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Network meta-analysis of ketamine regimens for pediatric ED procedural sedation safety and efficacyKetamine combos ease pain in kids with less nausea

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Key Takeaway
Note that IM ketamine prolongs sedation and recovery, while IV ketamine with midazolam increases hypoxia risk.

This network meta-analysis assessed the safety and efficacy of various ketamine-based regimens compared to IV ketamine for sedating pediatric patients during painful emergency department procedures. The analysis synthesized data from 24 randomized controlled trials to compare outcomes across different administration routes and adjunctive medications.

Results indicate that intramuscular ketamine is associated with longer sedation duration compared to IV ketamine, with a mean difference of +19.6 minutes (95% CI 17.5-21.6). Recovery time is also extended with intramuscular administration, showing a mean difference of +37.7 minutes (95% CI 1.6-73.8). When atropine is added to intramuscular ketamine, recovery time increases further by a mean difference of +73.5 minutes (95% CI 10.9-136.1).

Regarding adverse events, the combination of IV ketamine and midazolam significantly raised the risk of hypoxia, with a relative risk of 4.71 (95% CI 1.05-21.08). Conversely, adding propofol to IV ketamine reduced the risk of nausea, with a relative risk of 0.34 (95% CI 0.17-0.68). Intramuscular ketamine also demonstrated a lower risk of emergence reactions compared to IV ketamine, with a relative risk of 0.38 (95% CI 0.20-0.69).

The authors note that follow-up duration was not reported for the included studies. Serious adverse events, discontinuations, and overall tolerability were not reported in the source data. While the network meta-analysis provides comparative insights, the absence of reported follow-up and specific safety metrics limits the ability to fully assess long-term outcomes or rare adverse events in this pediatric population.

This doesn't mean this treatment is available yet.

One shot, two paths Ketamine given by muscle injection does its job deeply and lasts longer. That sounds good. But it also means kids take much longer to wake up—nearly 38 minutes more than IV ketamine. And adding atropine, a common drug to prevent saliva buildup, makes recovery even slower. That’s tough on parents waiting in the hall.

On the flip side, IV ketamine acts faster. But used alone, it raises the risk of low oxygen levels. Midazolam, another sedative, makes this worse. The data shows IV ketamine with midazolam nearly five times more likely to cause breathing issues. That’s a real danger in a busy ER.

The magic mix The standout winner? Ketamine plus propofol. Kids who got both had strong sedation, woke up quicker, and were far less likely to vomit. The combo cut nausea risk by more than half. It also avoided the breathing problems seen with other mixes.

This matters because nausea isn’t just uncomfortable. It can lead to choking, longer stays, and fear of future care. A calmer recovery means less stress for the child and the team.

But there's a catch. Propofol isn’t approved for sedation in all pediatric cases. It carries its own risks if not given carefully. And most of the studies reviewed were small. Some didn’t track long-term effects or included only certain age groups. So while the results are promising, they’re not a one-size-fits-all answer.

Experts say this analysis adds strong evidence for rethinking how we sedate kids. For years, ketamine stood alone as the gold standard. Now, we’re seeing the value of smart combinations. The goal isn’t just to sedate—it’s to protect the child’s whole experience.

What this means for families If your child needs emergency sedation, ask what drugs are being used. Ketamine alone may still work well in some cases. But if faster recovery and less nausea are priorities, the ketamine-propofol combo could be worth discussing. It’s not yet standard everywhere, but more ERs are starting to adopt it.

The biggest limit? Most data comes from short-term observations. We don’t yet know how these regimens affect kids over time. Also, IV access isn’t always easy in crying or injured children. That’s why muscle shots are still common.

The road ahead More large-scale trials are needed to confirm the best mix and dose. Researchers are now looking at how age, weight, and injury type affect outcomes. Some hospitals are already updating their sedation guidelines based on this evidence. Approval for broader use of propofol in kids could take years, but the momentum is building.

For now, the message is clear: combining ketamine with other drugs isn’t just possible—it may be better. And for a scared child in pain, a gentler, smoother sedation could make all the difference.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedApr 2026
View Original Abstract ↓
The purpose of this study is to compare the safety and efficacy of different ketamine-based regimens for emergence pediatric procedural sedation. We searched PubMed, Scopus, and Web of Science for RCTs enrolling pediatric patients undergoing painful procedures in the emergency department. Studies comparing ketamine alone with ketamine combined with other sedatives or alternative agents were included. A frequentist random effects NMA was conducted using R (netmeta package). Results were expressed as mean differences (MD) or risk ratios (RR) with 95% confidence intervals, and treatments were ranked according to relative efficacy and safety. A total of 24 RCTs were included in this NMA. Using IV ketamine as the reference, IM ketamine was associated with longer sedation (MD + 19.6 min, 95% CI 17.5-21.6) and longer recovery times (MD + 37.7 min, 95% CI 1.6-73.8). Recovery time was extended even further when atropine was added to IM ketamine (MD + 73.5 min, 95% CI 10.9-136.1). IM ketamine was associated with less emergence reactions (RR = 0.38, 95% CI 0.20-0.69). Regarding the adverse events, IV ketamine and midazolam significantly raised the risk of hypoxia (RR = 4.71, 95% CI 1.05-21.08), whereas the combination of IV ketamine with propofol led to less nausea (RR = 0.34, 95% CI 0.17-0.68). In conclusion, across ketamine-based sedation regimens, IM administration achieved deeper and longer sedation but was accompanied by prolonged recovery. IV combinations offered faster recovery and fewer emetic events. Among these, ketamine combined with propofol provided the most balanced profile, maintaining sedation efficacy while minimizing nausea and hypoxia.
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