Difference between revisions of "Salicylate toxicity"

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(Dialysis)
 
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== Background==
+
==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.<ref>[https://online.epocrates.com/u/29311129/Salicylate+poisoning Epocrates - Salicylate Poisoning] Accessed 06/20/15.</ref>
 
 
*Fatal dose:  
 
*Fatal dose:  
 
**~10-30g by adult  
 
**~10-30g by adult  
 
**~3g by child  
 
**~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===
+
===Salicylate Sources===
 +
*[[Aspirin]]
 +
*Oil of Wintergreen
 +
**Oil of Wintergreen is very concentrated - 5mL contains equivalent of 7.5g of aspirin.<ref>[https://online.epocrates.com/u/29311129/Salicylate+poisoning Epocrates - Salicylate Poisoning] Accessed 06/20/15.</ref>
 +
*[[Bismuth subsalicylate|Pepto-Bismol]]
 +
*Wart removers
 +
*[[Bismuth subsalicylate|Maalox]]
 +
*Alka-Seltzer
 +
 
 +
===Pathophysiology===
 +
''Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia''
 
*As level rises, switches from hepatic to renal clearance (slower)  
 
*As level rises, switches from hepatic to renal clearance (slower)  
*N/V
+
*[[Nausea/vomiting]]
 
**Stimulates chemoreceptor trigger zone
 
**Stimulates chemoreceptor trigger zone
 
**May cause metabolic alkalosis (contraction alkalosis)
 
**May cause metabolic alkalosis (contraction alkalosis)
 
*Respiratory alkalosis
 
*Respiratory alkalosis
 
**Activates respiratory center of medulla  
 
**Activates respiratory center of medulla  
**If have resp acidosis, consider: pulmonary edema, co-ingestion of respiratory depressant or fatigue
+
**If have respiratory acidosis, consider: pulmonary edema, co-ingestion of respiratory depressant or fatigue
*Anion gap metabolic acidosis
+
**Leads to compensatory alkaluria: urinary excretion of potassium and sodium bicarb
**Interferes w/ cellular metabolism  
+
*[[Metabolic Acidosis|Anion gap metabolic acidosis]]
**Normal AG does not exclude ASA toxicity in patient w/ an unknown ingestion (mixed picture)
+
**Interferes with cellular metabolism  
*Hyperthermia
+
**Normal AG does not exclude ASA toxicity in patient with an unknown ingestion (mixed picture)
 +
*[[Hyperthermia]]
 
**Uncouples oxidative phosphorylation
 
**Uncouples oxidative phosphorylation
 
**As pH drops more ASA is uncharged; able to cross BBB
 
**As pH drops more ASA is uncharged; able to cross BBB
*Altered mental status  
+
*[[Altered mental status]]
 
**Direct toxicity of salicylate species in the CNS  
 
**Direct toxicity of salicylate species in the CNS  
 
**Cerebral edema  
 
**Cerebral edema  
 
**Neuroglycopenia  
 
**Neuroglycopenia  
*** Salicylate toxicity increases CNS utilization of glucose, serum glucose levels may not reflect CNS levels.  
+
***Salicylate toxicity increases CNS utilization of glucose, serum glucose levels may not reflect CNS levels.  
*Pulmonary edema  
+
*[[Pulmonary edema]]
 
**Usually occurs in elderly  
 
**Usually occurs in elderly  
 
**Due to increased pulmonary vascular permeability
 
**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==
+
==Clinical Features==
 
===Mild (<150mg/kg)===
 
===Mild (<150mg/kg)===
 
*[[Tinnitus]]
 
*[[Tinnitus]]
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*[[Dizziness]]
 
*[[Dizziness]]
 
*[[Nausea and vomiting]]
 
*[[Nausea and vomiting]]
 +
**Common with acute toxicity
  
 
===Moderate (150-300mg/kg)===
 
===Moderate (150-300mg/kg)===
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*[[Altered mental status]]
 
*[[Altered mental status]]
 
*[[Seizure]]
 
*[[Seizure]]
 +
*[[Coma]]
 +
*Cerebral edema
 
*Acute lung injury
 
*Acute lung injury
 
*[[Nausea and vomiting]]
 
*[[Nausea and vomiting]]
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*Cardiac [[arrhythmias]]
 
*Cardiac [[arrhythmias]]
 
*[[Shock]]
 
*[[Shock]]
 +
 +
===Chronic Toxicity===
 +
*Usually neurologic abnormalities, especially in elderly
 +
**[[Agitation]]
 +
**Paranoia
 +
**Memory deficits
 +
**[[Confusion]]
 +
**Stupor
 +
*Hyperventilation
 +
*[[Tremor]]
 +
*[[Papilledema]]
 +
*Higher morbidity ([[pulmonary edema]], [[seizures]], [[renal failure]]) and mortality rate compared with acute toxicity
  
 
==Differential Diagnosis==
 
==Differential Diagnosis==
 
{{Anion gap metabolic acidosis}}
 
{{Anion gap metabolic acidosis}}
  
==Diagnosis==
+
==Evaluation==
=== Work-Up===
+
===Work-Up===
 
*[[ASA]] level
 
*[[ASA]] level
 
*Acetaminophen level (possible co-ingestant)
 
*Acetaminophen level (possible co-ingestant)
 
*Metabolic panel
 
*Metabolic panel
 
**Renal failure prevents ASA clearance
 
**Renal failure prevents ASA clearance
**Hypokalemia requires aggressive repletion  
+
**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+
 
***Urinary alkalinization inhibited by excretion of H+ in order to reabsorb K+
 
*Mag and phos
 
*Mag and phos
*Utox
+
*[[Urine toxicology screen]]
*UA
+
*[[Urinalysis]]
 
*VBG
 
*VBG
 
*CBC
 
*CBC
*ECG
+
*PTT, PT/INR
 +
*LFTs
 +
*[[ECG]]
 +
*Chest and abdominal radiographs
  
 
===Evaluation===
 
===Evaluation===
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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==
+
===Levels===
=== Airway===
+
*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!  
 
*Avoid intubation unless absolutely necessary!  
 
**Very difficult to achieve adequate minute ventilation on vent
 
**Very difficult to achieve adequate minute ventilation on vent
***Inadequate minute ventilation → ↑ resp acidosis → ↑ ASA crossing BBB
+
***Inadequate minute ventilation → ↑ respiratory acidosis → ↑ ASA crossing BBB
 
***While on ventilator, adjust RR to maintain goal serum pH 7.5 - 7.59  
 
***While on ventilator, adjust RR to maintain goal serum pH 7.5 - 7.59  
 
**Indications for intubation: hypoxemia or hypoventilation  
 
**Indications for intubation: hypoxemia or hypoventilation  
**Give Na bicarb 50-100 meq prior to intubating
+
**Give [[sodium bicarbonate]] 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  
 
**Give multiple doses if tolerated  
 
**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
 
*[[Whole-bowel irrigation]]
 
*[[Whole-bowel irrigation]]
 
**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 [[dextrose|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
*Alkalemia from resp alkalosis is NOT a contraindication to NaHCO3 tx
+
*Alkalemia from respiratory alkalosis is NOT a contraindication to NaHCO3 treatment
 
*Mechanism
 
*Mechanism
 
**Traps ASA in blood and in renal tubules  
 
**Traps ASA in blood and in renal tubules  
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**Urine pH goal: 7.5-8  
 
**Urine pH goal: 7.5-8  
 
*Monitor serum electrolytes (to include potassium and magnesium) q2-4hrs during urine alkalinization<ref>Waseem M et al. Salicylate Toxicity. eMedicine. Dec 5, 2015. http://emedicine.medscape.com/article/1009987-workup.</ref>
 
*Monitor serum electrolytes (to include potassium and magnesium) q2-4hrs during urine alkalinization<ref>Waseem M et al. Salicylate Toxicity. eMedicine. Dec 5, 2015. http://emedicine.medscape.com/article/1009987-workup.</ref>
 +
**HCO3 will drive potassium into cells during drip
 +
**Ensure replacement of magnesium and potassium, as urine will not alkalinize otherwise
 
*Dosing
 
*Dosing
**NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W @ 2-3mL/kg/hr
+
**NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W at 2-3mL/kg/hr
 
***Maintain urine pH >7.5
 
***Maintain urine pH >7.5
 
   
 
   
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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]]  
+
*[[Altered mental status]]  
 
*[[Seizure]]  
 
*[[Seizure]]  
*Pulmonary edema  
+
*[[Pulmonary edema]]
*New hypoxemia
+
*[[Coagulopathy]]
 +
*Inability to tolerate volume load from bicarb drip (e.g. [[CHF]])
 +
*New [[hypoxemia]]
 
*pH ≤7.20
 
*pH ≤7.20
*High ASA levels<ref>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.</ref>
+
*High ASA levels<ref>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.
 +
.</ref>
 
**Initial levels
 
**Initial levels
***>7.2 mmol/L (100 mg/dL)
+
***>7.2 mmol/L (100mg/dL)
***>6.5 mmol/L (90 mg/dL) in the setting of AKI
+
***>6.5 mmol/L (90mg/dL) in the setting of AKI
 
**After standard therapy
 
**After standard therapy
***>6.5 mmol/L (90 mg/dL)
+
***>6.5 mmol/L (90mg/dL)
***>5.8 mmol/L (80 mg/dL) in the setting of AKI
+
***>5.8 mmol/L (80mg/dL) in the setting of AKI
  
 
==Disposition==
 
==Disposition==
 
*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]]  
Line 165: Line 204:
 
{{#widget:YouTube|id=_t2rFDnmxJw}}
 
{{#widget:YouTube|id=_t2rFDnmxJw}}
  
== References==
+
==References==
 
<references/>
 
<references/>
  
 
[[Category:Toxicology]]
 
[[Category:Toxicology]]

Latest revision as of 19:20, 1 February 2021

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

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. .