An Effective Alternative to Opioids for Acute Pain?

Fran Lowry

April 29, 2021

Intranasal (IN) ketamine may be a safe and effective alternative to intravenous opioids for acute pain in adult patients, new research suggests.

In a systematic literature review of 15 studies that included 2218 adult patients, IN ketamine was associated with improved pain scores.

Dr Anne Hermon

"While covering the acute pain service, myself and my co-author, Dr Nadkarni [Anisha Nadkarni, MD] noticed how effective intravenous ketamine was in treating acute postoperative pain, even in adult patients with chronic pain who were not opioid naive," study investigator Anne Hermon, MD, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.

"We knew ketamine has multiple routes of administration and wanted to identify whether intranasal ketamine could prove to be a safe and effective alternative to opioids. We did a basic literature search and found that IN ketamine has been used to treat acute pain in multiple settings and patient populations, and we wanted to do a more extensive review," she added.

The findings were presented at the virtual American Academy of Pain Medicine (AAPM) 2021 Annual Meeting.

Early Promise

Using as keywords "ketamine" and "acute pain," the researchers conducted a literature search of three popular medical databases for studies published through June 2020.

Studies were included in the review if they detailed primary outcomes related to IN ketamine for the management of acute pain. Exclusion criteria included primary outcomes related to procedural sedation, intraoperative analgesia, neuropathic pain, chronic pain, depression, or other psychiatric problems.

Of the 15 articles that met the inclusion criteria, 12 were prospective randomized control trials, and three were observational studies. The studies included a total of 2218 adolescent and adult patients aged 15 years and older. Ketamine doses ranged from 0.4 mg/kg to 84 mg/kg.

The most common methods for evaluating pain were the Visual Analogue Scale, which was used in 12 studies, and the Numeric Rating Scale, which was used in three studies.

Intravenous ketamine was used in the following settings:

  • paramedic administration (1)

  • emergency department (11)

  • wound dressing changes (1)

  • post dental surgery (1)

  • post spinal surgery (1)

In all studies reviewed, pain scores significantly improved with use of IN ketamine.

Five studies compared IN ketamine to IV opioids. None showed IN ketamine to be significantly more effective, but 75% demonstrated similar efficacy.

"Due to a limited number of articles and heterogeneity in both study types and methods, we were unable to perform a meta-analysis," Hermon said.

"We look forward to seeing prospective randomized control trials comparing IN ketamine to opioids in the post-op and post-discharge period," she said.

If such research indicates that IN ketamine effectively reduces pain, there would be reason to explore it as an adjunct or substitute for opioids to manage pain post discharge, she added.

"In the context of an ongoing opioid epidemic, it is important to identify strategies to mitigate the harm that opioids can cause. By targeting the postoperative period, when many people are exposed to opioids for the first time, there is potential to limit the number of patients who become opioid dependent," she said.

Dr W. Michael Hooten

Commenting on the study for Medscape Medical News, W. Michael Hooten, MD, professor of anesthesiology, Mayo Clinic, Rochester, Minnesota, and president-elect of the AAPM, noted that in only one of the included studies was IN ketamine used for acute postoperative pain, indicating that "an unrecognized knowledge gap exists in this important area of clinical practice."

Hooten agreed that randomized controlled trials are needed to further investigate the efficacy, appropriate dose, and appropriate duration of treatment with IN ketamine for acute postoperative pain.

Hermon and Hooten report no relevant financial relationships.

American Academy of Pain Medicine (AAPM) 2021 Annual Meeting.

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