Continuous Midazolam Versus Diazepam Infusion for Refractory Convulsive Status Epilepticus

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.

Quality assurance evaluation of a simple linear protocol for the treatment of impending status epilepticus in a pediatric emergency department 2 years postimplementation

“…[2][3][4] Our results are comparable to those reported in the literature assessing the use of midazolam for seizure control in the emergency setting and reporting success rates of 56 to 96.7%. 3,5,8,10,11,[13][14][15][16][17] To our knowledge, there are no studies comparing IV midazolam to either lorazepam or diazepam IV in the ED setting. Silbergleit and colleagues published a double-blind, randomized, noninferiority trial comparing the efficacy of IM midazolam to that of IV lorazepam: IM midazolam was at least as safe and effective as IV lorazepam.…”

“…12 Multiple studies have proven that midazolam is at least as effective as diazepam in terms of safety and risk of recurrence, with the advantage of providing a faster initiation of treatment, leading to more rapid seizure cessation. 3,5,8,10,11,[13][14][15][16][17][18][19] Midazolam has emerged as a highly efficacious drug in the treatment of impending SE, with several routes of administration exhibiting high bioavailability. 19 In a recent article proposing evidence-based and expert consensus practice guidelines, the Neurocritical Care Society lists midazolam as Class I, Level A for the emergent treatment of SE, as Class IIB, Level B for urgent treatment (continuous infusion), and as Class IIa, Level B for refractory treatment using the evidence rating system of the American Heart Association. )…”

The Limitations of Diazepam as a Treatment for Nerve Agent–Induced Seizures and Neuropathology in Rats: Comparison with UBP302

“…Second, benzodiazepines are among the anticonvulsants with the most serious side effects (Mehta et al, 2007;Kellinghaus and Stögbauer, 2012). Third, seizures often recur after termination of the initial SE by benzodiazepines (Mayer et al, 2002;Singhi et al, 2002), and at least in the case of nerve agent-induced SE, it is unclear whether DZP compares favorably with other anticonvulsant treatments in the duration of its antiseizure effects. This is particularly significant considering that the duration and intensity of seizures clearly correlate with the severity of the resulting neuropathology (Shih et al, 2003;Prager et al, 2013).…”

Status Epilepticus

“…It is metabolized in the liver and excreted by the kidneys. Encouraging results have been seen with midazolam infusion in refractory status epilepticus in children [34][35][36][37].…”