Summary

Salicylate toxicity is a serious complication of aspirin overdose and is characterized by mixed respiratory alkalosis and increased anion gap metabolic acidosis. Early symptoms include tinnitus, nausea, vomiting, and tachypnea. Late symptoms include altered mental status, seizures, and hyperthermia. Fluid resuscitation, oral activated charcoal, and alkalinization of the serum and urine are the most important aspects of treatment. In severe cases, hemodialysis may be indicated. Intubation should be avoided, as it can precipitate clinical decompensation if ventilation needs are not met. For other side effects related to aspirin use, see antiplatelet agents.

Clinical features

Early symptoms: tinnitus, nausea, vomiting, tachypnea, hyperpnea
Late symptoms: hyperthermia, agitation, delirium, seizures, noncardiogenic pulmonary edema

Salicylate toxicity severity ^[1]
	Serum salicylate level	Clinical features
Mild toxicity	Adults: 30–60 mg/dL Children/elderly: 20–45 mg/dL	Tinnitus Nausea/vomiting Lethargy
Moderate toxicity	Adults: 60–80 mg/dL Children/elderly: 45–70 mg/dL	Tachypnea Diaphoresis
Severe toxicity	Adults: > 80 mg/dL Children/elderly: > 70 mg/dL	Coma Seizures Pulmonary edema Renal failure Hypercarbia

Diagnostics

ABG
- Mixed respiratory alkalosis; and increased anion gap metabolic acidosis in early stages ^[2]
- Progresses to mixed metabolic acidosis-respiratory alkalosis
Serum salicylate level: > 40 mg/dL ^[1]
BMP: hypokalemia, ↑ BUN, ↑ creatinine
Toxicology screen: evaluate for concurrent ingestions

Because salicylate levels are not always elevated initially and do not necessarily correlate with clinical presentation, a high index of suspicion should be maintained when caring for a patient with symptoms of salicylate toxicity. Rapid treatment is essential!

Treatment

General principles ^[1]^[2]

Stabilization of vitals
Oral/orogastric activated charcoal
IV sodium bicarbonate
Hemodialysis

Initial assessment and airway management

Stabilize the patient.
Assess the severity of salicylate toxicity (see salicylate toxicity severity above).
For symptomatic patients: Consult ICU, nephrology, and toxicology.
Evaluate the need for intubation but avoid intubation, if possible.
- If intubation is necessary
  - Administer bicarbonate prior to intubation
  - Maximize minute ventilation (e.g., at least 8–10 mL/kg/breath)

Indications for intubation in salicylate toxicity

Deteriorating mental state
Seizures
ARDS
Hypoventilation (e.g., hypercarbia)

Indications for hemodialysis in salicylate toxicity ^[3]

Serum salicylates > 100 mg/dL (> 90 mg/dL if renal function impaired)
Serum salicylates > 90 mg/dL (> 80 mg/dL if renal function impaired) or arterial pH ≤ 7.2 despite supportive care
Altered mental status
Hypoxemia requiring supplemental O₂

Intubating patients with salicylate toxicity is dangerous! If intubation is required, extra care should be taken to maximize minute ventilation, as there is a high risk of worsening acidosis and death.

Salicylate combinations with other substances (like opioids) can lead to mixed intoxications that require specific management (e.g., naloxone).

Gastric decontamination ^[1]^[4]

Considerations for gastric lavage
- The ingested aspirin dose is known to be > 500 mg/kg.
- Ingestion occurred < 1 hour prior to presentation.
Considerations for oral activated charcoal
- The patient must have a secure airway (i.e., is awake and alert or is intubated with an orogastric tube).
- Timing of ingestion: There are no specific recommendations. ^[4]
  - 2–4 hours of known ingestion: Giving at least one dose is most likely beneficial.
  - Within 4–24 hours of known ingestion: may be beneficial in some patients (e.g., ingestion of a large amount, severe toxicity)

Fluid and acid-base management ^[1]

Fluid resuscitation
- Preferred fluids: LR and/or 5% dextrose
- Isotonic bicarbonate solutions, if alkalinization is required (see below)
- Avoid normal saline, as it can aggravate acidosis.
- Add IV dextrose even if blood glucose is normal to prevent cerebral hypoglycemia.
Alkalinization of serum and urine with IV sodium bicarbonate ^[2]^[1]
- Indications: any symptomatic patient, or if serum salicylates > 60 mg/dL
- Bicarbonate dosage
  - Consider bicarbonate loading dose , especially if arterial pH < 7.3 or patient requires intubation.
  - Continuous bicarbonate in D5W to achieve and maintain urine alkalization ^[1]^[2]
  - Targets ^[1]
    - Serum pH 7.5–7.55
    - Urine pH 7.5–8.5
    - Urine output: 2–3 mL/kg/hour ^[2]
    - Serum potassium: 4–4.5 mEq/L

Monitoring and additional concerns

Repeat labs every 2 hours.
- Blood glucose, BMP, ABG
- Serum salicylates (until consistently < 40 mg/dL)
ICU level of care
Continuous cardiac monitoring, continuous pulse oximetry, frequent neurological checks
Evaluate and treat suicidal ideation.

Acute management checklist for salicylate toxicity

Establish IV access.
Fluid resuscitation with LR and/or D5W (avoid normal saline)
Assess the severity of intoxication (see salicylate toxicity severity).
Consult ICU, nephrology, and toxicology.
Avoid intubation if possible, but secure the airway if necessary (see indications for intubation in salicylate toxicity).
Assess the need for hemodialysis (see indications for hemodialysis in salicylate toxicity).
Start alkalization of serum and urine (see fluid and acid-base management in “Treatment”).
Avoid and correct hypoglycemia and hypokalemia.
Check toxicology screen for concurrent ingestions.
Evaluate for suicidal ideation.
Order repeat labs (BMP, glucose, salicylate levels) every 2 hours.
Admit to the ICU.

General principles [1][2]