Benzocaine

Benzocaine is a poorly water-soluble ester local anaesthetic used only on skin and mucous membranes. It has rapid onset and a short duration, and it is a recognised cause of methaemoglobinaemia, especially after sprays to the oropharynx and in young children. It is used for oropharyngeal and airway surface anaesthesia, lozenges for sore throat, and minor skin and dental surface pain.

Class. Ester local anaesthetic (topical only).

Mechanism. Reversible blockade of voltage-gated sodium channels in nerve endings. It lacks the ionisable amine group of other agents, so it acts only at surface layers and is not suitable for injection.

Pharmacokinetics. Onset within 30 seconds to 1 minute on mucosa. Duration 15 to 30 minutes. Absorption through broken skin or inflamed mucosa is variable and increases with the area treated. Hydrolysed by plasma pseudocholinesterase to para-aminobenzoic acid. Metabolism also forms aromatic amines that oxidise haemoglobin.

Indications are surface anaesthesia of the oropharynx before endoscopy or awake airway procedures (where other agents are not available), pharyngeal discomfort (lozenges), and topical relief of minor skin, dental and haemorrhoidal pain.

Adults

• Mucosal spray (14 to 20%): the lowest number of brief sprays that achieves anaesthesia. Avoid repeated or prolonged spraying; the dose that causes methaemoglobinaemia is not predictable.
• Lozenges (typically 6 to 15 mg): one lozenge every 2 to 3 hours as needed, up to the maximum on the label.
• Gel or ointment (up to 20%): thin layer to the affected area up to 3 to 4 times daily.
• No loading dose, titration or fixed maximum; use the smallest effective amount and area.

Children

• Under 2 years: contraindicated for teething and oral mucosal use. Do not use.
• Older children: avoid sprays in the airway; if surface anaesthesia is essential, use lidocaine instead.

Contraindications. Children under 2 years; methaemoglobinaemia; glucose-6-phosphate dehydrogenase deficiency; hypersensitivity to benzocaine, ester anaesthetics or para-aminobenzoic acid; application to large areas or damaged skin; concurrent drugs that cause methaemoglobinaemia.

Boxed-warning-level risks. Methaemoglobinaemia, sometimes fatal, with sudden cyanosis and falling oxygen saturation (a typical reading near 85% that does not rise with oxygen) within minutes to hours of use.

Adverse effects. Common: transient burning, stinging, contact dermatitis. Serious: methaemoglobinaemia, anaphylaxis, local tissue irritation, delayed hypersensitivity, laryngospasm if the airway is sprayed, systemic toxicity with large areas.

Interactions. Dapsone, nitrates, nitrites, phenytoin, primaquine, sulphonamides and prilocaine increase methaemoglobin risk. Sulphonamide antibacterials are antagonised by para-aminobenzoic acid. Cholinesterase inhibitors slow hydrolysis.

Common prescribing errors. Using benzocaine gel for teething in infants; spraying repeatedly during awake airway procedures; applying to large areas or inflamed mucosa; not recognising that cyanosis with a low saturation reading and chocolate-brown blood suggests methaemoglobinaemia.

Special groups

• Pregnancy: limited data; use the smallest amount, since maternal methaemoglobinaemia reduces oxygen delivery to the foetus.
• Breastfeeding: compatible at small doses.
• Older adults: use the smallest amount.
• Kidney impairment: no dose change.
• Liver impairment: reduce the amount used; ester hydrolysis is plasma-based but clearance of metabolites may be slowed.
• Regional: glucose-6-phosphate dehydrogenase deficiency is relatively common in parts of East Africa, and methylene blue given for methaemoglobinaemia can cause haemolysis in these patients, so avoid benzocaine in children and in anyone with known or suspected deficiency.

Formulations. Mucosal sprays (14 to 20%), gels and ointments (up to 20%), lozenges (6 to 15 mg), dental gels.

Administration. Apply to the target area only. Wait for onset before starting the procedure. Do not apply under occlusive dressings. Do not spray into the airway repeatedly.

Baseline. Age, allergy history (ester, para-aminobenzoic acid), G6PD status where known, haemoglobin and concurrent medicines that cause methaemoglobinaemia.

Monitoring. Pulse oximetry during and after any airway use. Skin colour (grey-blue or cyanosis). In suspected methaemoglobinaemia, blood gas with co-oximetry for methaemoglobin level.

Therapeutic drug monitoring. Methaemoglobin level (co-oximetry) when symptoms occur.

Dose reduction and stopping thresholds. Stop immediately for cyanosis, falling saturation or any systemic symptoms. Reduce the number and duration of sprays.

Referral and escalation. Methaemoglobinaemia over 20 to 30%, or with symptoms at lower levels, needs oxygen and methylene blue 1 to 2 mg/kg intravenously over 5 minutes, repeated once after 30 to 60 minutes if needed (not in G6PD deficiency, where ascorbic acid, exchange transfusion or hyperbaric oxygen are alternatives). Anaphylaxis needs intramuscular adrenaline.