Ketamine Infusions for Chronic Pain Clinical Practice Guidelines (2018)

American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine, and American Society of Anesthesiologists

Reviewed and summarized by Medscape editors

August 09, 2018

The clinical practice guidelines on ketamine infusions for chronic pain were released in July 2018 by the ASRA, AAPM, and ASA.[1]

For spinal cord injury pain, there is weak evidence supporting ketamine infusions (0.42 mg/kg per hour to 0.4 mg/kg ranging from 17 minutes to 5 hours for 7 consecutive days) for short-term improvements in pain.

For complex regional pain syndrome (CRPS), there is moderate evidence supporting ketamine infusions (22 mg/h for 4 days or 0.35 mg/kg per hour over 4 hours daily for 10 days) to provide improvements in pain for up to 12 weeks.

For mixed neuropathic pain, phantom limb pain (PLP), postherpetic neuralgia (PHN), fibromyalgia, cancer pain, ischemic pain, migraine headache, and low-back pain, there is weak or no evidence supporting ketamine infusions for immediate improvements in pain. Excluding CRPS, there was no evidence supporting ketamine infusions for intermediate or long-term improvements in pain.

Ketamine should not be used in patients with poorly controlled cardiovascular disease and should be avoided in individuals with certain poorly controlled psychoses.

For hepatic dysfunction, it should be avoided in individuals with severe impairment but may be administered judiciously with proper monitoring in people with moderate disease.

In patients with elevated intracranial and intraocular pressure, there is grade C evidence that ketamine should not be used or used only in lower dosages with extreme caution.

Serial ketamine infusions should not be undertaken in patients with an active substance abuse problem and should be used along with universal precautions to monitor for abuse.

There is moderate evidence to support higher dosages of ketamine over longer time periods, and more frequent administration, for chronic pain. Similar to the strategy used for opioids and other analgesic drugs with significant adverse effect profiles, it is reasonable to start dosing with a single, outpatient infusion at a minimum dose of 80 mg lasting more than 2 hours and reassess before initiating further treatments, similar to what is widely recommended for epidural steroid injections.

We conclude that there is low-level evidence to support the use of oral ketamine (150 mg/d or 0.5 mg/kg every 6 hours) and other NMDA-receptor antagonists such as dextromethorphan (0.5–1 mg/kg every 8 hours) as follow-up therapy following IV infusions, and moderate evidence to support intranasal ketamine (1–5 sprays of ketamine 10 mg, 0.2–0.4 mg/kg (S)-ketamine, and single dose ketamine 25 mg every 6 hours as needed) as a treatment for breakthrough pain.

From a clinical practice perspective, oral ketamine has significant abuse potential and a high street value. For these reasons, in patients with a history of abuse or who are at high risk of abuse, the risks of prescribing it chronically in a community-based setting should be weighed against the potential benefits, and proper surveillance, similar to what is done for patients on chronic opioid therapy, should be used.

There is insufficient evidence supporting preinfusion testing prior to the administration of IV ketamine for chronic neuropathic pain conditions in healthy individuals. In individuals at high risk of cardiovascular events or symptoms suggestive of cardiovascular disease, baseline ECG testing may be considered to exclude individuals with uncontrolled ischemic heart disease.

In individuals with baseline liver dysfunction, at risk of liver toxicity (eg, alcohol abusers, people with chronic hepatitis), or who are expected to receive high doses of ketamine at frequent intervals, baseline and postinfusion liver function tests should be considered on a case-by-case basis.

This panel agrees with the APA recommendation that only a licensed physician who can administer a Drug Enforcement Administration Schedule III medication with Advanced Cardiac Life Support certification be in charge of administering ketamine, but because of the higher dosages used for chronic pain, we believe that person should also meet ASA requirements for the delivery of moderate sedation. For the person who actually administers subanesthetic IV bolus sedation, recommended credentials include a registered nursing degree with Advanced Cardiac Life Support certification, along with training in the administration of moderate sedation and specifically the pharmacology of ketamine. The training can be via courses given internally or by accredited organizations (eg, American Association of Moderate Sedation Nurses).

There is limited direct evidence supporting the preemptive use of benzodiazepines and α2 agonists and no evidence to support antidepressant, antihistamine, or anticholinergic premedicants prior to the initiation of subanesthetic ketamine for chronic pain treatment.

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