Methods

Pragmatic randomised controlled trial, single‐blind, multicentric

Participants

Participants: adults (> 16 years) with RSE not due to cerebral anoxia, who clinically required coma

Sex (female/male): propofol group: 50%/50%; barbiturate group: 66%/34%

Age (median (range)): propofol group: 57 years (26 to 87 years); barbiturate group: 64 years (16 to 78 years)

Ethnic groups: not reported

Duration of epilepsy: not reported

Inclusion criteria: patients > 16 years of age suffering from RSE receiving at least 1 first‐line and 1 second‐line drug in adequate doses

Exclusion criteria: patients with known pregnancy, known intolerance to the study drugs, mitochondrial disorders, egg allergy, hypertriglyceridaemia (> 5 mmol/L) or significant rhabdomyolysis (creatinine kinase > 1500 U/L) on admission

Diagnostic criteria: RSE not due to cerebral anoxia, defined as ongoing clinical or electrographic seizures, or repetitive seizures without return to baseline for at least 30 minutes despite administration of 1 first‐line (benzodiazepine) and 1 second‐line antiepileptic drug (phenytoin, valproate, phenobarbital and levetiracetam) in adequate doses

Comorbidities: none

Co‐medications: none

Total randomised: 24 patients; 14 allocated to propofol group and 10 allocated to barbiturate group (thiopental and pentobarbital); (1 patient in thiopental sodium group did not require treatment and so was excluded, remaining 9 analysed)

Interventions

Number of control centres: 2

Country/location: Switzerland and the US

Setting: CHUV et Université de Lausanne, Lausanne and Brigham and Women's Hospital, Harvard School of Medicaine, Boston

Intervention I: 2 mg/kg titrated to burst suppression or 4 mg/kg until EEG was available

Intervention II: 2 mg/kg iv titrated to burst suppression or 5 mg/kg if no EEG available

Treatment before study: first‐ and second‐line antiepileptic drugs

Time to treatment since onset of status: not reported

Duration of follow‐up: 3 months

2 treatment arms: propofol and barbiturates (thiopental sodium or pentobarbital)

Outcomes

Primary outcomes (as stated in the publication): to assess the effectiveness (RSE control, adverse events) of a first course of propofol versus barbiturates

Secondary outcomes (as stated in the publication): none

Additional outcomes

Outcomes used in our review:

• total control of seizures

• mortality

• adverse events

• duration of mechanical ventilation

• functional outcome

Notes

Stated aim of study: "This prospective study was undertaken to assess the effectiveness (SE control, adverse events) of a first course of PRO versus barbiturates, the two most commonly used agents according to the aforementioned surveys"

Language of publication: English

Commercial funding: yes

Non‐commercial funding: no

Publication status (peer review journal): yes

Publication status (journal supplement): no

Publication status (abstract): no

Funded by AstraZeneca (Switzerland) and UCB (Switzerland)

No conflict of interest

Clinical Trial.gov ID: NCT00265616

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"After written consent was obtained by proxy, randomisation was stratified by institution using sealed envelopes."

Comment: The authors do not explain how the randomization was done.

Allocation concealment (selection bias)

Unclear risk

Not mentioned.

Comment: authors contacted. No information provided.

Blinding (performance bias and detection bias)
Subjective Outcomes

High risk

Being a single‐blind study, only the patient was blinded. Assessors were not blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss to follow‐up. All participants randomised completed the study and were included in the final analysis.

Selective reporting (reporting bias)

Low risk

All outcomes that were mentioned in the methodology have been reported.

Other bias

Unclear risk

The trial was terminated before completion due to inadequate recruitment. The calculated sample size for this study was 150 patients, 75 in each arm.

Funding by pharmaceutical companies.