Salicylate Toxicity Treatment & Management

Salicylate toxicity continues to be seen in the emergency department as a result of unintentional ingestions or suicide attempts. A high index of suspicion is necessary, with prompt recognition of clinical signs and symptoms of salicylate poisoning, such as tinnitus, hyperventilation, tachycardia, and metabolic acidosis.^[7] Early treatment can prevent organ damage and death.

Principles of treatment include stabilizing the ABCs as necessary, 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 alone is not a substitute for clinical evaluation of the patient. When considering treatment options, the final decision should be individualized according to the clinical status of the patient and should not depend only 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 for 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.^[8] 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 sometimes caused a prompt improvement in mental status and therefore should be given to any patient with a salicylate overdose who has a change in mental status, despite a serum glucose level within the reference range.

Oral ingestion of a large amount of acetylsalicylate, given for treatment of ear pain, has resulted in severe metabolic derangements and death. Brain histopathology revealed sparse gray matter changes and acute white matter damage.^[9]

Onset of chronic salicylism may be insidious; elderly individuals may consume an increasing amount over several days to alleviate arthralgias, subsequently becoming confused because salicylate pharmacokinetics change at higher concentrations. This may lead to a perpetual spiral of increased salicylate consumption and increased confusion. Similar scenarios occur in persons with underlying psychiatric disorders.

Follow-up

Patients with accidental ingestions of less than 150 mg/kg and no signs of toxicity can be discharged 6 hours post ingestion. Arrange a follow-up for these patients in 24 hours.

Consultations

Early consultation with a medical toxicologist is prudent to assist in guiding patient management. Also, consultation with a nephrologist is indicated in serious overdoses to arrange for hemodialysis, if it becomes necessary.

Patients with intentional ingestions should have psychiatric consultation prior to discharge in the emergency department or on the ward.

In one study, authors reviewed US poison center data for 2004 and determined that over 40,000 exposures to salicylate-containing products occurred.^[10] They published guidelines on triage care of these patients, discussed below.

Immediate emergency department referral by local poison control centers

Patients who state that an intentional ingestion occurred or in whom a large administration is suspected should immediately be referred to the emergency department. In addition, typical symptoms of salicylate toxicity warrant referral to the emergency department for evaluation.

Further triage care

Determine the dose, time of ingestion, presence of symptoms, history of other medical conditions, and presence of co-ingestants in all 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; the patient can be observed at home.

Ocular exposure to 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. An evidence-based consensus guideline to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with a suspected exposure to salicylates is also available from the Department of Health and Human Services.^[10]

Therapeutic objectives include cardiopulmonary stabilization, prevention of absorption, correction of fluid deficits, correction of acid-base abnormalities, and enhancement of excretion and elimination. Large-bore vascular access catheters may be required to facilitate emergent hemodialysis.

Endotracheal intubation may be required for the following reasons:

• Ventilatory support in patients with severe hypoxemia from aspirin-induced pulmonary edema
• Maintenance of hyperventilation (as compensation for metabolic acidosis) - Hyperventilate a patient with severe salicylate poisoning who has just been intubated (when acid-base status had been maintained previously by the patient's own hyperventilation) to prevent lethal acidemia
• Protection of patients who are too agitated and delirious for central line placement, hemodialysis, and other necessary medical procedures without therapeutic sedation
• Protection of the airway against aspiration during lavage or activated charcoal administration or in obtunded patients who cannot protect their own airway

ABCs

As with all significant overdoses the airway, breathing, and circulation (ABC) should be evaluated and stabilized as necessary. Dehydration and concomitant electrolyte abnormalities must be immediately corrected.

GI tract decontamination

Some authorities recommend performing gastric lavage in all symptomatic patients regardless of time of ingestion. Gastric lavage may be beneficial, unless contraindicated, up to 60 minutes after salicylate ingestion. Warmed (38°C) isotonic sodium chloride solution may be used. Protect the airway before gastric lavage.

Initial treatment should include the use of oral activated charcoal, especially if the patient presents within 1 hour of ingestion. Activated charcoal can limit further gut absorption by binding to the available salicylates. The recommended initial dose of activated charcoal is 1 g/kg of body weight to a maximum of 50 g in children and 1-2 g/kg to a maximum of 100 g in adults. The minimum dose is 30 g.

Use of cathartics is not routinely indicated with activated charcoal; however, many clinicians administer the first dose of activated charcoal with sorbitol. Sorbitol should not be used in young children. Repeat cathartic dosing generally should be avoided because of concern over resultant electrolyte imbalances.

Repeated doses of charcoal may enhance salicylate elimination and may shorten the serum half-life.^[11] Although no convincing data support the administration of multidose activated charcoal, some experts strongly recommend this for patients with a very serious ingestion. Repeated doses of charcoal may remove salicylates from the circulation into the GI tract. Repeated doses of activated charcoal may assist in treating bezoars with ongoing absorption of salicylates, which should be suspected when salicylate levels continue to rise or fail to decrease, despite appropriate management. Repeated doses of activated charcoal have also been used to treat overdoses of enteric-coated or sustained-release aspirin; however, whole-bowel irrigation (WBI) with polyethylene glycol is probably more effective in this setting, as noted below.

The passage of stool with charcoal and the resolution of serious clinical manifestations may be the reasonable criteria for discontinuing multiple doses of activated charcoal.

WBI with polyethylene glycol was found to be more effective than single-dose activated charcoal in reducing salicylate absorption. The study was carried out in volunteer subjects 4 hours after they had ingested enteric-coated aspirin.^[12] When enteric-coated aspirin has been ingested or when salicylate levels do not decrease despite treatment with charcoal, which may indicate that concretions are present, WBI should probably be used in addition to charcoal therapy.

The use of ipecac syrup is controversial, and many studies indicate that it does not alter the clinical outcome. It is most effective if given within 30 minutes of ingestion; however, it is relatively contraindicated in the presence of severe aspirin ingestion because of the risk of seizures and decreased mental status from aspirin, with the induced vomiting possibly leading to aspiration pneumonitis. In addition, the induced vomiting may cause a delay in administering activated charcoal.

Urinary excretion and alkalization

Provide treatment for correction of fluid deficits and enhancement of excretion and elimination. Administer lactated Ringer or isotonic sodium chloride solution for volume expansion at 10-20 mL/kg/h until a 1- to 1.5-mL/kg/h urine flow is established. Provide maintenance fluids to maintain urinary alkalization. Forced diuresis is not recommended. The greater the urine flow, the more difficult it is to alkalinize the urine. Be cautious of excessive fluid volumes in cases of salicylate-induced pulmonary edema.

Renal excretion of salicylic acid depends on urinary pH. Increasing the urine pH to 7.5 prevents reabsorption of salicylic acid from the urine.^[13] 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 alkalization 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.

Most experts alkalinize the urine by giving an initial intravenous bolus of 1 mEq/kg of sodium bicarbonate and then start a sodium bicarbonate intravenous infusion. The continuous intravenous infusion is made by adding 3 ampules of sodium bicarbonate (each ampule containing 44 mEq of sodium bicarbonate) to a liter of D5W. The infusion is initially run at 2 times the maintenance rate and then titrated to keep the urinary pH greater than 7.5. Once the patient is putting out good amounts of urine, and it has been established that the patient is not in renal failure and is not hypokalemic, then 40 mEq of potassium can be added to each liter of this solution.

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 or borderline-low serum potassium concentration. 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.

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 charcoal hemoperfusion has a slightly higher rate of drug clearance than does hemodialysis, dialysis is recommended because of its ability 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.

Admit patients with major signs and symptoms (eg, neurologic, cardiopulmonary, metabolic) to an intensive care unit under the care of a medical toxicologist, if available. Consult psychiatric service personnel for patients with intentional overdose.

Admit patients with minor signs and symptoms (eg, tinnitus, nausea) to an extended care observational unit or medical floor.

Admit the following patients, regardless of salicylate levels:

• Infants and elderly persons
• Individuals with chronic salicylism
• Those with ingestions of sustained-release products

A patient may be discharged following adequate GI tract decontamination with activated charcoal if toxicity is mild, clinical improvement is progressive, acid-base disturbance is not significant, and serial decrease in serum salicylate levels towards the therapeutic range is documented. If any doubt is noted, the patient should be admitted to an appropriate facility.