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Oliveira J E Silva L, Lee JY, Bellolio F, et al. Intranasal ketamine for acute pain management in children: A systematic review and meta-analysis. Am J Emerg Med. 2020 Jun 1;38(9):1860-1866. doi: 10.1016/j.ajem.2020.05.094. (Systematic review)
Abstract

STUDY OBJECTIVE: To assess the efficacy and safety of intranasal analgesic-dose ketamine as compared to intranasal fentanyl for pediatric acute pain.

METHODS: A systematic review and meta-analysis was performed following the PRISMA guidelines. We searched PubMed, Embase, and Scopus databases for randomized controlled trials from inception to December 2019. We conducted meta-analysis with random-effects models to evaluate pain reduction, rescue analgesia, adverse events and sedation between intranasal ketamine and intranasal fentanyl. Random-effects models were used to estimate weighted mean differences (WMD) and pooled relative risks (RR).

RESULTS: A total of 546 studies were screened and 4 trials were included. In the meta-analysis of 4 studies including 276 patients, ketamine had similar reductions in pain scores from baseline to all post-intervention times (10 to 15?min: WMD -1.42, 95% CI -9.95 to 7.10; 30?min: WMD 0.40, 95% CI -6.29 to 7.10; 60?min: WMD -0.64, 95% CI -6.76 to 5.47). Ketamine was associated with similar rates of rescue analgesia (RR 0.74, 95% CI 0.44 to 1.25). Ketamine had a higher risk of non-serious adverse events (RR 2.00, 95% CI 1.43 to 2.79), and no patients receiving ketamine had a serious adverse event. There was one serious adverse event (hypotension) with fentanyl that self-resolved. No patients receiving either IN fentanyl or ketamine had significant sedation.

CONCLUSION: Intranasal analgesic-dose ketamine may be considered as an alternative to opioids for acute pain management in children. Its accepted use will depend on the tolerability of non-serious adverse events and the desire to avoid opioids.


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Ratings
Discipline Area Score
Emergency Medicine 7 / 7
Pediatric Hospital Medicine 6 / 7
Pediatric Emergency Medicine 6 / 7
Special Interest - Pain -- Physician 6 / 7
Comments from MORE raters

Emergency Medicine rater

This systematic review and meta analysis demonstrates similar pain relief with intranasal administration of ketamine compared to fentanyl in children. Nonserious adverse events and mild sedation were more common with ketamine. I see no need to look for a reason to routinely use intranasal ketamine for pain in children or adults, though it is effective and can be used as a backup strategy in some cases.

Emergency Medicine rater

The PICO question of this meta-analysis is, "in children with painful conditions (excluding sickle cell crisis), does intranasal ketamine compared to fentanyl reduce pain without adverse effects? The search was exhaustive. The risk of bias in the included studies was low. The 4 studies showed no difference in analgesia at 15, 30 and 60 minutes and no difference in the need for rescue analgesia. However, ketamine had about a two-fold higher risk of sedation and adverse events (none of them serious) than fentanyl. The number needed to treat to prevent one sedation or adverse event for fentanyl vs. ketamine was 4.2 and 2.5, respectively. The overall conclusion is that there is no difference in pain control, but ketamine causes more sedation and adverse events than fentanyl; although, it obviously avoids exposure to opioids.

Pediatric Emergency Medicine rater

This systematic review provides some evidence that IN ketamine is similar to IN fentanyl: it would be interesting to know how it compares to IV ketamine or other agents. It is a relatively small review, and I couldn't figure out if they included foreign language literature, which might be important with a drug like ketamine.

Pediatric Emergency Medicine rater

IN Ketamine is noninferior to IN Fentanyl for sedation in ED in this meta-analysis. Most patients were of extremity injury requiring analgesia.

Pediatric Emergency Medicine rater

Although children under 3 are not included, it is promising to see the emergence of a non-opioid rapid-onset pain medication that works similarly to fentanyl. I'd like to see more information about more subtle sedation side effects (rather than simply not unrousable or significantly sedated), and wonder if that use of IN ketamine impacts choice of medication and dose for procedural sedation.

Special Interest - Pain -- Physician rater

The SR shows very little basis for choosing between the two options. The determinant for many will be simply the degree of opiate aversion in the ED.
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