This document provides guidelines on the management of status epilepticus. It defines status epilepticus and discusses types. It outlines common etiologies and systemic complications. Treatment protocols are discussed including first, second, and third line anticonvulsant medications for both adults and children. Precautions and side effects of different medications are mentioned. The importance of early treatment and monitoring is emphasized to terminate seizures and prevent complications.

1. DR KIRAN RAJAGOPAL DA DNB.
ANAESTHESIOLOGIST
STATUS EPILEPTICUS
MANAGEMENT PROTOCOLS

2. Evidence-Based Guideline: Treatment of Convulsive
Status
Epilepticus in Children and Adults: Report of the
Guideline
Committee of the American Epilepsy Society
Epilepsy Currents 16.1 - Jan/Feb 2016

3. DEFINITION
 Seizures lasting longer than 30 minutes, or 30
minutes of recurrent seizures without return to
baseline neurologic status between events.
 This has been largely replaced by an operational
definition, which is a 5-minute duration of
continued seizure activity, or two or more
seizures between which there is incomplete
recovery.

4. TYPES
 GENERALISED CONVULSIVE SE
Patient does not regain consciousness between
repeated generalized tonic-clonic attacks
 SIMPLE PARTIAL SE
Characterized by continuous or repetitive focal
seizures without loss of consciousness

5.  NON CONVULSIVE SE (NCSE),
seizures produce a continuous or fluctuating
“epileptic twilight” state

6. REFRACTORY STATUS EPILEPTICUS
 Do not repond to standard treatment regimen for
status epilepticus (adequate doses of intial BZD
followed by a second acceptable antiepileptic drug )
 Nearly 40% of status epilepticus are refractory.
 Predictors- encephalitis / nonstructural causes(HIE) /
delayed diagnosis & treatment .

7. STATUS EPILEPTICUS –COMMON
ETIOLOGY

9. SYSTEMIC COMPLICATIONS- CVS
 Cardiac arrhythmias occur due to autonomic overactivity, acidosis,
and hyperkalemia.
 Further complicated by shock due to lactic acidosis
 Early signs include tachycardia & hypertension
 Late(>30 min) includes bradycardia, hypotension, even shock and
arrest

10. RS
 Mechanical impairment from tonic muscle contraction
 Disturbed respiratory center function
 Massive autonomic discharge producing increased bronchial
constriction and secretions, aspiration pneumonia & Neurogenic
pulmonary edema.
 Early signs include tachypnea or apnea with co2 retention
 Late signs include apnea, variations in breathing pattern, aspiration
pneumonia.

11. RENAL
 Renal impairment may occur from a combination of
rhabdomyolysis with myoglobinuria
 Acute tubular necrosis
 Hypotension with poor renal perfusion.

12. METABOLIC
 Increased lactate production from maximally
exercised muscles results in metabolic acidosis
within minutes after the start of SE.
 Variable respiratory contribution to the acidosis from
carbon dioxide retention.
 Degree of acidosis does not correlate with the extent
of neuropathologic damage.

13.  After cessation of the seizure, lactate is rapidly
metabolized, resulting in spontaneous resolution of
the acidosis.
 Initially, hyperglycemia develops due to
catecholamine and glucagon release; later,
hypoglycemia occurs due to increased plasma
insulin, increased cerebral glucose consumption,
and excessive muscle activity

14. ANS
 Hyperthermia can result from excessive muscle
activity and hypothalamic dysfunction
 Alternatively, it may be due to an underlying infection
that is responsible for the initiation of SE.

17. Results and conclusion
Evidence-Based Guideline: Treatment of Convulsive
Status
Epilepticus in Children and Adults: Report of the
Guideline
Committee of the American Epilepsy Society

18. Which Anticonvulsants Are Efficacious as
Initial and Subsequent Therapy?
 In adults, IM midazolam, IV lorazepam, IV diazepam (with or without
phenytoin), and IV phenobarbital are established as efficacious at
stopping seizures lasting at least 5 minutes (level A).
 Intramuscular midazolam has superior effectiveness compared
with IV lorazepam in adults with convulsive status epilepticus without
established IV access (level A).
 Intravenous lorazepam is more effective than IV phenytoin in
stopping seizures lasting at least 10 minutes (level A).

19.  Intravenous valproic acid has similar efficacy to IV phenytoin or
continuous IV diazepam as second therapy after failure of a
benzodiazepine (level C).
 Insufficient data exist in adults about the efficacy of levetiracetam
as either initial or second therapy (level U).

20.  In children, IV lorazepam and IV diazepam are established as
efficacious at stopping seizures lasting at least 5 minutes (level A).
 Rectal diazepam, IM midazolam, intranasal midazolam,
and buccal midazolam are probably effective at stopping
seizures lasting at least 5 minutes (level B).
 Insufficient data exist in children about the efficacy of intranasal
lorazepam, sublingual lorazepam, rectal lorazepam, valproic acid,
levetiracetam, phenobarbital, and phenytoin as initial therapy (level
U).

21.  Intravenous valproic acid has similar efficacy but better tolerability
than IV phenobarbital (level B) as second therapy after failure of
a benzodiazepine.
 Insufficient data exist in children regarding the efficacy of phenytoin
or levetiracetam as second therapy after failure of a benzodiazepine
(level U).

22. What Adverse Events Are Associated With
Anticonvulsant Administration?
 Respiratory and cardiac symptoms are the most common
encountered treatment-emergent adverse events associated with IV
anticonvulsant administration in adults with status epilepticus (level
A).
 The rate of respiratory depression in patients with status epilepticus
treated with benzodiazepines is lower than in patients with status
epilepticus treated with placebo (level A), indicating that respiratory
problems are an important consequence of untreated status
epilepticus.
 No substantial difference exists between benzodiazepines and
phenobarbital in the occurrence of cardiorespiratory adverse events
in adults with status epilepticus (level A).

23.  Respiratory depression is the most common clinically significant
treatment-emergent adverse event associated with anticonvulsant
drug treatment in status epilepticus in children (level A).
 No substantial difference probably exists between midazolam,
lorazepam, and diazepam administration by any route in children
with respect to rates of respiratory depression (level B).
 Adverse events, including respiratory depression, with
benzodiazepine administration for status epilepticus have been
reported less frequently in children than in adults (level B).

24. Which Is the Most Effective Benzodiazepine?
 In adults with status epilepticus without established IV access, IM
midazolam is established as more effective compared with IV
lorazepam (level A).
 No significant difference in effectiveness has been demonstrated
between lorazepam and diazepam in adults with status
epilepticus (level A).

25.  In children with status epilepticus, no significant difference in
effectiveness has been established between IV lorazepam and IV
diazepam (level A).
 In children with status epilepticus, non-IV midazolam
(IM/intranasal/buccal) is probably more effective than diazepam
(IV/rectal) (level B).

26. Is IV Fosphenytoin More Effective Than IV
Phenytoin?
 Insufficient data exist about the comparative efficacy
of phenytoin and fosphenytoin (level U).
 Fosphenytoin is better tolerated compared with
phenytoin (level B).
 When both are available, fosphenytoin is preferred
based on tolerability, but phenytoin is an acceptable
alternative (level B).

27. When Does Anticonvulsant Efficacy Drop
Significantly
 In adults, the second anticonvulsant administered is less effective
than the first “standard” anticonvulsant, while the third anticonvulsant
administered is substantially less effective than the first “standard”
anticonvulsant (level A)
 In children, the second anticonvulsant appears less effective, and
there are no data about third anticonvulsant efficacy (level C).

28. MANAGEMENT
 SE is a medical emergency and must be treated
immediately in a critical care setting.
 Mortality rate- 20%.
 Pharmacologic intervention is more effective at an
early stage of SE than after a delay.

29.  Aims of management of Status Epilepticus are as
follows :-
1. Termination of Status Epilepticus
2. Prevention of Seizure Recurrence
3. Management of Precipitating cause
4. Management of complications

30. Approach: Diagnostic workup
 All patients
 Obtain IV access
 Monitor vital signs (ABC).
 Head CT (appropriate for most cases)
 Labs: blood glucose, CBC, renal function tests, Calcium,
Magnesium, electrolytes, AED levels.
 cEEG monitoring (preferably)
 Consider based on clinical presentation
 Brain MRI
 Lumbar puncture
 Toxicology panel (i.e. isoniazid, TCAs, theophylline,
cocaine, sympathomimetics, organophosphates,
cyclosporine)
 Other relevant investigations as per the need

33. intranasal midazolam 0.2mg /kg

34.  Initial therapy should be administered as an
adequate single full dose rather than broken into
multiple smaller doses.
 Initial therapies should not be given twice except for
IV lorazepam and diazepam that can be repeated at
full doses once (level A, two class I, one class II
RCT).

35. BENZODIAZEPINES
 Appropriate initial treatment.
 Diazepam (10 to 25 min) and lorazepam (2 to 24
hours)are both effective.
 Although lorazepam has slower CNS penetration
than diazepam, the onset of action is less than 3
minutes
 So ,lorazepam is the recommended first-line agent in
status epilepticus.

36.  Diazepam
One of the drug of choice for first line management of SE
 Good results, easy to administer. (fast acting, short
lasting)
 More lipid soluble, hence short distribution half-life.
• Anti-seizure effect 15-30min.
• Sufficient cerebral levels are achieved within 1 min of IV
administration and about 20 mins after rectal administration.
• Elimination half life abt 24 hrs (may accumulate)
 Side effects -- hypotension, bradycardia,
respiratory depression, cardiac arrest,
tolerance, depresses mental status.
 In children and elderly :
Rectal Diazepam 0.5 mg / kg in children and 10
mg
in elderly are also good alternatives.

37.  Lorazepam
 Has emerged as preferred BZD for treatment of SE
 The veteran affairs (VA) co-operative study
demonstrated advantage of IV Lorazepam over
Phenytoin.
• Less lipid distribution with distribution half life of 2-3
hours
• So Fast acting, longer lasting compared to
Diazepam
 Longer therapeutic half-life. Anti-seizure effect for
6-12hrs.
 2mg dose, upto a max dose of 8mg in total
 Main disadvantage is rapid devlopment of
tolerance, hence repeated doses are less effective
and has no role in long term therapy.

38. There is no clear evidence that any one of these options is better than the
others.

39. PHENYTOIN
 To control the SE and prevent recurrent seizures.
 Serum level - 15 to 30 μg/mL.

40. S/E
 IM administration should not be used because it results in
precipitation at the injection site and has slow, erratic absorption.
 Hypotension, ECG changes, and respiratory depression can occur
and may be due partly to the propylene glycol diluent.
 Simultaneous cardiac monitoring should be performed.
 I.V infusion of phenytoin carries a risk of medication extravasation
into adjacent tissue
 Tissue necrosis can rarely occur.
 PURPLE GLOVE SYNDROME

41. FOSPHENYTOIN
 Water-soluble prodrug of phenytoin, is rapidly converted
enzymatically to phenytoin.
 Rapid and complete absorption occurs after IM administration.
 Therapeutic phenytoin concentrations are attained in most patients
within 10 minutes of rapid IV infusion (150 mg per minute) within 30
minutes of slower IV infusion or IM injection.
 Levels maintained in the high therapeutic range (15 to 25 μg/ mL).

42.  Dosing for fosphenytoin is the same as for
phenytoin, but needs to be given in “phenytoin
equivalents.”
 Cardiac monitoring is required during IV infusions of
fosphenytoin.

43. Phenytoin Fosphenytoin
• 15-20 mg/kg i.v.
@50mg/min
• 100 mg phenytoin =
• 20 mg PE/kg i.v @
150mg/min
Fosphenytoin 150 mg
pH 12
Extravasation causes
severe tissue injury
pH 8.6
Extravasation well
tolerated
• Onset 10-30 min • Onset 5-10 min
•May cause hypotension,
dysrhythmia
(may be because of rapid administration
and propylene glycol which is used as
diluent)
• less cardiac complications as it
is water soluble and propylene
glycol is not used as diluent.
• Cheap • Expensive

44. Fosphenytoin Vs. Phenytoin
 SO Fosphenytoin injection has the following advantages
over phenytoin
100% bioavailability
better tolerated at site of injection.
can be given IV more rapidly .
can be given IM when cardiac monitoring is not
necessary
 But has the following disadvantages
 conversion of fosphenytoin to phenytoin takes about 15
minutes. Hence inappropriate for the initial treatment of
status epilepticus (SE).
 transient paraesthesia and pruritus occur more
frequently than with phenytoin.
 the use of phenytoin equivalents may be confusing.

45. PHENOBARBITAL
 dose – 15 mg/kg
 Causes sedation and hypotension, so airway
protection should be done.
 Diluted in Polyethylene Glycol which results in
complications like renal failure, myocardial depresion
and seizures.

46. SOD.VALPROATE
 I.V could be an appropriate second-line therapy.
 Well tolerated, with few adverse effects
 dose of 40 mg/kg IV, single dose

47. S/E
 Hyperammonemia
 Pancreatitis
 Thrombocytopenia
 Hepatotoxicity

48. LEVITIRACETAM
 S-enantiomer of Piracetam
 Was introduced for treatment of SE in 2006
 Insufficient data on safety and efficacy of this drug in
status epilepticus.
 Several case reports its use in SE.
 European federation of neurological societies
proposes its usefulness in refractory complex partial
SE. (Meiekord H et al, EFNS guideline on the management of
status epilepticus in adults, Eur Journal 2010)

49.  Levetiracetam has been used to control SE,
typically as second line drug.
 Levels peak within 2 hrs. Steady state in 2 days.
No significant interactions.
 dose : 60 mg/kg IV

51. 40-60 min THIRD PHASE

52.  Intubation and ventilation to maintain normal PaO2
and PaCO2 .
 RSI should be performed
 Fluid resuscitation to maintain adequate systemic
blood pressure and cerebral perfusion pressure.

53. REMEMBER
Muscle relaxants stop the seizure movements,
but not the abnormal cerebral activity, therefore
in the paralysed patient, anticonvulsants are also
essential.

54. NCSE Rx
 NCSE must be treated quickly, although the urgency
is not as great as for convulsive SE.
 Diazepam and lorazepam are both effective in
treating complex partial, partial motor, and absence
SE.
 Response to BZDSs may be helpful in confirming the
diagnosis

55.  Patient should also be started on antiepileptic
medication appropriate for long-term management,
given as a loading dose if appropriate.
 Valproic acid is an ideal drug for absence SE
myoclonic status and can be given intravenously.
 Dose is 15-20 mg /kg/day.

56. REFRACTORY STATUS EPILETICUS
 Failure of initial therapy, such as benzodiazepines
and phenytoin, with seizures persisting beyond 1–2
hours and usually requiring agents that induce
general anesthesia to control them
 Worst prognosis

57. Future Directions
 Class III trials support efficacy and safety of valproic acid as first-line
therapy , second-line therapy , and refractory therapy
 The current National Institute of Neurological Disorders and Stroke
funded ESETT trial compares IV fosphenytoin levetiracetam, and
valproate in children and adults with status epilepticus who did not
respond to initial benzodiazepine therapy.
 ESETT is designed to be a class I RCT that will identify the optimal
second therapy for benzodiazepine-resistant status epilepticus .

58. REFERENCES
 IRWIN RIPPE
 OH’S
 Evidence-Based Guideline: Treatment of Convulsive
Status
Epilepticus in Children and Adults: Report of the
Guideline
Committee of the American Epilepsy Society

61. THANK YOU

62. PREOPERATIVE ASSESSMENT
 Type of seizure (e.g., grand mal, absence)
 Specific symptoms (e.g., staring, focal findings) are
important to document.
 Absence (previously petit mal) seizures may be
particularly difficult to recognize because they lack
generalized motor signs.

63.  More typical symptoms such as staring and
obtundation may be misinterpreted as residual
anesthetic effects in the postoperative period.
 Determining the etiology of the seizure disorder is
also important because of possible associated
morbidities.

64.  Important associated comorbidities include brain
tumors, aneurysms, arteriovenous malformations
(AVMs), classic epilepsy, drug toxicity, electrolyte
disorders, infections, cerebrovascular disease, sickle
cell disease, and SLE.

65.  Careful documentation of anticonvulsants and
adequacy of seizure control is necessary.
 Routine measurement of serum drug levels of
anticonvulsants is not indicated unless toxicities or
ongoing breakthrough seizures pose a concern.

66.  Medications to control seizures have multiple side
effects and testing should be directed based on
suspected abnormalities
 The most commonly ordered tests are CBC and
electrolyte levels.

67.  Poorly controlled or new-onset seizures entail a
consultation with a neurologist before the patient
undergoes anything other than emergency surgery.
 Continuation of anticonvulsant therapy in the
perioperative period is necessary, including children
and pregnant pts.

68. SX MGT OF EPILEPSY
 Preop investigations may include
 MRI
 PET
 Thiopentone test
 Wada test
 Intracranial EEG

69. INTRAOP GOALS
 To maintain haemodynamic stability.
 Avoidance of any increase in ICP
 Minimal impact on electrocorticographic monitoring.
 Provide brain protection.
 To avoid any secondary systemic insults.
 Rapid and smooth emergence

70. INTRAVENOUS AGENTS
 Thiopentone and benzodiazepines have
anticonvulsant properties.
 However benzodiazepines can induce brief periods
of EEG and clinical seizure activity in patients with
Lennox-Gastaut syndrome, a form of secondary
generalized epilepsy.
 Methohexitone on the other hand produces seizure
activity during its administration.

71.  Ketamine, however activates epileptogenic foci in
epileptic patients & non-epileptic patients.
 Etomidate possesses both pro and anticonvulsant
properties.

72.  Higher dose suppresses and low dose etomidate
induces involuntary motor activity.
 Therefore, the dose and the rate of etomidate
administration determines which of the contrasting
effects on the seizure threshold will occur in a
particular setting

73.  Intravenous droperidol when given along with
fentanyl as a component of neurolept anaesthesia.
 Role of propofol in epileptiform surgery is somewhat
controversial.

74.  Although the clinical reports suggest that it has
anticonvulsant properties, abnormal EEG activity
have been documented following administration of
propofol in epileptic patients.

75. INHALATIONAL AGENTS
 Nitrous oxide (N2O) has extremely low epileptogenic
potential, and is considered to be safe in epileptic
patients.
 Halothane and isoflurane do not provoke seizure
activity in anaesthetized patients.
 Enflurane, however produces both EEG changes
and abnormal motor activities

76.  Seizure manifestations are evident at MAC of 1 to 2,
which are accentuated by hyperventilation, auditory,
visual and tactile stimulations.
 There are EEG evidence of seizure activity with
sevoflurane.
 Suppression of refractory status epilepticus and EEG
has been reported both with isoflurane and
desflurane.

77. OPIOIDS
 Morphine - No epileptiform activity has been
reported during and following the use of morphine.
 Meperidine’s neurotoxicity is well known in inducing
seizures and is attributable to its metabolite
normeperidine.

78. FENTANYL AND ANALOGUES
 Recently, it has been documented that fentanyl,
alfentanil and remifentanil activates epileptiform
activity in patients with temporal lobe epilepsy

79. MUSCLE RELAXANTS
 None of the muscle relaxants including atracurium
have been reported to cause either EEG or clinical
seizure activity

80. ANTICHOLINESTERASES
 NO Clinical seizure or EEG activity have been
reported

81. LOCAL ANAESTHETICS
 Possess both proconvulsant and anticonvulsant
properties due to their membrane stabilizing effects.
 At subtoxic doses, LA can act as anticonvulsants,
sedatives and analgesics, while at higher
concentration, resistant excitatory pathways can
cause frank convulsions.

82. DRUG INTERACTIONS
 Pts treated chronically with various anticonvulsants
are resistant toNDMRs and to usual clinical dose of
opioids.
 Mechanism of this resistance to opioids and
neuromuscular agents is possibly due to hepatic
enzyme induction by antiepileptics which tends to
increase clearance and decrease the half life of
opioids and nondepolarizers.

83.  Blood levels of an antiepileptic drug can significantly
be affected by anaesthetics and the changes in body
physiology resulting from surgery.
 The blood levels of carbamazepine and phenytoin
increases substantially after anaesthesia and
surgery.

84.  Increasing levels of antiepileptic drugs may cause
clinical toxicity, which may mimic an intracranial
complications.
 Conversely, if the antiepileptic drug levels decrease
unexpectedly, seizure can be precipitated.
 Thus the blood levels of anti-epileptic drugs should
be obtained preoperatively and closely monitored in
the postoperative period.

85. ICP MGT
 Thiopentone and propofol produces the most
consistent reduction in cerebral blood volume and
ICP
 Isoflurane and sevoflurane have similar effects when
used in sub MAC concentrations and in the
background of opioids and hyperventilation.

86.  Increased ICP can result from poor positioning and
venous obstruction, light plane of anaesthesia,
inadequate analgesia and hypercarbia.

87. FLUID MGT
 To maintain normovolemia.
 NS is regarded as fluid of choice because of slightly
high osmolality.
 Rarely, epilepsy surgery can be associated with
large blood loss.
 In children avoiding blood transfusion may become
hazardous particularly in anaemic or hypovolemic
child.

88. EMERGENCE
 Early awakening is a priority in epileptic patients as
most of the surgeries are non-emergent procedures
and the patients have a good preoperative conscious
level and neurological status.
 Moreover, early awakening allows a rapid and
complete neurological examination.

89.  Suitable pharmacological agents (i.e, lignocaine,
esmolol
 or labetolol) should be administered so as to blunt
the hypertensive response to extubation and
emergence.

90. POST OP CONSIDERATIONS
 Anticonvulsant drugs should be restarted as soon as
possible after surgery, according to the time of
fasting.
 If the fasting time is 12-24 hours, there is no need to
replace the oral by the parenteral route, and
treatment should be restarted when the oral route is
cleared.

91.  In the case of fasting over 24 hours and in the
chronic use of the orally administered anticonvulsant
drugs phenytoin or phenobarbital, we replace
through the enteral route for venous 2-3 times a day.

92.  After surgery, whenever possible, the monitoring of
plasma levels of antiepileptic drugs for at least 48
hours should be performed because there are
significant variations in the apparent volume of
distribution, linked to plasma proteins, hepatic
metabolism and renal elimination.

93. PERIOPERATIVE SEIZURES
 The seizures of epileptic origin are rare in the
perioperative period, usually occurring in the
induction and recovery from anesthesia.
 Up to 72 hours after surgery.
 Important to remember that the anesthetic drugs
which commonly induce epileptogenic activity rarely
progress to seizures in the perioperative period,
although there is greater propensity to occur more
frequently in epileptic patients than in non-epileptic
patients.

94.  Incidence of perioperative seizures in epileptic
patients is low and does not require anticonvulsant
therapy in most patients.
 MC in children and in patients with refractory
epilepsy whorequire multiple anticonvulsant drugs.

95.  Initial approach is to maintain a patent airway with
adequate ventilation and protect the patient from
injuries resulting from seizures
 Monitoring should be performed .
 Seizures lasting < 5 min do not usually require
treatment
 Convulsions persist for > 5 min, I.V benzodiazepine
should be used.
 Preferred drug is lorazepam/ the best alternative is
diazepam (5-20 mg)

96.  Convulsions persist, a second dose of
benzodiazepine associated with phenytoin (20
mg/kg,30 minutes) should be used
 In the case of refractory seizures, phenobarbital (1.5
mg/kg/min or 100 mg/70 kg/min can be used with a
maximum dose of 15 mg/kg or 1,000 mg/70 kg)

97.  Midazolam (0.1-0.3 mg/kg in 2 to 5 minutes, followed
by infusion of 0.05 to 0.4 mg/kg/hr)
 Propofol (1-2 mg/kg followed infusion of 2-10
mg/kg/h)
 Thiopental (5-10 mg/kg in 10 minutes, followed by
infusion of 100-400 mg/h)

98.  Lidocaine (1.5-2 mg/kg-1 in 2-5 minutes, followed by
infusion of 2-3 mg/kg/h for 12 hours)
 Isoflurane (0.5 to 1.5%).