Epilepsy 2

1. Epilepsy 2 Dr. Hawar A. Mykhan

2. Epilepsy and Pregnancy • Most women with epilepsy who become pregnant will have an uncomplicated gestation and deliver a normal baby. • Seizure frequency during pregnancy will remain unchanged in ~50% of women, increase in 30%, and decrease in 20%. • It is useful to see patients at frequent intervals during pregnancy and monitor serum antiepileptic drug levels. • The overall incidence of fetal abnormalities in children born to mothers with epilepsy is 5–6%, in comparison with 2–3% in healthy women. • Part of the higher incidence is due to teratogenic effects of antiepileptic drugs, and the risk increases with the number of medications used.

3. Because the potential harm of uncontrolled seizures on the mother and fetus is considered greater than the teratogenic effects of antiepileptic drugs, it is recommended that pregnant women be maintained on effective drug therapy. • Keep the patient on monotherapy at the lowest effective dose, especially during the first trimester. • Patients should take folate (1–4 mg/d), since the antifolate effects of anticonvulsants are thought to play a role in the development of neural tube defects. • Mother should be treated with oral vitamin K (20 mg/d) in the last 2 weeks of pregnancy, and the infant should receive vitamin K (1 mg) at birth.

4. Status Epilepticus • Classical definition: 30 minutes of continuous seizure activity or two or more seizures in 30 minutes without recovery of consciousness. • New definition: more than 5 minutes of seizure activity or two or more seizures without recovery of consciousness. • Advocates for old definition point out that neuronal damage begins after 30 minutes. • Advocates for new definition point out that seizures usually stop in less than 2 minutes.

5. Status Epilepticus Treatment Protocol

6. Step 1 (0 to 5 minutes) • Make the diagnosis of impending status epilepticus after observing more than 5 minutes of continuous seizure activity or one additional seizure in a patient with recent seizures. • Airway, breathing, and circulation. • Give oxygen. • Assess airway and apply pulse oximeter. • Perform venipuncture and secure IV access. • Send blood for immediate basic metabolic panel, liver function tests, calcium, magnesium, phosphate, complete blood count, toxicology screens, troponin, and antiepileptic drug levels. • Check finger-stick glucose. • Start a normal saline drip.

7. Step 2 (6 to 10 minutes) • Administer thiamine and dextrose (unless normoglycemic) 100-mg thiamine IV plus 50 mL of 50% dextrose IV. • Give IV lorazepam at 0.1 mg/kg by IV push at a rate no greater than 2 mg/min. • Repeat if seizures persist. • Lorazepam is the preferred benzodiazepine because it not only has an onset of action as fast as that of diazepam but also a longer duration of action (24 hours vs. 30 minutes).

8. It can also be given as a continuous intravenous infusion for refractory status epilepticus. • Adverse effects: respiratory depression, hypotension, decreased level of consciousness. • Diazepam is an alternative to lorazepam but there is risk of recurrence of the seizure because of short duration of action. • Dose (adults): 0.2 mg/kg intravenously at 2 mg/min.

9. Step 3 (11 to 30 minutes) • Give IV fosphenytoin (20 mg PE/kg), no faster than 150 mg PE/min or IV phenytoin (20 mg/kg) by slow IV push no faster than 50 mg/min. • Phenytoin is incompatible with glucose-containing solutions. • Monitor cardiac rhythm and blood pressure. • If seizures persist, give additional IV fosphenytoin or phenytoin to a maximum total dose 30 mg/kg. • Phenytoin is water insoluble, so formulation is alkaline (pH 12) with propylene glycol and ethanol (responsible for tissue toxicity and purple glove syndromeand, to some degree, cardiac effects).

10. Note that administration of phenytoin is slow because of the risk of cardiovascular side effects (hypotension, arrhythmias, QT prolongation). • Fosphenytoin is more expensive than phenytoin, but has a better side-effect profile. • It is water soluble, with no risk of purple glove syndrome and less risk of cardiac adverse effects.

11. Step 4 (31 to 50 minutes) • If seizures persist, the patient should be intubated; also consider one of the following: • IV phenobarbital 20 mg/kg slow push (<100 mg/min). • IV pentobarbital 5 mg/kg (<50 mg/min), then 0.5 mg/kg/h to 5 mg/kg/h. • IV midazolam 0.2 mg/kg given over 20 to 30 seconds. Dose may be repeated in 5 minutes if seizures persist. Then continuous infusion at 0.05 mg/kg/h to 2.0 mg/kg/h. • IV propofol 1-mg/kg to 2-mg/kg bolus. Dose may be repeated in 5 minutes if seizures persist.

12. Phenobarbital has marked side effects. It Depresses respiratory drive and consciousness, has a high risk of hypotension, and decreased cardiac contractility. Because of the long half-life (48 hours), the effects are prolonged. • Midazolam is a benzodiazepine with a short half-life, used as an intravenous drip for its anesthetic properties in refractory status epilepticus. It has a fast onset and offset, well tolerated, and causes less hypotension than with phenobarbital or propofol.

13. Summary of Pharmacologic management • First-line agent: benzodiazepines. • Second-line agent: phenytoin and fosphenytoin. • Third-line agent: phenobarbital vs. anesthetic agent (midazolam, propofol). • If refractory to midazolam or propofol, consider inhalent anesthetic (isoflurane is the first choice).