Diferencia entre revisiones de «Salicylate toxicity»

(Major update: EXTRIP HD indications, intubation danger, CNS glucose deficiency, alkalinization protocol with K requirement, oil of wintergreen warning, zero-order kinetics, references with PMIDs)
(Strip excess bold)
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==Background==
==Background==
*Aspirin (acetylsalicylic acid) is the most common salicylate
*Aspirin (acetylsalicylic acid) is the most common salicylate
*Other salicylate sources: bismuth subsalicylate (Pepto-Bismol), oil of wintergreen ('''most concentrated — 1 teaspoon = ~7g aspirin'''), topical agents (Ben-Gay)
*Other salicylate sources: bismuth subsalicylate (Pepto-Bismol), oil of wintergreen (most concentrated — 1 teaspoon = ~7g aspirin), topical agents (Ben-Gay)
*Therapeutic level: '''10-30 mg/dL'''
*Therapeutic level: 10-30 mg/dL
*Toxic ingestion: '''>150 mg/kg'''
*Toxic ingestion: >150 mg/kg
*Lethal dose: '''~500 mg/kg'''
*Lethal dose: ~500 mg/kg
*Mechanism of toxicity:
*Mechanism of toxicity:
**'''Uncouples oxidative phosphorylation''' → impaired aerobic metabolism, heat generation
**Uncouples oxidative phosphorylation → impaired aerobic metabolism, heat generation
**Direct CNS stimulation of respiratory center → respiratory alkalosis (early)
**Direct CNS stimulation of respiratory center → respiratory alkalosis (early)
**'''Accumulation of organic acids''' → anion gap metabolic acidosis (late)
**Accumulation of organic acids → anion gap metabolic acidosis (late)
**Inhibits Krebs cycle, disrupts lipid and amino acid metabolism
**Inhibits Krebs cycle, disrupts lipid and amino acid metabolism
*Pharmacokinetics change in overdose:
*Pharmacokinetics change in overdose:
**'''Zero-order kinetics at toxic levels''' (saturable metabolism)
**Zero-order kinetics at toxic levels (saturable metabolism)
**'''Delayed absorption''' with enteric-coated or sustained-release formulations
**Delayed absorption with enteric-coated or sustained-release formulations
**'''Bezoar formation''' possible with massive ingestion
**Bezoar formation possible with massive ingestion


==Clinical Features==
==Clinical Features==
===Acute Toxicity===
===Acute Toxicity===
*'''Early''': tinnitus, nausea, vomiting, [[tachypnea]] (respiratory alkalosis)
*Early: tinnitus, nausea, vomiting, [[tachypnea]] (respiratory alkalosis)
*'''Moderate''': diaphoresis, [[tachycardia]], [[hyperthermia]], agitation, confusion
*Moderate: diaphoresis, [[tachycardia]], [[hyperthermia]], agitation, confusion
*'''Severe''': '''altered mental status''', [[seizures]], '''pulmonary edema''' (noncardiogenic), [[cerebral edema]], coma
*'''Severe''': '''altered mental status''', [[seizures]], '''pulmonary edema''' (noncardiogenic), [[cerebral edema]], coma
*'''Classic acid-base pattern''':
*Classic acid-base pattern:
**Adults: '''mixed respiratory alkalosis + metabolic acidosis'''
**Adults: mixed respiratory alkalosis + metabolic acidosis
**Children: metabolic acidosis predominates (may not have initial respiratory alkalosis phase)
**Children: metabolic acidosis predominates (may not have initial respiratory alkalosis phase)


===Chronic Toxicity===
===Chronic Toxicity===
*More insidious and '''often misdiagnosed''' (especially in elderly)
*More insidious and often misdiagnosed (especially in elderly)
*Presents with confusion, tinnitus, dehydration, metabolic acidosis
*Presents with confusion, tinnitus, dehydration, metabolic acidosis
*May be diagnosed as [[sepsis]], altered mental status workup
*May be diagnosed as [[sepsis]], altered mental status workup
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==Differential Diagnosis==
==Differential Diagnosis==
*[[Sepsis]] (similar presentation with tachypnea, metabolic acidosis, AMS)
*[[Sepsis]] (similar presentation with tachypnea, metabolic acidosis, AMS)
*Other causes of '''anion gap metabolic acidosis''' (MUDPILES: methanol, uremia, DKA, propylene glycol, INH/iron, lactic acidosis, ethylene glycol, salicylates)
*Other causes of anion gap metabolic acidosis (MUDPILES: methanol, uremia, DKA, propylene glycol, INH/iron, lactic acidosis, ethylene glycol, salicylates)
*[[Theophylline toxicity]] (similar features)
*[[Theophylline toxicity]] (similar features)
*[[Acetaminophen toxicity]] (common coingestion)
*[[Acetaminophen toxicity]] (common coingestion)
Línea 37: Línea 37:


==Evaluation==
==Evaluation==
*'''Salicylate level''':
*Salicylate level:
**Therapeutic: 10-30 mg/dL
**Therapeutic: 10-30 mg/dL
**Toxic: '''> 30 mg/dL'''
**Toxic: > 30 mg/dL
**Severe: '''>90 mg/dL'''
**Severe: >90 mg/dL
**'''Repeat level every 2 hours''' until declining (delayed absorption, bezoar)
**Repeat level every 2 hours until declining (delayed absorption, bezoar)
**'''Done nomogram''' (not well validated for chronic or enteric-coated ingestions)
**Done nomogram (not well validated for chronic or enteric-coated ingestions)
*'''ABG/VBG''': assess pH ('''acidemia dramatically worsens toxicity by driving salicylate into CNS''')
*ABG/VBG: assess pH (acidemia dramatically worsens toxicity by driving salicylate into CNS)
*'''BMP''': anion gap, '''glucose''' (CNS hypoglycemia may occur despite normal serum glucose), potassium, bicarbonate, creatinine
*BMP: anion gap, glucose (CNS hypoglycemia may occur despite normal serum glucose), potassium, bicarbonate, creatinine
*'''Acetaminophen level''' (common coingestion)
*Acetaminophen level (common coingestion)
*'''LFTs, coagulation studies''' (hepatotoxicity, coagulopathy)
*LFTs, coagulation studies (hepatotoxicity, coagulopathy)
*'''Lactate'''
*Lactate
*'''Urine pH''': target alkalinization to pH 7.5-8.0
*Urine pH: target alkalinization to pH 7.5-8.0
*'''CXR''' if concern for pulmonary edema
*CXR if concern for pulmonary edema


==Management==
==Management==
===GI Decontamination===
===GI Decontamination===
*'''Activated charcoal''' 1 g/kg (max 50g): effective if '''within 1-2 hours''' of ingestion
*Activated charcoal 1 g/kg (max 50g): effective if within 1-2 hours of ingestion
**May benefit later with large ingestions, enteric-coated tablets, or bezoar
**May benefit later with large ingestions, enteric-coated tablets, or bezoar
**Multiple doses may be considered
**Multiple doses may be considered
*'''Whole bowel irrigation''' for massive ingestions or sustained-release/enteric-coated tablets
*Whole bowel irrigation for massive ingestions or sustained-release/enteric-coated tablets


===Alkalinization (Cornerstone of Treatment)===
===Alkalinization (Cornerstone of Treatment)===
*'''IV sodium bicarbonate'''
*IV sodium bicarbonate
*'''Goal: urine pH 7.5-8.0''' and '''serum pH 7.50-7.55'''
*Goal: urine pH 7.5-8.0 and serum pH 7.50-7.55
**Alkaline urine traps ionized salicylate in renal tubules → enhanced elimination
**Alkaline urine traps ionized salicylate in renal tubules → enhanced elimination
**Alkaline serum prevents salicylate from crossing blood-brain barrier
**Alkaline serum prevents salicylate from crossing blood-brain barrier
*'''Protocol''':
*Protocol:
**'''Bolus: 1-2 mEq/kg IV NaHCO3'''
**Bolus: 1-2 mEq/kg IV NaHCO3
**'''Infusion: 150 mEq NaHCO3 in 1L D5W''' at 150-250 mL/hr
**Infusion: 150 mEq NaHCO3 in 1L D5W at 150-250 mL/hr
**'''Add 20-40 mEq KCl per liter''' (hypokalemia impairs urinary alkalinization)
**Add 20-40 mEq KCl per liter (hypokalemia impairs urinary alkalinization)
*'''CRITICAL''': '''alkalinization will NOT work without adequate potassium replacement'''
*CRITICAL: alkalinization will NOT work without adequate potassium replacement
*Monitor serum pH, urine pH, and potassium every 1-2 hours
*Monitor serum pH, urine pH, and potassium every 1-2 hours


===Dextrose===
===Dextrose===
*'''Give D50W (50 mL IV)''' empirically if any CNS symptoms (altered mental status, seizures)
*'''Give D50W (50 mL IV)''' empirically if any CNS symptoms (altered mental status, seizures)
*'''CNS glucose may be low even with normal serum glucose''' (salicylate impairs CNS glucose transport)
*CNS glucose may be low even with normal serum glucose (salicylate impairs CNS glucose transport)
*Add dextrose to maintenance fluids
*Add dextrose to maintenance fluids


===Hemodialysis===
===Hemodialysis===
*'''Most effective method of salicylate removal'''
*Most effective method of salicylate removal
*'''EXTRIP Workgroup Indications'''<ref>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. PMID 25986310</ref>:
*EXTRIP Workgroup Indications<ref>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. PMID 25986310</ref>:
**'''Recommended''': salicylate level '''> 90 mg/dL''' (acute) or '''> 80 mg/dL''' (chronic)
**Recommended: salicylate level > 90 mg/dL (acute) or > 80 mg/dL (chronic)
**'''Recommended''': altered mental status, new hypoxemia requiring supplemental O2
**'''Recommended''': altered mental status, new hypoxemia requiring supplemental O2
**'''Recommended''': pH ≤ 7.20 despite bicarbonate therapy
**Recommended: pH ≤ 7.20 despite bicarbonate therapy
**'''Suggested''': salicylate level > 80 mg/dL (acute), renal failure limiting salicylate clearance, clinical deterioration despite treatment
**Suggested: salicylate level > 80 mg/dL (acute), renal failure limiting salicylate clearance, clinical deterioration despite treatment
*Also dialyzes out the metabolic acidosis
*Also dialyzes out the metabolic acidosis
*Consult nephrology early
*Consult nephrology early
Línea 90: Línea 90:
**'''Loss of respiratory compensation''' (even brief during intubation) causes '''rapid acidemia → CNS salicylate accumulation → cardiac arrest'''
**'''Loss of respiratory compensation''' (even brief during intubation) causes '''rapid acidemia → CNS salicylate accumulation → cardiac arrest'''
**If intubation required: '''maximize bicarb, match minute ventilation''' to pre-intubation rate
**If intubation required: '''maximize bicarb, match minute ventilation''' to pre-intubation rate
*'''Avoid acetazolamide''' (causes metabolic acidosis)
*Avoid acetazolamide (causes metabolic acidosis)
*'''Avoid excessive IV fluids''' without bicarb (dilutes serum alkalinity)
*Avoid excessive IV fluids without bicarb (dilutes serum alkalinity)


==Disposition==
==Disposition==
*'''ICU admission''' for: level >50 mg/dL, acidemia, AMS, pulmonary edema, renal failure
*ICU admission for: level >50 mg/dL, acidemia, AMS, pulmonary edema, renal failure
*'''Monitored bed''' for moderate toxicity with improving levels
*Monitored bed for moderate toxicity with improving levels
*'''Serial salicylate levels''' every 2 hours until clearly declining
*Serial salicylate levels every 2 hours until clearly declining
*'''Poison control: 1-800-222-1222'''
*Poison control: 1-800-222-1222
*Psychiatric evaluation for intentional ingestions
*Psychiatric evaluation for intentional ingestions


Revisión del 09:30 22 mar 2026

Background

  • Aspirin (acetylsalicylic acid) is the most common salicylate
  • Other salicylate sources: bismuth subsalicylate (Pepto-Bismol), oil of wintergreen (most concentrated — 1 teaspoon = ~7g aspirin), topical agents (Ben-Gay)
  • Therapeutic level: 10-30 mg/dL
  • Toxic ingestion: >150 mg/kg
  • Lethal dose: ~500 mg/kg
  • Mechanism of toxicity:
    • Uncouples oxidative phosphorylation → impaired aerobic metabolism, heat generation
    • Direct CNS stimulation of respiratory center → respiratory alkalosis (early)
    • Accumulation of organic acids → anion gap metabolic acidosis (late)
    • Inhibits Krebs cycle, disrupts lipid and amino acid metabolism
  • Pharmacokinetics change in overdose:
    • Zero-order kinetics at toxic levels (saturable metabolism)
    • Delayed absorption with enteric-coated or sustained-release formulations
    • Bezoar formation possible with massive ingestion

Clinical Features

Acute Toxicity

  • Early: tinnitus, nausea, vomiting, tachypnea (respiratory alkalosis)
  • Moderate: diaphoresis, tachycardia, hyperthermia, agitation, confusion
  • Severe: altered mental status, seizures, pulmonary edema (noncardiogenic), cerebral edema, coma
  • Classic acid-base pattern:
    • Adults: mixed respiratory alkalosis + metabolic acidosis
    • Children: metabolic acidosis predominates (may not have initial respiratory alkalosis phase)

Chronic Toxicity

  • More insidious and often misdiagnosed (especially in elderly)
  • Presents with confusion, tinnitus, dehydration, metabolic acidosis
  • May be diagnosed as sepsis, altered mental status workup

Differential Diagnosis

  • Sepsis (similar presentation with tachypnea, metabolic acidosis, AMS)
  • Other causes of anion gap metabolic acidosis (MUDPILES: methanol, uremia, DKA, propylene glycol, INH/iron, lactic acidosis, ethylene glycol, salicylates)
  • Theophylline toxicity (similar features)
  • Acetaminophen toxicity (common coingestion)
  • Iron toxicity

Evaluation

  • Salicylate level:
    • Therapeutic: 10-30 mg/dL
    • Toxic: > 30 mg/dL
    • Severe: >90 mg/dL
    • Repeat level every 2 hours until declining (delayed absorption, bezoar)
    • Done nomogram (not well validated for chronic or enteric-coated ingestions)
  • ABG/VBG: assess pH (acidemia dramatically worsens toxicity by driving salicylate into CNS)
  • BMP: anion gap, glucose (CNS hypoglycemia may occur despite normal serum glucose), potassium, bicarbonate, creatinine
  • Acetaminophen level (common coingestion)
  • LFTs, coagulation studies (hepatotoxicity, coagulopathy)
  • Lactate
  • Urine pH: target alkalinization to pH 7.5-8.0
  • CXR if concern for pulmonary edema

Management

GI Decontamination

  • Activated charcoal 1 g/kg (max 50g): effective if within 1-2 hours of ingestion
    • May benefit later with large ingestions, enteric-coated tablets, or bezoar
    • Multiple doses may be considered
  • Whole bowel irrigation for massive ingestions or sustained-release/enteric-coated tablets

Alkalinization (Cornerstone of Treatment)

  • IV sodium bicarbonate
  • Goal: urine pH 7.5-8.0 and serum pH 7.50-7.55
    • Alkaline urine traps ionized salicylate in renal tubules → enhanced elimination
    • Alkaline serum prevents salicylate from crossing blood-brain barrier
  • Protocol:
    • Bolus: 1-2 mEq/kg IV NaHCO3
    • Infusion: 150 mEq NaHCO3 in 1L D5W at 150-250 mL/hr
    • Add 20-40 mEq KCl per liter (hypokalemia impairs urinary alkalinization)
  • CRITICAL: alkalinization will NOT work without adequate potassium replacement
  • Monitor serum pH, urine pH, and potassium every 1-2 hours

Dextrose

  • Give D50W (50 mL IV) empirically if any CNS symptoms (altered mental status, seizures)
  • CNS glucose may be low even with normal serum glucose (salicylate impairs CNS glucose transport)
  • Add dextrose to maintenance fluids

Hemodialysis

  • Most effective method of salicylate removal
  • EXTRIP Workgroup Indications[1]:
    • Recommended: salicylate level > 90 mg/dL (acute) or > 80 mg/dL (chronic)
    • Recommended: altered mental status, new hypoxemia requiring supplemental O2
    • Recommended: pH ≤ 7.20 despite bicarbonate therapy
    • Suggested: salicylate level > 80 mg/dL (acute), renal failure limiting salicylate clearance, clinical deterioration despite treatment
  • Also dialyzes out the metabolic acidosis
  • Consult nephrology early

What to Avoid

  • Do NOT intubate unless absolutely necessary
    • Salicylate patients compensate with profound hyperventilation
    • Loss of respiratory compensation (even brief during intubation) causes rapid acidemia → CNS salicylate accumulation → cardiac arrest
    • If intubation required: maximize bicarb, match minute ventilation to pre-intubation rate
  • Avoid acetazolamide (causes metabolic acidosis)
  • Avoid excessive IV fluids without bicarb (dilutes serum alkalinity)

Disposition

  • ICU admission for: level >50 mg/dL, acidemia, AMS, pulmonary edema, renal failure
  • Monitored bed for moderate toxicity with improving levels
  • Serial salicylate levels every 2 hours until clearly declining
  • Poison control: 1-800-222-1222
  • Psychiatric evaluation for intentional ingestions

See Also

References

  1. ↑ 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. PMID 25986310
  • Palmer BF, Clegg DJ. Salicylate toxicity. N Engl J Med. 2020;382(26):2544-2555. PMID 32579815
  • O'Malley GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25(2):333-346. PMID 17482022
  • Pearlman BL, Gambhir R. Salicylate intoxication: a clinical review. Postgrad Med. 2009;121(4):162-168. PMID 19641282
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