Authored by Alex Ponce, PharmD and Kris Nanagas, MD
Imagine arriving at the bedside of a patient who has taken a massive overdose of a tricyclic. Though you are well trained and utterly prepared to treat the wide complex tachycardia that appears before your eyes, your Pyxis is bare and there is no bicarb to be had. Luckily, all you have to do is calculate the equivalent millimoles of sodium found in a “Hot Salt” formulation and give that. Or, keep reading for tips and tricks to avoid the math and find an easier alternative.
The proposed mechanism for the resolution of the wide complex and improved hemodynamics is due to increased sodium concentration1,2,3. Picture an enormous crowd of sodium gathering around the channel like shoppers at the doors of a retail store near opening time on Black Friday. As soon as the channel opens, all the sodium tries to rush in at once. It has also been proposed that part of the treatment may be attributed to change in serum pH (there is bicarbonate in the sodium bicarb, after all) which may affect sodium channel receptor affinity (acidic conditions promote sodium channel blockade). However, two animal studies showed similar efficacy between hypertonic saline and sodium bicarbonate in the setting of tricyclic antidepressant induced QRS widening2,3.
This is good news, as it indicates that the sodium component is far more important than the bicarbonate in reversing the blockade. A case report of a nortriptyline ingestion showed resolution of QRS widening and improved hemodynamics after a 200 mL bolus of 7.5% NaCl that was previously refractory to 200 mL of 8.4% sodium bicarbonate4. This is the closest thing to a definitive non-inferiority study that toxicology can get! Given the ability of products at our institutions, 3% NaCl would be a reasonable alternative to sodium bicarbonate for QRS widening.
You could do math to find out all your equivalent dosing. I think math is fun and it is good for you! But it might be a bit stressful when your patient is experiencing a non-perfusing rhythm and they don’t want to wait for you to calculate dosing for their life saving treatment. Alternatively, you could simply use the ED QRS Prolongation PowerPlan developed for just this occasion. It is in the toxicology folder within Cerner and looks like this:
For the philomaths among you, the recommended dose of sodium bicarbonate for QRS widening is 1-2 mEq/kg over 1-2 minutes with a maximum of 200 mEq per dose. In an 8.4% sodium bicarbonate vial, the concentration of sodium is 1 mEq/1 mL. In 3% NaCl, the concentration of sodium is approximately 0.5 mEq/1 mL. Therefore, the recommended dose of 3% NaCl is 2-4 mL/kg over 1-2 minutes with a maximum of 400 mL per dose5. If both sodium bicarbonate and 3% NaCl were to be unavailable, sodium acetate may be used as an alternative. The 40 mEq in 20 mL vial contains a concentration of sodium of 2 mEq/1 mL, however there are multiple concentrations available on the market. The recommended dose is 1 mEq of Na/kg which equates to 0.5 mL/kg over 20 minutes of the 40 mEq/20 mL solution5. The sodium acetate product needs to be administered over a longer period due to concerns for adverse effects including hypotension related to a rapid increase in serum concentration of acetate6.
Adverse effects including hypernatremia and hyperchloremic acidosis should be monitored.
That is one crisis averted! But what about another great poisoning- ASPIRIN! You actually do need alkalinization for that, not just sodium. An infusion of 150 mEq of sodium bicarbonate in one liter of D5W is typically started at twice the maintenance fluid rate to achieve a goal serum pH of 7.40-7.45. Aspirin and salicylates are weak acids, and alkalinization therapy helps to prevent salicylate distribution into the central nervous system and enhance urinary excretion of salicylates1. But, with no sodium bicarb to be had, what is a person to do? Substitute it with sodium acetate. A case with an initial salicylate level of 57 mg/dL was managed by a 150 mEq/L of sodium acetate during a previous bicarbonate shortage7. This is obviously solid proof by toxicology standards! Sodium acetate is converted to acetyl CoA which is subsequently converted to carbon dioxide as a biproduct of the citric acid cycle6. Carbon dioxide is then quickly converted to bicarbonate by carbonic anhydrase6. Based on the above, a dosing strategy of 150 mEq of sodium acetate in 1 liter of D5W infused at twice maintenance rate is a reasonable alternative when sodium bicarbonate is unavailable. Or. . .use the PowerPlan and don’t think very much about it.
In conclusion, PowerPlans are awesome, convenient, and there for your benefit. Also, math is great and you should try it sometime. But really: sodium bicarbonate remains the treatment of choice for both QRS widening and serum and urine alkalinization during toxicologic emergencies. If unavailable, a bolus of 2-4 mL of 3% NaCl is an alternative regimen for QRS widening, and a 150 mEq of sodium acetate in 1L of D5W at twice normal maintenance rate serves as an alternative regimen for alkalinization therapy.
Wax PM, Haynes A. Sodium Bicarbonate. In. Nelson LS, Howland MA, Lewin NA, et al. Goldfrank’s Toxicologic Emergencies. 11th ed. McGraw-Hill; 2019. p 567-573.
Pentel P, Benowitz N. Efficacy, and mechanism of action of sodium bicarbonate in the treatment of desipramine toxicity in rats. J Pharmacol Exp Ther. 1984 Jul;230(1): 2-9.
McCabe JL, Cobaugh DM, Menegazzi JJ, Fata J. Experimental tricyclic antidepressant toxicity: a randomized, controlled comparison of hypertonic saline solution, sodium bicarbonate, and hyperventilation. Ann Energ Med. 1998 Sep;32)3 Pt 1):329-33.
McKinney PE, Rasmussen. Reversal of severe tricyclic antidepressant-induced cardiotoxicity with intravenous hypertonic saline solution. Ann Emerg Med. 2003 Jul;42(1):20-4.
Sodium Bicarbonate Shortage Recommendations. American College of Medical Toxicology. Article on the web. Accessed 2022 Mar. Updated 2017 Aug 15. Available from: https://www.acmt.net/_Library/Positions/ACMT_Bicarb_Final.pdf
Neavyn MJ, Boyer EW, Bird SB, Babu KM. Sodium acetate as a replacement for sodium bicarbonate in medical toxicology: a review. J Med Toxicol. 2013 Sep;9(3):250-4.
Boyd M, Geller R. Acute aspirin overdose managed with sodium acetate due to sodium bicarbonate shortage. In. Chavez C, Melendez M. Abstracts of the 2013 ACMT Annual Scientific meeting – March 15-17, 2013 San Juan, Puerto Rico, US. J Med Toxicol. 2013 Mar; 9(1):82-105.
The views expressed in this content represent the perspective and opinions of the author and may or may not represent the position of Indiana University School of Medicine.
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