Salicylate toxicity: Difference between revisions
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==Background== | ==Background== | ||
*Fatal dose: | *Salicylates are commonly available in numerous over-the-counter products, and toxicity may occur from acute (intentional or accidental) and chronic ingestion. | ||
**~10-30g by adult | *Fatal dose: | ||
**~3g by child | **~10-30g by adult | ||
**~3g by child | |||
== | ===Salicylate Sources=== | ||
* | *[[Aspirin]] | ||
* | *Oil of Wintergreen | ||
* | **Oil of Wintergreen is very concentrated - 5mL contains approximately 7g of aspirin.<ref>Wintergreen. Drugs.com. https://www.drugs.com/npp/wintergreen.html. Published January 2, 2025. Accessed July 30, 2025.</ref> | ||
* | *[[Bismuth subsalicylate|Pepto-Bismol]] | ||
*Wart removers | |||
*[[Bismuth subsalicylate|Maalox]] | |||
*Alka-Seltzer | |||
* | |||
* | |||
* | |||
* | |||
== | ===Pathophysiology=== | ||
* | ''Uncouples oxidative phosphorylation → increased metabolic rate and hyperthermia'' | ||
**May | *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 | ||
* | *[[Metabolic Acidosis|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 | |||
==Work-Up== | ===Moderate (150-300mg/kg)=== | ||
*ASA level | *[[Tachypnea]] | ||
** | *[[Hyperpyrexia]] | ||
* | *[[Diaphoresis]] | ||
* | *[[Ataxia]] | ||
* | *[[Anxiety]] | ||
* | |||
===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 | |||
**[[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== | |||
{{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 | *VBG | ||
*CBC | *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=== | ===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 → ↑ respiratory acidosis → ↑ ASA crossing BBB | ||
** | ***While on ventilator, adjust RR to maintain goal serum pH 7.5 - 7.59 | ||
*Indications | **Indications for intubation: hypoxemia or hypoventilation | ||
* | **Give [[sodium bicarbonate]] 50-100 meq prior to intubating | ||
===Breathing=== | ===Breathing=== | ||
| Line 77: | Line 135: | ||
===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) | ||
**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]] | |||
**Consider for ingestion of large amount of enteric-coated or extended-release forms | |||
===Glucose=== | ===Glucose=== | ||
*Give D50 to altered | *Give [[dextrose|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 | **ASA toxicity impairs glucose metabolism | ||
===Alkalinization of plasma and urine=== | ===Alkalinization of plasma and urine=== | ||
*Traps ASA in blood and in | *Not a substitute for dialysis in severe salicylism | ||
**Increases elimination | *Continuous IV infusion of [[sodium bicarbonate]] is indicated even in the presence of alkalemia from respiratory alkalosis<ref>American College of Medical Toxicology (ACMT). Guideline Document: Management Priorities in Salicylate Toxicity. https://www.acmt.net/wp-content/uploads/2022/06/PRS_130313_Management-Priorities-in-Salicylate-Toxicity.pdf. Published March, 2013. Accessed July 30, 2025.</ref> | ||
* | **Serum bicarbonate is still deficient | ||
**Blood pH goal = >7.5, <7.6 | *Mechanism | ||
**Urine pH goal | **Traps ASA in blood and in renal tubules | ||
* | ***Increases elimination; prevents diffusion across BBB | ||
**NaHCO3 1-2mEq/kg IV bolus then D5W | *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<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 | |||
**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== | ===Dialysis=== | ||
Indicated for: | Indicated for: | ||
* | *[[Altered mental status]] | ||
* | *[[Seizure]] | ||
* | *[[Pulmonary edema]] | ||
* | *[[Coagulopathy]] | ||
* | *Inability to tolerate volume load from bicarb drip (e.g. [[CHF]]) | ||
* | *New [[hypoxemia]] | ||
** | *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; 66 (2):165-81. | ||
.</ref> | |||
**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 | |||
== | ==Disposition== | ||
*Admit all patients who have ingested enteric-coated or extended-release preprarations | |||
==See Also== | |||
*[[Toxicology (Main)]] | |||
*[[General Psych Workup]] | |||
*[[Acetaminophen (Tylenol)]] | |||
*[[Antidotes]] | |||
*[[Aspirin]] | |||
==References== | |||
<references/> | |||
[[Category: | [[Category:Toxicology]] | ||
Latest revision as of 14:50, 30 July 2025
Background
- Salicylates are commonly available in numerous over-the-counter products, and toxicity may occur from acute (intentional or accidental) and chronic ingestion.
- Fatal dose:
- ~10-30g by adult
- ~3g by child
Salicylate Sources
- Aspirin
- Oil of Wintergreen
- Oil of Wintergreen is very concentrated - 5mL contains approximately 7g 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 alkalemia from respiratory alkalosis[2]
- Serum bicarbonate is still deficient
- 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[3]
- 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
- Coagulopathy
- Inability to tolerate volume load from bicarb drip (e.g. CHF)
- New hypoxemia
- pH ≤7.20
- High ASA levels[4]
- 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
References
- ↑ Wintergreen. Drugs.com. https://www.drugs.com/npp/wintergreen.html. Published January 2, 2025. Accessed July 30, 2025.
- ↑ American College of Medical Toxicology (ACMT). Guideline Document: Management Priorities in Salicylate Toxicity. https://www.acmt.net/wp-content/uploads/2022/06/PRS_130313_Management-Priorities-in-Salicylate-Toxicity.pdf. Published March, 2013. Accessed July 30, 2025.
- ↑ 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. .