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Weight of evidence favours ketamine for children having fracture reduction

BMJ 2006; 332 doi: (Published 06 April 2006) Cite this as: BMJ 2006;332:0-e

Research question What is the best way to provide sedation and pain relief to children having a fracture reduced in the emergency department?

Answer It's hard to say for certain, but for systemic sedation and pain relief, ketamine plus midazolam seems safer and more effective than other combinations.

Why did the authors do the study? No consensus exists on the best way to provide children with sedation and pain relief during fracture reductions in the emergency department. These authors wanted to weigh up all the randomised evidence comparing different methods of sedation and pain relief to find out which was the safest and most effective.

What did they do? They systematically searched research databases including Medline, the Cochrane Collaboration and Clinical Trials Database, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) for randomised controlled trials published in English. They also hand searched reference lists and made limited attempts to find relevant unpublished trials. They included all comparative trials that were adequately randomised, whether or not blinding had been attempted.

The authors found eight relevant trials, but they were too heterogeneous to combine in a meta-analysis. Instead, they extracted and compared data on pain reported by children after various forms of sedation and analgesia. They also looked for data on surrogate measures for pain, such as patient or parent satisfaction, and for data on complications such as apnoea and hypotension.

What did they find? Eight randomised controlled trials were included in this systematic review. The data on biers blocks (regional anaesthesia) and nitrous oxide were too limited to make useful comparisons.

Of the intravenous combinations, ketamine plus midazolam seemed to work best, providing better pain relief with fewer respiratory complications than midazolam plus fentanyl or propofol plus fentanyl. In the biggest trial (n = 260), children given ketamine plus midazolam were less likely to have hypoxia (6% v 25%, P < 0.001), had significantly lower pain scores, and significantly lower parental anxiety scores than children given midazolam plus fentanyl. But they took significantly longer to recover (127.6 (SD 56.2) minutes v 113.7 (36.9); P = 0.05). Ketamine was not associated with an increased risk of agitation in this trial, but it did cause more vomiting than midazolam plus fentanyl. In a second, smaller trial (n = 113) ketamine plus midazolam was associated with less distress, fewer respiratory problems, and a longer recovery time than propofol plus fentanyl.

What does it mean? Although the weight of evidence in this review favours the ketamine plus midazolam combination for these children, the overall body of research is too weak to be conclusive. The trials were generally small and used different, often unvalidated outcome scores. Few were adequately blinded, so it's hard to rule out bias. Ketamine, etomidate, propofol, and nitrous oxide all need further study, say the authors, preferably in big trials using standardised instruments such as the Children's Hospital of Eastern Ontario pain score.

Migita RT et al. Sedation and analgesia for pediatric fracture reduction in the emergency department: a systematic review. Arch Pediatr Adolesc Med 2006;160: 46-51

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