Select Page

Table 12.1 Opioids for the Acute Management of ABI

Author Year

Country

Research Design

PEDro

Sample Size

Methods Outcomes
Remifentanil

Engelhard et al. (2004)

Germany

Pre-Post

N=20

 

Population: TBI; Mean Age=46 yr; Gender: Male=13, Female=7; GCS Range<8.

Intervention: Remifentanil was administered first as as intravenous bolus (0.5 ug/kg), and subsequently as a 20 min continuous infusion (0.25 ug/kg/min)    . Outcomes were assessed for 20min before and after remifentanil administration.

 

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

1.        No changes were observed in ICP, CPP, MAP, or CBFV following administration of bolus or continuous infusion of remifentanil.
Sufentanil

Werner et al.

(1995)

Germany/USA

Pre-Post

N=30

 

Population: TBI; Gender: Male=21, Female=9; GCS Range<6.

Intervention: Patients received an intravenous bolus of 3 μg/kg sufentanil for 10 sec. Patients were monitored for 30min.

 

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

1.       MAP decreased by more than 10 mmHg in 12 patients.

 

2.       ICP was constant in patients with stable MAP (n=18), but was significantly increased in those with decreased MAP (p<0.05).

Albanese et al.

(1993)

France

Case Series

N=10

Population: TBI; Age Range=18-50 yr; Gender: Male=10, Female=0; GCS Range≤8.

Intervention: Patients received an intravenous bolus of sufentanil (1 µg/kg, 6 min), followed by continuous intravenous infusion (0.005 µg/kg/min).

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

1.       There was a significant increase in ICP (53%, p<0.05) that peaked after 5 min and gradually returned to baseline after 15min.

2.       There was a significant decrease in MAP (24%, p<0.05) and in CPP (38%, p<0.05). Though they gradually increased after 5min, they remained significantly reduced from baseline (22% and 23%, respectively).

3.       There was a significant decrease in HR (15%, p<0.05).

Multimodal Opioid Interventions

Karabinis et al.

(2004)

Greece

RCT

PEDro=5

N=161

Population: TBI; Remifentanil Group (n=84): Mean Age=46.8 yr; Gender: Male=44, Female=40; Time Post Injury<24 hr; Mean GCS=8.4. Fentanyl Group (n=37): Mean Age=49.6 yr; Gender: Male=24, Female=13; Time Post Injury<24 hr; Mean GCS=8.8. Morphine Group (n=40): Mean Age=47.3 yr; Gender: Male=25, Female=15; Time Post Injury<24 hr; Mean GCS=8.6.

Intervention: Patients were randomized in a 2:1:1 ratio into one of three treatment arms: 1) analgesia-based sedation with 9 µg/kg/hr remifentanil for 5-10 min (and propofol at 0.5 mg/kg/hr if necessary); 2) hypnotic-based treatment with fentanyl; or 3) hypnotic-based treatment with morphine. Opioids were titrated to achieve optimal sedation in all three treatment groups.

Outcome Measures: Time to neurological assessment, Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP).

1.       Sedation with remifentanil required significantly less time to neurological assessments (0.41 hr), compared to fentanyl (0.71 hr, p=0.001) or morphine (0.82 hr, p<0.001).

2.       No differences in ICP or CPP between remifentanil and fentanyl/morphine groups were found.

De Nadal et al.

(2000)

Spain

RCT Crossover

PEDro=8

N=30

 

Population: TBI; Mean Age=30 yr; Gender: Male=23, Female=7; Mean Time Post Injury=17.8hr; GCS Range≤8.

Intervention: Patients were randomized to receive intravenous morphine (0.2 mg/kg) or fentanyl (2 µg/kg) over 1 min. Crossover occurred after 24 hr. Treatment was initiated at 0 min and measurements were repeated at 5-10 min intervals until 60 min.

 

Outcome Measures: Autoregulation, Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Mean Arterial Pressure (MAP), Central Venous Pressure (CVP), CO2 and O2 Partial Pressures (PP), Heart Rate (HR).

1.       Autoregulation was abolished in 18 patients and preserved in 12. No significant changes in ICP were observed between those with preserved and abolished autoregulation after treatment.   2.       Both morphine and fentanyl induced significant increases in ICP at 5 min (p=0.008 and p=0.044, respectively), which remained significantly higher up to 60 min (p=0.008 and p=0.044, respectively).   3.       Both morphine and fentanyl induced significant decreases in MAP at 5min (p=0.002 and p=0.016, respectively), which remained significantly lower with fentanyl up to 60 min (p=0.016).   4.       Increase in ICP coupled with decrease in MAP resulted in a transient decrease in CPP, reaching a minimum value of 6 4mmHg at 5 min after morphine and 65 mmHg after fentanyl. Both values were significantly lower than baseline (p=0.001 and p<0.0001, respectively).   5.       No significant differences were observed after the use of either opioidfor CVP, PPs, or HR.

Albanese et al.

(1999)

France

RCT Crossover

PEDro=5

N=6

Population: TBI; Age Range=20-45 yr; Gender: Male=6, Female=0; GCS Range≤8.

Intervention: Patients were randomized to receive an initial 6 min injection of either 1 μg/kg sufentanil, 100 μg/kg alfentanil, or 10 μg/kg fentanyl, followed by a 1 hr infusion of the same drug at 0.005 μg/kg/min, 0.7 μg/kg/min, and 0.075 μg/kg/min, respectively. Crossovers occurred at 24 hr intervals.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Mean Arterial Pressure (MAP), Heart Rate (HR), End-Tidal CO2, O2 Saturation.

1.       Sufentanil, alfentanil, and fentanyl were associated with significant mean increases in ICP peaking before 6 min (9 mmHg, 8 mmHg, and 5.5 mmHg, respectively; p<0.05) that returned to baseline by 15 min.

2.       Sufentanil, alfentanil, and fentanyl were associated with significant mean decreases in MAP (21 mmHg, 24 mmHg, and 26 mmHg, respectively; p<0.05) and thus in CPP (30 mmHg, 31 mmHg, and 34 mmHg, respectively; p<0.05). MAP and CPP gradually increased after 5 min, but they remained significantly reduced compared to baseline.

3.       No significant difference were observed after the use of any opioid with regard to HR, or End-Tidal CO2/ O2 saturation.

Kelly et al.

(1999)

USA

RCT

PEDro=8

N=42

Population: TBI; Propofol (PROP, n=23): Mean Age=39 yr; Gender: Male=18, Female=5; Mean Time Post Injury=34 hr; Median GCS=7. Morphine (MOR, n=19): Mean Age=38 yr; Gender: Male=17, Female=2; Mean Time Post Injury=38 hr; Median GCS=6.

Intervention: Patients were randomized to receive sedation with either PROP (20 mg/mL) or MOR (Avg. 10 mg/h). Both groups received additional bolus of MOR (1-3 mg/hr) for at least 48 hr for analgesic purposes. Assessments were made at baseline, days 1, 2, 3, and 4, and at 6 mo.

Outcome Measures: Intracranial pressure (ICP), Glasgow Outcome Scale (GOS), Disability Rating Scale (DRS).

1.       On day 3, ICP was significantly lower in PROP compared to MOR (p<0.05).

2.       ICP therapy in PROP was also less intensive than MOR.

3.       At 6 mo, scores were not significantly different between groups for mortality or favourable outcome rates (GOS>4).

4.       In subgroup analysis, PROP was divided into high-dose (100 mg/kg, n=10) and low-dose (<100 mg/kg, n=13) groups. The high-dose group showed higher mean CPP on day 2 (81 mmHg versus 68 mmHg) and lower mean ICP on day 3 (14 mmHg versus 15 mmHg) compared to low-dose (p>0.05).

5.       High-dose group demonstrated more favourable outcomes in the GOS (70% versus 38.5%) and the DRS (80% versus 46.2%) compared to the low-dose group (p>0.05).

Lauer et al.

(1997)

USA

RCT

PEDro=5

N=15

Population: TBI; Morphine Group (n=5): Mean Age=21 yr; Mean GCS=6. Fentanyl Group (n=5): Mean Age=22 yr; Mean GCS=5. Sufentanil Group (n=5): Mean Age=35 yr; Mean GCS=6.

Intervention: Patients were randomized to receive continuous intravenous morphine, fentanyl, or sufentanil over a 5 min interval. Continuous bolus infusion was initiated for 4 hr with the same opioid, if the blood pressure did not change >5%. Assessments were made every 15 min for the first 2 hr, and then in every 30min for the last 2hr.

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

1.       Mean doses of morphine, fentanyl, and sufentanil were 2.98 µg/kg, 0.07 mg/kg, and 0.37 µg/kg, respectively.

2.       There was no significant difference in MAP from baseline in any group, except the sufentanil group had reduced MAP at 10 and 45 min post bolus administration (p<0.05).

3.       There was no significant change in ICP from baseline in any group. However, the fentanyl group had reduced ICP at 150 and 180 min post bolus administration compared to the morphine and sufentanil groups (p<0.05).

4.       There was no significant change in CPP from baseline in any group. However, the fentanyl group had reduced CPP at 60 min post bolus administration compared to with the morphine group, and at 70 min compared to the morphine and sufentanil groups (p<0.05).

Sperry et al.

(1992)

USA

RCT Crossover

PEDro=7

N=9

 

Population: TBI; Mean Age=34 yr; Gender: Male=6, Female=3; Time Post Injury Range=1-3 days; Mean GCS=6.

Intervention: Patients were randomized to receive an intravenous bolus of 3 μg/kg fentanyl or 0.6 μg/kg sufentanil over 1 min. Crossover occurred after 24 hr. Outcomes were recorded for 1hr after administration.

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

1.       Fentanyl resulted in significant increases in mean ICP (8 mmHg, p=0.004), and significant reductions in mean MAP (11 mmHg, p<0.05) from baseline.

2.       Sufentanil resulted in significant increases in mean ICP (6 mmHg, p=0.006), and significant reductions in mean MAP (10 mmHg, p<0.05).

3.       Both Fentanyl and Sufentanil treatment resulted in significant decreases in CPP from baseline (-17mmHg and -13 mmHg, respectively, p<0.05).

4.       No significant change in HR was noted after the use of either opioid.

Colton et al.

(2014b)

USA

Case Series

N=117

 

Population: TBI; Mean Age=40.0 yr; Gender: Male=93, Female=24; Median GCS=6.

Intervention: Participants were included in retrospective analysis after having received one of the following ICP therapies: hypertonic saline (HTS), mannitol, propofol, fentanyl, and barbiturates.

Outcome Measure: Intracranial Pressure (ICP).

1.       Treatment with HTS resulted in the largest ICP decrease of the treatments examined.

2.       Propofol and fentanyl escalations resulted in smaller but significant ICP reductions.

3.       Mannitol resulted in statistically insignificant reductions in the first hr but rebounded by the second hr.

Scholz et al.

(1994)

Germany

Pre-Post

N=10

 

Population: TBI; Median Age=34 yr; Gender: Male=7, Female=3; GCS Range<6.

Intervention: Patients received an intravenous bolus of 2 μg/kg sufentanil for 30 min, after which they received an intravenous infusion of sufentanil (150 (25-200) µg base h-1) and midazolam (9.0 (3.6-13.5) mg h-1) for 48 hr.

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

1.       Following treatment, a significant decrease in mean ICP (16.1 mmHg to 10.8 mmHg, p<0.05) was noted within 1 5min.

2.       At 15 min, mean MAP was significantly decreased (85.5 mmHg to 80.2 mmHg, p<0.05).

3.       CPP remained stable after treatment.

  4.       The same results were observed at 2 days.

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.