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 � �
- >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 " �very 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 " �
- Emergency telephone numbers (poison control centers): (800) 222 " �1222 (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 toxicity
- 60 to 80 mg/dL moderate toxicity
- >80 mg/dL severe toxicity
- Mild 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 intoxication
- Onset 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 ages
- Infection
- Sepsis
- Diabetic ketoacidosis
- Other causes of metabolic acidosis
- In the elderly
- Delirium
- Cerebral vascular accident
- Myocardial infarction
- Ethyl alcohol intoxication
- Congestive 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 radiograph
- Noncardiogenic pulmonary edema
- Variable 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 � �
- Use of the Done nomogram in managing patients is not recommended.
Test Interpretation
- Acid " �base abnormalities common
- Usually respiratory alkalosis or mixed respiratory alkalosis and metabolic acidosis
- Metabolic 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 results
- Diflunisal (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 � �
- GI
- Antral and prepyloric ulcers
- Small bowel ulcerations with enteric-coated salicylates
- Renal
- Interstitial nephritis
- Acute tubular necrosis
- Minimal change nephrotic syndrome
- Pulmonary
- Noncardiogenic 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/hospital
- Activated 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 hypoglycemia
- With 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
- Precautions
- Intravascular 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 " �base, blood glucose, and electrolyte status until stable; urine pH (to enhance elimination of salicylate)
- Psychiatric follow-up after intentional ingestions
DIET
No special diet � �
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 � �P. Activated charcoal revisited. Clin Pediatr Emerg Med. 2005;6:76 " �80.22 Heard � �K. Gastrointestinal decontamination. Med Clin North Am. 2005;89(6):1067 " �1078.33 Chyka � �PA, Erdman � �AR, Christianson � �G, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(2):95 " �131.44 Proudfoot � �AT, Krenzelok � �EP, Vale � �JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol. 2004;42(1):1 " �26.55 Juurlink � �DN, Gosselin � �S, Kielstein � �JT, et al. Extracorporeal treatment for salicylate poisoning: systematic review and recommendations from the EXTRIP workgroup. Ann Emerg Med. 2015;66(2):165 " �181.66 Dargan � �PI, Wallace � �CI, Jones � �AL. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J. 2002;19(3):206 " �209.77 O 'Malley � �GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25(2):333 " �346.
ADDITIONAL READING
Bronstein � �AC, Spyker � �DA, Cantilena � �LRJr, 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 " �1164. � �
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.