ToxCard: Sodium Bicarbonate for Toxicology – When to Use It and Why!

Authors: Tyler Siekmann, MD (Emergency Medicine Resident, Carolinas Medical Center), Kathryn T Kopec, DO (Emergency Medicine Attending, Medical Toxicologist, Carolinas Medical Center) // Reviewed by: Cynthia Santos, MD (@Cynthia Santos, MD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)


A 32-year-old female with a history of depression presents to the emergency department (ED) for a reported overdose. The patient was found next to an empty bottle of amitriptyline (150mg) that was recently filled with 50 tablets. She was last seen normal 8 hours prior to arrival. Patient was noted to be drowsy and confused, with emesis on her shirt. Vitals: T: 98.2 F, HR 112 bpm, BP 120/72 mmHg, RR 22 breaths/min, SpO2 97% on room air.

Her EKG is shown here:


  • What are the roles of sodium bicarbonate in treating toxicology emergencies?
  • What specific mechanisms contribute to sodium bicarbonate’s utility in overdose treatment?
  • What dosing and goal-directed endpoints should be utilized in sodium bicarbonate administration?


The bicarbonate buffer system is the primary system in the human body that regulates serum pH.1 Carbonic acid is a weak acid that is formed from carbon dioxide and water via carbonic anhydrase. Carbonic acid exists in equilibrium with the HCO3 ion and its associated proton via the reaction below:

This reaction exists in equilibrium in the body with natural shifts back and forth to maintain balance, thereby regulating serum pH. This buffer system is directly tied to the pulmonary and renal systems responsible for the removal of carbon dioxide and bicarbonate respectively.1,2


Sodium bicarbonate is commonly available in the United States as an 8.4% solution 50mL “ampule” containing 50mEq NaHCO3. This formulation is both alkaline (pH 8.0) and highly osmotic (2000mOsmol/kg) in comparison to normal physiologic serum.1

The other most commonly used formulation is the “bicarb drip” which is made by mixing 3 ampules (150 mL) of 8.4% NaHCO3 with 850mL D5W solution. A benefit of this mixture is an osmolality that is much more physiologic (300mOsmol/kg).1

Mechanisms of Action for Sodium Bicarbonate Use in Toxicology:

1. Sodium Channel Blockade Reversal

Sodium channels are ion channels which have effects primarily on the cardiac and neurologic systems. In the cardiac system, sodium channel blockade results in QRS prolongation, cardiac dysrhythmias and hypotension.1,3 In the CNS, effects can include seizures, altered mental status and coma. Sodium bicarbonate works to overwhelm these ion channels with increased extracellular sodium, allowing for higher electrochemical gradients and resolving the channel blockade.3

Common Na+ channel blocking agents:1-3

  • Tricyclic antidepressants
  • Class I anti-arrhythmics
  • Amiodarone
  • Local anesthetics
  • Anti-epileptics including: phenytoin, carbamazepine, lacosamide, lamotrigine, topiramate
  • Quinidine, quinine, chloroquine
  • Propranolol
  • Cyclobenzaprine
  • Citalopram
  • Phenothiazine
  • Propafenone
  • Bupropion
  • Diphenhydramine
  • Amantadine
  • Cocaine


  • Bolus dosing of 8.4% NaHCO3 ampules is preferred over infusions.
  • Start with 1-2mEq/kg bolus and repeat to clinical effect.

The primary endpoint of treatment is controversial, but goal is a QRS <100msec. A pH of 7.5 or greater and/or Na+ of 150mEq are also stopping points for any further NaHCO3 therapy.1-4

2. Serum and Urine Alkalization

Weak acid xenobiotics commonly exist in equilibrium between uncharged acidic compounds and their charged conjugate bases. A common example of such a compound is acetylsalicylic acid (aspirin). These uncharged weak acids can cross cellular membranes and the blood brain barrier leading to increased toxicity.1,5,6 However, alkaline agents like sodium bicarbonate can increase serum and urine pH, which will “trap” the charged base forms of these drugs in the serum and limit their toxicity. It also assists in increasing the renal elimination of these drugs.6

Common treatment regiments for salicylate toxicity recommend an initial bolus of 1-2 mEq/kg of 8.4% NaHCO3 followed by a NaHCO3 infusion starting at 200-250cc/hr.

Goal of therapy is a urine pH > 7.5.2,4-6

Drugs that are Responsive to Urinary Alkalization:6

  • Salicylates
  • Phenobarbital
  • Chlorpropramide
  • Chlorophenoxy Herbicides
  • Methotrexate

Toxic Alcohols:

Methanol and ethylene glycol are harmful in ingestion primarily as a result of their downstream metabolites, formic acid and oxalic acid.1,7 Both formic acid and oxalic acid are weak acids that exist in equilibrium with their charged conjugate bases, similar to acetylsalicylic acid. Formic acid, the metabolite of methanol, accumulates in the retina and basal ganglia resulting in blindness and permanent CNS damage. Oxalic acid accumulates in the renal calyxes, forming calcium oxalate stones and causing acute kidney failure.1,2,7

Sodium bicarbonate works to convert these uncharged acids to their de-protonated and charged conjugate bases, effectively sequestering these agents in the serum. The charged molecules are thereby unable to easily cross cell membranes or tissues and damage can be limited.2

Sodium bicarbonate dosing in toxic alcohol ingestion varies as there is no definitive standard. It is reasonable to give 1-2mEq/kg 8.4% NaHCO3 amp for a pH < 7. The goal of treatment being a physiologic pH of 7.35-7.45. This therapy should be noted to be an adjunct in addition to antidote therapy with fomepizole or hemodialysis, which is the standard of care.2,5,6

Sodium Bicarbonate Adverse Effects:

Generally considered a safe medication, sodium bicarbonate does have several potential adverse effects including:2

  1. Metabolic alkalosis
  2. Hypernatremia
  3. Hypokalemia (due to intracellular shift)
  4. Hyper-osmolality
  5. Paradoxical lactic acidosis
  6. Local infiltration with skin and vascular damage

Take Home Points:

  • Sodium bicarbonate can be a useful therapy in toxic ingestions of multiple compounds including: sodium channel blocking agents, salicylates and toxic alcohols.
  • Primary mechanisms of action include:
    • Overwhelming of the sodium channel blockades
    • Alkalizing serum and urine pH to limit toxicity and enhance elimination
  • Treatment should be started with bolus dosing of 1-2 mEq/kg of 8.4% NaHCO3.
  • Endpoints of treatment include: QRS < 100 msec, pH > 7.5, Na+ > 150mEq or clinical improvement.

Case Conclusion:

The patient’s EKG demonstrated prolonged QRS which was consistent with an amitriptyline overdose. She was given multiple boluses of 8.4% NaHCO3 with subsequent narrowing of her QRS segment to < 100 msec. She was admitted to the ICU for further cardiac monitoring and management of her toxic ingestion.


References/Further Reading:

  1. Mirrakhimov AE et al. The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions. International Journal of Nephrology, vol. 2017. ID 7831358, 8 pages, 2017.
  2. Goldfrank’s Toxicologic Emergencies, 10th Antidotes in Depth (A5): Sodium Bicarbonate. New York, New York. McGraw-Hill. 2015.
  3. Bruccoleri RE and Burns MM. A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening. J Med Toxicol. Mar 2016; 12(1): 121-129.
  4. Smollin C. The Use of Sodium Bicarbonate in Medical Toxicology. California Poison Control System. Mar 2007.
  5. American College of Medical Toxicology. Guidance Document: Management Priorities in Salicylate Toxicity. J Med Toxicol. Mar 2015; 11(1): 149-152.
  6. Proudfoot AT et al. Position Paper on Urine Alkalinization. J Toxicol Clin Toxicol. 2004;42(1): 1-26.
  7. Barceloux DG et al. American Academy of Clinical Toxicology Practice Guidelines on the Treatment of Methanol Poisoning. J Toxicol Clin Toxicol. 2002;40(4):415-46.

2 thoughts on “ToxCard: Sodium Bicarbonate for Toxicology – When to Use It and Why!”

  1. There is actually a second important mechanism of sodium bicarbonate’s effect in TCA overdose:

    TCAs are weak bases. Most of a TCA’s binding at the intracellular side of the sodium channel occurs when the TCA is in its ionized state. When the ambient pH is low, the weak base will ionize more, making more TCA available to bind at the hydrophilic sodium channel [1]. When we give sodium bicarbonate, the ambient pH increases and more of the TCA is in its neutral state. It will move toward the hydrophobic lipid membrane and bind less to the sodium channel [2].

    Sasniuk et al showed the additive utility of increasing sodium concentration and increasing pH in a dog model. This team used Purkinje fibers from amitriptyline-treated canine myocardial tissue. The amplitude of phase 0 in this tissue was higher after exposure to sodium bicarbonate than after exposure to hypertonic saline (increased Na+ concentration) or reduced CO2 concentration (increased pH) alone [3].

    1. Valento M, Liebelt EL. Cyclic Antidepressants. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e New York, NY: McGraw-Hill; . Accessed December 19, 2019.

    2. Wax PM, Haynes A. Sodium Bicarbonate. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e New York, NY: McGraw-Hill; . Accessed December 19, 2019.

    3. Sasyniuk BI, Jhamandas V. Mechanism of reversal of toxic effects of amitriptyline on cardiac Purkinje fibers by sodium bicarbonate. J Pharmacol Exp Ther. 1984;231(2):387-94.

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