Status Epilepticus

30
Rajesh Chawla and Chirag Madan

A 42-year-old male patient, with a known case of epilepsy for 6 years on irregu-
lar treatment, was brought to the hospital with recurrent generalized tonic–clonic
seizures and he was unconscious for 40 min.

Status epilepticus (CSE) for adults and older children (>5 years old) is “a con-
tinuous, generalized, convulsive seizure lasting more than 5 min, or two or more
seizures during which the patient does not return to baseline consciousness.”

• This definition is based on the observations that spontaneous cessation of gener-

alized convulsive seizures is unlikely after 5 min.
• Initial assessment and treatment of status epilepticus should proceed
simultaneously.
• For the purpose of standardization, initial pharmacotherapy of seizure has been
divided into four stages (Table 30.1):
1. Stabilization phase (0–5 min)
2. Initial therapy phase (5–20 min)
3. Second therapy phase (20–40 min)
Third therapy phase (40–60 min)
4. Refractory status epilepticus (RSE) (>60 min)

Status epilepticus or recurrent seizures carry a mortality as high as 30% in adults

and should be managed in a proper manner.

R. Chawla (*) · C. Madan

Department of Respiratory, Critical Care & Sleep Medicine, Indraprastha Apollo Hospitals,
New Delhi, India

© Springer Nature Singapore Pte Ltd. 2020 301

R. Chawla, S. Todi (eds.), ICU Protocols, https://doi.org/10.1007/978-981-15-0898-1_30
302 R. Chawla and C. Madan

Table 30.1 Treatment algorithm for convulsive status epilepticus

1. Stabilization phase (0–5 min)
• Perform ABCD,IV access, fingerstick glucose
• Consider IV Thiamine + IV Glucose
2. Initial therapy phase (5–20 min)
• IV Lorazepam (0.1 mg/kg/dose; max: 4 mg/dose, may repeat dose once,)
          OR
  • IM Midazolam (10 mg for >40 kg; 5 mg for 13-40 kg, single dose)
          OR
  • IV Diazepam (0.15-0.2 mg/kg/dose; max: 10 mg/dose, may repeat dose once,)
If no IV access:Midazolam 10 mg IM can be given
3. Secondary therapy phase (20–40 min)
• IV Fosphenytoin 20 mg phenytoin equivalent (PE) IV mg/kg at 100 to150mg PE/minute,
max: 1500 mg PE/dose, single dose,
          OR
 • IV Phenytoin 20 mg/kg at 25-50 mg/min
          OR
 • IV Valproic acid (40 mg/kg, at 10 mg/kg/minute, max: 3000 mg/dose, single dose,
          OR
• IV Levetiracetam (40 to 60 mg/kg, max: 4500 mg/dose, single dose,) over 15 min
If none of the above is available, then:
 • IV Phenobarbital (15 mg/kg, single dose, Level B)
Third therapy phase (40–60 min)
No clear evidence to guide therapy
Intubate and start mechanical ventilation
Repeat second line therapy repeat fosphenytoin if given previously (5 mg/kgPE),
          OR
 Anaesthetic doses of thiopental, midazolam, pentobarbital, propofol (with continuous EEG
monitoring)
4. Refractory status epilepticus (>60 min)
• Adults and children: Midazolam 0.2 mg/kg IV (maximum 10 mg) bolus over 2 min
followed by 0.05–0.5 mg/kg/h cIV or propofol 2–5 mg/kg IV bolus followed by 5–10 mg/
kg/h cIV or thiopental 10–20 mg/kg IV bolus followed by 0.5–1 mg/kg/h cIV or
pentobarbital bolus 10 mg/kg at <25 mg/min followed by cIV 0.5–2 mg/kg/h
If seizures continue, consider the following emerging therapies
• Inhalational anesthetic agents: Isoflurane at 0.8–2 vol.%, titrated to obtain the EEG burst
suppression pattern
• Ketamine: 1.5 mg/kg bolus, cIV 0.01–0.05 mg/kg/h
IV intravenous, cIV continuous intravenous infusion, NGT nasogastric tube, GCSE generalized
convulsive status epilepticus

Step 1: Stabilize the Patient

• Stabilize patient initially as described in Chap. 23, Vol. 2.

• Initial priority in an ongoing seizure patient is airway protection.
• This can be achieved by proper positioning, oral suctioning, and oral/nasopha-
ryngeal airway devices.
30 Status Epilepticus 303

• Assess oxygenation, give oxygen via nasal canula/mask. If necessary, the patient
should be intubated.
• Urgent peripheral intravenous (IV) access should be established and simultane-
ously collect sample for electrolytes (sodium, calcium, magnesium), LFT, Blood
sugar hematology, toxicology screening.
• Check fingerstick blood glucose, if <60 mg/dL
–– Adults: Give 100 Thiamine IV then 50 mL 50% Dextrose
–– Children >2 yrs.: 2 mL/kg 25% D IV
–– Children<2 yrs.: 4 mL/kg 12.5% D IV

Step 2: Terminate the Seizure

• Immediate measures should be taken to end ongoing seizure activity

(Table 30.1).
• When it is clear the seizure requires medical intervention, a benzodiazepine (spe-
cifically IM midazolam, IV lorazepam, or IV diazepam) is recommended as the
initial therapy of choice.
• When intravenous access is readily available intravenous lorazepam is the drug
of choice. If seizure continues one additional dose of lorazepam can be given
after waiting for a minute.
• Benzodiazepines (lorazepam, midazolam, and diazepam) are effective in termi-
nating seizures in 59–78% of patients.
• In patients who are actively seizing despite two initial doses of lorazepam, intra-
venous infusion of midazolam (preferred in patients with hypotension) or propo-
fol (preferred in patients without hypotension)should be started along with the
loading dose of a second line drug.

Step 3: Prevent Further Seizures (Table 30.1)

• Once the initial seizure is controlled, in addition to benzodiazepines a loading

dose of second-line drug like fosphenytoin or Valproic acid or Levetiracetam
should be given.
• Fosphenytoin is preferred to phenytoin because of its water solubility and neutral
pH, thereby allowing more rapid intravenous administration with less adverse
effects and its compatibility with all IV fluids.
• Phenytoin or fosphenytoin are incompatible with dextrose-containing solution.
• IV levetiracetam is a efficacious and safe drug.
• Phenytoin should be given through a larger vein and caution should be taken to
prevent extravasation as it is highly irritant.

Experience with IV valproic acid suggests that it is as effective as phenytoin/

fosphenytoin in terminating SE in patients who have previously failed benzodiaze-
pines and also as first-line treatment to prevent recurrent seizures.
304 R. Chawla and C. Madan

Table 30.2 Status epilepticus—general measures

1. Stabilization phase (5 min)
 • Secure airway, breathing, and circulation, physical safety; check random blood glucose
(glucometer)
2. Initial phase (5–20 min)
• Oxygen supplement; obtain IV access; stabilize airway, respiration, and hemodynamics as
needed; monitor ECG and SpO2
• Thiamine 100 mg IV, 50 mL of 50% dextrose if low glucose (less than 60 mg/dL). In
children younger than 2 years, pyridoxine should be added.
• Investigations: Random blood glucose, LFT, RFT, electrolytes, toxicology screening,
magnesium, phosphorous, CSF if CNS infection a possibility, and CT/MRI of brain
3. Second & Third therapy phase (20–60 min)
• Cardiorespiratory function monitoring: ECG, blood pressure, SpO2; identify and treat
medical complications, treat acidosis
• Investigations: EEG monitoring if the facilities are available
4. Refractory status epilepticus (>60 min)
• Shift to the ICU with facility for hemodynamic monitoring and cEEG monitoring,
identification and treatment of medical complications including hyperthermia
• Consider treating acidosis if pH <7.2 or if hemodynamically unstable
CNS central nervous system, CSF cerebrospinal fluid, CT computer tomography, ECG electrocar-
diogram, EEG electroencephalogram, cEEG continuous electroencephalography, LFT liver func-
tion tests, RFT renal function tests, BUN blood urea nitrogen, MRI magnetic resonance imaging

 tep 4: Initiate General Measures of Support Simultaneously

S
and Further Investigation (Table 30.2)

• General supportive measures should be started concurrently with seizure

treatment.
• Appropriate investigations to ascertain cause of seizures and any associated
complication should also be undertaken.

Step 5: Manage Refractory Status Epilepticus (RSE) (Fig. 30.1)

• Protect airway of patient with refractory seizures Start ventilation, and monitor
hemodynamics.
• Most experience is with continuous infusion (cIV) of agents such as midazolam,
propofol, and pentobarbital.
• No difference is found in mortality among the groups treated with these agents.
• Pentobarbital is associated with a lower frequency of acute treatment failures and
breakthrough seizures.
• Superior pharmacokinetics and favorable adverse effect profile makes propofol a
useful drug in RSE in both adults and children and successfully terminates RSE
in about two-thirds of patients.
30 Status Epilepticus 305

Fig. 30.1 Recurrent Refractory Status Epilepticus

seizure management

Continuous EEG monitoring

IV Midazolam 0.2 mg/kg bolus followed by infusion at 0.1

mg/kg/hr; max: 3mg/kg/hr

IV Propofol infusion at 1-2 mg/kg loading dose over 5 mins

Max: 10-12 mg/kg/hr but for <48 hrs

IV Pentobarbital 5 mg/kg over 10 mins followed by 1-5

mg/kg/hr for 24 hours till seizure free

• Midazolam is an effective, short-acting benzodiazepine, which is given as an

infusion, and has an efficacy in RSE.
• If available, continuous EEG monitoring should be performed.
• Pharmacologic coma should be maintained for 12 h after the last seizure, with
EEG goal of attaining burst suppression, after which gradually taper off infusion
of the anesthetic agent every 3 h with EEG monitoring, and if there are no clini-
cal or electrographic seizures, then discontinue the infusion.
• Continue EEG monitoring for at least 24 h after end of infusion.
• If clinical or electrographic seizures recur, reinstitute coma therapy with the
same anesthetic agent to which the seizures were responsive.
• Make another attempt after 24 h of seizure freedom.
• Look for complications and manage hypotension, bradycardia, pulmonary
edema, nosocomial sepsis, ileus, venous thromboemboli, skin breakdown, and
exposure keratitis.

Step 6: Initiate Maintenance Treatment (Table 30.2)

• In parallel with emergency treatment, attention must be given to maintain anti-

epileptic drug (AED) therapy to prevent recurrence of seizures in close consulta-
tion with the neurologist.
• In patients known to have epilepsy, their usual AEDs should be maintained and
dose adjustments should be made depending on AED levels.
• In patients presenting de novo, the AEDs, phenytoin/fosphenytoin, or valproic
acid used to control the status can in principle be continued as oral maintenance
therapy.
306 R. Chawla and C. Madan

• In others, unless relatively short-lived treatment is anticipated, the preference is

to initiate oral maintenance therapy with valproic acid or carbamazepine or any
of the newer AEDs, topiramate or levetiracetam.
• Duration of antiepileptic is variable, depending on reversibility of underlying
etiology, and should be decided with neurology consultation.

Step 7: Identify and Manage the Nonconvulsive Status

• The nonconvulsive status may present as unexplained coma and fluctuating level
of consciousness and is diagnosed by seizure activities in EEG monitoring.
• No concurrent motor activity is usually noticed.
• IV benzodiazepines—lorazepam or diazepam—are the drugs of choice.
• Allow 5 min to determine whether seizures terminate; if there is no response,
repeat benzodiazepines once.
• If EEG monitoring still shows continuous electrographic seizures, consider val-
proic acid in case of absence type of nonconvulsive status epilepticus and con-
sider phenytoin/fosphenytoin or valproic acid in case of other types of
nonconvulsive status epilepticus. The alternative option, particularly in the
elderly will be intravenous levetiracetam.

Suggested Reading
American Epilepsy Society issues guideline and treatment algorithm for convulsive status epilep-
ticus 2016, https://www.aesnet.org/about_aes/press_releases/guidelines2016.
Bassin S, Smith TL, Bleck TP. Clinical review: status epilepticus. Crit Care. 2002;6(2):137–42.
This review discusses current definitions of SE, as well as its clinical presentation and clas-
sification. The recent literature on epidemiology is reviewed, including morbidity and mortality
data. An overview of the systemic pathophysiologic effects of SE is presented. Finally, signifi-
cant studies on the treatment of acute SE and refractory SE are reviewed, including the use of
anticonvulsants, such as benzodiazepines and other drugs.
Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status
epilepticus. Neurocrit Care. 2012;17:3. A comprehensive guidelines for the management of
status epilepticus.
Claassen J, Hirsch LJ, Emerson RC, et al. Treatment of refractory status epilepticus with pento-
barbital, propofol, or midazolam: a systematic review. Epilepsia. 2002;41:146–53. Treatment
with pentobarbitone, or any cIV-AED infusion to attain EEG background suppression, may be
more effective than other strategies for treating RSE. However, these interventions were also
associated with an increased frequency of hypotension, and no effect on mortality was seen.
Meierkord H, Holtkamp M. Non-convulsive status epilepticus in adults: clinical forms and treat-
ment. Lancet Neurol. 2007;6:329–39. An excellent review on nonconvulsive status epilepticus.
Millikan D, Rice B, Silbergleit R. Emergency treatment of status epilepticus: current thinking.
Emerg Med Clin North Am. 2009;27(1):101–13. Current thinking about the acute treatment of
status epilepticus (SE) emphasizes a more aggressive clinical approach to this common life-
threatening neurologic emergency. In this review, the authors consider four concepts that can
accelerate effective treatment of SE. These include (1) updating the definition of SE to make it
more clinically relevant, (2) consideration of faster ways to initiate first-line b­ enzodiazepine
30 Status Epilepticus 307

therapy in the prehospital environment, (3) moving to second-line agents more quickly in
refractory status in the emergency department, and (4) increasing detection and treatment of
unrecognized nonconvulsive SE in comatose neurologic emergency patients.
Treiman DM, Meyers PF. Walton NY. A comparison of four treatments for generalized convul-
sive status epilepticus: Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J
Med. 1998;339:792–8. As initial intravenous treatment for overt generalized convulsive status
epilepticus, lorazepam is more effective than phenytoin. Although lorazepam is no more effica-
cious than phenobarbital or diazepam plus phenytoin, it is easier to use.