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). |