The report in this issue of Anesthesia & Analgesia by Knichwitz et al.  of a technique for continuous monitoring of gastrointestinal intramucosal pH may provide a means of continuously assessing the adequacy of tissue perfusion in anesthetized or critically ill patients. They describe use of a fiberoptic PCO (2) sensor for continuous measurement of PCO2 values in the gut lumen. This report represents a major technological advance over the standard tonometric technique. This new technique may advance our understanding of changes in tissue perfusion in the splanchnic bed during shock and will be valuable as a measure of the adequacy of resuscitation.
An approach that measures adequacy of tissue perfusion has been the Holy Grail of anesthesia and critical care medicine. Traditional measures of tissue perfusion have included urine output, arterial pH, blood lactate, and, more recently, mixed venous oxygen saturation. These measures have major limitations, and changes in these measures may significantly lag behind clinical interventions. Urine output and blood pH are altered by multiple factors, and lactate levels reflect tissue hypoperfusion only when a patient is grossly underresuscitated. Mixed venous oxygen saturation is more sensitive than the "traditional" measures but reflects global rather than regional perfusion so that critical hypoperfusion of important organs may occur despite a normal venous oxygen saturation. After trauma and major surgery, patients who appear to have been adequately resuscitated by these traditional measures may subsequently develop and die of multiorgan failure. One possible explanation for this phenomenon is the existence of hypoperfusion of important organs despite seemingly adequate resuscitation. This hypothesis has led to the concept of "supranormal" hemodynamic therapy, whereby cardiac outputs above the normal critical values are required to maintain adequate tissue perfusion to all vascular beds . This approach uses aggressive intravascular fluid administration and inotropic support to increase cardiac index to supranormal values (approximately 4.5 L centered dot min-1 centered dot m-2) with the goal of reversing regional tissue hypoperfusion and thereby improving survival. Although initial studies of this approach were positive , recent large, prospective clinical studies have demonstrated increased , decreased , and unchanged survival . The largest such study involved 56 intensive care units in Italy and demonstrated equivalent survival with standard hemodynamic therapy, hemodynamic therapy designed to achieve supranormal values for cardiac index, and hemodynamic therapy designed to achieve normal values for mixed venous oxygen saturation . The discordant results of these three similarly designed large clinical trials suggest that supranormal hemodynamic therapy may have both beneficial and adverse effects. Beneficial effects may occur from reversal of regional hypoperfusion, while adverse effects may occur from excess fluid administration and complications of inotropic support. The overall balance may depend upon the specific patient population and the specific application of the therapy. Since some patients may benefit from such therapy while others may not, rational application of goal-oriented hemodynamic therapy should be based upon a measure that accurately assesses the adequacy of systemic cardiac output. Gut intramucosal pH may be that measure.
The gut mucosa has been called the "canary" of the body, since it is usually the first organ system affected by inadequate systemic perfusion. Gut mucosa, because it lacks some of the microvasculature control mechanisms found in more "vital" organs such as the brain and the heart, develops ischemia and acidosis before global hypoperfusion occurs . Monitoring of gut intramucosal pH (pHi) may therefore allow early detection of those patients whose cardiac index is inadequate to meet their needs. Multiple studies have demonstrated that gastric mucosal pH is an indicator of prognosis in critically ill and perioperative patients [8-15]. Fiddian-Green and Baker  demonstrated that stomach wall pH predicted complications after cardiac surgery with greater power than did arterial blood pressure, cardiac index, arterial pH, and urine output; similar results have been demonstrated in trauma patients , in patients with acute circulatory failure , and in patients after orthotopic liver transplantation  and cardiac surgery . Gutierrez et al.  demonstrated that using pHi to guide resuscitation improved survival in critically ill patients. Using pHi to identify the underresuscitated patients instead of using arbitrarily predetermined cardiac index goals in all patients may allow appropriate application of goal-oriented hemodynamic therapy [16-18].
The importance of gut ischemia in the critically ill patient, however, does not stop at its simply being the "canary" or monitor of inadequate perfusion. Gut ischemia may itself be a factor in the development of multiorgan failure . Gut ischemia increases the permeability of the gastrointestinal mucosa and thereby allows bacteria and endotoxin inside the gut lumen to enter the systemic circulation, resulting in the sepsis syndrome and eventually in multiorgan failure and death. Therapy designed to monitor and prevent gut hypoperfusion may therefore be able to prevent the development of multiorgan failure.
Gastric tonometry was designed to allow measurement of gastric pHi [20,21]. Gut ischemia results in increased production of hydrogen ion from accelerated hydrolysis of adenosine 5 prime-triphosphate, increased lactic acid production, and accumulation of CO2. Gastric tonometry relies on the principle that CO2 diffuses freely across tissue and cell membranes. Measurement of luminal PCO2 by tonometry therefore allows estimation of gut mucosal PCO2. The standard tonometric technique for measuring luminal PCO2 uses a nasogastric tube with a silicone balloon that is permeable to CO2. The nasogastric tube is inserted into the stomach and the balloon is filled with saline. A period of at least 30-60 min is allowed for CO2 to equilibrate between the intraluminal fluid and the saline inside the balloon. The saline is then aspirated and sent to the blood gas laboratory for analysis of PCO2. A correction factor for the incomplete equilibration of PCO2 across the balloon is used to estimate luminal PCO2. Intramucosal pH is then estimated using the Henderson-Hasselbalch equation, pH = 6.1 + log (HCO (3)-)/PCO2 centered dot 0.03, where (HCO3-) is the bicarbonate value from a simultaneous arterial blood sample, 6.1 corresponds to the dissociation constant of carbonic acid, and 0.03 represents the solubility of CO2 in plasma.
While tonometry is an effective technique for measuring gut PCO2, its actual implementation requires significant physician and nursing effort and cost. In addition to the logistical difficulties in obtaining data, there are other limitations to standard gastric tonometry. There is a significant time delay in obtaining values of pHi. As described above, saline must be injected into the balloon, left for at least 30 min, then aspirated and sent to the laboratory. There are also sources of error in the PCO2 measurement. Reports have indicated that standard blood-gas analyzers have significant error when measuring PCO2 in saline [22,23]. Takala et al.  demonstrated that the Nova Registered Trademark analyzer (Nova Biomedical, Waltham, MA) underestimated PCO2 by 50%-60%. Both Takala et al.  and Knichwitz et al.  have shown that the error is decreased by buffering the saline with a phosphate buffer. Luminal PCO2 can be altered by factors unrelated to intramucosal PCO2 such as the systemic administration of bicarbonate and the presence of acid, bacteria and stool in the stomach . Some institutions believe that gastric tonometry is only reliable when H2 blockers are used. Despite these limitations, clinical studies demonstrate that pHi trends in a single patient are an important predictor of outcome.
The new technique for gut intraluminal PCO2 monitoring described by Knichwitz et al.  in Anesthesia & Analgesia represents a significant technological advance over the saline-filled silicone balloon. Instead of estimating luminal PCO (2) by analyzing PCO2 from saline inside a silicone balloon, they directly measure luminal PCO2 with a fiberoptic PCO2 probe (Paratrend 7 Registered Trademark; Biomedical Sensors, High Wycombe, UK) that was originally developed for continuous intraarterial blood gas monitoring . Knichwitz et al.  point out that the small size of the probe, 0.5 mm in diameter and 60 cm in length, allows it to be placed easily through a standard nasogastric tube. Knichwitz et al. demonstrate that the fiberoptic PCO2 sensor accurately measures PCO2 under conditions that stimulate the gut lumen. In an in vitro experiment, known gas mixtures were allowed to equilibrate with water and the PCO2 of the water was measured by the fiberoptic sensor and by standard tonometric techniques. The fiberoptic sensor was markedly more accurate and had no significant time delay. In vivo performance was evaluated in pigs by measuring PCO2 in the ileal lumen with the fiberoptic sensor and comparing this with arterial and superior mesenteric vein PCO2. Fiberoptic PCO2 values correlated with both arterial and mesenteric vein PCO2 when PCO2 values were rapidly changed by hyperventilation and hypoventilation. Overall, this report demonstrates that measurement of luminal PCO2 by the fiberoptic technique is accurate and reflects physiological changes. Additional studies are, however, required to demonstrate its accuracy during mesenteric ischemia.
The impact of this technological advance may be profound because it provides a method of monitoring tissue perfusion that is continuous, real-time, easily obtainable, and noninvasive. Given the fact that packaging may eventually allow the probes to be reusable, it may also be relatively low cost. While some of the limitations of traditional tonometry still exist, the logistics of obtaining data and the errors in using blood gas machines are eliminated by this new technique. This advance may well propel tonometry from its use in intensive care units in a handful of academic medical centers into the operating room. As clinicians, we have already shifted our focus from monitoring blood pressure to monitoring cardiac output in order to assess the adequacy of therapy in patients undergoing major surgery. With the advent of easily obtainable pHi data, we may further shift our focus to maintaining normal gastric pHi in such patients. If this new technique allows accurate and continuous assessment of pHi, the true clinical implications of gut ischemia may be better defined in the next several years. Future clinical trials will need to focus on the cost-benefit implications of this therapy. However, treatment of multiorgan failure is extraordinarily expensive. If continuous monitoring of pHi does in fact result in a decreased incidence of multiorgan failure, such monitoring is likely to decrease costs as well as to decrease morbidity and mortality .
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