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
Impaired Responsiveness to Catecholamine Vasopressors (Nat Rev Nephrol, 2012) [MEDLINE]
Indications
pH <7.1: however, evidence for this recommendation is lacking
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
Prospective 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
Prospective, Randomized Trial of Sodium Bicarbonate in Lactic Acidosis (Crit Care Med, 1991) [MEDLINE]
Sodium Bicarbonate Administration Did Not Improve Hemodynamic Variables in Patients with Lactic Acidosis, But Did Not Worsen Tissue Oxygenation
French Multi-Center, Randomized BICAR-ICU Trial of Sodium Bicarbonate for ICU Patients with Severe Acidemia and Lactic Acidosis (Lancet. 2018) [MEDLINE]: n = 389 (from 26 French ICU’s)
Total Group
Sodium Bicarbonate Therapy for Severe Acidemia (pH ≤7.20, pCO2 ≤45 mm Hg, Serum Bicarbonate ≤20 mmol/L, SOFA ≥4. Arterial Lactate ≥2 mmol/L) Targeting a Serum pH >7.30 Did Not Significantly Decrease the 28-Day Mortality Rate (45%), as Compared to Control (54%)
Sodium Bicarbonate Did Not Decrease the Occurrence of at Least One Organ Failure at Day 7
Prespecified Acute Kidney Injury Network Group (with a Score of 2-3)
Sodium Bicarbonate Therapy Decreased the Mortality Rate (46%), as Compared to Control (63%)
Sodium Bicarbonate Decreased the Occurrence of at Least One Organ Failure at Day 7
Metabolic Alkalosis, Hypernatremia, and Hypocalcemia were Observed More Frequently in the Bicarbonate Group than in the Control Group
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 Events 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 Intracellular Acidosis May Occur with Bicarbonate Therapy
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
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
Administration
PO
XXXX
IV
Sodium Bicarbonate Intravenous Vials: these are hypertonic (for reference, 100 mEq/50 mL = 2000 mOsm/L)
8.4% Solution (50 mEq/50 mL): standard 1 ampule of sodium bicarbonate (found on standard code cart)
7.2% Solution (44.6 mEq/50 mL)
Sodium Bicarbonate Intravenous Infusion: 3 amps sodium bicarbonate per liter of D5W (gives sodium bicarbonate at approximately 150 mEq/L)
Insulin Induces Metabolism of Ketoacid Anions with the Generation of Bicarbonate
Paradoxical Decrease in Cerebral pH
Physiology
Bicarbonate Administration Decreases Ventilatory Drive, Increasing pCO2 with Resulting Increased pCO2 More Quickly Reflected Across the Blood-Brain Barrier than Increased Bicarbonate
Results in 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)
Leftward Shift of the Hemoglobin-Oxygen Dissociation Curve (see Hypoxemia)
Physiology
Alkalosis Results in a Leftward Shift of the Hemoglobin-Oxygen Dissociation Curve, Increasing Hemoglobin Affinity for Oxygen and Decreasing Oxygen Delivery to Tissues
Single 50 mL Ampule of Sodium Bicarbonate (Containing 50 mEq of Sodium Bicarbonate) Increases the Serum Sodium of a 70 kg Patient Approximately 1 mEq/L
Clinical: administration of bicarbonate to normal patients (with normal renal function) usually results in only a modest metabolic alkalosis
In One Study with 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 (XXXXX) [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
Increased Net Lactic Acid Production
Physiology
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]
Clinical
May Be Detrimental when Sodium Bicarbonate is Used to Treat Lactic Acidosis (see Lactic Acidosis)
Increased Tissue Capillary pCO2
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]
Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018 Jul 7;392(10141):31-40. doi: 10.1016/S0140-6736(18)31080-8. Epub 2018 Jun 14 [MEDLINE]
