Table 15.19 Mannitol for the Multimodal Acute Management of Intracranial Pressure Post ABI
Author Year Country Research Design PEDro Sample Size |
Methods | Outcome |
Ichai et al. (2009) France RCT PEDro=6 N=34 |
Population: TBI; Mannitol (MAN, n=17): Mean Age=33.8 yr; Gender: Male=11, Female=6; Time Post Injury<8 hr; Median GCS=6. Sodium Lactate (SL, n=17): Mean Age=37.6 yr; Gender: Male=13, Female=4; Time Post Injury<8 hr; Median GCS=4. Intervention: Patients were randomized to receive intravenous infusion of 20% MAN (1.5 mL/kg) and/or SL over 15 min. Outcome Measure: Intracranial Pressure (ICP). |
1. Both treatments were effective in reducing ICP from baseline (p<0.0001). 2. SL showed significantly lower ICP levels compared to MAN (p=0.016). 3. The effect of SL alone on ICP was more pronounced (p=0.0061) and more prolonged (p=0.0049) than MAN alone. 4. The percentage of episodes requiring rescue treatment was higher with mannitol than lactate (29.6% versus 9.6%, p=0.053). |
Francony et al. (2008) France RCT PEDro=6 N=20 |
Population: TBI=17, ABI=3. Mannitol (MAN, n=10): Mean Age=43 yr; Gender: Male=7, Female=3; Mean GCS=8; Mean Time Post Injury=6 days. Hypertonic Saline (HTS, n=10): Mean Age=37 yr; Gender: Male=9, Female=1; Mean GCS=7; Mean Time Post Injury=5d. Intervention: Patients were randomized to receive a single intravenous infusion of 20% MAN (231 mL) or of 7.45% HTS (100 mL) administered over 20 min. Outcome Measures: Intracranial Pressure (ICP), Mean Arterial Pressure (MAP), Cerebral Perfusion Pressure (CPP), Urine Output (UO), Serum Sodium/Chloride. |
1. ICP was reduced in both groups of patients following treatment. 2. In MAN, ICP was significantly reduced by 45% of baseline values (-14mmHg,) at 60 min (p=0.01) and by 32% of baseline values (-10 mmHg) at 120 min (p=0.01). 3. In HTS, ICP was significantly reduced by 35% of baseline values (-10mmHg) at 60 min (p=0.01) and by 23% of baseline values (-6 mmHg) at 120min (p=0.01). 4. MAP was unchanged and comparable between groups (F=1.2, p=0.32). 5. CPP was significantly elevated only in the MAN (p<0.05). 6. MAN showed significantly greater increase in UO (p<0.05). 7. HTS showed significantly greater increase in serum sodium and chloride after 120 min (p<0.01). |
Cruz et al. (2004) Brazil RCT PEDro=5 N=44 |
Population: TBI; High-Dose Mannitol (HDM, n=23): Mean Age=34 yr; Mean GCS=3. Conventional-Dose Mannitol (CDM, n=21): Mean Age=31 yr; Mean GCS=3. Intervention: Patients were randomized to receive rapid intravenous infusion of HDM (up to 1.4 g/kg) or CDM (up to 0.7 g/kg). Both groups received normal saline infusions immediately after the mannitol infusions. Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS), Mortality, Additional Therapy Required. |
1. At 6 mo, mortality rates were 39.1% and 66.7% for the HDM and CDM groups, respectively. 2. Clinical outcome on the GOS was significantly better for the HDM group, with a greater number of patients in this group showing a favourable outcome (GOS>4) compared with the CDM group (43.5% versus 9.5%, p<0.02). 3. No significant difference was found between the HDM and CDM groups in percentage of patients requiring decompressive surgery for refractory ICP elevations (43.5% versus 47.6%). |
Cruz et al. (2002) Brazil RCT PEDro=5 N=141 |
Population: TBI; High-Dose Mannitol (HDM, n=72): Mean Age=29 yr; Mean GCS=5.3. Conventional-Dose Mannitol (CDM, n=69): Mean Age=31 yr; Mean GCS=5.5. Intervention: Patients were randomized to receive rapid intravenous infusion of HDM (up to 1.4 g/kg) or CDM (up to 0.7 g/kg). Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS), Additional Therapy Required. |
1. At 6mo, mortality rates were 19.4% and 36.2% for the HDM and CDM groups, respectively. 2. Clinical outcome on the GOS was significantly better for the HDM group, with a greater number of patients in this group showing favourable outcome (GOS>4) compared with the CDM group (61.1% versus 33.3%, p<0.005). 3. A greater proportion of patients in the CDM group required decompressive surgery for refractory ICP elevations than the HDM group (24.6% versus 9.7%, p<0.03). |
Cruz et al. (2001) Brazil RCT PEDro=4 N=178 |
Population: TBI; High-Dose Mannitol (HDM, n=91): Mean Age=30 yr; Mean GCS=6. Conventional-Dose Mannitol (CDM, n=87): Mean Age=28 yr; Mean GCS=6.2. Intervention: Patients were randomized to receive intravenous infusion of HDM (Conventional dose + 0.6 to 0.7 g/kg in the absence of pupillary widening or 1.2 to 1.4 g/kg with pupillary widening) or CDM (0.6-0.7 g/kg). Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS), Additional Therapy Required. |
1. At 6 mo, mortality rates were 14.3% and 25.3% for the HDM and CDM groups, respectively. 2. Clinical outcome on the GOS was significantly better for the HDM group, with a greater number of patients in this group showing favourable outcome (GOS>4) compared with the CDM group (69.2% versus 46%, p<0.01). 3. No significant difference between HDM and CDM groups in percentage of patients requiring barbiturate therapy for refractory ICP elevations (46.1% versus 54%). |
Smith et al. (1986) USA RCT PEDro=4 N=77 |
Population: TBI; Mean Age=27 yr; Gender: Male=60, Female=17; Time Post Injury ≤6 hr; GCS ≤8. Intervention: Patients were randomized to receive intravenous infusion of mannitol based on careful monitoring (Group 1; n=37) or irrespective of monitoring (Group 2; n=40). For Group 1, an initial bolus of 20% mannitol (250 mL, 0.75 gm/kg) was administered at ICP>25mmHg; pentobarbital coma was induced if ICP>25 mmHg while mannitol was administered. For Group 2, initial bolus of 20% mannitol (250 mL, 0.75 gm/kg) was given, followed by 0.25g m/kg boluses administered every 2 hr. Outcome Measures: Mortality, Glasgow Outcome Scale (GOS), Intracranial Pressure (ICP). |
1. There was no significant difference in mortality between Groups 1 and 2 (35% versus 42.5%, p=0.26). 2. There were no significant differences in GOS between groups. 3. The proportion of patients achieving favourable outcome (GOS>4) in Group 1 was 54% and in Group 2 was 47.5%. 4. Mean highest ICPs for survivors in Groups 1 and 2 were 35.2mmHg and 29.7mmHg, respectively, and for non-survivors were 46.2 mmHg and 40.7 mmHg, respectively. 5. Mean highest ICP in all non-survivors was significantly higher (by approx. 11 mmHg) than that in all survivors (p=0.0002). |
Scalfani et al. (2012) USA Pre-Post N=8 |
Population: TBI; Mean Age=37.4 yr; Gender: Male=7, Female=1; Median Time Post Injury=3 days; Median GCS=7. Intervention: Participants received 20% mannitol (n=6) or 23.4% saline (n=2) infused over 15 min. Outcome Measures: Intracranial Pressure (ICP), Mean Arterial Pressure (MAP), Cerebral Perfusion Pressure (CPP). |
1. Results from patients who received saline and mannitol were not different and were combined for all analyses 2. Treatment resulted in a significant reduction in ICP (22.4 mmHg to 15.7 mmHg, p<0.05). 3. Treatment resulted in a significant elevation in CPP (75.7 mmHg to 81.9 mmHg, p<0.05). 4. Treatment resulted in a stable MAP (103.3 mmHg versus 102.6 mmHg, p>0.05). |
Sorani et al. (2008) USA Case Control N=28 |
Population: TBI; Mean Age=39.3 yr; Gender: Male=24, Female=4; Median GCS=8. Intervention: Patients treated with 100 g, 50 g, or both doses of mannitol were included in retrospective analysis. Outcome Measure: Intracranial Pressure (ICP). |
1. Initial mean ICP was slightly higher in the 100 g group compared to the 50g group (23.9 mmHg versus 20.9 mmHg, p=0.14). 2. By 100 min post treatment, mean ICP was significantly lower in the 100 g group compared tothe 50 g group (14.2 mmHg versus 18.6 mmHg, p=0.001). 3. Over time, mean ICP decrease in the 50 g group was 3.6 mmHg, which was nearly two-fold lower than that of the 100 g group (8.8 mmHg). 4. ICP response to mannitol was dose-dependent: every 7 g achieved an additional reduction of ~1.0 mmHg in ICP. |