Difference between revisions of "Salicylate toxicity"

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(Text replacement - " ==" to "==")
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== Background ==
+
== Background==
 
*Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia
 
*Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia
 
*Sources: [[Aspirin]], Oil of Wintergreen, Pepto-Bismol, Wart removers
 
*Sources: [[Aspirin]], Oil of Wintergreen, Pepto-Bismol, Wart removers
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**100 mg/dL = 1000 mg/L = 7.24 mmol/L
 
**100 mg/dL = 1000 mg/L = 7.24 mmol/L
  
=== Pathophysiology ===
+
=== Pathophysiology===
 
*As level rises, switches from hepatic to renal clearance (slower)  
 
*As level rises, switches from hepatic to renal clearance (slower)  
 
*N/V
 
*N/V
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**Due to increased pulmonary vascular permeability
 
**Due to increased pulmonary vascular permeability
  
== Clinical Features ==
+
== Clinical Features==
 
===Mild (<150mg/kg)===
 
===Mild (<150mg/kg)===
 
*[[Tinnitus]]
 
*[[Tinnitus]]
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==Diagnosis==
 
==Diagnosis==
=== Work-Up ===
+
=== Work-Up===
 
*[[ASA]] level
 
*[[ASA]] level
 
*Acetaminophen level (possible co-ingestant)
 
*Acetaminophen level (possible co-ingestant)
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**May be deceptively low early after ingestion and with chronic toxicity
 
**May be deceptively low early after ingestion and with chronic toxicity
  
== Treatment ==
+
== Treatment==
=== Airway ===
+
=== Airway===
 
*Avoid intubation unless absolutely necessary!  
 
*Avoid intubation unless absolutely necessary!  
 
**Very difficult to achieve adequate minute ventilation on vent
 
**Very difficult to achieve adequate minute ventilation on vent
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**Give Na bicarb 50-100 meq prior to intubating
 
**Give Na bicarb 50-100 meq prior to intubating
  
=== Breathing ===
+
=== Breathing===
 
*Acute lung injury may lead to high O2 requirements
 
*Acute lung injury may lead to high O2 requirements
  
=== Circulation ===
+
=== Circulation===
 
*Hypotension is common due to systemic vasodilation  
 
*Hypotension is common due to systemic vasodilation  
 
*IVF +/- K+ (if no cerebral edema, no pulmonary edema)
 
*IVF +/- K+ (if no cerebral edema, no pulmonary edema)
 
**If these are present consider pressors
 
**If these are present consider pressors
  
=== Decontamination ===
+
=== Decontamination===
 
*[[Charcoal]] 1g/kg up to 50g PO  
 
*[[Charcoal]] 1g/kg up to 50g PO  
 
**Effectively absorbs ASA  
 
**Effectively absorbs ASA  
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**Consider for ingestion of large amount of enteric-coated or extended-release forms
 
**Consider for ingestion of large amount of enteric-coated or extended-release forms
  
=== Glucose ===
+
=== Glucose===
 
*Give D50 to altered patients regardless of serum glucose concentration  
 
*Give D50 to altered patients regardless of serum glucose concentration  
 
*Except for fluids used for initial resuscitation, all IVF should be D5W
 
*Except for fluids used for initial resuscitation, all IVF should be D5W
 
**ASA toxicity impairs glucose metabolism
 
**ASA toxicity impairs glucose metabolism
  
=== Alkalinization of plasma and urine ===
+
=== Alkalinization of plasma and urine===
 
*Not a substitute for dialysis in severe salicylism
 
*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
 
*Continuous IV infusion of sodium bicarbonate is indicated even in the presence of mild alkalemia from the early respiratory alkalosis per 2013 ACMT guidelines
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**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
 
**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 ===
+
=== Dialysis===
 
Indicated for:  
 
Indicated for:  
 
*[[AMS]]  
 
*[[AMS]]  
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*Admit all patients who have ingested enteric-coated or extended-release preprarations
 
*Admit all patients who have ingested enteric-coated or extended-release preprarations
  
== See Also ==
+
== See Also==
 
*[[Toxicology (Main)]]
 
*[[Toxicology (Main)]]
 
*[[General Psych Workup]]  
 
*[[General Psych Workup]]  

Revision as of 02:13, 5 July 2016

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.[1]
  • 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)

Moderate (150-300mg/kg)

Severe (>300mg/kg)

Differential Diagnosis

Anion gap metabolic acidosis

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[2]
  • 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[3]
    • 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

Video

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; 15:Epub ahead of print.