507 Lecture 4: Status Epilepticus

Learning Objectives

• Define status epilepticus (SE).

• State the goals of therapy for treatment of adult patients in SE.

• Describe the initial approach to therapy for an adult patient in SE.

• Recommend initial pharmacological agents in an adult patients with SE.

• Recognize common side effects associated with drugs used in SE.

What is status epilepticus?

• Status epilepticus (SE) = neurological emergency

  • Defined by two or more episodes of seizure activity between which the patient does not regain consciousness.

  • Continuous seizure activity for 5 minutes

What is the epidemiology of status epilepticus?

• Males > females

• 20% in elderly

• High risk groups: African American, Children, Elderly

What are the types (2) of status epilepticus?

1) Generalized Convulsive SE (GCSE) – positive for physical signs (e.g., rhythmic jerking of extremities)

2) Non-Convulsive SE (NCSE) – negative for physical signs (only activity on an electroencephalograph or EEG)

What are acute causes of status epilepticus?

• Traumatic brain injury (TBI)

• Toxic substances/overdose

• CNS infection

• Stroke (ischemic/hemorrhagic)

• Metabolic disturbances

• Hypoxia/anoxia

What are chronic causes of status epilepticus?

• Epilepsy (subtherapeutic drug therapy or new onset)

• Alcohol abuse

• CNS tumors

• Stroke

What kinds of drugs can induce seizures?

• Antibiotics – beta-lactams, quinolones, carbapenems, metronidazole

• Antidepressants – TCAs, SSRIs, MAOIs

• Analgesics – tramadol, meperidine

• Diabetes drugs – insulin, metformin

• Drugs of abuse – amphetamines, cocaine, MDMA

• Miscellaneous – baclofen, DDAVP, methylphenidate, flumazenil

• Also, drug interactions!

What is a major drug interaction that can induce seizures? (Tesoro highlighted this one)

Carbapenems (i.e. mero, imi-) + Valproic acid

What is the pathophysiology of seizures?

Imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters

• Glutamate

  • Excitatory neurotransmitter

  • Stimulates post-synaptic NMDA receptors causing calcium influx and depolarization

• GABA

  • Inhibitory neurotransmitter

  • Stimulates GABA_A receptors and promotes hyperpolarization through chloride mediated inhibition

  • GABA inhibition decreases as SE progresses

What is the presentation of SE?

◼ Convulsions (tonic-clonic movements)

◼ Impaired consciousness (lethargy to coma)

◼ Post-ictal

• Disorientation

• Pain from convulsions (secondary injury)

What are the two phases of status epilepticus?

Phase 1 - early phase (< 30 minutes)

Phase 2 - after 30 minutes

• If a patient is in phase 2, it’s difficult to break up the seizures

What are systemic signs of phase 1 of SE?

• Hypertension

• Tachycardia

• Hyperglycemia

• Hyperthermia

• Sweating

• Salivation

What are systemic signs of phase 2 of SE?

• Hypotension

• Bradycardia

• Hypoglycemia

• Hyperthermia

• Hypoxia

• Uremia - high levels of waste products, such as urea and creatinine, build up in the blood

• Elevated intracranial pressure

• Acidosis

• Hyperkalemia

• Hyponatremia

What’s the overall management plan for SE? What are the goals of therapy?

• Stabilize ABC’s (vital signs)

• History (Time of onset ◼ Medical/surgical history ◼ Epilepsy ◼ Diabetes ◼ Head injury/trauma ◼ Alcoholism)

• Medication history (Antiseizure medications ◼ Toxins ◼ Herbals)

• Obtain IV access

• Labs (Electrolytes, Blood glucose, Antiseizure medication levels, Toxicology screen, Arterial blood gas (ABG))

• CT scan of head

• Evaluation by neurologist

• Electroencephalography (EEG)

Goals of therapy:

• Identify the source of seizures.

• Stop both clinical and subclinical seizure activity (convulsions + electrical activity of brain)

• Prevent future seizures (if necessary).

• Minimize side effects of medications used to treat SE.

• Treat complications of SE.

• AND DO IT QUICKLY - TIME IS BRAIN!!!

What should we do in the first 10 minutes for a patient presenting with status epilepticus?

EMERGENT TREATMENT - WITHIN 10 MINUTES

• ABC - check for airway, breathing, circulation

• Give parenteral (IV) benzodiazepine

What should we do in within 20 minutes for a patient presenting with status epilepticus?

URGENT TREATMENT - WITHIN 20 MINUTES

• Send labs, obtain history

• Give parenteral (IV) antiseizure medications (to prevent subsequent seizures)

What should we do in within 30 minutes for a patient presenting with status epilepticus?

• Identify and treat any underlying causes

• Re-bolus ASM if needed

In emergent SE treatment, which benzodiazepines can we give?

• Intravenous (IV) benzodiazepines

  • Lorazepam 0.1mg/kg IVP @ 2mg/min (MAX: 4mg, may repeat once)

  • Diazepam 0.15mg/kg IVP @ 5mg/min (MAX: 10mg, may repeat once)

• Intramuscular (IM) benzodiazepine

  • 13-40kg: midazolam 5mg IM

  • >40kg: midazolam 10mg IM

Which IV benzos are most commonly used in emergent treatment?

Lorazepam and Diazepam

What should we monitor when giving benzodiazepines?

• Respiratory rate/oxygen saturation

• Blood pressure

  • Diazepam/lorazepam injections contain propylene glycol (↓BP)

  • Recommend diluting 1:1 with NS before administering

• Seizure recurrence

  • Diazepam has shortest duration – may need to redose more frequently (lorazepam preferred)

• IV site reactions

Why do we need to monitor BP when giving benzos (Lorazepam/Diazepam)?

Diazepam and Lorazepam injections contain propylene glycol which decrease BP

• Diluting 1:1 with NS before administering helps to mitigate hypotensive effect

Which ASMs do we give in URGENT therapy (within 20min)?

Phenytoin (Dilantin)

Fosphenytoin (Cerebyx)

Phenobarbital

Valproate sodium (Depacon)

Newer agents: Levetiracetam and Lacosamide

What is the loading dose + maintenance for Phenytoin?

• LD: 15-20 mg/kg IV (rate: 50mg/min)

• MD: 4-6 mg/kg/day (IV or PO) started 8-12 hours after loading dose

What is the loading dose + maintenance for Fosphenytoin?

• LD: 15-20mg PE/kg IV (rate: 150mgPE/min) or IM

• MD: 4-6mg PE/kg/day (IV or IM) started 12 hours after loading dose

PE = phenytoin equivalents

What are the differences between Phenytoin and Fosphenytoin?

Phenytoin:

• Compatible with NS only

• Max rate: 50mg/min

• IV only, no IM

• Contains propylene glycol

• pH 12

Fosphenytoin:

• Compatible with NS, dextrose, or LR

• Max rate of 150 mgPE/min

• Can give IV or IM

• DOES NOT CONTAIN PROPYLENE GLYCOL

• pH 8.5

What is the loading dose + maintenance for Phenobarbital?

• LD: 15-20 mg/kg IV (rate: 100mg/min)

• MD: 1-3 mg/kg/day (IV or PO)

What is the loading dose + maintenance for Valproate sodium? (VPA)

• LD: 30-40 mg/kg IV (rate: 3-6mg/kg/min)

• MD: 15-60 mg/kg/day (IV or PO)

What is the mini-loading dose eq for Phenytoin?

LD = (weight(kg) V_d (0.7L/kg) (C_desired - C_observed) / (S X F)

What should we monitor when giving ASMs?

• Sedation

• Respiratory rate – phenobarbital

• Blood pressure

  • IV phenytoin/phenobarbital – hypotension

  • Fosphenytoin/IV VPA – better tolerated

• Heart rate – Fos/phenytoin (arrhythmias)

• Infiltration – Purple Glove Syndrome (phenytoin)

• Therapeutic levels (aim for higher end of range)

• Other labs (LFTs, platelets)

  • Amylase/lipase/NH3 for VPA

Which ASMs contain propylene glycol?

IV Phenytoin and Phenobarbital - monitor for hypotension

What are the therapeutic levels for ASMs? (Phen/Fos/Pheno/VPA)

• Phenytoin/fosphenytoin

  • 10-20mcg/mL (total)

  • 1-2mcg/mL (free)

• Phenobarbital → 15-40mcg/mL

• VPA → 50-100mcg/mL

What are some advantages of using Levetiracetam in urgent tx of SE?

• Few drug interactions

• Linear kinetics

• Not hepatically metabolized

  • But, renally eliminated (maintenance doses must be adjusted for renal function)

What are the loading + maintenance doses of Levetiracetam?

• Loading dose regimens

  • Doses of 1 - 4.5 grams IV have been given (rate of 500mg/min)

  • 60mg/kg (MAX: 4500mg) IV

• MD: 500-1500mg IV/PO q12h

What are advantages of using Lacosamide in urgent tx of SE?

• Few drug interactions

• Linear kinetics

• Hepatically metabolized, but renally eliminated

What are the loading + maintenance doses for Lacosamide (Vimpat)?

• Loading doses: 200-400mg IV push (80mg/min)

• MD: 100-200mg IV/PO q12h