Critical action: Do not use acetazolamide in the treatment of salicylate poisoning.

Mechanical Ventilation

Patients with salicylate poisoning may develop metabolic acidosis with respiratory alkalosis. Although early respiratory alkalosis may be a direct effect of salicylate on the medullary neurons controlling respiration, later hyperventilation is a compensatory reaction to worsening acidosis.²⁷ When a salicylate poisoned patient’s respiratory status leads you to consider intubation, give priority to emergency hemodialysis if available.¹⁹ In fact, such patients may not tolerate sedation and paralysis during rapid sequence induction and intubation because those actions can eliminate respiratory compensation and worsen acidosis. Case reports illustrate abrupt cardiac arrest in the minutes following intubation.^16–18 Failure to hyperventilate after intubation likely contributes to this.

Critical action 1: When considering intubation, call for emergency hemodialysis, if available.

Critical action 2: If intubation is unavoidable, pre-treat with sodium bicarbonate and match the pre-intubation respiratory rate.

Persistence of Aspirin in the Upper GI Tract

Aspirin tablets can persist in the stomach and may coalesce to form a bezoar.^21,31–33 This results in delayed or ongoing absorption of aspirin. The earliest clue may be a rising or persistently elevated salicylate level despite optimal treatment with IV fluids, sodium bicarbonate, and potassium replacement.

Critical action 1: Monitor salicylate, basic metabolic panel, and venous blood gases as frequently as every 2 hours until the patient clearly improves.

Critical action 2: Give repeated doses of activated charcoal unless endoscopy is available to remove retained pills or bezoars from stomach.

Recognizing Chronic Salicylate Poisoning

Some older adults may use over-the-counter ASA to self-treat arthritis or other persistent pain. Chronic salicylate toxicity can mimic sepsis with insidious onset of hyperthermia, confusion, tachycardia, tachypnea, metabolic acidosis, and acute kidney injury.^34–37 Recognizing this possibility early can prevent morbidity and mortality, especially in older patients.³⁸

Critical action 1: Include salicylism in your differential diagnosis of an older adult who is unwell without apparent cause.

Critical action 2: Inquire about the patient’s use of over-the-counter medications.

Dr. Hebbard is an emergency physician, medical toxicology fellow, and biochemist.

Dr. Mullins is a professor of emergency medicine and faculty member of the medical toxicology fellowship at Washington University School of Medicine.

References

1. Gummin DD, Mowry JB, Beuhler MC, et al. 2021 annual report of the national poison data system (NPDS) from America’s poison centers: 39th annual report. Clin Toxicol. 2022;60(12):1381-1643.
2. Done AK. Salicylate intoxication. Significance of measurements of salicylate in blood in cases of acute ingestion. Pediatrics. 1960;26:800-7.
3. Dugandzic RM, Tierney MG, Dickinson GE, et al. Evaluation of the validity of the Done nomogram in the management of acute salicylate intoxication. Ann Emerg Med. 1989;18(11):1186-1190.
4. Shively RM, Hoffman RS, Manini AF. Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol. 2017;55(3):175-180.
5. Welcher F. Organic Analytical Reagents Vol II. D. Van Nostrand Co.; 1947:118.
6. DeMarco JD, Marcus AD. Colorimetric determination of salicylic acid. J Pharm Sci. 1962;51:1010-11.
7. Warrick BJ, King A, Smolinske S, et al. A 29-year analysis of acute peak salicylate concentrations in fatalities reported to United States poison centers. Clin Toxicol. 2018;56(9):846-51.
8. Wang T, Diamandis EP, Lane A, et al. Variable selectivity of the Hitachi chemistry analyzer chloride ion-selective electrode toward interfering ions. Clin Biochem. 1994;27(1):37-14.
9. Mori L, Waldhuber S. Salicylate interference with the Roche Cobas Integra chloride electrode. Clin Chem. 1997;43(7):1249-50.
10. Jacob J, Lavonas EJ. Falsely normal anion gap in severe salicylate poisoning caused by laboratory interference. Ann Emerg Med. 2011;58(3):280-1.
11. Emmett M. Approach to the patient with a negative anion gap. Am J Kidney Dis. 2016;67(1):143-50.
12. Kaul V, Imam SH, Gambhir HS, et al. Negative anion gap metabolic acidosis in salicylate overdose—a zebra! Am J Emerg Med. 2013;31(10):1536.e3-1536.e4.
13. Wiederkehr MR, Benevides R, Santa Ana CA, et al. Pseudohyperchloremia and negative anion gap – think salicylate! Am J Med. 2021;134(9):1170-1174.
14. Thurston JH, Pollock PG, Warren SK, et al. Reduced brain glucose with normal plasma glucose in salicylate poisoning. J Clin Invest. 1970;49(11):2139- 45.
15. Cotton EK. Hypoglycemia with salicylate poisoning: a report of two cases. Am J Dis Child. 1964;108(2):171.
16. Limbeck GA, Ruvalcaba RH, Samols E, et al. Salicylates and hypoglycemia. Am J Dis Child. 1960. 1965;109:165-167.
17. Lutwak-Mann C. The effect of salicylate and cinchophen on enzymes and metabolic processes. Biochem J. 1942;36(10-12):706-28.
18. Kuzak N, Brubacher JR, Kennedy JR. Reversal of salicylate-induced euglycemic delirium with dextrose. Clin Toxicol. 2007;45(5):526-9.
19. Juurlink DN, Gosselin S, Kielstein JT, et al. Extracorporeal treatment for salicylate poisoning: systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165-81.
20. Robin ED, Davis RP, Rees SB. Salicylate intoxication with special reference to the development of hypokalemia. Am J Med. 1959;26(6):869-82.
21. Done AK. Treatment of salicylate poisoning: review of personal and published experiences. Clin Toxicol. 1968;1(4):451-67.
22. Thongprayoon C, Petnak T, Kaewput W, et al. Hospitalizations for acute salicylate intoxication in the United States. J Clin Med. 2020;9(8):2638.
23. Schwartz R, Fellers FX, Knapp J, et al. The renal response to administration of acetazolamide (Diamox) during salicylate intoxication. Pediatrics. 1959;23(6):1103-14.
24. Feuerstein RC, Finberg L, Fleishman E. The use of acetazolamide in the therapy of salicylate poisoning. Pediatrics. 1960;25(2):215-27.
25. Hill JB. Experimental salicylate poisoning: observations on the effects of altering blood pH on tissue and plasma salicylate concentrations. Pediatrics. 1971;47(4):658-65.
26. Kaplan SA, Del Carmen FT. Experimental salicylate poisoning: observations on the effects of carbonic anhydrase inhibitor and bicarbonate. Pediatrics. 1958;21(5):762-70.
27. Akada S, Takeda S, Ogawa R. Salicylate action on medullary inspiratory neuron activity in a brainstem spinal cord preparation from newborn rats. Anesth Analg. 2003;96(2):407-11, table of contents.
28. Greenberg MI, Hendrickson RG, Hofman M. Deleterious effects of endotracheal intubation in salicylate poisoning. Ann Emerg Med. 2003;41(4):583-4.
29. Stolbach AI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with acidemia in a case series of salicylate‐poisoned patients. Acad Emerg Med. 2008;15(9):866-9.
30. Hill JB. Salicylate Intoxication. N Engl J Med. 1973;288(21):1110-3.
31. Sogge MR. Lavage to remove enteric-coated aspirin and gastric outlet obstruction. Ann Intern Med. 1977;87(6):721.
32. Salhanick S, Levy D, Burns M. Aspirin bezoar proven by upper endoscopy [abstract]. J Toxicol Clin Toxicol. 2002;40(5):688.
33. Wong O, Fung H, Lam T. Case report of aspirin overdose: bezoar formation and controversies of multiple dose activated charcoal in salicylate poisoning. Hong Kong J Emerg Med. 2010;17(3):276-80.
34. Greer HD. Chronic salicylate intoxication in adults. J Am Med Assoc. 1965;193(7):555.
35. Bailey RB, Jones SR. Chronic salicylate intoxication: a common cause of morbidity in the elderly. J Am Geriatr Soc. 1989;37(6):556-61.
36. Delaney TM, Helvey JT, Shiffermiller JF. A case of salicylate toxicity presenting with acute focal neurologic deficit in a 61-year-old woman with a history of stroke. Am J Case Rep. 2020;21.
37. Gittelman DK. Chronic salicylate intoxication. South Med J. 1993;86(6):683-5.
38. Anderson RJ. Unrecognized adult salicylate intoxication. Ann Intern Med. 1976;85(6):745.