INTRODUCTION:
Neonatal seizures is defined clinically as a paroxysmal alteration
in neurologic function, i.e.motor, behavior and/or autonomic function.
According to National Neonatal Perinatal Database (NNPD; 2002-03)- incidence of
neonatal seizure is 10.3 per 1000 live-births. The incidence was
found to increase with decreasing gestation and birth weight. Seizure incidence
in preterm infants is 20.8 per 1000 live-births and very low birth
weight infants have 36.1 per 1000 live-births. Based on EEG ,neonatal seizure
classified into Epileptic seizures, Non-epileptic seizures
and EEG seizures. Phenobarbitone(PB) is the usual initial
anticonvulsant for neonatal seizures treatment
with efficacy of 33 and 77% .PB can cause neuronal
apoptosis in animal model and have highly variable pharmacokinetics
in neonates. CNS
depression and respiratory depression are the common side effect of
PB. Levetiracetam (LEV) may have a better safety profile and seizure cessation
was achieved in 77% and 86% in various studies.In recent stud Sharpe C et.al
during EEG based seizure free at 24 hour PB was better than LEV, but more side
effects.The efficacy of AED depends on study population, dose ,etiology of
seizure,definition of seizure control,which are widely varied in clinical
studies. we want to
compare PB vs LEV as first line antiepileptic in preterm
neonatal seizure AIMS AND OBJECTIVES
Hypothesis- Leveteracetam will be equal efficacious to phenobarbitone in treatment preterm
neonatal seizure.
Primary objective-
Evaluate the
efficacy of PB and LEV as the initial anti convulsant in preterm neonatal
seizure
Secondary objective-
Adverse effect of PB and
LEV in preterm neonates
Clinical response based
on the etiology of seizure.
MATERIALS AND METHODOLOGY:
PLACE OF STUDY: kalinga institute of
Medical sciences, Bhubaneswar
STUDY DURATION: From OCTOBER 2020
to OCTOBER 2022
STUDY DESIGN: Interventional study - A Randomised, non blinded, parallel trial.
Patients will be of allocated -computer
generated randomlist .
Allocation concealment- opaque sealed envelop.
STUDY POPULATION: preterm neonates
admitted in the NICU in the paediatrics department of pradyumna bal memorial hospital,
kims will be enrolled into this study after taking informed
consent .
Sample size
No of Cases
(expected/calculated): 53
No of Controls:53
Inclusion criteria-
Neonate with gestational
age <37 week with diagnosis of clinical seizure admitted within 28 days of
life in NICU.
Exclusion criteria-
Multiple
congenital malformation
Seizure secondary to
hypoglycemia and hypocalcemia controlled with glucose or calcium bolus
respectively.
Arm of the trial-
One
arm will receive iv inj PB
Other
arm will receive iv inj LEV.
METHODOLOGY
All
preterm neonates with clinical diagnosis of seizure will be
assessed to ensure patency of the airway, breathing &
circulation. Random blood sugar will be checked by glucometer
blood sample will be collected for serum electrolytes and inj calcium
gluconate will be given.
After
excluding hypoglycaemia and inj cal.gluconate bolus, if seizure persist,
babies will be randomized to receive either LEV (40mg/kg/dose) or
PB (15mg/kg/dose) intravenously.Levetiracetam(40 mg/kg) will be diluted
in 10 ml normal saline and administered intravenously under cardiorespiratory
monitoring over 10 min.
If
seizure persisitent another loading dose of levetiracetam 20mg/kg will be
given.If seizure terminated LEV was maintained at 20mg/kg/dose in
twice daily.If seizure still persisited, neonate will be switched over to PB
(15 mg/kg).
Phenobarbital
will be administrated in the dose of 15 mg/kg/dose diluted in normal saline and
given intravenously over 20 min .If seizure persist, another loading dose of
10mg/kg of phenobarbital will be over 10 min.
If
seizure subsided it will be continued as mantainance dose 3-5mg/kg/day in two
divided doses. If seizure still persist after 2 loading doses PB, neonate
will be switched over to LEV(40mg/kg).
P- Pre term neonates with seizures
I- IV inj leveteracetam
C-IV inj phenobarbitone
O-Clinical cessation of seizure for 24
hours
T- Till nicu discharge
Data lnclusion
Clinical details- antenatal, intrapartum,neonatal course,clinical
symptoms, seizure types and antiepileptic administration, sequence of
drugs with dosage, timing and duration of therapy were recorded. Investigations
– random blood glucose, serum calcium, electrolytes ,complete blood counts,
Creactive protein, blood culture, csf analysis,liver function tests, renal
function tests, arterial blood gas, cranial ultrasonography,MRI Imaging, IEM
screening, serum ammonia & lactate EEG based on clinician adv.
Hemodynamic instability ,Apnoea, respiratory depression, increased
ventilator support requirement, arrhythmias, , Heart rate fluctuations more
than 10 % compared to previous two hours, if vasopressors were intiated
or increased, blood pressure, increased ventilator requirement was
considered.
Statistical analysis:
Continous variables will
be compared between the two groups using independent samples t-test . seizures
control and occurrence of adverse effect in each in each anti epileptic drug
will be compared with chi-square test. Effect size and its 95% CI will be
computed for the primary and secondary outcomes. P value of less than 0.05 will
be considered as significant. The analyses will be carried out using stat 1.5
software.
REFERENCES
1) Maitre NL, Smolinsky C,
Slaughter JC, et al. Adverse neurodevelopmental outcomes after exposure to
phenobarbital and levetiracetam for the treatment of neonatal
seizures. Journal of Perinatology. 2013. 33, 841- 846.
2) Ramantani G, Ikonomidou
C, Walter B, et al. Levetiracetam: safety and efficacy in neonatal seizures.
European Journal of
Paediatric Neurology. 2011; 1-7. 14
3) Gowda, V.K., Romana, A.,
Shivanna, N.H. et al. Levetiracetam versus Phenobarbitone in Neonatal Seizures
— A Randomized Controlled Trial. Indian Pediatr 56,
643–646 (2019). https://doi.org/10.1007/s13312-019-1586-3
4) Mruk AL, Garlitz
KL, Leung NR. Levetiracetam in neonatal seizures: A review. J Pediatr
Pharmacol Ther. 2015;20:76-89. 10. McHugh DC, Lancaster S, Manganas LN. A
systematic review of the efficacy of levetiracetam in neonataL seizures.Neuropediatrics.
2018;49:12-17
5) Falsaperla R, Vialiti G, Mauceri L, et al.
Levetiracetam in neonatal seizures as first line treatment: a prospective
study.
6) Journal of Pediatric Neurosciences. 2017; 12:
24-28. 15.
7) Mruk AL, Garlitz KL, Leung NR, et al. Levetiracetam in neonatal
seizures: a review. Journal of Pediatric Pharmacology and Therapeutics.
2015; 20(2): 76-89 Granelli SP, McGrath JM. Neonatal seizures: diagnosis,
pharmacologic interventions, and outcomes.
|