Sodium Bicarbonate

Indications

Hyperkalemia (see Hyperkalemia, [[Hyperkalemia]])

  • Mechanism: sodium bicarbonate drives potassium intracellularly

Metabolic Acidosis

Diabetic Ketoacidosis (DKA) (see Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State)

  • Indications: pH <6.9-7.0 (however, evidence for this recommendation is lacking)
    • Patients with Hemodynamic Compromise (Due to Impaired Myocardial Contractility and Vasodilation) or Life-Threatening Hyperkalemia May Particularly Benefit from Bicarbonate Administration to Correct the pH

Lactic Acidosis (see Lactic Acidosis)

  • Adverse Effects of Acidemia: these (selected adverse effects) provide a rationale for administering bicarbonate with pH <7.1
    • Arrhythmias
    • Arterial Vasodilation and Venoconstriction
    • Decreased Left Ventricular Contractility
    • Impaired Responsiveness to Catecholamine Vasopressors (Nat Rev Nephrol, 2012) [MEDLINE]
  • Indications: pH <7.1 (however, evidence for this recommendation is lacking)
    • This is due to the fact that at pH <7.1, small changes in pCO2 and serum bicarbonate result in large changes in the serum pH
  • Clinical Efficacy: neither of these trials demonstrated clinical benefit with bicarbonate administration in patients with pH >7.1
    • Trial of Sodium Bicarbonate in Critically Ill Patients with Lactic Acidosis (Ann Intern Med, 1990) [MEDLINE]
      • Sodium Bicarbonate Did Not Improve Hemodynamics in Critically Ill Patients with Metabolic Acidosis and Hyperlactatemia
      • Sodium Bicarbonate Did Not Increase the Cardiovascular Response to Infused Catecholamines in in Critically Ill Patients with Metabolic Acidosis and Hyperlactatemia
      • Sodium Bicarbonate Decreased Plasma Ionized Calcium and Increased the pCO2
    • Trial of Sodium Bicarbonate in Lactic Acidosis (Crit Care Med, 1991) [MEDLINE]
      • Administration of sodium bicarbonate did not improve hemodynamic variables in patients with lactic acidosis, but did not worsen tissue oxygenation

Non-Anion Gap Metabolic Acidosis (NAGMA) (see Metabolic Acidosis-Normal Anion Gap)

  • xxx

Pharmacology

Sodium Bicarbonate

  • Initial Event After Sodium Bicarbonate Infusion: Sodium Bicarbonate Rapidly Diffuses into the Extracellular Space (and Some into the Intracellular Space) and Combines with a Hydrogen Ion to Form H2CO3 (Carbonic Acid)
    • Some Bicarbonate Will Also Be Titrated by Organic Acids
  • Next Event After Sodium Bicarbonate Infusion: H2CO3 Dehydrates to CO2, H20, and CO2 -> CO2 must then be removed from the body via ventilation
    • If the CO2 Generated is Not Efficiently Removed by Ventilation, the Increased pCO2 will Prevent Carbonic Acid Dehydration and the pH Will Not Increase: for this reason, adequate perfusion and ventilation are required for the clinical effect of exogenous bicarbonate therapy
    • Even with Adequate Ventilation, Tissue pCO2 May Increase After Bicarbonate Therapy, Resulting in Paradoxical Intracellular Acidosis (Despite an Increase in Arterial pH): due to the fact that CO2 readily diffuse across cell membranes
    • Paradoxical Cerebrospinal Fluid Acidemia May Also Occur with Bicarbonate Therapy
      • Due to Local Increase in pCO2 in the Brain and CSF: described above
      • Due to Decreased Systemic Acidemia, Resulting in a Decreased Respiratory Drive: systemic pCO2 then increases and is quickly transmitted to the CSF, while the increased serum bicarbonate is more slowly transmitted to the CSF
        • This may result in paradoxical CSF acidemia, resulting in neurologic deterioration

Physiology of Bicarbonate Distribution Space

  • Infused bicarbonate rapidly diffuses into the extracellular space (some will enter the intracellular space), some will be titrated by hydrogen ions (released from buffers), and some will be titrated by organic acids (which may occur as part of the primary disease or be formed in response to the bicarbonate load and increased pH)

Effect of Bicarbonate Administration on the Intracellular pH

  • Effect of Bicarbonate to Decrease the Intracellular pH Depends on the Extracellular Non-Bicarbonate Buffering Capacity (Crit Care Med, 2001) [MEDLINE]
    • Effect Depends on the pCO2 in the Extracellular Medium: increased extracellular pCO2 correlates with the extracellular non-bicarbonate buffering capacity because of the release of hydrogen ions coming from the back-titration of these buffers
    • Authors Concluded that Sodium Bicarbonate May Exacerbate Intracellular Acidosis Under Buffering Conditions Close to Those In Vivo: the initial changes in cell pH caused by sodium bicarbonate depend on the extracellular non-bicarbonate buffering capacity

Administration

  • PO: xxxx
  • IV
    • Sodium Bicarbonate Intravenous Vials: these are hypertonic (for reference, 100 mEq/50 mL = 2000 mOsm/L)
      • 7.2% Solution (44.6 mEq/50 mL)
      • 8.4% Solution (50 mEq/50 mL)
    • Sodium Bicarbonate Intravenous Infusion: 3 amps sodium bicarbonate per liter of D5W (gives sodium bicarbonate at approximately 150 mEq/L)

Adverse Effects

Cardiovascular

Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])

  • Physiology: due to sodium load

Renal Adverse Effects

Hypocalcemia (see Hypocalcemia, [[Hypocalcemia]])

  • Physiology: pH-dependent decrease in ionized calcium level (see Hypocalcemia, [[Hypocalcemia]]): ionized calcium levels modulate cardiac contractility

Hypernatremia(see Hypernatremia, [[Hypernatremia]])

  • Physiology: due to sodium load

Hypokalemia (see Hypokalemia, [[Hypokalemia]])

  • Physiology: sodium bicarbonate drives potassium intracellularly

Metabolic Alkalosis (see Metabolic Alkalosis, [[Metabolic Alkalosis]])

  • Clinical: administration of bicarbonate to normal patients (with normal renal function) usually results in only a modest metabolic alkalosis
    • In one study of normal patients, administering a large quantity of oral sodium bicarbonate (1000-1400 meq/day in a 70 kg patient) for 2-3 wks only raised the serum bicarbonate concentration to 36 meq/L [MEDLINE]: most of the bicarbonate was rapidly excreted by the kidney
    • However, Metabolic Alkalosis Can Easily Occur in the Setting of Hypovolemia with Renal Dysfunction

Potential Adverse Effects with Sodium Bicarbonate Administration in the Setting of Diabetic Ketoacidosis (DKA) (see Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State, [[Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State]])

  • Hypokalemia (see Hypokalemia, [[Hypokalemia]])
    • Physiology: sodium bicarbonate drives potassium intracellularly
    • Clinical: close monitoring of potassium is required when bicarbonate therapy is used (see Hypokalemia, [[Hypokalemia]])
  • Post-Treatment Metabolic Alkalosis (see Metabolic Alkalosis, [[Metabolic Alkalosis]]): due to fact that insulin induces metabolism of ketoacid anions with generation of bicarbonate
  • Paradoxical Decrease in Cerebral pH: due to fact that bicarbonate administration decreases ventilatory drive, increasing pCO2 -> increased pCO2 is more quickly reflected across the blood-brain barrier than increased bicarbonate
  • Slowed Rate of Ketone Clearance

Potential Adverse Effects with Sodium Bicarbonate Administration in the Setting of Lactic Acidosis (see Lactic Acidosis, [[Lactic Acidosis]])

  • Extracellular Volume Expansion
    • Single 50 mL Ampule of Sodium Bicarbonate (Containing 50 mEq of Sodium Bicarbonate) Expands the Extracellular Fluid Volume by Approximately 250 mL
  • Formation of Carbon Dioxide from Bicarbonate with Free Diffusion of Carbon Dioxide Across the Cell Membrane, Resulting in Paradoxical Intracellular Acidification: this may be more significant when large quantities of bicarbonate are administered quickly to patient with circulatory failure (impairing tissue clearance of carbon dioxide and pulmonary excretion of carbon dioxide)
  • Hypernatremia (see Hypernatremia, [[Hypernatremia]])
    • Single 50 mL Ampule of Sodium Bicarbonate (Containing 50 meQ of Sodium Bicarbonate) Increases the Serum Sodium of a 70 kg Patient Approximately 1 mEqL
  • Hyperosmolality
    • Sodium Bicarbonate is a Hypertonic Solution
  • Increased Arterial and Tissue Capillary pCO2
  • Increased Net Lactic Acid Production
    • Acidosis Normally Inhibits Phosphofructokinase, Inhibiting Glycolysis and Resulting in Decreased Lactate Formation
    • Alkalinization Due to Bicarb Administration May Actually Allow Glycolysis to Continue, Increasing the Formation of Lactate (NEJM, 1998) [MEDLINE]
  • Leftward Shift of the Hemoglobin-Oxygen Dissociation Curve
    • Alkalosis Results in a Leftward Shift of the Hemoglobin-Oxygen Dissociation Curve, Increasing Hemoglobin Affinity for Oxygen and Decreasing Oxygen Delivery to Tissues
  • pH-Dependent Decrease in Ionized Calcium (see Hypocalcemia, [[Hypocalcemia]])
    • Results in Decreased Myocardial Contractility
  • Sodium Load/Volume Overload
    • Single 50 mL Ampule of Sodium Bicarbonate (Containing 50 mEq of Sodium Bicarbonate) Expands the Extracellular Fluid Volume by Approximately 250 mL

References

  • The effect of prolonged administration of large doses of sodium bicarbonate in man. Clin Sci (Lond). 1954;13(3):383 [MEDLINE]
  • Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis: a prospective, controlled clinical study. Ann Intern Med 1990, 112:492-498 [MEDLINE]
  • Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med 1991, 19:1352-1356 [MEDLINE]
  • Initial effect of sodium bicarbonate on intracellular pH depends on the extracellular nonbicarbonate buffering capacity. Crit Care Med 2001, 29:1033-1039 [MEDLINE]
  • Bench-to-bedside review: treating acid-base abnormalities in the intensive care unit – the role of buffers. Crit Care. 2004 Aug;8(4):259-65. Epub 2004 May 5 [MEDLINE]
  • Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol. 2012 Oct;8(10):589-601. doi: 10.1038/nrneph.2012.186. Epub 2012 Sep 4 [MEDLINE]