EMA Cited · Toxicology
Salicylate toxicity
Bottom line
- One level is not enough. Levels can be undetectable up to 4 hours after ingestion and can peak late. Repeat every 2 hours until they are clearly falling.1
- Altered mental status means dialysis, whatever the level. EXTRIP also recommends it for levels above 100 mg/dL (above 90 with impaired kidney function) and suggests it for pH ≤ 7.20.2
- Alkalinize with sodium bicarbonate. Aim for a urine pH of at least 7.5. Bicarbonate beat forced diuresis at clearing salicylate.3,4
- Keep potassium normal. Urine can't be alkalinized while the patient is hypokalemic, and hypokalemia is the most common complication of bicarbonate.1,3
- Avoid intubation if you can. Losing the patient's own hyperventilation can deepen acidemia and push salicylate into the brain. If you must intubate, match their minute ventilation.1,5
Recognize
- Early (< 6 h): nausea, vomiting and abdominal pain. Most toxicity develops 4–12 hours after ingestion.1
- Tinnitus or reduced hearing appears around 30 mg/dL, sometimes from about 20 mg/dL. It was present in 78% of patients in one study.1
- Tachypnea and hyperpnea. The recorded respiratory rate is often wrong; look at the depth of breathing yourself.1
- Late or severe: altered mental status, seizures, coma, noncardiogenic pulmonary edema and arrhythmias. High fever is uncommon and usually preterminal.1
- Chronic toxicity is common in older adults and easily missed: delirium, dehydration, fever and unexplained acidosis. Cerebral and pulmonary edema are more common than in acute overdose.6
- Hidden sources: bismuth subsalicylate, oil of wintergreen, combination headache powders and topical methyl salicylate.1
| Acute aspirin dose | Expected toxicity |
|---|---|
| < 150 mg/kg | Minimal symptoms |
| 150–300 mg/kg | Mild to moderate: hyperpnea, tinnitus, vomiting |
| > 300 mg/kg | Severe: metabolic acidosis, altered mental status, seizures |
| > 500 mg/kg | Potentially lethal |
Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.
Dose bands from LITFL.6 Therapeutic levels are 15–30 mg/dL (1.1–2.2 mmol/L).1,6 For salicylate, 1 mg/dL = 10 mg/L.
Workup
- Blood gas (venous or arterial), electrolytes, renal and liver function, CBC, glucose, ECG, and both salicylate and acetaminophen levels.1
- Repeat salicylate levels every 2 hours after an acute ingestion. Enteric-coated tablets, pylorospasm and bezoars delay absorption.1
- Read the gas as a pattern. The classic finding is a respiratory alkalosis with an anion gap metabolic acidosis. Sedative co-ingestants can blunt the respiratory alkalosis.1
- Don't trust a normal anion gap. Some analyzers read salicylate as chloride, falsely lowering the gap.1,6
- Test for salicylate in any overdose without a clear history, and in unexplained altered mental status, metabolic acidosis or respiratory alkalosis.1
- Predicting severity: in a prospective ED cohort (n = 48), the initial level alone did not predict a severe outcome. After adjusting for it, age (OR 1.13) and respiratory rate (OR 1.29) did. A lactate above 2.25 mmol/L was 78% sensitive.7
- Glucose: early hyperglycemia, later hypoglycemia. Brain glucose can be low even when blood glucose is normal.1
Treatment
- Call a toxicologist or poison center for every suspected or confirmed case.1
- Activated charcoal is on the 2026 international list for salicylates, including an additional dose to complete decontamination. Give it only if the airway is safe and vomiting is controlled.8,1
- Replace fluid. Vomiting and hyperventilation cause large losses.1
- Start sodium bicarbonate for metabolic acidosis, an acute level above 30 mg/dL, or significant symptoms.1
- Replete potassium to normal, or alkalinization will fail.1
- Give IV dextrose for hypoglycemia, and consider it for mild encephalopathy even when glucose is normal.1
- Treat seizures with benzodiazepines.1,6
- Check whether the patient meets dialysis criteria (below), and call nephrology early.2
| Agent | Adult dose | Target and notes |
|---|---|---|
| Sodium bicarbonate 8.4% | Per toxicologist and protocol. The label gives about 2–5 mEq/kg over 4–8 h for non-urgent metabolic acidosis. | Urine pH ≥ 7.5.3 Serum pH 7.50–7.55 is a common goal.1 Labeled for salicylate poisoning.9 |
| Potassium | Per serum level | Keep normal; hypokalemia blocks urinary alkalinization.1,3 |
| Activated charcoal | Per protocol and label | Single dose plus an additional dose for salicylates.8 |
| Forced diuresis | Not recommended | Little effect on clearance, causes fluid retention and dilutes the level.4 |
Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.
Alkalinization
- Why it works: acidemia shifts salicylate into its uncharged form, which enters tissues and the brain. Raising the pH pulls it back into the blood and traps it in the urine.1
- Bicarbonate, not volume. In 44 adults with aspirin poisoning, bicarbonate alone cleared salicylate better than forced alkaline diuresis. Renal clearance depended far more on urine pH than on urine flow.4
- AACT/EAPCCT position: urine alkalinization is first-line for moderately severe poisoning that does not meet dialysis criteria. Hypokalemia is the most common complication; alkalemia up to pH 7.70 has been recorded.3
- Stopping it: after bicarbonate was stopped, levels rebounded in 8 of 377 patients (2.1%), all after acute ingestions. Only one had recurrent symptoms (tinnitus).10
Hemodialysis
| EXTRIP indication | Grade |
|---|---|
| Recommended | |
| Altered mental status, at any level | 1D |
| New hypoxemia needing supplemental oxygen | 1D |
| Level > 100 mg/dL (7.2 mmol/L) | 1D |
| Level > 90 mg/dL (6.5 mmol/L) with impaired kidney function | 1D |
| Failure of standard therapy | 1D |
| Suggested | |
| Level > 90 mg/dL (6.5 mmol/L) | 2D |
| Level > 80 mg/dL (5.8 mmol/L) with impaired kidney function | 2D |
| pH ≤ 7.20 | 2D |
EXTRIP 2015.2 Hypoxemia and failure of standard therapy are as listed in a 2025 review of the EXTRIP recommendations.1 All grades are D: very low quality evidence, from 84 articles that were nearly all case reports or series.2
- Intermittent hemodialysis is preferred. Hemoperfusion or continuous renal replacement therapy are alternatives if it is unavailable.2
- Continue until the patient improves and, where levels are available, the level is below 19 mg/dL.1
- Don't wait for a number. Most deaths reported to poison centers had peak levels below 100 mg/dL. Patients who can't tolerate the fluid needed for alkalinization, such as those with pulmonary edema, may need dialysis sooner.1
Airway
- Avoid sedation and intubation where possible. Apnea and hypercarbia drop the pH and push salicylate into the brain and heart.1
- If intubation is unavoidable (airway protection, seizures, severe hypercapnia): give a bicarbonate bolus before induction, minimize apnea, have the most experienced operator intubate, and set the ventilator to match the patient's pre-intubation rate and tidal volume. Then arrange dialysis.1,6
Sources disagree
In a poison center series, all 7 ventilated patients with post-intubation gases had a pH below 7.4, and 3 deteriorated within hours (2 died).5 In a 2024 single-center ED cohort, 11 of 32 patients with severe poisoning were intubated. The pH barely changed (mean difference −0.02), and there were no severe complications in the next 6 hours.11 Both studies are small and retrospective. Intubation is still best avoided, and done carefully when needed.1
Disposition
- Severe toxicity: ICU, with labs every 2–4 hours.1
- Milder toxicity: a ward bed may be enough.1
- Slightly raised level, no acid-base disturbance: observe in the ED until stable with falling levels, then psychiatric assessment or discharge as appropriate.1
- Intentional overdose: ask about intent, and check for co-ingestants.1
Pitfalls
- Stopping after one low level taken too early.1
- Being reassured by a normal anion gap.1,6
- Waiting for the level to reach 100 mg/dL in a confused patient. Altered mental status alone is an indication for dialysis.2
- Running bicarbonate without potassium.1,3
- Intubating without matching the patient's minute ventilation.1,5
- Missing chronic toxicity in a confused older adult.6
How strong is the evidence?
Evidence is weak throughout. Every EXTRIP recommendation is graded D.2 Alkalinization rests on volunteer and small clinical studies.3,4 There is no study supporting a specific bicarbonate regimen.1 The airway data are small retrospective series that point in different directions.5,11 The EXTRIP full text was not openly accessible; its recommendations come from the abstract and a 2025 open-access review.2,1
On-shift teaching
Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.
Q1What blood gas pattern is classic for salicylate toxicity, and what can hide it?
Respiratory alkalosis with an anion gap metabolic acidosis. Sedative co-ingestants can blunt the respiratory alkalosis, and some analyzers falsely lower the anion gap.1
Q2A patient is confused with a salicylate level of 60 mg/dL. Does the patient need dialysis?
Yes. EXTRIP recommends dialysis for altered mental status regardless of the level.2
Q3What are EXTRIP's level thresholds for dialysis?
Recommended above 100 mg/dL (above 90 with impaired kidney function). Suggested above 90 mg/dL (above 80 with impaired kidney function), or for pH ≤ 7.20.2
Q4Why does hypokalemia matter during alkalinization?
Q5Which predicted a severe outcome in the prospective ED cohort: the initial level, age or respiratory rate?
Age (OR 1.13) and respiratory rate (OR 1.29). The initial salicylate level alone did not. Lactate above 2.25 mmol/L was 78% sensitive.7
Q6Why is intubation dangerous, and how do you reduce the risk?
Losing the patient's hyperventilation drops the pH and drives salicylate into the brain. Give bicarbonate first, minimize apnea, and match the pre-intubation minute ventilation.1
References
Evidence base
What this page is built on
11 sources, cited 80 times. Dots are sources, filled by how far each was read; stronger color means a larger share of the citations. Tap a tier to see its sources.
Read in full · 3Abstract read · 5Record only · 3Link checked · 0
Checked by the writer, not a physician. The dots show how each source was read, not that anyone has confirmed the claims.
- 1Sidlak AM, Spadaro A, Koyfman A, Long B. Acute salicylate toxicity: a narrative review for emergency clinicians. Cureus. 2025;17(9):e91505.
- 2Juurlink DN, Gosselin S, Kielstein JT, et al.; EXTRIP Workgroup. Extracorporeal treatment for salicylate poisoning: systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165–181.
- 3Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization (AACT/EAPCCT). J Toxicol Clin Toxicol. 2004;42(1):1–26.
- 4Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT. Diuresis or urinary alkalinisation for salicylate poisoning? Br Med J (Clin Res Ed). 1982;285(6352):1383–1386.
- 5Stolbach 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):866–869.
- 6Long N. Salicylate toxicity. Life in the Fast Lane, Toxicology Library; November 2020.
- 7Shively RM, Hoffman RS, Manini AF. Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol (Phila). 2017;55(3):175–180.
- 8Hoegberg LCG, Gosselin S, Buckley NA, et al. Recommendations from the Clinical Toxicology Recommendations Collaborative on the administration of activated charcoal in acute oral overdose. Clin Toxicol (Phila). 2026;64(6):419–475.
- 9Sodium bicarbonate injection, USP 8.4%. FDA label (Civica).
- 10O'Keefe M, Stanton M, Feldman R, Theobald J. Incidence of rebound salicylate toxicity following cessation of urine alkalinization. Clin Toxicol (Phila). 2023;61(7):536–542.
- 11McDonald BA, Conlon M, Ulici A, et al. Tracheal intubation and mechanical ventilation in adults with severe salicylate poisoning. J Emerg Med. 2024;67(3):e268–e276.
Not for clinical use
AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms