Basics
Description
- Respiratory alkalosis and metabolic acidosis:
- Secondary to inhibition of Krebs cycle and uncoupling of oxidative phosphorylation
- Dehydration, hyponatremia or hypernatremia, hypokalemia, hypocalcemia:
- Owing to increased sweating, vomiting, tachypnea
- Noncardiogenic pulmonary edema:
- Because of toxic effect of salicylate on pulmonary endothelium resulting in extravasation of fluids
- Salicylate pharmacokinetics change from first order to zero order in overdose setting; i.e., a small dosage
increment results in a large increase in salicylate concentration.
- Greater morbidity
- Respiratory distress/altered mental status indicative of severe toxicity
- Diagnosis of salicylate intoxication delayed because underlying disease states mask signs and symptoms; e.g., CHF
- Children exhibit faster onset and more severe signs and symptoms than adults:
- Results from salicylate being distributed more quickly into target organs such as brain, kidney, and liver
- Respiratory alkalosis (hallmark of salicylate poisoning in adults) may not occur in children.
- Metabolic acidosis occurs more quickly in children than in adults.
- Hypoglycemia more common than hyperglycemia
- Ingestion of more than "a taste " ť of oil of wintergreen (98% methyl salicylate) by children <6 yr or >4 mL of oil of wintergreen by patients >6 yr warrants ED assessment.
Etiology
Sources of salicylate: ‚
- Aspirin:
- Ingestion of >150 mg/kg can cause serious toxicity
- Oil of wintergreen:
- Any exposure should be considered dangerous.
- Bismuth subsalicylate
- Salicylsalicylic acid (salsalate)
Diagnosis
Signs and Symptoms
- GI:
- Nausea
- Vomiting
- Epigastric pain
- Hematemesis
- Pulmonary:
- Tachypnea
- Noncardiogenic pulmonary edema
- CNS:
- Tinnitus
- Deafness
- Delirium
- Seizures
- Coma
History
- Ask if taking aspirin or aspirin products:
- Many patients do not list aspirin among their regular medications, may not consider aspirin a medication.
- Patients may not know the difference between aspirin, acetaminophen, and the OTC NSAIDs
Essential Workup
- Salicylate level:
- At presentation and then q2h until level begins to decline
- Verify that units are correct, generally mg/dL.
- Watch for recurrence of signs of salicylate toxicity and increasing levels even after levels have declined due to intestinal absorption of enteric-coated products and salsalate
Guidelines for Assessing Severity of Salicylate Poisoning ‚
- Acute ingestion of:
- <150 mg/kg or <6.5 g of aspirin equivalent " ”considered nontoxic
- 150 " “300 mg/kg " ”mild to moderately toxic
- >300 mg/kg " ”potentially lethal
- In the chronic overdose setting:
- Manage patient on clinical findings and not solely on levels
- Clinical findings are better indication of severity than plasma salicylate levels
- No valid nomogram exists for salicylate level interpretation
- Salicylate levels needed to achieve anti-inflammatory effect (20 " “25 mg/dL) approach toxic levels
- Enteric-coated aspirin absorbed in intestine; peak level delayed
Diagnosis Tests & Interpretation
Lab
- Arterial blood gas (ABG):
- Respiratory alkalosis
- Metabolic acidosis
- CBC
- Electrolytes, BUN/creatinine, glucose:
- Anion-gap metabolic acidosis
- Hypokalemia
- Baseline renal function
- Urinalysis:
- PT/PTT with significant ingestions
- Ferric chloride test:
- Purple if salicylate present
- Positive 30 min postingestion
- In the presence of salicylate, Phenistix turn brown-purple; may detect concentrations as low as 20 mg/dL
Imaging
- Abdominal flat-plate radiograph for concretions
- Chest radiograph for pulmonary edema
Differential Diagnosis
- Acute salicylate poisoning:
- Consider with change in mental status, unexplained noncardiogenic pulmonary edema, mixed acid " “base disorder.
- Methanol
- Ethylene glycol
- Conditions causing noncardiogenic pulmonary edema
- Chronic salicylate poisoning:
- Impending myocardial infarction
- Alcohol withdrawal
- Organic psychoses
- Sepsis
- Dementia
Treatment
Pre-Hospital
In suspected overdose settings, medication bottles must be brought in for review ‚
Initial Stabilization/Therapy
- Management of airway, breathing, and circulation (ABCs)
- Naloxone, thiamine, glucose (or Accu-Chek) for altered mental status
- IV rehydration with 0.9% normal saline (NS) for hypotension
Ed Treatment/Procedures
- Morbidity from chronic salicylate poisoning may be greater than from acute poisoning.
- Aggressively manage all salicylate intoxication.
Gastric Decontamination
- Administer activated charcoal in alert patients.
- Whole-bowel irrigation of theoretical benefit:
- For concretions visible on abdominal radiograph
- For ingestion of sustained-release preparation
- If salicylate levels continue to increase despite appropriate management
- Do not use in patients who may develop altered mental status
Enhanced Elimination
- Alkalinization:
- Enhances elimination of ionized salicylate
- Indications:
- Acidosis
- Presence of symptoms
- Elevated salicylate levels
- 1 or 2 ampules of sodium bicarbonate followed by
IV D5W 1L with 3 ampules of sodium
bicarbonate:- Goal: Urine pH of 7.5 " “8 at the rate of 3 " “6 mL/kg/h
- Add 20 " “40 mEq KCl per liter to avoid hypokalemia
- Avoid fluid overload with CHF or CAD
- Closely monitor serum potassium
- Indications for hemodialysis include:
- CHF
- Noncardiogenic pulmonary edema
- CNS depression
- Seizures
- Unstable vital signs
- Severe acid " “base disorder
- Hepatic compromise
- Coagulopathy
- Underlying disease state compromising elimination of salicylate
- Absolute salicylate level should not be used as sole criterion for deciding to dialyze without considering patients clinical status unless level is >80 " “100 mg/dL in acute ingestion.
- Threshold to dialyze is lower in patients with chronic overdose.
Medication
- Activated charcoal slurry: 1 " “2 g/kg up to 90 g PO
- Dextrose: D50W 1 amp (50 mL or 25 g) (peds: D25W 2 " “4 mL/kg) IV
- Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
- Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM
Follow-Up
Disposition
Admission Criteria
- Monitor patients with salicylate levels >25 mg/dL until level drops <25 mg/dL and symptoms abate.
- Salicylate levels increasing after having trended downward to nontoxic levels:
- In patients who ingest sustained-release aspirin, enteric-coated aspirin, and any aspirin product with delayed absorption
- ICU admission for altered mental status, metabolic acidosis, pulmonary edema
Discharge Criteria
Repetitive salicylate levels <25 mg/dL and resolution of symptoms ‚
Follow-Up Recommendations
- Psychiatric referral for intentional ingestions
- Close primary care follow-up for chronic ingestions
Pearls and Pitfalls
- Patients need to maintain their respiratory drive to reverse acidemia, respiratory acidosis:
- Do not intubate prematurely.
- It is extremely difficult to achieve and maintain mechanical hyperventilation in these patients.
- Salicylate poisoning may result from topical exposure to salicylate-containing lotions or creams, rectal suppositories, oral antidiarrheal preparations.
- Salicylate levels may trend downward only to begin increasing again due to absorption of product from the intestine or from a salicylate bezoar in the gut.
Additional Reading
- Kent ‚ K, Ganetsky ‚ M, Cohen ‚ J, et al. Non-fatal ventricular dysrhythmias associated with severe salicylate toxicity. Clin Toxicol (Phila). 2008;46:297 " “299.
- Stolbach ‚ AI, Hoffman ‚ RS, Nelson ‚ LS. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerg Med. 2008;15:866 " “869.
- West ‚ PL, Horowitz ‚ BZ. Delayed recrudescence to toxic salicylate concentrations after salsalate overdose. J Med Toxicol. 2010;6:150 " “154.
Codes
ICD9
- 276.2 Acidosis
- 276.3 Alkalosis
- 965.1 Poisoning by salicylates
ICD10
- E87.2 Acidosis
- E87.3 Alkalosis
- T39.011A Poisoning by aspirin, accidental (unintentional), init
- T39.012A Poisoning by aspirin, intentional self-harm, init encntr
SNOMED
- 7248001 Poisoning by salicylate (disorder)
- 35528000 Metabolic acidosis due to salicylate (disorder)
- 111378004 Respiratory alkalosis
- 290145004 Intentional aspirin poisoning (disorder)
- 290149005 Salicylic acid salt poisoning of undetermined intent (disorder)