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Table 15.17 Hypertonic Saline for the Acute Management of Intracranial Pressure Post ABI

Author Year

Country

Research Design

PEDro

Sample Size

Methods Outcomes

Jagannatha et al. (2016)

India

RCT

PEDro=5

N=38

Jagannatha et al. (2018)

India

Post-Hoc Analysis

N= 38

 

Population: TBI; Hypertonic Saline (HTS, n=18): Mean Age=27 yr; Gender: Male=16, Female=2; Mean Time Post Injury=6.1 hr; Median GCS=4. Mannitol (MAN, n=20): Mean Age=31 yr; Gender: Male=18, Female=2; Mean Time Post Injury=6.7 hr; Median GCS=5.

Intervention: Participants were randomized to receive HTS (3%) or MAN (20%). Outcomes were assessed daily for 6 days.

Outcome Measures: Intracranial Pressure (ICP), Mean Arterial Pressure (MAP), Heart Rate (HR), Blood Glucose, Fluid Balance, Serum Osmolality, Serum Sodium.

 

 

Intervention: A post-hoc analysis of the study conducted by Jagannatha et al. (2016), focusing on comparing urinary sodium and urine osmolarity in the HTS and Mannitol groups.

Outcome Measures: Urinary Sodium, Urinary Osmolarity.

1.        There was no significant difference between groups in reduction in ICP (p=0.135).

2.        Blood Glucose significantly decreased over 6 d in the HTS group (p=0.003).

3.        There was no significant difference in Blood Glucose over 6 d in the MAN group (p=0.36).

4.        There was no significant difference in HR, MAP, Fluid Balance, Serum Osmolality, or Serum Na+ (all p>0.05) for both MAN and HTS groups over 6 days.

1.        Urinary sodium excretion was significantly higher in the HTS group compared to the Mannitol group (p=0.02)

2.        Urinary Osmolarity was not different between groups (=0.63)

Bourdeaux et al. (2011)

UK

RCT

PEDro=6

N=11

 

Population: TBI; Age>16 yr.

Intervention: Participants were randomized to receive 5% hypertonic saline (HTS, n=10) or 8.4% sodium bicarbonate (SBC, n=10).

Outcome Measure: Intracranial Pressure (ICP).

1.        Overall, there was a significant decrease in ICP at all time points (p<0.001).

2.        There was no significant difference in ICP with time between HTS and SBC (p=0.504).

3.        After 150 min, the mean ICP was higher in HTS group compared to SBC group (p<0.05).

Cottenceau et al. (2011)

Israel

RCT

PEDro=6

N=47

Population: TBI; Hypertonic Saline (HTS, n=22): Mean Age=42.7 yr; Median GCS=5. Mannitol (MAN, n=25): Mean Age=36.1 yr; Median GCS=7.

Intervention: Participants were randomized to receive HTS (7.5%, 2 mL/kg) or MAN (20%, 4 mL/kg). Outcomes were assessed at baseline, 30 min, 120 min, and 6 mo.

Outcome Measures: Intracranial Pressure (ICP), Mean Arterial Pressure (MAP), Cerebral Perfusion Pressure (CPP), Global Cerebral Blood Flow Oxygen (CBF), Arterial Jugular Difference for Oxygen Content (AVDO2), Global Cerebral Metabolic Rate of Oxygen (CMRO2).

1.        The HTS group had significantly greater CBF when compared to the MAN group (p=0.0087) over time.

2.        There was no significant difference between groups over time in ICP, MAP, CPP, AVDO2, or CMRO2 (all p>0.05).

Battison et al. (2005)

UK

RCT Crossover

PEDro=5

N=9

Population: TBI=6, SAH=3.

Intervention: Participants received intravenous infusions of 20% mannitol (200 mL), a solution of 7.5% hypertonic saline (100mL) and 6% dextran-70 (HSD) over 5 min in a randomized order. Outcomes were assessed before and after treatment.

Outcome Measure: Intracranial Pressure (ICP).

1.        Both mannitol and HSD were effective in reducing ICP.

2.        HSD caused a significantly greater decrease in median ICP than mannitol (13 mmHg versus 7.5 mmHg, p=0.044).

3.        HSD had a longer duration of effect than mannitol (p=0.044).

Harutjunyan et al. (2005)

Germany

RCT

PEDro=5

N=40

Population: TBI; Hypertonic Saline group (HTS; n=17): Mean Age=47 yr; Gender: Male=9, Female=8; Mean GCS=6. Mannitol group (MAN; n=15): Mean Age=47 yr; Gender: Male=8, Female=7; Mean GCS=5.8.

Intervention: Patients at risk of increased ICP were randomized to receive either 7.2% hypertonic saline or 15% mannitol. Treatment was stopped when ICP was <15 mmHg.

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

1.        There was no significant difference over time or between groups for HR (all p>0.05).

2.        There was no significant difference in MAP between groups (p>0.05).

3.        There was a significant reduction in ICP over time for both the HTS and MAN groups (all p<0.0001), however, there was no significant difference between groups (p>0.05).

4.        There was a significant increase in CCP over time for both the HTS and MAN groups (all p<0.0001); with the HTS group significantly higher than the MAN group (p<0.05).

Cooper et al. (2004)

Australia

RCT

PEDro=9

N=229

Population: TBI; Hypertonic Saline (HTS, n=114): Mean Age=38 yr; Gender: Male=75, Female=39; Mean GCS=4. Ringer’s Lactate Solution (RLS, n=115): Mean Age=37 yr; Gender: Male=76, Female=39; Mean GCS=4.

Intervention: Participants were randomized to receive intravenous infusion of 7.5% HTS (250 mL) or RLS (250 mL). Outcomes were assessed at discharge, 3 mo, and 6 mo.

Outcome Measures: Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), GOS Extended (GOSE), Length of Stay (LOS), Functional Independence Measure (FIM), Rancho Los Amigos Scale (RLAS), Return to Work (RTW), Survival, Intracranial Pressure (ICP).

1.        Survival rate was similar in HTS and RLS at discharge (55% versus 50%, p=0.32), 3 mo (55% versus 48%, p=0.26), and 6 mo (55% versus 47%, p=0.23).

2.        LOS was similar in HTS and TLS at discharge (12 days versus 11 days, p=0.52).

3.        Median GCS was similar in both groups at 3 mo (15, p=0.62) and 6 mo (15, p=0.96).

4.        Median GOS was similar in both groups at 3 mo (4, p=0.64) and 6 mo (4, p=0.43).

5.        Median GOSE was similar in both groups at 3 mo (5, p=0.65) and 6 mo (5, p=0.45).

6.        Median FIM was similar in HTS and RLS at 3 mo (97.5 versus 99.6, p=0.76) and 6 mo (109 versus 109, p=0.96).

7.        Median RLAS was similar in HTS and RLS at 3 mo (6.82 versus 7.15, p=0.24) and 6 mo (7.32 versus 7.57, p=0.22).

8.        RTW was similar in HTS and RLS at 3 mo (51% versus 48%, p=0.35) and 6 mo (62% versus 53%, p=0.17).

9.        There was no significant difference between groups in those with baseline GCS>5 (n=101, p=0.48), shorter time to treatment (<60 min; n=95, p=0.26), or longer time to treatment (>60 min; n=96, p=0.85).

10.     Median ICP after treatment was not significantly different between groups

Vialet et al. (2003)

France

RCT

PEDro=7

N=20

Population: TBI;. Hypertonic Saline (HTS, n=10): Mean Age=35 yr; Gender: Male=5, Female=5; Mean GCS=4.7. Mannitol (MAN, n=10): Mean Age=31 yr; Gender: Male=4, Female=6; Mean GCS=6.0.

Intervention: Participants were randomized to receive intravenous infusions of 7.5% HTS or 20% MAN.  Infused volume was the same for both medications: 2 ml/kg of body weight in 20min. Outcomes were assessed over a mean of 7 days.

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

1.        HTS had significantly fewer mean episodes of ICP>25 mmHg per day (6.9 versus 14.6, p<0.01) and shorter mean daily duration of these episodes (67 min versus 131 min, p<0.01) than MAN.

2.        There was no significant difference between HTS and MAN in mean episodes of CPP<70 mmHg (4.0 versus 3.1, p>0.05) or mean daily duration of these episodes (58 min versus 62 min, p>0.05).

3.        Failure of treatment was significantly greater in MAN than HTS (70% versus 10%, p=0.01).

4.        There was no significant difference between HTS and MAN in poor GOS (60% versus 50%, p>0.05) or mortality (40% versus 50%, p>0.05).

Shackford et al. (1998)

USA

RCT

PEDro=5

N=34

Population: TBI. Hypertonic Saline (HTS, n=18): ­Mean Age=33 yr; Gender: Male=17, Female=1; Mean GCS=4.7. Ringer’s Lactate Solution (RLS, n=16): Mean Age=31 yr; Gender: Male=10, Female=6; Mean GCS=6.7.

Intervention: Participants were randomized to receive intravenous infusions of 1.6% HTS or RLS.

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

1.        Mean ICP was significantly greater in the HTS than RLS at baseline (p<0.05).

2.        Mean ICP decreased in both groups, and there were no significant differences between groups in ICP at any time after entry (p>0.05).

3.        Average total number of interventions to control ICP was significantly greater in the HTS than in the RLS (p<0.01).

4.        Change in maximum ICP was positive in the RLS group but negative in the HTS group (-9.1 mmHg versus +2.5 mmHg, p<0.05).

5.        There were no significant differences between the HTS and RLS in mean GOS at discharge (2.7 versus 2.5, p>0.05).

Tan et al. (2016b)

Canada

Case Control

N=231

Population: TBI; Hypertonic Saline (HTS, n=124): Mean Age=31 yr; Gender: Male=99, Female=25; Mean GCS=5. Control (n=107): Mean Age=40 yr; Gender: Male=82, Female=25; Mean GCS=6.

Intervention: Participants who received HTS or did not (controls) were compared in retrospective analysis.

Outcome Measures: Mortality, Intracranial Pressure (ICP), Length of Stay (LOS), Additional Treatments.

1.        HTS and control groups were significantly different in mean age (p<0.001).

2.        There was no significant difference in hospital mortality between HTS and control groups (28 versus 31, p=0.34), and HTS was not an independent predictor of hospital mortality (HR 1.07, p=0.84).

3.        HTS group showed a significant decrease in ICP (4 mmHg, p<0.001), while controls did not (<2 mmHg, p=0.14).

4.        Mean values were significantly higher in the HTS group than in the controls for LOS in ICU (15 versus 8, p<0.001), desmopressin use (24 versus 9, p=0.03), and mannitol use (63 versus 20, p<0.001).

5.        There was significant association between HTS use and hypernatremia (p<0.001).

6.        There was no association between hypernatremia and mortality (P=0.53).

7.        In the HTS group, desmopressin use was associated with increased hospital mortality (HR 4.27, p<0.001), but mannitol use (HR 1.13, p=0.58) was not.

Major et al. (2015)

UK

Case Series

N=15

Population: TBI; Mean Age=36 yr; Gender: Male=11, Female=4.

Intervention: Participants who received a single bolus of 30% hypertonic saline (HTS) were included in retrospective analysis.

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

1.        There was a rapid and significant reduction in ICP over 8 hr (p=0.0004).

2.        There was no significant difference in CPP, MAP, or HR (all p>0.05).

Mangat et al.

(2015)

USA

Case Control

N=1238

Population: TBI; Hypertonic Saline (HTS, n=45): Mean Age=38.37 yr; Mean GCS=5.46. Mannitol (MAN, n=477): Mean Age=36.13 yr; Mean GCS=4.75. Hypertonic Saline & Mannitol (HTS+MAN; n=137): Mean Age=31.42 yr; Mean GCS=4.82. Control (n=589): Mean Age=42.63 yr; Mean GCS=4.96.

Intervention: Patients who received HTS, MAN, or neither (control) were retrospectively analyzed.

Outcome Measures: Intracranial Pressure (ICP) Length of Stay (LOS), Mortality.

1.        There was no significant difference in total number of ICP recording days between the HTS and MAN groups (p=0.09).

2.        The cumulative and daily ICP burdens were significantly lower in patients who received HTS compared to patients who received MAN (p=0.003 and p=0.001, respectively).

3.        LOS was significantly lower in the HTS compared to MAN with a 1:1 match (p=0.004); however, this became insignificant with a 1:2 match (p=0.06).

4.        There was no significant difference between HTS and MAN in mortality rate (p=0.53).

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.

Colton et al. (2014c)

USA

Case Series

N=46

Population: TBI; Mean Age=34.4 yr; Gender: Male=37, Female=9; Median GCS=6.

Intervention: Participants who received hypertonic saline (HTS) were included in retrospective analysis.

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

1.        ICP was significantly reduced from 21.5 mmHg to 14.4 1mmHg immediately after HTS (p<0.05) and to 12.5mmHg 2 hr after HTS (p<0.05).

2.        There was no significant difference in MAP or CPP after HTS.

Dias et al. (2014)

Portugal

Pre-Post

N=11

Population: TBI; Mean Age=40 yr; Gender: Male=9, Female=2; Mean GCS=6.

Intervention: Participants received 20% hypertonic saline (HTS). Outcomes were assessed before and after treatment.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Cerebral Blood Flow index (CBFx), Cerebrovascular Pressure Reactivity Index (PRx).

1.        Mean ICP decreased significantly from 20.5 to 14.3 mmHg at 128 min (p<0.001), with a final value of 16.8mmHg at 210 min.

2.        Mean CPP increased significantly from 85.1 to 88.2 mmHg at 119 min (p<0.001), with a final value of 86.3mmHg at 210 min.

3.        Significant improvements in CBFx (p=0.04) and PRx (p=0.01) were found after treatment.

Lewandowski-Belfer et al. (2014)

USA

Case Series

N=55

Population: TBI; Mean Age=50.1 yr; Gender: Male=24, Female=31.

Intervention: Participants who received hypertonic saline (HTS) were included in retrospective analysis. Patients were divided based on HTS concentration (14.6% or 23.4%).

Outcome Measures: Intracranial Pressure (ICP), Serum Sodium.

1.        There was a significant increase in mean serum sodium after HTS administration (p<0.0001).

2.        There was a significant decrease in ICP after HTS administration (p<0.0001).

3.        The efficacy of 23.4% HTS in decreasing ICP was not found to be significantly different than 14.6% HTS (p=0.23).

Eskandari et al. (2013)

USA

Pre-Post

N=11

Population: TBI; Mean Age=33.7yr; Gender: Male=10, Female=1; Mean GCS=7.18.

Intervention: Participants received repeated 15min intravenous infusions of 14.6% hypertonic saline (HTS) over 12 hr. If after 60mins the patient once again met the criteria of having refractory ICP, then repeated boluses were administered. Outcomes were assessed for 60 min after each bolus and at 12 hr.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Heart Rate (HR), Systolic Blood Pressure (SBP).

1.        Mean ICP was reduced from 4 0mmHg at baseline to 33 mmHg after 5 min (p<0.05), to 28 mmHg after 10min (p<0.05), and to 23mmHg after 12hr (p<0.05).

2.        Mean CPP increased from 60 mmHg at baseline to 63 mmHg after 5 min (p<0.05) and to 77 mmHg after 20 min (p<0.05); it was 70 mmHg by 12 hr.

3.        There was no significant difference in HR or SBP after HTS treatment.

Paredes-Andrade et al. (2012)

USA

Case Series

N=18

Population: TBI; Mean Age=35 yr; Gender: Male=16, Female=2; Median GCS=6.

Intervention: Patientss who received hypertonic saline (HTS) were retrospectively analyzed.

Outcome Measure: Intracranial Pressure (ICP).

1.        There was a significant reduction of 8.8 mmHg in ICP (p<0.0001) following HTS treatment.

Roquilly et al. (2011)

France

Case Series

N=50

Population: TBI; Mean Age=36 yr; Gender: Male=46, Female=4; Mean GCS=6.

Intervention: Patients who received hypertonic saline (HTS) were retrospectively analyzed.

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Plasma Osmolarity, Natremia.

1.        ICP significantly decreased after HTS administration (p<0.05).

2.        CPP significantly increased after HTS administration (p<0.05).

3.        Natremia significantly increased after HTS administration (p<0.05).

4.        Plasma Osmolarity significantly increased after HTS administration (p<0.05).

Sakellaridis et al. (2011)

Greece

Case Control

N=29

Population: TBI; Mean Age=36 yr; Mean GCS=5.4.

Intervention: Participants who received hypertonic saline (HTS) or mannitol were retrospectively analyzed.

Outcome Measures: Intracranial Pressure (ICP), Duration of effectiveness.

1.        There was no significant difference between HTS and mannitol in reducing ICP.

2.        There was no significant difference between HTS and mannitol in duration of effectiveness.

Kerwin et al. (2009)

USA

Cohort

N=22

Population: TBI; Mean Age=35.7 yr; Gender: Male=16, Female=6; Mean GCS=6.9. Intervention: Patients received intravenous infusions of 23.4% hypertonic saline (HTS) or mannitol (15-75 g, at the discretion of the neurosurgeon). Outcome Measure: Intracranial Pressure (ICP).

1.        Mean ICP reduction was significantly greater by HTS than mannitol (9.3mmHg versus 6.4 mmHg, p=0.0028).

2.        Patients with initial ICP>30 mmHg had a significantly greater mean ICP reduction by HTS than mannitol (12.6 mmHg versus 8 mmHg, p=0.0105).

3.        More patients responded to HTS than mannitol (93% versus 74%, p=0.002).

4.        HTS was more likely to yield an ICP reduction of >10 mmHg, while mannitol was more likely to yield a reduction of <5 mmHg.

5.        There was no significant difference between HTS and mannitol in amount of time ICP>20 mmHg (9.7 hr versus 7.4 hr, p=0.236) or duration of response (4.1 hr versus 3.8hr, p=0.854).

Oddo et al. (2009)

USA

Cohort

N=12

Population: TBI; Mean Age=36 yr; Gender: Male=9, Female=3; Mean GCS=3; Mean Time Post Injury=8 hr.

Intervention: Participants received intravenous infusions of 7.5% hypertonic saline (HTS) or 25% mannitol.

Outcome Measures: Intracranial Pressure (ICP), Mean Arterial Pressure (MAP), Cerebral Perfusion Pressure (CPP), Brain Tissue Oxygen Tension (PbtO2), Central Venous Pressure (CVP), Cardiac Output (CO).

1.        Mean ICP was more significantly reduced (p<0.001) by HTS than mannitol after 60min (15 mmHg versus 23 mmHg) and 120min (15 mmHg versus 24 mmHg).

2.        Mean CPP was more significantly increased by HTS than mannitol after 120min (76 mmHg versus 65 mmHg, p=0.02).

3.        Mean CO was more significantly increased by HTS than mannitol after 30 min (7.5 L/min versus 5.3 L/min, p=0.003), 60 min (7.8 L/min versus 6.6 L/min, p=0.007), and 120min (7.5 L/min versus 6.1 L/min, p=0.002).

4.        Mean PbtO2 was significantly increased by HTS (p<0.01) and decreased by mannitol (p>0.05) over time, with significant differences at 60min (37 mmHg versus 28 mmHg, p<0.05) and 120 min (41 mmHg versus 27.5 mmHg, p<0.01).

5.        There were no significant differences in MAP or CVP between groups.

Rockswold et al. (2009)

USA

Pre-Post

N=25

Population: TBI; Mean Age=33.5 yr; Gender: Male=21, Female=4; Mean GCS=5.7.

Intervention: Participants received intravenous infusions of 23.4% hypertonic saline (HTS) over 15 min. Patients were stratified into 3 different risk categories according to their presenting ICP, MAP, and CPP values at treatment time. These 3 groups represent low, medium, and high risk for being refractory to ICP management.

Outcome Measures: Intracranial Pressure (ICP), Mean Arterial Pressure (MAP), Cerebral Perfusion Pressure (CPP), Brain Tissue Oxygen Tension (PbtO2), Glasgow Outcome Scale (GOS), Mortality.

1.        Mean ICP decreased by 8.3 mmHg over time (p<0.0001). ICP level was positively affected for all 3 groups (P<0.05).

2.        Mean ICP reduction was positively correlated with initial ICP (p<0.05): 14.2 mmHg in those with ICP>31 mmHg, 9.3mmHg in those with ICP=26-30 mmHg, and 6.4 mmHg in those with ICP=20-25.

3.        Mean CPP increased in those with initial CPP=60-69 mmHg (p<0.05) and increased even more in those with CPP>70 mmHg (p<0.05).

4.        Mean MAP increased in those with initial MAP<79 mmHg (p<0.05) and decreased in those with initial MAP>100 mmHg (p<0.05).

5.        PbtO2 was significantly improved at 1, 3, and 4 hrs post treatment, but not at 2, 5, and 6 hrs.

6.        At 6 mos, mortality was 28% and favourable outcome (GOS).

Pascual et al. (2008)

USA

Pre-Post

N=12

Population: TBI; Mean Age=36.5 yr; Gender: Male=9, Female=3; Mean GCS=4.5.

Intervention: Participants received intravenous infusions of 7.5% hypertonic saline (HTS).

Outcome Measures: Intracranial Pressure (ICP), Cerebral Perfusion Pressure (CPP), Brain Tissue Oxygen Tension (PbtO2), Mean Arterial Pressure (MAP), Central Venous Pressure (CVP), Heart Rate (HR), Cardiac Output (CO).

1.        ICP significantly decreased after HTS (>40%, p<0.01) and remained significantly lower than baseline up to 4 hr (~20%, p<0.05).

2.        CPP significantly increased after HTS (>25%, p<0.01) and remained significantly greater than baseline up to 6 hrs (~30%, p<0.01).

3.        PbtO2 significantly increased over time after HTS (p<0.05).

4.        There was no significant difference in MAP, CVP, HR, or CO after HTS.

Lescot et al. (2006)

France

Pre-Post

N=14

Population: TBI; Mean Age=36 yr; Gender: Male=12, Female=2; Median GCS=7.

Intervention: Participants received intravenous infusions of 20% hypertonic saline (HTS, 40 mL) for 20 min.

Outcome Measures: Intracranial Pressure (ICP), Contused Brain Tissue (Specific Gravity, Volume), Non-Contused Brain Tissue (Specific Gravity, Volume), Natremia.

1.        HTS significantly increased natremia from 143 mmol/L to 146 mmol/L.

2.        HTS significantly decreased ICP from 23 mmHg to 17 mmHg.

3.        Volume of non-contused brain tissue decreased by 13 mL whereas the specific gravity increased by 0.029%.

4.        Volume of contused brain tissue increased by 5 mL without any concomitant change in density.

5.        There was wide individual variability in the response of the non-contused brain tissue, with changes in specific gravity varying between -0.0124% and 0.0998%.

Ware et al. (2005)

USA

Case Control

N=13

Population: TBI; Mean Age=42.0 yr; Gender: Male=10, Female=3; Time Post Injury<12 hr; Mean GCS=7.7.

Intervention: Participants received intravenous infusions of 23.4% hypertonic saline (HTS) and mannitol.

Outcome Measure: Intracranial Pressure (ICP).

1.        Both HTS and mannitol significantly reduced ICP (p<0.001) and there was no significant difference between them (p=0.174).

2.        Mean duration of ICP reduction by HTS was significantly longer than mannitol (96 min versus 59 min, p=0.016).

Horn et al. (1999)

Germany

Case Series

N=10

Population: TBI=6, SAH=4; Mean Age=41 yr; Gender: Male=5, Female=5; Mean GCS=5.4.

Intervention: Participants received intravenous infusions of 7.5% hypertonic saline (HTS, 20 mL/min, 2 mL/kg) after the failure of standard agents.

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

1.        Mean ICP significantly decreased (p<0.05) from 33 mmHg to 18mmHg at the time of maximum effect (~100 min).

2.        Mean CPP significantly increased (p<0.05) from 68 mmHg to 79 mmHg after 1hr and to 81 mmHg at maximum effect.

Schatzmann et al. (1998)

Germany

Case Series

N=6

Population: TBI=5, SAH=1; Mean Age=40 yr; Gender: Male=4, Female=2; Median GCS=6.

Intervention: Participants received intravenous infusions of 10% hypertonic saline (HTS, 100 mL) after the failure of standard agents.

Outcome Measure: Intracranial Pressure (ICP).

1.        ICP decreased by an average of 43% (18 mmHg) after HTS.

2.        Reduction in ICP lasted for an average of 93min and minimum ICP was reached at an average of 26 min after infusion.

Qureshi et al. (1998)

USA

Case Series

N=10

Population: TBI; Mean Age=44.4 yr; Mean GCS=7.1.

Intervention: Participants received intravenous infusion of 3% hypertonic saline/acetate solution (75-150 mL/hr).

Outcome Measures: Intracranial Pressure (ICP), Glasgow Outcome Scale (GOS), Serum Sodium.

1.        ICP reduction correlated with increasing serum sodium concentration (r2=0.91, p=0.03).

2.        Mean ICP was reduced from 14.2mmHg to 7.3 mmHg after treatment.

3.        Mean GCS improved from 7.1 to 7.4 after treatment.

4.        GOS was 3.6 1 mos after treatment.