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Midazolam in treatment of various types of seizures in children
Brain & Development 19 (1997) 571–572
Short communication
Midazolam in treatment of various types of seizures in children Cengiz Yakıncı a ,*, Bu¨lent Mu¨ngen b, Sabit S¸ahın a, Hamza Karabıber a, Yas¸ar Durmaz a a˙
Ino¨nu¨ University Medical School, Department of Pediatrics, 44069 Malatya, Turkey b Fırat University Medical School, Department of Neurology, 23200 Elazıgˇ, Turkey
Received 19 May 1997; revised version received 1 September 1997; accepted 9 October 1997
Abstract Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. There are limited studies that midazolam can be used successfully to treat seizures in adults and children. In this study, 0.2 mg/kg intramuscular (IM) midazolam was administered to 11 children (eight boys and three girls), aged 3 days to 4 years (mean age 1.8 ± 1.4 years), with seizures of various types. In all but one child, seizures stopped in 15 s–5 min after injection. No side effects were observed. These results suggest that IM administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (IV) line problem. 1997 Elsevier Science B.V. Keywords: Midazolam; Child; Convulsion
1. Introduction
2. Materials and methods
Midazolam is a recently developed water-soluble benzodiazepine used widely as a preanesthetic medication. Preclinical and clinical analysis of the drug indicate that it shares anxiolytic, muscle relaxant, hypnotic, and anticonvulsant actions with other members of this class [1]. Animal models showed that midazolam is a potent and effective suppressor of seizure disorders [2,3]. Compared with diazepam, it is more active efficacious for the rapid arrest of convulsions in the acute phase [3,4]. Midazolam has been shown to have a wide margin of safety and a broad therapeutic index [5,6]. There are a few studies that midazolam can be used successfully to treat seizures in human adults and children [7–9], and status epilepticus [6,10]. In this study we planned to investigate efficiency of midazolam in various types of acute convulsions in children.
The study was performed in 11 children (eight boys and three girls) with various types of acute convulsions, aged between 3 days and 4 years (mean age 1.8 ± 1.4 years). The causes of convulsion were as follows; epilepsy in six children, febrile convulsion in two children, electrolyte imbalance in two children, sepsis in one child. During convulsion attacks, 0.2 mg/kg intramuscular (IM) midazolam was administered. If the convulsion did not stop within 5 min, a second dose of IM midazolam was administered, and if the convulsion did not stop within 10 min, a third dose of IM midazolam was administered. In order to investigate causes of convulsion; history, physical examination, laboratory evaluations including determination of electrolytes, glucose, blood gasses and EEG were performed in all patients.
3. Results
* Corresponding author. Yakıncı Eczanesi 44300 Malatya, Turkey. Tel.: +90 422 3254000; fax: +90 422 3410610.
0387-7604/97/$17.00 1997 Elsevier Science B.V. All rights reserved PII S0387-7604 (97 )0 0090-9
Nine out of 11 children had no recurrence of convulsion. Only in one patient (Case 5) convulsion recurred 1 h after midazolam injection. The same dose of IM midazolam was
572
C. Yakıncı et al. / Brain & Development 19 (1997) 571–572
Table 1 Documentation of the patients Case no. 1 2 3 4 5 6 7 8 9 10 11
Age
3 3 2 4 4 1 2 18 2 30 6
days years years years years year years months months months months
Sex
Boy Boy Boy Boy Boy Boy Girl Girl Girl Girl Boy
Convulsion Cause
Type
Duration
Stopped time
Epilepsy Epilepsy Febrile convulsion Epilepsy Epilepsy Electrolyte imbalance Febrile convulsion Epilepsy Electrolyte imbalance Epilepsy Sepsis
Generalized Focal Generalized Focal Focal Generalized Generalized Focal Focal Focal Generalized
3 20 10 5 13 25 3 9 14 17 7
50 s 5 min 3 min 15 s 5 min Did not cease 1s 2 min 2 min 3.5 min 5 min
administered and convulsions were ceased within 20 s. In one patient (Case 6) convulsion did not stop in spite of the administration of midazolam three times (in 5 min intervals). This patient’s convulsion was ceased after correction of Na + deficiency. The duration of convulsion after midazolam injection is given in Table 1. Although we monitored respiration and circulation, we did not observe apnea, changes in blood pressure and other side effects of midazolam.
4. Discussion According to our results convulsions were ceased within 5 min in 10 (90%) out of 11 children. Five of them had generalized and five had focal convulsion. These results showed that midazolam is effective in both focal and generalized convulsive seizures and anticonvulsive effect begins within 15 s–5 min. Lahat et al. [7] reported that focal and generalized convulsive seizures were stopped with IM midazolam in 48 (100%) children within 1–10 min. Ghilain et al. [8] demonstrated that various types of convulsive seizures were controlled with 0.2 mg/kg IM midazolam in 14 (82%) adult patients. Galvin et al. [9] showed 0.2 mg/kg intravenous (IV) midazolam is effective to stop convulsive seizures in 20 (100%) adult patients. These studies support our results. On the other hand, it is reported that IV midazolam is effective to control status epilepticus [6,10]. In our study and in aforementioned studies, serious side effects of midazolam were not seen. This can be accepted as an advantage of midazolam. In emergency medicine, IV anticonvulsants, especially
min min min min min min min min min min min
diazepam is used to control convulsions. Establishment of IV route is an important problem especially in children with convulsion attacks. In this condition, midazolam takes the advantage of administration via IM route. We suggested that more detailed studies will enlighten new horizons in treatment of acute childhood convulsions.
References [1] Amrein R, Hetzel W. Pharmacology of dormicum (midazolam) and anexate (flumazenil). Acta Anaesthesiol Scand 1990;34:6–15. [2] Krutak-Krol H, Domino EF. Comparative effects of diazepam and midazolam on paraoxam toxicity in rats. Toxicol Appl Pharmacol 1985;81:545–550. [3] Domino EF. Comparative seizure inducing properties of various cholinesterase inhibitors: antagonism by diazepam and midazolam. Neurotoxicology 1987;8:113–122. [4] Raines A, Henderson TR, Swinyard EA. Comparison of midazolam and diazepam by the intramuscular route for the control of seizures in a mouse model of status epilepticus. Epilepsia 1990;31:313–317. [5] Bell DM, Richards G, Dhillon S. et al. A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy. Epilepsy Res 1991;10:183–190. [6] Rivera R, Segnini M, Baltodano A. et al. Midazolam in the treatment of status epilepticus in children. Crit Care Med 1993;21:991–993. [7] Lahat E, Aladjem M, Eshel G. et al. Midazolam in treatment of epileptic seizures. Pediatr Neurol 1992;8:215–216. [8] Ghilain S, Van Ruckevorsel-Harmant K, Harman J. Midazolam in the treatment of epileptic seizures. J Neurol Neurosurg Psychiatry 1988;51:732–735. [9] Galvin GM, Jelinek GA. Midazolam: an effective agent for seizure epilepsy control. Arch Emerg Med 1987;4:169–172. [10] Parent JM, Lowenstein DH. Treatment of refractory generalized status epilepticus with continuous infusion of midazolam. Neurology 1994;44:1837–1840.
Short communication
Midazolam in treatment of various types of seizures in children Cengiz Yakıncı a ,*, Bu¨lent Mu¨ngen b, Sabit S¸ahın a, Hamza Karabıber a, Yas¸ar Durmaz a a˙
Ino¨nu¨ University Medical School, Department of Pediatrics, 44069 Malatya, Turkey b Fırat University Medical School, Department of Neurology, 23200 Elazıgˇ, Turkey
Received 19 May 1997; revised version received 1 September 1997; accepted 9 October 1997
Abstract Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. There are limited studies that midazolam can be used successfully to treat seizures in adults and children. In this study, 0.2 mg/kg intramuscular (IM) midazolam was administered to 11 children (eight boys and three girls), aged 3 days to 4 years (mean age 1.8 ± 1.4 years), with seizures of various types. In all but one child, seizures stopped in 15 s–5 min after injection. No side effects were observed. These results suggest that IM administration of midazolam may be useful in a variety of seizures during childhood, especially in case of intravenous (IV) line problem. 1997 Elsevier Science B.V. Keywords: Midazolam; Child; Convulsion
1. Introduction
2. Materials and methods
Midazolam is a recently developed water-soluble benzodiazepine used widely as a preanesthetic medication. Preclinical and clinical analysis of the drug indicate that it shares anxiolytic, muscle relaxant, hypnotic, and anticonvulsant actions with other members of this class [1]. Animal models showed that midazolam is a potent and effective suppressor of seizure disorders [2,3]. Compared with diazepam, it is more active efficacious for the rapid arrest of convulsions in the acute phase [3,4]. Midazolam has been shown to have a wide margin of safety and a broad therapeutic index [5,6]. There are a few studies that midazolam can be used successfully to treat seizures in human adults and children [7–9], and status epilepticus [6,10]. In this study we planned to investigate efficiency of midazolam in various types of acute convulsions in children.
The study was performed in 11 children (eight boys and three girls) with various types of acute convulsions, aged between 3 days and 4 years (mean age 1.8 ± 1.4 years). The causes of convulsion were as follows; epilepsy in six children, febrile convulsion in two children, electrolyte imbalance in two children, sepsis in one child. During convulsion attacks, 0.2 mg/kg intramuscular (IM) midazolam was administered. If the convulsion did not stop within 5 min, a second dose of IM midazolam was administered, and if the convulsion did not stop within 10 min, a third dose of IM midazolam was administered. In order to investigate causes of convulsion; history, physical examination, laboratory evaluations including determination of electrolytes, glucose, blood gasses and EEG were performed in all patients.
3. Results
* Corresponding author. Yakıncı Eczanesi 44300 Malatya, Turkey. Tel.: +90 422 3254000; fax: +90 422 3410610.
0387-7604/97/$17.00 1997 Elsevier Science B.V. All rights reserved PII S0387-7604 (97 )0 0090-9
Nine out of 11 children had no recurrence of convulsion. Only in one patient (Case 5) convulsion recurred 1 h after midazolam injection. The same dose of IM midazolam was
572
C. Yakıncı et al. / Brain & Development 19 (1997) 571–572
Table 1 Documentation of the patients Case no. 1 2 3 4 5 6 7 8 9 10 11
Age
3 3 2 4 4 1 2 18 2 30 6
days years years years years year years months months months months
Sex
Boy Boy Boy Boy Boy Boy Girl Girl Girl Girl Boy
Convulsion Cause
Type
Duration
Stopped time
Epilepsy Epilepsy Febrile convulsion Epilepsy Epilepsy Electrolyte imbalance Febrile convulsion Epilepsy Electrolyte imbalance Epilepsy Sepsis
Generalized Focal Generalized Focal Focal Generalized Generalized Focal Focal Focal Generalized
3 20 10 5 13 25 3 9 14 17 7
50 s 5 min 3 min 15 s 5 min Did not cease 1s 2 min 2 min 3.5 min 5 min
administered and convulsions were ceased within 20 s. In one patient (Case 6) convulsion did not stop in spite of the administration of midazolam three times (in 5 min intervals). This patient’s convulsion was ceased after correction of Na + deficiency. The duration of convulsion after midazolam injection is given in Table 1. Although we monitored respiration and circulation, we did not observe apnea, changes in blood pressure and other side effects of midazolam.
4. Discussion According to our results convulsions were ceased within 5 min in 10 (90%) out of 11 children. Five of them had generalized and five had focal convulsion. These results showed that midazolam is effective in both focal and generalized convulsive seizures and anticonvulsive effect begins within 15 s–5 min. Lahat et al. [7] reported that focal and generalized convulsive seizures were stopped with IM midazolam in 48 (100%) children within 1–10 min. Ghilain et al. [8] demonstrated that various types of convulsive seizures were controlled with 0.2 mg/kg IM midazolam in 14 (82%) adult patients. Galvin et al. [9] showed 0.2 mg/kg intravenous (IV) midazolam is effective to stop convulsive seizures in 20 (100%) adult patients. These studies support our results. On the other hand, it is reported that IV midazolam is effective to control status epilepticus [6,10]. In our study and in aforementioned studies, serious side effects of midazolam were not seen. This can be accepted as an advantage of midazolam. In emergency medicine, IV anticonvulsants, especially
min min min min min min min min min min min
diazepam is used to control convulsions. Establishment of IV route is an important problem especially in children with convulsion attacks. In this condition, midazolam takes the advantage of administration via IM route. We suggested that more detailed studies will enlighten new horizons in treatment of acute childhood convulsions.
References [1] Amrein R, Hetzel W. Pharmacology of dormicum (midazolam) and anexate (flumazenil). Acta Anaesthesiol Scand 1990;34:6–15. [2] Krutak-Krol H, Domino EF. Comparative effects of diazepam and midazolam on paraoxam toxicity in rats. Toxicol Appl Pharmacol 1985;81:545–550. [3] Domino EF. Comparative seizure inducing properties of various cholinesterase inhibitors: antagonism by diazepam and midazolam. Neurotoxicology 1987;8:113–122. [4] Raines A, Henderson TR, Swinyard EA. Comparison of midazolam and diazepam by the intramuscular route for the control of seizures in a mouse model of status epilepticus. Epilepsia 1990;31:313–317. [5] Bell DM, Richards G, Dhillon S. et al. A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy. Epilepsy Res 1991;10:183–190. [6] Rivera R, Segnini M, Baltodano A. et al. Midazolam in the treatment of status epilepticus in children. Crit Care Med 1993;21:991–993. [7] Lahat E, Aladjem M, Eshel G. et al. Midazolam in treatment of epileptic seizures. Pediatr Neurol 1992;8:215–216. [8] Ghilain S, Van Ruckevorsel-Harmant K, Harman J. Midazolam in the treatment of epileptic seizures. J Neurol Neurosurg Psychiatry 1988;51:732–735. [9] Galvin GM, Jelinek GA. Midazolam: an effective agent for seizure epilepsy control. Arch Emerg Med 1987;4:169–172. [10] Parent JM, Lowenstein DH. Treatment of refractory generalized status epilepticus with continuous infusion of midazolam. Neurology 1994;44:1837–1840.