Salicylate toxicity: Difference between revisions
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== Background== | ==Background== | ||
*Fatal dose: | *Fatal dose: | ||
**~10-30g by adult | **~10-30g by adult | ||
**~3g by child | **~3g by child | ||
=== 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) | ||
* | *[[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 | **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 | *[[Metabolic Acidosis|Anion gap metabolic acidosis]] | ||
**Normal AG does not exclude ASA toxicity in patient | **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}} | ||
== | ==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 | ||
* | *[[Urine toxicology screen]] | ||
* | *[[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 | ||
== | ===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 → ↑ | ***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 | **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 | *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 | **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: | ||
*[[ | *[[Altered mental status]] | ||
*[[Seizure]] | *[[Seizure]] | ||
*Pulmonary edema | *[[Pulmonary edema]] | ||
*New hypoxemia | *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; | *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 ( | ***>7.2 mmol/L (100mg/dL) | ||
***>6.5 mmol/L ( | ***>6.5 mmol/L (90mg/dL) in the setting of AKI | ||
**After standard therapy | **After standard therapy | ||
***>6.5 mmol/L ( | ***>6.5 mmol/L (90mg/dL) | ||
***>5.8 mmol/L ( | ***>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]] | ||
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{{#widget:YouTube|id=_t2rFDnmxJw}} | {{#widget:YouTube|id=_t2rFDnmxJw}} | ||
== References== | ==References== | ||
<references/> | <references/> | ||
[[Category:Toxicology]] | [[Category:Toxicology]] |
Revision as of 11:57, 22 February 2020
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)
- Tinnitus
- Tinnitus is early sign - providers used to dose ASA to onset of tinnitus.
- Hearing loss
- Dizziness
- Nausea and vomiting
- Common with acute toxicity
Moderate (150-300mg/kg)
Severe (>300mg/kg)
- Altered mental status
- Seizure
- Coma
- Cerebral edema
- Acute lung injury
- Nausea and vomiting
- Acute renal failure
- Cardiac arrhythmias
- Shock
Chronic Toxicity
- Usually neurologic abnormalities, especially in elderly
- Hyperventilation
- Tremor
- Papilledema
- Higher morbidity (pulmonary edema, seizures, renal failure) and mortality rate compared with acute toxicity
Differential Diagnosis
Anion gap metabolic acidosis
- Lactic acidosis
- Sepsis, shock, liver disease, CO, CN, metformin, methemoglobin
- Short bowel syndrome
- Propylene glycol infusions for lorazepam and phenobarbital
- Renal failure
- Ketoacidosis
- Ingestions
- Acetaminophen toxicity
- Aspirin toxicity
- Increased osm gap
- Normal osm gap
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
- Very difficult to achieve adequate minute ventilation on vent
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
- 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
- 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
- NaHCO3 1-2mEq/kg IV bolus; then 3amp bicarb in 1L D5W at 2-3mL/kg/hr
- 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:
- Altered mental status
- Seizure
- Pulmonary edema
- New hypoxemia
- pH ≤7.20
- High ASA levels[3]
- Initial levels
- >7.2 mmol/L (100mg/dL)
- >6.5 mmol/L (90mg/dL) in the setting of AKI
- After standard therapy
- >6.5 mmol/L (90mg/dL)
- >5.8 mmol/L (80mg/dL) in the setting of AKI
- Initial levels
Disposition
- Admit all patients who have ingested enteric-coated or extended-release preprarations
See Also
Video
{{#widget:YouTube|id=_t2rFDnmxJw}}
References
- ↑ Epocrates - Salicylate Poisoning Accessed 06/20/15.
- ↑ Waseem M et al. Salicylate Toxicity. eMedicine. Dec 5, 2015. http://emedicine.medscape.com/article/1009987-workup.
- ↑ 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. .