Treatment of Refractory Status Epilepticus

• Clinical Outcome at Day 21 [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  Return to baseline clinical conditions (i.e.: no new handicap, no death)
• Patients With Infectious Complications Requiring Specific Treatment [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
• Patients With Hypotension Requiring Specific Treatment [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
• Patients With Propofol Infusion Syndrome [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
  Propofol infusion syndrome (PRIS) is a severe metabolic alteration with elevation of lactate, CK, and triglycerides.
• Intubation Time in Survivors [ Time Frame: Up to 3 months ] [ Designated as safety issue: Yes ]

• · Clinical outcome at day 21, assessed by a functional score,
• · Time of ventilator treatment in survivors,
• · Incidence of thromboembolism ,
• · Incidence of infectious complications requiring specific treatment ,
• · Incidence of hypotension requiring specific treatment ,
• · Incidence of propofol infusion syndrome.

The purpose of this study is to determine whether propofol or barbiturates should be preferred in the treatment of status epilepticus (continuous seizure activity) refractory to 2 standard antiepileptic agents.

Refractory status epilepticus (SE) develops in 31%-44% of patients with SE, with a mortality of 16%-23%. Coma induction is advocated for its management. Propofol and barbiturates are the most used agents, but no comparative study has been performed. In consideration of the uncertainty regarding the relative effectiveness, despite several retrospective data, a prospective investigation is needed.

The objective is to assess the effectiveness (SE control, adverse events) of a first course of propofol versus barbiturates in the treatment of refractory SE, in adults with refractory SE not due to cerebral anoxia.

Comparison: Coma induction with standardized doses of propofol or barbiturates titrated towards burst-suppression on EEG, then assessment of the proportion of patients achieving a control of SE.

• Drug: propofol
  liquid, mg/kg.h, titrated after EEG
  Other Name: Disoprivan
• Drug: thiopental/pentobarbital
  liquid, mg/kg.h, titrated after EEG
  Other Name: Pentotal /Thiopentone

• Active Comparator: 1
  propofol, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined
  Intervention: Drug: propofol
• Active Comparator: 2
  thiopental/pentobarbital, 2mg/kg as bolus, then titrated up to EEG burst-suppression as a continuous infusion; no maximum doses defined
  Intervention: Drug: thiopental/pentobarbital

Inclusion Criteria:

• Patients with refractory status epilepticus not due to cerebral anoxia, needing coma induction for clinical management.

Exclusion Criteria:

• Age < 16 years old.
• Known pregnancy.
• Cerebral anoxia as SE etiology.
• Epilepsia partialis continua (simple partial SE).
• Known intolerance to the study drugs.
• Known mitochondrial disorder, hyperlipidemia, or significant rhabdomyolysis.