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Communications to the Editor |

Monitoring of Tissue pH : The Critical Measurement FREE TO VIEW

Richard G. Fiddian-Green, BM, BCh, MA
Author and Funding Information

Affiliations: Constantia, South Africa,  University of Pittsburgh Medical School Pittsburgh, PA

Correspondence to: Richard G. Fiddian-Green, BM, BCh, MA, Silverhill, Southern Cross Drive, Constantia, Western Cape, 7806 South Africa; e-mail: richardfg@excite.com



Chest. 1999;116(6):1839-1841. doi:10.1378/chest.116.6.1839
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Published online

To the Editor:

Dr. Fink’s editorial on tonometry in CHEST (September 1998)1 addresses the ability of tonometry to monitor tissue perfusion to the exclusion of its ability to monitor the adequacy of tissue oxygenation. Indeed, his editorial confuses the two in referring to the intramucosal pH (pHi) as a measure of tissue perfusion rather than of tissue oxygenation. Most surprising is Dr. Fink’s failure to address the predictive value of the different measurements and the impact that they have not only on patient outcome, but also on costs, when used to assist in routine patient management. Surely, these are the most critical issues in recommending any form of monitoring for routine patient care.

Dr. Fink’s editorial focuses on the physiologic basis of the measurements. He concedes that knowing that the tissue pH is normal is enough for him to conclude that “perfusion is sufficient to meet the metabolic demands of the cells in that tissue.” He appears to acknowledge that the severity of tissue acidosis in anaerobiosis is related to the degree of impairment of oxidative phosphorylation and to the associated unreversed adenosine triphosphate (ATP) hydrolysis,2whether it is due to the retention of protons from increased glycolytic ATP turnover or to ATP breakdown,3which is the degree to which oxidative phosphorylation, which consumes the protons released by ATP hydrolysis, has failed to replenish depleted ATP stores and, hence, to maintain the“ adequacy of tissue oxygenation.” This is consistent with the conclusion of the National Institutes of Health (NIH) Task Force on Cardiopulmonary Dysfunction in Critical Care Medicine in 1994 that gastric pHi is a “metabolic signal of tissue hypoxia.”4

Maintaining tissue acid-base balance and adequate aerobic ATP synthesis by oxidative phosphorylation is essential for all bodily activities, including tissue repair, wound healing, bacterial phagocytosis, and cellular survival. The accumulation of protons in anaerobiosis compromises nonessential functions, such as lactate efflux from muscles and acid secretion, and essential functions, such as myocardial contractility. The continued accumulation of protons and later net ATP degradation compromises essential ATP-dependent functions, such as the sodium pump, and cells swell and die. ATP degradation allows free radicals to be generated on resuscitation.23

In view of these data, it is not surprising that the measurement of pHi has proven to be a good early predictor of organ dysfunctions and failures, of death, or of both. It is also not surprising that measures directed toward preventing a fall in gastric pHi5and restoring the gastric pHi to normal in a timely manner in anaerobiosis are associated with improved outcomes and reduced ICU and hospital stays and costs.69 In this respect, it is important, in terms of monitoring, to note that using a measure of normal gastric pHi as a goal in resuscitation is significantly better in achieving a normal pHi in a timely manner than is using the empirical goals of global oxygen delivery and consumption, which are often redundant or ineffective.7

Despite this logic and the weight of these clinical data, Dr. Fink dismissed the indirect measurement of pHi because it appeared to underestimate the magnitude of the tissue acidosis present in low-flow and no-flow states in his and our earlier validation studies due, Dr. Fink claims, to the bicarbonate assumption being invalid and to several other variables that he cites. Not only is his conclusion unwarranted, even in no-flow and low-flow states as previously argued,2 but it is clinically irrelevant whether the indirect measurement of pHi underestimates the severity of acidosis or not. Moreover, the measurement has proved to be remarkably robust in clinical practice despite earlier concerns.7

The gastric pHi measured in healthy volunteers who were given H2-receptor antagonists falls within a narrow range, and a fall below these tight statistical limits of a normal range establishes the presence of an intramucosal acidosis and provides the means to measure the degree of tissue acidosis and, hence, the degree to which oxidative phosphorylation has been compromised. In septic patients, a fall in gastric pHi appears to be a particularly sensitive indication of the degree of global anaerobiosis present because pHi can be reversed in a dose-related manner, and when it is elevated, arterial lactate can be reduced in parallel by incremental increases in oxygen delivery induced by dobutamine.10

There are three other reasons why gastric pHi is an indicator of the degree of systemic anaerobiosis. First, the superficial layers of the gut mucosa are the “canary” of the body, being among the first parts of the body to be compromised in low-flow states. Second, gut mucosal injury releases substances into the circulation that may further compromise, either directly or indirectly, tissue oxygenation. Third, the incorporation of the arterial bicarbonate level into the indirect measurement of pHi allows it to reflect the systemic contributions of anaerobiosis and to add to the predictive value of intramucosal Pco2 for adverse clinical events.11

Systemic metabolic indexes of anaerobiosis, which are the product of tissue washout, are inevitably less sensitive and potentially more specific predictors of outcome in patients with advanced disease,1213 these indexes being paradoxically more abnormal in patients with perfused tissues than in those with unperfused tissues.2,10 The intramucosal Pco2 alone is not as good a predictor of outcome as the gastric pHi.,7,11 The more specific indexes of regional tissue “perfusion” and/or “dysoxia,” namely, pH-gap and Pco2-gap, also have proven to be less sensitive and accurate, but in patients with severe sepsis they are more specific predictors of outcome and in patients with advanced cardiopulmonary failure they are more accurate predictors.,2,78,1417 In this respect, it is worthwhile noting that the pulse, a poor predictor of outcome in hemodynamic stability, is a most accurate predictor of impending death, a patient having no pulse in cardiac arrest and a pulse not in arrest. The deficiencies in these indexes of regional tissue “perfusion” and/or “dysoxia” in predicting outcome relative to gastric pHi is not surprising, because the gastric pHi may fall in anaerobiosis not only as a result of a rise in tissue Pco2 above arterial Pco2 in low-flow states but also as a result of a fall in tissue bicarbonate in conjunction with a rise in Pco2 or of a fall in bicarbonate alone in perfused tissues.

The pHi correlates poorly with tissue perfusion (flow) and was never intended to be a measure of flow, as Dr. Fink suggests. The Pco2, and especially the Pco2-gap, is a regional measure of tissue perfusion (flow) to the degree that it allows the intramucosal Pco2 to equilibrate with that in arterial blood. But Dr. Fink used proton accumulation in anaerobiosis, not proton consumption, by oxidative phosphorylation in restoring the tissue acid-base balance in his consideration of the fate of tissue CO2.2 The relative contributions of intramucosal Pco2 and arterial bicarbonate to pH depend on the degree of CO2 removal by flowing blood and by exhalation from the lungs.

On-line tonometric monitoring of tissue Pco2 in less invasive extra-enteric locations, such as the esophagus, the sublingual space, or even the urinary bladder, is appealing for simplicity, ease of access, and absence of variables such as acid secretion, especially as an aid in the detection of acute circulatory failure. Caution is due because of the unique role of the gut as the “canary” of the body, as Dr. Fink acknowledges, and, hence, it is the preferred choice as the monitoring site for the early detection of low flow when small changes may be clinically significant. Caution is also due with the indwelling sensors that Dr. Fink considers, because all sensors may become “poisoned,” may drift, and may not be able to be recalibrated in vivo. Even if the sensors are drift free, as Dr. Fink claims, the question is whether there is any outcome or cost benefit to making tonometric measurements any more often than routine blood gas analyses.

Dr. Fink concludes that “in contrast to the complexity of sepsis, patients with elevated tissue Pco2 values during a major surgical procedure or during resuscitation from hemorrhagic or cardiogenic shock have a relatively straightforward problem: oxygen delivery in the microvasculature is inadequate to meet metabolic demand.” Agreed. But the detection of a fall in pHi in perfused tissues caused partially or wholly by a fall in bicarbonate might be delayed or missed if one relied on the measurement of intramucosal Pco2, and even Pco2-gap alone, in monitoring patients, especially in an extra-enteric site. He adds: “The solution to the problem is equally straightforward: improve perfusion or the oxygen content of arterial blood.” Is he that sure? Beware the development of unreversed ATP hydrolysis in perfused tissues that is reflected in a fall in bicarbonate during and after conventional resuscitation, the adverse effects of inotropes that increase oxygen consumption, and the assumption that increases in arterial oxygen content improve capillary oxygen content especially when increased with transfusions of RBCs > 10 days old. This is exactly where we have been misled in the past by global measurements of oxygen transport, consumption, and extraction.2

Contrary to Dr. Fink’s statement, manual gastric balloon tonometry can be easily incorporated into routine clinical care, as has been the case in Argentina6 and at the University of Miami,9 and this inclusion has been rewarded with substantial improvements in outcomes, seemingly even in patients with advanced disease in whom reductions in treatment costs also were observed. The failure of gastric tonometry to have been incorporated into routine clinical care is surprising, given its long-established physiologic and clinical credentials. In my view, it has not been because it is cumbersome and too expensive, as Dr. Fink claims. Indeed, when considered in terms of incremental dollars spent per life-year saved, pHi-guided resuscitation with manual measurements that are performed in all ICU patients would seem infinitely more cost-effective than any other form of established management protocol in adequately ventilated patients.18

Finally, let us not lose site of the overriding importance of mitochondrial ATP synthesis by oxidative phosphorylation in all bodily activity at all times. The NIH Task Force on Cardiopulmonary Dysfunction in Critical Care Medicine recognized the need for monitoring alterations in the “energetic state of the tissues.” The intramucosal pHi is a physiologically appropriate and clinically validated measurement that, despite its imperfections, appears to do this very simply and better than I ever would have thought. Most importantly, when incorporated into routine care, gastric pHi measurement has improved our understanding of disease processes, has aided in management decisions, and has helped to improve outcomes and to reduce costs substantially. Let us use pHi in conjunction with measures of Pco2 Po2, and Pco2-gap to audit and direct care until better and more representative measures of tissue energetics emerge and have been shown in routine clinical practice to improve outcomes and to reduce costs further.

I have had no business dealings with the Tonometrics Division of Datex-Ohmeda (Helsinki, Finland), the company commercializing silicone balloon tonometry in both its manual and on-line forms. I am not receiving financial support from any company. Furthermore, due to the indirect nature of my contracts, I have absolutely no idea whether I still have any financial interest in any viable company remotely related to the commercialization of tissue gas analysis, including Datex-Ohmeda. I have absolutely no legal or political agenda. I simply remain concerned that the opportunity to improve outcome and reduce costs on a large scale is not being realized.

Fink, MP (1998) Tissue capnography as a monitoring strategy in critically ill patients: just about ready for prime time.Chest114,667-669. [PubMed] [CrossRef]
 
Fiddian-Green, RG Gastric intramucosal pH, tissue oxygenation and acid-base balance.Br J Anaesth1995;74,591-606. [PubMed]
 
Dennis, SC, Gevers, W, Opie, LH Protons in ischemia: where do they come from; where do they go.J Mol Cell Cardiol1991;23,1077-1086. [PubMed]
 
National Heart, Lung, and Blood Institute. Report of the Task Force on Research in Cardiopulmonary Dysfunction in Critical Care Medicine: U.S. Department of Health and Human Services. Bethesda, MD: Public Health Service, National Institutes of Health, October 1994; 75.
 
Mythen, MG, Webb, AR Perioperative volume expansion reduces incidence of gut mucosal hypoperfusion during cardiac surgery.Arch Surg1995;130,423-429. [PubMed]
 
Gutierrez, G, Palizas, F, Doglio, G, et al Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.Lancet1992;339,195-199. [PubMed]
 
Ivatury, RR, Simon, RJ, Islam, S, et al A prospective randomized study of end points of resuscitation after major trauma: global oxygen transport indices versus organ-specific gastric mucosal pH.J Am Coll Surg1996;183,145-154. [PubMed]
 
Ivatury, RR, Simon, RJ, Islam, S, et al Gastric mucosal pH and oxygen delivery and consumption indices in the assessment of the adequacy of resuscitation: a prospective, randomized study.J Trauma Injury Infect Crit Care1995;39,128-136
 
Barquist, E, Kirton, O, Windsor, J, et al The impact of antioxidant and splanchnic-directed therapy on persistent uncorrected gastric mucosal pH in the critically injured patient.J Trauma1998;44,355-360. [PubMed]
 
Gutierrez, G, Clark, C, Brown, SD, et al Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients.Am J Respir Crit Care Med1994;150,324-329. [PubMed]
 
Fiddian-Green, RG, McGough, E, Pittenger, G, et al Predictive value of intramural pH and other risk factors for massive bleeding from stress ulceration.Gastroenterology1983;85,613-620. [PubMed]
 
Boyd, O, Mackay, CJ, Lamb, G, et al Comparison of clinical information gained from routine blood-gas analysis and from gastric tonometry for intramural pH.Lancet1993;341,142-146. [PubMed]
 
Maynard, ND, Bihari, D, Beale, E, et al Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure.JAMA1993;270,1203-1210. [PubMed]
 
Gomersall, CD, Joynt, GM, Ho, KM, et al Gastric tonometry and prediction of outcome in the critically ill.Anaesthesia1997;52,619-623. [PubMed]
 
Miller, PR, Kincaid, EH, Meredith, JW, et al Threshold values of intramucosal pH and mucosal-arterial CO2gap during shock resuscitation.J Trauma1998;45,868-872. [PubMed]
 
Friedman, G, Berlot, G, Kahn, RJ, et al Combined measurements of blood lactate and gastric intramucosal pH in patients with severe sepsis.Crit Care Med1995;23,1184-1193. [PubMed]
 
Duke, T, Butt, W, South, M, et al The Dco2measured by gastric tonometry predicts survival in children receiving extracorporeal life support: comparison with other hemodynamic and biochemical information.Chest1997;111,174-179. [PubMed]
 
Fiddian-Green, RG Tonometry: Part 2. Clinical use and cost implications.Intensive Care World1992;9,130-135. [PubMed]
 
To the Editor:

I appreciate the opportunity to respond to the very long letter by Dr. Fiddian-Green. I will keep my comments brief.

Tissue Pco2 is a function of a number of parameters, including the rate at which CO2 is produced by oxidative metabolism in the tissue, the rate at which CO2 is produced by titration of bicarbonate anions (HCO3) by protons in the tissue, and the rate at which CO2 is removed from the tissue by blood flowing through its capillary network. Intraluminal Pco2 in certain locations, like the stomach or colon, is a function of mucosal Pco2 but also can be influenced by other factors, including titration of secreted HCO3 by secreted protons and production of CO2 as a result of the fermentation of various fuels in food or feces by microbes. Finally, in all locations perfused by arterial blood, tissue Pco2 is directly influenced by arterial Pco2.1 In view of this information, it seems reasonable to conclude that tissue Pco2 and intraluminal Pco2 are measures of neither the adequacy of tissue perfusion nor the adequacy of tissue oxygenation but, rather, are clinically useful parameters that can be influenced in complex ways by a number of factors.

Tissue pH and tissue Pco2 tend to be inversely related, and both of these parameters often are determined by the“ adequacy” of tissue oxygenation (ie, tissue Po2). In most circumstances, a low tissue pH or a high tissue Pco2 can be interpreted as evidence of low tissue Po2. In sepsis, however, systemic and/or tissue acidosis can occur despite a high tissue Po2.25 Accordingly, it is not valid to state that intramucosal pH (pHi) always provides unambiguous information about tissue oxygenation.

Tissue Pco2, whether used directly or used to calculate a derived variable (eg, gastric pHi) is a very appealing index for monitoring critically ill patients. Yet, despite the publication of hundreds of articles and abstracts regarding the value of tissue Pco2 (or pHi) monitoring, the use of gastric tonometry or related approaches remains largely a research tool. Certainly, routine monitoring of tissue Pco2 is currently used in very few ICUs or operating rooms in the United States. There are probably many reasons for why clinicians have been reluctant to adopt this technology. Certain issues, however, such as unfamiliarity, inconvenience, and perceptions about the acquisition costs for commercially available devices seem likely to be playing a role. It is my view that wide adoption of tissue capnometry is unlikely to occur until inexpensive devices that provide a continuous readout, analogous to that provided by a pulse oximeter, become available. It is my understanding that one such device is being developed by a commercial entity (Optical Sensors, Inc; Minneapolis, MN). I have no connection with or financial interest whatsoever in this company.

References
Salzman, AL, Strong, KE, Wang, H, et al Intraluminal “balloonless” air tonometry: a new method for determination of gastrointestinal mucosal Pco2.Crit Care Med1994;22,126-134. [PubMed]
 
Boekstegers, P, Weidenhofer, S, Pilz, G, et al Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock.Infection1991;19,317-323. [PubMed] [CrossRef]
 
Boekstegers, P, Weidenhofer, S, Kapsner, T, et al Skeletal muscle partial pressure of oxygen in patients with sepsis.Crit Care Med1994;22,640-650. [PubMed]
 
Rosser, DM, Stidwill, RP, Jacobson, D, et al Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis.J Appl Physiol1995;79,1878-1882. [PubMed]
 
VanderMeer, TJ, Wang, H, Fink, MP Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock.Crit Care Med1995;23,1217-1226. [PubMed]
 

Figures

Tables

References

Fink, MP (1998) Tissue capnography as a monitoring strategy in critically ill patients: just about ready for prime time.Chest114,667-669. [PubMed] [CrossRef]
 
Fiddian-Green, RG Gastric intramucosal pH, tissue oxygenation and acid-base balance.Br J Anaesth1995;74,591-606. [PubMed]
 
Dennis, SC, Gevers, W, Opie, LH Protons in ischemia: where do they come from; where do they go.J Mol Cell Cardiol1991;23,1077-1086. [PubMed]
 
National Heart, Lung, and Blood Institute. Report of the Task Force on Research in Cardiopulmonary Dysfunction in Critical Care Medicine: U.S. Department of Health and Human Services. Bethesda, MD: Public Health Service, National Institutes of Health, October 1994; 75.
 
Mythen, MG, Webb, AR Perioperative volume expansion reduces incidence of gut mucosal hypoperfusion during cardiac surgery.Arch Surg1995;130,423-429. [PubMed]
 
Gutierrez, G, Palizas, F, Doglio, G, et al Gastric intramucosal pH as a therapeutic index of tissue oxygenation in critically ill patients.Lancet1992;339,195-199. [PubMed]
 
Ivatury, RR, Simon, RJ, Islam, S, et al A prospective randomized study of end points of resuscitation after major trauma: global oxygen transport indices versus organ-specific gastric mucosal pH.J Am Coll Surg1996;183,145-154. [PubMed]
 
Ivatury, RR, Simon, RJ, Islam, S, et al Gastric mucosal pH and oxygen delivery and consumption indices in the assessment of the adequacy of resuscitation: a prospective, randomized study.J Trauma Injury Infect Crit Care1995;39,128-136
 
Barquist, E, Kirton, O, Windsor, J, et al The impact of antioxidant and splanchnic-directed therapy on persistent uncorrected gastric mucosal pH in the critically injured patient.J Trauma1998;44,355-360. [PubMed]
 
Gutierrez, G, Clark, C, Brown, SD, et al Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients.Am J Respir Crit Care Med1994;150,324-329. [PubMed]
 
Fiddian-Green, RG, McGough, E, Pittenger, G, et al Predictive value of intramural pH and other risk factors for massive bleeding from stress ulceration.Gastroenterology1983;85,613-620. [PubMed]
 
Boyd, O, Mackay, CJ, Lamb, G, et al Comparison of clinical information gained from routine blood-gas analysis and from gastric tonometry for intramural pH.Lancet1993;341,142-146. [PubMed]
 
Maynard, ND, Bihari, D, Beale, E, et al Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure.JAMA1993;270,1203-1210. [PubMed]
 
Gomersall, CD, Joynt, GM, Ho, KM, et al Gastric tonometry and prediction of outcome in the critically ill.Anaesthesia1997;52,619-623. [PubMed]
 
Miller, PR, Kincaid, EH, Meredith, JW, et al Threshold values of intramucosal pH and mucosal-arterial CO2gap during shock resuscitation.J Trauma1998;45,868-872. [PubMed]
 
Friedman, G, Berlot, G, Kahn, RJ, et al Combined measurements of blood lactate and gastric intramucosal pH in patients with severe sepsis.Crit Care Med1995;23,1184-1193. [PubMed]
 
Duke, T, Butt, W, South, M, et al The Dco2measured by gastric tonometry predicts survival in children receiving extracorporeal life support: comparison with other hemodynamic and biochemical information.Chest1997;111,174-179. [PubMed]
 
Fiddian-Green, RG Tonometry: Part 2. Clinical use and cost implications.Intensive Care World1992;9,130-135. [PubMed]
 
Salzman, AL, Strong, KE, Wang, H, et al Intraluminal “balloonless” air tonometry: a new method for determination of gastrointestinal mucosal Pco2.Crit Care Med1994;22,126-134. [PubMed]
 
Boekstegers, P, Weidenhofer, S, Pilz, G, et al Peripheral oxygen availability within skeletal muscle in sepsis and septic shock: comparison to limited infection and cardiogenic shock.Infection1991;19,317-323. [PubMed] [CrossRef]
 
Boekstegers, P, Weidenhofer, S, Kapsner, T, et al Skeletal muscle partial pressure of oxygen in patients with sepsis.Crit Care Med1994;22,640-650. [PubMed]
 
Rosser, DM, Stidwill, RP, Jacobson, D, et al Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis.J Appl Physiol1995;79,1878-1882. [PubMed]
 
VanderMeer, TJ, Wang, H, Fink, MP Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock.Crit Care Med1995;23,1217-1226. [PubMed]
 
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