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)
- Tinnitus
- Hearing loss
- Dizziness
- Nausea and vomiting
Moderate (150-300mg/kg)
Severe (>300mg/kg)
- Altered mental status
- Seizure
- Acute lung injury
- Nausea and vomiting
- Acute renal failure
- Cardiac arrhythmias
- Shock
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
- Very difficult to achieve adequate minute ventilation on vent
- 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
- Traps ASA in blood and in renal tubules
- 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
- NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W @ 2-3mL/kg/hr
- 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
- Initial levels
Disposition
- Admit all pts who have ingested enteric-coated or extended-release preprarations
See Also
Source
- ↑ 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.