Comparison of midazolam and target control based propofol infusion in refractory status epilepticus

Background: Refractory status epilepticus (RSE) is defined as SE that fails to respond to first- and any two drugs in the second-line therapy. Propofol and midazolam are commonly used drugs for RSE; however, there is no consensus regarding superiority of either drug. This study was conceived to compare these two drugs for efficacy for RSE control and clinical outcome. Methodology: Twenty-three patients of diagnosed RSE were recruited prospectively and randomised to receive either propofol or midazolam infusion for seizure control, under electroencephalography monitoring according to a standardised protocol. Baseline demographics, time to seizure control, drug utilisation trends, adverse events, haemodynamic, acid-base data and outcome data were collected. Trend based parameters were analysed using mixed models ANOVA, between-group comparison was done using Mann–Whitney U-test or Chi-square test as applicable. Drug trends were analysed using Kaplan–Meier survival curves. Results: There was significant difference between the groups for duration of mechanical ventilation (propofol vs. midaolam) (median [interquartile range]) (9 [4.5–12.5] vs. 15 [14–23] days, P = 0.006), duration of Intensive Care Unit stay (11 [6–13.5] vs. 15 [14.25–23] days, P = 0.006) and duration of hospital stay (11 [7–13.5] vs. 22 [15.75–43.25] days, P = 0.006). The difference of time taken for seizure control between the groups was trending toward significance (4 [3–4.5] vs. 5 [4–12] h, P = 0.091). Survival curve analysis showed a significant difference between the groups for stoppage of infusions due to either hypotension or inadequate seizure control, with midazolam recording earlier infusion discontinuation (Breslow’s test, P = 0.005) [Figure 1]. Termination of infusions due to successful seizure control did not show any significant difference (P = 0.609). Conclusion: Despite the limitation of small sample size, outcomes seem to be better with propofol infusion rather than midazolam. Future studies with larger sample sizes are likely to validate this finding.

Figure 1: Kaplan–Meier curve shows that the early stoppage of midazolam secondary to the failure of control of refractory status epilepticus or infusion termination due to severe hypotension (P = 0.005)

No conflict of interest has been declared by the author(s).