Elsevier

Annals of Emergency Medicine

Volume 54, Issue 2, August 2009, Pages 158-168.e4
Annals of Emergency Medicine

Pediatrics/original research
Predictors of Airway and Respiratory Adverse Events With Ketamine Sedation in the Emergency Department: An Individual-Patient Data Meta-analysis of 8,282 Children

https://doi.org/10.1016/j.annemergmed.2008.12.011Get rights and content

Study objective

Although ketamine is one of the most commonly used sedatives to facilitate painful procedures for children in the emergency department (ED), existing studies have not been large enough to identify clinical factors that are predictive of uncommon airway and respiratory adverse events.

Methods

We pooled individual-patient data from 32 ED studies and performed multiple logistic regressions to determine which clinical variables would predict airway and respiratory adverse events.

Results

In 8,282 pediatric ketamine sedations, the overall incidence of airway and respiratory adverse events was 3.9%, with the following significant independent predictors: younger than 2 years (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.47 to 2.72), aged 13 years or older (OR 2.72; 95% CI 1.97 to 3.75), high intravenous dosing (initial dose ≥2.5 mg/kg or total dose ≥5.0 mg/kg; OR 2.18; 95% CI 1.59 to 2.99), coadministered anticholinergic (OR 1.82; 95% CI 1.36 to 2.42), and coadministered benzodiazepine (OR 1.39; 95% CI 1.08 to 1.78). Variables without independent association included oropharyngeal procedures, underlying physical illness (American Society of Anesthesiologists class ≥3), and the choice of intravenous versus intramuscular route.

Conclusion

Risk factors that predict ketamine-associated airway and respiratory adverse events are high intravenous doses, administration to children younger than 2 years or aged 13 years or older, and the use of coadministered anticholinergics or benzodiazepines.

Introduction

The efficacy and safety of ketamine to facilitate painful procedures for children in the emergency department (ED) have been documented in 57 published series totaling nearly 10,000 patients.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 This dissociative agent is the most commonly used sedative in the United States for this indication.58, 59, 60, 61, 62, 63, 64 Airway and respiratory adverse events occur in 1.4% to 6.6% of ketamine sedations,2, 19 including laryngospasm in approximately 0.4%.2 Given the rarity of these airway events, previous investigations have, because of their small size, been unable to determine whether they are related to ketamine dose, administration route, or coadministered drugs (eg, anticholinergics, benzodiazepines) or whether they are related to patient variables such as age or underlying illness.55

If specific differences in ketamine technique or patient variables are predictive of airway adverse events, then emergency physicians may elect to modify their administration technique or patient selection to minimize such adverse events.

We pooled original data from all available series of ED ketamine sedation in children to identify clinical predictors of airway and respiratory adverse events. Secondary goals were to perform similar analyses for the subsets of children with laryngospasm and apnea.

Section snippets

Study Design

We performed a meta-analysis in accordance with Quality of Reporting of Meta-analyses (QUOROM) guidelines65 of all available original data from existing ketamine case series. All included trials had local ethics committee approval.

We searched the PubMed electronic database for articles of any language published between 1966 and May 2008, using the key words “ketamine” and “emergency.” The reference lists of identified articles were examined for additional studies missed by the MEDLINE search.

Results

The results of the literature search and article processing are shown in Figure 1. Data from 32 reports were ultimately included (Table 1), comprising 8,353 aggregate ketamine sedations. We then excluded 71 individual sedations (0.85%) from the overall database for the following reasons: missing total ketamine dose (n=47), missing documentation of benzodiazepine use (n=12), use for intubation rather than procedural sedation (n=10), missing age (n=1), and age greater than 21 years (n=1). There

Limitations

The principal limitation of this report is the heterogeneity of the collated studies and the observational nature of the data. Although the studies are similar in that they include children receiving ketamine for ED procedures, there is substantial variation in procedural indications, ages, doses, and other clinical variables, as might be expected from 32 studies coming from multiple countries. As shown in Table 1, there were differences in the rates of outcome measures between studies; these

Discussion

In this original-data meta-analysis of 8,282 sedations collated from 32 previously published series, we report the largest ED ketamine sample to date. In contrast to a previous study of 1,021 children that failed to identify any significant predictors of ketamine-associated airway and respiratory adverse events,55 our much larger study identified multiple independent predictors of such events. Clinicians can use these findings to modify their patient selection, dosing, and use of coadministered

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      Citation Excerpt :

      Although ketamine is known to be associated with vomiting and respiratory adverse events,26 the literature is conflicted about this risk being dose dependent. Green et al2 reported dose-dependent increased odds of ketamine-associated respiratory adverse events. A multicenter study also reported increased odds of both vomiting and desaturations with increased ketamine dosages.6

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    Provide feedback on this article at the journal's Web site, www.annemergmed.com.

    Supervising editors: Kathy N. Shaw, MD, MSCE; Michael L. Callaham, MD.

    Drs. Shaw and Callaham were the supervising editors on this article. Dr. Green did not participate in the editorial review or decision to publish this article.

    Author contributions: SMG conceived and designed the study. The methodology was critiqued and revised with extensive input from MGR, BK, LB, DA, RDP, JEW, and GT. All authors reviewed and recoded their data to comply with study definitions, and before data analysis the study protocol was critiqued and refined by all authors. SMG performed the data analysis, and a writing committee composed of SMG, MGR, and BK then created the article. All authors critiqued the draft, and there were substantial revisions. SMG takes responsibility for the paper as a whole.

    Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement.

    Earn CME Credit: Continuing Medical Education is available for this article at: www.ACEP-EMedHome.com.

    Publication date: Available online February 7, 2009.

    Reprints not available from the authors.

    All members are listed in the Appendix.

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