pH-Stat or alpha-Stat? ….Doing the Right Thing for the Wrong Reasons?

[Jens]

In heart surgery of children in case of strong cooling (deep hypothermal) there are two strategies with regards of pH regulation:
pH-stat: keeping the measured pH constant
alpha-stat: let the measured pH increase with falling temperature (actually doing nothing)

(If you search in google scholar with "pH-stat alpha-stat" you will see the corresponding publications)

I had a discussion with my daughter about it and we came to the following explanation (see chapter explanation below). Anything wrong with this thoughts?


Theory:
An pH electrode is measuring the absolute concentration of H₃O⁺ (not the relation of [H₃O⁺] to [OH^-]). pH value changes caused by temperature changes are biochemically to a large extend irrelevant, because the concentration of OH^- is simultaneously also increased (in case of increase of temperature) or also decreased (in case of decrease of temperature). H₃O⁺ and OH^- have opposite effect of all those other molecules which can accept or release H⁺. This means a decrease in temperature also decreases the concentration of H₃O⁺ and thereby increases the pH value (measured by an electrode), but the concentration relation of other buffering substances is unchanged: For example the relation of [H₂PO₄^- ] to [HPO₄^2- ] remains the same. If we could measure the relation of [H₂PO₄^- ] to [HPO₄^2- ] directly and in a simple way, we had a much more appropriate quantity for the acid-base-relation in living organisms or directly in cells.

Practice:
Out of this considerations you should expect that it is better to not correct the measured pH value of patients which are strongly cooled for a operation at the heart (called alpha-stat strategy). This is because the pOH is increasing simultaneously and the measured change is misleading. But there have been teams which have corrected the increased pH value. (This correction is achieved by adding CO₂ in the air breathed in by the patients [1]. This CO₂ is partially transforming into H₂CO₃ , which is releasing H⁺.)
Clinical studies have shown [1] that heart operations with strongly cooled patients statistically have less complications, if the measured pH value had been corrected (pH-Stat strategy). This seems paradox.

Explanation:
The moderately increased concentration of CO₂ in the blood puts the body into the same position as a diver, which has stopped breathing for a while (or more relevant from biological evolution point of view: a child fallen into water). This is valid also because the cooled state also resembles the diving with regards of the temperature (see the diving reflex). It is just reasonable to assume, that the body – caused by the increase of CO₂ concentration – takes all measures intended by the evolution, to avoid damages caused by lack of oxygen. A part of this is especially the increase in peripheral resistance to concentrate the blood flow for the survival critical organs [2]. This explains directly the decrease of complications (especially decrease of brain damage) caused by CO₂ supply.
pH-Stat strategy therefore is a wrong term. You should better call it CO₂-supply strategy. Keeping the misleading measured pH constant is just by chance and has most likely nothing to do with the effect.

Consequences:
Supplying even more CO₂ (and simlutaneaously keeping a high oxygen concentration) could have an even improved effect. It is also possible (but less likely) that a combination of alpha-Stat and CO₂-supply gives the best results. However, this means you have to compensate the pH-effect of the CO₂-supply by other means (infusion?). (preferably of course to be tested with mamals which also show a weak diving reflex like humans).

References:
[1] Du Plessis AJ et. al. “Perioperative Effects of Alpha-Stat Versus pH-Stat Strategies for Deep Hypothermic Cardiopulmonary Bypass in Infants”, J Thorac Cardiovasc Surg 1997; 114:991-1001
http://intl-jtcs.ctsnetjournals.org/cgi/content/full/114/6/991
[2] Angell James J, De Burgh Daly M “Cardiovacular Responses in Apnoeic Asphyxia: Role of Arterial Chemoreceptors and the Modification of their effects by a Pulmonary Vagal Inflation Reflex, J. Physiol. (1969), 201, pp. 87-104
http://jp.physoc.org/content/201/1/87.full.pdf

(sorry for reference [2] which is very old, but I could not qickly find a newer one which is publicly available for free)

Edited January 1, 2013 by Jens