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Keywords ABSTRACT
Anti-epileptic drugs, Electroencephalogram, There is a lack of scientific evidence to support the best management of neonatal seizures.
Newborn, Phenobarbital, Status epilepticus
Current strategies for neonatal seizure management were investigated by analysis of all
Correspondence surveys published during the time period 20002012. Methods for seizure diagnosis and
m-Westas, Department of Womens and
L Hellstro
Childrens Health, Uppsala University Hospital,
availability of electroencephalogram (EEG), including monitoring, varied. Phenobarbital was
SE-751 85 Uppsala, Sweden. the drug of first choice, and the use of off-label drugs and treatment times varied.
Tel: +46-18-611 00 00 | Conclusion: We conclude that there is an urgent need for more evidence-based studies
Fax: +46-18-6115833 |
Email: lena.westas@kbh.uu.se
to guide neonatal seizure management.
Received
21 April 2014; revised 11 July 2014;
accepted 19 September 2014.
DOI:10.1111/apa.12812
2014 The Authors. Acta Pdiatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Pdiatrica 2015 104, pp. 123129 123
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,
provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Review of neonatal seizure management m-Westas et al.
Hellstro
METHOD
PubMed was searched in November 2012 using three
search strategies. First, we searched PubMed using the
MeSH terms: Infant, Newborn AND Seizures/diagnosis;
Infant, Newborn AND Seizures/therapy; Infant, New-
born AND Seizures/drug therapy; Infant, Newborn Figure 2 Terms used for PubMed search, number of references within
AND Seizures/prevention and control; Infant, Newborn brackets.
AND Seizures/epidemiology, Figure 1.
124 2014 The Authors. Acta Pdiatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Pdiatrica 2015 104, pp. 123129
m-Westas et al.
Hellstro Review of neonatal seizure management
Sz diagnosis/monitoring
quoted in more than one table. Table 1 shows data from six
Preterm 34/53.5%
aEEG/EEG and/or EEG
at-risk newborns:
studies that included methods for seizure diagnosis, mainly
Term: 33/66.5
aEEG/EEG and EEG (1924). Table 2 presents data from
seven studies, five of which are surveys to professionals or
institutions while two studies contain data on administered
anti-epileptic treatment in newborn infants retrieved from
large databases covering multiple institutions (20,22,24
29). Table 3 displays views on neonatal seizure manage-
Preterm 58%
Term 58.2%
Sz diagnosis:
neurologists, retrieved from four studies (20,22,3032).
by 59%
EEG
DISCUSSION
This literature search of current practices in neonatal
Neonatologists 70.5%
aEEG availability:
Europe, Canada
USA (75%), UK,
UK
36/55 (65%)
13/20 (65%)
214/214
193 of an
Paediatric/Neurologists (15%)
Neonatologists at 20 European
Neonatal neurologist/
Table 1 Surveys assessing methods for diagnosis of neonatal seizures
Neurologists (56%),
in the UK
Web-based survey; 23
Glass et al. 2012 (24).
Telephone survey
multiple choice,
2014 The Authors. Acta Pdiatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Pdiatrica 2015 104, pp. 123129 125
126
Table 2 Surveys investigating preferred, or actually administered, anti-epileptic drug treatment of neonatal seizures
Study Subjects Country 1st AED 2nd AED 3rd AED Prophylactic AED
Review of neonatal seizure management
Wheless et al. 2005 (25). Paediatric neurologists USA Benzodiazepine/ Lorazepam Fosphenytoin Infant with NE, mean
33 questions, 645 treatment (epileptologists), 39/41 (95%) Phenobarbital (SD) 8. 2 (5.5) weeks
options, scenarios
Bartha et al. 2007 (26). Infants with seizure diagnosis, USA (5 NICUs) Phenobarbital 82% Lorazepam 9% Phenytoin 2% 75%
Administered AED, database all gestational ages (n = 480)
Silverstein & Ferriero 2008 (27). Paediatric neurologists at 2007 71% USA, Levetiracetam 47%, topiramate 55%
Off-label use of AED, survey Annual Child Neurology 20% Canada, Levetiracetam and/or topiramate 73%
Society meeting, 55 replies 9% other
Blume et al. 2009 (28). Infants with seizure diagnose USA (31 states) Phenobarbital 76% Phenytoin 16% Benzodiazepines 67% (day prior
Administered AED, database (ICD-9 779.0, 345.19), to discharge)
all gestational ages (n = 6099)
Vento et al. 2010 (22). Neonatologists at European 10 European countries, Phenobarbital 100% 85% midazolam, 85% lidocaine,
Questionnaire with 3 parts university hospitals, 13/20 (65%) see table 1 7.5% clonazepam, 7.5% lidocaine/phenyl,
(diagnosis, treatment) 7.5% phenytoin 7.5% midazolam/diaz
Koppelstatter et al. 2011 (29). German University Hospitals, Germany 45.7% used levetiracetam;
Levetiracetam use, survey 35/36 (97.2%) 20% used levetiracetam in preterms
Glass et al. 2012 (24). Neonatologists (24.9%), USA (75%), UK, Preterm: Phenobarbital Preterm: Preterm:
Web survey, 23 multiple choice Paediatric neurologists (55.9%), Europe, Canada 72.2%, Lorazepam 21.9% Phenytoin 40.6%, Phenytoin 35.2%,
Neonatal neurologist/neurocritical care Phenobarbital 26.2% Levetiracetam 21%
(19.2%), 193/400500 (~45%) Term: Term: Term:
Phenobarbital 70.9%, Phenytoin 42.8%, Phenytoin 34.9%,
Lorazepam 23.1% Phenobarbital 27.2% Levetiracetam 18.9%
AED = Anti-epileptic drug; ICD-9 = International Classification of Diseases, version 9; NE = Neonatal encephalopathy; NICU = Neonatal intensive care unit.
Hellstro
m-Westas et al.
2014 The Authors. Acta Pdiatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Pdiatrica 2015 104, pp. 123129
m-Westas et al.
Hellstro Review of neonatal seizure management
72% no reply
Duration of AED
Median 12 w
other drug (9). The two drugs were comparable as first-line
Median 8 w
3 months:
treatments, and the combined efficacy of both drugs was
HIE/IVH:
81.4%
94.8%
86.2%
91.3%
3 mo
53%
more than 60%. Benzodiazepines and lidocaine are other
drugs commonly used for anti-epileptic treatment. Although
these drugs were only compared in a small randomised
controlled trial (10), they are commonly used and several
Prophylactic AED
Seldom/never:
Rarely/never:
observational studies have investigated their acute effects
No: 89%
No: 56%
2% 8%
and pharmacokinetics (35). Two studies investigated neo-
72.9%
10.5%
36.2%
21.7%
natologists and paediatric neurologists preferred treat-
ments of seizures in preterm infants, which were very
similar to that of term infants (24,32).
Benzodiazepines 69.2%,
Benzodiazepines 71.4%,
Phenytoin 14.3%
Phenobarbital 14.7%
Phenytoin 85,3.1%,
Midazolam
Midazolam
Midazolam
Midazolam
Phenytoin
Phenytoin
Benzodiazepines 10.9%
Phenobarbital 87.5%,
Phenobarbital 85.7%,
85.7%
86.2%
78.2%
100%
(37).
Phenobarbital 97%
Phenobarbital 94%
Questionnaire, 20 items.
Questionnaire, 20 items,
Bassan et al. 2008 (20).
5 scenarios. Sweden
selected specialists,
2014 The Authors. Acta Pdiatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Pdiatrica 2015 104, pp. 123129 127
Review of neonatal seizure management m-Westas et al.
Hellstro
128 2014 The Authors. Acta Pdiatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Pdiatrica 2015 104, pp. 123129
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Hellstro Review of neonatal seizure management
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