Salicylate toxicity: Difference between revisions
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==Background==
== Background ==
*Fatal dose:
*Chronic toxicity can produce severe neuro changes that do not correlate w/ ASA levels
**~10-30g by adult
*Fatal dose:  
**~3g by child
**~10-30g by adult  
*Levels:
**~3g by child  
**Therapeutic: 10-30mg/dL
*Levels:  
**Intoxication: >40-50 mg/dL
**Therapeutic: 10-30mg/dL  
**Peak occurs ~6hr after absorption
**Intoxication: >40-50 mg/dL  
***Up to 24hr if enteric-coated or extended release
**Peak occurs ~6hr after absorption (up to 60hr if enteric-coated or extended release)


==Pathophysiology==
== Pathophysiology ==
*As level rises, hepatic detox is saturated, switches to renal clearance (slower)
*As level rises, switches from hepatic to renal clearance (slower)  
*As pH drops more ASA is uncharged > crosses BBB
*N/V
*Altered mental status
**Stimulates chemoreceptor trigger zone
**Causes:
*Respiratory alkalosis
***1. Direct toxicity of salicylate species in the CNS
**Activates respiratory center of medulla  
***2. Cerebral edema
***3. Neuroglycopenia
****May occur despite normal serum glucose levels
*Pulmonary Edema
**Usually occurs in elderly
*Anion gap metabolic acidosis (interferes w/ cellular metabolism)
*Nausea/vomiting (stimulates chemoreceptor trigger zone)
*Respiratory alkalosis (activates respiratory center of medulla)
**If have resp acidosis consider pulm edema, resp depressing co-ingestant, or fatigue
**If have resp acidosis consider pulm edema, resp depressing co-ingestant, or fatigue
*Anion gap metabolic acidosis
**Interferes w/ cellular metabolism
*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
***May occur despite normal serum glucose levels
*Pulmonary Edema
**Usually occurs in elderly
**Due to increased pulmonary vascular permeability


==Signs/Symptoms==
== Clinical Features ==
*Tinnitus
#Mild (<150mg/kg)
**May occur within therapeutic range
##Tinnitus
*Fever
##Hearing loss
*Vertigo
##Dizziness
*N/V
##N/V
*Diarrhea
#Moderate (150-300mg/kg)
*AMS
##Tachypnea
*Coma
##Hyperpyrexia
*Noncardiac pulmonary edema
##Diaphoresis
*Death
##Ataxia
**Correlated with CNS salicylate levels
##Anxiety
 
#Severe (>300mg/kg)
==Vital signs==
##AMS
*Tachypnea
##Seizure
*Increase body temperature
##Acute lung injury
**Lack of hyperthermia does not rule out toxicity!
##N/V
*Tachycardia (due to hypovolemia, agitation, or general distress)
##Renal failure
##Cardiac arrhythmias
##Shock


==Work-Up==
== Work-Up ==
*ASA level
*ASA level  
**Check q2hr until two consec levels show a decrease
**Check q2hr until two consecutive levels show a decrease  
*Tylenol level
*APAP level  
*ETOH level
*ETOH level  
*Utox
*Utox  
*UA
*UA  
*VBG
**Proteinuria
*CBC
*VBG  
*Chem
*CBC  
**If renal failure unable to clear ASA
*Chem  
**Hypokalemia requires aggressive repletion
**Renal failure prevents ASA clearance
***K+/H+ pump in distal tubule > decr ur. alkalinization
**Hypokalemia requires aggressive repletion  
*LFT
***K+/H+ pump in distal tubule > decr urinary alkalinization  
*Coags
*LFT  
**Rarely may cause hepatotoxicity
*Coags  
*hCG
**Rarely may cause hepatotoxicity  
*ekg
*hCG  
**level >30mg/dL s/s of tox or >35 at any time
*ECG


==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  
***Leads to resp acidosis > incr ASA crossing BBB
***Leads to resp acidosis &gt; incr ASA crossing BBB  
**Sedation/paralysis > incr ASA crossing BBB
**Sedation/paralysis &gt; incr ASA crossing BBB  
*Indications = Hypoxemia or hypoventilation
*Indications = Hypoxemia or hypoventilation  
*If intubate maintain pH 7.50 - 7.59, hyperventilate
*If intubate maintain pH 7.50 - 7.59, hyperventilate


===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
 
**Give fluids if no cerebral edema, no pulmonary edema
*Hypotension is common due to systemic vasodilation  
**Give fluids 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
 
**Effectively absorbs ASA
*Charcoal 1g/kg up to 50g PO  
**Give multiple doses if tolerated
**Effectively absorbs ASA  
**Give multiple doses if tolerated  
***25g PO q2hr x 3 doses OR 50g q4hr x 2 doses after initial dose
***25g PO q2hr x 3 doses OR 50g q4hr x 2 doses after initial dose


===Glucose===
=== Glucose ===
*Give D50 to altered pts regardless of serum glucose concentration
 
*Give D50 to altered pts regardless of serum glucose concentration  
**ASA toxicity impairs glucose metabolism
**ASA toxicity impairs glucose metabolism


<br>
=== Alkalinization of plasma and urine ===


===Alkalinization of plasma and urine===
*Traps ASA in blood and in rental tubules  
*Traps ASA in blood and in rental tubules
**Increases elimination, prevents diffusion across BBB  
**Increases elimination, prevents diffusion across BBB
*Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx  
*Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
**Blood pH goal = &gt;7.5, &lt;7.6  
**Blood pH goal = >7.5, <7.6
**Urine pH goal = 7.5-8  
**Urine pH goal = 7.5-8
*Consider bicarb if ASA&gt;35 or suspect serious toxicity  
*Consider bicarb if ASA>35 or suspect serious toxicity
**NaHCO3 1-2mEq/kg IV bolus then D5W w/ 3amps bicarb/L @ 2x maintenance for goal ur pH&gt;7.5
**NaHCO3 1-2mEq/kg IV bolus then D5W w/ 3amps bicarb/L @ 2x maintenance for goal ur pH>7.5


==Dialysis==
=== Dialysis ===
Indicated for:
Indicated for:  
*[[AMS]]
*[[AMS]]  
*Coma
*Coma  
*[[Seizure]]
*[[Seizure]]  
*Refractory acidosis
*Refractory acidosis  
*Pulmonary edema
*Pulmonary edema  
*Acute/chronic [[Renal Failure]]
*Acute/chronic [[Renal Failure]]  
**Will not be able to clear ASA
**Will not be able to clear ASA  
*6hr level > 100
*6hr level &gt; 100


==See Also==
== See Also ==
*[[General Psych Workup]]
*[[General Psych Workup]]  
*[[Acetaminophen (Tylenol)]]
*[[Acetaminophen (Tylenol)]]  
*[[Antidotes]]
*[[Antidotes]]


==Source==
== Source ==
UpToDate
*UpToDate
*Tintinalli


[[Category:Tox]]
[[Category:Tox]]

Revision as of 01:57, 7 January 2012

Background

  • Chronic toxicity can produce severe neuro changes that do not correlate w/ ASA levels
  • 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)

Pathophysiology

  • As level rises, switches from hepatic to renal clearance (slower)
  • N/V
    • Stimulates chemoreceptor trigger zone
  • Respiratory alkalosis
    • Activates respiratory center of medulla
    • If have resp acidosis consider pulm edema, resp depressing co-ingestant, or fatigue
  • Anion gap metabolic acidosis
    • Interferes w/ cellular metabolism
  • 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
      • May occur despite normal serum glucose levels
  • Pulmonary Edema
    • Usually occurs in elderly
    • Due to increased pulmonary vascular permeability

Clinical Features

  1. Mild (<150mg/kg)
    1. Tinnitus
    2. Hearing loss
    3. Dizziness
    4. N/V
  2. Moderate (150-300mg/kg)
    1. Tachypnea
    2. Hyperpyrexia
    3. Diaphoresis
    4. Ataxia
    5. Anxiety
  3. Severe (>300mg/kg)
    1. AMS
    2. Seizure
    3. Acute lung injury
    4. N/V
    5. Renal failure
    6. Cardiac arrhythmias
    7. Shock

Work-Up

  • ASA level
    • Check q2hr until two consecutive levels show a decrease
  • APAP level
  • ETOH level
  • Utox
  • UA
    • Proteinuria
  • VBG
  • CBC
  • Chem
    • Renal failure prevents ASA clearance
    • Hypokalemia requires aggressive repletion
      • K+/H+ pump in distal tubule > decr urinary alkalinization
  • LFT
  • Coags
    • Rarely may cause hepatotoxicity
  • hCG
  • ECG

Treatment

Airway

  • Avoid intubation unless absolutely necessary!
    • Very difficult to achieve adequate minute ventilation on vent
      • Leads to resp acidosis > incr ASA crossing BBB
    • Sedation/paralysis > incr ASA crossing BBB
  • Indications = Hypoxemia or hypoventilation
  • If intubate maintain pH 7.50 - 7.59, hyperventilate

Breathing

  • Acute lung injury may lead to high O2 requirements

Circulation

  • Hypotension is common due to systemic vasodilation
    • Give fluids 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

Glucose

  • Give D50 to altered pts regardless of serum glucose concentration
    • ASA toxicity impairs glucose metabolism


Alkalinization of plasma and urine

  • Traps ASA in blood and in rental tubules
    • Increases elimination, prevents diffusion across BBB
  • Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
    • Blood pH goal = >7.5, <7.6
    • Urine pH goal = 7.5-8
  • Consider bicarb if ASA>35 or suspect serious toxicity
    • NaHCO3 1-2mEq/kg IV bolus then D5W w/ 3amps bicarb/L @ 2x maintenance for goal ur pH>7.5

Dialysis

Indicated for:

  • AMS
  • Coma
  • Seizure
  • Refractory acidosis
  • Pulmonary edema
  • Acute/chronic Renal Failure
    • Will not be able to clear ASA
  • 6hr level > 100

See Also

Source

  • UpToDate
  • Tintinalli
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