PEDIATRIC REVIEW OF STATUS EPILEPTICUS

 

I.               INTRODUCTION

·      Definition: > 30 min. of constant or repetitive seizing without recovery

·      2 types of status epilepticus exist:

                                      i.     Convulsive (clinical) – usually generalized tonic-clonic seizures. Has the highest morbidity (subsequent CNS deficits) & mortality

1.    A clinical diagnosis

                                    ii.     Non-convulsive (subclinical– either absence or partial-complex seizures. Highly undiagnosed; less morbidity & mortality

1.    May be difficult to clinically diagnose; seen on EEGs

II.              ETIOLOGY

·      Many different etiologies:

                                      i.     Infection (meningoencephalitis in all age groups)

                                    ii.     Febrile seizure in otherwise healthy child

                                   iii.     Progressive neurologic disease

                                   iv.     Known epilepsy: sub-therapeutic drug levels, stress

                                     v.     Hypoxia

                                   vi.     Metabolic disturbance: low dexi, Ca, Mg, Na; high uremia, IEMs

                                  vii.     Structural disturbance: cyst, abscess, tumor

                                viii.     Toxins: EtOH ingestion/withdrawal, drugs

                                   ix.     Vascular disturbance: old infarct, AVM, hemorrhage, stroke

                                     x.     Psych: pseudoseizures

III.            PRESENTATION

·      Depends on the variety of status epilepticus

                                      i.     Convulsive SE presents with GTCs that last > 30 minutes or that repeatedly occur without resolution between seizures

                                    ii.     Non-convulsive SE may simply present as an extended staring spell or focal CNS deficit (e.g. arm twitch) that does not resolve

IV.           MANAGEMENT

·      Depends on the duration of the seizure

                                      i.     Monitor patient with EEG if possible to watch for ablation of spike/wave complexes characteristic of seizure activity (either convulsive or non-convulsive)

·      0 to 5 minutes

                                      i.     Usually, we don’t know it’s SE at this point

                                    ii.     Ensure safety of patient

                                   iii.     Monitor cardiopulmonary function and vital signs

                                   iv.     Give oxygen

                                     v.     Obtain history and perform complete physical examination

                                   vi.     Note time

·      5 to 10 minutes

                                      i.     Obtain intravenous access and start a short-acting agent

                                    ii.     Give Lorazepam: 0.05 to 0.1 mg/kg (Maximum dose, 4 mg) or Diazepam: Pediatric, 0.2 to 0.5 mg/kg Adult, 5 to 10 mg/dose

                                   iii.     Give 2 mL/kg of 50% glucose and B vitamins

1.    In case this is a related metabolic phenomenon

                                   iv.     Labs-CBC, BMP, drug levels, Utox

·      >10 minutes

                                      i.     Start a long acting agent

                                    ii.     Neonatal patient: Phenobarbital 20 mg/kg

                                   iii.     Pediatric and adult patients: Phenytoin 20 mg/kg (Prescribe as: Fosphenytoin at 20 mg phenytoin equivalents/kg)

·      >30 minutes

                                      i.     Intubate, ventilate, and secure vital sign monitoring

                                    ii.     Load with second long-acting agent

1.    Phenobarbital 10 mg/kg. May give additional 5- to 10-mg doses until 40 mg/kg or max dose of 1 g is reached

                                   iii.     IV Valproate may be used as a 3rd line agent

                                   iv.     Start Midazolam 0.05-0.10 mg/kg IV drip as a last resort (place the patient into a medically-induced coma)

1.    NOTE: buccal and intranasal Midazolam are also options

V.             POTENTIAL SEQUELAE

·      Respiratory compromise/hypoxia

·      Muscle breakdown leading to myoglobinuria and renal failure

·      Hypo/hyperthermia

·      Drug toxicity from anticonvulsants-respiratory depression, arrhythmia

·      Morbidity and Mortality more associated with the underlying cause of the seizure (e.g. abscess à sepsis, tumor à mass effects, etc.)

VI.           PHARMACOTHERAPY SPECIFICS

·      Lorazepam

                                      i.     Route: Intravenous, IO

                                    ii.     Dose: 0.05 to 0.1 mg/kg up to 4 mg/dose

                                   iii.     Rate: IV push over 2 min; can be given 5 to 10 minutes apart

                                   iv.     Maximum dose: 4.0 mg

                                     v.     Onset of action: 2 to 3 minutes

                                   vi.     Duration: Usually 12 to 24 hours

                                  vii.     Side effects: Confusion, drowsiness, respiratory depression, hypotension

·      Diazepam

                                      i.     Route: Intravenous, IO, PR

                                    ii.     Dose: Pediatric: 0.2 to 0.5 mg/kg

1.    Adult: 0.2 mg/kg (10 mg average adult dose)

                                   iii.     Rate: May repeat every 15 to 30 minutes

                                   iv.     Maximum dose: Usually not more than three doses given at 5 mg/min

                                     v.     Onset of action: 1 to 3 minutes; PR doses take 1 to 2 hours

                                   vi.     Duration of action: 5 to 15 minutes

                                  vii.     Side effects: Somnolence, confusion, hypotension, ataxia, bradycardia, respiratory depression

·      Phenytoin (not used as often anymore due to skin irritation if infiltrated)

                                      i.     Route: Intravenous, IO

                                    ii.     Dose: 20 mg/kg

                                   iii.     Maximum dose: 1,000 mg

                                   iv.     Rate: <0.5 mg to 1.0 mg/kg per min to a maximum rate of 50 mg/min

                                     v.     Onset of action: 10 to 30 minutes after infusion

                                   vi.     Duration of action: 12 to 24 hours

                                  vii.     Side effects: Hypotension, respiratory depression, risk of cardiac arrhythmia, skin irritation if infiltrating

·      Fosphenytoin

                                      i.     Route: Intravenous, intramuscular

                                    ii.     Dose: 20 mg/kg phenytoin equivalents

                                   iii.     Rate: Children: 3 mg/kg per min phenytoin equivalents

1.    Adult: 150 mg/min phenytoin equivalents

                                   iv.     Onset of action: Within 2 to 3 minutes after loading dose

                                     v.     Duration: 12 to 24 hours

                                   vi.     Side effects: Pruritus, paresthesia in groin area

·      Phenobarbital:

                                      i.     Route: Intravenous, IO

                                    ii.     Dose: 20 mg/kg

                                   iii.     Maximum dose: Additional 5 to 10 mg/g dose every 20 minutes until maximum dose of 40 mg/kg or total dose of 1 g

                                   iv.     Rate: <100 mg/min

                                     v.     Onset of action: 10 to 20 minutes; intramuscular may take up to 2 to 4 hours

                                   vi.     Duration of action: 1 to 3 days

                                  vii.     Side effects: Respiratory depression, hypotension, circulatory collapse

·      Valproate PO or PR

                                      i.     Dose: NG: 67 mmg/kg; RP: 200 mg suppositories; enema: 60 mg/kg

                                    ii.     Side effects: gastrointestinal irritation, tremor, ataxia, liver failure, pancreatitis

·      Valproate IV

                                      i.     Dose: In valproate-naive patient, 15 mg/kg divided qid

·      Midazolam

                                      i.     Route: IV (oral, intravenous available)

                                    ii.     Dose: 0.05 to 0.1 mg/kg IV

                                   iii.     Rate: Load with 0.2 mcg/min and titrate continuous infusion to 0.4 to 0.6 mcg/kg per min

                                   iv.     Onset of action: IV within 5 to 10 minutes

                                     v.     Duration: 1 to 6 hours

                                   vi.     Side effects: hypotension, bradycardia, central nervous system and respiratory depression

 

 

 

References:

  1. Fenichel, GM. Clinical Pediatric Neurology, 4th edition. WB Saunders Co, 2001.
  2. Mitchell, WG. Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: etiology, outcome, and treatment. Epilepsia.1996;37 Suppl 1:S74-80.
  3. Sabo-Graham T. and Seay A. Management of Status Epilepticus in Children Pediatrics in Review September 1998
  4. Lowenstein D. Alldridge D. Current Concepts Status Epilepticus. NEJM April 2, 1998 Vol. 338:970-976
  5. Diagnostic Assessment f the Child with Status Epilepticus Neurolgy 2006
  6. Management of Prolonged Seizures and Status Epilepticus in Childhood: A Systematic Review. Journal of Child Neurology. 2009 Vol 24