Abstract
Objective:
To determine whether pediatric emergency medicine physicians are compliant with the 9-year-old simple febrile seizure guideline created by the American Academy of Pediatrics (AAP).
Methods:
A retrospective chart review of patients, ages 6 to 60 months, who presented to the emergency department between May 2011 and December 2019. Key variables abstracted were urine, blood, nasal viral swab, and radiographic results.
Results:
The retrospective cohort of 285 children met inclusion criteria. Among 285 children, 342 studies were performed with a median of 1.2 studies per patient. There were 77 urine cultures obtained with 6 bacterial pathogens. Nasal viral swabs were performed on 65 children with 9 positive results. Blood cultures were obtained for 28 children and none were positive. Chest radiographs were performed on 37 children with 4 showing pneumonia.
Conclusion:
The study results reflect areas of opportunity to update guidelines with a focus to consider obtaining urine studies, viral sampling, and chest x-rays.
Introduction
A febrile seizure is a convulsion that occurs between the ages of 6 and 60 months in the setting of a fever (100.4°F or greater) and without evidence of intracranial infection.1-3 Febrile seizures are the most common convulsion of childhood with a prevalence of 2% to 5%. 4 Febrile seizures are classified into 2 categories: simple and complex. According to the American Academy of Pediatrics (AAP), simple febrile seizures (SFSs) are described as lasting less than 15 minutes, occurring once in 24 hours, and are generalized tonic-clonic without focal features.1-3 Complex febrile seizures last for 15 minutes or more, are focalized, and/or recur within 24 hours.1-4
Children experiencing a first SFS are often evaluated in the emergency department (ED). Before AAP guidelines were introduced, the work-up for febrile seizures was varied and included lumbar punctures to rule out meningitis, head computed tomography (CT) to rule out intracranial pathology, and an inpatient admission. 1 In a multicenter study led by Trainor et al, 5 they determined most laboratory and radiographic studies were not indicated in the work-up for SFS unless clinically indicated. In 2011, the AAP published updated guidelines in an effort to standardize the diagnosis and management of SFSs and to reduce any unnecessary testing of common serum labs, cerebral spinal fluid, and head imaging. 1
The purpose of our study was to describe the SFS work-up and management in a pediatric ED, and determine the frequency of laboratory and radiographic studies.
Methods
We performed a retrospective chart review of patients, ages 6 to 60 months, who presented to the ED between the dates of May 1, 2011 and December 31, 2019. Charts were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes for febrile and complex febrile seizures (R56.0 and R56.01, respectively). Those excluded from the study were patients classified as a complex febrile seizure, premature birth (<36-week gestation), history of a non-febrile seizure disorder, placement of a ventriculoperitoneal shunt, history of stroke, atrioventricular malformation, Moya-Moya, cerebral palsy, genetic or inborn error of metabolism, or were considered medically complex. Medically complex children were defined as requiring a gastrostomy or gastrojejunostomy tube, tracheostomy, diabetic, or having a thyroid or parathyroid condition. We relied on the ED physician’s classification of the seizure as simple or complex and focused solely on those determined to have SFSs. Variables abstracted were the following: age and gender, temperature at ED presentation, white blood cell (WBC) count, blood culture, C-reactive protein (CRP), urine studies, radiographic studies of chest radiographs (CXR), head imaging of either a magnetic resonance imaging (MRI) or CT, disposition, and consultation with neurology. The Institutional Review Board deemed the study human subject except.
Study Site
The ED and hospital are an urban, quaternary care children’s hospital that adjoins an adult facility. The ED has an annual census of approximately 17 000 patients and is staffed 24/7 with pediatric emergency medicine and emergency medicine-pediatric physicians.
Data Analysis
Statistics for this descriptive cohort study were calculated using R software version 4.0.5, and included distribution percentiles for continuous variables and frequencies for categorical variables.
Results
An initial 387 charts were identified. After applying the exclusion criteria, 285 children were diagnosed with SFSs. Table 1 details demographics and prior history of febrile seizures. The mean age was 1.9 years and there was a male predominance of 59%. Of these, 226 (79%) experienced their first SFS.
Demographics and Seizure Presentations.
Abbreviation: IQR: interquartile range.
All 285 patients had a temperature recorded by either an axillary or rectal thermometer. The mean temperature was 102.0°F (interquartile range [IQR]: 101°F, 103.2°F) and ranged from 96.3°F to 105.7°F. Three children arrived at the ED actively seizing. The seizures were described as generalized tonic-clonic, staring, or lip-smacking and all self-resolved without the need for anti-epileptic medication and lasted less than 15 minutes.
The ED frequency of laboratory with radiographic (if obtained) studies per patient was a median of 1.2 and results are shown in Table 2. For patients presenting with an SFS, 28 had a blood culture, 65 underwent a nasal viral swab, 77 had a urinalysis with a urine culture, and 37 underwent a chest x-ray. Not shown, 36 children had a WBC (median: 12.9 × 109/L; IQR: 8.9, 14.4) and 16 had a CRP (median: 9.8 mg/L; IQR: 7.3, 17.3).
Microbiology and Diagnostic Imaging Results.
Abbreviation: CT, computed tomography.
All 28 blood culture samples were negative for any bacterial growth. Among the urine cultures, there were 6 positive cultures with pathogenic bacteria. Nine nasal swabs were positive, with 5 children positive for influenza A. Of the chest radiographs, 4 children had opacities consistent with a bacterial pneumonia as interpreted by the pediatric radiologist. One patient had a head CT scan secondary to a prolonged Todd’s paralysis that showed a 1.0 cm× 0.5 cm × 1.1 cm sharply defined left temporal lobe neuroglial cyst. This patient also underwent an outpatient neurology follow-up evaluation and had a normal electroencephalogram. Given the normal results, neurology documented that the cyst was likely an inconsequential finding in the setting of SFS. There were no patients that underwent an MRI, lumbar puncture, or returned to the ED within 72 hours.
Discussion
The exact cause of febrile seizures is unknown but thought to be multifactorial. 6 A release of high levels of cytokines in response to fever, along with certain predisposing environmental or genetic factors in a developing and neurologically vulnerable brain, may alter neuronal activity and result in a seizure.7,8 Risk factors for febrile seizures include male gender, history of first-degree relatives with febrile seizures, exposure to certain chemicals in utero, viral illnesses, specific childhood vaccinations, neonatal intensive care unit (NICU) admission for greater than 28 days, and daycare attendance. 7 The viruses most linked to febrile seizure activity are herpesvirus 6, influenza, adenovirus, and parainfluenza.7,9
The AAP has published several guidelines on the evaluation and management of febrile seizures, the most recent of which was published in 2011 and stated that a well-appearing child presenting with SFS “does not usually require further evaluation, specifically electroencephalography, blood studies, or neuroimaging.” In addition, a “lumbar puncture should [only] be performed if there are clinical signs or symptoms of concern.” The guideline 1 also discussed refraining from obtaining laboratory studies of WBC, blood culture, and electrolytes. There was no mention of the utilization of urine, viral sampling, or chest radiographic studies. The lack of guidance, in our opinion, may lead to untreated children with clinically significant infections. The data from this study highlight that of the 77 children who had urine cultures, 6 (7%) were positive. A study by Ayazi et al also demonstrated that the overall rate of urinary tract infections (UTIs) among their febrile seizure cohort children was 7%, which is an identical result to our data. The study by Trainor et al 5 found a 3% UTI rate while another determined a rate of only 0.7%. 6 The majority of our positive cultures grew Escherichia coli followed by group B Streptococcus. These results are in line with prior studies 10 indicating that E coli is the most common cause of UTIs. In addition, recent studies among febrile children have better delineated the risk of UTI among infants. In fact, when determining who should be screened with a urinalysis and culture after presenting with fever, the most important risk factors include female sex, age < 12 months, high-grade vesicoureteral reflux, congenital anomalies of the kidneys and/or urinary tract (CAKUT), and/or instrumentation within the urinary tract (particularly indwelling bladder catheters).11,12 The University of Pittsburgh published a web-based calculator to help clinicians determine at bedside whether testing for UTI in febrile infants was necessary: https://uticalc.pitt.edu.
Suspected viral etiology is a common diagnosis for the etiology of an SFS given a clinically well-appearing child with any signs or symptoms of an upper respiratory tract infection. 5 Viruses are rarely treatable aside from influenza A or B.12,13 The complications from influenza include febrile seizures, encephalopathy, Guillain-Barre syndrome, respiratory distress, pneumonia, hospitalization, and death.13,14 In 2001, researchers found an astonishingly high rate of influenza infections associated with SFS and hospitalizations. In this study, 15 the rate of infection was 35% to 44%. The treatment is controversial given mixed efficacy, 16 but nevertheless, both the AAP and CDC (Centers for Disease Control and Prevention) recommend treating with oseltamivir phosphate to decrease duration of disease, hospitalization, and death. However, the oral medication should only be prescribed if initiated within 48 hours onset of illness and if the patient is considered high risk.17,18
The utility of obtaining a CXR is not supported by AAP guidelines and is not mentioned as a diagnostic consideration among other publications11,12,19,20 despite the incidence of pneumonia among children in North America as 34 to 40 per 1000 children and association with an annual hospitalization rate of 124 000.21,22 Interestingly, in our data, 4 children had pneumonia defined as opacities consistent with pneumonia, a positive rate of 11% among children who had this procedure. Unfortunately, vital signs, subjective descriptions of respiratory distress, or auscultative findings of rales were not collected. Thus, risk factors for obtaining CXR could not be determined.
Our data highlight 2 important factors. First, there was over utilization of serum labs: WBC, CRP, and blood culture. No pathologic or contaminant bacteria were documented among the blood culture sampling. It is unknown if these particular children were ill-appearing or lacked immunization. According to Minnesota public health data, 23 immunization rates have slowly declined and current rates for Haemophilus influenzae type b (Hib) are 84.3%, packed cell volume (PCV) 82%, DTap (diphtheria, tetanus, and acellular pertussis) 78.3%, and MMR (measles, mumps, and rubella) 91.7%. Although we could not confirm the reasoning, the declining rates may have prompted some providers to obtain serum studies.
The second pertinent message from our study demonstrated a clinically significant number of children with SFS also had treatable infection. These infections, if left untreated, could potentially have led to morbidity and mortality. From our findings as well as support from other publications,15,24 we suggest future recommendations in the evaluation of SFS should include the use of urine sampling, nasal swabs for influenza, and CXR when appropriate. This would ensure children who present with SFS are evaluated and treated appropriately.
Limitations
Immunization status of each child was not collected, and under-immunized or non-immunized children may have biased the decision-making process of ED providers. Based on the data presented above, it appears ED physicians may have utilized lab and imaging studies unnecessarily in the setting of SFS. However, the difficulty is in determining if the child was well-appearing or ill-appearing after presenting to the ED and if further testing was truly necessary in order to find the source of fever. This is an objectively gray area and could only be determined by talking to each provider directly, which still leaves room for subjective determination of illness. As stated previously, another limitation to the study is the subjective determination of ill versus well-appearing patients in their post-ictal state. Cases may have been missed or misidentified, which is the weakness of a retrospective study. We strongly feel, however, the clinically significant infection rate of 7% (19/285) cannot be dismissed and should influence future work-up guidelines.
Conclusion
The study results may not be generalizable but reflected areas of opportunity to update SFS AAP guidelines locally and nationally.
Author Contributions
KFV and JPL: Conceptualized the study; drafted the initial manuscript; analyzed the data; and reviewed and revised the manuscript for publication. KB and RK: Aided in analysis and interpretation of the data and revised the final manuscript. RS: Transformed and analyzed the data; as well as reviewed and revised the final manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Ethical Approval
Our study did not require an ethical board of approval. This article did not contain any human or animal subjects.
Informed Consent
Verbal informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article.
