Bedside Snapshot
- Recognize
- Salicylate toxicity: tinnitus, fast breathing, confusion. Early respiratory alkalosis, then metabolic acidosis (mixed). A level above 30 mg/dL (2.2 mmol/L) is acute toxicity.
- Red Flags
- Altered mental status, seizures or coma
- Level above 30 mg/dL. EXTRIP dialysis: above 100 mg/dL (90 with impaired kidneys), or at any level with altered mentation, ARDS needing oxygen, or failing therapy
- Pulmonary edema, hypoxia, or pH ≤7.20
- First Actions
- Airway and breathing: keep minute ventilation high and avoid sedation. Check glucose. Draw a level, blood gas and electrolytes. Start IV sodium bicarbonate with potassium replacement. Call toxicology or the poison center.
- Key Doses
- Sodium bicarbonate 1–2 mEq/kg IV bolus, then 150 mEq/L in D5W at 2–3 mL/kg/hr (per protocol)
- Dextrose 10 g IV, repeated in 5 g steps until alert (field max 25 g)
- Don't Miss
- Intubation without matching minute ventilation (acidemia and CNS toxicity). A negative early level. A normal anion gap from chloride interference. Low brain glucose with a normal serum glucose.
- Escalate & Transport
- Consult toxicology early. ICU for mental status change, pulmonary edema or pH ≤7.20. Hemodialysis per EXTRIP criteria: transfer to a center with dialysis and ICU care.
Definition & Pathophysiology
Salicylate toxicity comes from salicylic acid or its esters: aspirin (acetylsalicylic acid), topical methyl salicylate, oil of wintergreen and bismuth subsalicylate. Salicylate uncouples oxidative phosphorylation and disrupts glucose metabolism. It also drives ventilation harder. That extra minute ventilation causes the early respiratory alkalosis. Later, the metabolic acidosis and the rising level take over the course.
- Acute ingestion: One big dose, or repeated doses over hours. Pylorospasm, enteric-coated tablets or a bezoar can delay absorption.
- Chronic toxicity: Repeated doses taken as prescribed, often in older adults. Serious toxicity can happen at lower serum levels than in an acute overdose.
- Methyl salicylate: Oil of wintergreen and topical rubs. In a child, a small volume can be toxic.
- Saturated elimination: Once the level climbs, elimination saturates and shifts to zero-order kinetics. The half-life lengthens. Toxicity outlasts what the dose suggests.
Recognition & Red Flags
Typical and Severe Presentation
- Early: Tinnitus, nausea, vomiting, tachypnea or hyperpnea. Tinnitus can start near 20 mg/dL. Some patients with toxicity never have it.
- Late: Confusion or delirium, agitation, seizures and coma. Non-cardiogenic pulmonary edema shows up here too.
- End-stage: Hyperthermia above 40 °C (104 °F) is uncommon. When it shows up, it is usually a preterminal sign.
Red Flags
- Serum salicylate above 30 mg/dL (2.2 mmol/L), the level at which acute toxicity is usually seen.
- Altered mental status, seizures, or coma at any level.
- Hypoxia, pulmonary edema, or a PaCO₂ that rises as the pH falls (failing compensation).
- Low brain glucose (neuroglycopenia) with a normal serum glucose.
Assessment & Diagnostics
Start with the level and the time it was drawn. One level can mislead, so repeat it until it is clearly falling. Draw the blood gas and chemistry together. No validated risk score for salicylate was identified, so work from the table.
Amount triage: 150 mg/kg or more over fewer than 8 hours is an acute exposure. A single therapeutic aspirin dose is about 10 mg/kg. Intentional or unknown-amount ingestions go to an emergency department, whatever the estimated dose. Toxicity typically shows up 4–12 hours after ingestion, so one early level cannot clear the patient.
| Check | Why | Act If |
|---|---|---|
| Salicylate level (salicylate) | Measures exposure; an early level can be undetectable | Above 30 mg/dL (2.2 mmol/L): acute toxicity, start treatment. Repeat until clearly falling |
| Blood gas (ABG panel) | Shows early respiratory alkalosis, then a mixed picture | pH ≤7.20: dialysis suggested (see ED & ICU). PaCO₂ rising as pH falls: ventilate |
| Potassium (potassium) | Urinary alkalinization fails if K⁺ is low | Below normal: replace alongside bicarbonate; do not delay bicarbonate for it |
| Anion gap (anion gap) | Chloride ion-selective electrodes can read chloride falsely high at high levels, which masks the gap | A normal or negative gap does not exclude toxicity; check the level and the gas |
| Glucose | Early hyperglycemia is possible; brain glucose can be low with a normal serum glucose | Low glucose or altered mentation: give IV dextrose |
| Lactate (lactate) | In an adult ED cohort, higher lactate, older age, and faster breathing predicted severe outcome | Elevated lactate or altered mentation: ICU-level assessment |
| Creatinine (creatinine) | Impaired kidney function lowers the dialysis thresholds | Impaired kidney function: use the lower thresholds in ED & ICU Management |
| Chest X-ray and SpO₂ | Non-cardiogenic pulmonary edema is a late complication | Hypoxia or crackles: ICU, and consider dialysis per EXTRIP |
Differential & Mimics
- Sepsis in an older adult: fever, tachypnea and confusion look alike. Fever is an end-stage sign of salicylate toxicity. Check the level, then look for a source. See sepsis and septic shock.
- Diabetic ketoacidosis or another high-gap acidosis: the anion gap and the breathing pattern can look alike. The level is what tells them apart. See diabetic ketoacidosis.
- Hypoglycemia or a sedative toxidrome: altered mentation can show up with no tinnitus and no tachypnea. Check glucose and the level. See toxidromes and hypoglycemia.
- Acetaminophen or another co-ingestant: salicylate is often one of several drugs on board. Check acetaminophen too. See acetaminophen toxicity.
BLS Management
- Scene and history: identify the product (aspirin, topical methyl salicylate, oil of wintergreen, or bismuth subsalicylate), the amount, and the time. Bring the containers.
- Airway and breathing: support the airway and ventilation. Do not sedate or restrain a patient who is breathing fast, because sedation can cause apnea.
- Vomiting: position the patient to protect the airway and suction as needed. Oral activated charcoal is given only on poison center advice.
- Glucose and mental status: check glucose where protocol allows. Report confusion, seizure, or a rising breathing rate.
- Notify and transport: call the receiving facility and the poison center early. Any intentional or unknown-amount ingestion goes to an emergency department. Do not delay transport for a level.
ALS Management
Doses vary by protocol; follow local protocols and medical direction.
- IV access and labs (Paramedic/RN/CCT): establish IV access. Draw glucose, electrolytes, a blood gas, and a salicylate level, with the time of ingestion on the requisition.
- Sodium bicarbonate (Paramedic/RN/CCT, per local protocol): 1–2 mEq/kg IV/IO bolus, then 150 mEq/L in D5W at 2–3 mL/kg/hr. No study supports a specific infusion rate. Adjust to the blood gas and urine pH. See Sodium Bicarbonate.
- Potassium (Paramedic/RN/CCT): do not delay bicarbonate for a low K⁺. Start potassium replacement at the same time, within the limits on the Potassium Chloride page (peripheral concentration up to 40 mEq/L), and recheck K⁺ with each gas. Some references add 40–60 mEq K⁺ to the bicarbonate infusion; in a 1 L bag that is 40–60 mEq/L, at or above that peripheral limit; follow local protocol and the Potassium Chloride page.
- Dextrose (Paramedic/RN/CCT): for low glucose or altered mentation, 10 g IV, repeated in 5 g steps until alert, with a field maximum of 25 g. See Dextrose.
- Seizures (Paramedic/RN/CCT): benzodiazepine per local protocol, particularly when the co-ingestant is unknown.
- Ventilation: keep the breathing rate high and avoid sedation that lowers minute ventilation. Intubation is a planned step, not a reflex (see ED & ICU Management).
- Monitoring: cardiac monitor, SpO₂, and capnography where available. Recheck mental status and breathing rate at each contact.
ED & ICU Management
- Alkalinization goals: a serum pH of 7.50–7.55 pulls salicylate out of tissue and into the serum. A urine pH above 7.5 is a secondary goal that shortens toxicity. Measure urine pH with each gas check. Do not use acetazolamide. In mice, it caused respiratory acidosis, and that made salicylate toxicity worse (the 1975 mouse study in References). Treatment is alkalinization with fluid resuscitation. The 2025 review doesn't describe forced diuresis, so this page leaves it out.
- Potassium: you can't alkalinize the urine while K⁺ is low. Do not hold bicarbonate for a low K⁺. Replace potassium alongside it, within the limits on the Potassium Chloride page.
- Gastrointestinal decontamination: activated charcoal, 1 g/kg orally up to 100 g, after an acute ingestion. Give it on poison center advice and only with a protected airway. Do not give it with refractory vomiting, ileus or bowel obstruction. Repeat doses (50 g every 4 hours for two more doses, or 25 g every 2 hours for three doses) only if tolerated, and only for confirmed or suspected delayed absorption from an enteric-coated product or bezoar. Check bowel sounds before each repeat. An Australian retrospective series found charcoal associated with a lower median peak level. For children, follow poison center guidance on dose and airway. Do not intubate only to give charcoal. The 2026 collaborative recommendations advise against intubation solely to give activated charcoal to a patient not expected to develop clinically significant complications of poisoning (Hoegberg 2026, in References).
- Ventilation: Minute ventilation must not fall. Before intubation, consider a bicarbonate bolus of 2 mEq/kg 5–10 minutes before induction, plus bag-valve-mask hyperventilation. After intubation, set a higher rate or tidal volume to match the pre-induction breathing. See RSI and mechanical ventilation.
- Fluids: resuscitate with crystalloid, and use a bicarbonate-containing solution when you have one. Non-cardiogenic pulmonary edema can cap the fluid, and then dialysis may be needed.
- Monitoring during alkalinization: recheck blood gas, K⁺ and urine pH every 1–2 hours. Check Na⁺ and ionized Ca²⁺ every 2–4 hours (per the Sodium Bicarbonate page). Reassess volume status and lungs every hour. Stop or slow the infusion for pulmonary edema, Na⁺ above 150 mEq/L (ceiling 150–155 mEq/L), or serum pH 7.55 or higher.
- Escalation: ICU care for altered mentation, pulmonary edema, pH ≤7.20, or a rising PaCO₂. Consult toxicology and nephrology early.
Hemodialysis Criteria (EXTRIP)
| Finding | EXTRIP recommendation | Grade |
|---|---|---|
| Altered mental status | Recommended | 1D |
| ARDS needing supplemental oxygen | Recommended | 1D |
| Standard therapy failing | Recommended | 1D |
| Level above 100 mg/dL (7.2 mmol/L) | Recommended, with or without symptoms | 1D |
| Level above 90 mg/dL (6.5 mmol/L), impaired kidney function | Recommended | 1D |
| Level above 90 mg/dL (6.5 mmol/L), normal kidney function | Suggested | 2D |
| Level above 80 mg/dL (5.8 mmol/L), impaired kidney function | Suggested | 2D |
| pH ≤7.20, no other indication | Suggested | 2D |
Intermittent hemodialysis is the preferred modality. When it isn't available, hemoperfusion is the alternative. Continuous renal replacement therapy is acceptable when neither one is available. For neonates, when dialysis is unavailable, exchange transfusion is an EXTRIP option (1D). Continue until clinical improvement. Where levels are available, continue until the level is below 19 mg/dL.
Transport Considerations
- Destination: The nearest emergency department with ICU care and access to hemodialysis or nephrology. Step up to critical-care transport when mentation is altered, pulmonary edema is present, or the pH is 7.20 or lower, per local protocol.
- In transit: Monitor continuously with SpO₂, check glucose and count the breathing rate. Keep the bicarbonate running at the protocol rate and check the pump. For crackles, falling SpO₂ or rising breathing effort, stop the infusion and call medical direction.
- Avoid: Sedation or restraint that slows the breathing rate or drops minute ventilation.
- Handoff: product and amount, time of ingestion, each level with its time, bicarbonate given with volume, potassium given, glucose, blood gas, urine pH, and ventilator settings.
- Equipment: A ventilator that can match the pre-intubation minute ventilation. A second check on the weight-based bicarbonate math.
Special Populations
- Pediatrics: use weight-based dosing. Bicarbonate is 1–2 mEq/kg, within the pediatric limits on the Sodium Bicarbonate page. Dextrose is 0.5–1 g/kg with a 25 g maximum per the Dextrose page. See weight-based dosing and pediatric vital signs. A child under 6 years with a suspected ingestion of 1 teaspoon or more of a topical or liquid salicylate product goes to a health facility. That is the threshold poison control uses for topical salicylate analgesics. Oil of wintergreen is concentrated methyl salicylate. Call poison control for any ingestion, since a small volume can be toxic.
- Pregnancy: the sources reviewed don't identify salicylate-specific pregnancy dosing. Use the same level, pH and EXTRIP targets. Bring in obstetrics and toxicology, and follow local protocol.
- Older Adults: in an adult ED cohort, age and faster breathing predicted a severe outcome. Chronic toxicity can make people seriously ill at lower levels. Their confusion may be put down to dementia or sepsis.
- Renal Impairment: With impaired kidneys, EXTRIP lowers the dialysis thresholds to above 90 mg/dL (1D) and above 80 mg/dL (2D).
- Hepatic Impairment: no specific adjustment established.
- Obesity: no specific adjustment established. Dosing weight per local protocol.
- Chronic Aspirin Users: a patient on daily aspirin for cardiovascular prevention can reach toxicity at lower levels. Read the clinical picture, not the level alone.
Pitfalls & Safety Checks
- Error: taking a negative early level as proof of no exposure. Do instead: repeat the level until it is clearly falling. In one bicarbonate-treated retrospective cohort with levels above 30 mg/dL, 3.5% started with an undetectable level. The longest interval to undetectable was 225 minutes.
- Error: Sedating a patient who is breathing fast. Do instead: treat the cause. Correct glucose. Protect ventilation.
- Error: calling a normal or negative anion gap clean. Do instead: check the level and the blood gas. Ask the laboratory which chloride method it uses.
- Error: holding bicarbonate for a low K⁺. Do instead: give bicarbonate now. Replace K⁺ alongside it, within the potassium page limits.
- Error: reaching for acetazolamide to alkalinize the urine. Do instead: avoid it. It causes respiratory acidosis, and that increased salicylate toxicity in mice (see References). Use IV bicarbonate with normal K⁺.
- Error: judging severity by the reported dose or the first level. Do instead: use mental status, breathing rate, lactate, age and the trend. In the adult cohort, the first level alone did not predict severity.
- Error: missing neuroglycopenia. Do instead: give dextrose for low or altered mentation even when the serum glucose is normal.
- Error: discharging after a normal early look. Do instead: finish the serial levels and reassess before disposition.
Clinical Pearls
References
- Juurlink DN, Gosselin S, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, Hoffman RS; EXTRIP Workgroup. Extracorporeal treatment for salicylate poisoning: systematic review and recommendations from the EXTRIP workgroup (the current EXTRIP salicylate recommendations). Ann Emerg Med. 2015;66(2):165–181. https://doi.org/10.1016/j.annemergmed.2015.03.031
- Sidlak AM, Spadaro A, Koyfman A, Long B. Acute salicylate toxicity: a narrative review for emergency clinicians. Cureus. 2025;17(9):e91505. https://doi.org/10.7759/cureus.91505
- Shively RM, Hoffman RS, Manini AF. Acute salicylate poisoning: risk factors for severe outcome. Clin Toxicol (Phila). 2017;55(3):175–180. https://doi.org/10.1080/15563650.2016.1271127
- Moss MJ, Fisher JA, Kenny TA, Palmer AC, Thompson JA, Wolfer H, Hendrickson RG. Salicylate toxicity after undetectable serum salicylate concentration: a retrospective cohort study. Clin Toxicol (Phila). 2019;57(2):137–140. https://doi.org/10.1080/15563650.2018.1502442
- Isoardi KZ, Henry C, Harris K, Isbister GK. Activated charcoal and bicarbonate for aspirin toxicity: a retrospective series. J Med Toxicol. 2022;18(1):30–37. https://doi.org/10.1007/s13181-021-00865-0
- Wiederkehr MR, Benevides R Jr, Santa Ana CA, Emmett M. Pseudohyperchloremia and negative anion gap: think salicylate! Am J Med. 2021;134(9):1170–1174. https://doi.org/10.1016/j.amjmed.2021.03.017
- Liddell NE, Maren TH. CO2 retention as a basis for increased toxicity of salicylate with acetazolamide: avoidance of increased toxicity with benzolamide. J Pharmacol Exp Ther. 1975;195(1):1–7. https://pubmed.ncbi.nlm.nih.gov/241836/
- Hoegberg LCG, Gosselin S, Buckley NA, Wood DM, 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. https://doi.org/10.1080/15563650.2025.2609807
- Arriola K, Cantrell L. Risk of toxicity from pediatric topical salicylate ingestions. Clin Toxicol (Phila). 2021;59:655–657. https://doi.org/10.1080/15563650.2020.1849716
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- For Educational Purposes Only: This content is intended for educational reference and should not be used for clinical decision-making.
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