Procaine

Procaine is a short-acting ester local anaesthetic with low potency and slow onset. It has largely been replaced by amide agents for most uses but remains in use for infiltration, some dental practice, and as the procaine salt in long-acting penicillin preparations. It is hydrolysed by plasma pseudocholinesterase to para-aminobenzoic acid, which can cause allergy.

Class. Ester local anaesthetic (short duration).

Mechanism. Reversible blockade of voltage-gated sodium channels.

Pharmacokinetics. Onset 5 to 10 minutes. Duration 30 to 60 minutes (longer with adrenaline). Protein binding about 6%. Plasma half-life under 10 minutes, with rapid hydrolysis by pseudocholinesterase to para-aminobenzoic acid and diethylaminoethanol. Renal excretion of metabolites. Prolonged in pseudocholinesterase deficiency.

Indications are infiltration and field block, peripheral nerve block, dental anaesthesia in some settings, and diagnostic nerve block.

Maximum doses (adults)

• Without adrenaline: about 10 mg/kg, not above 1000 mg, in older references. Typical single doses are far lower.
• With adrenaline: higher limits are quoted, but they are rarely needed.
• Concentrations: 0.5 to 1% for infiltration; 2% for nerve block.

Techniques

• Infiltration: 0.25 to 1% in the volume needed, up to the maximum dose.
• Nerve block: 1 to 2% in 10 to 20 mL.
• Spinal use is historical and not advised.
• No loading dose or titration; repeat dosing is limited by the weight-based ceiling.

Children. Reduce to a maximum of 5 to 7 mg/kg. Not preferred in routine paediatric practice.

Contraindications. Hypersensitivity to ester anaesthetics or para-aminobenzoic acid (including sulphonamide-allergic patients with true cross reaction); pseudocholinesterase deficiency; infection at the site; adrenaline-containing preparations in end-arterial sites.

Boxed-warning-level risks. Systemic toxicity with seizures and cardiovascular collapse after intravascular injection or overdose. Allergic reactions (rash to anaphylaxis) from the para-aminobenzoic acid metabolite are more frequent than with amides.

Adverse effects. Common: injection pain, transient dizziness, nausea. Serious: seizures, hypotension, bradycardia, methaemoglobinaemia (rare), allergic reactions, and reactions to procaine penicillin (sudden fear, hallucination, tachycardia after intramuscular injection), which are not allergic.

Interactions. Para-aminobenzoic acid antagonises sulphonamide antibacterials. Suxamethonium and procaine compete for pseudocholinesterase, prolonging neuromuscular block. Cholinesterase inhibitors (neostigmine, organophosphates) slow hydrolysis and increase toxicity. Adrenaline interacts with tricyclic antidepressants and non-selective beta blockers.

Common prescribing errors. Using it in a patient with ester allergy; giving to a patient with known pseudocholinesterase deficiency; assuming procaine penicillin and procaine anaesthetic reactions are the same; using it in place of amides when a longer block is needed.

Special groups

• Pregnancy: acceptable for minor procedures; reduced plasma cholinesterase in pregnancy slows hydrolysis.
• Breastfeeding: compatible.
• Older adults: reduce dose.
• Kidney impairment: no adjustment for single doses.
• Liver impairment: reduced pseudocholinesterase production, so use lower doses and longer intervals.
• Regional: confirm formulations before drawing up, as strengths vary by supplier; organophosphate exposure (pesticides) lowers cholinesterase and makes ester agents more toxic.

Formulations. Solutions 0.5, 1 and 2%; procaine as a salt in intramuscular penicillin preparations.

Administration. Aspirate before injection and inject slowly. Use sterile technique.

Baseline. Allergy history (ester, para-aminobenzoic acid), pseudocholinesterase deficiency history (prior prolonged paralysis), cardiac and liver status, pesticide exposure, current sulphonamide therapy.

Monitoring. Observe for at least 30 minutes after large doses. Watch for signs of toxicity (perioral numbness, tinnitus, confusion, twitching), allergy and prolonged block.

Therapeutic drug monitoring. Not used.

Dose reduction and stopping thresholds. Stop injection at the first sign of toxicity or allergy. Reduce doses in older adults, liver disease and low-cholinesterase states.

Referral and escalation. Seizures or collapse: stop injection, give oxygen and airway support, benzodiazepine, and 20% lipid emulsion 1.5 mL/kg over 1 minute then 15 mL/kg/hour (maximum cumulative 12 mL/kg). Anaphylaxis needs intramuscular adrenaline.