Special Feature: Assessing Tissue Oxygenation in the Critically Ill Patient
June 1, 2001 7 minutes read
Special Feature
Assessing Tissue Oxygenation in the Critically Ill Patient
By Francisco Baigorri, MD, PhD
Present day monitoring offers us increasing possibilities of measuring tissue gas tensions.1 Electrode miniaturization, fiberoptics, and spectrophotometry are among the technological advances that have made this feasible. As tissue hypoxia seems to play a significant role in the development of organ failure in critically ill patients, these advances may assist greatly in the evaluation of end points of treatment of our patients. However, it remains to be seen whether these new techniques can add value to therapeutics and patient outcome.
The objective of this essay is to briefly review basic concepts about detecting critical oxygen deprivation in the light of the new techniques currently available for bedside assessment of tissue perfusion and oxygenation.
Tissue Energetics2,3
The cells are always using oxygen because it is required for the efficient production of energy in order to maintain their structural integrity. Tissue PO2 reflects a balance between the rate of oxygen transport to the tissues in the blood and the rate at which the oxygen is used by those tissues. However, the distance between the capillaries and the cells is not homogeneous. In many instances, there is a considerable diffusion distance. Consequently, the normal intracellular PO2 ranges from as low as 5 mm Hg to as high as 40 mm Hg, averaging 23 mm Hg. Studies suggest that oxidative phosphorylation can be optimally carried out at a cellular PO2 in the 1-3 mm Hg range. This low operating level would make any change in tissue PO2 too subtle to use as a clinical indicator of a correctable problem.4 This brings us to the question of whether direct measurements of individual tissue PO2, were they clinically available, would be of help. Ultimately, what we really need to know is the state of tissue energetics.3
Carbohydrate, lipid, and protein are partially digested in the cytoplasm, and then enter mitochondria, where they are oxidized by the tricarboxylic acid (TCA) cycle. Reducing equivalents in the form of FADH2 and NADH are produced to enter the electron-transport chain, which generates ATP by oxidative phosphorylation. Energy-rich electrons flow down a "waterfall" of progressively less energetic oxidation-reduction (redox) couples: NADH/NAD; reduced/oxidized NADH dehydrogenase; reduced/oxidized cytochrome C; and reduced/oxidized cytochrome a,a3. Cytochrome a,a3 catalyzes the final reaction wherein electrons are transferred to oxygen to form water.
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The redox state of cytochrome a,a3 is determined by the flow of electrons through the electron-transport chain and by the availability of oxygen; thus, it reflects the overall activity of oxidative metabolism in the cell.
As oxygen becomes progressively more scarce, the redox value of each redox couple increases, reflecting a high "voltage" of electrons, stimulated by energy demand that cannot flow down the electron-transport chain to produce ATP because of the "resistance" produced by decreased oxygen availability. A second consequence of oxygen deprivation is intracellular metabolic acidosis. It seems that this phenomenon represents unreversed ATP hydrolysis.
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Notably, it can occur in the absence of lactate. Hyperlactatemia occurs during anaerobic metabolism because the TCA cycle is shut down and NAD+ is not available to be converted to NADH. Because glycolysis requires a constant supply of NAD+, pyruvate is converted to lactate in the cytosol, producing a molecule of NAD+.
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Lactate diffuses back into the bloodstream and is converted back into pyruvate and glucose in the liver. Elevated lactate accumulates in the blood in low flow states from decreased clearance by the liver. Alternately, lactate levels can also be increased by nonhypoxic mechanisms, mainly in sepsis. The nonhypoxic mechanisms of hyperlactatemia in the critically ill were already commented on in Critical Care Alert.5
Targets of Monitoring
Figure 1 summarizes the possibilities of monitoring as a consequence of the facts we have already mentioned.
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Figure 1. Targets of Monitoring for Assessment of Tissue Perfusion and Oxygenation |
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Adapted from: Beilman GJ, Cerra FB. The feature: Monitoring cellular energetics. Crit Care Clin. 1996;12:1031-1042. |
Oxygen transport, measured as a product of flow and the arterial oxygen content, is a commonly evaluated clinical indicator of adequate tissue oxygenation. Under conditions in which oxygen supply becomes limited but microvascular regulation is intact, such as may occur during hypovolemic shock, corrections of global hemodynamics and oxygen-derived variables would be expected to restore tissue oxygenation. Nevertheless, in most critically ill patients, factors that determine the regional distribution of blood flow as well as events that may alter the normal control of the microvascular bed prevent any simple translation of changes in oxygen transport into similar quantitative or even qualitative changes in oxygen delivery.6
Thus, measurement of individual organ and tissue oxygenation is an important goal. These measurements are difficult, require specialized techniques, and are not widely available. Presently, only gastric tonometry and near-infrared spectroscopy (NIRS) are used in clinical practice.
Near-Infrared Spectroscopy (NIRS)
The oxidation state of cytochrome a,a3 can be measured with NIRS.7 Each cytochrome in the electron-transport chain has characteristic light absorption bands varying in intensity with its redox state. NIRS uses the ability of near-infrared light to pass through biologic materials such as skin, bone, and muscle with much less scattering than occurs with shorter wavelengths of light. A known amount of incident light is used to illuminate a tissue of interest. The amount of light recovered after the photons pass through the tissue depends on the amount of light absorption by chromophores in the tissue and the degree of light scatter in the tissue. The only major chromophores known to have significant oxygen-dependent absorption spectra are hemoglobin, myoglobin, and cytochrome a,a3. However, absolute concentrations cannot be ascertained by this method because of as-yet unquantified biophysical variables. Therefore, this technique remains semi-quantitative.
Most of the studies concerning NIRS have been performed in experimental and clinical settings and focused on brain and muscle after different types of hypoxic injuries.8 On the other hand, high-energy phosphate levels can be measured using 31P nuclear magnetic resonance (NMR) spectroscopy. Data from NMR spectroscopy are obtained as peaks of various compounds. Unfortunately, this technology still has a number of significant limitations when applied to the ICU setting.
Gastric Tonometry
Gastric tonometry has been the object of a recent essay in Critical Care Alert.9 Briefly, this technique determines intraluminal PCO2 that is assumed to be in equilibrium with the PCO2 in the gastric mucosa. The gut mucosa is highly susceptible to diminished tissue perfusion, and it has been found that a rise in intraluminal PCO2 is an early indicator of inadequate intestinal tissue oxygenation.10 However, in resuscitated endotoxemic pigs, endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia, as measured with multi-wired PO2 electrodes.11
This observation brings us to the question of whether gastric acidosis seen in sepsis is due to a derangement in cellular energy pathways or is based on a pathologic redistribution of flow, giving rise to hidden hypoxic microcirculatory units next to well-perfused units. Monitoring of subcutaneous PO2 might become a complementary technique to gastric tonometry in shock resuscitation. Subcutaneous tissue is readily accessible and, using rapidly responsive sensors in the subcutaneous tissue and in the ileum, it has been demonstrated that subcutaneous PO2 is more rapidly responsive than gut luminal PCO2 and arterial lactate in an animal model of evolving hemorrhagic shock.12 Moreover, there was close concordance between subcutaneous PO2 and gut luminal PO2 and PCO2. An elevated tissue PCO2 on its own does not distinguish between ischemic and septic etiologies as it was previously commented. However, as tissue PO2 is reduced in ischemia and often increased in sepsis,11,13 combining the 2 measurements may be useful to distinguish between these states.
Conclusion
Current monitoring of critically ill patients mainly uses measurement of global hemodynamic and oxygen-derived variables. Limitations of these parameters to detect critical oxygen deprivation in individual organs are well known. Fortunately, an increasing number of techniques are becoming available in clinical practice for assessment of tissue perfusion on an organ or tissue level. Among these techniques, estimation of organ redox state and assessment of organ metabolic acid production appear particularly promising.
References
1. Venkatesh B, Morgan TJ. Monitoring tissue gas tensions in critical illness. In: Vincent JL, ed. Yearbook of Intensive Care and Emergency Medicine. Berlin, Germany: Springer-Verlag; 2001:251-265.
2. Schlichtig R, Tønnessen TI, Nemoto EM. In: SCCM, ed. Critical Care—State of the Art. Society of Critical Care Medicine; 1987:239-273.
3. Beilman GJ, Cerra FB. The future. Monitoring cellular energetics. Crit Care Clin. 1996;12:1031-1042.
4. Dantzker DR. Monitoring tissue oxygenation: The search for the Grail. Chest. 1997;111:12-14.
5. Russell JA, Baigorri F. Is measuring serum lactate clinically useful? Critical Care Alert. 1995;3:14-16.
6. Ince C, Sinaasappel M. Microcirculatory oxygenation and shunting in sepsis and shock. Crit Care Med. 1999;27:1369-1377.
7. Simonson SG, Piantadosi CA. Near-infrared spectroscopy. Clinical applications. Crit Care Clin. 1996;
8. Guery BPH, et al. Redox status of cytochrome a,a3: A noninvasive indicator of dysoxia in regional hypoxic or ischemic hypoxia. Crit Care Med. 1999; 27:576-582.
9. Durbin CG. Gastric tonometry—Research toy or clinical tool? Critical Care Alert. 2000;7:78-80.
10. Schlichting E, Lyberg T. Monitoring of tissue oxygenation in shock: An experimental study in pigs. Crit Care Med. 1995;23:1703-1710.
11. van der Meer TJ, et al. Endotoxemia causes ileal mucosal acidosis in the absence of mucosal hypoxia in a normodynamic porcine model of septic shock. Crit Care Med. 1995;23:1217-1226.
12. Venkatesh B, Morgan TJ, Lipman J. Subcutaneous oxygen tensions provide similar information to ileal luminal CO2 tensions in an animal model of haemorrhagic shock. Intensive Care Med. 2000;26: 592-600.
13. Rosser DM, et al. Oxygen tension in the bladder epithelium rises in both high and low cardiac output endotoxemic sepsis. J Appl Physiol. 1995;79: 1878-1882.
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