pH and acid–base metabolism

The normal pH of arterial blood is 7.4 (± 0.05). Bicarbonate and non-bicarbonate systems play important roles in buffering pH changes.

Alpha-stat and pH-stat strategies for blood gas management

The optimal pH management strategy during hypothermic CPB is as yet undetermined. The two main strategies utilized clinically, alpha-stat and pH-stat, differ in their approach to the acid–base alterations that occur with hypothermia. As blood temperature falls, gas solubility rises and the partial pressure of carbon dioxide decreases (PCO₂ decreases 4.4% for every °C drop in temperature). With alpha-stat management, arterial gas samples are not corrected for sample temperature and the resulting alkalosis remains untreated during cooling; with pH-stat management, arterial blood gas samples are temperature corrected and carbon dioxide is added to the gas inflow of the CPB circuit so that the PCO₂ and hence pH, is corrected to the same levels as during normothermia. The advocates of alpha-stat point to potential benefits in terms of the function of intracellular enzyme systems and the advantage of preserving cerebral autoregulation. Proponents of pH-stat, which results in cerebral vasodilation, cite, as advantages, higher levels of oxygen delivery to the brain and enhanced distribution of blood flow. However, the higher cerebral blood flows associated with pH-stat also have the potential to carry more gaseous or particulate emboli to the brain.

Alpha-stat management is based on the concept that the dissociation constant, pK, of the histidine imidazole group changes with temperature in a manner nearly identical to physiological blood buffers. Hence, the ionization state (α) of this group stays the same, irrespective of temperature. As the imidazole group’s ionization state is a key determinant of intracellular protein function, advocates of alpha-stat management contend that this strategy promotes normal protein charge states and function, even at low temperatures.

The pH-stat approach requires increases in the total carbon dioxide content of the blood as the temperature falls in order to maintain fixed temperature-corrected pH values. The optimal pH of most enzymatic reactions does vary with hypothermia, mostly in accordance with the predictions of the alpha-stat hypothesis. Hence, the relative acidosis of pH-stat would be expected to lower enzymatic reaction rates. Whether this is beneficial in reducing energy consumption, or harmful by impairing key cellular homeostatic mechanisms, is unclear.

Differences in alpha-stat and pH-stat management become progressively greater as temperature is reduced. The effect is quite profound below 25°C, but above 32°C the change in CO₂ solubility is small and of much less clinical and physiological relevance. This is further evident when one appreciates how little CPB time most adult cardiac surgical patients spend at hypothermic temperatures. Most cases are conducted with mild hypothermia and in those much of CPB time is spent transitioning to, or from, those temperatures; the actual time on CPB spent below 32°C may only be 25% of the total CPB time. Thus, although frequently discussed, alpha-stat versus pH-stat management is of little actual relevance in most adult cardiac surgery.

Potassium (K⁺)

Hyperkalemia is the most common electrolyte disturbance during CPB. Potassium levels can be lowered using diuretics, insulin, and dextrose administration, or hemofiltration. The treatment of choice is dictated by the potassium level, the persistence of rise in potassium levels, and the presence or absence of electrophysiological disturbances. Serum potassium levels transiently rise with the administration of cardioplegia and this will usually correct without treatment within a short period after ceasing delivery of cardioplegia. Potassium levels in the range 5.5–6.5 mmol/l can be treated with administration of a diuretic, usually furosemide 20–40 mg. In some centers, levels between 6.5 and 7 mmol/l are treated using insulin and dextrose infusions. Levels above 7 mmol/l or persistently raised potassium levels can be lowered using “zero balance hemofiltration.” A crystalloid solution, typically normal saline, is added to the CPB circuit to maintain circulatory volume and then removed by hemofiltration causing concomitant removal of potassium. As this technique can result in the loss of significant amounts of bicarbonate through the hemofilter, it should be replaced using sodium bicarbonate titrated to blood bicarbonate levels.

The urgency or need to treat hyperkalemia should in part be determined by the presence or absence of electrophysiological disturbance. In the absence of ECG changes, moderate hyperkalemia may not require treatment. If treatment is chosen, its effect should not be longer than the anticipated period of hyperkalemia. It is important to note that during CPB extracellular potassium may rise but typically, even untreated, increases in K⁺ levels are nearly always transient, as the extracellular potassium concentration in the plasma is quite small relative to the intracellular capacity for its uptake. Rapid shifts to the intracellular space and urinary excretion often correct K⁺ levels quite quickly after CPB.

Hypokalemia, usually less than 4.5 mmol/l, is treated by administration of potassium chloride, normally in 10–20 mmol boluses. It is worth bearing in mind that rapid bolus administration of potassium during CPB may cause transient vasodilatation. Potassium levels alter with temperature. Treatment should thus be undertaken in the context of:

Ideally, potassium is finally corrected before separation from CPB using results of electrolyte measurements taken at a body temperature of not less than 35°C.

Calcium (Ca²⁺)

Calcium levels are reduced by hemodilution, chelation by preservatives in bank blood or by hemofiltration. Significantly low serum Ca²⁺ levels are generally corrected close to the termination of CPB, when the aortic cross-clamp has been removed, a cardiac rhythm has been established, and the temperature is approaching normothermia. One gram (or 3–5 mg/kg) of calcium chloride is usually all that is required to normalize serum ionized calcium levels (1–1.5 mmol/l). Administration of Ca²⁺ may exacerbate reperfusion injury and should be avoided immediately before or after cross-clamp removal. Timing of administration can be guided by normalization of cardiac conduction indicating adequate reperfusion.

Magnesium (Mg⁺)

Magnesium depletion occurs during CPB if hemofiltration is used or if there is high volume diuresis, particularly with loop diuretics. In these situations, a 2 mg bolus of Mg⁺ may be added empirically into the circuit after the core temperature has reached 34°C and the aortic cross-clamp has been removed. Ideally, if Mg⁺ levels are available, Mg⁺ administration should be titrated according to blood levels.