pH Stat vs Alpha Stat

Cerebral Autoregulation

• Cerebral autoregulation is the body’s adaptive response to maintain stable blood flow to the brain despite environmental variables, including PaCO₂, PaO₂, and blood pressure.
• Cerebral blood flow (CBF) is maintained within a mean arterial pressure (MAP) range of 60-150 mmHg. MAPs above or below this range produce higher or lower CBF, respectively.^1,2
• Oxygen and carbon dioxide partial pressures also affect CBF. As carbon dioxide builds up in the blood, cerebral vasodilation ensues, thereby increasing CBF. The CBF-PaCO₂ relationship is direct and positive (Figure 1). By contrast, the relationship between blood oxygen content and CBF is indirect and negative. CBF will increase with hypoxemia (PaO₂ less than 60 mmHg), and extreme hypoxemia provokes even more significant increases in CBF.¹
• Carbon dioxide plays a major role in CBF during CPB, and clinicians should understand that manipulation of PaCO2 can have both beneficial and deleterious effects. See the OA summary on carbon dioxide for more details. Link

Temperature and Solubility

• Solubility and temperature are inversely proportional.
  • As blood temperature decreases, gas solubility increases, and therefore the partial pressures of CO₂ and O₂ decrease (Henry’s Law).³
• As PaCO₂ decreases under hypothermic conditions, including during CPB cooling, blood pH increases.

Oxyhemoglobin Dissociation Curve

• Dissolved oxygen is only a small proportion of total oxygen in the blood. Most oxygen is attached to hemoglobin, and environmental conditions alter the avidity with which oxygen associates with hemoglobin (Figure 3).⁴

• As pH is manipulated during cardiac surgery, the interaction between dissolved and hemoglobin-associated oxygen changes.

Alpha Stat

• The “alpha” of “alpha stat” refers to a basic biochemical concept. Imidazole is a side chain on the amino acid histidine that acts as a critical acid-base buffer essential to enzyme activity. Imidazole groups can be either protonated or unprotonated, and the degree of protonation is determined by the surrounding pH. The ratio of protonated to total imidazole side chains is referred to as “alpha.”
• Mathematically we can depict this relationship as: pH = protein kinase A (pKa) + log([A^–]/[HA])
• When using the fractional alpha terms: pH = pKa + log(α / (1 – α))
• When pH = pKa: The concentrations of the protonated (HA) and deprotonated (A^–) forms are equal. Therefore, if alpha = 0.5, then α / (1 – α) = 1. Therefore, log(α / (1 – α)) = 0, which means pH = pKa
• When pH > pKa: The solution is more alkaline, leading to a higher concentration of the deprotonated form (A^–), so α > 0.5.
• When pH < pKa: The solution is more acidic, favoring the protonated form (HA), so α < 0.5.
• At a normal physiologic pH of 7.4, the pH is greater than the pKa of imidazole, which is 6.8; therefore, the alpha would be a value greater than 0.5. In reality, the alpha is 0.55. This means there are many more protonated imidazole groups at a higher pH.
• Imidazole has a temperature-dependent pKa, resulting in a stable proton-to-unprotonated histidine ratio (0.55 alpha value) across temperatures.
• Alpha-stat acid-base management relies on the assumption that the temperature-independent alpha value of imidazole residues preserves cellular enzymatic function during hypothermic conditions.
• Blood acid-base values on CPB are not corrected; they are evaluated after warming blood to 37°C on the arterial blood gas (ABG) analyzer.
• Although the clinician should understand that a hypothermic patient on CPB with normal PaCO₂ and pH, as measured at 37°C on an ABG analyzer, has in vivo respiratory alkalosis (i.e., the actual PaCO₂ and pH are lower and higher, respectively).

Advantages of Alpha Stat and Preferred Settings^5,6

• Preservation of cerebral autoregulation (potentially decreased microembolic cerebral events)
• Improved tissue metabolic suppression
• Better neurological outcomes in adults
• Preferred method, particularly in adults undergoing hypothermic circulatory arrest

Disadvantages of Alpha Stat

• Potential for nonuniform brain cooling and regionally inadequate cerebral protection
• Congenital heart surgery
  • Vasoconstriction in cerebral circulation and vasodilation in the pulmonary circulation can create a shunt away from the brain in pediatric patients.

pH Stat

• This method seeks to optimize blood gas values at the patient’s in vivo temperature rather than under normothermic conditions. CO₂ is therefore added to the patient’s blood in sufficient amounts to achieve a neutral pH at their given hypothermic temperature.

Advantages of pH Stat and Preferred Settings^5,6

• Particularly in pediatric populations, results in more rapid achievement of target cerebral hypothermia levels
• Yields more uniform cerebral perfusion due to CO₂-induced cerebral vasodilation and preserved CBF
• Theoretically, increased oxygen availability to tissues via the rightward shift of the oxyhemoglobin curve
• May protect against ischemic stroke due to increased CBF
• Potentially better neuro outcomes in children
  • Particularly favored in cyanotic neonates and infants in whom the cerebral autoregulatory response is immature and incomplete

Disadvantages of pH Stat

• Potential for a steal phenomenon away from stenotic sites in the brain
• Increased risk of cerebral hyperemia and/or microembolic events