Continuous midazolam versus diazepam infusion for refractory convulsive status epilepticus
Sunit Singhi1, Aruna Murthy, Pratibha Singhi
1Department of Pediatrics, Advance Pediatric Centre, Post-Graduate Institute of Medical Education and Research, Chandigarh, India. drsinghi@glide.net.in
Insights
Continuous midazolam and diazepam infusions effectively controlled refractory status epilepticus in children. However, midazolam showed higher seizure recurrence and mortality rates, particularly in cases of central nervous system infections.
Area of Science:
- Pediatric Neurology
- Critical Care Medicine
- Pharmacology
Background:
- Refractory status epilepticus (RSE) is a neurological emergency requiring prompt and effective treatment.
- Benzodiazepines, such as midazolam and diazepam, are first-line agents, but continuous infusions are often necessary for RSE.
Purpose of the Study:
- To compare the efficacy and safety of continuous midazolam versus diazepam infusion for controlling RSE in children.
- To evaluate seizure control rates, time to control, seizure recurrence, hypotension, and need for ventilation.
Main Methods:
- An open-label, randomized controlled study involving 40 children (2-12 years) with RSE.
- Patients received either continuous midazolam (n=21) or diazepam (n=19) infusion.
- RSE was defined as seizures uncontrolled after two doses of diazepam and phenytoin infusion.
Main Results:
- Both midazolam and diazepam infusions achieved high seizure control rates (86% vs. 89%, P=NS).
- Seizure recurrence was significantly higher with midazolam (57% vs. 16%, P < .05).
- Midazolam was associated with higher mortality (38% vs. 10.5%, P < .1 > .05) and similar rates of hypotension and ventilation needs.
Conclusions:
- Continuous midazolam and diazepam infusions are equally effective in controlling RSE.
- Midazolam infusion is linked to increased seizure recurrence and mortality, especially in RSE caused by CNS infections.
- Diazepam may be a safer alternative for RSE management in pediatric populations, particularly those with CNS infections.
Abstract:
The objective of this study was to compare the efficacy of continuous midazolam and diazepam infusion for the control of refractory status epilepticus. An open-label, randomized control study was undertaken at the Pediatric Emergency and Intensive Care Service of a multidisciplinary teaching and referral hospital. Subjects included 40 children, 2 to 12 years of age, with refractory status epilepticus (motor seizures uncontrolled after two doses of diazepam, 0.3 mg/kg per dose, and phenytoin infusion, 20 mg/kg). Either continuous midazolam (n = 21) or diazepam infusion (n = 19) in incremental doses was administered. The primary outcome measure was the proportion of children in each group with successful control of refractory status epilepticus. The secondary outcome measure was the time to control seizure activity, recurrence of seizure after initial control, if any, the frequency of hypotension, and the need for ventilation. The two groups were similar in age (mean +/- SD = 4.9 +/- 43.6 months) and etiology. Twenty-three (57.5%) patients had acute central nervous system infection. Refractory status epilepticus was controlled in 18 (86%) and 17 (89%) patients in the midazolam and diazepam groups, respectively (P = not significant). The median time to seizure control was 16 minutes in both groups, but in the midazolam group, seizures recurred in more children (57% versus 16% in diazepam group; P < .05). The maximum dose (mean +/- SD) of midazolam and diazepam required was 5.3 +/- 2.6 microg/kg/min and 0.04 +/- 0.02 mg/kg/min, respectively. About half of the patients needed mechanical ventilation and 40% had hypotension in both groups, but the mortality was higher in the midazolam group (38%) as compared to the diazepam group (10.5%, P < .1 > .05). Continuous midazolam and diazepam infusions were equally effective for control of refractory status epilepticus. However, midazolam was associated with more seizure recurrence and higher mortality in refractory status epilepticus predominantly caused by central nervous system infections.
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