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Toxicity, Salicylate: Treatment & Medication
Updated: Feb 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Principles of treatment include limiting absorption, enhancing elimination, correcting metabolic abnormalities, and providing supportive care. No specific antidote is available for salicylates. Although determination of serial serum salicylate concentrations offers valuable information regarding the effectiveness of the treatment implemented, assessment of these levels is a poor substitute for clinical evaluation of a patient. When considering treatment options, the final decision should be individualized according to the clinical status of the patient and should not depend on a particular salicylate level.
Optimal management of a salicylate poisoning depends on whether the exposure is acute or chronic. Gastric lavage and activated charcoal are useful for acute ingestions but not in cases of chronic salicylism. Patients with chronic rather than acute ingestions of salicylates are more likely to develop toxicity, especially of the CNS, and require intensive care. Salicylate poisoning has been shown to cause metabolic derangements with significant inhibition of Krebs cycle enzymes.6 It also uncouples oxidative phosphorylation. Because of impaired glucose homeostasis, CNS glucose supply is sometimes lowered, which results in hypoglycorrhachia and delirium, even when serum glucose concentration is normal. Glucose boluses in euglycemic patients with salicylate-induced delirium have shown a prompt improvement in mental status.
- Triage Care: In one study, authors reviewed US poison center data for 2004 and determined that over 40,000 exposures to salicylate-containing products occurred.7 They published guidelines on triage care of these patients which are divided as follows:
- Immediate emergency department referral by local poison control centers
- Patients who state ingestion or in whom a large administration is suspected should immediately be referred to the emergency department.
- Typical symptoms of salicylate toxicity warrant referral to the emergency department for evaluation.
- Further triage care can be given
- Determine the dose, time of ingestion, presence of symptoms, history of other medical conditions, and presence of co-ingestants in patients without evidence of self-harm.
- Do not induce vomiting for salicylate ingestion.
- Activated charcoal for acute ingestions of a toxic dose can be given if no contraindications are observed.
- Asymptomatic dermal exposures to methyl salicylate or salicylic acid: The skin should be thoroughly washed with soap and water and the patient can be observed at home.
- Ocular exposure of methyl salicylate or salicylic acid: The eye or eyes should be irrigated with room-temperature tap water for 15 minutes. If pain, decreased visual acuity, or persistent irritation is reported after irrigation, referral to an ophthalmologist is recommended.
- Poison centers should monitor the onset of symptoms at periodic intervals for approximately 12-24 hours after ingestion.
- GI tract decontamination
- Initial treatment should include the use of oral activated charcoal, especially if the patient presents within one hour of ingestion. Some authorities recommend performing gastric lavage in all symptomatic patients regardless of time of ingestion.
- Activated charcoal can limit further gut absorption by binding to the available salicylates. The recommended initial dose of activated charcoal is 1-2 g/kg of body weight. Use of cathartics is not indicated with activated charcoal.
- Repeated doses of charcoal may enhance salicylate elimination and may shorten the serum half-life.8 A potential indication for repeated doses of activated charcoal may be a plateau in serum salicylate concentrations, which may suggest a bezoar with ongoing absorption.
- The passage of stool with charcoal and the resolution of clinical manifestations may be the reasonable criteria for discontinuing multiple doses of activated charcoal.
- Whole bowel irrigation (WBI) with polyethylene glycol has been compared with single-dose activated charcoal in salicylate absorption in volunteer subjects 4 hours after ingesting enteric-coated aspirin.9 WBI was more effective in reducing absorption. When enteric-coated aspirin has been ingested or when salicylate levels do not decrease despite treatment with charcoal, WBI should probably be used in addition to charcoal therapy.
- Urinary alkalization
- Renal excretion of salicylic acid depends on urinary pH. Increasing the urine pH to 7.5 prevents reabsorption of salicylic acid from the urine.10 Because acidosis facilitates transfer of salicylate into tissues, especially in the brain, it must be aggressively treated by raising blood pH higher than brain pH, thereby shifting the equilibrium from the tissues to the plasma.
- Concomitant alkalinization of blood and urine keeps salicylates away from brain tissue and in the blood, in addition to enhancing urinary excretion. When the urine pH increases to 8 from 5, renal clearance of salicylate increases 10-20 times. Raising the urinary pH level from 6.1 to 8.1 results in a more than 18-fold increase in renal clearance by preventing nonionic tubular back-diffusion, which decreases the half-life of salicylates from 20-24 hours to less than 8 hours. Because aspirin is a weak acid, it ionizes when exposed to a basic environment, such as alkaline urine. Ions are poorly reabsorbed in the tubules and are excreted more readily. This phenomenon is called ion trapping and also works well for overdoses of other weak acids, such as phenobarbital.
- Hypokalemia and dehydration limit the effectiveness of urine alkalization. Hypokalemia prevents excretion of alkaline urine by promoting distal tubular potassium reabsorption in exchange for hydrogen ions. Symptomatic patients typically have low serum potassium concentrations or serum potassium concentrations low in the reference range. Treatment with sodium bicarbonate alone may produce further intracellular shift of potassium ions, which further impairs the ability to excrete alkaline urine. Repletion of potassium is often necessary, even when serum potassium levels are in the low reference range (eg, <4.5 mEq/L).
- Urinary alkalization should be continued at least until serum salicylate levels decrease into the therapeutic range (<30 mg/dL). Although acetazolamide results in the formation of a bicarbonate-rich alkaline urine, it unfortunately also causes metabolic acidosis that can worsen toxicity and, therefore, should not be used.
- Hemodialysis
- Indications for hemodialysis include a serum level greater than 120 mg/dL (acutely) or greater than 100 mg/dL (6 h postingestion), refractory acidosis, coma or seizures, noncardiogenic pulmonary edema, volume overload, and renal failure.
- In chronic overdose, hemodialysis may be required for a symptomatic patient with a serum salicylate level greater than 60 mg/dL.
- Although hemoperfusion has a slightly higher rate of drug clearance than hemodialysis, dialysis is recommended because of its ability both to correct for fluid and electrolyte disorders and to remove salicylates.
- Peritoneal dialysis is only 10-25% as efficient as hemoperfusion or hemodialysis and is not even as efficient as renal excretion.
Consultations
Early consultation with a medical toxicologist is prudent.
Medication
No specific antidote for salicylate poisoning is available. Therapy is focused on immediate resuscitation, correction of volume depletion and metabolic derangement, GI tract decontamination, and reduction of the body's salicylate burden. Early consultation with a medical toxicologist is prudent.
Decontamination agents
Consider activated charcoal decontamination in any patient who presents within 4 hours of ingestion. Activated charcoal is used for drug absorption and may be all that is required in mild-to-moderate toxicity. Activated charcoal is not absorbed and is excreted entirely through the GI tract.
Activated charcoal (Actidose-Aqua, Liqui-Char)
Activated charcoal can limit further gut absorption by binding to available salicylate. This is effective both for regular and SR preparation. No convincing data support the use of repeated doses of activated charcoal in salicylate toxicity. Some authorities recommend repeated doses of activated charcoal to enhance elimination.
Adult
1-2 g/kg PO (50-100 g); usually administered with sorbitol for first dose only
Pediatric
Administer as in adults; avoid administering cathartics (eg, sorbitol) in children <2 y; package insert recommends avoiding the use of sorbitol in children <32 kg and avoiding use as a repeated agent.
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; ileus; associated poisoning with caustics or hydrocarbons
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Protect airway first in obtunded patients
Alkalinizing agents
Sodium bicarbonate is used as a gastric, systemic, and urinary alkalinizer and has been used in the treatment of acidosis resulting from metabolic and respiratory causes. It also increases renal clearance of acidic drugs.
Sodium bicarbonate
Constant infusion of sodium bicarbonate produces urinary alkalinization if the serum potassium is adequate (typically, >4.5 mEq/L). Urinary alkalinization promotes the excretion of salicylate.
If serum potassium level is low or in the lower end of the reference range (eg, <4.5 mEq/L), hydrogen ions, instead of potassium ions, follow bicarbonate ions into the urine. Hence, the urine may remain acidic during bicarbonate infusion without potassium repletion.
Adult
100-150 mEq IV with 40 mEq of potassium chloride in each liter of D5W; administer at 150-250 mL/h to maintain higher than normal urine output
Pediatric
100-150 mEq IV with 40 mEq of potassium chloride in each liter of D5W; administer at twice maintenance rate to maintain higher than normal urine output
Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, and methotrexate; conversely, increases levels of amphetamines pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine
Alkalosis, hypernatremia, hypocalcemia, severe pulmonary edema, unknown abdominal pain, and renal failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor urine pH with serial bedside testing to confirm successful alkalinization, aim for a urinary pH level of 7.5 or greater; caution in electrolyte imbalances (eg, CHF, cirrhosis, edema, corticosteroid use, renal failure); when administering, should avoid extravasation because it can cause tissue necrosis
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| Overview: Toxicity, Salicylate |
| Differential Diagnoses & Workup: Toxicity, Salicylate |
 Treatment & Medication: Toxicity, Salicylate |
| Follow-up: Toxicity, Salicylate |
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Further Reading
Keywords
salicylate toxicity, salicylic toxicity, aspirin, oil of wintergreen, salicylic acid, salicylate toxicity, salicylate poisoning, salicylate intoxication, aspirin overdose, analgesic overdose, tinnitus, bedside ferric chloride testing, activated charcoal, methyl salicylate, Pepto-Bismol, Ben-Gay, respiratory alkalosis, ketosis, wide anion-gap metabolic acidosis, noncardiogenic pulmonary edema, hypoxia, dehydration, tinnitus, cerebral edema, hyperthermia, pylorospasm, hepatitis, Reye syndrome, hypoprothrombinemia, rhabdomyolysis
