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Three Part Question

In Children with moderate to severe pain brought to the emergency department] would [nasal Ketamine be better than nasal Fentanyl] at [sedation, pain management]

Clinical Scenario

The mother of a 3-year-old boy, who was in excruciating pain and distress, accompanied him to the emergency room. The mother recounts the sequence of events: The boy's goal was to get his cereal from the cupboard. In order to reach it, he stood on a chair, which unfortunately toppled over, causing him to strike the underside of his chin against the corner of a table. When medical staff entered the room, the child would cry out loud, and the mother said that the boy had a large, heavily bleeding cut under his chin. Out of two medications you may use to sedate the youngster before examination and therapy, which would you prefer: nasal ketamine or nasal fentanyl?

Search Strategy

PubMed using Mesh
Web of Science

(((((("Child"[Mesh] OR "Child*" [tw] OR "preschool"[tw] OR "children"[tw] OR "paed*"[tw]) AND ("Acute Pain"[Mesh] OR "distress" [tw] OR "acute pain*" [tw])) AND ("Nasal Sprays"[Mesh] OR "nasal* mist" [tw] OR "nasal aerosol"[tw] OR "intranasal"[tw])) AND ("Ketamine"[Mesh] OR "ketalar*" [tw] OR "Ketaset"[tw] OR "calipsol" [tw])) OR ("Fentanyl"[Mesh] OR "Alfentanil" [tw] OR "Sufentanil"[tw])) AND ("pain management"[MeSH] OR "mild sedation*" [tw] OR "pain management*" [tw])) AND ("Emergency setting" [tw])
("pain management"[MeSH Terms] OR ("pain"[All Fields] AND "management"[All Fields]) OR "pain management"[All Fields]) AND ("child"[MeSH Terms] OR "child"[All Fields] OR "children"[All Fields]) AND ("acute pain"[MeSH Terms] OR ("acute"[All Fields] AND "pain"[All Fields]) OR "acute pain"[All Fields]) AND intranasal[All Fields] AND ("fentanyl"[MeSH Terms] OR "fentanyl"[All Fields]) AND vs[All Fields] AND Intranasal[All Fields] AND ("Esketamine"[Supplementary Concept] OR "Esketamine"[All Fields] OR "ketamine"[All Fields] OR "ketamine"[MeSH Terms])
Web Of Science
pain management nasal ketamine (Title) OR Fentanyl (Title) AND in Children (Title) and Intranasal (Should – Search within topic) and Emergency Department (Should – Search within topic) and Analgesia (Should – Search within topic) and Or Fentanyl (Should – Search Within topic)

Search Outcome

A total of 38 articles were retrieved. After reading the abstracts, only five articles were deemed relevant to the subject. Both the PICHFORK and PRIME randomized trials included a substantial patient population, ensuring sufficient data for a meaningful outcomes.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Frey, T. M. Florin, T. A. Caruso, M. Zhang, N. Zhang, Y. Mittiga, M. R. 2019 Cincinnati	90 Children aged 8–17 years of age presenting to the emergency department with moderate to severe pain treated with intranasal Ketamine 1.5mg/kg or intranasal fentanyl 2 mg/kg, respectively	A randomized clinical trial	Time duration for a decrease in pain levels	30 minutes after the medication the pain VAS was 30.6mm (95% CI, 25.4 - 35.8) for Ketamine and 31.9mm (95% CI, 26.6 - 37.2) for Fentanyl	Prior pain management by pre-hospital staff. focused study of only muscular and skeletal injuries routine co-administration of 10 mg/kg ibuprofen orally, limiting the precision of the pain score. convenience sampling with no data on missed eligible patients Convenience sampling can introduce sampling bias and selection bias.
			is ketamine inferior to Fentanyl	Ketamine is noninferior to fentanyl
Graudins, A. Meek, R. Egerton-Warburton, D. Oakley, E. Seith, R. 2015 Australia	80 Children age 3–13 that weigh less than 50kg with an isolated musculoskeletal injury and pain of more than 6 out of 10 at triage. Given 1.5ug/kg Fentanyl or ketamine at 1mg/kg intranasal	prospective, randomized, controlled, double-blind equivalence trial	median reduction in the VAS pain score at 30minutes	after 30 minutes, median reduction for ketamine and fentanyl were 45 and 40mm, respectively (difference 5mm; 95% [CI] - 10 to 20mm)	was a convenience sampling study that left the possibility of selection bias. Some patients received prior pain management by pre-hospital staff. Focused study of only muscular skeletal injuries.
			VAS change in pain severity at 15minutes and 60miutes	pain rating reduction was maintained at 60minutes in both groups

Comment(s)

The result of this rapid search was to discover if ketamine may also be utilized to treat anxiety and control pain in kids. There has been a lot of research done on controlling pain in cancer patients, but not enough was done on the above 3-part question. Providing intranasal analgesia in pediatrics is a frequent procedure in the emergency department these days; however, fentanyl was the favored agent at the time. The preceding research suggests that ketamine can also be used to alleviate pain effectively.

Clinical Bottom Line

Insufficient pain control in the pre-hospital environment remains a significant issue, despite heightened awareness. Due to the necessity of securing an intravenous (IV) line, paramedics continue to undertreat pain, especially in children. These studies have demonstrated that intranasal ketamine provides good pain relief and is comparable to fentanyl, the current preferred medication of choice. Ketamine could serve as a suitable substitute for fentanyl. Ketamine exhibits a swift initiation of effects, causes minimal discomfort, and is relatively straightforward to give.

References

1. Frey, T. M. Florin, T. A. Caruso, M. Zhang, N. Zhang, Y. Mittiga, M. R. Effect of Intranasal Ketamine vs Fentanyl on Pain Reduction for Extremity Injuries in Children The PRIME Randomized Clinical Trial JAMA Pediatrics 2019; 140 -146
2. Graudins, A. Meek, R. Egerton-Warburton, D. Oakley, E. Seith, R. The PICHFORK (Pain in Children Fentanyl or Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine and Fentanyl for the Relief of Moderate to Severe Pain in Children With Limb Inj Ann Emerg Med 2015 Mar;65(3):248-254.e1.