Acid-base balance

The precise functions of enzymes and proteins within cells are dependent on pH; therefore, a number of mechanisms exist to maintain hydrogen ion concentration ([H⁺]) within a very narrow range in the face of CO₂, H⁺, and OH⁻ production during normal metabolism and despite physiologic and pathologic challenges. Intracellular and extracellular chemical buffering, transcellular diffusion or transport of electrically charged ions, and excretion or retention of acid or alkali by the kidneys and of CO₂ by the lungs maintain acid-base homeostasis. The most important buffer in the extracellular space is NaHCO₃, also referred to as the carbonic acid/bicarbonate buffer.

The carbonic acid/bicarbonate buffering system

Because CO₂ is not sufficiently soluble in blood, a number of mechanisms have had to evolve over time to facilitate the transport of CO₂ from the periphery to the lungs (Chapter 22). The most efficient of these mechanisms combines CO₂ with H₂O to form carbonic acid, which in turn dissociates into hydrogen ions and bicarbonate ions.

The reactions are reversible and subject to the law of mass action:

< ?xml:namespace prefix = "mml" />H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3−

In peripheral tissues—where CO₂ is continuously produced—the reaction proceeds from the left to the right, whereas in the lung the reaction proceeds in the opposite direction. The H⁺ created by the reaction must be buffered in order to preserve physiologic pH.

The carbonic acid/bicarbonate buffer

A buffer is typically a weak acid in equilibrium with its conjugate base that minimizes changes in the pH of a solution when an acid or a base is added; bicarbonate in the previous reaction is the conjugate base of carbonic acid. The Henderson-Hasselbalch equation describes the effects of changes in carbonic acid and bicarbonate on pH. Because the blood concentration of H₂CO₃ is so low, it can be replaced by α × PCO₂, wherein α is the solubility coefficient for CO₂ in plasma:

pH=pK+logHCO3–α×PCO2

In human plasma, pK is 6.1, α = 0.03 mmol·L⁻¹ ·mm·Hg⁻¹ and pH is 7.4 at a body temperature of 37°C. This yields:

7.4=6.1+logHCO3–0.03×PCO2

The amount of hydrogen any chemical can buffer is highest when its pH equals pK. Yet, in human plasma, the pK of 6.1 of the carbonic acid [CO₂]/bicarbonate buffer is not within the optimal buffer range. Therefore, the buffering capacity is dependent on the HCO₃⁻/PCO₂ ratio, which is kept in a narrow range by means of neuroventilatory PCO₂ control. To preserve a pH of 7.4, the ratio of bicarbonate to partial pressure of CO₂ must be maintained at 20:1 because the log of 20 is 1.3 (1.30103). Indeed, this is the case because the normal HCO₃⁻ concentration is 24 mEq/dL and the normal PaCO₂ is 40 mm Hg. Substituting in the preceding equation yields

pH = 6.1 + log of [24/(0.03 × 40)] = 6.1 + log of [24/1.2]= 6.1 + log of 20 = 6.1 + 1.3= 7.4

Metabolic acidosis

Several causes of metabolic acidosis (Box 95-1) may occur simultaneously in patients with critical illness. Acidemia may impair cardiac contractile function, constrict pulmonary arteries, and reduce adrenergic receptor responsiveness to catecholamines; therefore, many clinicians often restore the HCO₃⁻/PCO₂ ratio to 20 by administering bicarbonate. Treatment of the underlying problem is then undertaken to ultimately restore and maintain a pH of 7.4.

Formulation

NaHCO₃ is available for injection as an 8.4% solution. It is a highly hypertonic sodium solution in which Na⁺ is 1 mEq/mL and HCO₃⁻ is 1 mEq/mL.

Therapeutic uses of sodium bicarbonate

NaHCO₃ is administered intravenously to patients to treat a variety of conditions, including, but not limited to, lactic acidosis, metabolic acidosis during cardiopulmonary resuscitation, circulatory failure in infants and children, neonatal acidosis from apnea and circulatory collapse, hemodynamic instability during aortic surgery, postreperfusion syndrome during liver transplantation, acidosis associated with malignant hyperthermia, as a buffer during cardiopulmonary bypass, diabetic ketoacidosis, and others.

Lactate acidosis

Lactate acidosis caused by anaerobic glycolysis due to inadequate O₂ delivery (see Box 95-1) is probably the most common cause of metabolic acidosis faced by the anesthesia provider. If the pH is below 7.2 to 7.25 or is decreasing to those levels despite all measures to restore O₂ delivery (e.g., normalization of blood volume and composition, restoration of adequate ventilation, or pharmacologic or mechanical support of cardiac function), many clinicians will administer NaHCO₃.

The following rules must be carefully observed when NaHCO₃ is used: (1) it is more important to treat the underlying problem than to correct pH; (2) only severe acidosis should be corrected (i.e., base excess less than −14 (3) pH should not be reversed to normal but to about 7.25 to 7.3 (overcorrection should be avoided); (4) adequate ventilation to remove the generated CO₂ is crucial; (5) NaHCO₃ must be administered slowly or in several small doses; and (6) treatment with NaHCO₃ must be guided by repeated blood gas measurements.

Dose recommendations

One formula to calculate an NaHCO₃ dose to treat a metabolic acidosis established by the base excess (BE) is determined from an arterial blood gas measurement and body weight (BW):

NaHCO3 (mEq) = 0.3 · BW (kg) · BE (mEq/L)

Initially only half of the calculated dose should be administered; administration of the second half of the calculated dose should be guided by a repeat blood gas analysis or the initial dose should be 1 mEq/kg NaHCO₃ and may be followed by 0.5 mEq/kg if justified by a repeat arterial blood gas analysis. In severe circulatory failure, arterial blood gas analysis may not reflect the severity of the tissue and venous acidosis.

Because alkalosis shifts K⁺ from the plasma into cells, NaHCO₃ is a primary agent for acute treatment of hyperkalemia.

Toxicity

Treatment with NaHCO₃ is not without side effects, which include but are not limited to cellular dysfunction, central nervous system acidosis and impaired adrenergic activity, metabolic alkylosis, hypernatremia and hyperosmolarity, and milk alkali syndrome.