Jackson, K., Ashby, M., Howell, D., Petersen, J., Brumley, D., Good, P., … Woodruff, R. (2010). The effectiveness and adverse effects profile of \"burst\" ketamine in refractory cancer pain: The VCOG PM 1-00 study. Journal of Palliative Care, 26(3), 176-183.

To assess the efficacy and adverse effects of a ketamine burst protocol for pain relief in patients with refractory pain

Patients received IV ketamine at three dose levels (100, 300, and 500 mg per 24 hours) over 3–5 days in inpatient palliative care settings. All other medications remained, and benzodiazepines or haloperidol could be used to minimize adverse psychotomimetic events. Maintenance doses of 24 opioids and breakthrough pain opioid dosing could be reduced as appropriate for pain control. Data were collected on pain scores and total opioid intake during ketamine infusions and for 48 hours post infusion.

• The sample consisted of 44 patients.
• The median age was 61 years, with a range of 35–82 years.
• The sample was 52% female and 48% male.
• The majority of primary malignancies were lung, breast, colorectal, head and neck, mesothelioma, and multiple myeloma.
• Patients had various types of pain, including neuropathic (64%), pain from bony metastases (25%), and somatic pain (32%).
• All patients had pain scores of 4 or more at baseline, using a verbal rating scale.
• Pretreatment morphine-dose equivalents for opioid intake ranged from 3–1,050 mg per 24 hours.

This was a multisite study conducted in an inpatient setting in Australia.

This was an open-label, prospective study.

Patients were assessed based on the European Cooperative Oncology Group (ECOG) performance status, National Cancer Institute (NCI) Common Toxicity Criteria, and a pain verbal rating scale (which was not described).

• In all, 77% of patients required 300 mg or more of ketamine and 41% required 500 mg per 24 hours. Half of the participants were classified as responders to the ketamine.
• The longest documented response was 3 months in one patient; 11 patients continued with defined response for 2 weeks.
• More than half (61%) of patients experienced low-grade adverse effects. All grade 3 and 4 side effects occurred in patients who needed at least  300 mg per 24 hours of ketamine.
• Injection site toxicity was the most frequent grade 3 toxicity, and the most frequent grade 4 toxicity was hallucinations. No responding patient required withdrawal because of neurological adverse events.

Findings suggest that use of a ketamine burst infusion may be helpful for pain relief in some patients with cancer-related refractory pain.

• The sample size was small, with fewer than 100 patients.
• No comparison or control group was included.
• Opioid intake and episodes of breakthrough pain were not reported, although these were stated as outcomes of interest in the study.
• Refractory pain was defined as at least 4 on the rating scale, but duration of pain was not described in the population.
• Use of adjuvant pain medications was not described; therefore, subgroup analyis could not be done based on other medication intake.
• Statistical analysis of findings was not included.

In patients with pain that is not effectively controlled by other means, approaches such as ketamine infusions may have some benefit. More research in ketamine use is warranted. Although some patients responded and had a duration of effect as long as three months, 50% of patients did not respond as defined. Use of this approach requires hospitalization with continuous infusion and monitoring.