Abstract
The objective of this study is to compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of acute childhood seizures. A randomized controlled study was conducted in a pediatric emergency department in a tertiary general hospital. Fifty children aged from 1 month to 12 years presenting with acute seizures of at least 10 min duration were enrolled during a 12 month period. Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg) were administered. The main outcome measures were interval between arrival at hospital and starting treatment and interval between arrival at hospital and cessation of seizures. Intranasal midazolam and intravenous diazepam were equally effective. Overall 18 of 27 seizures were controlled with midazolam and 15 of 23 with diazepam. The mean interval between arrival at hospital and starting treatment was significantly shorter in the midazolam group [3.37 min (SD 2.46)] as compared to the diazepam group [14.13 min (SD 3.39)]. The mean interval between cessation of seizures and arrival at hospital was significantly shorter in the midazolam group [6.67 min (SD 3.12)] as compared to the diazepam group [17.18 min (SD 5.09)]. The mean interval between control of seizures and administration of the drug was shorter in the diazepam group [2.67 min (SD 2.31)] as compared to the midazolam group [3.01 min (SD 2.79)]. No significant side effects were observed in either group. Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam. Midazolam was as safe and effective as diazepam. The overall interval between arrival at hospital and cessation of seizures was shorter with intranasal midazolam than with intravenous diazepam. The intranasal route can be possibly used not only in medical centres, but with appropriate instruction by the parents of children with acute seizures at home.
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References
(1993) Treatment of convulsive status epilepticus: recommendations of the Epilepsy Foundation of America’s Working Group in status epilepticus. JAMA 270:854–49
Chamberlain JM, Altieri MA, Futterman C et al (1997) A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care 13:92–94
Lahat E, Aladjem M, Eshel G et al (1992) Midazolam in treatment of epileptic seizures. Pediatr Neurol 8:215–216
Conner JT, Katz RL, Pagano RP et al. (1978) PO21-3981 for intravenous surgical pre-medication and induction of anesthesia. Anesth Analg 57:1–5
De Jong RH, Bonin JD (1981) Benzodiazepines protect mice from local anesthetic convulsions and death. Anesth Analg 60:385–389
Jawad S, Oxley J, Wilson J et al (1988) A pharmacodynamic evaluation of midazolam as an antiepileptic compound. J Neurol Neurosurg Psychiatr 49:1050–1054
Latson LA, Cheatham JP, Gumbiner CH et al (1991) Midazolam nose drops for outpatient echocardiography sedation in infants. Am Heart J 121:209–210
Lacon A, Reddy VG (1994) Nasal midazolam and ketamine for pediatric sedation during computerized tomography. Acta Anesthesiol Scand 38:259–261
Wilton NCT, Leight J, Rosen DR et al (1988) Preanesthetic sedation of preschool children using intranasal midazolam. Anesthesiology 69:972
Saint-Maurice C, Landais A, Delleur MM et al (1990) The use of midazolam in diagnostic and short surgical procedures in children. Acta Anesthisiol Scand 94(suppl 92):39–41
O’Regan ME, Brown JK, Clarke M (1996) Nasal rather than rectal benzodiazepines in the management of acute childhood seizures. Develop Med Child Neurol 38:1037–1045
Lahat E, Goldman M, Barr J et al (1998) Intranasal midazolam for childhood seizures. Lancet 352:620
Lahat E, Goldman M, Barr J et al. (2000) Comparison of intranasal midazolam with intravenous diazepam for treating febrile seizures in children: prospective randomized study. BMJ 83–86
Greenblatt DJ, Arendt RM, Abernethy DR et al (1983) In vitro quantitation of benzodiazepine lipophilicity: relation to in vivo distribution. Br J Anesth 55:985–989
Arendt RM, Greenblatt DJ, de Jong RH et al (1983) In vivo correlates of benzodiazepine cerebrospinal fluid uptake pharmacodynamic action and peripheral distribution. J Pharmacol Exp Ther 227:98–106
Rey E, Delaunay G, Pons IM et al (1991) Pharmacokoinetics of midazolam in children: comparative study of intranasal and intravenous administration. Eur J Clin Pharmacol 41:355–357
Mahmoudian T, Zadeh MM (2004) Comparison of intranasal midazolam with intravenous diazepam for treating acute seizures in children. Epilepsy Behav 5:253–255
Mittal P, Manohar R, Rawat AK (2006) Comparative study of intranasal midazolam and intravenous diazepam sedation for procedures and seizures. Indian J Pediatr 73:975–978
Koul RL, AIthala GR, Chacko A et al (1997) Continuous midazolam infusion as treatment of status epilepticus. Arch Dis Child 76:445–448
Ghialin S, Van Ruckevorsel-Harmant K, Harmant J et al (1988) Midazolam in the treatment of epileptic seizures. J Neurol Neurosurg Psychiatry 51:732–735
Scott RC, Nevile BGR, Besag FMC et al (1997) Nasal rather than rectal benzodiazepines in the management of acute childhood seizures. Develop Med Child Neurol 39:137–138
Lombroso CT (1989) Intermittent home treatment for status and clusters of seizures. Epilepsia 30(suppl 2):11–14S
Seigler RS (1990) The administration of rectal diazepam for acute management of seizures. J Emerg Med 8:155–159
De Haan GJ, Van Der Geest P, Doelman G et al (2010) A comparison of midazolam nasal spray and diazepam rectal solution for the residential treatment of seizure exacerbations. Epilepsia 51:478–482
Bhattacharya M, Kalra V, Gulati S (2006) Intranasal midazolam vs rectal diazepam in acute childhood seizures. Pediatr Neurol 34:355–359
Nakken KO, Lossius MI (2011) Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizure or status epilepticus. Acta Neurol Scand 124:99–103
Mcintyre J, Robertson S, Norris E et al (2005) Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomized controlled trial. Lancet 366:205–210
Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, NETT Investigators (2012) Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 366(7):591–600
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We thank our Dean, Dr Sandhya Kamath, and Head of Department, Dr Mamta V Manglani, for giving us the permission to publish this article.
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This Randomised Controlled Trial has approval of Ethics Committee, Staff and Research Society, Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai, India.
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Thakker, A., Shanbag, P. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures. J Neurol 260, 470–474 (2013). https://doi.org/10.1007/s00415-012-6659-3
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DOI: https://doi.org/10.1007/s00415-012-6659-3