Thiopental

Thiopental was the first agent used in a well-organized, randomized, clinical study. It was successfully tested in a primate model of global ischemia (16) and in successful pilot studies in humans (17). As a barbiturate, it can ameliorate injury by reducing metabolism, edema formation, intracranial pressure (ICP), seizure activity, and damage by focal and incomplete ischemia (15). The thiopental study was also known as the BRCT 1.

The BRCT 1 included all comatose patients after return of spontaneous circulation (ROSC). Clinical parameters, such as initial cardiac rhythm, the duration of CA and resuscitation, and place of arrest (in-hospital or out-of-hospital), were not stratified or controlled. The BRCT trials (18) developed a functional outcome measure as defined by the five-point scale of the Glasgow-Pittsburgh Outcome Categories, as follows: Cerebral Performance Category (CPC) 1, conscious and normal, without disability; CPC 2, conscious with moderate disability; CPC 3, conscious with severe disability; CPC 4, comatose or vegetative state; CPC 5, death. This scale was divided into favorable outcome, defined as CPC 1 and 2, and unfavorable outcome, CPC 3, 4, and 5. For the BRCT trial, the outcome was determined at 48 and 72 hours, 10 days, and 1, 3, 6, and 12 months (18).

BRCT 1 compared a thiopental intravenous (IV) loading dose of 30 mg/kg at 10 to 50 minutes after ROSC to placebo, and both arms enrolled 131 participants (15). The primary outcome, as measured by a treatment-blinded investigator using the five-point CPC scale, showed no difference between treated and control groups. Overall good outcome with thiopental treatment was seen in 20% of patients, and good outcome in the control group was 15%. Mortality was 70% in the thiopental group and 80% in the control group. A significant factor that may have contributed to the failure of thiopental was the excess in hypotensive episodes (60%), compared to the control group (29%) (15 ).

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