Hypertonic Resuscitation Following Traumatic Injury | NCT00316017

NCT00316017

ID	Type	Description	Link
5U01HL077863-05	U.S. NIH Grant/Contract		View source
IND #12506 (shock cohort)	Other Identifier	FDA

Status Module

Sponsor/Collaborators Module

Collaborators

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
National Institute of Neurological Disorders and Stroke (NINDS)	NIH
The Institute of Circulatory and Respiratory Health (ICRH)	UNKNOWN

Oversight Module

Description Module

Detailed Description

Specific Aim: To determine if prehospital administration of 7.5% hypertonic saline /6% Dextran-70 (HSD) OR 7.5% hypertonic saline alone (HS), compared to current standard therapy with normal saline (NS), as an initial resuscitation fluid, affects survival following traumatic injury with hypovolemic shock.

Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. The majority of these deaths result from hypovolemic shock or severe brain injury. Patients in hypovolemic shock develop a state of systemic tissue ischemia then a subsequent reperfusion injury at the time of fluid resuscitation. Conventional resuscitation involves the IV administration of a large volume of isotonic or slightly hypotonic (lactated ringers, LR) solutions beginning in the prehospital setting. Although not conclusive, prior studies have suggested that alternative resuscitation with hypertonic saline (7.5%) solutions may reduce morbidity or mortality in these patients. Furthermore, hypertonic fluids may have specific advantages in the brain-injured patient, as they may aid in the rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thereby limiting secondary brain injury. In addition, recent studies have demonstrated that hypertonicity significantly alters the activation of inflammatory cells, an effect that may reduce subsequent organ injury from ischemia-reperfusion and decrease nosocomial infection. The majority of previous clinical trials have focused on the use of HSD. The potential for 7.5% saline alone (HS) to have similar effects has not been well studied. Removal of the dextran component may enhance the anti-inflammatory effects of this solution, which could improve secondary outcomes such as acute respiratory distress syndrome (ARDS), multiple organ failure syndrome (MOFS) and rates of nosocomial infections.

This study is a randomized, double-blind, three-arm placebo controlled trial designed to evaluate the clinical outcome of trauma patients with hypovolemic shock, as manifested by prehospital hypotension. Patients will be randomized to a single 250cc IV dose of 7.5% saline in 6% Dextran-70 (HSD), 7.5% saline (HS) or normal saline as the initial fluid for prehospital resuscitation. No additional interventions will occur once the patient is admitted to the hospital. In hospital data collection will last up to 28 days.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
1	Experimental	7.5% hypertonic saline/6% Dextran-70 (HSD)	Drug: 7.5% hypertonic saline/6% Dextran-70 (HSD)
2	Experimental	7.5% hypertonic saline (HS)	Drug: 7.5% hypertonic saline (HS)
3	Placebo Comparator	0.9% normal saline	Drug: 0.9% normal saline

Name	Type	Description	Arm Group Labels	Other Names
7.5% hypertonic saline/6% Dextran-70 (HSD)	Drug	250 cc dose given as a one-time intravenous (IV) bolus in the pre-hospital setting.	1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
28 Day Survival	The day of episode is counted as "Day 0". So for measures using a 28 day period, the maximum value is 29 (i.e. days 0 through 28).	28 days from time of Emergency Department (ED) arrival

Secondary Outcomes

Measure	Description	Time Frame
Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 28	Absence of diagnosis of Adult Respiratory Distress Syndrome and alive through day 28	28 days from time of ED arrival
Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 28

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Myron L Weisfeldt, MD	Resuscitation Outcomes Consortium	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Alabama Resuscitaion Center, University of Alabama		Birmingham	Alabama	35249	United States
UCSD-San Diego Resuscitation Research Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21178763	Result	Bulger EM, May S, Kerby JD, Emerson S, Stiell IG, Schreiber MA, Brasel KJ, Tisherman SA, Coimbra R, Rizoli S, Minei JP, Hata JS, Sopko G, Evans DC, Hoyt DB; ROC investigators. Out-of-hospital hypertonic resuscitation after traumatic hypovolemic shock: a randomized, placebo controlled trial. Ann Surg. 2011 Mar;253(3):431-41. doi: 10.1097/SLA.0b013e3181fcdb22.
25072443	Derived	Tisherman SA, Schmicker RH, Brasel KJ, Bulger EM, Kerby JD, Minei JP, Powell JL, Reiff DA, Rizoli SB, Schreiber MA. Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the Resuscitation Outcomes Consortium. Ann Surg. 2015 Mar;261(3):586-90. doi: 10.1097/SLA.0000000000000837.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
FG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

FG000231 subjects11 of 11 not completed due to "Bag Opened Not Given" (BONG)

FG001269 subjects12 of 13 not completed due to BONG; 1 not completed was a prisoner who was excluded

FG002395 subjects19 of 19 not complete due to BONG

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
BG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
BG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age Categorical

The HSD group included one subject with no age data available.

Number

participants

Title

Denominators

Categories

<=18 years

Title	Measurements
	BG00013 BG00113 BG00223 BG003

Age Continuous

The HSD group included one subject with no age data available.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00037.7± 17.3 BG00136.8± 16.1

Sex: Female, Male

Description only includes those subjects who received the study fluid.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00050 BG00151 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000177 BG001212 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

28 Day Survival

The day of episode is counted as "Day 0". So for measures using a 28 day period, the maximum value is 29 (i.e. days 0 through 28).

Per protocol, analysis was done on only those subjects who received the study fluid per randomization; this was defined as that the study fluid had been connected to the patient's IV.

Posted

Jul 2010

Number

participants

28 days from time of Emergency Department (ED) arrival

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000220 OG001256 OG002376

Title

Denominators

Categories

Title	Measurements
	OG000164 OG001187 OG002279

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	The null hypothesis is that there are no differences in the percent of patients who survived to day 28 day between the three groups.	test for proportions		0.91	The Statistical Analysis applies to the 7.5% hypertonic saline/6% Dextran-70 (HSD),7.5% hypertonic saline (HS), and 0.9% normal saline groups.						95						No	Superiority or Other

Secondary

Adult Respiratory Distress Syndrome(ARDS)-Free Survival Through Day 28

Absence of diagnosis of Adult Respiratory Distress Syndrome and alive through day 28

Posted

Jul 2010

Number

participants

28 days from time of ED arrival

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Worst Multiple Organ Dysfunction Score (MODS) Mean Through Day 28

Multiple Organ Dysfunction Score is described as:

Six organ systems were chosen, and a score of 0-4 allotted for each organ according to function (0 being normal function through to 4 for most severe dysfunction) with a maximum score of 24. The worst score based on available data (missing values were assumed normal) in each 24-hour period is taken for calculation of the aggregate score.

Posted

Jul 2010

Mean

Standard Deviation

Scores on a scale

28 days from time of ED arrival

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants

Secondary

Presence of Nosocomial Infection Through Day 28

Includes one or more nosocomial infections from the following list: pneumonia, blood stream infection, urinary tract infection and wound infection

Posted

Aug 2010

Number

participants

Within 28 days of injury, while hospitalized

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Packed Red Blood Cells (PRBC) First 24 Hours

The numbers of units of packed red blood cells transfused in the first 24 hours

Posted

Aug 2010

Mean

Standard Deviation

units of packed red blood cells

First 24 hours from the time of 911 call

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Total Fluids First 24 Hours

The total amount of IV fluids given in the pre-hospital setting and the hospital setting in the first 24 hours following the time of 911 call

Posted

Aug 2010

Mean

Standard Deviation

Liters

First 24 hours from the time of of 911 call

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Ventilator-free Days Through Day 28

The number of days beginning with the day of 911 call counted as "Day O" through day 28 that the patient did not require mechanical ventilation

Posted

Aug 2010

Mean

Standard Deviation

days

Duration of hospital stay through day 28

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Days Alive Out of the Intensive Care Unit (ICU) Through Day 28

The number of days the patient is alive and not being cared for in the intensive care unit

Posted

Aug 2010

Mean

Standard Deviation

days

First 28 days from the time of 911 call

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Days Alive Out of the Hospital Through Day 28

The number of days the patient is alive and no longer an inpatient in the hospital through day 28

Posted

Aug 2010

Mean

Standard Deviation

days

First 28 days from the time of 911 call

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Survival at Hospital Discharge

Alive at the time of discharge from the Level One or Two trauma hospital. This did not include disposition from rehabilitation facilities.

Posted

Aug 2010

Number

participants

Duration of hospital stay through to discharge

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Zero Units PRBC in First 24 Hours

This is the total number of subjects who received no blood products in the first 24 hours from the time of the 911 call.

Posted

Aug 2010

Number

participants

From the time dispatch received the 911 call to the end of the first 24 hours

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Zero Units PRBC and Died in Field or Emergency Department (ED)

This is the total number of subjects who died in the field or the ED from the set of subjects who received no blood products.

Posted

Aug 2010

Number

participants

From the time dispatch received 911 call to the time of death in the field or ED

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Zero Units PRBC and Died Within 6 Hours of Admission to the Hospital

This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received no blood products.

Posted

Aug 2010

Number

participants

The first 6 hours from the time of admission to the hospital

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Zero Units PRBC and Died Within 28 Days From the Time of the 911 Call

This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received no units of PRBC.

Posted

Aug 2010

Number

participants

From the time dispatch received the 911 call to 28 days

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

1-9 Units PRBC in First 24 Hours

This is the total number of subjects who received 1 to 9 units of packed red blood cells (PRBC) in the first 24 hours from the time of the 911 call.

Posted

Aug 2010

Number

participants

From the time dispatch received the 911 call to the end of the first 24 hours

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

1-9 Units PRBC and Died in Field or ED

This is the total number of subjects who received 1 to 9 units of packed red blood cells (PRBC) among the patients who died in the field or the ED.

Posted

Aug 2010

Number

participants

From the time dispatch received 911 call to the time of death in the field or ED

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

1-9 Units PRBC and Died Within 6 Hours of Admission to the Hospital

This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received 1 to 9 units of packed red blood cells (PRBC).

Posted

Aug 2010

Number

participants

The first 6 hours from the time of admission to the hospital

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

1-9 Units PRBC and Died Within 28 Days From the Time of the 911 Call

This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received 1 to 9 units of packed red blood cells (PRBC).

Posted

Aug 2010

Number

participants

From the time dispatch received the 911 call to 28 days

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Greater Than 10 Units PRBC in First 24 Hours

This is the total number of subjects who received greater than 10 units of packed red blood cells (PRBC) in the first 24 hours from the time of the 911 call.

Posted

Aug 2010

Number

participants

From the time dispatch received the 911 call to the end of the first 24 hours

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Greater Than 10 Units PRBC and Died in Field or ED

This is the total number of subjects who died in the field or the ED among the patients who received greater than 10 units of packed red blood cells (PRBC).

Posted

Aug 2010

Number

participants

From the time dispatch received 911 call to the time of death in the field or ED

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Greater Than 10 Units PRBC and Died Within 6 Hours of Admission to the Hospital

This is the total number of subjects who died within the first 6 hours from the time of admission to the hospital among the patients who received greater than 10 units of packed red blood cells (PRBC).

Posted

Aug 2010

Number

participants

The first 6 hours from the time of admission to the hospital

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Secondary

Greater Than 10 Units PRBC and Died Within 28 Days From the Time of the 911 Call

This is the total number of subjects who died within 28 days from the time of the 911 call among the patients who received greater than 10 units of packed red blood cells (PRBC).

Posted

Aug 2010

Number

participants

From the time dispatch received the 911 call to 28 days

ID	Title	Description
OG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml
OG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose
OG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	7.5% Hypertonic Saline/6% Dextran-70 (HSD)	7.5% hypertonic saline/6% Dextran-70 (HSD) 250 ml	21	220	1	220
EG001	7.5% Hypertonic Saline (HS)	7.5% hypertonic saline (HS) 250ml dose	25	256	1	256
EG002	0.9% Normal Saline	0.9% normal saline 250 ml dose as placebo	21	376	1	376

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Hypernatremia that required therapeutic intervention	Blood and lymphatic system disorders	Systematic Assessment	Serum sodium>160 mEq/L requiring therapeutic intervention	EG0002 events2 affected220 at risk EG0015 events5 affected256 at risk EG0025 events5 affected376 at risk
Increased intracranial hemorrrhage	Nervous system disorders	Systematic Assessment	Evidence observed on serial head CT scanning	EG00012 events12 affected220 at risk EG00114 events14 affected256 at risk EG00215 events15 affected376 at risk
Hypernatremia that did not required therapeutic intervention	Blood and lymphatic system disorders	Systematic Assessment	Serum sodium>160 mEq/L that did not require therapeutic intervention	EG0007 events7 affected220 at risk EG0016 events6 affected256 at risk EG0021 events1 affected376 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Pain, rash, hypotension secondary to a transfusion reaction	Blood and lymphatic system disorders	Non-systematic Assessment	200 cc red blood cells typed for another patient and not felt to be related to study intervention	EG0000 events0 affected220 at risk EG0010 events0 affected256 at risk EG0021 events1 affected376 at risk
Complete placental abruption leading to fetal demise	Pregnancy, puerperium and perinatal conditions	Non-systematic Assessment	Protocol violation: enrolled obviously pregnant woman, 6 months gestation	EG0000 events0 affected220 at risk EG0011 events1 affected256 at risk EG0020 events0 affected376 at risk
Seizure activity	Nervous system disorders	Non-systematic Assessment	Observed in prehospital setting during 7.5% hypertonic saline/6% dextran-70 (HSD) fluid administration	EG0001 events1 affected220 at risk EG0010 events0 affected256 at risk EG0020 events0 affected376 at risk

The trial was stopped early for futility in the presence of a potential safety concern regarding increased mortality among patients receiving hypertonic solutions and no blood transfusions. This was no longer evident 6 hr after hospital admission.

Certain Agreements

ID	Term
D012774	Shock, Traumatic
D014947	Wounds and Injuries
D012769	Shock

ID	Term
D012462	Saline Solution, Hypertonic
D000077330	Saline Solution

OG000220
OG001256
OG002376

ID	Term
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D006982	Hypertonic Solutions
D012996	Solutions
D004364	Pharmaceutical Preparations
D000077324	Crystalloid Solutions
D007552	Isotonic Solutions