Salicylate poisoning is potentially fatal. Salicylates are present in aspirin medications, Pepto-Bismol® and in high concentrations of oil of wintergreen (methyl salicylate: 1 teaspoon = 7 g of salicylate). The local poisons service should be contacted for advice:

• UK National Poisons Information Service - www.npis.org - Tel: 0844 892 0111.
• 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 but 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, central nervous system (CNS) features, hyperpyrexia
• Metabolic acidosis
• Salicylate concentration above 700 mg/L (5.1 mmol/L)

Presentation¹

• 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, renal failure and non-cardiac pulmonary oedema.
• CNS: confusion, disorientation, coma and convulsions (less common in adults than in children).

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 2 hours (symptomatic patients) or 4 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 2 hours because of the possibility of continuing absorption. Measurements should be repeated every 3 hours until concentrations are falling.
• Renal function and electrolytes, full blood count, coagulation studies (raised INR/PTR), urinary pH, and blood glucose.
• Plasma potassium should be checked every 3 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.

Management¹

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 1 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 1 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. 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 2 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.
  • The plasma salicylate concentration should be repeated 1-2 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.
  • Urinary alkalinisation does not need to be delayed while awaiting haemodialysis but volume overload must be avoided in a patient who is oliguric.
• 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)
  • Renal failure
  • 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.

Prevention

• Small retail pack size.²
• Measures to prevent accidental overdose by children, e.g. safe storage, child-proof caps.

Document references

1. Toxbase; (Registration is free for doctors who are employed by an NHS practice)
2. Hawton K, Townsend E, Deeks J, et al; Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study. BMJ. 2001 May 19;322(7296):1203-7. [abstract]

Acknowledgements