Perioperative Analgesic Adjuncts

Perioperative analgesic adjuncts are non-opioid drugs added to paracetamol, NSAIDs and regional anaesthesia to improve pain control and lower opioid requirement. The group includes gabapentinoids, ketamine, intravenous lidocaine, alpha-2 agonists, magnesium sulphate and dexamethasone. Benefit is greatest in major surgery and in patients at risk of persistent postsurgical pain or opioid tolerance.

Mechanisms.

• Gabapentin and pregabalin bind the alpha-2-delta subunit of voltage-gated calcium channels, reducing excitatory neurotransmitter release.
• Ketamine blocks NMDA receptors and reduces central sensitisation and opioid-induced hyperalgesia.
• Lidocaine blocks sodium channels and has anti-inflammatory and anti-hyperalgesic effects at low plasma levels.
• Dexmedetomidine and clonidine stimulate alpha-2 receptors, reducing noradrenaline release.
• Magnesium blocks NMDA channels.
• Dexamethasone reduces inflammatory mediators.

Principle. Multimodal analgesia builds on a base of scheduled paracetamol and, if no contraindication, an NSAID, with local anaesthetic infiltration or nerve block, then adds an adjunct selected for the patient and the surgery.

Gabapentinoids.

• Gabapentin 300 to 1200 mg orally 1 to 2 hours before surgery, then 300 mg two to three times daily for 1 to 3 days.
• Pregabalin 75 to 150 mg orally before surgery, then 75 mg twice daily.
• Sedation, dizziness, visual disturbance; respiratory depression with opioids; evidence for benefit is mixed.

Ketamine.

• Bolus 0.1 to 0.3 mg/kg at induction; intraoperative infusion 0.1 to 0.25 mg/kg/h; postoperative infusion 0.05 to 0.2 mg/kg/h on a monitored ward.
• Useful in opioid-tolerant patients and chronic pain.
• Hallucination, nightmares, raised blood pressure and heart rate.

Intravenous lidocaine.

• 1.5 mg/kg (ideal body weight) bolus, then 1.5 to 2 mg/kg/h during surgery, continued for up to 24 hours on a monitored ward.
• Benefit in abdominal surgery (earlier return of bowel function, lower opioid use).
• Do not combine with large local anaesthetic doses for regional block unless total dose is controlled.

Dexmedetomidine. Intraoperative infusion 0.2 to 0.5 micrograms/kg/h without a loading dose, or 0.5 microgram/kg over 10 minutes before the end of surgery; bradycardia and hypotension; sedation without respiratory depression. Clonidine 1 to 2 micrograms/kg orally or intravenously is a cheaper alternative.

Magnesium sulphate. 30 to 50 mg/kg intravenously over 15 minutes at induction, then 6 to 15 mg/kg/h; modest opioid-sparing effect; potentiates neuromuscular blockers.

Dexamethasone. 4 to 8 mg intravenously once at induction; analgesic, antiemetic and anti-inflammatory; glucose rises for 24 hours.

• First-line adjuncts. Dexamethasone 4 to 8 mg at induction for most major surgery; local anaesthetic infiltration or nerve block.
• Alternative. Ketamine for major surgery and opioid-tolerant patients; intravenous lidocaine for open and laparoscopic abdominal surgery when regional anaesthesia is not possible; dexmedetomidine when opioid-free anaesthesia is attempted; gabapentin in selected patients at risk of persistent pain.
• Specialist. Opioid-free or opioid-sparing anaesthesia, continuous ketamine or lidocaine infusions, spinal and epidural adjuvants (clonidine 15 to 150 micrograms epidurally).
• Emergency. Ketamine 0.1 to 0.3 mg/kg for severe breakthrough pain where respiratory depression from more opioid is dangerous.

Selection.

• Match the adjunct to surgery and patient: ketamine and lidocaine in major abdominal and spinal surgery; gabapentin only after weighing sedation and respiratory risk.
• Avoid routine gabapentinoids in older adults, in obstructive sleep apnoea and with high-dose opioids.
• Review all adjuncts at 24 to 72 hours and stop; do not discharge on new gabapentinoids without a stop date.

Contraindications.

• Gabapentinoids: hypersensitivity; severe renal impairment without dose reduction; caution with respiratory disease and sleep apnoea.
• Ketamine: severe hypertension, eclampsia, active psychosis, raised intracranial or intraocular pressure (relative), cardiac failure with high catecholamine states.
• Lidocaine infusion: heart block, severe bradycardia, hepatic failure, concurrent large local anaesthetic doses, allergy.
• Dexmedetomidine: advanced heart block, severe hypotension.
• Magnesium: myasthenia gravis, heart block, renal failure without monitoring.
• Dexamethasone: uncontrolled diabetes, active infection (relative).

Serious adverse effects. Respiratory depression and sedation (gabapentinoids with opioids); psychotomimetic reactions and hypertension (ketamine); local anaesthetic toxicity (lidocaine); bradycardia and hypotension (alpha-2 agonists); weakness and hypotension (magnesium); hyperglycaemia and delayed wound healing (dexamethasone).

Major interactions. Opioids, benzodiazepines and alcohol with gabapentinoids; neuromuscular blockers with magnesium; beta-blockers and calcium channel blockers with dexmedetomidine; amiodarone and beta-blockers raise lidocaine levels; CYP3A4 inhibitors have minor effects on ketamine.

Common prescribing errors.

• Gabapentinoid dose not reduced for kidney function.
• Lidocaine dosed on actual rather than ideal body weight in obesity.
• Ketamine infusion on a ward without monitoring.
• Gabapentinoids continued after discharge without review.
• Combining several sedating adjuncts with opioids.

Special groups.

• Pregnancy: avoid gabapentinoids unless essential; ketamine and lidocaine used in obstetric practice with caution; magnesium used in pre-eclampsia.
• Breastfeeding: gabapentin and pregabalin pass into milk; single perioperative doses are generally acceptable; dexamethasone compatible.
• Children: ketamine 0.1 to 0.25 mg/kg bolus; dexmedetomidine 0.3 to 0.5 micrograms/kg; limited data for other adjuncts.
• Older adults: avoid gabapentinoids and use lower ketamine and lidocaine doses; monitor for delirium.
• Kidney: gabapentin is cleared unchanged; with CrCl 30 to 59 mL/min give 400 to 1400 mg daily, 15 to 29 mL/min 200 to 700 mg daily; reduce pregabalin in the same way; avoid magnesium infusion without level monitoring.
• Liver: reduce lidocaine infusion rate and avoid in hepatic failure.
• East Africa: ketamine, dexamethasone and magnesium are often available and low cost; lidocaine infusion needs ECG monitoring and a lipid emulsion plan, which many facilities lack.

Monitoring. Sedation score and respiratory rate hourly for gabapentinoid and opioid combinations; ECG and saturation during lidocaine and dexmedetomidine; blood pressure, heart rate and mental state with ketamine; magnesium levels and reflexes; blood glucose after dexamethasone in diabetes.

Referral and escalation. Respiratory depression, local anaesthetic toxicity (perioral numbness, tinnitus, seizure, arrhythmia), psychosis, persistent hypotension or bradycardia, delirium; patients with chronic pain or opioid tolerance should have a pain team plan before surgery.

Comparison with alternative classes. Adjuncts lower opioid use and may reduce persistent postsurgical pain, but each carries its own toxicity, and the evidence for routine use is strongest for dexamethasone, local anaesthetic techniques and ketamine in selected surgery. Regional anaesthesia is usually more effective than any systemic adjunct.