1. Seizures LMH ER Rounds March 22, 2016 Prepared by Shane Barclay

2. OBJECTIVES Assessing the seizing patient in the ER Treatment of seizures in the ER

3. Seizures Definitions Seizure: manifestation of abnormal hyper excitable discharges of cortical neurons. Status epilepticus: greater than 5 minutes of seizure activity or.. more than 2 discrete seizures with incomplete recovery between events or.. continuing seizure after administration of anti-seizure medication. Epilepsy: the occurrence of at least 2 unprovoked seizures more than 24 hours apart.

4. Causes of Seizures 1. Epilepsy – may be first presentation 2. Hypoxia 3. Metabolic (hypoglycemia, uremic, hepatic..) 4. Electrolyte (hypo/hypernatremia, hypercalcemia) 5. Drug intoxication (anticonvulsants, antidepressants, antipsychotics, opioids, …) 6. Drug withdrawal (alcohol, benzodiazepines, …)

5. Causes of Seizures 7. Trauma (occur ~15% blunt severe traumatic brain injury) 8. CNS neoplasm 9. Stroke 10. Intracranial hemorrhage 11. CNS Infection 12. CNS dysfunction (Alzheimer's – incidence ~ 12%)

6. Differential Diagnosis Eclampsia Pseudo-seizures Syncope Acute Dystonic reactions Rigors

7. Examination Vitals – make sure to check temperature. Tongue biting. Although not sensitive, is quite specific for tonic-clonic seizures ~ 98%. Urinary incontinence – low sensitivity and specificity. Neurological exam: check for lateralizing signs.

8. Examination Lab: Overall low yield ie only abnormal in around 15% of patients: CBC, glucose, lytes, Ca, Mg, renal, LFT, cultures, toxicology screen, ECG, preg test if female. Serum antiepileptic med if on them. LP, CT imaging and EEG should be done, but typically in a tertiary care facility.

9. Overview of Treatment First Goal is to restore normal neuronal function. The second goal is to determine if the seizure is due to some treatable systemic condition or some intrinsic CNS dysfunction.

10. Treatment ABCD Secure the airway if necessary, especially in status patients. Even if seizure has stopped, always establish an IV in case of a second seizure.

11. Medications Most patients, unless in status epilepticus, will have stopped seizing by the time they reach the emergency department. In that case one can still consider a benzodiazepine as well as a second line medication to prevent a second seizure.

12. Medications However if seizing or if a recurrent seizure occurs: If unable to establish IV: Midazolam 10 mg IM (if > 40 Kg) or 5 mg (if < 40Kg), or Midazolam 0.2 mg/kg intranasal or buccal or Diazepam 0.5 mg/kg rectally If IV established: Lorazepam 0.1 mg/kg, or midazolam 0.2 mg/kg or diazepam 0.2 mg/kg IV

13. Second Line Medication Follow benzodiazepines with Phenytoin 20 mg/kg IV at 50 mg/min max. If allergic to Phenytoin may use Phenobarbital 20 mg/kg IV at 100 mg/min. If patient known epileptic and on medications, usually give ½ the loading dose of their medication.

14. “Third line” Medications Valproic acid 20-40 mg/kg loading dose at 5 mg/kg/min. Propofol 3-5 mg/kg then infusion at 30-100 mcg/kg/min.

15. Pharmacology of Benzodiazepines Lorazepam has ~ 12 hours of anti-seizure property Diazepam has only about 20 minutes. Therefore if you use Diazepam, a second line antiepileptic medication must be started soon after. Studies have shown that IM Midazolam is actually faster at terminating seizures than IV Diazepam. Even though Midazolam has a serum half life of 2.5 hours, brain levels remain at near peak concentrations for at least 4 hours.

16. Status Epilepticus Status epilepticus: greater than 5 minutes of seizure activity or more than 2 discrete seizures with incomplete recovery between events or failure to stop seizure after one med. Neuronal damage starts to occur after 20-30 minutes of seizure activity due to impaired cerebral perfusion and reduced brain oxygen and glucose levels. The longer the seizure activity, the more refractory to treatment.

17. Status Epilepticus First line treatment is benzodiazepines as discussed prior. Consider intubating earlier than later. The rationale for intubation is that using second and third line anti-seizure medications usually take much longer than 30 minutes to administer.

18. Status Epilepticus The most reliable way to achieve seizure control under 30 minutes is a benzodiazepine, Propofol and ketamine. Propofol is a powerful antiepileptic. However the longer the seizure occurs, GABA receptors, which Propofol acts on, decrease in number and the seizure becomes less responsive to Propofol. You may need vasopressors to counteract the hypotensive effect of Propofol.

19. Status Epilepticus Ketamine blocks NMDA receptors thus giving it anti- epileptic and neuroprotective properties. As the seizure continues, NMDA receptors increase making ketamine at least theoretically more effective. Ketamine may also help obviate some of the hypotensive effects of Propofol. As well always consider antibiotics, as a common cause of status is infection.

20. Rapid Sequence Termination of Status Epilepticus Antiepileptic if possible – phenytoin, valproate

21. Disposition Admission or discharge is often determined by the clinical features and causes that were related to the seizure. Patients who present with a generalized seizure with no other worrisome history have been discharged home with close follow-up for investigations etc. Even with a normal EEG and normal CT scan, 1 and 4 year recurrence rates are 14% and 24%, respectively. However, antiepileptic medications do not affect this recurrence rate.

22. Questions?