What is the efficacy of ketamine (Ketamine) intravenous (IV) for treating chronic pain?

Efficacy of IV Ketamine for Chronic Pain Management

IV ketamine provides significant short-term analgesic benefit for refractory chronic pain, but its long-term efficacy remains uncertain and it should be considered as a third-line option after conventional analgesics have failed. 1

Dosing and Administration

For chronic pain management, ketamine should be administered at specific subanesthetic doses:

• Initial bolus: <0.35 mg/kg IV
• Maintenance infusion: 0.5-1 mg/kg/h 2
• For postsurgical patients: 1-2 μg/kg/min (0.06-0.12 mg/kg/h) 2
• When used as IV-PCA: 1-5 mg per dose 2
• Maximum total dose should not exceed 1 mg/kg for subanesthetic pain control 2

Evidence for Efficacy in Different Pain Conditions

Neuropathic Pain

• Ketamine shows moderate evidence of efficacy for neuropathic pain components 2
• For phantom limb pain and postherpetic neuralgia, studies provide objective evidence of reduced hyperpathia with substantial pain relief following parenteral or oral ketamine 3
• However, for nonspecific neuropathic pain, studies report divergent results with questionable long-term effects 3

Complex Regional Pain Syndrome (CRPS)

• Meta-analysis shows immediate pain relief event rate of 69% (95% CI 53%, 84%) 4
• Pain relief event rate at 1-3 months follow-up was 58% (95% CI 41%, 75%) 4
• Only level IV evidence exists for efficacy of epidural ketamine in CRPS 3

Fibromyalgia

• Level II evidence supports pain relief, reduced tenderness at trigger points, and increased endurance 3
• Case reports demonstrate significant improvement with long-term ketamine infusions, including improved quality of life and reduced opioid use 5

Other Pain Conditions

• For central pain: level II and IV evidence supports efficacy for parenteral and oral ketamine 3
• For ischemic pain: level II evidence shows potent dose-dependent analgesic effect, but with a narrow therapeutic window 3

Duration of Effect

• Meta-analysis reveals a small but significant analgesic effect up to 2 weeks after infusion (mean difference in pain scores: -1.83 points on a 0-10 scale; 95% CI, -2.35 to -1.31; P<.0001) 1
• Long-term efficacy beyond 3 months is poorly established and largely anecdotal 4, 3

Responder Rates

• Studies show a significantly greater proportion of positive outcomes in ketamine groups compared to placebo (51.3% vs 19.4%; relative risk 2.43; 95% CI 1.10-5.40; P=.029) 1

Role in Multimodal Analgesia

• Ketamine is most effective when used as part of multimodal analgesia, combined with opioids for synergistic effect 2
• Can be used as an adjuvant to opioids to reduce opioid requirements in patients with chronic pain that is refractory to opioids 6
• Can be combined with acetaminophen or NSAIDs when not contraindicated 2

Contraindications and Precautions

• Should not be used in patients with:
  • Uncontrolled cardiovascular disease
  • Pregnancy
  • Active psychosis
  • Severe liver dysfunction
  • High intracranial or ocular pressure 2
• Regular assessment of sedation levels and respiratory status is necessary 2
• Observation for psycho-perceptual adverse effects is required 2

Clinical Application

• Best used as a "third-line analgesic" when standard analgesic options have failed 3
• May be particularly beneficial for elderly patients due to fewer respiratory and cardiovascular side effects compared to opioids 2
• Evidence suggests a possible dose-response relationship, with high-dose ketamine potentially providing greater pain reduction 1

Limitations of Current Evidence

• High heterogeneity among studies
• Most studies have small sample sizes
• Limited long-term follow-up data
• Many studies have high risk of bias 1, 4

While ketamine shows promise for chronic pain management, particularly for refractory cases, larger multicenter studies with longer follow-ups are needed to better select patients and determine optimal treatment protocols.