Abstracts

Rationale: Super refractory status epilepticus (SRSE) is defined as status epilepticus resistant to initial treatment with a benzodiazepine and a standard antiepileptic medication as well as an anesthetic medication (Brophy, Bell 2012). In prolonged refractory status epilepticus, inhibitory GABAa receptors become internalized and agonists such as midazolam become less effective over time (Goodkin 2005; Claassen 2002). In contrast, excitatory NMDA receptor concentration increases over time and receptor antagonists such as ketamine may represent effective treatments (Kapur 1990). Our goal is to understand how the addition of ketamine to high-dose midazolam potentially affects outcomes after SRSE. Methods: Guidelines for the use of ketamine in SRSE were approved at our institution in August 2015.  Ketamine could be added in any patient who had failed to respond to first and second line agents as well as continuous infusion of high-dose midazolam (defined as at least 1 mg/kg/hr), propofol, or pentobarbital.   Patients treated for SRSE with midazolam and/or ketamine between March 2014 and March 2017 were included to assess both pre- and post-protocol cohorts.  Analysis included patient demographics, APACHE II score, presumptive etiology of SRSE, seizure control, time to seizure control, medication doses, ICU and total hospital length of stays, and mortality. Results: From 2014-2017, 32 patients had SRSE (18%), 15 patients received both high-dose midazolam and ketamine in the post-ketamine protocol period (MDZ+KET group) and 17 patients received high-dose midazolam in the pre-ketamine protocol period (MDZ group).  The groups were similar in age, sex, ethnicity, and APACHE II score. 5 of the 15 patients (33%) in the MDZ+KET group and 5 of the 17 (29%) patients in the MDZ group had SRSE secondary to anoxic brain injury.   The mean maximum dose of midazolam (mg/kg/hr) was 1.93 for MDZ+KET and 2.29 for the MDZ group (p=0.73).  Patients in the MDZ+KET group reached a mean maximum of 3.14 mg/kg/hr of ketamine.   Seizure control was achieved in 80% (12/15) of the MDZ+KET group and 65% (11/17) of the MDZ group (p=0.34).   Mean time to seizure control based on EEG reports was 15 hours for the MDZ+KET group and 33 hours for the MDZ group (p=0.26).  A subgroup analysis excluding anoxic brain injury patients had a time to seizure control of 6 hours for MDZ+KET and 23 hours for MDZ, respectively (p=0.15).  Length of ICU and total hospital stay were similar  with MDZ+KET at 20 and 25 days respectively and MDZ at 14 and 15 days respectively (p= 0.78, 0.51, respectively).  Mortality was also similar between MDZ+KET and MDZ at 33% and 47%, respectively (p=0.49). Conclusions: Midazolam plus ketamine appears similar to high-dose midazolam in terms of seizure control and mortality. There is a trend for faster time to seizure control in the midazolam plus ketamine group for etiologies other than anoxic brain injury, though these results are not statistically significant. Further study is warranted and a larger sample size is needed to be able to draw firm conclusions. A larger sample size would additionally help in the assessment of other potential variables related to the critical care of these patients such as ventilator days, vasopressor burden, and volume overload. Funding: No funding was received in support of this abstract.