Overview
Salicylate Overdose
Quick Reference
Critical Alerts
- Salicylate poisoning can be rapidly fatal - aggressive treatment is essential
- Mixed acid-base disorder: Respiratory alkalosis + metabolic acidosis
- Never intubate without addressing acidosis - rapid deterioration can occur
- Hemodialysis is definitive treatment for severe toxicity
- Serial salicylate levels are essential - delayed absorption and enteric-coated formulations
Key Diagnostics
- Serum salicylate level (therapeutic: 10-30 mg/dL)
- Arterial blood gas (mixed disorder characteristic)
- Basic metabolic panel (anion gap acidosis)
- Lactate (elevated in severe toxicity)
- Urine pH (target >7.5 with alkalinization)
Emergency Treatments
- Activated charcoal: 1 g/kg if within 2 hours (or later for enteric-coated)
- Urinary alkalinization: Sodium bicarbonate 150 mEq in 1L D5W at 150-200 mL/hr
- Glucose: Supplement despite normal serum glucose (CNS depletion)
- Hemodialysis: Severe toxicity, level >90-100 mg/dL, altered mental status
- Avoid intubation if possible - if needed, hyperventilate and correct acidosis
Definition
Salicylate toxicity is a potentially life-threatening poisoning resulting from acute ingestion or chronic accumulation of aspirin (acetylsalicylic acid) or related salicylate compounds. The condition is characterized by complex metabolic derangements, including a mixed respiratory alkalosis and metabolic acidosis, and can progress rapidly to multi-organ failure.
Sources of Salicylates
| Source | Common Products |
|---|---|
| Aspirin (ASA) | Multiple brands, combination products |
| Oil of wintergreen (methyl salicylate) | Topical preparations - HIGHLY CONCENTRATED |
| Bismuth subsalicylate | Pepto-Bismol |
| Topical salicylates | Muscle rubs, wart removers |
| Willow bark | Herbal preparations |
Toxicity Thresholds
| Ingested Amount | Expected Severity |
|---|---|
| <150 mg/kg | Minimal to mild toxicity |
| 150-300 mg/kg | Moderate toxicity |
| 300-500 mg/kg | Severe toxicity |
| >00 mg/kg | Potentially fatal |
Classification
| Type | Description | Features |
|---|---|---|
| Acute | Single large ingestion | Clear onset, rising levels |
| Chronic | Repeated supratherapeutic dosing | Subtle onset, worse prognosis at lower levels |
| Acute-on-chronic | Acute ingestion on chronic therapy |
Pathophysiology
Mechanism of Toxicity
Direct Stimulation of Respiratory Center
- Salicylates directly stimulate medullary respiratory center
- Leads to hyperventilation → respiratory alkalosis (early)
Uncoupling of Oxidative Phosphorylation
- Disrupts mitochondrial electron transport chain
- Impaired ATP production despite increased oxygen consumption
- Increased heat production (hyperthermia)
- Metabolic acidosis (lactate, ketoacids)
Metabolic Effects
| Effect | Mechanism |
|---|---|
| Anion gap acidosis | Lactate, ketones, salicylic acid |
| Hypokalemia | Alkaline urine traps K+; vomiting |
| Hypoglycemia (CNS) | Increased cellular glucose utilization |
| Dehydration | Vomiting, fever, hyperventilation |
CNS Glucose Paradox
- Serum glucose may be normal or elevated
- CNS glucose is depleted due to increased metabolic demand
- Neuroglycopenia occurs despite normoglycemia
- Always supplement glucose in severe toxicity
Tissue Distribution
- At therapeutic pH, salicylate exists partially ionized
- With acidemia, more salicylate becomes unionized
- Unionized salicylate crosses blood-brain barrier more readily
- Acidosis worsens CNS toxicity
This is why:
- Intubation without addressing acidosis is dangerous
- Respiratory alkalosis is protective
- Bicarbonate therapy is critical
Clinical Presentation
Staged Progression
| Stage | Timing | Features |
|---|---|---|
| Early | 0-12 hours | Nausea, vomiting, tinnitus, hyperventilation |
| Moderate | 12-24 hours | Tachypnea, diaphoresis, fever, agitation |
| Severe | >4 hours | Altered mental status, seizures, coma, pulmonary edema, ARDS, death |
Symptoms by System
Gastrointestinal
Neurological
Respiratory
Metabolic
Physical Examination
| Finding | Stage |
|---|---|
| Tachypnea, hyperpnea | Early (critical finding) |
| Tachycardia | Early |
| Fever | Moderate to severe |
| Diaphoresis | Moderate |
| Altered mental status | Severe |
| Seizures | Severe (ominous) |
| Pulmonary edema | Severe |
Classic Acid-Base Pattern
Mixed Respiratory Alkalosis + Metabolic Acidosis
| Timing | pH | PaCO2 | HCO3 | Anion Gap |
|---|---|---|---|---|
| Early | High (alkalosis) | Low | Normal | Normal |
| Intermediate | Normal | Low | Low | Elevated |
| Late | Low (acidosis) | Low or normal | Very low | Very elevated |
Nausea and vomiting (often early)
Common presentation.
Abdominal pain
Common presentation.
GI bleeding (from direct irritation and antiplatelet effects)
Common presentation.
Red Flags (Life-Threatening)
Critical Findings
| Red Flag | Concern | Action |
|---|---|---|
| Salicylate level >0-100 mg/dL | Severe toxicity | Emergent hemodialysis |
| Altered mental status | CNS toxicity | Hemodialysis, ICU |
| Seizures | Severe CNS toxicity | Benzodiazepines, hemodialysis |
| Pulmonary edema | Non-cardiogenic | ICU, hemodialysis |
| pH <7.2 | Severe acidosis | Bicarbonate, hemodialysis |
| Rising level on repeat | Continued absorption | Extended charcoal, consider WBI |
| Respiratory fatigue | Impending respiratory failure | Prepare for intubation with precautions |
Danger of Intubation
Critical Concept: Patients with salicylate toxicity compensate for metabolic acidosis with respiratory alkalosis (hyperventilation). Intubation with normal ventilator settings can:
- Reduce minute ventilation
- Allow PaCO2 to rise
- Cause rapid acidemia
- Increase CNS salicylate penetration
- Lead to cardiovascular collapse and death
If Intubation Required:
- Pre-intubate with IV sodium bicarbonate
- Use high respiratory rate (20+) and large tidal volumes
- Target PaCO2 at or below pre-intubation levels
- Have vasopressors ready
- Arrange emergent hemodialysis
Differential Diagnosis
Other Causes of Anion Gap Metabolic Acidosis
MUDPILES Mnemonic
| Letter | Cause |
|---|---|
| M | Methanol |
| U | Uremia |
| D | Diabetic ketoacidosis |
| P | Propylene glycol |
| I | Isoniazid, Iron |
| L | Lactic acidosis |
| E | Ethylene glycol |
| S | Salicylates |
Conditions with Similar Presentations
| Condition | Distinguishing Features |
|---|---|
| Sepsis | Positive cultures, source of infection |
| DKA | Hyperglycemia, ketones, diabetes history |
| Toxic alcohol ingestion | Osmol gap, specific levels |
| Iron overdose | Abdominal x-ray, serum iron level |
| Theophylline toxicity | Level, seizures prominent |
| Serotonin syndrome | Drug history, hyperreflexia, myoclonus |
Diagnostic Approach
Initial Assessment
Key History
- Type and amount of salicylate ingested
- Time of ingestion
- Enteric-coated vs immediate-release
- Intentional vs unintentional
- Chronic use history
- Co-ingestants
Laboratory Studies
| Test | Purpose | Key Findings |
|---|---|---|
| Salicylate level | Diagnosis and severity | See interpretation below |
| ABG/VBG | Acid-base status | Mixed pattern |
| BMP | Anion gap, electrolytes | Elevated AG, hypokalemia |
| Lactate | Tissue perfusion | Elevated in severe |
| Glucose | Hypoglycemia | May be normal but CNS depleted |
| Urine pH | Monitor alkalinization | Target >.5 |
| Coagulation | Bleeding risk | May be prolonged |
| LFTs | Hepatotoxicity | May be elevated |
| Acetaminophen level | Co-ingestion | Always check |
Salicylate Level Interpretation
| Level (mg/dL) | Interpretation |
|---|---|
| 10-30 | Therapeutic |
| 30-60 | Mild toxicity |
| 60-90 | Moderate toxicity |
| >0-100 | Severe toxicity (hemodialysis indicated) |
Important Considerations:
- Peak levels may be delayed 6+ hours (especially enteric-coated)
- Chronic toxicity is severe at lower levels (50-60 mg/dL can be serious)
- Serial levels essential - repeat every 2-4 hours until declining
Done Nomogram (Historical)
- Historically used to predict severity
- No longer recommended for clinical decision-making
- Does not account for acidemia, chronic toxicity, or clinical status
- Clinical assessment is more important
Treatment
Decontamination
Activated Charcoal
Dose: 1 g/kg (max 50g)
Timing: Most effective <2 hours
Extended window: Enteric-coated, large ingestions, delayed presentation
Contraindications: Altered mental status, unprotected airway
Multi-dose activated charcoal (MDAC):
- Consider for large ingestions
- 25-50g every 4-6 hours
- Enhanced elimination
Whole Bowel Irrigation
- Consider for enteric-coated or sustained-release formulations
- Polyethylene glycol solution via NG at 1-2 L/hour
- Continue until rectal effluent is clear
Urinary Alkalinization
Primary Treatment for Moderate Toxicity
Solution: 150 mEq NaHCO3 in 1L D5W
Rate: 150-200 mL/hr initially (2-3x maintenance)
Goals:
- Urine pH 7.5-8.0
- Blood pH 7.45-7.55 (mild alkalemia preferred)
- Serum K+ >4.0 mEq/L
Mechanism:
- Ionized salicylate cannot cross membranes
- Alkaline urine traps salicylate in renal tubules
- Enhances elimination
Critical Adjuncts:
- Potassium replacement: Alkalinization won't work with hypokalemia (H+/K+ exchange)
- Glucose: D5W or D10W to provide CNS glucose
- Monitor: Serial electrolytes, urine pH, salicylate levels
Hemodialysis
Indications (EXTRIP Guidelines)
Recommended if ANY of:
- Salicylate level >90-100 mg/dL (acute) or >70 mg/dL (chronic)
- Altered mental status
- New hypoxia requiring supplemental oxygen
- pH ≤7.2
Suggested if ANY of:
- Salicylate level >90 mg/dL
- Level 70-90 with clinical toxicity
- Failure of standard therapy
Benefits:
- Removes salicylate directly
- Corrects acidosis rapidly
- Corrects electrolytes
- Removes any co-ingestants
Supportive Care
| Issue | Management |
|---|---|
| Hyperthermia | Active cooling |
| Seizures | Benzodiazepines |
| Hypotension | IV fluids, vasopressors |
| Cerebral edema | Hemodialysis, supportive |
| Pulmonary edema | Hemodialysis, supportive |
| Coagulopathy | Vitamin K, FFP if bleeding |
Airway Management (If Unavoidable)
Pre-intubation:
1. Push IV NaHCO3 100-150 mEq
2. Have vasopressors ready
3. Consider ketamine for induction (maintains spontaneous breathing longer)
Post-intubation:
1. Set RR 20-24, TV 8-10 mL/kg (mimic pre-intubation minute ventilation)
2. Target PaCO2 at pre-intubation level or lower
3. Continue aggressive bicarbonate
4. Arrange emergent hemodialysis
Disposition
ICU Admission Indications
- Salicylate level >50 mg/dL (acute)
- Any altered mental status
- Acid-base disturbance requiring intervention
- Need for urinary alkalinization
- Need for hemodialysis
- Unstable vital signs
- Rising salicylate levels
Monitoring Requirements
- Continuous cardiac monitoring
- Serial salicylate levels (every 2-4 hours until peak and declining)
- Hourly urine pH if alkalinizing
- Frequent electrolytes (K+, HCO3-)
- ABG/VBG every 2-4 hours
Discharge Criteria (Mild Toxicity Only)
- Asymptomatic
- Single low-risk ingestion
- Salicylate level declining and <30 mg/dL
- Normal acid-base status
- Psychiatric clearance if intentional
Toxicology/Poison Control
- Contact poison control for all salicylate ingestions
- 24/7 consultation available
- Can assist with hemodialysis decisions
Patient Education
Understanding Salicylate Toxicity
- Aspirin and other salicylates can cause serious poisoning
- Even therapeutic doses can accumulate and cause toxicity
- Treatment is effective when started early
Prevention of Recurrence
For Intentional Ingestions
- Mental health evaluation and follow-up
- Secure medications
- Suicide prevention resources
For Chronic Toxicity
- Medication reconciliation
- Avoid multiple aspirin-containing products
- Know signs of toxicity (ringing in ears, confusion)
Warning Signs
Seek immediate care if:
- Ringing in ears
- Rapid breathing
- Confusion or agitation
- Nausea and vomiting
- Sweating and fever
Special Populations
Chronic Salicylate Toxicity
Key Differences from Acute:
- Subtle onset (days to weeks of supratherapeutic dosing)
- Often misdiagnosed as sepsis, dementia, delirium
- More severe toxicity at lower levels (e.g., 50-60 mg/dL)
- Higher mortality than acute toxicity
- More common in elderly
Common Scenarios:
- Elderly on chronic aspirin therapy with illness
- Renal impairment + aspirin use
- Multiple aspirin-containing products
Pediatric Considerations
- More susceptible to toxicity
- Lower lethal dose (150-200 mg/kg concerning)
- Metabolic acidosis may predominate earlier
- Consider oil of wintergreen ingestion (1 tsp = 6g aspirin)
Pregnancy
- Salicylates cross placenta
- Risk of fetal hemorrhage, premature closure of ductus arteriosus
- Treat aggressively - benefits outweigh risks
- Hemodialysis safe in pregnancy
Elderly
- More susceptible to chronic toxicity
- Often on chronic aspirin therapy
- May present atypically (confusion, lethargy)
- Higher mortality
Quality Metrics
Performance Indicators
| Metric | Target |
|---|---|
| Salicylate level ordered for suspected toxicity | 100% |
| ABG obtained for moderate-severe toxicity | 100% |
| Activated charcoal within 2 hours (if indicated) | >0% |
| Urinary alkalinization initiated appropriately | >0% |
| Nephrology consulted for hemodialysis criteria | 100% |
| Poison control contacted | 100% |
Documentation Requirements
- Time and amount of ingestion
- Serial salicylate levels with times
- Acid-base status (ABG/VBG)
- Treatments provided and response
- Urine pH monitoring
- Hemodialysis consideration and decision
- Psychiatric assessment (if intentional)
Key Clinical Pearls
Diagnostic Pearls
- Check salicylate level in any unexplained anion gap acidosis
- Chronic toxicity is worse at same level as acute
- Enteric-coated formulations cause delayed peak levels
- Mixed acid-base pattern (respiratory alkalosis + metabolic acidosis) is classic
- Tinnitus is an early warning sign
Treatment Pearls
- Alkalinization before intubation - if you must intubate
- Potassium replacement essential for effective alkalinization
- Give glucose even with normal serum levels (CNS depletion)
- Hemodialysis saves lives - don't delay if indicated
- Serial levels - a single level is not enough
Disposition Pearls
- All moderate-severe toxicity requires ICU
- Levels should be trending down before any consideration of discharge
- Psychiatric evaluation for all intentional ingestions
- Poison control is your friend - call them
- Chronic toxicity has worse prognosis - treat aggressively
References
- Juurlink DN, et al. Extracorporeal Treatment for Salicylate Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup. Ann Emerg Med. 2015;66(2):165-181.
- Chyka PA, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol. 2007;45(2):95-131.
- O'Malley GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25(2):333-346.
- Proudfoot AT, et al. Position Paper on Urine Alkalinization. J Toxicol Clin Toxicol. 2004;42(1):1-26.
- Dargan PI, Wallace CI, Jones AL. An evidenced based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J. 2002;19(3):206-209.
- Pearlman BL, Gambhir R. Salicylate intoxication: a clinical review. Postgrad Med. 2009;121(4):162-168.
Version History
| Version | Date | Changes |
|---|---|---|
| 1.0 | 2025-01-15 | Initial comprehensive version with 14-section template |