1. PICU RESIDENT LECTURE SERIES LUCILE PACKARD CHILDREN’S HOSPITAL (UPDATED: JUNE 2014) Status Epilepticus

2. Objectives To learn the definition/pathophysiology of SE To learn some common etiologies To learn physiologic sequela To learn the acute management/work-up To learn about management of refractory SE

3. Definition & Pathophysiology

4. Definition The International Classification of Epileptic Seizures:  Seizure that lasts 30 minutes or longer  Seizures that are frequent enough that the individual does not regain consciousness between seizures If seizure lasts >5 minutes, higher risk of lasting >30 minutes. Delayed treatment can lead to permanent sequela. [1] Both mortality and the need for anticonvulsant therapy are greater in SE than seizures lasting shorter durations, i.e. < 30 min. [2]

5. Classification Simple partial — Continuous or repeated focal motor or sensory seizures without impaired consciousness. Complex partial — Continuous or repeated episodes of focal motor, sensory, or cognitive symptoms with impaired consciousness. Generalized — Tonic, clonic, or tonic-clonic and always associated with loss of consciousness. Absence status epilepticus — Generalized seizure activity, characterized clinically by altered awareness, but not necessarily unconsciousness.

6. Pathophysiology Status epilepticus (SE) occurs because of failure of the normal mechanisms that limit the spread and recurrence of isolated seizures [3]. Failure occurs because excitation (glutamate) is excessive and/or inhibition (GABA) is ineffective.

7. Common etiologies EtiologiesPercentages Fever36 Medication change20 Other - Trauma/Vascular/Infection / Tumor/Drugs 15 Unknown9 Metabolic8 Congenital7 Anoxic injury5

8. Physiologic Consequences

9. Physiologic consequences 1. Phases of SE 2. Respiratory Effects 3. Hyperpyrexia 4. Metabolic derangements 5. Laboratory changes 6. Summary

10. Phases of SE Hyperdynamic Phase  Increased cerebral metabolic demand  Massive catecholamine/autonomic discharge  Increased CBF, HTN, tachycardia Exhaustive Phase (with persistent SE)  Catecholamine depletion  Hypotension, decreased CBF  Can lead to neuronal damage due to ongoing metabolic demand with subsequent tissue hypoxia

11. Respiratory Effects Hypoxia and Hypercarbia  Chest wall rigidity (muscle spasms, oral secretions)  Hypermetabolic state with increased 0 2 demand and increased C0 2 production  Neurogenic pulmonary edema is rare complication  Marked increased in pulmonary vascular pressure is presumed etiology

12. Hyperpyrexia Can lead to seizures or be a result of SE Exacerbates mismatch of cerebral metabolic demand and substrate delivery Fevers should be treated aggressively

13. Metabolic derangements Acidosis  Lactic acidosis due to poor tissues oxygenation with increased energy expenditure  Respiratory acidosis due to respiratory effects Glucose  Initial hyperglycemia from catecholamine surge followed by hypoglycemia  Can be detrimental to the brain and can further worsen lactic acidosis

14. Metabolic derangements Rhabdomyolysis  Protracted tonic-clonic activity  muscle breakdown  Resultant hyperkalemia and myoglobinuria Leukocytosis  Stress response causes demargination  CSF leukocytosis in 15% of cases of SE

16. Treatment & Work-UP

17. Treatment ABCs Initial management Labs Other diagnostic testing

18. ABCs Avoid hypoxia by providing oxygen  Facemask or NC  Oral airway can be helpful (but difficult to place)  Nasal trumpet is good alternative Optimize position, jaw thrust, chin lift If poor respiratory effort, begin bag-mask ventilation and consider intubation

19. ABCs Intubation  Inability to maintain/protect airways  Unable to manage oral secretions  Ineffective respiration  Hypoxia/Hypercarbia  CNS pathology  SE >30 minutes despite appropriate treatments REMEMBER: paralytics DO NOT control CNS epileptiform discharges

20. ABCs Obtain IV/IO access  Can give IM or Rectal meds but venous access is necessary Blood pressure management  Hypertension likely to resolve with seizure control  Volume resuscitate if hypotensive

21. Initial Management TimelineSeizure Therapy 0 – 5 minutesBenzodiazepine (first-round) Ativan 0.05-0.1 mg/kg IV/IO Diastat 0.5 mg/kg PR Versed 0.1-0.2 mg/kg IM 5 – 10 minutesBenzodiazepine (second-round) Ativan 0.05-0.1 mg/kg IV/IO Diastat 0.5 mg/kg PR Versed 0.1-0.2 mg/kg IM 10 – 15 minutesFosphenytoin 20 mg/kg IV/IO OR Phenobarbital 20 mg/kg IV/IO 15 – 30 minutesPhenobarbital 20 mg/kg IV/IO

22. Labs CBC (leukocytosis 2/2 demargination vs. infx) Chem panel (hyponatremia, hypocalcemia) Bedside glucose LFTs and Ammonia

23. Labs Anticonvulsant levels Urine/Blood tox screen LP  defer in signs of increased ICP or unstable  do not delay therapy i.e. abx

24. Other diagnostic testing CT scan  Focal seizures  Neurologic deficits  History of trauma Type  Non-contrast: mass lesions, hemorrhage, hydrocephalus  Contrast: meningitis, abscess, encephalitis

25. Other diagnostic testing EEG-indicated in ALL patients with SE  Standard  one time study in SE that has resolved  Continuous  difficult to control SE, burst suppression, subclinical seizures  Video  can be used as adjunct for seizures that are difficult to characterize

26. Refractory Status Epilepticus

27. Refractory SE Iatrogenic coma  CNS electrical quiescence by continuous infusion  Pentobarbital: 1-3mg/kg/hr after bolus (10mg/kg)  Midazolam: 1-10mcg/kg/min after bolus (0.15mg/kg)  Propofol 20-70 mcg/kg/min Continuous EEG  “Burst suppression”  Electrical activity noted once per screen (15-20sec)

28. Refractory SE Normal physiologic activity also suppressed  Intubation necessary Central line placement  For delivery of continuous infusion  May cause hypotension so pt may require rapid fluid bolus or inotropes  Treat hypotension aggressively in these pts

29. Refractory SE Pt must be started on a long acting anticonvulsant  Check for therapeutic levels Burst suppression for 24-48 hrs  Coma gradually lifted while monitoring for seizure activity

30. References 1. Shinnar S, Berg AT, Moshe SL, Shinnar R. How long do new-onset seizures in children last? Ann Neurol 2001; 49:659. Shinnar S, Berg AT, Moshe SL, Shinnar R. How long do new-onset seizures in children last? Ann Neurol 2001; 49:659. 2. DeLorenzo RJ, Garnett LK, Towne AR, et al. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia 1999; 40:164. DeLorenzo RJ, Garnett LK, Towne AR, et al. Comparison of status epilepticus with prolonged seizure episodes lasting from 10 to 29 minutes. Epilepsia 1999; 40:164. 3. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998; 338:970. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998; 338:970.

31. Supplemental material