Ketamine Infusions for Chronic Pain Clinical Practice Guidelines

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.