Take Home Points
- Sodium bicarbonate is a nonspecific antidote for a variety of poisonings such as:
- Tricyclic antidepressants (TCAs) and other sodium channel blockers
- Salicylates and aspirin (ASA)
- Phenobarbital
- Methotrexate
- Toxic alcohols
- Sodium bicarbonate has 3 main mechanisms used in toxicology:
- 1) Alters interaction between xenobiotic and sodium channels
- 2) Alters xenobiotic ionization, distribution and enhances elimination
- 3) Corrects metabolic acidosis
- Sodium bicarbonate might not be effective in bupropion toxicity
- QRS widening associated with bupropion is not due to sodium channels
- Excessive sodium bicarbonate use has associated risks of:
- Hypernatremia (if using hypertonic formulation)
- Hypokalemia
- Hypocalcemia
- Alkalemia
- Fluid overload
Sodium Bicarbonate1-2
Outside of toxicology, sodium bicarbonate has limited utility, and its routine use is controversial. Sodium bicarbonate is typically used as a buffering agent that reacts with hydrogen ions to correct acidemia and produce alkalemia but does little to treat the underlying cause of acidosis. It is also used for the treatment of acute hyperkalemia as alkalinization causes an intracellular shift of potassium. Sodium bicarbonate functions as a ‘Band-Aid’ to temporarily improve lab values but may do little to address underlying causes.
In toxicology, however, it is all about benzodiazepines and sodium bicarbonate. Sodium bicarbonate is used as a nonspecific antidote effective in the treatment of a variety of poisonings by means of a number of distinct mechanisms. It is primarily used to manage patients with prolonged QRS duration due to sodium channel blockade, facilitate elimination of weak acids, dissociate toxic metabolites from receptors, and correct severe metabolic acidosis.
Reversal of Sodium Channel Blockade
Indication: TCA Toxicity
TCA overdoses can be some of the most difficult patients to manage, due to the variety of affected receptors. TCAs block ?-adrenergic receptors causing hypotension, have anticholinergic properties and cause cardiotoxicity through sodium channel blockade and subsequent QRS prolongation. Sodium bicarbonate helps to narrow the QRS and prevent associated dysthymias through a sodium-dependent effect and pH-dependent effect. One ‘amp of bicarb’ typically refers to 50 mL of 8.4% sodium bicarbonate given as an IV bolus. This dose contains 150 mEq sodium, the equivalent of 100 mL 3% sodium chloride, and helps overcome sodium channel blockade. Increasing the pH increases the fraction of the more freely diffusible nonionized TCA, assisting dissociation from receptors and promoting protein binding
- Mechanism of Action: Increasing the number of open sodium channels, thereby partially reversing fast sodium channel blockade. This decreases QRS prolongation and reduces life-threatening cardiovascular toxicity, such as ventricular dysrhythmias and hypotension
- Indications for Treatment
- QRS > 100 msec OR
- R wave in aVR ? 3 small boxes (mm)
- NOTE: QT prolongation alone is NOT an indication to alkalinize. Sodium bicarbonate shifts potassium intracellularly and will therefore worsen QT prolongation as a result of hypokalemia.
- Dosing
- Administer one amp of sodium bicarbonate (or 1 mEq/kg) at 5-minute intervals until clinically stable, not to exceed 6 mEq/kg
- Initiate infusion at 150 to 200 mL/hr (adults), titrated to pH 7.5 – 7.55
- Goal
- Serum pH 7.5 - 7.55
- Monitoring
- Venous blood gas and serum electrolytes within 2 hours of administration
- Direct QRS narrowing on EKG, or telemetry may be observed shortly after administering sodium bicarbonate
- Stop Criteria
- QRS < 120, HR < 140, R wave in aVR < 3mm, systolic BP > 100 mmHg
- If criteria are met, turn off infusion and recheck EKG and electrolytes in 1 hour
- Infusions are generally not needed for more than 8-12 hours
Other Indications: type IA and IC antidysrhythmics, cocaine, massive diphenhydramine overdose, lamotrigine, hydroxychloroquine, bupivacaine
Urine Alkalinization1-3
Indication: Salicylate (i.e., aspirin) Toxicity
Patients who present with salicylate toxicity can be difficult to identify and may develop severe toxicity. Salicylate elimination increases with higher urine pH. The role of sodium bicarbonate in salicylate poisoning is not to overcome sodium channel blockade, but rather to alkalinize the urine. As a weak acid, an increase in pH shifts salicylate to its ionized form, “trapping” it in the urine.
- Mechanism of Action: Urine and serum alkalinization to draw salicylate out of tissues and eliminate drug in urine
Indications for Treatment
- Salicylate level > 30 mg/dL OR
- If salicylate concentrations are unavailable: symptomatic (tinnitus or increased respiratory rate) OR acidosis by venous blood gas or elevated anion gap (>12)
- Dosing
- Bolus sodium bicarbonate 1 mEq/kg IV
- Infusion sodium bicarbonate 150 mEq in 1L D5W at 200-250 mL/hr
- Add 40 mEq potassium chloride to the infusion to prevent hypokalemia
- Goals
- Urine pH 7.5 - 8.0
- Serum pH 7.5 - 7.55
- Potassium > 4.0 mEq/L
- Monitoring
- Baseline: blood chemistries, electrolyte values, and an arterial or venous blood gas and correct any fluid or electrolyte deficits (especially potassium because alkalemia will push potassium intracellularly)
- Hypokalemia will make it impossible to alkalinize the urine because of the potassium and hydrogen ion exchange in the kidneys, which will excrete hydrogen ions into the urine if serum potassium is low
- Check urine pH every 60 minutes until the goal pH level of 7.5-8.5 is achieved
- Serum potassium, blood gas, and salicylate concentrations should be measured every 1-2 hours
- Stop Criteria
- Salicylate: level < 30 mg/dL
- Repeat salicylate level 4-6 hours after stopping alkalinization
- Salicylate: level < 30 mg/dL
Other Indications: phenobarbital, methotrexate, chlorophenoxy herbicides
Unreliable Use: Bupropion (Wellbutrin) Toxicity4-5
Case reports of bupropion toxicity and the use of sodium bicarbonate have been mixed. While bupropion may cause QRS prolongation in overdose, this is not due to sodium channel blockade but rather due to reduction of cardiac intercellular coupling by inhibition of gap junction communication. Lack of efficacy is likely due to this alternate QRS prolonging mechanism. As ingestion history is often unreliable, consider sodium bicarbonate in bupropion overdose with QRS widening as other sodium channel blocking agents may be present. If a patient with bupropion toxicity develops ventricular dysrhythmias, consider antidysrhythmic agents like lidocaine. Extracorporeal life support may be necessary in such cases.
Sodium Bicarbonate Adverse Effects1-2
- Severe alkalemia (pH > 7.6) may cause seizures or respiratory depression
- Hypernatremia
- Hypokalemia
- Hypocalcemia
- Fluid overload
- Cerebral vasoconstriction
- Coronary vasoconstriction
Call the Utah Poison Control Center 24 hours a day, 7 days a week, for help with appropriate sodium bicarbonate use in overdose patients. UPCC Protocols are available for health care professionals on our website for the use of sodium bicarbonate in sodium channel blockers/TCAs toxicity and salicylates/aspirin toxicity.
References
- Wax, Paul M., and Ashley Haynes. "Sodium Bicarbonate." Goldfrank's Toxicologic Emergencies, 11e Eds. Lewis S. Nelson, et al. McGraw-Hill Education, 2019, https://accesspharmacy.mhmedical.com/content.aspx?bookid=2569§ionid=210262080.
- Jiang, Anthony. "BICARBONATE, SODIUM." Poisoning & Drug Overdose, 8e Eds. Kent R. Olson, et al. McGraw Hill, 2022, https://accessmedicine.mhmedical.com/content.aspx?bookid=3195§ionid=266330677.
- Proudfoot, A T et al. “Position Paper on urine alkalinization.” Journal of toxicology. Clinical Toxicology vol. 42,1 (2004): 1-26. doi:10.1081/clt-120028740
- Stork, Christine M. "Serotonin Reuptake Inhibitors and Atypical Antidepressants." Goldfrank's Toxicologic Emergencies, 11e Eds. Lewis S. Nelson, et al. McGraw-Hill Education, 2019, https://accesspharmacy.mhmedical.com/content.aspxbookid=2569§ionid=210274776.
- Benowitz, Neal L., and Nathaniel West. "ANTIDEPRESSANTS, GENERAL (NONCYCLIC)." Poisoning & Drug Overdose, 8e Eds. Kent R. Olson, et al. McGraw Hill, 2022, https://accessmedicine.mhmedical.com/content.aspx?bookid=3195§ionid=266328358.
- Chan, B. S., & Buckley, N. A. (2024). Common pitfalls in the use of hypertonic sodium bicarbonate for cardiac toxic drug poisonings. Clinical Toxicology, 62(4), 213–218. https://doi.org/10.1080/15563650.2024.2337028