Pediatrics/original research
Risk Factors for Apnea in Pediatric Patients Transported by Paramedics for Out-of-Hospital Seizure

Presented at the Society for Academic Emergency Medicine Western regional meeting, March 2013, Long Beach, CA.
https://doi.org/10.1016/j.annemergmed.2013.09.015Get rights and content

Study objective

Apnea is a known complication of pediatric seizures, but patient factors that predispose children are unclear. We seek to quantify the risk of apnea attributable to midazolam and identify additional risk factors for apnea in children transported by paramedics for out-of-hospital seizure.

Methods

This is a 2-year retrospective study of pediatric patients transported by paramedics to 2 tertiary care centers. Patients were younger than 15 years and transported by paramedics to the pediatric emergency department (ED) for seizure. Patients with trauma and those with another pediatric ED diagnosis were excluded. Investigators abstracted charts for patient characteristics and predefined risk factors: developmental delay, treatment with antiepileptic medications, and seizure on pediatric ED arrival. Primary outcome was apnea defined as bag-mask ventilation or intubation for apnea by paramedics or by pediatric ED staff within 30 minutes of arrival.

Results

There were 1,584 patients who met inclusion criteria, with a median age of 2.3 years (Interquartile range 1.4 to 5.2 years). Paramedics treated 214 patients (13%) with midazolam. Seventy-one patients had apnea (4.5%): 44 patients were treated with midazolam and 27 patients were not treated with midazolam. After simultaneous evaluation of midazolam administration, age, fever, developmental delay, antiepileptic medication use, and seizure on pediatric ED arrival, 2 independent risk factors for apnea were identified: persistent seizure on arrival (odds ratio [OR]=15; 95% confidence interval [CI] 8 to 27) and administration of field midazolam (OR=4; 95% CI 2 to 7).

Conclusion

We identified 2 risk factors for apnea in children transported for seizure: seizure on arrival to the pediatric ED and out-of-hospital administration of midazolam.

Introduction

Seizure is the most common chief complaint for pediatric patients in the out-of-hospital setting, accounting for approximately 15% of all emergency medical services (EMS) transports of pediatric patients in the United States.1 Given the significant morbidity and mortality from prolonged seizures, including risk of permanent neurologic sequelae, treatment is recommended for any seizure lasting more than 10 minutes.1, 2, 3 The sooner the seizure is treated, the more likely it is to be controlled.1 For this reason, initiating treatment for persistent seizures in the out-of-hospital setting is common practice in EMS systems in the United States. Benzodiazepines are first-line therapy, and their out-of-hospital administration shortens overall seizure duration.4, 5 Traditionally, diazepam was most often used to treat pediatric seizures. However, in the past decade, midazolam has emerged as a favored therapy because of its ease of administration by multiple routes and its rapid onset and clearance, making it less likely to result in adverse effects, including cardiovascular depression and apnea.2, 6, 7, 8 Los Angeles County EMS Agency protocol was changed in July 2009, designating midazolam (through the intravenous, intramuscular, or intranasal route) as the treatment for pediatric seizure.

Editor's Capsule Summary

What is already known on this topic

Seizing children can develop apnea.

What question this study addressed

When is such apnea more likely?

What this study adds to our knowledge

In this multicenter retrospective study of 1,584 children with out-of-hospital seizures, predictors of the 71 who developed apnea were continuing seizure on emergency department arrival and receiving midazolam.

How this is relevant to clinical practice

Although apnea can result from both ongoing seizures and midazolam, these data suggest that the benefit of using midazolam to stop seizures in children outweighs the risk of persistent seizures.

Respiratory depression is a potential complication of treatment with benzodiazepines, especially in children.5, 6, 9, 10, 11, 12, 13 The high risk of respiratory depression in several studies has caused some to question the use of benzodiazepines as first-line therapy for seizure.12 Others have argued that the risk of complications with benzodiazepines may be outweighed by the benefits of reduced seizure duration, which itself could lead to respiratory compromise.4 There is little knowledge of what other factors may contribute to respiratory depression in children with seizure. It has been suggested that children with developmental delay, those receiving previous seizure medications, and those with high fever may be more susceptible, but this is not well studied.14 Furthermore, prolonged seizure is likely a risk factor for apnea.15 Children with persistent seizure activity are more likely to receive medication, so the true contribution of benzodiazepines in the onset of apnea remains unclear. It is important to account for these potential risk factors when evaluating the risk of apnea during paramedic treatment of out-of-hospital seizure. By identifying patients at higher risk of apnea, protocols may be tailored with consideration of these special populations for additional monitoring.

We sought to quantify the risk of apnea in children presenting with out-of-hospital seizure treated with midazolam by paramedics and to identify other risk factors associated with apnea in this population.

Section snippets

Study Design and Setting

We conducted a multicenter retrospective chart review of pediatric patients with seizure who were transported by paramedics to the pediatric emergency department (ED) at Harbor-UCLA Medical Center and Los Angeles County/University of Southern California Medical Center during a 2-year period, from January 2010 to December 2011. The study was approved with waiver of informed consent by the institutional review board at both institutions. Harbor-UCLA Medical Center and Los Angeles

Characteristics of Study Subjects

As seen in the Figure, 2,403 patients were reviewed for study inclusion, of whom 815 were excluded. The remaining 1,584 pediatric patients transported by paramedics during the study period make up the study cohort, 770 patients transported to Harbor-UCLA Medical Center and 813 patients transported to Los Angeles County/University of Southern California Medical Center. Table 1 shows the characteristics of the study population as a whole and by treatment group. Of the 214 patients (14%) treated

Limitations

This study has several limitations. Although it represents a large number of children treated for seizure by multiple EMS provider agencies and transported to 2 different hospitals, it is limited to a single urban area of Los Angeles County and may not be generalizable to all populations.

The retrospective nature of the study could lead to bias, given that the investigators were not blinded to the outcome when extracting the data and we did not calculate the interrater reliability between

Discussion

We determined that the occurrence of apnea in children with out-of-hospital seizure is multifactorial, and risk factors likely include treatment with midazolam and prolonged seizure. Other patient factors hypothesized to influence apnea risk, including age, fever, treatment with antiepileptic medication, and developmental delay, did not significantly contribute to outcomes in our patient population. To our knowledge, our study is the first to quantify the risk of apnea in children with

References (25)

  • C.M. Verity

    Do seizures damage the brain? the epidemiological evidence

    Arch Dis Child

    (1998)
  • B.K. Alldredge et al.

    A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus

    N Engl J Med

    (2001)
  • Please see page 303 for the Editor's Capsule Summary of this article.

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    Supervising editor: Steven M. Green, MD

    Author contributions: MG-H conceived the study and supervised the conduct of the study and data collection. NB, GS, AHK, and MG-H collaborated on the design. NB, GS, TF, MH, and JL collected the data. NB, GS, and AF managed the data, including quality control. AHK provided statistical advice on study design and NB analyzed the data. NB drafted the article, and all authors contributed substantially to its revision. NB 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 as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist.

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