Salicylate toxicity

Revision as of 19:43, 11 June 2015 by Neil.m.young (talk | contribs)

Background

  • Causes: Aspirin, Wintergreen, Pepto-Bismol
  • Uncoupling oxidative phosphorylation at mitochondrial - increased metabolic rate and hyperthermia
  • Fatal dose:
    • ~10-30g by adult
    • ~3g by child
  • Levels:
    • Therapeutic: 10-30mg/dL
    • Intoxication: >40-50 mg/dL
    • 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 pt w/ an unknown ingestion (mixed picture)
  • Hyperthermia
    • Uncouples oxidative phosphorylation
    • As pH drops more ASA is uncharged; able to cross BBB
  • Altered mental status
    • 1. Direct toxicity of salicylate species in the CNS
    • 2. Cerebral edema
    • 3. 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)

Moderate (150-300mg/kg)

Severe (>300mg/kg)

Diagnosis

  • 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 pt's clinical status stabilizes
    • May be deceptively low early after ingestion and with chronic toxicity

Work-Up

  • ASA level
  • Chem
    • Renal failure prevents ASA clearance
    • Hypokalemia requires aggressive repletion
      • Urinary alkalinization inhibited by excretion of H+ in order to reabsorb K+
  • Utox
  • UA
    • Proteinuria
  • VBG
  • CBC
  • ECG
  • Tylenol levels to assess for possible co-ingestions

Treatment

Airway

  • Avoid intubation unless absolutely necessary!
    • Very difficult to achieve adequate minute ventilation on vent
      • Sedation/paralysis -> decreased RR -> resp acidosis -> incr ASA crossing BBB
  • Indications: hypoxemia or hypoventilation
  • If mechnically ventilate must set increased RR to to maintain pH 7.50 - 7.59
  • give Na bicarb 50-100 meq prior intubation

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 pts 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
  • 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 ito 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[1]
    • 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 pts who have ingested enteric-coated or extended-release preprarations

See Also

Source

  1. Juurlink DN, et al. Extracorporeal treatment for salicylate poisoning: Systematic review and recommendations from the EXTRIP workgroup.Ann Emerg Med. 2015; 15:Epub ahead of print.