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Review Article
Online Published: 18 Jun 2026
 


Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review

Abdullah Khaled Aldakhel, Ali Saud Alsaud, Mohammed Khaled Aldakhel, Rayan Mohammed Alsuhaibani, Majed Fahad A Alharbi, Jawad Ali Alduraibi, Haitham Shaffaqah Alanazi, Bader Sulaiman Althunayyan, Khaled Mounir Almoutairi, Muhammed Fahad Almishali, Mohammed Yousef Alfurayhi.


Abstract
Acute pain is a common reason for pediatric emergency department presentation, yet it remains frequently undertreated. Intranasal fentanyl is an established initial analgesic in this setting, but concerns about opioid-related adverse effects have increased interest in opioid-sparing alternatives. Intranasal sub-dissociative ketamine has shown promise, although direct comparisons with fentanyl remain limited. This systematic review compared the efficacy, onset of analgesia, need for rescue medication, and side-effect profile of intranasal ketamine versus intranasal fentanyl in children presenting to the emergency department with acute moderate to severe pain. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. PubMed, Web of Science, and EBSCO databases were searched up to March 30, 2026. Eligible studies were randomized controlled trials involving children aged 0-18 years, and risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Four randomized controlled trials including 263 patients were analyzed: Graudins et al. PICHFORK trial, Reynolds et al., Quinn et al., and Frey et al. PRIME trial. Both intranasal ketamine and intranasal fentanyl produced clinically meaningful pain reduction from baseline, with no statistically significant difference in primary analgesic outcomes. In the PRIME trial, ketamine was declared non-inferior to fentanyl, with a pain-score improvement difference of 1.3 millimeters, within the predefined 10-millimeter margin. Rescue analgesia use was similar between groups. Side effects were more frequent with ketamine but were minor, transient, and required no intervention. No serious adverse events occurred. Overall, intranasal ketamine appears to be a clinically effective and manageable opioid-sparing alternative to intranasal fentanyl in pediatric emergency pain management.

Key words: Intranasal ketamine, intranasal fentanyl, pediatric emergency department, acute pain, opioid-sparing, systematic review


 
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How to Cite this Article
Pubmed Style

Aldakhel AK, Alsaud AS, Aldakhel MK, Alsuhaibani RM, Alharbi MFA, Alduraibi JA, Alanazi HS, Althunayyan BS, Almoutairi KM, Almishali MF, Alfurayhi MY. Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. IJMDC. Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245

Web Style

Aldakhel AK, Alsaud AS, Aldakhel MK, Alsuhaibani RM, Alharbi MFA, Alduraibi JA, Alanazi HS, Althunayyan BS, Almoutairi KM, Almishali MF, Alfurayhi MY. Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. https://www.ijmdc.com/?mno=317021 [Access: June 27, 2026]. doi:10.24911/IJMDC.51-1775818245

AMA (American Medical Association) Style

Aldakhel AK, Alsaud AS, Aldakhel MK, Alsuhaibani RM, Alharbi MFA, Alduraibi JA, Alanazi HS, Althunayyan BS, Almoutairi KM, Almishali MF, Alfurayhi MY. Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. IJMDC. Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245


Vancouver/ICMJE Style

Aldakhel AK, Alsaud AS, Aldakhel MK, Alsuhaibani RM, Alharbi MFA, Alduraibi JA, Alanazi HS, Althunayyan BS, Almoutairi KM, Almishali MF, Alfurayhi MY. Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. IJMDC, [cited June 27, 2026]; Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245


Harvard Style

Aldakhel, A. K., Alsaud, . A. S., Aldakhel, . M. K., Alsuhaibani, . R. M., Alharbi, . M. F. A., Alduraibi, . J. A., Alanazi, . H. S., Althunayyan, . B. S., Almoutairi, . K. M., Almishali, . M. F. & Alfurayhi, . M. Y. (2026) Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. IJMDC, Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245


Turabian Style

Aldakhel, Abdullah Khaled, Ali Saud Alsaud, Mohammed Khaled Aldakhel, Rayan Mohammed Alsuhaibani, Majed Fahad A Alharbi, Jawad Ali Alduraibi, Haitham Shaffaqah Alanazi, Bader Sulaiman Althunayyan, Khaled Mounir Almoutairi, Muhammed Fahad Almishali, and Mohammed Yousef Alfurayhi. 2026. Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. International Journal of Medicine in Developing Countries, Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245


Chicago Style

Aldakhel, Abdullah Khaled, Ali Saud Alsaud, Mohammed Khaled Aldakhel, Rayan Mohammed Alsuhaibani, Majed Fahad A Alharbi, Jawad Ali Alduraibi, Haitham Shaffaqah Alanazi, Bader Sulaiman Althunayyan, Khaled Mounir Almoutairi, Muhammed Fahad Almishali, and Mohammed Yousef Alfurayhi. "Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review." International Journal of Medicine in Developing Countries Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245


MLA (The Modern Language Association) Style

Aldakhel, Abdullah Khaled, Ali Saud Alsaud, Mohammed Khaled Aldakhel, Rayan Mohammed Alsuhaibani, Majed Fahad A Alharbi, Jawad Ali Alduraibi, Haitham Shaffaqah Alanazi, Bader Sulaiman Althunayyan, Khaled Mounir Almoutairi, Muhammed Fahad Almishali, and Mohammed Yousef Alfurayhi. "Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review." International Journal of Medicine in Developing Countries Online First: 18 Jun, 2026. Web. 27 Jun 2026 doi:10.24911/IJMDC.51-1775818245


APA (American Psychological Association) Style

Aldakhel, A. K., Alsaud, . A. S., Aldakhel, . M. K., Alsuhaibani, . R. M., Alharbi, . M. F. A., Alduraibi, . J. A., Alanazi, . H. S., Althunayyan, . B. S., Almoutairi, . K. M., Almishali, . M. F. & Alfurayhi, . M. Y. (2026) Comparative Effectiveness and Safety of Intranasal Fentanyl versus Intranasal Ketamine for Acute Pain Management in Pediatric Emergency Departments: A Systematic Review. International Journal of Medicine in Developing Countries, Online First: 18 Jun, 2026. doi:10.24911/IJMDC.51-1775818245




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