Laboratory Testing for First Nonfebrile Seizure - Critically Appraised Topic (CAT)

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Laboratory Testing for First Nonfebrile Seizure - Critically Appraised Topic (CAT) PICOT Question: For the child who presents to the emergency department (ED) after a first nonfebrile should laboratory studies be obtained as part of the acute evaluation? Clinical bottom line based on literature appraisal below: The most recent AAN Practice Parameter (Hirtz et al, 2000) states laboratory studies may be obtained when history or clinical findings such as vomiting, diarrhea, or dehydration are present. Children with these types of symptoms are excluded from this guideline. The literature was searched for studies that addressed this question since 2000 and five studies were identified. The quality of the evidence since the AAN Practice Parameter (Hirtz et al, 2000) is VERY LOW. The primary reasons for this GRADE are: (a) Study type, all but one were retrospective s. The one prospective included children in status epilepticus (Aydogan, Aydogan, Kara, Basim, & Erdogan, 2007). (b) Inconsistency across studies- the studies included some subjects nonfebrile, but also children with febrile, and in status epilepticus. Therefore, First Nonfebrile Seizure CPG team recommends that laboratory tests should not be obtained for children who present with their first nonfebrile to the ED. Synthesis of relevant studies: Author, date, country, and Patient Group industry of funding (Aydogan, Aydogan, Kara, Basim, & Erdogan, 2007) Turkey Children mean age 4 ±3.6 y (range 6 m- 13 y) Presenting afebrile Strength of Evidence (GRADE) Very low Research design cohort All subjects with afebrile between Jan 2000 and March 2002 were Significant results 62 subjects were enrolled- 50% male 9 subjects had leukocytosis (14.5%), a second CBC was obtained and leukocytosis did not persist. Leukocytosis was more prevalent in children with status epilepticus SE defined as a continuous Limitations (Aydogan, Aydogan, Kara, Basim, & Erdogan, 2007) Turkey

(Hirtz et al., 2000) (Landau, Waisman, & Shuper, 2010) Israel Children and adolescents unprovoked 85 subjects average age 7.5 y (range 0-18 y) who made 104 visits to the ED Excluded febrile or other primary diagnosis The guideline was ed by two team members using the AGREE tool. The consensus was to accept the guideline with alterations inconsisten t includes subjects that do not apply to this guideline enrolled Guideline lasting longer than 30 minutes or repeating s last 30 minutes with recovering consciousness between them. The Practice Parameter addresses the following: Laboratory studies- may be obtained when history or clinical findings such as vomiting, diarrhea, or dehydration are present. Lumbar puncture (LP)- should not be obtained unless meningitis is suspected. EEG- should be performed as part of the evaluation of first non-febrile. Timing of the study (within the first 48 hours or later) is not clear. Neuroimaging- CT scan- should not be obtained. MRI- should not be obtained for the child with a first non-febrile who has returned to baseline. Laboratory tests were obtained in 84% of visits. Eight percent provided useful information and < 5% were helpful in diagnosis and management. Only one lumbar puncture was performed. Eight percent of visits had electrocardiography performed and all were normal Seven percent of visit had electroencephalography performed and was consistently useful and was *Concerns with the AAN Guideline (Hirtz et al., 2000) include: The development group did not include Pediatric Emergency Medicine, patient/parent/family representatives Methods for formulating the recommendations, cost implications and conflicts of interest are not reported transparently Mix of children and those already on medication for. Only 30 (35%) subjects presented.

(Nypaver, Reynolds, Tanz, & Davis, 1992) USA (Scarfone, Pond, Thompson, & Fall, 2000) USA 308 ED s, 108 febrile (mean age 2.1 years) 200 non febrile s. (mean age 5.7 years Included lab tests: electrolytes Calcium, magnesium, ammonia, glucose, Dextrostix Infants < or equal to 12 months of age presenting to the ED of a tertiary care children s hospital. Serum chemistry results were classified as normal, outside of range always performed along with a neurology consultation 41 were having their first non febrile. 26 subjects (63%) had at least one laboratory test performed. No changes in therapy were made as the result of the laboratory findings. In 1992 US dollars, the mean cost of the laboratory tests was $122.00 per subject. 214 patient visits made by infants with febrile and non febrile s. 134/214 were non-febrile s and 70 of these were a first, or 52% of all presenting non febrile s. 51 of 70 had lab drawn 8/51 (16%) had a clinically significant abnormality. Is there a Working Group on Status Epilepticus recommendation that serum chemistries should be obtained for adults and children with status epilepticus? Small sample size. Important changes in newborn screening since this study need to be considered, that is the need for lab studies may be even lower. Would expanded newborn screening change any of this?

(Valencia et al., 2003) normal and clinically significantl y abnormal Urban hospital, All children unprovoked. Separated out those with history of from those Total of 107 children met criteria. Mean age 6.6 years (range 0.1-20 years). 58% male 42% Black 33% Hispanic 19% White 7% Other 75% (N=80) had previous s 68% of these were taking anti epileptic medications For those who had chemistries drawn 2/33 in the previous group had abnormal electrolytes For those who had chemistries drawn 5/21 in the no previous group had abnormal electrolytes. Patients with abnormal electrolytes were significantly younger (mean age 1.7 vs. 7.2 years) symptoms included vomiting or diarrhea, or presented with a changed in mental status. Date created- February 13 2015, Date approved- April 15 2015

References: Aydogan, M., Aydogan, A., Kara, B., Basim, B., & Erdogan, S. (2007). Transient peripheral leukocytosis in children with afebrile s. J Child Neurol, 22(1), 77-79. Hirtz, D., Ashwal, S., Berg, A., Bettis, D., Camfield, C., Camfield, P.,... Shinnar, S. (2000). Practice parameter: evaluating a first nonfebrile in children: report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology, 55(5), 616-623. Landau, Y. E., Waisman, Y., & Shuper, A. (2010). Management of children with nonfebrile s in the emergency department. Eur J Paediatr Neurol, 14(5), 439-444. doi: 10.1016/j.ejpn.2010.02.006 S1090-3798(10)00032-2 [pii] Nypaver, M. M., Reynolds, S. L., Tanz, R. R., & Davis, A. T. (1992). Emergency department laboratory evaluation of children with s: dogma or dilemma? Pediatr Emerg Care, 8(1), 13-16. Scarfone, R. J., Pond, K., Thompson, K., & Fall, I. (2000). Utility of laboratory testing for infants with s. Pediatr Emerg Care, 16(5), 309-312. Valencia, I., Sklar, E., Blanco, F., Lipsky, C., Pradell, L., Joffe, M., & Legido, A. (2003). The role of routine serum laboratory tests in children presenting to the emergency department with unprovoked s. Clin Pediatr (Phila), 42(6), 511-517.