Salicylate Overdose

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Introduction

Salicylates are a group of medications of which aspirin (acetylsalicylic acid) is the most common.

Other salicylates exist, including magnesium salicylate, diflunisal, and bismuth subsalicylate. These are all non-steroidal anti-inflammatory drugs (NSAIDs) and have a dual-action as an antiplatelet at lower doses and an analgesic at higher doses.1

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Aetiology

Types of salicylates

Even though aspirin is the most commonly used salicylate, other common household preparations that contain salicylates include:2

  • Non-steroidal anti-inflammatory drugs: both oral and topical preparations
  • Oil of wintergreen: a mint smelling fragrance used in many products, and low concentrations are found in chewing gum and mints
  • Selected antacids and antidiarrhoeal medications

Intentional overdose

An intentional overdose can be a means of causing self-harm or a suicide attempt. Exploring the intention of an overdose is a key part of assessing a patient’s psychological state and associated risk.

Accidental overdose

With the widespread use of salicylates, accidental ingestion of more than the recommended dose is common. Incorrect dosing in children and the elderly may also result in overdose.

Many non-prescription aspirin-containing products are available, and many cold and flu remedies also contain aspirin, increasing the risk of patients unknowingly exceeding the safe dose.2

Pathophysiology

In mild toxicity, salicylates directly irritate the gastric lining. They can also cause ototoxicity through a multifactorial process, involving reduced cochlear blood flow secondary to vasoconstriction and changes to cochlear cells.

In higher doses, the pharmacodynamics of salicylate poisoning leads to a mixed respiratory alkalosis and metabolic acidosis. In moderate/severe toxicity, salicylates stimulate the cerebral medulla, leading toย hyperventilation and respiratory alkalosis.

Metabolisation of salicylates then causes uncoupling of oxidative phosphorylation, resulting in anaerobic metabolism. This causes heat production and pyrexia and increased lactic acid production, resulting in metabolic acidosis. The acidic effects of salicylates also contribute to the associated acidosis. Hyperventilation then worsens in response to the acidosis until the body can no longer compensate.3,4


Clinical features

History

Typical symptoms of salicylate overdose are dependent on the severity of the poisoning.3

Symptoms of mild toxicity include:

  • Nausea and vomiting
  • Epigastric pain
  • Tinnitus
  • Dizziness
  • Lethargy

Symptoms of moderate toxicity include:

  • Sweating
  • Fever
  • Dyspnoea

Symptoms of severe toxicity include:

  • Confusion
  • Convulsions
  • Coma

Other important areas to cover in the history include:

  • The amount and preparation of the salicylate taken
  • Intentional or accidental overdose
  • Isolated or mixed overdose
Mixed overdose

Consider the possibility of a mixed overdose in any patient presenting with acute drug toxicity.

Patients may even be unaware that they have consumed potentially toxic quantities of several substances. It is important to determine the exact preparations, ingredients and doses of each medication consumed. The management of different toxidromes varies. TOXBASE provides comprehensive guidance.

Clinical examination

Clinical findings are dependent on the severity of toxicity.ย 

Typical clinical findings in moderate/severe toxicity include:

  • Warm peripheries and bounding pulse
  • Tachypnoea and hyperventilation
  • Cardiac arrhythmia
  • Acute pulmonary oedema

Investigations

Bedside investigations

Relevant bedside investigations include:2

  • Observations: to indicate patient stability and guide physiological support (e.g. oxygen). Tachypnoea and tachycardia are common findings.
  • ECG: to monitor for arrhythmias. It is essential to monitor QRS duration and QT interval for evidence of prolongation.
  • Capillary blood glucose: to exclude hypoglycaemia or ketoacidosis if the main presenting complaint is vomiting and confusion. However, hypoglycaemia or hyperglycaemia may be seen in salicylate toxicity.
  • Arterial blood gas: to monitor acid-base balance. Initially, hyperventilation causes respiratory alkalosis, but this will then progress to metabolic acidosis with a partial respiratory compensation, with a normal or high pH.

Laboratory investigations

Relevant laboratory investigations include:2

  • Plasma salicylate concentration: taken at least 2 hours after ingestion and repeated every 2 hours until salicylate concentration peaks.
  • Plasma paracetamol concentration: paracetamol concentration should be measured in all patients to identify mixed overdose.
  • FBC: to exclude an infectious aetiology for the presenting features.
  • U&Es: to assess for electrolyte disturbances. Hyperkalaemia is common and should be monitored closely and promptly corrected. Urea and creatinine may be raised, indicating an acute kidney injury.
  • LFTs: to assess for hepatic dysfunction.
  • Coagulation: INR and prothrombin time may be increased in hepatic dysfunction.

Imaging

Relevant imaging investigations may include:

  • CT head: if the patient has an altered mental state and an intracranial pathology is suspected.4

Diagnosis

TOXBASE classifies salicylate overdose as mild, moderate, or severe toxicity, according to clinical features and peak salicylate levels:3

  • Mild toxicity: <300 mg/L
  • Moderate toxicity: 300 to 700 mg/L
  • Severe toxicity: >700 mg/L

Management

As with any acutely unwell patient, they should be managed using an ABCDE approach. Patients with severe salicylate toxicity may lose control of their airway and soย itโ€™s crucial to ensure airway patency and adequate ventilation is maintained.ย 

There is no antidote for salicylate poisoning, and the mainstay of management is supportive care. ICU admission should be considered for those with moderate to severe toxicity.2

TOXBASE

The National Poisons Information Service has created a clinical toxicology database listing nearly every toxin. They provide gold-standard information and management guidance for toxin consumption in the UK. Information can be found via their website or by calling the service. A login is required to access the website, and most institutions will provide this.

Initial management

The initial management of salicylate overdose includes:2,3,5

  • Activated charcoal: this should be considered for patients presenting within 1 hour of ingestion of >125mg/kg salicylates unless there are concerns around airway protection.
  • Intravenous fluid resuscitation: patients may be volume-depleted requiring large volumes of fluid (0.9% sodium chloride is typically used).
  • Potassium replacement: hypokalaemia should be treated urgently with an intravenous infusion. The aim is to maintain plasma potassium of 4-4.5 mmol/L. Bicarbonate therapy can precipitate hypokalaemia, so any pre-existing hypokalaemia must be urgently corrected.
  • Sodium bicarbonate: this reduces the transfer of salicylates into the central nervous system and enhances the urinary excretion of salicylates (otherwise known as urinary alkalinisation). Urine pH should be monitored with the optimal pH 7.5-8.5. As mentioned, plasma potassium should be corrected before starting sodium bicarbonate, as it can potentiate hypokalaemia.

Ongoing management

The ongoing management of salicylate overdose includes:2,3

  • Cooling measures: hyperthermia should be addressed by removing clothes and using wet towels, fans and icepacks. More invasive internal cooling devices or sedation are indicated in temperatures exceeding 39ยฐC.
  • Haemodialysis: the treatment of choice for severe salicylate poisoning with renal failure, severe metabolic acidosis or seizures. Haemodialysis should be arranged urgently for those with a salicylate concentration โ‰ฅ900 mg/L (โ‰ฅ700 mg/L with a metabolic acidosis) or coma secondary to salicylate poisoning.
  • Intravenous benzodiazepines (e.g. lorazepam): for the management of frequent or prolonged convulsions.
  • Continuous positive airway pressure (CPAP): this is considered for patients with acute pulmonary oedema or acute lung injury, secondary to the salicylate overdose.
  • Psychological support: patients require access to psychological services if the overdose was intentional. If the patient refuses treatment, a psychiatric assessment should be organised to assess capacity.
Haemodialysis vs Haemofiltration

Haemodialysis involves the diffusion of solutes from a high concentration to a low concentration across a semipermeable membrane. Haemofiltration uses convection and high pressure to force solutes from the blood to the dialysis fluid for disposal.6 Haemodiafiltration combines the two processes.

Haemofiltration is much slower than haemodialysis, and so haemodiafiltration or haemodialysis alone should be used to remove salicylates from the plasma and correct the metabolic acidosis.


Complications

Complications due to salicylate poisoning are common. The specific management of which should be carried out in addition to the management of the acute overdose.

Acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is typified by bilateral pulmonary oedema with hypoxia, which is not explained by heart failure. Its incidence in salicylate poisoning is dose-dependent, with a high incidence in salicylate levels โ‰ฅ800 mg/L.

Management involves intubation and ventilation with elevated positive end-expiratory pressures to prevent alveolar collapse.2

Seizures

Like ARDS, the incidence of seizures rises with the ingested dose. Anticonvulsants are generally unnecessary if single and brief. However, benzodiazepines are used to terminate prolonged seizures.

With frequent seizures comes the risk of failure to ventilate, and these patients may require intubation and ventilation.2,3

Drug-induced hepatitis

The incidence of hepatitis is low and generally resolves with the resolution of toxicity. Itโ€™s important to be aware of this when reviewing the LFTs.2

Cardiac arrest

Salicylate toxicity can significantly affect cardiac physiology. Prolongation of the QT interval is regularly seen, which can lead to polymorphic ventricular tachycardia and/or ventricular fibrillation.

Advanced cardiac life support guidelines should be followed as standard, with good CPR, IV adrenaline and defibrillation, if indicated. Sodium bicarbonate administration is recommended in salicylate-induced cardiac arrest, although there is no evidence base behind this.2


Key points

  • Aspirin is the most commonly purchased salicylate and is available over the counter (OTC).
  • Many household medications contain salicylates, including cold and flu relief, antacids and antidiarrhoeals.ย 
  • A detailed history is required in any overdose, determining the exact preparations, ingredients and doses of each medication consumed.
  • Nausea, vomiting, and tinnitus are the features of mild intoxication, and these can be easily confused with another aetiology.
  • Salicylate toxicity first causes respiratory alkalosis followed by metabolic acidosis.
  • Plasma salicylate concentration should be taken 2 hours after ingestion in a symptomatic patient and every 2 hours until the concentration begins to fall.
  • Management is generally supportive, involving IV fluids and correcting electrolytes. In more severe toxicity, sodium bicarbonate and haemodialysis play a more significant role.
  • Psychological support must always be offered in the context of intentional overdose including assessment of capacity if necessary.
  • Complications may include ARDS, seizures, and cardiac arrest.

Reviewer

Dr Grace McKay

Honorary Clinical Lecturer

Cardiff University


Editor

Dr Chris Jefferies


References

  1. Steven B Abramson. Aspirin: Mechanism of action, major toxicities, and use in rheumatic diseases. UpToDate. Published 2021. Available from: [LINK]
  2. BMJ Best Practice. Salicylate poisoning. Published 2021. Available from: [LINK]
  3. National Poisons Information Service. TOXBASEยฎ. Salicylic Acids and Salicylates (Salicylates). Published 2019. Available from: [LINK]
  4. Tyler J. Runde TMN. Salicylates Toxicity. In: StatPearls [Internet]. StatPearls Publishing; 2021. Available from: [LINK]
  5. Joint Formulary Committee. Poisoning, emergency treatment. In: British National Formulary (Online). BMJ Group and Pharmaceutical Press.
  6. Hall NA, Fox AJ. Renal replacement therapies in critical care. Contin Educ Anaesth Crit Care Pain. 2006;6(5):197-202. doi:10.1093/bjaceaccp/mkl038

 

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