Can t Stop the Seizing! Joseph Miller, MD, MS MCEP Critical Care March, 2019 Objectives Describe the importance of time to treatment Delineate treatment based on best evidence Describe novel diagnostic and therapeutic tools Adult Status Epilepticus 1 2 1
Case Prehospital Treatment 21 year-old male PMH: seizure disorder GTC Sz at work Duration 7 minutes EMS Midazolam 10mg IM stops 3 4 2
Most effective benzodiazepine in adults - conclusions In adults with status epilepticus without established IV access, IM midazolam is established as more effective compared with IV lorazepam (level A) No significant difference in effectiveness has been demonstrated between lorazepam and diazepam in adults with status epilepticus (level A) Triage Vitals: 138/87, 105, 22, 97% RA, 37.3 GCS 10 Resumes GTC seizure Case American Epilepsy Society, 2017 5 6 3
ED Treatment What next? Urgency? Options? 7 8 4
Pitfalls Neuro-injury occurs < 30 minutes Longer the status tougher to break Insufficient anticonvulsant doses Delay in escalating treatment Paralyzed but still seizing Meldrum BS, Arch Neurol. 1973 2 9 10 5
% Subjects (PHTSE) Small dose safer or more dangerous? Small dose safer or more dangerous? Do benzos cause cardio-respiratory compromise? However PHTSE trial data suggest that under-treatment is more dangerous. Cardio-respiratory compromise 25 p=0.08 20 15 10 5 0 Initial therapy should an adequate single full dose rather than broken into multiple smaller doses Initial therapies should not be given twice except for IV lorazepam and diazepam that can be repeated at full doses once (level A, two class I, one class II RCT). American Epilepsy Society, 2017 N Engl J Med. 2001 Aug 30;345(9):631-7. 11 12 6
Case Basics GTC Air movement seems poor 92% on RA 2 PIVs, O2, monitor Airway positioning Check glucose 13 14 7
Drugs VA Comparative Trial PIV #1: 4mg IV Lorazepam (repeat as needed) PIV #2: Non-benzo antiseizure drug 15 16 Treiman, NEJM 1998 8
Kaplan Meier Curves Comparing the Durations of Out-of- Hospital Status Epilepticus after Treatment with Lorazepam, Diazepam, or Placebo. Drugs Non-Benzo AEDs Fosphenytoin (FOS) 20 mg/kg Levetiracetam (LVT) up to 60 mg/kg (max 4.5 gm) Valproic acid (VPA) - 30 mg/kg Published head-to-head trials lacking Alldredge BK et al. N Engl J Med 2001;345:631-637. 17 18 9
ESSET Randomized, double blind comparison Fosphenytoin (FOS) Levetiracetam (LVT) Valproic acid (VPA) Outcome: Sz cessation within 60 minutes without use of additional anti-seizure meds 19 20 DSMB Teleconference March 13, 2015 20 10
Case Refractory Treatment 10 mg IM midazolam 8 mg IV lorazepam 3.5 grams Levetiracetam 20 minutes in resusc room and still seizing Mechanical ventilation Midazolam 0.2 mg/kg bolus, repeat q5min Infusion 0.1 mg/kg/hour titrate as needed Propofol Pentobarbital 21 22 11
Refractory Treatment Neuro-ICU Continuous EEG Immunomodulatory consideration Anti-NMDA encephalitis Other autoimmune encephalitis Prolonged Status Chronic epilepsy, withdrawal of AED CNS tumor, infection, stroke, TBI, hypoxic injury Drug toxicity Withdrawal from opioid, benzodiazepine, barbiturate, or alcohol PRES Autoimmune encephalitis 23 24 12
Case Case 68 M obtunded 39.0, 122, 76/54, 38, 72% RA PMH: DM, HTN, TBI GCS: 2V, 2E, 4M Labored Sux wears off Faint myotonic activity in LUE Eyes 25 26 13
Before Case F 1 - F F3- C3 CJ- P3 P3-0 Treat severe sepsis Stat EEG Common pitfall missed non-convulsive status Trial of lorazepam, other AEDs F4- ' P4-0 _..., --,-------...-- -...----- - ---_.-,...r----.ṭ_..-.,_,/.:... F p 1 - F 7 P7-0 F7- F8- - P7 $......,.. r:. -.. l4ar w:... Fz : Cz Hill, Ann Neurol 2017 27 28 14
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New Diagnostics New Diagnostics Hobbs, Neuro Crit Care, 2018 31 32 16
New Therapeutics CONCLUSIONS Broader TTM Be mindful of futility NOT LIVE YET June? Arctic sun training coming 33 34 17
jmiller6@hfhs.org 35 18