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Table 15.13 Bradycor for the Acute Management of Intracranial Pressure Post ABI

Author Year

Country

Research Design

PEDro

Sample Size

Methods

Outcomes

Anatibant

Shakur et al. (2009)

UK

RCT

PEDro=9

N=228

Population: TBI; Mean Age=36 yr; Gender: Male=203, Female=25; Mean Time Post Injury=6 hr; Mean GCS=8.

Intervention: Patients were randomized to receive placebo (n=57), high-dose Anantibant (n=57; 15mg/dY), medium-dose Anantibant (n=56; 10 mg/day) or low-dose Anantibant (n=58; 5 mg/day).  Maintenance doses were administered for 4 days. Outcomes were assessed at 2 wk post injury.

Outcome Measures:  Glasgow Coma Scale (GCS), Disability Rating Scale (DRS), Modified Oxford Handicap Scale (HIREOS), Serious Adverse Event (SAE), Mortality.

1.        The trial was ended early due to concerns with patient safety.

2.        Mortality was slightly higher in patients treated with Anatibant than those with placebo (19.0% versus 15.8%), but the risk was not significant (RR=1.20, p=0.38).

3.        There was a greater proportion of SAEs in patients treated with Anatibant than those with placebo (26.4% versus 19.3%), but the risk was not significant (RR=1.37, p=0.19).

4.        Mean GCS was higher in the Anatibant group than the placebo group, but the difference was not significant (12.48 versus 9.73, δ=-0.55, p>0.05).

5.        Mean DRS was higher in the Anatibant group than the placebo group, but the difference was not significant (11.18 versus 9.73, δ=1.61, p>0.05).

6.        Mean HIREOS was slightly higher in the Anatibant group than the placebo group, but the difference was not significant (3.94 versus 3.54, δ=0.42, p>0.05).

Marmarou et al. (2005)

USA

RCT

PEDro=4

N=25

Population: TBI; GCS Range<8. Low Dose (n=10): Mean Age=31.2 yr; Gender: Male=9, Female=1; Mean Time Post Injury=10.6 hr. High Dose (n=10): Mean Age=39.1 yr; Gender: Male=9, Female=1; Mean Time Post Injury=11.3 hr. Placebo (n=4): Mean Age=33.5 yr; Gender: Male=2, Female=2; Mean Time Post Injury=8.2 hr.

Intervention: Participants were randomized to receive placebo, low-dose Anatibant (3.75 mg), or high dose Anatibant (22.5 mg). Monitoring occurred for 5 days and outcomes were assessed at 1 mo, 3 mo, and 6 mo.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Glasgow Outcome Scale (GOS).

1.        A greater proportion of patients treated with high dose Anatibant showed favourable outcomes on GOS at 3 mo and 6 mo than those with low dose or placebo.

2.        Given small sample size and heterogeneity between groups, conclusions could not be drawn regarding ICP or CPP.

Marmarou et al. (1999)

USA

RCT

PEDro=8

N=136

Population: TBI; Bradycor (n=66): Mean Age=30 yr; Gender: Male=47, Female=19; Mean Time Post Injury=10 hr; Mean GCS=6.0. Placebo (n=67): Mean Age=34 yr; Gender: Male=55, Female=12; Mean Time Post Injury=10 hr; Mean GCS=6.1.

Intervention: Participants were randomized to receive continuous intravenous infusion of either Bradycor (3.0 µg/kg/min) or placebo for 5 days. Monitoring occurred for 5 days and outcomes were assessed at 3 mo and 6 mo.

Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS), Therapeutic Intensity Levels (TIC), Mortality.

1.        Percentage of time ICP>15 mmHg on 4-5 days was significantly lower in the Bradycor group compared with placebo (p=0.035).

2.        There were fewer deaths in the Bradycor group than placebo (20% versus 27%).

3.        The Bradycor group showed a 10.3% and 12% improvement in GOS at 3mo and 6mo respectively (p=0.26).

4.        The Bradycor group had significantly lower TIC than placebo (p<0.05).

Narotam et al. (1998)

South Africa

RCT

PEDro=6

N=20

Population: TBI; Time Post-Injury=24-96 hr; GCS Range=9-14.

Intervention: Participants were randomized to receive continuous intravenous infusion of Bradycor (3.0 µg/kg/min) or placebo for 7 days.

Outcome Measures: Intracranial Pressure (ICP), Glasgow Coma Scale (GCS), Therapeutic Intensity Levels (TIL).

1.        Bradycor group had a longer interval from time of injury to initiation of drug infusion (p=0.027).

2.        The mean increase in peak ICP from baseline was greater in the placebo group than Bradycor group (21.9 mmHg versus 9.5 mmHg, p=0.018).

3.        The mean reduction in GCS score in the placebo group was significantly greater than in the Bradycor group (4 versus 0.6, p=0.002).

4.        Bradycor had a significant effect in preventing elevation of ICP>20 mmHg compared to placebo (91% versus 78%, p=0.005).

5.        Braydcor group had significantly lower TIL than placebo (p<0.05).