Tissue CO2 Clinical References

Non-Invasive Early Warning System of Systemic Hypoperfusion: Circulatory Shock and Sepsis

 

by Michael R. Pinsky, MD and Jacques Creteur, MD

 

The Problem: Circulatory shock is defined as an inadequate oxygen (O2) delivery to tissue to sustain metabolic demand. If arterial oxygen content is adequate, then tissue ischemia develops only at the very extremes of low blood flow. Well before that time, normal physiologic adaptive mechanisms controlled by the autonomic nervous system and mediated primarily through increased sympathetic tone tend to sustain an adequate central arterial blood pressure despite falling total blood flow. Once this regulatory process is exhausted, however, systemic hypotension develops. Thus, systemic hypotension, defined as a mean arterial pressure <65 mmHg or a systolic arterial pressure <90 mmHg, occurs late in shock when tissue hypoperfusion is already compromising metabolic function. If circulatory shock associated with systemic hypotension persists, then generalized tissue ischemia manifests as end-organ failure, lactic acidosis and autonomic failure. If the bedside clinician waits for systemic hypotension to recognize circulatory insufficiency before treating their patient for circulatory shock, then he will have waited too long.

 

Tissue CO2 as a Solution: What is needed is a monitoring device that can identify decreasing tissue blood flow prior to impaired metabolic function. Since tissue can sustain oxidative phosphorylation (the central process of energy production of the cell) well into low blood flow states, both O2 extraction by the tissue and carbon dioxide (CO2) production remain relatively constant in a tissue bed as local blood flow initially declines. Although tissue O2 can be measured, owing to the heterogeneity of metabolic rates and the slow diffusion of O2 into the tissues from the blood, its measure to assess early forms of circulatory shock is poor. CO2 can also be measured and, in contrast to O2 measurement, changes in tissue CO2 levels can accurately track changes in local blood flow within physiologic limits owing to the high diffusing capacity of CO2 to cross lipid barriers and fluid spaces. Thus, a device that measures tissue CO2 levels could be very helpful in identifying early shock, as CO2 levels will rise well before tissue ischemia. This same device could be used to tract the effectiveness of resuscitation efforts, as CO2 levels will decline to their baseline values again once local blood flow returns to its baseline values.

 

Buccal CO2 as a Measure of Convenience: The oral mucosal constitutes an ideal site to measure tissue CO2, especially if the sensing probe is isolated from ambient air and can be seated in a patient’s mouth with minimal discomfort. Numerous studies have documented that both sublingual and buccal mucosal CO2 levels track circulatory stress in a quantitative fashion. In experimental models of hemorrhagic shock, sublingual CO2 levels rapidly rise before hypotension develops and fall during resuscitation only after total cardiac output is restored, even though blood pressure is restored earlier.

 

All forms of circulatory shock, if associated with an initial decrease in cardiac output, will be associated with a rise in buccal CO2, and this rise will occur early during the adaptive stage of shock when blood pressure remains normal. The two most common forms of shock are hemorrhagic and septic shock. Both initially present with decreased blood flow, though for different reasons. Thus, monitoring buccal CO2 levels for its increase in a patient at risk for sepsis or bleeding constitutes a reasonable cost-effective early warning monitor. Indeed, buccal CO2 monitoring may represent an ideal tool for a non-invasive monitor that can be applied early so as to target high-risk patient subgroups without fear of iatrogenic complications or false negative results. Buccal CO2 may also be used to titrate resuscitation therapies, although most clinical studies show that the major benefit of any monitoring in septic shock comes from its early identification, triggering early appropriate antibiotic use and initial fluid resuscitation.

Jin, et al “Decreases in Organ Blood Flows Associated with Increases in Sublingual PCO2 During Hemorrhagic Shock”; Journal American Physiological Society 1998; 8750-7587: 2360-4

 

Pernat, et al “Effects of Hyper- and Hypoventilation on Gastric and Sublingual PCO2”; Journal American Physiological Society 1999; 8750-7587: 933-937

 

Povoas, et al “Comparisons Between Sublingual and Gastric Tonometry During Hemorrhagic Shock”; CHEST 2000; 118:1127-1132

 

Sproesser, et al “Capnometry for Diagnosing and Monitoring Cardiopulmonary Crises”; Resident & Staff Physician 2000; 46:17-27

 

Weil, “Tissue PCO2 as Universal Marker of Tissue Hypoxia”; Minerva Anestesiologica 2000; 66:343-7

 

Yee & Susanto, “Sublingual Capnometry: In Search of its Holy Grail”; CHEST 2000; 118:894-96

 

Pinsky MR. Both perfusion pressure and flow are essential for adequate resuscitation. Sepsis 4(2): 143-146, 2001.

 

Dantzker, “Monitoring Tissue Oxygenation: The Quest Continues” CHEST 2001; 120:701-2

 

Marik, “Sublingual Capnography: A Clinical Validation Study”; CHEST 2001; 120:923-37

 

Baron, et al “Diagnostic Utility of Sublingual PCO2 for Detecting Hemorrhage in Patients with Penetrating Trauma”; Abstract SAEM 2002 (361)

 

De Backer, et al “Microvascular Blood Flow is Altered in Patients with Sepsis”; American Journal of Respiratory and Critical Care Medicine 2002; 166:98-104

 

Creteur, et al “Sublingual PCO2 Monitoring in Patients with Septic Shock”; Presentation #65 Critical Care Congress 2003

 

Laine, et al “Regional vs. Global Oxygenation Following Left Ventricular Assist Device Implantation”; Abstract #205 Critical Care Congress 2003

 

Marik, “Sublingual Capnometry versus Traditional Markers of Tissue Oxygenation in Critically Ill Patients”; Critical Care Medicine 2003; Vol 31, No 3:818-22

 

Verdant, et al “Sublingual Microcirculation Reflects Intestinal Mucosal Microcirculation in Sepsis: A Quantitative Analysis”; Oral Abstract #191 Critical Care Congress 2003

 

Ward, et al “Performance of Noninvasive Tissue Oxygenation Indicators in Detecting Shock Due to Hemorrhage”; Oral Abstract #92 Critical Care Congress 2003

 

Grindlinger, et al “Use of the Esophageal Doppler and Sublingual Capnometer in the Hemodynamic Assessment of Mechanically Ventilated Surgical Patients”; Poster Presentation CHEST 2004

 

Creteur, et al “Sublingual capnometry tracks microcirculatory changes in septic patients”; Intensive Care Medicine 2006; 32: 516-523

 

Zenker S, Polanco PM, Torres A, Vodovotz Y, Puyana JC, Pinsky MR, Clermont G. Continuous sublingual pCO2 as a rapid indicator of changes in tissue perfusion in hemorrhagic shock: an experimental study. Shock 25 (6) Supplement 1:57, 2006.

 

Baron, et al “Sublingual Capnometry for Rapid Determination of the Severity of Hemorrhagic Shock”; Journal of Trauma 2007; 62:120-124

 

Jones, et al “Sepsis-Induced Tissue Hypoperfusion”; Crit Care Clin 25 (2009): 769-779

 

Xu, et al “Fluid Resuscitation Guided by Sublingual Partial Pressure of Carbon Dioxide During Hemorrhagic Shock in a Porcine Model”; Shock Society 2013