Transcript - Blood CME Center

Hemorrhagic Shock
John B. Holcomb, MD, FACS
Commander, US Army Institute of
Surgical Research
Trauma Consultant for the
Surgeon General
Fort Sam Houston, Texas
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
2
Carrico CJ, et al. Crit Care Med. 1976;4:46-54.
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
3
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
4
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.
5
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.
6
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.
7
The “Bloody Vicious Cycle”
Coagulopathy Develops Over Time—1997
Major Torso Trauma
Active
Hemorrhage
Progressive
Coagulopathy
Iatrogenic
Factors
Core
Hypothermia
Metabolic
Acidosis
Contact
Activation
Clotting Factor
Deficiencies
Cellular
Shock
Tissue
Injury
Massive
Transfusion
Pre-existing
Diseases
8
Adapted from Cosgriff N, et al. J Trauma. 1997;42:857-861; discussion 861-862.
The Lethal Triad After 2003
Hypothermia
Acidosis
Death
Coagulopathy
Brohi K, et al. J Trauma. 2003;54:1127-1130.
MacLeod J, et al. J Trauma. 2003;55:39-44.
9
The Cycle of Coagulopathy
Trauma
Inflammation
Hemorrhage
Blood loss
Resuscitation
Shock
Other Diseases
Medications
Genetics
Dilution
Hypothermia
COAGULOPATHY
Data from International Group of Coagulation Investigators, 2008.
Acidemia
Hypothermia
Fibrinolysis
Factor
Consumption
CoTS
10
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.
11
Mortality by Level of Coagulopathy
60
Mortality (%)
50
40
N=391 transfused casualties
30
20
10
0
INR <1.5
Niles S, et al. J Trauma. 2008. In press.
INR 1.5-2.0
INR 2.0
12
Mortality by Coagulopathy and ISS
60
Normal
INR 1.5
Mortality (%)
50
P.001
40
30
P.001
20
P=.13
10
P=.06
0
0-14
15-24
25
?
Total
Injury Severity Score
Niles S, et al. J Trauma. 2008. In press.
13
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.
14
A Predictive Model for Massive
Transfusion in Combat Casualty Patients
• 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)
McLaughlin DF, et al. J Trauma. 2008;64(suppl):57-63.
15
Variables in MT Equation
Wald Value
Coefficient
Standard
Error
Odds
Ratio
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.
16
MT Scoring System
90
n=62
80
% Probability of MT
SBP <110
HR >105
HCT<32
pH <7.25
n=115
70
60
50
n=151
40
30
20
ROC=.839
n=202
n=168
10
0
0
1
2
3
4
Score
Adapted with permission from McLaughlin DF, et al. J Trauma. 2008;64(suppl):57-63.
Lippincott Williams & Wilkins http://lww.com.
©2008
17
Comparison of 4 MT Prediction Studies
Author
McLaughlin et al.
Yücel et al.
Moore et al.
Schreiber et al
Variables
ROC Value
SBP, HR, pH, HCT
0.839
SBP, HR, BD, Hgb
Male, +FAST, long bone/pelvic
fracture
SBP, pH
ISS >25
Hgb ≤11
INR >1.5
Penetrating injury
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.
0.892
0.804
0.804
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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:
500 mL WARM
• HCT: 38%-50%
• Plt: 150K-400K
• Coag: 100%
• 1000 mg fibrinogen
PRBC=packed red blood cells; Plt=platelet; FFP=fresh frozen plasma; cryo=cryoprecipitate.
Armand R, et al. Transfus Med Rev. 2003:17:223-231.
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Plasma Factor Concentration (%)
A Mathematical Model for FFP Transfusion Strategies During
Major Trauma Resuscitation With Ongoing Hemorrhage
0.5
v/V=0.005
0.45
v/V=0.02
0.4
0
20
40
60
80
100 120 140 160 180 200 220 240 260 280 300
Time, min
Rate of blood loss as a
fraction of total blood
volume per min
v/V=0.005
v/V=0.0075
v/V=0.01
v/V=0.0125
v/V=0.015
v/V=0.0175
v/V=0.02
Factor concentration during resuscitation; transfusate PRBC 3 U: FFP 1 U: crystalloid
100 mL (factor concentration 0.5 at time 0).
v/V = rate of blood loss as a fraction
of total volume per minute.
“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
20
The Cellular, Metabolic, and Systemic Consequences of
Aggressive Fluid Resuscitation Strategies (review,
Cotton et al, 2006)
• 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.
21
Supranormal Trauma Resuscitation Causes More
Cases of Abdominal Compartment Syndrome
• 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.
22
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.
23
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.
24
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.
25
The Ratio of Blood Products Transfused Affects
Mortality in Patients Receiving MTs at a Combat
Support Hospital
Odds Ratio Predicting Survival Using Multivariate Logistic Regression
Variable
Odds Ratio (95% CI)
P value
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
0.89 (0.84–0.95)
<.001
Plasma:RBC ratio
BD
AIS=Abbreviated Injury Scale.
Adapted with permission from Borgman MA, et al. J Trauma. 2007;63:805-813.
©2007 Lippincott Williams & Wilkins http://lww.com.
26
Mortality by Plasma:RBC Ratio
(n=246 MTs [2003-2005])
70
65
P<.001
Mortality (%)
60
50
40
34
30
19
20
10
0
(Low) 1:8
(Medium) 1:2.5
(High) 1:1.4
Plasma:RBC Ratio Groups
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.
Adapted with permission from Borgman MA, et al. J Trauma. 2007;63:805-813.
©2007 Lippincott Williams & Wilkins http://lww.com.
27
Comparison of the Primary Causes of Death in Each
Plasma:RBC Ratio Group
100
18.5
Time to Death
Low = 2 hr
Med = 4 hr
High = 38 hr
90
14
80
70
60
50
11.5
40
30
20
10
7
6
4
2
1
0.5
1
1
2.5
0
Low n=20
Medium n=18
Adapted with permission from Borgman MA, et al. J Trauma. 2007;63:805-813.
©2007 Lippincott Williams & Wilkins http://lww.com.
High n=31
28
UT Houston 4-Year Experience
Pre—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
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%
Variable
ED INR
Gonzalez E, et al. Paper presented at: 38th Annual Meeting of the Western
Trauma Association; February 24-29, 2008; Squaw Creek, CA. No. 29.
<.05
29
The Effect of rVIIa on Mortality in Combat-Related
Casualties With Severe Trauma and MT
• 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
Spinella PC, et al. J Trauma. 2008;64:286-294.
30
Kaplan-Meier Curve of 24-Hour Mortality
for rVIIa+ Patients vs rVIIa- Patients
24-Hour Survival
100
Cumulative Survival (%)
P<.05
80
60
40
rVIIa
No
Yes
20
0
0
5
10
15
20
25
Hour of Death
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.
31
Kaplan-Meier Curve of 30-Day Mortality for
rVIIa+ Patients vs rVIIa- Patients
30-Day Survival
100
Cumulative Survival (%)
P<.05
80
60
40
rVIIa
No
20
Yes
0
0
5
10
15
20
25
30
Day of Death
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.
32
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 optimal
plasma and platelet to RBC ratios. Survival in MT civilian patients
is improved by increasing plasma and platelet ratios. Current
survival 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.
33
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.
34
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.
35
Combat Case—IED, May 2006
36
Combat Case—IED, May 2006 (cont)
37
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
38
Radiographic Findings
39
Combat Case
40
The Surgical Field
41
Fragment
42
The Surgical Team
43
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
44
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
45
Multiple Papers Presented and Submitted on
This Topic
•
•
•
•
•
•
•
•
Military experience
AAST 07 Denver paper
AAST 07 Vanderbilt paper
AAST 07 Tulane paper
EAST 08 Vanderbilt paper
German Trauma Society
WTA Glue grant
WTA Houston
• ASA 08 abstract
252 patients
140 (1:1)
139
135
69
409
405
192
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.
46
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
47
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
48
Back to the Future?
Changing early
resuscitation
practices for the severely
injured from crystalloidbased to primarily
blood products
Over the past 12 months,
lyophilized plasma
transfused into injured
pigs—it is equivalent
to fresh whole blood
and FFP
• MGH, OHSU, USAISR
MGH=Massachusetts General Hospital; OHSU=Oregon Health Sciences
University; USAISR=US Army Institute of Surgical Research.
49
The Trauma Team
50