Ghori et al. (2008)

Ireland

RCT

PEDro=8

N=30

Population: TBI; Midazolam (MDZ, n=15): Age Range: 18-65 yr; Gender: Male=14, Female=1; Mean Time Since Injury=12.86 hr; Median GCS=4.73. Propofol (PROP, n=13): Age Range: 18-65 yr; Gender: Male=13, Female=0; Mean Time Since Injury=9.07 hr; Median GCS=5.07.

Intervention: Patients were randomly allocated to receive MDZ (n=15) or PROP (n=13) sedation. Outcomes were assessed at baseline and 3 mo.

Outcome Measures: Glasgow Outcome Score (GOS), Mortality, Disability.

1.        There was no significant difference between MDZ and PROP groups in number of patients with good outcomes (53% versus 54%).

2.        Of the patients who had a poor outcome, there was no significant difference in the mortality rate between MDZ and PROP groups (20% versus 38%; p=0.07).

3.        Of the patients who had a poor outcome, there was no significant difference in the severe disability rate between MDZ and PROP groups (20% versus 15%; p=0.8).

Sanchez-Izquierdo-Riera et al. (1998)

Spain

RCT

PEDro=5

N=100

Population: TBI; Mean Age=35.4 yr; Gender: Male=75, Female=25.

Intervention: Patients were randomized to receive continuous intravenous infusion of midazolam (0.1-0.35 mg/kg/hr,n=34), propofol at 1.5- 6mg/kg/hr (n=33), or propofol at 0.1-0.2 mg/kg/hr (n=33). All patients received morphine.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Triglyceride levels, Wake-up time, Sedation.

1.        No significant differences were found in ICP or CPP among treatment groups.

2.        High levels of triglyceride were found in patients receiving propofol (p<0.05).

3.        Wake-up time was significantly shorter in patients receiving propofol compared to those receiving midazolam (110 min/190 min versus 660 min, p<0.01).

4.        All regimens achieved similar levels of sedation and had similar incidences of adverse effects.

Davis et al. (2001)

USA

Case Series

N=184

Population: TBI; Northern Cohort (n=66): Mean Age=32.9 yr; Gender: Male=53, Female=13. Southern Cohort (n=118): Mean Age=31.2 yr; Gender: Male=89, Female=29.

Intervention: Patients received 0.1 mg/kg midazolam without a restricted maximal dose (Group 1) or with a maximal dose of 5 mg (Group 2).

Outcome Measures: Systolic Blood Pressure (SBP), Hypotension, Dose.

1.        Patients in the Group 1 received significantly higher doses than those in Group 2 (0.106 mg/kg versus 0.059mg/kg, p<0.0001).

2.        A significant relationship was found between dose and hypotension following intubation (p=0.032) as well as decrease in SBP (p=0.022).

Papazian et al. (1993)

France

Case Series

N=12

Population: TBI; Mean Age=28.3 yr; Gender: Male=11, Female=1; Mean GCS=5.2.

Intervention: Patients received intravenous infusion of 0.15 mg/kg midazolam over a 1min period.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Mean Arterial Pressure (MAP).

1.        Significant reductions in MAP (89 mmHg to 75 mmHg, p<0.0001) and CPP (71 mmHg to 55.8 mmHg, p<0.0001) were observed, but not in ICP.

2.        Patients with low initial ICP (<18 mmHg) experienced greater reductions in MAP and greater increases in ICP compared to those with high initial ICP (≥18 mmHg; p<0.0001).

Stewart et al.

(1994)

UK

PCT

N=15

Population: ABI; Propofol (PROP, n=9): Mean Age=30.5 yr; Gender: Male=8, Female=1; Severity of Injury: Moderate=2, Severe=7; Morphine and Midazolam (M+M, n=6): Mean Age=30.5 yr; Gender: Male=6, Female=0; Severity of Injury: Moderate=1, Severe=5.

Intervention: Patients received sedation with either PROP (150-400 mg/hr) or morphine (0-4 mg/hr) with midazolam (0-5 mg/hr).

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Mean Arterial Pressure (MAP), Global Brain Metabolism (AVDO₂), Glasgow Outcome Scale (GOS).

1.        PROP led to a decrease in AVDO₂ at 4 hr (6.0±2.6 mL/dL to 3.0±0.6 mL/dL, p<0.02).

2.        No difference was reported between groups in ICP, CPP, and MAP.

3.        No difference was reported between groups in functional outcomes on GOS at 6mo.