Prilocaine

Prilocaine is an amide local anaesthetic of intermediate duration and low systemic toxicity, but its metabolite o-toluidine oxidises haemoglobin and can cause methaemoglobinaemia. It is used for dental anaesthesia, intravenous regional anaesthesia and, in combination with lidocaine, for topical skin anaesthesia.

Class. Amide local anaesthetic (intermediate duration).

Mechanism. Reversible blockade of voltage-gated sodium channels.

Pharmacokinetics. Onset 2 to 5 minutes. Duration 1 to 2 hours plain and longer with a vasoconstrictor. Protein binding about 55%. Half-life about 1.5 hours. Rapid hepatic and extrahepatic metabolism (including kidney) to o-toluidine, which oxidises haemoglobin. Higher doses (over 600 mg) produce clinically significant methaemoglobinaemia.

Indications are dental infiltration and nerve block, intravenous regional anaesthesia, infiltration, and topical anaesthesia of intact skin (in combination with lidocaine).

Maximum doses (adults)

• Plain: 6 mg/kg, not above 400 mg, in a single dose. With felypressin or adrenaline: up to 8 mg/kg in some labels.
• Dental: 4% plain or 3% with felypressin, 1.8 mL cartridges (72 mg for 4%). Usual dose 1 to 2 cartridges.

Techniques

• Intravenous regional anaesthesia (arm, Bier block): 0.5% plain, 3 mg/kg (about 40 mL for a 70 kg adult). This is the preferred agent for this block. Release the cuff no earlier than 20 to 30 minutes after injection, and deflate and reinflate in stages.
• Infiltration: 0.5 to 1%.
• Peripheral nerve block: 1 to 2%, up to the maximum dose.
• Topical lidocaine-prilocaine cream (2.5% each): apply about 1 g for each 10 cm² under an occlusive dressing for at least 1 hour (maximum 5 hours before the procedure). Maximum area depends on age and weight.

Children

• Dental: reduce by weight; lower maximum dose than adults.
• Topical cream, up to 3 months (term infants): 1 g over 10 cm² for no more than 1 hour.
• Topical cream, 3 to 12 months: up to 2 g over 20 cm² for 1 hour.
• Topical cream, 1 to 5 years: up to 10 g over 100 cm² for up to 4 hours, and older children proportionally more.
• Avoid in preterm infants and in those on methaemoglobin-inducing drugs.

Contraindications.

• Congenital or acquired methaemoglobinaemia.
• Glucose-6-phosphate dehydrogenase deficiency.
• Anaemia, cardiac or respiratory failure with hypoxia.
• Concurrent drugs that cause methaemoglobinaemia (dapsone, sulphonamides, nitrates, phenytoin, paracetamol in large doses, primaquine).
• Hypersensitivity to amide anaesthetics.
• Use of topical cream on broken skin or mucous membranes.
• Infants under 3 months in some settings.
• Adrenaline-containing preparations in end-arterial sites.

Boxed-warning-level risks. Methaemoglobinaemia (dose-related, can be severe in children, anaemia and enzyme deficiency); systemic toxicity with seizures and cardiovascular collapse after overdose or intravascular injection.

Adverse effects. Common: injection pain, dizziness, transient numbness, erythema and blanching with topical use. Serious: methaemoglobinaemia (cyanosis unresponsive to oxygen, chocolate-brown blood), seizures, arrhythmias, hypotension, local anaesthetic systemic toxicity, anaphylaxis (rare).

Interactions. Dapsone, sulphonamides, nitrates, nitrites, phenytoin, primaquine and paracetamol overdose increase methaemoglobin formation. Other local anaesthetics add systemic toxicity. Class 3 antiarrhythmics add cardiac depression.

Common prescribing errors. Exceeding 400 mg or applying large areas of cream in infants; using prilocaine in G6PD deficiency or on a patient taking dapsone; failing to count cartridges in dental use; leaving a tourniquet leaking or releasing it early in an intravenous regional block.

Special groups

• Pregnancy: acceptable at usual doses; avoid near term where methaemoglobinaemia in the neonate is a concern.
• Breastfeeding: compatible at usual doses.
• Older adults: reduce dose by 20 to 30%.
• Kidney impairment: no dose change for single doses.
• Liver impairment: reduce repeat dosing.
• Regional: glucose-6-phosphate dehydrogenase deficiency is relatively common in parts of East Africa. Methylene blue treatment of methaemoglobinaemia can cause haemolysis in affected patients, so screen or ask before using prilocaine in children and avoid dapsone and primaquine coexposure.

Formulations. Dental cartridges 4% plain and 3% with felypressin; vials 0.5%, 1% and 2%; lidocaine-prilocaine cream 5% (2.5% of each) and patch.

Administration. Aspirate before injection and inject slowly. For the cream, apply a thick layer, cover with an occlusive dressing, and remove it before the procedure. For intravenous regional anaesthesia, exsanguinate the arm, inflate the double cuff to 100 mmHg over the systolic pressure, check for leaks, and inject through a cannula in the dorsum of the hand.

Baseline. Allergy history, G6PD status where available, haemoglobin, cardiac and respiratory status, weight, and current medicines.

Monitoring. Oxygen saturation (pulse oximetry can read falsely around 85% in methaemoglobinaemia), skin colour and symptoms. Observe for at least 30 minutes after large doses. For topical use in infants, observe for cyanosis.

Therapeutic drug monitoring. Methaemoglobin level by co-oximetry when cyanosis occurs.

Dose reduction and stopping thresholds. Stop any application or injection at the first sign of toxicity or cyanosis. Reduce area and time of cream in infants.

Referral and escalation. Methaemoglobinaemia over 20 to 30% or with symptoms: give oxygen and methylene blue 1 to 2 mg/kg intravenously over 5 minutes (not in G6PD deficiency, where ascorbic acid and exchange transfusion are alternatives). Seizures or collapse: stop injection, airway support, benzodiazepine, and 20% lipid emulsion 1.5 mL/kg over 1 minute then 15 mL/kg/hour (maximum cumulative 12 mL/kg).