What is the role of ketamine infusion in cancer pain management?

Ketamine Infusion for Cancer Pain

Ketamine should NOT be used routinely for cancer pain management, but may be considered as a last-resort option in highly selected patients with opioid-refractory pain, particularly those with suspected central sensitization or "wind-up" phenomenon. 1

Evidence Quality and Guideline Recommendations

The most recent and authoritative guidelines are clear about ketamine's limited role:

• ESMO 2018 guidelines explicitly state there is a lack of evidence to support routine use of ketamine in cancer neuropathic pain (Level II, Grade D recommendation). 1

• NCCN 2019 guidelines acknowledge that while ketamine has theoretical benefits as an NMDA antagonist, a double-blind RCT found no significant difference between ketamine and placebo for cancer pain. 1 However, they note a subsequent systematic review suggested "modest analgesic potential" despite limited data. 1

• Earlier NCCN 2013 guidelines similarly reported negative RCT results. 1

• Older ESMO guidelines (2005,2008) only mention ketamine as a potential option for "intractable pain" at subanesthetic doses, without strong endorsement. 1

When to Consider Ketamine (Highly Selective Use)

The only patient population where ketamine may have a theoretical benefit is those with central sensitization presenting as "clinical wind-up." 1 This remains investigational and no routine clinical recommendation exists. 1

Practical criteria for consideration:

• Pain refractory to optimized opioid therapy (including dose escalation and rotation) 1
• Failure of appropriate adjuvants (gabapentin, pregabalin, duloxetine, or tricyclic antidepressants for neuropathic pain) 1
• Evidence of central sensitization or hyperalgesia 1
• Situations where invasive interventions are inappropriate 1

Dosing When Used

If ketamine is attempted despite limited evidence, use subanesthetic doses only:

• Infusion dosing: 0.05 to 0.5 mg/kg/hour IV or subcutaneously 2
• Oral dosing: 0.2-0.5 mg/kg/dose two to three times daily, maximum 50 mg/dose three times daily 2
• Bolus for acute severe pain: <0.35 mg/kg 3
• Continuous infusion: 0.5-1 mg/kg/hour 3

Critical Safety Considerations

Ketamine requires monitoring consistent with general anesthesia standards when used for procedural sedation. 3 For cancer pain infusions:

• Maintain vascular access throughout administration 3
• Monitor for hallucinations, depersonalization/derealization, somnolence, and feelings of insobriety 2
• Co-administration with benzodiazepines reduces psychiatric side effects (hallucinations, depersonalization not reported when combined) 2
• Children experience fewer adverse effects (sedation, anorexia, urinary retention, myoclonic movements) 2

Contraindications include: uncontrolled cardiovascular disease, pregnancy, active psychosis, severe liver dysfunction, elevated intracranial or ocular pressure 3

Practical Algorithm

1. First-line: Optimize opioid therapy (morphine, oxycodone, fentanyl) using oral route when possible 1

2. Second-line for neuropathic pain: Add gabapentin, pregabalin, duloxetine, or TCA (≥75 mg/day) 1

3. Third-line: Consider opioid rotation, methadone (requires specialist consultation), or interventional techniques (nerve blocks, intrathecal delivery) 1

4. Last resort only: Trial ketamine in patients with suspected central sensitization who have failed all conventional approaches 1

5. Novel approach: Consider a test bolus before committing to continuous infusion to identify responders 4

Common Pitfalls

• Do not use ketamine as a routine adjuvant – the highest quality RCT evidence shows no benefit over placebo 1
• Do not continue ketamine postoperatively – this increases hallucination risk without enhancing analgesia 3
• Do not use without benzodiazepine coverage if psychiatric side effects emerge 2
• Do not use in place of proper opioid optimization – ensure adequate opioid dosing and appropriate adjuvants first 1

Bottom Line

The evidence does not support routine ketamine use for cancer pain. 1 While some case reports and small studies suggest benefit in highly selected patients, the best available RCT evidence is negative. 1 Reserve ketamine for truly refractory cases with suspected central sensitization, use it cautiously with appropriate monitoring, and consider it an investigational approach rather than standard care. 1