Ketamine and opioids

There is level I evidence from studies of acute postoperative pain that ketamine is opioid-sparing, without significantly reducing pain scores or the incidence of opioid-adverse events.77 However, ketamine is useful in the treatment of opioid nonresponsive (opioid tolerance or hyperalgesia) acute or cancer pain (as burst therapy), or in neuropathic, or visceral pain. The role of ketamine in pain management is as an antihyperalgesic, anti-allodynic, and tolerance-protective agent, rather than as an analgesic per se.78

Practically speaking, a short-term parenteral ketamine infusion may be useful in the treatment of severe breakthrough or incident pain (such as surgery), in patients on long-term opioid therapy. The use of regular sublingual or oral ketamine lozenges reduces opioid requirements and improves analgesia in selected patients with severe CNCP, although this practice has yet to be validated (personal data).

and the development of opioid tolerance, dependence, and withdrawal. The addition of low-dose methadone to morphine may have specific beneficial effects by inducing this protective endocytosis mechanism.87 It is interesting to note that most animal and human studies of COOA have used morphine as the baseline opioid, adding in low-dose oxycodone, methadone, fentanyl, tramadol, or antagonists such as naltrexone.

Conceptually, COOA is a form of partial opioid rotation with similar indications, particularly the management of reduced analgesic efficacy. However, further clinical trials are required to determine if COOA is truly beneficial in pain management.

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