Salicylate Poisoning

Salicylate poisoning is potentially fatal. Salicylates are present in aspirin medications and in high concentrations of oil of wintergreen (methyl salicylate: one teaspoon = 7 g of salicylate). The local poisons service should be contacted for advice:

• UK National Poisons Information Service - www.npis.org (see website for telephone number, as different for England and Wales, Scotland and Northern Ireland).
• Toxbase (see below for link).^[1]Provides information about routine diagnosis, treatment and management of patients exposed to drugs, household products, and industrial and agricultural chemicals.

Children and adults who have ingested less than 125 mg/kg aspirin and have no symptoms do not require hospital admission. However, ingestion of more than 250 mg/kg aspirin is likely to cause moderate toxicity and ingestion of more than 500 mg/kg aspirin causes severe and possibly fatal toxicity. Risk factors for death include:^[1]

• Children and the elderly
• Late presentation
• Pulmonary oedema, CNS features, hyperpyrexia
• Metabolic acidosis
• Salicylate concentration above 700 mg/L (5.1 mmol/L)

Presentation^[1]

• Mild poisoning causes nausea, vomiting, tinnitus, lethargy or dizziness.
• More severe poisoning causes dehydration, restlessness, sweating, warm extremities with bounding pulses, increased respiratory rate, hyperventilation and deafness.
• A degree of disturbance of acid-base balance is present in most cases.
• Hyperglycaemia, normoglycaemia or hypoglycaemia (all with intracellular glucose depletion) may occur.
• Uncommon features include haematemesis, hypokalaemia, hyponatraemia/hypernatraemia, hypocalcaemia, thrombocytopenia, abnormal blood coagulation (increased prothrombin ratio/INR), disseminated intravascular coagulation, acute kidney injury and non-cardiac pulmonary oedema.
• CNS: confusion, disorientation, coma and convulsions (less common in adults than in children).

Chronic salicylate poisoning^[2]

• Chronic salicylate poisoning is more common in the elderly and requires lower levels of salicylate ingestion. Chronic salicylate toxicity often goes unrecognised.
• The onset of chronic salicylate poisoning may be insidious. An increasing amount of salicylate may be taken over several days to alleviate pain such as joint pain.
• Chronic salicylate poisoning may cause anxiety, tachypnoea, diffuse sweating, difficulty concentrating, confusion, hallucinations and even agitated delirium. Elderly individuals may present with a deterioration in functional status.
• Salicylate poisoning should be considered in the differential diagnosis of an adult patient with acid-base abnormalities of uncertain cause, especially when there are also neurological symptoms. 
• Delayed diagnosis results in increased morbidity and mortality, particularly in the elderly.

Investigations

• Plasma salicylate concentrations:^[1]
  • The severity of poisoning cannot be assessed from plasma salicylate concentrations alone and the clinical and biochemical features should also be considered.
  • Should be measured urgently for patients who are thought to have ingested more than 125 mg/kg of aspirin as well as those who have taken methyl salicylate or salicylamide.
  • The sample should be taken at least two hours (symptomatic patients) or four hours (asymptomatic patients) following ingestion, as it may take several hours for peak plasma concentrations to occur.
  • A repeat sample should be taken after a further two hours because of the possibility of continuing absorption. Measurements should be repeated every three hours until concentrations are falling.
• Renal function and electrolytes, FBC, coagulation studies (raised INR/PTR), urinary pH, and blood glucose.
• Plasma potassium should be checked every three hours and plasma potassium levels maintained at between 4.0-4.5 mmol/L.
• Arterial blood gases (capillary gases or venous blood gases are alternatives in children): some degree of acid-base disturbance is present in most cases:
  • Adults and older children over the age of 4 years: mixed respiratory alkalosis and metabolic acidosis, with normal or high arterial pH.
  • Young children: metabolic acidosis is common.

Toxicity

The likelihood of toxicity can be gauged to a degree by:

• The ingested dose:^[1]
  • Greater than 125 mg/kg body weight: likely toxicity is mild.
  • Greater than 250 mg/kg body weight: likely toxicity is moderate.
  • Greater than 500 mg/kg body weight: likely toxicity is severe, possibly fatal.
• Salicylate concentration:
  • Severity of poisoning cannot be assessed from plasma salicylate concentrations alone but salicylate intoxication is usually associated with plasma concentrations greater than 350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1 mmol/L).
• Clinical grading:
  • Mild (nausea, vomiting, tinnitus).
  • Moderate (hyperventilation and confusion).
  • Serious (hallucinations, seizures, coma, cerebral oedema or pulmonary oedema).
• Acid-base staging:
  • Stage I: blood pH >7.4, urine pH >6.0 - respiratory alkalosis, increased urinary excretion of bicarbonate.
  • Stage II: blood pH >7.4, urine pH <6.0 - metabolic acidosis with compensating respiratory alkalosis, urinary hydrogen excretion, intracellular potassium depletion.
  • Stage III: blood pH <7.4, urine pH <6.0 - severe metabolic acidosis and hypokalaemia.

Management^[1]

Treatment must be in hospital where plasma salicylate, pH and electrolytes can be measured. Absorption of aspirin may be slow and the plasma-salicylate concentration may continue to rise for several hours, requiring repeated measurement of plasma-salicylate concentration.

• General measures for poisoning.
• Consider oral activated charcoal (50 g for an adult, 1 g/kg for a child) if ingested more than 125 mg/kg body weight salicylate less than one hour previously.
• A second dose of charcoal may be required in patients whose plasma salicylate level continues to rise or who have taken enteric-coated preparations (absorption may be slower).
• Gastric lavage if the patient has ingested more than 500 mg/kg body weight salicylate within one hour.
• Aggressive rehydration.
• Have a low threshold to give glucose, as intracellular glucose depletion may not be reflected in the blood glucose level.
• Urinary alkalinisation:
  • Elimination of salicylate may be increased by alkalinisation of the urine.^[3] The optimum urine pH is 7.5-8.5.
  • If the salicylate concentration in an adult is above 500 mg/L (3.6 mmol/L): 225 mmol sodium bicarbonate (225 mL of 8.4% over 60 minutes or 1.5 L of 1.26% over two hours).
  • If the salicylate concentration in a child is above 350 mg/L (2.5 mmol/L): 1 mL/kg 8.4% bicarbonate diluted in 0.5L 5% dextrose or normal saline at 2-3 mL/kg/hour.
  • The urinary pH should be checked hourly. Further amounts of sodium bicarbonate (8.4%) may be required to maintain the urine pH at 7.5-8.5.
  • Urinary alkalinisation does not need to be delayed while awaiting haemodialysis but volume overload must be avoided in a patient who is oliguric.
• The plasma salicylate concentration should be repeated 1- to 2-hourly to ensure that treatment has been effective.
• Hypokalaemia:
  • May make alkalinisation of the urine less effective and it is important to recheck the plasma potassium 1- to 2-hourly and to give potassium if the plasma potassium falls below 4.0 mmol/L.
  • Hypokalaemia should be corrected before giving sodium bicarbonate.
• Forced diuresis: should not be used, as it does not enhance salicylate excretion and may cause pulmonary oedema.
• Haemodialysis is the treatment of choice for severe poisoning and should be seriously considered in patients with:^[1]
  • Plasma concentrations greater than 700 mg/L (5.1 mmol/L)
  • Acute kidney injury
  • Congestive cardiac failure
  • Non-cardiogenic pulmonary oedema
  • Coma
  • Convulsions
  • CNS effects not resolved by correction of acidosis
  • Persistently high salicylate concentrations unresponsive to urinary alkalinisation
  • Severe metabolic acidosis (pH below 7.2)
• Patients aged under 10 years or over 70 years have increased risk of salicylate toxicity and may require dialysis at an earlier stage.
• Haemofiltration is much less efficient than haemodialysis or haemodiafiltration, but may be an alternative in hospitals without dialysis facilities, especially if transfer is likely to be delayed.
• Mechanical ventilation:^[4]
  • Endotracheal intubation may be indicated for deteriorating mental status or acute lung injury and should be considered in those with significant, uncontrollable agitation.
  • Hyperventilation is not itself an indication for intubation.
  • Endotracheal intubation and mechanical ventilation can be associated with rapid worsening of clinical salicylate toxicity and increased mortality unless a normal or slightly alkalaemic blood pH is maintained by hyperventilation (causing a low pCO₂) and/or intravenous sodium bicarbonate.

Prevention

• Small retail pack size.^[5]
• Measures to prevent accidental overdose by children - eg, safe storage, child-proof caps.