Cerebral Oxygenation during Deep Hypothermic Cardiopulmonary Bypass: Is Hemoglobin Relevant?

To the Editor:--I was fascinated by Dexter and Hindman's model of cerebral oxygen delivery. [1]To examine the behavior of their model in more detail, I loaded the equations into a Hewlett Packard HP-48GX programmable calculator and examined their behavior under a variety of conditions, using the calculator's Equation Solverapplication.

This examination led me to conclude that it is not the shift in P⁵⁰alone that is responsible for the change in the relation between SV^O2and CMR%(percentage of maximal CMRO²) seen with hypothermia, but rather the interaction between that shift and the relation between interstitial oxygen tension (PinO²) and CMR%. In brief, the target (or basal) CMR% determines the PinO²(and therefore the PV^O2) needed to support that CMR%. The authors chose a model (Michaelis-Menten kinetics, eq. 9)[2,3]that requires relatively high Pin^O2to support high CMR%. As the P⁵⁰shifts left with hypothermia, it is not surprising to find that the high PV^O2, which is determined by the high PinO², corresponds to higher and higher SV^O2. Although this model for the relation between Pin^O2and CMR% has some support experimentally, [4]neither this relation nor the target CMR% has been measured in humans. If the true target CMR% or the relation between Pin^O2and CMR% in humans were such that lower values of Pin sub O²could support adequate CMR% at hypothermia, then the shift in P⁵⁰with hypothermia would not result in such dramatic alterations in the relation between CMR% and SV^O2. In examining this issue, I found that even very subtle, minor changes in the relation between Pin^O2and CMR% produced major alterations in the way the relation between SV^O2and CMR% changes with temperature.

The simplest example of this would be a reduction in the target CMR%, as might be seen with anesthesia, bypass, or hypothermia. Using the authors' data for an infant at 17 degrees Celsius (Figure 1), it can be seen that if the target CMR% were 90 +/- 5%, the SV^O2would lie in the range 97.3–100%, making it impossible to rely on SV^O2to follow changes in CMR% until they become quite severe. Conversely, if the target CMR% were 85 +/- 5%, the SV^O2would lie in the range 78.6–97.3%; although this is different from the relation between SV^O2and CMR% at normothermia, it might still be possible to use SV^O2to follow trends in CMR%.

Further examination of the Dexter-Hindman model suggested that hemoglogin saturation, and hemoglobin per se, are essentially irrelevant to cerebral oxygen delivery during deep hypothermia, because dissolved oxygen is adequate to provide almost all cerebral oxygen needs. For an infant at Pa^O2greater or equal to 300 mmHg and T < 18 degrees Celsius, more than 90% of CMR^O2is provided by dissolved oxygen. Although there may be reasons to avoid hyperoxia during bypass (formation of bubbles during rewarming, generation of free radicals), this interpretation of the author's model suggests the possibility of stroma-free perfusion during deep hypothermic bypass, which might have important implications for conservation of blood constituents and visualization of the surgical field during low-flow bypass. This interpretation also suggests that oxygen solubility enhancing agents (e.g., perfluorocarbons) may more effectively increase cerebral oxygen availability during low-flow deep hypothermic bypass than hemoglobin (erythrocytes or stroma-free hemoglobin); the ineffectiveness of hemoglobin preparations in this context is supported by other work from the authors. [5].

Dexter and Hindman are to be commended for recognizing the importance of the shift in P⁵⁰on interpretation of SV^O2during deep hypothermic bypass and for emphasizing the potential risks of widespread adoption of jugular venous bulb or cerebral near-infrared spectroscopy monitoring based on the assumption that a high SV^O2implies adequate, or even luxuriant, cerebral oxygen availability. However, given that very small changes in the model can produce major changes in how the relation between CMR% and SV^O2changes with temperature, before we can draw conclusions about the role of SV^Osub 2 monitoring during bypass, it will be necessary to determine the target CMR% and the relation between Pin^O2and CMR% in humans both awake and anesthetized, on and off bypass, and at normothermia and hypothermia.

Joel B. Gunter, M.D., Associate Professor of Clinical Anesthesia and Pediatrics, Department of Anesthesia, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229.

(Accepted for publication July 1, 1996.)