Post on 12-Jan-2016
Hemorrhagic ShockJohn B. Holcomb, MD, FACS Commander, US Army Institute ofSurgical ResearchTrauma Consultant for the Surgeon GeneralFort Sam Houston, Texas
2
Fluid Resuscitation Following Injury: Rationale for the Use of Balanced Salt Solutions
Rationale• Early use of type-specific whole blood remains the primary
treatment for shock due to blood loss• Lactated Ringer’s (LR) is used to replace interstitial fluid and to
support the intravascular volume until type-specific cross-matched blood is available
• LR is run at a very rapid rate—1000 to 2000 mL over 45 minutes—until whole blood is available
Subsequent Steps• Observe if the patient is a responder or nonresponder• Base further whole blood transfusion on the patient’s response
Seems very reasonable and sounds very similar to our recommendations
Carrico CJ, et al. Crit Care Med. 1976;4:46-54.
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Discussion Platform
• >80% of combat-related deaths occur within 6 hours of wounding
• >80% of potentially preventable combat deaths are attributable to uncontrolled bleeding Majority of deaths involve truncal (noncompressible)
areas not conducive to tourniquets
• Management strategy includes novel pharmaceuticals, dressings, biological agents, tourniquets, and directed energy to stop internal bleeding that cannot be controlled by external compression methods
• Standard IV fluids can cause damage to the endothelium and coagulation system
Hemorrhagic shock is a challenge to clinicians in both the civilian and combat casualty care setting
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A Definition of Hemorrhagic Shock
A clinical syndrome resulting from:• Decreased O2 perfusion of vital organs• Loss of blood volume
Characterized by:• Hypotension• Tachycardia• Pale, cold, and clammy skin• Oliguria• Decreased O2 delivery or utilization
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Combat-Related Trauma
• In Operation Iraqi Freedom and Operation Enduring Freedom,
>90% of casualties experience penetrating wounds Largely from fragment dispersal of improvised
explosive devises (IEDs)
• The Joint Theater Trauma Registry compared wounding patterns in these conflicts (Oct. 2001 to Jan. 2005) with available data from WWII, Korea, and Vietnam Proportion of head and neck wounds higher Proportion of thoracic wounds lower Proportion sustained from explosions 78%, the
highest seen in any large-scale conflict – Usually 50%-60%
Owens BD, et al. J Trauma. 2008;64:295-299.
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Markers for Hemorrhagic Shock
• HCT <32%
• SBP <110 mm Hg
• HR> 105 bpm
• Acidosis: pH <7.25
• BD <6 mmol/L
• INR> 1.5
• Temp <34°C
HCT=hematocrit; SBP=systolic blood pressure; HR=heart rate; BD=base deficit; INR=International Normalization Ratio.
Tieu BH, et al. World J Surgery. 2007;31:1055-1064. McLaughlin D, et al. J Trauma. 2008;64(suppl):57-63.
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Classes of Hemorrhagic Shock
Class I Hemorrhage (loss of <15%)• Little tachycardia• Usually no significant change in BP, pulse pressure,
respiratory rate
Class II Hemorrhage (loss of 15%-30%)• HR >100 bpm, tachypnea, decreased pulse pressure
Class III Hemorrhage (loss of 30%-40%)• Marked tachycardia and tachypnea, decreased SBP, oliguria
Class IV Hemorrhage (loss of >40%)• Marked tachycardia and decreased SBP, narrowed pulse
pressure, markedly decreased or no urinary output• Immediately life-threatening
Gutierrez G, et al. Crit Care. 2004;8:373-381.
8Adapted from Cosgriff N, et al. J Trauma. 1997;42:857-861; discussion 861-862.
Major Torso Trauma
ProgressiveCoagulopathy
CoreHypothermia
MetabolicAcidosis
ActiveHemorrhage
IatrogenicFactors
CellularShock
TissueInjury
ContactActivation
Clotting FactorDeficiencies
MassiveTransfusion
Pre-existingDiseases
The “Bloody Vicious Cycle”
Coagulopathy Develops Over Time—1997
99
The Lethal Triad After 2003
Acidosis Hypothermia
Coagulopathy
Death
Brohi K, et al. J Trauma. 2003;54:1127-1130.MacLeod J, et al. J Trauma. 2003;55:39-44.
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Trauma
Shock
COAGULOPATHY
Genetics
Hemorrhage
Fibrinolysis
Inflammation
AcidemiaDilution Medications
CoTS
Resuscitation
Blood loss
Factor Consumption
HypothermiaHypothermia
Other Diseases
Data from International Group of Coagulation Investigators, 2008.
The Cycle of Coagulopathy
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Acute Traumatic Coagulopathy in Combat Casualty Care
• Retrospective cohort study of 391 patients who received a transfusion
• Patient outcomes of Injury Severity Score (ISS) and mortality were assessed upon arrival to the ED– Physiologic associations of long bone fractures,
central nervous system injuries, BD, and temperature
• The prevalence of acute coagulopathy in this cohort was 38% and increased with ISS
Niles S, et al. J Trauma. 2008. In press.Brohi K, et al. J Trauma. 2003;54:1127-1130. MacLeod J, et al. J Trauma. 2003;55:39-44.
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0
10
20
30
40
50
60
INR <1.5 INR 1.5-2.0 INR 2.0
Mo
rtal
ity
(%)
12
Mortality by Level of Coagulopathy
N=391 transfused casualties
Niles S, et al. J Trauma. 2008. In press.
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Mortality by Coagulopathy and ISS
0
10
20
30
40
50
60
0-14 15-24 ?25 Total
Injury Severity Score
Mo
rtal
ity
(%)
Normal INR 1.5
P=.06P=.13
P.001
P.001
Niles S, et al. J Trauma. 2008. In press.
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Clinical Perspective
• Trauma patients who are the most severely injured (≈10%) also represent the majority of in-hospital deaths
• Considerable attention has been directed toward damage control surgery and reversing the acidosis and hypothermia present on admission
• Less attention has been directed toward reversing coagulopathy related to blood loss and predicting those patients who will need aggressive transfusion strategies
Holcomb JB, et al. J Trauma. 2007;62:307-310.
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• 3442 total patients• 680 received 1+ units blood in first 24 hours
• 204 transferred from another facility• 29 known younger than 18 years• 81 security internees
• Total of 302 patients in study population 80 patients (26.5%) required massive
transfusion (MT)
A Predictive Model for Massive Transfusion in Combat Casualty Patients
McLaughlin DF, et al. J Trauma. 2008;64(suppl):57-63.
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Variables in MT Equation
Wald Value CoefficientStandard
ErrorOddsRatio
HR >105 23.77 1.58 0.32 4.8
SBP <110 14.96 1.26 0.33 3.5
pH < 7.25 14.09 1.23 0.33 3.4
HCT <32 2.33 0.49 0.32 1.6
Adapted with permission from McLaughlin DF, et al. J Trauma. 2008;64(suppl):57-63. ©2008 Lippincott Williams & Wilkins http://lww.com.
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MT Scoring System
SBP <110HR >105HCT<32pH <7.25
ROC=.839
0
10
20
30
40
50
60
70
80
90
0 1 2 3 4
Score
% P
rob
abil
ity
of
MT
Adapted with permission from McLaughlin DF, et al. J Trauma. 2008;64(suppl):57-63. ©2008 Lippincott Williams & Wilkins http://lww.com.
n=168
n=202
n=151
n=115
n=62
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Comparison of 4 MT Prediction Studies
Author Variables ROC Value
McLaughlin et al. SBP, HR, pH, HCT 0.839
Yücel et al.SBP, HR, BD, Hgb
Male, +FAST, long bone/pelvic fracture
0.892
Moore et al. SBP, pH ISS >25
0.804
Schreiber et alHgb ≤11INR >1.5
Penetrating injury
0.804
Data from McLaughlin DF, et al. J Trauma. 2008;64:S57-S63; Yücel N, et al. J Trauma. 2006;60:1228-1236; discussion 1236-1237; Moore FA, et al. J Trauma. 2008;64:1010-1023; Schreiber MA, et al. J Am Coll Surg. 2007;205:541-545.
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Component Therapy vs Warm Whole Blood
Component Therapy:
1 U PRBC + 1 U Plt + 1 U FFP + 1 U cryo 680 COLD mL
• HCT 29%• Plt 80K• Coag 65% of initial concentration• 1000 mg fibrinogen
Warm Whole Blood:
PRBC=packed red blood cells; Plt=platelet; FFP=fresh frozen plasma; cryo=cryoprecipitate.Armand R, et al. Transfus Med Rev. 2003:17:223-231.
500 mL WARM• HCT: 38%-50%• Plt: 150K-400K• Coag: 100%• 1000 mg fibrinogen
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0.4
0.45
0.5
0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300
Time, min
Pla
sm
a F
ac
tor
Co
nc
en
tra
tio
n (
%)
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A Mathematical Model for FFP Transfusion Strategies During Major Trauma Resuscitation With Ongoing Hemorrhage
“A mathematical model for fresh frozen plasma transfusion strategies during major trauma resuscitation with ongoing hemorrhage”—Reprinted from, CJS December 2005; 48(6), Page(s) 470-478 by permission of the publisher. © 2005 Canadian Medical Association
v/V=0.005
v/V=0.02
Rate of blood loss as a fraction of total blood volume per min
v/V=0.005v/V=0.0075v/V=0.01
v/V=0.0125v/V=0.015
v/V=0.0175v/V=0.02
Factor concentration during resuscitation; transfusate PRBC 3 U: FFP 1 U: crystalloid100 mL (factor concentration 0.5 at time 0).
v/V = rate of blood loss as a fraction of total volume per minute.
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• McClelland RN, et al. JAMA. 1967;199:830-834
• Moore FD, et al. Ann Surg. 1967;166:300-301
• Rhee P, et al. Crit Care Med. 2000;28:74-78
• Brandstrup B, et al. Ann Surg. 2003;238:641-648
• NHLBI ARDS NET Clinical Trials Network; Wiedemann HP, et al. N Engl J Med. 2006;354:2564-2575
Cotton BA, et al. Shock. 2006;26:115-121.
The Cellular, Metabolic, and Systemic Consequences of Aggressive Fluid Resuscitation Strategies (review, Cotton et al, 2006)
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• Hypothesis: Normal resuscitation, compared with supranormal, requires less crystalloid volume, decreasing the incidence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS)
• 1999 to 2001 (n=85) versus 2001 to 2002 (n=71)
• Conclusion: Supranormal resuscitation, compared with normal resuscitation, was associated with more LR infusion, decreased intestinal perfusion (higher GAPCO2), and an increased incidence of IAH, ACS, multiple organ failure, and death
Balogh Z, et al. Arch Surg. 2003;138:637-643.
Supranormal Trauma Resuscitation Causes More Cases of Abdominal Compartment Syndrome
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Damage Control Resuscitation
• In the combat casualty care setting, clinicians treating coagulopathy often have:
Immediate access to PRBCs and thawed AB or A plasma
Rapid access to apheresis platelets, prepooled cryoprecipitate, fresh whole blood, and recombinant activated factor VIIa (rVIIa), as indicated
• Damage control resuscitation as a structured intervention begins immediately after rapid initial assessment in the ED and progresses through the OR into the ICU
Holcomb JB, et al. J Trauma. 2007;62:307-310.
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Damage Control Resuscitation (cont)
In the severely injured casualty, damage control
resuscitation consists of 2 parts:
• Resuscitation limited to keep BP at ≈90 mm Hg, preventing renewed bleeding from recently clotted vessels
• Intravascular volume restoration accomplished by using thawed plasma as a primary resuscitation fluid in at least a 1:1 or 1:2 ratio with PRBCs Minimizing crystalloid rVIIa is occasionally used
Holcomb JB, et al. J Trauma. 2007;62:301-310.
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Casualties Requiring Continued Resuscitation
• Blood bank notified to activate the massive transfusion protocol: Individual coolers
– 6 units of plasma– 6 units of PRBCs– 6 packs of platelets
The most severely injured also receive fresh warm whole blood as a resuscitative fluid
Crystalloid use is minimized and serves mainly as a drug carrier and to keep lines open
Multiple point-of-care lab checks– BD, Hgb, INR, Ca
• Lack of intraoperative coagulopathic bleeding has been remarkable
Holcomb JB, et al. J Trauma. 2007;62:307-310.Kauver DS, et al. J Trauma. 2006; 61:181-184.Spinella PC, et al. Crit Care Med. 2007;35:2576-2581.
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Adapted with permission from Borgman MA, et al. J Trauma. 2007;63:805-813. ©2007 Lippincott Williams & Wilkins http://lww.com.
The Ratio of Blood Products Transfused Affects Mortality in Patients Receiving MTs at a Combat Support Hospital
Variable Odds Ratio (95% CI) P value
Plasma:RBC ratio 8.6 (2.1–35) .003
AIS head/neck score 0.75 (0.61–0.94) .013
AIS thorax score 0.73 (0.57–0.92) .009
SBP 1.0 (0.98–1.01) .457
Hemoglobin 1.1 (0.91–1.2) .501
BD 0.89 (0.84–0.95) <.001
Odds Ratio Predicting Survival Using Multivariate Logistic Regression
AIS=Abbreviated Injury Scale.
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Mortality by Plasma:RBC Ratio(n=246 MTs [2003-2005])
Adapted with permission from Borgman MA, et al. J Trauma. 2007;63:805-813. ©2007 Lippincott Williams & Wilkins http://lww.com.
P<.00165
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19
0
10
20
30
40
50
60
70
(Low) 1:8 (Medium) 1:2.5 (High) 1:1.4
Plasma:RBC Ratio Groups
Mo
rta
lity
(%
)
Percentage mortality associated with low, medium, and high plasma to RBC ratios transfused at admission. Ratios are median ratios per group and include units of fresh whole blood counted both as plasma and RBCs.
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Comparison of the Primary Causes of Death in Each Plasma:RBC Ratio Group
Time to Death Low = 2 hr Med = 4 hr High = 38 hr
0
10
20
30
40
50
60
70
80
90
100
Low n=20 Medium n=18 High n=31
1 0.5 12
1
11.5
6
42.5
7
Adapted with permission from Borgman MA, et al. J Trauma. 2007;63:805-813. ©2007 Lippincott Williams & Wilkins http://lww.com.
18.5
14
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UT Houston 4-Year Experience
VariablePre—1:2 (N = 97)
Post—1:1 (N = 95) P value
Age 39±2 37±1.6 .44
ISS 29±1 28±1.2 .53
ED INR 1.8±0.2 1.62±0.08 .41
Pre-ICU Cryst (L) 9±1 7±0.4 .07
Pre-ICU PRBC 12±1 15±1.2 .06
Pre-ICU FFP 5±0.4 11±1.0 <.0001
ICU Admit INR 1.6±0.04 1.48±0.03 .02
6 hr FFP:PRBC 1: 2.4 1: 1.3 .05
24 hr FFP:PRBC 1:1.2 1: 1.0
Mortality 30% 15% <.05
Gonzalez E, et al. Paper presented at: 38th Annual Meeting of the Western Trauma Association; February 24-29, 2008; Squaw Creek, CA. No. 29.
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• rVIIa+ to rVIIa- patients 24-hour mortality was 7/49 (14%) and 26/75 (35%),
P=.01 30-day mortality was 15/49 (31%) and 38/75 (51%),
P=.03
• SBP was higher in the rVIIa+ group
• The use of rVIIa was associated with improved early and late survival after severe trauma and massive transfusion
• rVIIa was not associated with increased risk of thrombotic events
• Additional trials needed
The Effect of rVIIa on Mortality in Combat-Related Casualties With Severe Trauma and MT
Spinella PC, et al. J Trauma. 2008;64:286-294.
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Kaplan-Meier Curve of 24-Hour Mortality for rVIIa+ Patients vs rVIIa- Patients
P =.004 by the log rank test.
Adapted with permission from Spinella PC, et al. J Trauma. 2008;64:286-294. ©2008 Lippincott Williams & Wilkins http://lww.com.
0
20
40
60
80
100
0 5 10 15 20 25
Hour of Death
Cu
mu
lati
ve
Su
rviv
al
(%)
P<.05
rVIIa
No
Yes
24-Hour Survival
32
0
20
40
60
80
100
0 5 10 15 20 25 30
Day of Death
Cu
mu
lati
ve
Su
rviv
al
(%)
32
Kaplan-Meier Curve of 30-Day Mortality for rVIIa+ Patients vs rVIIa- Patients
P =.002 by the log rank test.
Adapted with permission from Spinella PC, et al. J Trauma. 2008;64:286-294. ©2008 Lippincott Williams & Wilkins http://lww.com.
rVIIa
No
Yes
30-Day Survival
P<.05
3333
Multicenter (16), Retrospective MT Study
Increased Plasma and Platelet to RBC Ratios Improves Outcome in 466 Massively Transfused Civilian Trauma Patients
Holcomb JB, Wade CE, Michalek JE, Chisholm GB, Schreiber MA, Gonzalez EA, Pomper G, Williams KL, Park MS, and The Trauma Outcomes Group.
Conventional MT guidelines underrepresent the optimalplasma and platelet to RBC ratios. Survival in MT civilian patientsis improved by increasing plasma and platelet ratios. Currentsurvival after MT varies up to 80% at 16 major Level 1 Trauma centers. Prospective trials should aim for a 1:1 ratio of plasma and platelet to RBC ratios.
Holcomb JB, et al. Abstract presented at: 128th Annual Meeting of the American Surgical Association; April 24-26, 2008; New York, NY. No. 6.
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Thawed Plasma
• FFP that is kept for up to 5 days at 4°C
• Present upon arrival in the ED Used as a primary resuscitative fluid
• This approach not only addresses the metabolic abnormality of shock, but initiates reversal of the early coagulopathy of trauma
• Multiple centers are now using this product Decreases waste by 60% to 70%
Malone DL, et al. J Trauma. 2006;60(suppl):91-96.Armand R, et al.Transfus Med Rev. 2003;17:223-231.
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Risks of FFP and Platelets
• Reports of transfusion-related acute lung injury (TRALI) from the UK hemovigilance Serious Hazards of Transfusion scheme suggest a risk from FFP in the region of 1 in 60,000 units
This may now be the most common cause of death from transfusion, and is the most frequent serious complication of FFP
• In 100% of the TRALI cases arising from FFP, a female donor was identified as the source of the HLA/HNA antibodies
• Must be alive to have some of these complications
MacLennan S, et al. J Trauma. 2006;60(suppl):46-50.
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Combat Case—IED, May 2006
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Combat Case—IED, May 2006 (cont)
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Combat Case
• Fragment wound in back• 30 min evac to CSH• Arrives pH=6.9• BD=25• Temp=35ºC• INR=2• HCT=10• SBP=60 mm Hg• HR=140 bpm• Upon arrival arrested in the ED• Clam shell/clamp aorta/to OR• Lines and DCR started in the ED
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Radiographic Findings
4040
Combat Case
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The Surgical Field
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Fragment
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The Surgical Team
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Outcome
• 30 FFP, 32 RBC, 10 cryo, 20 platelets, rVIIa, 5 liters of LR
• Bleeding stopped with packing
• No coagulopathic bleeding
• Abdomen closed day 3
• Recovered and discharged to local hospital in 14 days
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Prior Coordination and Cooperation
• Cannot be done in isolation and made up at 0200
• ED staff• Anesthesia• Surgery/Trauma• ICU• Transfusion/blood bank• Nursing• Very small numbers
3% of all civilian trauma admissions 15% to 70% mortality
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Multiple Papers Presented and Submitted on This Topic
• Military experience 252 patients +
• AAST 07 Denver paper 140 (1:1) - • AAST 07 Vanderbilt paper 139 + • AAST 07 Tulane paper 135 + • EAST 08 Vanderbilt paper 69 + • German Trauma Society 409 + • WTA Glue grant 405 +• WTA Houston 192 +
• ASA 08 abstract 467 +
• 8 papers + (2068) and 1 “negative” (140)
• ≈20 abstracts submitted to AAST-08 on this subject
AAST=American Association for the Surgery of Trauma; EAST=Eastern Association for the Surgery of Trauma; WTA=Western Trauma Association.
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Summary
• Uncontrolled hemorrhage is a major problem
MT used in 3% of all civilian trauma admissions
Very high mortality
• Predictive models are here
Rapid Dx of MT patients who are in shock
and coagulopathic
• Must start plasma and platelets much earlier
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Summary (cont)
• Use physiology (not tradition) to drive diagnosis and interventions
• Don’t make the presenting problems worse with repeated iatrogenic injury
• Accept known risks and benefits
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Changing earlyresuscitation practices for the severely injured from crystalloid- based to primarily blood products
Over the past 12 months,lyophilized plasmatransfused into injuredpigs—it is equivalentto fresh whole blood and FFP• MGH, OHSU, USAISR
Back to the Future?
MGH=Massachusetts General Hospital; OHSU=Oregon Health Sciences University; USAISR=US Army Institute of Surgical Research.
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The Trauma Team