Salicylate toxicity

Background

• Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia
• Sources: Aspirin, Oil of Wintergreen, Pepto-Bismol, Wart removers
  • Oil of Wintergreen is very concentrated - 5mL contains equivalent of 7.5g of aspirin.
• Fatal dose:
  • ~10-30g by adult
  • ~3g by child
• Levels:
  • Therapeutic: 10-30mg/dL
  • Toxicity: >40-50 mg/dL
  • Rapidly absorbed - measurable levels in 30 minutes
  • Peak occurs ~6hr after absorption (up to 60hr if enteric-coated or extended release)
• Unit Conversion
  • 100 mg/dL = 1000 mg/L = 7.24 mmol/L

Pathophysiology

• As level rises, switches from hepatic to renal clearance (slower)
• N/V
  • Stimulates chemoreceptor trigger zone
  • May cause metabolic alkalosis (contraction alkalosis)
• Respiratory alkalosis
  • Activates respiratory center of medulla
  • If have resp acidosis, consider: pulmonary edema, co-ingestion of respiratory depressant or fatigue
• Anion gap metabolic acidosis
  • Interferes w/ cellular metabolism
  • Normal AG does not exclude ASA toxicity in patient w/ an unknown ingestion (mixed picture)
• Hyperthermia
  • Uncouples oxidative phosphorylation
  • As pH drops more ASA is uncharged; able to cross BBB
• Altered mental status
  • Direct toxicity of salicylate species in the CNS
  • Cerebral edema
  • Neuroglycopenia
    • Salicylate toxicity increases CNS utilization of glucose, serum glucose levels may not reflect CNS levels.
• Pulmonary edema
  • Usually occurs in elderly
  • Due to increased pulmonary vascular permeability

Clinical Features

Mild (<150mg/kg)

• Tinnitus
  • Tinnitus is early sign - providers used to dose ASA to onset of tinnitus.
• Hearing loss
• Dizziness
• Nausea and vomiting

Moderate (150-300mg/kg)

• Tachypnea
• Hyperpyrexia
• Diaphoresis
• Ataxia
• Anxiety

Severe (>300mg/kg)

• Altered mental status
• Seizure
• Acute lung injury
• Nausea and vomiting
• Acute renal failure
• Cardiac arrhythmias
• Shock

Differential Diagnosis

Anion gap metabolic acidosis

• Lactic acidosis
  • Sepsis, shock, liver disease, CO, CN, metformin, methemoglobin
  • Short bowel syndrome
  • Propylene glycol infusions for lorazepam and phenobarbital
• Renal failure
  • Uremia
• Ketoacidosis
  • DKA
  • Alcoholic Ketoacidosis
  • Starvation ketoacidosis
• Ingestions
  • Acetaminophen toxicity
  • Aspirin toxicity
  • Increased osm gap
    • Methanol
    • Ethylene glycol
  • Normal osm gap
    • Salicylate toxicity
    • Iron
    • INH

Diagnosis

Work-Up

• ASA level
• Acetaminophen level (possible co-ingestant)
• Metabolic panel
  • Renal failure prevents ASA clearance
  • Hypokalemia requires aggressive repletion
    • Urinary alkalinization inhibited by excretion of H+ in order to reabsorb K+
• Mag and phos
• Utox
• UA
• VBG
• CBC
• ECG

Evaluation

• Triple-mixed acid-base disturbance
  • Respiratory alkalosis (earliest sign), AG metabolic acidosis, metabolic (contraction) alkalosis
  • Only other entity that produces this pattern is sepsis
• Elevated ASA level
  • Obtain levels q1-2hr until levels decline and patient's clinical status stabilizes
  • May be deceptively low early after ingestion and with chronic toxicity

Treatment

Airway

• Avoid intubation unless absolutely necessary!
  • Very difficult to achieve adequate minute ventilation on vent
    • Inadequate minute ventilation → ↑ resp acidosis → ↑ ASA crossing BBB
    • While on ventilator, adjust RR to maintain goal serum pH 7.5 - 7.59
  • Indications for intubation: hypoxemia or hypoventilation
  • Give Na bicarb 50-100 meq prior to intubating

Breathing

• Acute lung injury may lead to high O2 requirements

Circulation

• Hypotension is common due to systemic vasodilation
• IVF +/- K+ (if no cerebral edema, no pulmonary edema)
  • If these are present consider pressors

Decontamination

• Charcoal 1g/kg up to 50g PO
  • Effectively absorbs ASA
  • Give multiple doses if tolerated
    • 25g PO q2hr x 3 doses OR 50g q4hr x 2 doses after initial dose
• Whole-bowel irrigation
  • Consider for ingestion of large amount of enteric-coated or extended-release forms

Glucose

• Give D50 to altered patients regardless of serum glucose concentration
• Except for fluids used for initial resuscitation, all IVF should be D5W
  • ASA toxicity impairs glucose metabolism

Alkalinization of plasma and urine

• Not a substitute for dialysis in severe salicylism
• Continuous IV infusion of sodium bicarbonate is indicated even in the presence of mild alkalemia from the early respiratory alkalosis per 2013 ACMT guidelines
• Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
• Mechanism
  • Traps ASA in blood and in renal tubules
    • Increases elimination; prevents diffusion across BBB
• Indications
  • ASA>35 or suspect serious toxicity
• Goals
  • Blood pH goal: = >7.5, <7.6
  • Urine pH goal: 7.5-8
• Monitor serum electrolytes (to include potassium and magnesium) q2-4hrs during urine alkalinization
• Dosing
  • NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W @ 2-3mL/kg/hr
    • Maintain urine pH >7.5

• Bolus during intubation
  • If intubation is required, consider administration of sodium bicarbonate by IV bolus at the time of intubation to maintain a blood pH of 7.45-7.5 over the next 30 minutes

Dialysis

Indicated for:

• AMS
• Seizure
• Pulmonary edema
• New hypoxemia
• pH ≤7.20
• High ASA levels
  • Initial levels
    • >7.2 mmol/L (100 mg/dL)
    • >6.5 mmol/L (90 mg/dL) in the setting of AKI
  • After standard therapy
    • >6.5 mmol/L (90 mg/dL)
    • >5.8 mmol/L (80 mg/dL) in the setting of AKI

Disposition

• Admit all patients who have ingested enteric-coated or extended-release preprarations

See Also

• Toxicology (Main)
• General Psych Workup
• Acetaminophen (Tylenol)
• Antidotes
• Aspirin

Video

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