Salicylate toxicity

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Background

  • Fatal dose:
    • ~10-30g by adult
    • ~3g by child

Salicylate Sources

  • Aspirin
  • Oil of Wintergreen
    • Oil of Wintergreen is very concentrated - 5mL contains equivalent of 7.5g of aspirin.[1]
  • Pepto-Bismol
  • Wart removers
  • Maalox
  • Alka-Seltzer

Pathophysiology

Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia

  • As level rises, switches from hepatic to renal clearance (slower)
  • Nausea/vomiting
    • Stimulates chemoreceptor trigger zone
    • May cause metabolic alkalosis (contraction alkalosis)
  • Respiratory alkalosis
    • Activates respiratory center of medulla
    • If have respiratory acidosis, consider: pulmonary edema, co-ingestion of respiratory depressant or fatigue
    • Leads to compensatory alkaluria: urinary excretion of potassium and sodium bicarb
  • Anion gap metabolic acidosis
    • Interferes with cellular metabolism
    • Normal AG does not exclude ASA toxicity in patient with 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
  • Fetal Effects in pregnancy
    • Increased fetal morbidity and mortality
    • Un-ionized salicylate cross the placenta due to higher fetal pH, where it becomes ionized and accumulates in the fetus
    • Due to fetal inability to hyperventilate leads to worsening acidosis
    • There can be displacement of bilirubin from protein binding sites allowing it to cross the blood brain barrier, which can lead to kernicterus.
    • Due to inhibition of prostaglandin synthesis, can lead to premature closure of the ductus arteriosus

Clinical Features

Mild (<150mg/kg)

Moderate (150-300mg/kg)

Severe (>300mg/kg)

Chronic Toxicity

Differential Diagnosis

Anion gap metabolic acidosis

Evaluation

Work-Up

  • ASA level
  • Acetaminophen level (possible co-ingestant)
  • Metabolic panel
    • Renal failure prevents ASA clearance
    • Hyperglycemia in periphery (CSF will have low glucose due to CNS hypermetabolic state)
    • Hypokalemia requires aggressive repletion - this differentiates from DKA which tends to have hyperkalemia or normokalemia at initial presentation
      • Urinary alkalinization inhibited by excretion of H+ in order to reabsorb K+
  • Mag and phos
  • Urine toxicology screen
  • Urinalysis
  • VBG
  • CBC
  • PTT, PT/INR
  • LFTs
  • ECG
  • Chest and abdominal radiographs

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

Levels

  • Therapeutic: 10-30mg/dL
  • Toxicity: >40-50mg/dL
  • Rapidly absorbed - measurable levels in 30 minutes
  • Peak occurs ~6hr after absorption (up to 60hr if enteric-coated or extended release)
Unit Conversion
100mg/dL = 1000mg/L = 7.24 mmol/L

Management

Airway

  • Avoid intubation unless absolutely necessary!
    • Very difficult to achieve adequate minute ventilation on vent
      • Inadequate minute ventilation → ↑ respiratory 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 sodium bicarbonate 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 respiratory alkalosis is NOT a contraindication to NaHCO3 treatment
  • 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[2]
    • HCO3 will drive potassium into cells during drip
    • Ensure replacement of magnesium and potassium, as urine will not alkalinize otherwise
  • Dosing
    • NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W at 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:

Disposition

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

See Also

Video

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References

  1. Epocrates - Salicylate Poisoning Accessed 06/20/15.
  2. Waseem M et al. Salicylate Toxicity. eMedicine. Dec 5, 2015. http://emedicine.medscape.com/article/1009987-workup.
  3. Juurlink DN, et al. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP workgroup.Ann Emerg Med. 2015; 66 (2):165-81. .