NMDA Receptor Antagonists, Gabapentinoids, α-2 Agonists, and Dexamethasone and Other Non-Opioid Adjuvants: Do They...

Inadequate pain control and opioid-related adverse effects result in delayed patient recovery and discharge times. Adjuvants help to improve the quality of analgesia and decrease opioid consumption, consequently decreasing opioid-related effects, such as nausea and vomiting, sedation, ileus, and respiratory depression. We review the mechanisms and clinical evidence for nonopioid adjuvants.

MEDLINE, EMBASE, and the Cochrane Register were searched for meta-analyses, systematic reviews, and randomized, controlled trials that compared the adjuvants ketamine, gabapentin, pregabalin, dexmedetomidine, clonidine, and dexamethasone with placebo. Keywords used in the search included "plastic surgery," "reconstructive surgery," "opioid," "pain," "analgesia," and the names of each adjuvant. The references of included studies were searched for additional relevant studies.

Ketamine was found in 6 meta-analyses to have a significant reduction in opioid requirements and may reduce the hyperalgesia associated with opioids. This seems to be most beneficial in surgeries where high postoperative pain is expected. Multiple robust trials have demonstrated that the gabapentinoids and α-2 agonists significantly improve quality of analgesia and decrease opioid consumption. Two recent meta-analyses found that a single low-dose of dexamethasone used for postoperative nausea and vomiting prophylaxis may also improve postoperative analgesia. There is also emerging evidence for the use of low-dose naloxone, adenosine, and neuraxial neostigmine and acupuncture as part of a successful multimodal pain management regimen.

Although there is a lack of studies specifically focused in the plastic and reconstructive surgery patient population, the existing literature provides information about when the above adjuvants are likely to have the greatest impact.