Status Epilepticus

by

Robert S. Fisher, M.D., Ph.D.

Department of Neurology

Stanford, California USA

Definition of Status Epilepticus

A state of continuing seizures for greater than 30 minutes, or recurrent seizures for at least 30 minutes without intervening return of consciousness.

TYPES OF STATUS

Simple partial motorComplex partialAbsenceMyoclonicTonic-clonic

Epilepsia partialis cont.

Non-convulsive

Tonic-clonic

*

*Petit mal, spike-wave, absence

About 30,000per year

Rochester Richmond

The longer you wait, the harder to treat

With delay of treatment, more diazepam is required to stop seizures in an experimental model of status.

Walton & Treiman Epilepsia 1995 S4:45

0

1

2

3

4

5

mg

Val

ium

1st sz

2nd sz

EARLY TREATMENT IS KEY

0 5 10 15 20 25 30 3560

70

80

90

100

110

DAYS

% SURVIVING

DeLorenzo, 1992 Epilepsia S4:15

rapid treatment

delayed treatment

<1hr

>1hr

Symptomatic

Idiopathic

140,00060,000

2,000,000

Epilepsy Status

CONCEPT OF - Overt status- Subtle status

Encephalopathy

Mild twitching

Unresponsiveness

EEG general ictal

CAUSES OF STATUS: ADULTS

0 5 10 15 20 25 30

Cerebrovascular

Med change

Anoxia

ETOH-drug

Metabolic

Unknown

Fever/infection

Trauma

Tumor

Congenital%

from DeLorenzo et al. Epilepsia 1992; 33 (Suppl. 4): S15-25

COMPLICATIONS OF STATUS

HyperthermiaShockRhabdomyolysisArrhythmiasAspirationPhysical Injuries

PsychosocialBrain cell lossDeath in 5-30%Iatrogenic injury

Walker MC, Howard RS, Smith SJ, Miller DH, Shorvon SD, Hirsch NP. Diagnosis and treatment of status epilepticus on a neurological intensive care unit. QJM 1996; 89: 913-20.

26 pts admitted to neuro-ICU as status epilepticus Only 14 (54%) were in status epilepticus Six were in drug-induced coma or were encephalopathic Six had pseudo-status epilepticus: 4 were intubated.

MISDIAGNOSIS

Discrete seizures

Waxing ictal

Continuous ictal

Continuous ictal with flat

PLEDs on flat background

SEQUENCE OF EEG CHANGESIN STATUS EPILEPTICUS

Discrete seizures

FP1-F7

F7-T3

T3-T5

T5-O1

FP2-F8

F8-T4

T4-T6

T6-O2

1 sec 100 µV

Continuous ictal discharges

FP1-F7

F7-T3

T3-T5

T5-O1

FP2-F8

F8-T4

T4-T6

T6-O2

1 sec 200 µV

Fp1-F7

F7-T3

T3-T5

T5-O1

Fp2-F8

F8-T4

T4-T6

T6-O2

Fp1-F3

F3-C3

C3-P3

P3-O1

Fp2-F4

F4-C4

C4-P4

P4-O21 sec100 µV

PLEDS

0

10

20

30

40

50

60

70

80

%

Discrete Waxing Continuous Cont with flat PLEDs

STAGE OF EEG & RESPONSE TO THERAPY

Treiman et al. from VA study 1996

% recovery

In 1685, King Charles II of England suffered from an illness

that caused him to have convulsions. The treatments he underwent included: "letting" of one pint of blood; an enema of antimony, sacred bitters, rock salt, marrow leaves, violets,

beetroot, chamomile flowers, fennel seeds, linseed, cinnamon, cardamon seeds, and aloe; and

having his head shaved and blistered. Needless to say, the

King died.

quoted in:http://www.epilepsynl.com/newsletters/NewsletterFall2004.pdf

Charles II of EnglandKing of Scots, King of England and King of Ireland

(and Ruler of the American Colony)Reign: 29 May 1660 – 6 February 1685

Born: 29 May 1630 Died: 6 February 1685

A 42 year old male known alcoholabuser was brought to the ER stiffand trembling. He was thought tobe exhibiting DT's (1), and was there-fore given diazepam by NG tube.This precipitated emesis and associatedaspiration (2). Then all 4 extremitiesbegan to jerk rhythmically.

HOW NOT TO TREAT STATUS

An iv was established, and routinebloods sent to the lab (3). Anticonvul-sants were withheld for 45 minutespending arrival of the medical record (4).Seizure activity was terminated with 10mg diazepam iv push, but tonic-clonicmovements recurred 15 minutes later(5). Phenytoin 300 mg was given intra-muscularly to no effect (6).

HOW NOT TO TREAT STATUS

Phenobarbital 500 mg iv was given as athird drug, resulting in apnea and hypo-tension (7). The patient resided in anICU for 24 hours, whereupon he awoke,exhibited no further seizures, and wasdischarged that day (8)

HOW NOT TO TREAT STATUS

1. Secure the correct diagnosis2. Stabilize patient first3. Treat the treatable4. Stop within 30 minutes5. Immediate + long-term control6. Proper routes and doses of meds7. Expect cardiorespiratory trouble8. Diagnosis and follow-up

PRINCIPLES FOR STATUS

STABILIZE

Airway Breathing Circulation Oxygen Dextrose ?

Breathing Pulse Blood Pressure EKG EEG

MONITOR

Ten Centers, 530 evaluable patients

Four iv regimens for initial Rx GTC status PHT 18 mg/kg DZP 0.15 mg/kg, then PHT 18 mg/kg PBB 15 mg/kg LOR 0.1 mg/kg

Endpoint: seizure-free from 20-60 minutes Clinical

EEG

VA COOP STATUS STUDY

Treiman et al. from VA study 1996

0

10

20

30

40

50

60

70

%

LOR PBB DZP+PHT PHT

CONTROL BY DRUG

You stop the visible seizures,but the patient doesn’t wake upfor an hour.

What should you do?

20% had EEG statuscontinuing after behavioralseizures had stopped.

80%

20%

Treiman et al. from VA study 1996

Rate of recurrence39 day outcomeAdverse events

No differences amongfour treatment group for :

Treiman et al. from VA study 1996

Outcome Overt Subtle

Improved, discharged 53% 9%Still in hospital 21% 25%Died 27% 65%

Treiman et al. 1996 VA Coop

But – is usual outcome really this poor?

100 consecutive ICU NCSE patients. 18 (18%) died: 14/52 (27%) in acute medical group 1/31 (3%) in the epilepsy group 3/17 (18%) in the cryptogenic group

Mental status impairment was severe in 33 Complications occurred in 39

Shneker BF, Fountain NB. Assessment of acute morbidity and mortality in nonconvulsive status epilepticus. Neurology 2003;61:1066-1073.

lorazepam (Ativan) phenytoin (Dilantin) phenobarbital

pentobarbitalpropofol (Diprivan)midazolam (Versed)

isofluoraneetomidatelidocaineparaldehydemagnesiumfurosemide

cooling ???

DRUG THERAPY

PENTOBARBITAL

CVP line or Swan Load: 5-15 mg/kg in 250 cc NS over 1 hr Orders for neosynephrine or pressors Continuous EEG monitoring Maintain 1-20 mg/kg per minute Aim for about 70-90% EEG suppression Taper after a few days over half a day

FP1-F7F7-T3T3-T5T5-O1FP2-F8F8-T4T4-T6T6-O2FP1-F3F3-C3C3-P3P3-O1FP2-F4F4-C4C4-P4P4-O2

1 sec 100 µV

PROPOFOL: USE IN STATUS

Quicker wake-up

Maybe less respiratory depression

Bolus of 2 mg/kg

Continuous infusion 1-10 mg/kg/hr (17-170 ug/kg/m)

EEG monitoring with titration to burst-suppression

Supportive care for comatose patients

Be aware of expense

PROPOFOL: ADVERSE EFFECTS

Respiratory depression with induction > 2.5 mg/kg

Hypotension in about 15%

Bradycardia in about 5%

< 0.2% of 25,981 pts needed hemodynamic support

Increases serum triglycerides

Lipid, egg, glycerol solvent may get infected

Propofol infusion syndrome (rare)

Sometimes paradoxical induction of seizures

6 y/o Boy with Shunt Failure

Elderly Man Post-Anoxia

36 y/o man with 10 Tonic-Clonic Seizures Today

Prior EEG: Half-Speed

Triphasics vs. Nonconvulsive Status

• Difficult EEG distinction, perhaps impossible• Both show periodic frontal 3-phase sharp potentials• Triphasics can have an after-going slow wave• Both wax and wane• Both can have an anterior-posterior gradient• Triphasics tend to decline with sleep (but variably)• Waxing-waning awareness in both• Involves BDZ receptors in both• What is metabolic encephalopathy anyway?

6 y/o Girl with Status Epilepticus

Elderly Woman with Renal Failure

1 sec

100 µV

FP1-F7F7-T3T3-T5T5-O1FP2-F8F8-T4T4-T6T6-O2FP1-F3F3-C3C3-P3P3-O1FP2-F4F4-C4C4-P4P4-O2

Triphasic waves

SPECIAL CIRCUMSTANCES

Need IV medication phenytoin

fosphenytoin phenobarbital

diazepam, lorazepam, midazolam Depacon (valproic acid)

paraldehyde (if obtainable) levetiracetam (Keppra) lacosamide (Vimpat)

SPECIAL CIRCUMSTANCES

Need to avoid sedation

Most except

phenobarbital

benzodiazepines

SPECIAL CIRCUMSTANCES

Need to avoid WBC depression

Most OK, Except

carbamazepine

oxcarbazepine

valproic acid

felbamate

SPECIAL CIRCUMSTANCES

Need to avoid low sodium

Most OK, Except carbamazepine

oxcarbazepine

COMMON MISTAKES

1. Fail to recognize status

2. Fail to deliver emergency support

3. Not treating reversible causesHypoglycemiaHypocalcemiaHypoxiaToxic ingestionHyperthermiaOther reversible causes

4. Too slow with meds

5. Partial polypharmacy

CONCLUSIONS

1. Status is common and lethal

2. Early/effective treatment makes a difference

3. Subtle status can be missed

4. First support the patient & treat the treatable

5. Lorazepam is the favored therapy

6. Several other drugs can be used later: e.g., propofol or pentobarbital coma

7. With best therapy, mortality remains high