Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists

Abstract

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Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain

“…In conclusion, ketamine has been used for the treatment of chronic pain and depression, and there are common factors that indicate neurophysiological overlap between the two diseases 2. So it is not that surprising that the efficacy of (2R,6R)-HNK in a mouse depression model would carry over to mouse pain models.…”

“…So, ketamine infusion does have effectiveness in CRPS1 mice, but in our bolus protocol (2R,6R)-HNK was the more potent compound. A recent clinical review of intravenous ketamine infusion in chronic pain patients showed some efficacy, but higher dosages and more frequent infusions were associated with greater risks of adverse events 2. That is why there is a need for an alternative to ketamine itself.…”

“…Over the past two decades, the use of intravenous ketamine infusions as a treatment for chronic pain has increased dramatically, with wide variation in patient selection, dosing and monitoring. Short-term intravenous infusions of ketamine have been shown to reduce chronic pain for days or weeks afterwards, although not all studies show efficacy 2. However, the adverse events (eg, dissociate side effects) profile of ketamine, and the potential for abuse, makes it difficult to use long term in the chronic pain population even at subanesthetic doses 2.…”

“…Short-term intravenous infusions of ketamine have been shown to reduce chronic pain for days or weeks afterwards, although not all studies show efficacy 2. However, the adverse events (eg, dissociate side effects) profile of ketamine, and the potential for abuse, makes it difficult to use long term in the chronic pain population even at subanesthetic doses 2. In a recent clinical study of oral ketamine administration for postoperative pain, ketamine doses were limited to 1.0 mg/kg, due to hallucinations at higher doses 3…”

“…There are no published studies on the effect of injections of (2R,6R)-HNK in chronic or postoperative pain models. However, there is considerable overlap between chronic pain and depression in terms of both co-prevalence and treatment, with many therapies typically used to treat one being effective for the other, including ketamine 2. A single intraperitoneal injection of ketamine itself has a short-term therapeutic effect in a mice model of complex regional pain syndrome type-1 (CRPS1),7 and clinical infusions of ketamine have been used to treat complex regional pain syndrome 8…”