1. Managing and Detecting Seizures in the ICU Special thanks to: Katherine Nickels, MD Assistant Professor of Neurology and Pediatrics Mayo Clinic

2. Epileptic events Stereotyped, rhythmic, synchronous Not distractible or suppressible Eyes open Injury Incontinence Post-ictal confusion Onset during wakefulness or sleep

3. Generalized Status Epilepticus Duration: if szs last longer than 5-10 min, they are unlikely to stop spontaneously

4. Remember…..Non-convulsive status epilepticus in the ICU Simple partial, complex partial, or absence Can include twitching of extremity, rythmic facial movements, etc.. Affects the patient’s mental state, in the absence of obvious motor manifestations Need high level of suspicion in sedated intubated patient – consider EEG to confirm

5. Treatment ABCs Most pts breathe adequately as long as airway is clear 100% O 2 by mask. Intubate if evidence of respiratory compromise use short-acting NM blocker so one does not lose clinical ability to determine if seizure is persisting If a long-acting paralytic is used, will need EEG monitoring to determine if still seizing

6. Treatment R/O acute metabolic cause: hypoglycemia, electrolyte disturbance The longer the status has gone on, the less responsive it is to drug therapy TREAT EARLY Recurrent seizure after treatment with benzodiazepine warrants consideration of an antiepileptic drug as the next step

7. Further Hx and Px Prior sz history Other medical illnesses Trauma Focal neuro signs Signs of medical illness – infection, substance abuse, etc Labs to consider: glu, lytes, calcium, gas, renal and liver function, serum AED levels, tox screen, blood cultures

8. What is the first medication to give?

9. Drug Treatment (5 minutes) Benzodiazepines (1 st line): Lorazepam and diazepam equivalent in efficacy and lorazepam longer acting, therefore usually use the latter. Midazolam also can be used. Dose of lorazepam: 0.1 mg/kg slow IV push (2 mg/min) Dose of midazolam: 0.2 mg/kg Dose of diazepam: 0.5 mg/kg Median time to response 2-3 minutes Risks: respiratory depression, hypotension

10. Non-IV drug routes Rectal: diazepam, Diastat Buccal: diazepam, lorazepam, midazolam IM: fosphenytoin, midazolam, diazepam, lorazepam

11. Persistent Seizure after Benzodiazepine

12. May repeat benzodiazepine while drawing up: Phenytoin or Fosphenytoin (2 nd line) Fosphenytoin can be given IM without causing tissue necrosis Use if IV unattainable, or In small child with tenuous IV site Fosphenytoin is ++++ more expensive than phenytoin Dose 20 mg/kg of phenytoin or 20 mg/kg PE of fosphenytoin. Infuse fosphenytoin 1-3 mg/kg/min Side effects: hypotension, arrhythmias, tissue necrosis with phenytoin

13. Next steps if seizures persist despite phenytoin

14. Additional antiepileptic drug treatment IV Valproic acid 25 mg/kg at 5 mg/kg/min Unless <2 years or Known/suspected liver disease or Inborn error of metabolism, then use: Alternative: IV Levetiracetam 20 mg/kg at 5 mg/kg/min

15. Seizures continue…..

16. Next steps: Phenobarbital Can also be given as a first line drug after benzodiazepine Can be given as second line drug after Phenytoin Phenobarbital 20 mg/kg IV at rate of 50-75 mg/min Watch for respiratory depression Give slowly over about 20 minutes to avoid side effects if necessary

17. Still Seizing……

18. Anesthesia/ICU Management Indications for Anaesthesia/ICU Severe systemic complications such as severe hyperthermia Seizures lasting longer than 60 minutes Seizures refractory to adequate doses of benzodiazepines, phenytoin, VPA/LEV, and phenobarbital

19. Anesthesia/ICU options All require continuous EEG monitoring, central access, intubation Midazolam infusion Pentobarbital Goal is burst suppression: bursts <1 second in duration, interspersed by periods of suppression lasting at least 10 seconds. This pattern should be present for at least 90% of the recording.

20. Midazolam infusion Initiation: 0.2 mg/kg bolus followed by infusion at 0.12 mg/kg/hour, Still seizing Give additional 0.2 mg/kg bolus and increase to 0.24 mg/kg/hr Maintenance continue increasing by 0.12 mg/kg/hr every 10 minutes to a maximum of 1.92 mg/kg/hr to achieve burst suppression

21. Seizures refractory to multi-drug therapy and high dose midazolam infusion: Consider Pentobarbital Coma

22. IV anesthetics Thiopentol or pentobarb infusion Initiation: 5 mg/kg IV Maintenance: 1-3 mg/kg/hr Cardiac depression, agranulocytosis, hepatic injury Propofol infusion: In children, contra-indicated due to rhabdomyolysis, propofol infusion syndrome, metabolic acidosis

23. Anesthesia/ICU options Isoflurane inhalation therapy Must be done under the guidance of Pediatric Neurology, Pediatric Intensive Care, Pediatric Anesthesia Initiation: 1% to 2% and adjust by 0.1% every 5– 10 mins to a goal of controlling seizure activity. Any changes in administration should be done under by Pediatric Anesthesia.

24. Treatment Summary ABCs Treat early for best results! Benzos first line, followed by phenytoin, then VPA/LEV, then phenobarb ICU/Anaesthesia if prolonged >60 min, refractory or significant systemic complication