EM guidemap - Status epilepticus

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Introduction

History of present illness

Differential diagnosis

Features suggesting psychogenic seizures

Examination

Diagnostic testing

Medical decision-making/treatment Clinical pearls

Introduction

- this guidemap only deals with status epilepticus due to generalized convulsive seizures and it is mainly focused on the management of active ongoing seizures => see the seizures in adults guidemap for a basic approach to generalized seizures in adults

Definitions:

Overt GCSE – patient has recurrent or continuous motor convulsive activity lasting longer than 10 - 20 minutes without regaining consciousness

Subtle GCSE – prolonged coma (> 30 minutes) following generalized convulsions with minor motor activity still present (rapid nystagmoid jerking movements of the eyes or twitching of the limbs)

Silent GCSE – any patient who fails to arouse within 30 minutes and has continuous seizure activity present on an EEG, but who has no clinical signs of seizure activity

Refractory GCSE – seizures persisting after the administration of IV benzodiazepines and fosphenytoin +/- phenobarbital

Etiology of generalized seizures:-

- 1/3 of episodes are due to known seizure disorders

- 1/3 occur as initial manifestations of a seizure disorder

- 1/3 are due to a myriad of medical, neurological and toxic conditions

Commonest causes of generalized convulsive seizures in adults (in descending order of frequency)

- discontinuation/irregular use of anti-convulsant medications

- alcohol-related

- cerebro-vascular diseases

- drug overdoses (lithium, theophylline, cocaine, amphetamines, INH, antidepressants, antihistamines, salicylates, cyanide, mushrooms, camphor, carbon monoxide)

- metabolic disorders (hypoglycemia, hyperglycemia, hyponatremia, hypernatremia, hypocalcemia, hypomagnesemia, hepatic encephalopathy)

- CNS trauma

- CNS tumors

- CNS infection

(* also consider toxoplasmosis, cryptococcal meningitis, CNS lyphoma, tuberculous meningitis in the HIV positive patient)

Consequences of uncontrolled generalized convulsions:-

=> permanent neurological damage (cognitive impairment, hemiparesis, aphasia, ataxia, impaired LOC, permanent epilepsy) - usually irreversible after 60 minutes of continuous seizure activity

=> systemic effects (hyperpyrexia, hyper/hypotension, cardiac arrhythmias, pulmonary edema, aspiration pneumonia, secondary injuries, lacticacidosis, rhabdomyolysis, hyper/hypoglycemia, leucocytosis, CSF pleocytosis

=> death (mortality = 8 - 50%)

History of the present illness

- a detailed history should be taken from eyewitnesses, family members or friends, police and rescue personnel

"Did the attack begin abruptly or gradually?"

"Was the patient asleep or awake?"

"If awake, what was the patient doing at the time?"

"How long did the attack last?"

"What kind of abnormal movements and which extremities were involved?"

"What was the patient’s mental status during the attack?"

"Was there any precipitating event?"

"Did the patient fall or otherwise injure him/herself during the seizure?"

"Did the patient bite his tongue or develop urinary incontinence?"

- determine whether the patient has a previous history of seizures and whether the patient is reliably taking his anti-seizure medications

(-) previous seizures (-) history of blank spells/staring (-) anti-seizure medication non-compliance

- perform a secondary historical search for clues to the possible etiological cause of the seizure

(-) sedative drug or alcohol withdrawal (-) recent head trauma (-) recent headache (-) recent neuro symptoms (-) recent fever (-) recent URI (-) recent ear/sinus infection (-) recent neurosurgery (-) chronic neurological disorders (-) recreational drug abuse (-) alcohol abuse (-) intentional/accidental drug overdose (-) occupational exposure to insecticides, cyanide or carbon monoxide (-) recent suicide ideation (-) known malignancy (-) weight loss (-) night sweats (-) known HIV infection (-) possible cysticercosis exposure

Differential diagnoses

Features suggesting psychogenic seizures
Examination

-  check the vital signs including the rectal temperature

(* a fever may occur secondary to prolonged motor activity, but marked hyperpyrexia should suggest the possibility of CNS infection, neuroleptic malignant syndrome, heat stroke, thyroid storm or an anticholinergic/sympathomimetic toxidrome)

- assess the mental status, pupil position and reactivity, and perform a complete neurological examination specifically looking for the presence of any focal neurological signs

(* the patient may have widely dilated pupils during the seizure, while an ipsilateral unreactive pupil should suggest the possibility of decerebrate posturing secondary to an increased ICP)

- look for "automatisms" (lip smacking, swallowing, eyelid flickering, chewing movements, limb twitching) which may suggest ongoing seizure activity in the unresponsive, post-ictal patient

- look for evidence of tongue biting, incontinence or soft tissue or skeletal injuries secondary to the seizure or a subsequent fall

(* posterior shoulder dislocations are very rare, may be clinically subtle and are very suggestive of a previous seizure)

- look for signs of a toxidrome (anti-cholinergic, sympathomimetic, tricylic overdose)

- look for signs suggestive of an underlying disease, which may have precipitated the seizure

Diagnostic testing

Baseline blood studies

- CBC, blood glucose and electrolytes, calcium, magnesium, BUN and creatinine, CPK, serum anti-convulsant drug levels, serum alcohol, toxicology screening, serum HCG in women of child-bearing age, blood cultures if febrile or sepsis suspected

- other tests are perfomed prn - carboxyhemoglobin level, thyroid hormone levels, serum salicylate, serum theophylline, serum lithium

Arterial blood gas

- an ABG may reveal an anion gap acidosis secondary to a lacticacidosis from the prolonged seizure activity

- consider other causes of an anion gap acidosis (ethylene glycol/methanol, salicylate poisoning) if the acidosis persists for longer than one hour after the seizures cease

Urinalysis

- check the urine for myoglobin and evidence of infection

ECG

- a wide QRS complex or tachyarrhythmia may suggest certain drug overdoses (tricyclics or other antidepressants, cocaine or other sympathomimetics)

CT scan of the head

- ? is indicated in all cases of GCSE, especially if:-

EEG

- indicated if the patient doesn’t awaken within 30 minutes to rule-out "silent" status epilepticus; also indicated if the patient has been paralyzed with a long-acting paralytic agent, or if iatrogenic "barbiturate coma" has been induced

LP

- in all febrile patients, especially if meningitis is suspected => immediately administer empiric antibiotics IV if meningitis is possible and delay a spinal tap until adequate seizure control has been established

(* remember that GCSE may produce a CSF pleocytosis)

Medical decision-making and treatment

- the rationale for early and aggressive management of generalized seizures is based on studies showing that:-

i) the longer GCSE persists => the harder it is to stop the seizures

ii) neurological damage is primarily due to continuous neuro-excitatory activity and not due to the systemic effects of continuous seizures

- progressive neurological damage may be manifested during the seizure by the change in presentation from overt GCSE => subtle GCSE, and finally => silent GCSE

The essence of optimal treatment = ‘speed’

Remember the maxim - ‘Time’ saved = ‘Brain cells’ saved

Recommended time sequence for ED management
 
0 - 10 minutes ABC's, glucose, thiamine, benzodiazepines
 
10 - 20 minutes Fosphenytoin
 
20 - 30 minutes  Phenobarbital
 
30 - 60 minutes More phenobarbital +/- 4th drug

Initial treatment is focused on establishing monitoring and stabilization procedures

During the first 5 minutes - concentrate all efforts on airway management, ensuring 100% oxygenation, rapid glucose testing, acquiring IV access (preferably two lines), IV glucose and thiamine administration prn, establishing cardiac monitoring and continuous pulse oximetry

(* 100mg of thiamine +/- 2g of magnesium should be given empirically to malnourished or alcoholic patients)

If the seizures persist for longer than 2 minutes => proceed to step 1

STEP 1: - BENZODIAZEPINES

1) Lorazepam (Ativan) IV - 0.1 mg/kg. In the average-sized adult, give 1mg/min to a maximum of 10 mg over 10 minutes

or give:-

2) Diazepam (Valium) IV - 0.25 mg/kg. In the average-sized adult, give 2 mg every minute to a maximum of 20 mg over 10 minutes

(* lorazepam has the advantage of providing anti-seizure activity that lasts many hours (12 - 24 hours), while the anti-seizure effect of diazepam wears-off within 15 - 20 minutes => lorazepam may be effective when used alone, while a second drug (phenytoin/phenobarbital) will usually be required when diazepam is used as the first-line drug; diazepam has the theoretical advantage of entering the brain faster and having a faster clinical effect - although clinical studies do not show significantly faster anti-seizure control with diazepam)

If an IV cannot be readily established => the following options are available:-

1) Midazolam = 10 mg IM in the average-sized adult (0.15 - 0.3 mg/kg IM)

2) Diazepam = 0.5 - 1.0mg/kg rectally using the IV solution per rectal tube or the diazepam gel preparation

Midazolam may become the benzodiazepine-of-choice, because it can be given IM before an IV can be readily established; and also because IV midazolam may even be more efficacious than IV diazepam or IV lorazepam

If the seizures are not controlled within 8 - 10 minutes => proceed to step 2

STEP 2:- FOSPHENYTOIN

Fosphenytoin (Cerebryx) IV - 20 mg/kg, at a maximum IV rate of 150mg/min in the average-sized adult (~ 3mg/kg/min)

(* Fosphenytoin (Cerebryx) has the slight advantage over phenytoin (Dilantin) in that it can be given faster IV with less chance of producing hypotension or cardiac arrhythmias or QRS prolongation. Fosphenytoin can be infused over 10 minutes instead of the 30 minutes it takes to safely administer a loading dose of IV phenytoin. It is less of an venous-irritant and does not cause tissue necrosis when IV extravasation occurs. It is compatible with dextrose-containing IV solutions => it is questionable whether these benefits warrant the routine use of fosphenytoin in SE)

If the seizures are not controlled after the administration of IV fosphenytoin => proceed to step 3

STEP 3

1) An additional dose of 10 mg/kg of fosphenytoin IV over 5 minutes to a maximum total dose of 30 mg/kg (recommended treatment)

or :-

2) Phenobarbital IV - 20 mg/kg, at a maximum rate of 50 - 100mg/min in the average-sized adult (~ 1mg/kg/min)

(* VERY strong consideration should be given to intubating the patient - if you have not already decided that it was clinically necessary at an earlier stage - prior to administering phenobarbital, because marked respiratory depression should be expected during the administration of the loading dose of phenobarbital. The present formulation of phenobarbital has polypropylene glycol as the diluent => rapid IV infusion will cause hypotension and extravastion will result in marked tissue necrosis)

If the seizures persist after giving the loading dose of phenobarbital => proceed to step 4

STEP 4

1) An additional dose of 10 mg/kg of phenobarbital IV to a maximum total dose of 30 mg/kg, or give a 4th drug IV
 
Other drugs Loading dose

 

 Maintenance dose required to prevent seizure recurrence
Pentobarbital      5 - 15 mg/kg (max rate of 
25 - 50 mg/min)
 		 0.5 - 5.0 mg/kg/hour
Propofol  1 - 2 mg/kg 0.5 - 10 mg/kg/hour
 
Midazolam 0.2 mg/kg 0.1 - 0.4 mg/kg/hour (max of 2mg/kg/hour)
 
Thiopental 1- 2 mg/kg/minute until seizure   suppressed titrate up from 3 - 5mg/kg/hour 

- give the loading dose of the chosen 4th drug until the seizure ceases (or until the EEG shows spike suppression if the patient is paralysed) => increase the dose to obtain burst suppression with short intervals of < 1 second between pauses as a secondary EEG endpoint if the blood pressure is adequate), and then maintain EEG burst suppression utilizing maintenance infusions of the same anti-seizure medication for 12 hours before considering drug dose tapering

- pentobarbital is the "traditional" choice when using a 4th drug  - a loading dose of 5 mg/kg at a rate of 25 mg/min => maintenance infusion rate of 2.5 mg/kg/hour => repeat bolus of 1 - 2 mg/kg for persistent/recurrent seizure => increase infusion rate by 0.5 mg/kg/hour => repeat the process prn up to the maximum recommended loading/maintenance dose, or until EEG seizure activity is suppressed => maintain that maintenance dose for 12 hours after the patient is seizure-free => attempt to reduce dose by 50%

(* the recommended use of propofol and midazolam for refractory GCSE has been based on anecdotal reports and small studies; some neurologists prefer propofol or midazolam over pentobarbital because they believe that major hemodynamic compromise requiring aggressive hemodynamic support is less of a problem and that muscle weakess preventing early weaning from a ventilator is less likely; propofol may produce neuro-excitatory events - including opisthotonus, muscle rigidity, choreathetoid movements, myoclonus - which may be clinically difficult to differentiate from ongoing generalized convulsive seizures; tachyphylaxis occurs in 24 - 48 hours in some patients receiving midazolam => maintenance doses may have to be increased several-fold to a maximum of 2mg/kg/hour => delayed awakening will occur secondary to accumulation of certain midazolam metabolites)

- high doses of pentobarbital will cause cessation of motor activity, cessation of spontaneous respiratory activity and poikilothermia

- blood pressure support and mechanical ventilation will usually be required during this 4th phase of treatment

- continuous EEG monitoring is mandatory to assess whether brain seizure activity is still occurring in the motionless patient, who could be in a state of 'silent' GCSE

- a prompt neurological consultation and ICU admission is necessary

- search for, and expeditiously treat, the underlying cause of the seizure

(* blood cultures should always be performed, and early empiric IV antibiotic therapy should always be administered to all patients who may have meningitis)

- treat the secondary systemic effects of the seizure - hyperpyrexia, lacticacidosis, rhabdomyolysis, dysrhythmias, fractures, aspiration pneumonia, pulmonary edema and DIC

CLINICAL PEARLS

1) The same dose of fosphenytoin is used to treat patients who have a history of seizures and who are supposed to be taking maintenance dilantin po - because those patients usually have very low or non-existent serum phenytoin levels

2) In neonatal GCSE - phenobarbital can/should be used before fosphenytoin

3) Fosphenytoin is not useful for drug-induced or metabolic-induced seizures - rapid acting thiopental or midazolam or propofol may be the drug-of-choice after benzodiazepines

4) If GCSE is due to suspected INH overdose - add 5g pyridoxine (in 50cc saline over 5 minutes) to the treatment regimen

5) Avoid long-acting neuromuscular paralysing agents - unless continuous EEG monitoring is established

6) 4 - 6g of magnesium sulfate IV over 15 minutes is the initial anti-convulsant drug-of-choice in the patient with eclampsia

(* see the "eclampsia" guidemap for further details)

7) IV valproate - 15mg/kg loading dose at 3mg/kg/min - has been approved for status epilepticus, although its role remains uncertain => it may be suitable as the third line drug after fosphenytoin, and it may replace phenobarbital in the traditional algorithm

Disclaimer: My EM guidemaps reflect my personal approach to problem-solving/managing clinical cases in an ED setting and they should not be regarded as the standard of care. They merely represent the personal opinions of the author and they should only be used in clinical practice if the reader-user has substantial reason to believe that the clinical advice contained in the guidemaps is valid and accurate. The guidemaps are not meant to be "authoritative" and the reader-user should consult standard medical textbooks and expert opinion articles/guidelines for more authoritative advice. The reader-user should particularly confirm all drug doses, their indications and contra-indications, prior to their use.