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8 Articles in this Series
Introduction
AAPM's Advice for Evidence-Based Opioid Prescribing Guidelines
CBT for Chronic Pain and Insomnia Needs More Research
Farewell Opioid Therapy, Hello Mental and Behavioral Health
Ketamine’s Growing Use in Chronic Non-Cancer Pain Management
MR Neurography in CRPS Assessment
Navigating New Opioid Prescribing Requirements: Practical Legal Advice for PCPs & Pain Specialists
TACs: Identifying and Treating the Non-Migrainous Headache
Video: Dr. Aronoff on Shifts in Pain Care

Ketamine’s Growing Use in Chronic Non-Cancer Pain Management

With presentation by May L. Chin, MD

Key considerations for the use of infused ketamine in chronic pain care were addressed by May L. Chin, MD, director of the Division of Pain Medicine in the Department of Anesthesiology at the George Washington University Medical Center, during the American Academy of Pain Medicine’s 34th annual meeting in Vancouver, in April 2018. Dr. Chin noted that she has been using ketamine for patients with various intractable pain conditions for several years. One patient, in particular, who presented with complex regional pain syndrome (CRPS) and prior left femur fracture had tried blocks, spinal cord stimulation, intrathecal ziconotide, and below-knee amputation—she finally found the most relief with ketamine.

Pathological pain like that experienced by this patient, explained Dr. Chin, involves increased sensitivity to painful and nonpainful stimuli. It is often very difficult to treat, but by understanding how the pathways behind allodynia and hyperalgesia come together, the implications and diagnosis of chronic pain may be better understood.

Evolution from Anesthetic to Analgesic

Ketamine has been used in medicine for more than 50 years, primarily as an anesthetic, but it is now known to have several mechanisms that might make it a very useful analgesic in pathological and chronic pain. Often used by pain practitioners to manage opioid withdrawal, the medication is an NMDA antagonist that interacts with the mu opioid receptors (low dose).

Over the years, the medication has evolved from an anesthetic to an analgesic through widespread use and rekindled interest primarily because of its NMDA antagonist property, said Dr. Chin. She noted that S-ketamine is twice as potent but not available in the United States at this time.

Pharmacology & Research to Date

With a short half-life (about 2 hours), ketamine can be used to relieve chronic non-cancer pain, said Dr. Chin. It is opioid-sparing, and interacts with opioid, muscarinic and monaminergic receptors. (Dr. Chin noted that Niesters, et al, BJCP, 2013, provides sample uses of ketamine infusions in chronic non-cancer pain). More recently, Maher D, et al, Anesth Analg, Feb 2017, analyzed ketamine cases retrospectively to demonstrate extended duration of relief. Dr. Chin spoke about two studies from this review, both focusing on patients with CPRS.

In one (Sigtermans, et al, Pain, 2009), pain score and use of limb were significantly improved via ketamine infusion, with a pain score dropping dramatically in the first week of treatment and benefit remaining through week 12 compared to placebo. In the other (Schwartzman, et al, Pain, 2009), patients with severe CRPS who had tried multiple treatment approaches received ketamine infusion (100 mg/over 4 hours) as well as clonidine to manage side effects. Although a small sample (<25), in which some patients reported side effects such as nausea, the data overall showed a significant decrease in pain parameters.

Other retrospective data have demonstrated similar results, with the ketamine case review by D. Maher including periods of reported pain relief of up to 25 months. Infusion doses ranged from 10 minutes to a few hours – and up to 48 hours in cancer patients. The studies reviewed included patients with CPRS but also with fibromyalgia, neuropathy, and sickle cell disease.

Future Questions & Use

With regard to dosing, Dr. Chin said some patients may ask for a higher dose in hopes of longer benefit. But looking at the data to date, she recommends minimal dose and duration of treatment be utilized due to a lack of consistent optimal data in this regard. With CRPS patients, Dr. Chin said she does not go above 0.1 mg/kg/h in outpatient settings.

She also cautioned against side effects, noting that headache and nausea are reported most often by her patients, while hallucination and paranoia/anxiety are reported less frequently. These side effects seem to present no matter the duration and dosage, she clarified. Further, cognition returns upon infusion cessation with some reported dizziness among Dr. Chin’s patients. She pointed out, however, that other cases have documented hepatic, bladder, and psychological adverse effects – sometimes due to the nonclinical use of ketamine.

Looking ahead, are repeated ketamine infusions safe? Is ketamine neurotoxic or neuroprotective? Does it have abuse potential? These questions are still being addressed, concluded Dr. Chin. Overall, she said the medication has many actions but also many unknowns, mainly around dosing/duration and for which pain conditions it may work best . With better science and larger, observational studies, ketamine may very well help to stabilize patients suffering from intractable pain.

 

Source

Chin ML. Ketamine for Pain, Depression and PTSD: What Do We Know? Presented at the American Academy of Pain Medicine, April 26-29, 2018. Vancouver, British Columbia.

Next summary: MR Neurography in CRPS Assessment
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