometry. Changes of sublingual tonometric variables measured by the new probe, sublingual PCO2 (a) and sublingual PCO2 gap (b).
Microcirculatory parameters. Changes of microcirculatory parameters measured by orthogonal polarization spectral imaging, red blood cell velocity in postcapillary venules (a) and capillary perfusion rate (b).
Central venous blood gas derived parameters. Changes of central venous blood derived parameters, central venous-arterial PCO2 gap (a), central venous oxygen saturation (b), and oxygen extraction rate (c).
Statistically significant alterations were found regarding MAP, HR, CI, and GEDVI (Figures
Concerning the microcirculatory measurements, both RBCVSL and CPRSL increased significantly in the shock group compared to
Samples of the pictures in each phase can be seen as electronically submitted Supplementary Material (see Figure S1 available online at
Fluid resuscitation resulted in a significant decrease of the PcvaCO2 at
Statistically significant correlation was found between PSLCO2 gap and RBCVSL (
Correlations with sublingual capnometry. Relationships between sublingual mucosal-to-arterial carbon-dioxide partial pressure gap and sublingual red blood cell velocity in postcapillary venules (a), sublingual capillary perfusion rate (b), central venous oxygen saturation (c), and central venous-to-arterial carbon-dioxide partial pressure difference (d).
In this study we report on the first
There are different methods able to detect the increased concentrations of CO2 in the periphery. Gastric tonometry is based upon the monitoring of gastric mucosal PCO2 level; sublingual and buccal capnometry measure mucosal PCO2 of the proximal gastrointestinal tract [
The concept of monitoring complementary regional/local perfusion parameters in order to guide or fine-tune resuscitation strategies is rather old and well-established. Historically, one of the first methods was gastric tonometry. However, technical difficulties, long equilibration, and other confounding factors [
According to recent studies it was suggested that even the magnitude of blood loss can be estimated by tissue capnometry, and the method may also be useful in guiding fluid resuscitation during hemorrhage. Different authors [
Massive bleeding in our study resulted in severe perfusion abnormalities as indicated by significant deterioration of sublingual CPR and RBCV, which was also reflected by changes of the sublingual PSLCO2 gap. Although the close relationship between the sublingual perfusion and PCO2 has already been described [
Significant changes in MAP, HR, CI, and GEDVI were detected during the shock phase and during partial resuscitation, with the CI being significantly higher by the end of resuscitation as compared with the baseline, possibly because of the sustained tachycardia caused by the bleeding-related stress response. There are several studies showing that hemorrhage-caused hypovolemia is accompanied by sublingual hypoperfusion and/or the increase in PSLCO2 [
Although the most accurate way to assess cardiac output, oxygen delivery, and consumption is invasive hemodynamic monitoring, it is often unavailable in emergencies. Simple blood gas driven variables such as ScvO2 and PcvaCO2 can help the clinician in defining the need for fluid resuscitation and red blood cell transfusion or may serve as therapeutic targets of goal-directed therapy in high-risk surgical or septic patients [
This new capillary tonometer may be an appropriate tool for the indirect evaluation of the sublingual microcirculation. There are also some limitations to the use of this method, such as the relatively long equilibration time and the need to draw arterial blood samples to determine the PSLCO2 gap. However, the calculation of gap values is probably not necessary if the alveolar ventilation is considered stable. In our opinion, this device can be best utilized during emergency situations (in the ICU or ER and during major/high-risk surgery), where arterial and central venous catheters are commonly used, and excessive invasiveness should therefore not be a concern.
With these restrictions we concluded that capnometry-derived variables followed the microcirculatory changes and correlated with well-established indices of global hemodynamics in hypovolemia and hemorrhagic shock. Combination of these results with central venous oxygen saturation and central venous-to-arterial carbon-dioxide partial pressure differences may be complementary tools for monitoring and treating hypovolemia and hemorrhagic shock in the clinical setting.
The authors declare that they have no conflict of interests.
Péter Palágyi and József Kaszaki contributed equally to this work.
The authors are very grateful to Professor Domokos Boda for his outstanding technical support and guidance by the planning and the implementation of sublingual tonometric measurements. This publication is supported by the European Union and cofunded by the European Social Fund. The project title is Telemedicine-Focused Research Activities on the Field of Mathematics, Informatics and Medical Sciences. The study was also supported by research Grant OTKA K104656.