Published: 25. August, 2023

Based on new findings in a 2023 meta-analysis by Fjendbo Galili et al., which…

Based on new findings in a 2023 meta-analysis by Fjendbo Galili et al., which supports the previous 2016 meta-analysis by Michelet et al., there is now further evidence to support combining low doses of ketamine and opioids, such as sufentanil, in an intranasal spray for acute pain management:

  • The 2016 Michelet meta-analysis did not find a significant opioid-sparing effect of ketamine in children but was likely underpowered. It suggested further studies were needed with at least 188 more patients to draw conclusions.
  • The new 2023 meta-analysis by Fjendbo Galili et al. included more studies and found adjuvant subanesthetic ketamine does provide a significant reduction in pain scores at 60 minutes compared to opioids alone. It also reduces opioid requirements without increasing side effects.
  • Both reviews note ketamine’s synergistic effects with opioids for acute pain and its ability to counter opioid tolerance. The 2016 analysis highlighted ketamine’s lack of increased adverse events like nausea, vomiting or hallucinations.
  • Previous evidence already supported intranasal delivery for rapid analgesic onset. Sufentanil is suitable for intranasal use.
  • By combining intranasal ketamine and sufentanil in low doses, it may be possible to provide effective acute pain relief while avoiding side effects and reducing opioid needs compared to monotherapy.

In summary, the accumulating evidence confirms ketamine’s utility as a low-dose adjuvant to opioids like sufentanil for acute pain when given intranasally. The updated 2023 meta-analysis provides further support that this combination can improve pain relief and reduce opioid requirements without increasing adverse effects. Additional randomized controlled trials are still needed to confirm the optimal intranasal ketamine-sufentanil doses, stay tuned for updates on Cessatech’s pipeline.


Michelet, D., Hilly, J., Skhiri, A. et al., 2016. Opioid-Sparing Effect of Ketamine in Children: A Meta-Analysis and Trial Sequential Analysis of Published Studies. Pediatric Drugs, 18(5), pp.343–354. Link to article

Fjendbo Galili, S., Nikolajsen, L. and Papadomanolakis-Pakis, N., 2023. Subanaesthetic single-dose ketamine as an adjunct to opioid analgesics for acute pain management in the emergency department: a systematic review and meta-analysis. BMJ Open, 13(3), p.e066444. Link to article