According to research results published in Pain Medicine, intravenous (IV) ketamine has shown to be an effective and safe protocol for the treatment of cancer-related neuropathic pain (CNP) in patients with refractory pain control.

Previously, IV ketamine has been used to treat nononcologic neuropathic pain but has not been well studied for the treatment of CNP. In a single-centered, retrospective review, 57 consecutive patients who were diagnosed with CNP between April 2018 and May 2020 underwent an IV ketamine infusion protocol, which consisted of 192 infusions.

According to researchers, “Each patient’s pain was identified as being secondary to direct tumor compression (n = 13), CIPN (n = 25), surgery (n = 13), or radiation (n = 6).” The most common cancer diagnosis was breast cancer (13 patients), with nerve sheath tumors following (7 patients), and there were also 8 patients with metastases. Patients with underlying neuropathy or peripheral neuropathy prior to the onset of their CNP were excluded. 


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Treatment was a series of 4-hour infusion sessions. Before each session, the patient’s baseline parameters were obtained, including pain via the numeric pain rating scale, function, satisfaction, and use of analgesics. The first ketamine infusion started at 10 mg/h with a maximum titration of 25 mg/h, as tolerated.

After the initial session, all patients were eligible for a second and third infusion 1 week after the first session with an increase in the dosages each session as tolerated. Responders, or “patients who reported ≥30% reduction in pain based on NPRS or positive subjective qualifiers,” continued infusions about every 4 weeks with the maximum dose of 70 mg/h, as tolerated.

Overall, 73.7% (P<0.01) of the patients were responders. While on the IV ketamine protocol, all responders reported having improvement in function and mobility. Of the 42 responders, 26.7% (P=0.0003) discontinued treatment due to unsatisfactory pain relief or adverse effects. 71.8% of the responders had pain relief for more than 3 weeks (P< 0.01). 

Due to the pandemic, 14 of the patients who were enrolled in the IV ketamine protocol could not continue treatment. With that, 13 out of the 14 patients returned to baseline pain, with each of them reporting anorexia and/or function, mobility, and mood worsening.

The majority of the adverse effects were neurological (7.8%), including headache, dizziness, and somnolence. Gastrointestinal adverse events (3.6%) were nausea and vomiting. Cardiovascular events (2.1%) consisted of hypertension and tachycardia.

Results show that 64.7% of the adverse events self-resolved with changing the infusion rate or intervention. Contrary, 35.3% of adverse events resolved with the infusion rate being reduced or stopped, or the patient receiving as-needed medications. However, none of the adverse events were life-threatening or required hospitalization.

Study limitations include inconsistently used objective outcome measures, specifically neuropathic pain scales, NPRS scores, QOL, functional measures, and patient satisfaction. Though the sample size was small, it remains the largest study of IV ketamine as an adjuvant treatment for CNP to date.

“Additionally, these data demonstrate that an extended IV ketamine protocol is safe and well tolerated, with minimal adverse events and several patients who had long-term pain relief. Larger, prospective studies must be conducted to further illustrate the effects of IV ketamine on CNP and to explore the different parameters that may help prognosticate a good response to IV ketamine.”

Reference

Oh D, Haffey P, Patel A, Gulati A. Intravenous ketamine for cancer pain management, including flares during the COVID-19 pandemic: a retrospective study. Pain Medicine. Published online June 4, 2021. doi:10.1093/pm/pnab163