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Salicylate Poisoning

- All ages - Infection - Sepsis - Diabetic ketoacidosis - Other causes of metabolic acidosis

- Serum salicylate levels initially and ≥6 hours after ingestion; then repeat q2h until the levels are declining and patient 's condition has stabilized. - Levels are unreliable in chronic toxicity. Acidosis is considered an emergency regardless of the level. - Electrolytes, BUN, creatinine, glucose, LFTs, uric acid - Arterial blood gases - Lactic acid - PT/INR - Urinalysis: urine pH - Stool guaiac testing may be positive. - Chest radiograph - Noncardiogenic pulmonary edema - Variable severity, from mild to ARDS

- GI - Antral and prepyloric ulcers - Small bowel ulcerations with enteric-coated salicylates

- Renal - Interstitial nephritis - Acute tubular necrosis - Minimal change nephrotic syndrome

para>Increased risk for chronic toxicity because of decreased renal function

Increased risk for bleeding or perforated gastric ulcers in patients >70 years of age

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Pediatric Considerations

Acidosis is often more severe in the very young, particularly in chronic or repeated therapeutic-dose poisonings.

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Pregnancy Considerations

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EPIDEMIOLOGY

Incidence/prevalence in the United States пїЅ пїЅ

  • >11,100 single-substance ingestions of acetylsalicylic acid or ASA combination products reported by poison control centers in 2011.
  • 22 deaths in 2011, none in children <6 years of age
  • Occurs in children and adults at any age

ETIOLOGY AND PATHOPHYSIOLOGY

  • Accidental or intentional ingestion of salicylates or salicylate-containing medications (bismuth subsalicylate)
  • Percutaneous absorption of dermatologic medications containing salicylate (such as oil of wintergreen)
  • Breastfeeding by mothers ingesting salicylate-containing medications
  • Teething gels containing salicylates

RISK FACTORS

  • Dehydration
  • Conditions causing metabolic or respiratory acidosis
  • Extremes of age " пїЅvery young and elderly
  • Psychiatric illness
  • History of previous toxic ingestions or suicide attempts
  • Concurrent oral poisoning with other substances
  • Concurrent use of acetazolamide (Diamox)
  • Compromised skin: burns, psoriasis

GENERAL PREVENTION

  • Patient and parent/caregiver education essential; see "Patient Education " пїЅ
  • Emergency telephone numbers (poison control centers): (800) 222 " пїЅ1222 (American Association of Poison Control Centers)

COMMONLY ASSOCIATED CONDITIONS

  • Reye syndrome with salicylate use and varicella or influenza viral infection
  • Bezoars
  • Iatrogenic salicylate toxicity noted in 6 out of 143 children with malaria in Kenya.

DIAGNOSIS

PHYSICAL EXAM

  • Signs and symptoms may differ when the intoxication is acute or chronic.
  • Acute intoxication (adults) (1)[C]Symptoms vary with amount ingested, usually begin within 4 to 8 hours of ingestion. Enteric-coated aspirin ingestion may not show systemic symptoms for up to 12 hours. In general, children and elderly will exhibit symptoms more rapidly.30 to 60 mg/dL mild toxicity60 to 80 mg/dL moderate toxicity>80 mg/dL severe toxicityMild toxicity can present with lethargy, nausea, vomiting, and tinnitus.Moderate toxicity can also include tachypnea, fever, sweating, restlessness, and impaired coordination.Severe toxicity notes hypotension, renal failure, metabolic acidosis, and CNS manifestations including hallucinations, stupor, seizures, and coma.
  • Chronic intoxicationOnset of symptoms is usually gradual.Signs and symptoms similar to acute intoxication may occur and may be advanced at diagnosis and include severe hypotension and ARDS.Neurologic symptoms often predominate, particularly in the elderly; they include agitation, confusion, stupor, hyperactivity, paranoia, bizarre behavior, dysarthria, and restlessness.

DIFFERENTIAL DIAGNOSIS

  • All agesInfectionSepsisDiabetic ketoacidosisOther causes of metabolic acidosis
  • In the elderlyDeliriumCerebral vascular accidentMyocardial infarctionEthyl alcohol intoxicationCongestive heart failure

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • Serum salicylate levels initially and ≥6 hours after ingestion; then repeat q2h until the levels are declining and patient 's condition has stabilized.
  • Levels are unreliable in chronic toxicity. Acidosis is considered an emergency regardless of the level.
  • Electrolytes, BUN, creatinine, glucose, LFTs, uric acid
  • Arterial blood gases
  • Lactic acid
  • PT/INR
  • Urinalysis: urine pH
  • Stool guaiac testing may be positive.
  • Chest radiographNoncardiogenic pulmonary edemaVariable severity, from mild to ARDS
  • Abdominal plain film: nonspecific bowel gas pattern with retained contrast material in chronic bismuth subsalicylate ingestion
  • Head CT if there are clinical signs of cerebral edema

Diagnostic Procedures/Other

None, other than correlating serum salicylate concentration with clinical presentation пїЅ пїЅ

  • Use of the Done nomogram in managing patients is not recommended.

Test Interpretation

  • Acid " пїЅbase abnormalities commonUsually respiratory alkalosis or mixed respiratory alkalosis and metabolic acidosisMetabolic acidosis often predominates in chronic or severe acute poisonings and in poisonings in young children.
  • Increased anion gap, especially in acute poisonings and salicylate-only poisonings
  • Initial hyperglycemia may be followed by hypoglycemia.
  • Electrolyte abnormalities, such as hypernatremia or hyponatremia and hypokalemia, are common.
  • Dehydration findings are common, including an increased BUN: creatinine ratio.
  • Prothrombin time (PT)/international normalization ratio (INR) may be increased.
  • Liver function abnormalities may be present.
  • Proteinuria and renal function abnormalities may be present.
  • Stool guaiac testing may be positive.
  • Occasional hypouricemia
  • Drugs that may alter lab resultsDiflunisal (Dolobid) may cross-react with assay of salicylate concentration.Medications affecting similar organ systems, including oral anticoagulants and hypoglycemic agents
  • Disorders that may alter lab results: concurrent medical conditions involving similar organ systems

Other findings пїЅ пїЅ

  • GIAntral and prepyloric ulcersSmall bowel ulcerations with enteric-coated salicylates
  • RenalInterstitial nephritisAcute tubular necrosisMinimal change nephrotic syndrome
  • PulmonaryNoncardiogenic pulmonary edema

TREATMENT

MEDICATION

  • Prevent further absorption if the ingestion is felt to be life-threatening.Activated charcoal may be given within 1 hour of toxic ingestion (immediately after gastric lavage if performed) (2,3)[C].Gastric lavage is rarely indicated.Ipecac is no longer recommended for use at home or in health care facilities (4)[C].
  • Emergency facility/hospitalActivated charcoal 1 g/kg, single dose, within 1 hour of toxic ingestion (up to maximum 50 g in children, 100 g in adults)Fluid/electrolyte balance: IV fluids to restore intravascular volume and prevent hypoglycemiaWith hypotension, give isotonic fluid until orthostatic changes are no longer present.Fluids should contain ≥5% dextrose unless hyperglycemia is a problem.Normal saline or a mixture of 0.45% NaCl with 1 ampule of sodium bicarbonate (43 mEq NaHCO3) may be administered at 10 to 15 mL/kg/hr for 1 to 2 hours, depending on the degree of acidosis.When blood pressure is stable, fluid management is directed toward alkalinizing the urine to enhance salicylate excretion, preventing CNS hypoglycemia, and treating fluid and electrolyte abnormalities.Enhance elimination by alkaline diuresis (5)[C]Alkaline diuresis (urine pH >7.5) and prevention of hypoglycemia usually can be accomplished by initial bolus of NaHCO3 1 mEq/kg IV given over 1 hour, followed by infusion of 1,000 mL D5W plus 3 ampules of NaHCO3 (44 mEq NaHCO3/ampule) at 1.5 to 2 times maintenance rate (or, at 2 to 3 mL/kg/hr). Consider adding 40 mEq of potassium chloride to each liter; monitor potassium levels closely.Goal: bicarbonate to alkalinize the urine (pH >7.5) and, when appropriate, to correct severe systemic acidosis (for pH <7.1)Potassium should be added for potassium levels <4 mEq/L.Patients with cardiovascular compromise should be monitored closely for fluid overload.Alkalinization can be discontinued when the salicylate level decreases into the therapeutic range (<30 mg/dL)Serum electrolytes and glucose should be monitored frequently and urine pH checked hourly until stable at >7.5. Arterial blood gases should be monitored every 2 to 4 hours to ensure blood pH ≤7.5.Intermitted hemodialysis (with IV bicarbonate therapy between session) (6)[A] should be considered in poisonings with markedly elevated salicylate levels (>100 mg/dL in acute poisonings, >60 mg/dL in chronic poisonings), acidosis unresponsive to alkalinization and diuresis, renal and/or hepatic dysfunction with impaired salicylate clearance, endotracheal intubation (excluding for coingestants), noncardiac pulmonary edema, and new altered mental status.Dextrose-containing IV solution to prevent hypoglycemia; CNS hypoglycemia may be present despite a normal serum glucose level.
  • Contraindications: medication allergies
  • PrecautionsIntravascular overload may result from injudicious use of sodium bicarbonate.Dextrose should not be given to patients with severe hyperglycemia.Avoid utilization of acetazolamide (Diamox) to alkalinize urine, as it can worsen metabolic acidosis.Caution is advised in early mechanical intubation in those with depressed mental status, due to the increased metabolic demands and respiratory rate noted in those with severe salicylate poisoning.If intubation is required (e.g., development of pulmonary edema), it is recommended to hemodialyze the patient near simultaneously (7).

ISSUES FOR REFERRAL

  • Psychiatric and psychological evaluation in emergency department and in close follow-up for intentional overdose
  • Consider referral to obstetrics for pregnant women.

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Evaluate all patients at a health care facility.
  • Outpatient for nontoxic accidental ingestions
  • Inpatient for toxic and intentional ingestions (4)[C]

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Fluid, acid " пїЅbase, blood glucose, and electrolyte status until stable; urine pH (to enhance elimination of salicylate)
  • Psychiatric follow-up after intentional ingestions

DIET

No special diet пїЅ пїЅ

PATIENT EDUCATION

  • Education of parents/caregivers during well-child visits
  • Education of patients about chronic salicylate therapy
  • Anticipatory guidance for caregivers, family, and cohabitants of potentially suicidal patients
  • http://familydoctor.org/familydoctor/en/kids/home-safety/child-safety-keeping-medicines-out-of-reach.html
  • Poison control: (800) 222-1222

PROGNOSIS

  • Complete recovery with early therapy
  • Clinical course and prognosis are worse in the very young and elderly, chronic intoxications, and in patients with concurrent conditions that cause dehydration and/or acidosis.

COMPLICATIONS

  • Rare following recovery from poisoning
  • Noncardiogenic pulmonary edema
  • ARDS

REFERENCES

11 Gaudreault пїЅ пїЅP. Activated charcoal revisited. Clin Pediatr Emerg Med. 2005;6:76 " пїЅ80.22 Heard пїЅ пїЅK. Gastrointestinal decontamination. Med Clin North Am. 2005;89(6):1067 " пїЅ1078.33 Chyka пїЅ пїЅPA, Erdman пїЅ пїЅAR, Christianson пїЅ пїЅG, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(2):95 " пїЅ131.44 Proudfoot пїЅ пїЅAT, Krenzelok пїЅ пїЅEP, Vale пїЅ пїЅJA. Position paper on urine alkalinization. J Toxicol Clin Toxicol. 2004;42(1):1 " пїЅ26.55 Juurlink пїЅ пїЅDN, Gosselin пїЅ пїЅS, Kielstein пїЅ пїЅJT, et al. Extracorporeal treatment for salicylate poisoning: systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165 " пїЅ181.66 Dargan пїЅ пїЅPI, Wallace пїЅ пїЅCI, Jones пїЅ пїЅAL. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J. 2002;19(3):206 " пїЅ209.77 O 'Malley пїЅ пїЅGF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25(2):333 " пїЅ346.

ADDITIONAL READING

Bronstein пїЅ пїЅAC, Spyker пїЅ пїЅDA, Cantilena пїЅ пїЅLRJr, et al. 2011 Annual report of the American Association of Poison Control Centers ' National Poison Data System (NPDS): 29th annual report. Clin Toxicol (Phila). 2012;50(10):911 " пїЅ1164. пїЅ пїЅ

CODES

ICD10

  • T39.014A Poisoning by aspirin, undetermined, initial encounter
  • E87.2 Acidosis
  • T39.011A Poisoning by aspirin, accidental (unintentional), init
  • T39.012A Poisoning by aspirin, intentional self-harm, init encntr

ICD9

  • 965.1 Poisoning by salicylates
  • 276.2 Acidosis

SNOMED

  • Poisoning by salicylate (disorder)
  • Metabolic acidosis due to salicylate (disorder)
  • Accidental poisoning by salicylates (disorder)
  • Intentional salicylic acid salt poisoning (disorder)

CLINICAL PEARLS

  • Gastric decontamination should not be done in all poisonings, only in potentially life-threatening ingestions.
  • Think of salicylate toxicity with mixed metabolic acidosis and respiratory alkalosis, especially if anion gap.
  • Activated charcoal within 1 hour of toxic ingestion (immediately after gastric lavage, if performed) (2,3)[C]
  • Ipecac is no longer recommended for use at home or in health care facilities.
  • There is a bedside test to evaluate for the presence of salicylates. A few drops of 10% ferric chloride solution added to 1 mL of urine usually will produce a purple color if salicylates are present.