10 novembre 2006gabriella paglia simeu-torino1 torino, centro congressi lingotto 9-11 novembre 2006...

10 Novembre 2006 Gabriella Paglia SIMEU-Torino 1

Torino, Centro Congressi Lingotto 9-11 Novembre 2006

V CONGRESSO NAZIONALE SIMEUTHE SIMEU/ACEP

"Emergency Medicine Congress"

Gabriella Paglia, MD

Neurology Department

ASO S Giovanni Battista - Torino


Diagnosis: seizures

Seizures in the Emergency Department

Isolated uncomplicated seizureFlurry of seizures (SE risk)Status epilepticusRefractory status epilepticus


Status epilepticus

ILAE Classification 2001 Definitionfor SE

a seizure which shows no clinical signs of arresting after a duration encompassing the great majority of seizures of that type in most patients [at least 5 minutes commonly, postictal state not included]

or

recurrent seizures without resumption of baseline central nervous system function interictally

Refractory SE

SE lasting more than 30’ despite infusion of first and second line drugs


Status epilepticus: classification

Generalized SE: generalized tonic-clonic SE, clonic SE, absence SE, tonic SE, myoclonic SE

Focal SE: epilepsia partialis continua of Kojevnikov, aura continua, limbic SE (psychomotor status), hemiconvulsive status with hemiparesis, partial somatomotor SE

Convulsive SE (GCSE)

Nonconvulsive SE


Status epilepticus

GCSE differential diagnosis not difficult“the easier the diagnosis, the worse the prognosis”

P.Thomas 2002

Repetitive syncopes with clonic jerks Decerebration tonic seizures Myoclonic Nonepileptic Status

in some post-anoxic or metabolic encephalopathies myoclonic jerks are not related to a paroxystic EEG activity (Assal F, 2000): in these cases infusion of AEDs may be not appropriate

Psychogenic Nonepileptic Seizures Walker 1996: 6/26 patient admitted in Intensive Unit Care had only behavioral troubles and 4/6 had orotracheal intubation


Status epilepticus

Psychogenic SE

more frequent in women <40 years old with a history of epileptic seizures in childhood or exposure to epilepsy in others

more frequent in mentally retarded patients

not metabolic acidosis in ABG, prolactin and cortisol levels not increased

aspecific psychiatric pattern at MMPI or

personality disorder, conversion disorder, Műnchausen syndrome

critical pattern: progressive onset, eyes closed, back arching, pelvic thrusting, rarely morsus or respitarory disturbances with cyanosis, rarely traumatic lesions or bladder incontinence, not autonomyc disorders

behavioral troubles may be increased by inappropriate AED usePakalnis A 1991; Jagoda A, 1995


Status epilepticus

Incidence

9.9-15,8/100 000 in European studies (excluding SE after anoxic encephalopathy following cardiac arrest)

18,3-41/100 000 in US studies

Mortality rate (death within 30 days)

22% in Richmond study 21% in Rochester

10-33% in EU studies Logroscino G et al., 2005

Outcome is often related to the underlying cause of brain injury, to the duration of the seizure and to patient’s age

Lowenstein DH, 1999


Status epilepticus

Etiology

cerebrovascular disease 25% 41%

low levels of antiepileptic drug 20% 20%

alcohol/other drugs 15% 7%

CNS infection 10%

Hypoxia 10%

Metabolic and electrolyte disorders 10%

Tumor 5% 5%

Trauma 5% 10%

Hyperthermia 2%Hauser ey al, 1990; DeLorenzo et al, 1992; Vignatelli L et al, 2003

24%


Status epilepticus=emergency

Life-threatening condition

Neurological complicationsNeuronal loss (hippocampus especially)

cerebral metabolic demand increased

(but cerebral blood flow and oxygenation are normally preserved or even elevated)

abnormal electrical discharges

(studies with paralyzed and artificially ventilated animals)

(Huff SJ, 2005)


Status epilepticus=emergency

Systemic complications

metabolic lactic acidosis, hypercapnia, hypoglicemia, hyperkaliemia, hyponatriemia, leukocytosis

autonomic hyperprexia, vomiting, incontinence, hypotension (failure of cerebral autoregulation)

renal (acute renal failure from rhabdomyolysis, myoglobinuria)

cardiac/respiratory hypoxia, arrhythmia, pneumonia (high output failure)

Lowenstein DH, Alldredge BK. 1998


Status epilepticus: treatment

ED Priorities stop SE and prevent seizure or SE recurrence

earlier treatment is more effective than later treatment in halting SE and prevent evolution to subtle SE

begin to treat if seizure activity doesn’t terminate within 5’

stabilize the patient’s medical condition look for the etiology of the seizures coordinate care with appropriate physician make disposition to the appropriate service and medical unit



First line drugs: benzodiazepinesEtiological treatment, when possibleTreatment of systemic complicationSecond line drugs: PHT, VPA, PBGeneral Anaesthesia



EUOutin HD et al. Prise en charge des états de mal épileptique. Rev Neurol 2002;

158:1059-68 France

van Rijckevorsel K et al. Standards of care for adults with convulsive status epilepticus: Belgian consensus recommendations. Acta Neurol Belg 2005;105:111-8 Belgium

Kalviainen et al, Refractory generlized convulsive status epilepticus:a guide to treatment. CNS Drug 2005;19:759-68 Finland

USA

Treatment of convulsive status epilepticus. Epilepsy Foundation of America. JAMA 1993

Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998;338:970-6



Ideal AED for SE

Intravenous administration (it allows therapeutic tissue levels to be attained more rapidly)

Linear pharmacokinetics Rapid action Long-lasting epileptic effect Minimal cardiopulmonary and other systemic effect Minimal depression of neurological functions

Steinhoff BJ et al, Acta Neurol Scand 2003



Pre-hospital careTime 0-5: diagnosis

ABC O2 therapy

intravenous acces rapid glucose determination

ECG

Time 6-10: treatment

Thiamine 100 mg e.v.

Glucose infusion: 50 ml 50 % if hypoglycemia

First line drugs:

Lorazepam 4 mg iv or diazepam 10 mg iv



Lorazepam Diazepam

onset of effect 3-5’ 1-3’ (high lipid solubility)

effect duration 6-12 h 15-20’ (time redistribution)

elimination half-life 12h 24 h

dose 4 mg (A) 10-20mg (A)

0.1 mg/kg (C) 0.2-0.5 mg/kg (C)

route IV or IM IV or PR

readministration 10-15’ not indicated

side-effects hypotension, respiratory suppression

cautions myasthenia gravis, narrow angle glaucoma



First line drug: benzodiazepines

Diazepam vs lorazepam

“in patients with SE, lorazepam is better than diazepam, phenytoin or placebo for cessation of seizures, and diazepam is better than placebo. Lorazepam is better than diazepam for preventing SE requiring a different drug or general anaesthesia”

Prasad K et al, EBM 2006: a Cochrane Database Syst Rev



First line drug: benzodiazepinesDiazepam vs lorazepam

“as initial intravenous treatment for overt generalized convulsive SE, lorazepam is more effective than phenytoin. Although lorazepam is no more efficacious than phenobarbitale or diazepam plus pheytoin, it is easier to use”

Treiman DM et al, N Engl J Med 1998

Lorazepam 64.9%

Phenobarbital 58.2%

Diazepam + phenytoin 55.8%

Phenytoin 43.6%



Emergency Department careTime 10-20Intravenous access, ideally in a large vein

Serum test: including Ca++, Mg++

toxicologic testing (AED, theophylline, isoniazide, ethanol)

ABG (arterial blood gas: metabolic acidosis)

Second line drug

phenytoin, valproic acid, topiramate, levetiracetam

(phenobarbital)

ECG and Blood pressure monitoring

CT scan to determine etiology



Phenytoin Fosphenytoin

effect onset 15-30’ idem IV, longer IM

effect duration 12-24h idem

dose 18-20 mg/kg 15-20 mgPE/kg

administration rate 50 mg/min 100 mgPE/min

dose max 30 mg/kg

route IV IV or IM

advantages: lack of CNS and respiratory depression

controindication: SA block,AV block II-III,Adam Stoke S, BS

side-effects: hypotension, arrhythmias, cardiac arrest (QRS widening),

skin reaction (purple glove syndrome)



Valproic acid

Dose 25-30 mg/kg infusion rate 3-5 mg/Kg/min

Onset of effect: 15-20 min

Side effect: gastrointestinal distress, lethargy, tremors

Advantages: no respiratory or cardiac disturbances“easy-to-use, safe and efficient formulation…in all seizure emergency situation…further controlled comparison studies have to be performed in the future”

Useful in patients with absence or myoclonic SE, or in patients already receiving VPA as oral chronic therapy, in children

(Yu KT, 2003; Peters CN, 2005; Misra UK, 2006)



Emergency Department CareTime 20-30

phenobarbital

20mg/kg, maximum infusion rate 100 mg/min IV

Onset of effect: 15-20’ Half-life: 3-5 days

Ventilation and intubation may be necessary

Hypotension may need treatment.

Diluted in propylene glycol.

France: doses in succession (5-10 mg/kg every 30’) to avoid general anaesthesia.

Italy: used only in GA



Time 30+ : refractory status epilepticusneeds more aggressive treatment

Intensive Care Unit ventilation and haemodynamic support

EEG monitoring

GA given in doses that abolish all clinical and EEG epileptic activity, often till the burst-suppression pattern.

Once seizures have been controlled for 12-24 h continuous IV therapy should be gradually tapered off

During the withdrawal of GA, phenytoin or valproate should be given to ensure an adequate baseline of AED medication to prevent recurrence Kalviainen et al, 2005



Intensive Care Unit

propofol (Diprivan)

Phenolic compound

Growing anecdotal reports of use in RSE.

Dose: 1 mg/kg in 5’, then 5-10 mg/kg/h

Onset of effect 1’ duration 10’

To stop if no resolution after 45’.

If resolution slow tapering off after 12-24h

May have paradoxal proconvulsant effect



Intensive Care Unit

midazolam (Hypnovel)

0.2 mg/kg in 1’ infusion rate 1-10 μg/Kg/min

onset of effect: 1’ effect duration 15-60’

Respiratory depression, in EU used in general anaestesia.

To stop if no resolution after 60’

If resolution continue 12h, than attempt to stop



Intensive Care Unit

thiopental (Penthotal)

used in RSE since 1967

Dose: 3-5 mg/kg in 3’, then 1-3 mg/kg/h

onset of effect: 1’, effect duration 20’

Respiratory depression and hypotension

Deep anaesthesia, guided by EEG, seems related to a better outcome and fewer recurrence

Advantages: neuroprotective effect and lowering intracranial pressure Krishnamurthy KB et al, 1999



Intensive Care Unit

pentobarbital (Nembutal)

ketamine

lidocaine (may have paradoxal proconvulsant effect)


Status epilepticus

Role of EEG diagnosis in NCSE diagnosis in myoclonic nonepileptic seizure diagnosis of seizures or SE recurrence after a first episode

(24h monitoring) necessary if a patient doesn’t regain consciousness

after 30’despite resolution of clinical SE

to differentiate between subtle SE, sedation, post-ictal confusion

Thomas P 2002, Treiman 1998



Subtle Status Epilepticus

electrical seizure activity that endures when the associated movements are fragmentary or even absent.

Commonly, this pattern can be the evolution of a GCSE

Significantly lower response rates to all treatment

EEG monitoring 24 h


References

Lowenstein DH, Alldredge BK Status epilepticus. N Engl J Med 1998;338:970-6

DeLorenzo RJ, Hauser WA, Towne AR et al. A propsective, population based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology1996;46:1029-35

Logroscino G et al. Epilepsia 2005;46 Suppl 11:46-8

Lowenstein DH. Epilepsia 1999;40 Suppl 1:S3-8; discussione S21-2

van Rijckevorsel K et al. Acta Neurol Belg 2005;105:111-8

Fernandez-Torre JL et al. Clin EEG Neurosci 2006;37:215-8

Walker MC et al. Q J Med 1996;89:913-20

Walker MC et al, Anaesthesia 1995;50:130-5 ++

Pakanis A et al. Neuropsychiatric aspects of psychogenic status epilepticus. Neurology 1991;41:1104-1106

Kalviainen et al, Refractory generlized convulsive status epilepticus:a guide to treatment. CNS Drug 2005;19:759-68

Steinhoff BJ, Hirsch E, Mutani R, Nakken KO, Acta Neurol Scand 2003;107:87-95


References

Thomas P. Encycl Med Chir, Neurologie 2002, 17-045-A-40

Treiman DM et al. A comparison of four tretmente for GCSE. Veterans Affair SE Cooperative Study Group. N Engl J Med 1998;339:792-8

Assal F et al. L’état de mal résistant aux antiépileptiques. Neurol Clin 2000;30:139-145

Outin HD et al. Rev Neurol 2002; 158:1059-68

Jagoda A et al. Psychogenic status epilepticus. J Emerg Med 1995;13:31-5

Vignatelli L, Tonon C, D’Alessandro R. Epilepsia 2003;44:964-8

Treatment of convulsive status epilepticus. Recommendation of the Epilepsy foundation of America’s Working Group on SE. JAMA 1993, 270:854-9

Krishnamurthy KB et al. Depth of EEG suppression and outcom ein barbiturate anesthetic treatment for refractory status epilepticus. Epilepsia 1999;40:759-62

Misra UK et al. Sodium valproate vs phenytoin in SE: a pilot study. Neurology 2006;67(2):340-2

Peters CN, Pohlamann-Eden B. Intravenousvalproate…. Seizure 2005;14:164-9


“The end”

Grazie

Thanks

10 novembre 2006gabriella paglia simeu-torino1 torino, centro congressi lingotto 9-11 novembre 2006...

Documents

absence se

classificationgeneralized

limbic se psychomotor

hemiconvulsive status

myoclonic sefocal se

generalized tonicclonic

recurrent seizures

great majority of seizures