6 May 3 - Marc Maegele

Clinical Problem Acute Coagulopathy Acute Management TASH-Score RBC : FFP Coagulation Support Conclusion
Management of Critical Bleeding in Multiple Trauma

Marc Maegele, M.D. Department of Trauma and Orthopedic Surgery Intensive Care Unit (ICI 166) Cologne-Merheim Medical Center (CMMC) University of Witten-Herdecke Cologne, Germany
Day 0
Motor cycle accident

28 yrs., male GCS = 14 BP: 110 / 80 mmHg Flail Chest Tachypnea Bloody Sputum Ventilation right SpO2 70% Intubation Mechanical Ventilation (FiO2 1,0, PEEP 5 mbar) Chest drain right
Transport
Cardiopulmonary function Vasopressors 1500 ml blood aspirated from lung
Day 0
Emergency room
Vital Signs > Shock BP: 80 / 50 mmHg Tachycardia f = 110 bpm > Lung (Patient intubated and mechanically ventillated FiO2 1,0, PEEP 5 > SpO2 78%) Chest x-ray > Tensionpneumothorax left > Chest tube Bronchoscopy > Bleeding from > lower lobes > upper lobe right 700 ml blood aspirated from lung > Labs Hb 6.5 g/dl Platelets 188,000/nl
Quicks value 39% PTT 61 sec BE 4.2 mmol/l > Sono pH 7,22
Free intraabdominal uid
OR !
Day 0
Operation Theatre
Laparotomy > Spleen rupture > Spleenectomy > Liver laceration > Suture
Day 0
Operation Theatre
Laparotomy > Spleenectomy, Liver suture > Shock BP: 70 / 40 mmHg Tachycardia f = 130 bpm > Lunge (Patient intubated/mechanically ventilated FiO2 1,0, PEEP 5 > SpO2 61%) 2500 ml blood aspirated from lung > Labs Hb 4.8 g/dl Platelets 49,000/nl
Quicks value 30% PTT 80 sec TEG: Hyperbrinolysis > Fibrinogendecit (F1)
Polytrauma management=Coagulation management
12 RBCs + 11 FFPs + 1 PC + 500.000 IE Aprotinin + 2g Fibrinogen
Day 0
Intensive Care Unit (ICI 166)

> Circulation BP: 120 / 80 mmHg f = 100 bpm No vasopressors! > Labs Hb 9.8 g/dl Quicks value 87% PTT 40 sec
> Lung (Patient intubated an mechanically ventilated with FiO2 1,0, PEEP 5 > SpO2 61%) Bronchoscopy: ongoing bleeding both lower lobes + upper lobe right Coagulopathy management 5 RBCs + 14 FFPs + 1 PC heparine 7,500 IE/24h Axial Rotation
Quick > 90% and PTT < 40sec
Day 0

> Circulation stable! > No vasopressors! > Labs > Lung stable > no further transfusions! FiO2 1,0 0,6 and PEEP
Bronchoscopy: Bleeding from lower lobes + upper lobe right with changing aspect from fresh to old Completion of diagnostics
Bilateral Contusions/ lacerations Air-/Fluid cavity upper lobe right
axial rotation cont
Day 0

> Stabilisation > Lung FiO2 0,4 PEEP > Stabilisation > Lung FiO2 0,3 PEEP
Cave:
Temperature: 40,2oC WBCs: 29,000/nl CRP: 265 mg/l CT: Infiltrate left B.-scopy: Pus left Microbiology: Klebsiella pneumoniae
End axial rotation and alternating prone/supine 1350 degrees
axial rotation cont
Piperacillin/ Sulbactam
Day 0
12
18
45

24hrs after antibiotics improvement of: Clinical picture Temperature Labs B-socopy (no pus) Lung FiO2 0,3
Discharge Extubation
Re-visit after 6 months normal ward
Pulmonary Function 6 months after trauma normal!

EVC (best): Expiratorische Vitalkapazitt
A C B
FVC (best): Forcierte Vitalkapazitt
Synopsis
Trauma and sequalae of this this patient comprised three major characteristics:
Trauma (i.e. pulmonary injury)
Bleeding / Coagulopathy
Infection
Coagulopathy
Denition:
Failure of the blood to clot normally in response to tissue injury from > trauma > surgery > invasive procedures (in daily routine practice)
Coaguloathy is also known as > microvascular hemorrhage or > non-surgical bleeding
Development of Traumatic Coagulopathy: Key Factors

The Bloody Vicious Cycle
Cut vessels/vessicles
Tissue trauma + consumption Tissue trauma + hyperbrinolysis
> hard to break <
Haemorrhagic Shock
Pre-existing disorders, anticoagulants
Hypoperfusion Protein C Path
Injury Blood with loss multifocal bleeding
Haemodilution
Resuscitation with Nonclotting Fluids
Fibrinolysis Triad of malfunction

Kozek-Langenecker, Min Anest 2007; 73: 1-15
Consumption of Clotting factors
hypothermia, acidosis, hypocalcemia
Traumatic Coagulopathy: The Lethal Triad
! Coagulopathy ! Acidosis ! Hypothermia
If this lethal triad is present ..... surgical control of bleeding is unlikely to be successful!
Ferrara et al., Am J Surg 1990; 160: 515
Traumatic Coagulopathy: The Lethal Triad

! Coagulopathy due to consumption and dilution
Sufcient quantity of clotting factors to initiate coagulation and substrate to form clot and ...
! Acidosis
!Hypothermia
... enable them to work appropriately!
Decreased pH of the reactions decreased rate of FXa formation by FVIIa/TF complex (solid circles)
Decreased pH of the reactions VIIa activity reduced linearly decreased rate of FIIa formation by with reduced temperature; 50% FXa/Va activity activity at temperatures of 28oC!
Meng et al., J Trauma 2003; 55:886-891
Probability of Life-Threatening Coagulopathy Increases with Shock, Hypothermia and Acidosis

Clinical Status No risk factor ISS > 25 ISS > 25 + SBP < 70 mmHg ISS > 25 + pH < 7,1 ISS > 25 + temperature < 34oC ISS > 25 + SBP < 70 mmHg + temperature < 34oC ISS > 25 + SBP < 70 mmHg + temperature < 34oC + pH < 7,1 Conditional Probability of developing Coagulopathy 1% 10% 39% 58% 49% 85% 98%
ISS = Injury Severity Score SBP = Systolic Blood Pressure

Cosgriff et al., J Trauma 1997; 42: 857-861
Clinical Problem Acute Coagulopathy Acute Management TASH-Score RBC : FFP
Bleeding is the Major Cause of Death in Trauma

(Patients dying in-hospital within the rst 48 hours after trauma)
6 0 5 0 4 0 3 0 2 0 1 0 CNS CNS + Exsang. Organ failure Exsanguination Other
Conclusion
Mortality < 48 hours after Trauma in (%)
Coagulation Support
Sauaia et al., J Trauma 1995; 38: 185-193
The Incidence of Acute Post-Traumatic Coagulopathy upon ER Admission

4 0
Trauma Patients in (%)
3 0
25%
2 0
1 0
Brohi J Trauma 2003 n=1,088
MacLeod J Trauma 2003 n=10,790
Maegele Injury 2007 n=8,724
Brohi Ann Surg 2007 n=208
Rugeri J Th Hem 2007 n=88
Acute Post-Traumatic Coagulopathy: Data from the German Trauma Registry

Data source: German Trauma Registry data-base (DGU - Traumaregister) 17.200 data sets from severely multiply injured patients 8.724 data sets with complete data on coagulation parameters Presence/ Absence of coagulopathy upon ER admission Prothrombin time test (Quick`s value) < 70% Platelets < 100,000/microliter Standard statistical software (SPSS, Chicago, IL, USA) Data were compared between the two groups a.) with coagulopathy b.) without coagulopathy c2-test for categorical variables U-test for continuous variables Level of signicance p-value < 0.05
Data:
Screening criteria: Denitions:
Data analysis: Statistics:

Coagulopathy upon ER admission was present in 2.989 (34.2%) of all patients screened
100 Number of patients in (%) 8 0 6 0 4 0 2 0 Coagulapathy Non-Coagulapathy Maegele et al. Injury 2007; 38 298-304

Outcome worse in coagulopathy versus non-coagulopathy (all p < 0.001)
Coagulopathy Non-Coagulopathy
30 25 20 15 10 5 0
MOF Mortality (< 24h)
In-hospital Mortality (overall)

Maegele et al. Injury 2007; 38 298-304
The Clinical Signicance of Acute PostTraumatic Coagulopathy : Mortality

normal coagulation coagulopathy
6 0 Mortality in (%)
4 0
2 0
x 4,6
Brohi J Trauma 2003 n=1,088
MacLeod J Trauma 2003 n=10,790
Maegele Injury 2007 n=8,724
Brohi Ann Surg 2007 n=208
Clinical Problem Acute Coagulopathy Acute Management
Abnormal Coagulation upon ER Admission: Predictor for Outcome

Probability of Survival (%) 1.00
TASH-Score RBC : FFP Coagulation Support Conclusion
0,50
0,00 10 20 30 Analysis of Time (days) 10 20 30
Abnormal PT/PTT upon ER admission is a predictor (independent!) for mortality in trauma patients !
MacLeod et al., J Trauma 2003; 55: 39-44
Prothrombin Time is a Predictor for Survival after Major Trauma
Results: PT correlated with > severity of injury > level of therapeutic interventions ROC analysis and regression revealed PT as a signicant prognostic factor! Conclusion: PT > is readily available already in the ER > can be used as a screening variable in the assessment of trauma load > can help in the decision-making for further treatment
Raum et al., Eur J Trauma 2001; 3: 110-116
What can we do: How is Shock Treated?

Principles: !Identify and eliminate trigger ! ! Restore normal physiology !
Hemorrhage: Control the bleeding

Chest, Abdomen, Retroperitoneum, Long Bones,Vacular Injury
Spleen rupture
Lung laceration + active bleeding
Renal injury + bleeding
Gunshot Carotid Artery

www.trauma.org
Hemorrhage: Surgical Techniques

! Direct Pressure ! Tourniquet ! Ligation of vessels ! Tube Thoracostomy !Damage Control Surgery !Angiographic Embolization
How to x the Pelvis Acutely?

Closed Reduction of the Pelvic Ring in the ER

!Inner rotation and adduction of thighs !Flexion of knees !Wrapping with bandages/ towels
Before
After closed reduction Stahel P, Ertel W. In: Rter A et al.: Unfallchirurgie 2004
What else can we do?

Basic Measures in the Bleeding Trauma Patient

!Achieve and maintain normothermia !Achieve and maintain normal pH !Achieve and maintain normal ionised Ca2++ levels !Achieve and maintain normal blood pressure (volume + catecholamines)
Substitution of Fluids and Blood Components in Major Bleeding
Hct=21-24% PT,aPTT > 1,5x normal Fg=1,0g litre-1 Plt<80x109 litre-1
Values of various parameters represent trigger points at which relevant blood components should be transfused. RBC, red blood cells; FFP, fresh frozen plasma; PCC, prothrombin complex concentrate; Fg, brinogen; Plt, platelets; Hct, haematocrit; PT, prothrombin time; aPTT, activated partial thromboplastin time. Modied from Spahn D, Roissaint R, Br J Anaesth 2005; 95(2): 130-139
Battle Hypoperfusion: Volume!!

Organ Hypoperfusion and Mortality in Trauma Patients
6 0 Mortality in (%)
4 0
2 0
< 12
12-24
> 24
Duration of Organ Hypoperfusion (in hours)
Brohi K, unpublished data
Isotonic Crystalloid Infusions:

Widely accepted for resuscitation in trauma care, but ...

> Volume expansion, increase in cardiac output, increase in blood pressure > Hemodilution, reduction in hematocrit > Reduction in vasoconstriction > Reduction in temparature > Immune dysfunction
Coagulopathy !
Task: To provide enough fluid for perfusion, but not so much that it delutes the circulation or induces re-bleeding! > early vasopressors!
Blood Products
How many and what kind of transfusions do you want me to order from the blood bank ?
1/3 trauma patients in the ER is coagulopathic !
Is he continously bleeding ?
TASH
Trauma Associated Severe Hemorrhage
A simple scoring system to predict the need for massive blood transfusion in severe trauma patients
An analysis from the German Trauma Registry
TASH Trauma Associated Severe Hemorrhage

Aim:
To develop a simple scoring system to predict the need for massive transfusion
Data:
German Trauma Registry, 1993-2003
Patients:
- primary admissions - data on blood transfusion - data on potential predictors
Target:
Blood transfusion of at least 10 units of pRBC during emergency room management and initial surgery (mass transfusion)
Methods:
Pre-Analysis for identication of predictors (pilot phase) Split of data set: development / validation Model building by multivariate logistic regression
Clinical Problem Incidence of acute early coagulopathy TASH Transfusion practice Conclusion
TASH Database: German Trauma Registry

1993-2006: 29.353 patients from 125 hospitals in 6 countries
30000 25000 20000 15000 10000 5000 260 0 1.987 2.839 662 1.360 4.053 8.192 5.689
30.000 25.000
20.918 24.771
29.353
20.000
14.211 11.125
17.545
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
German Trauma Registry: Data Collection

Standardised Documentation at 5 time Points after Trauma
Intensive Care Unit Time point Follow-up Time point
Trauma
Time point
Time point
Time point
A
Prehospital
B
Emergency room
D
Discharge
TASH: Potential Predictor Variables (Pre-Analysis)

Age Sex SBPA SBPB Hb GCS Thr Lact BE AIS NISS HR Age at accident Male gender Systol. blood pressure [A=pre-clinical] Systol. blood pressure [B=emergency room] Hemoglobin Glasgow Coma Scale (pre-clinical) Thrombocytes Lactate Base Excess Injury pattern (max. AIS for 4 body regions: (head, thorax, abdomen, extremities) New ISS Heart rate
TASH: Final Predictor Variables

Age Sex SBPA SBPB Hb GCS Thr Lact BE AIS NISS HR
Age at accident Male gender Systol. blood pressure [A=pre-clinical] Systol. blood pressure [B=emergency room] Hemoglobin Glasgow Coma Scale (pre-clinical) Thrombocytes Lactate Base Excess Injury pattern (max. AIS for abdomen, extremities) New ISS Heart rate
Others excluded due to strong variation, missing values and no impact!
TASH: Final Score

Variable Hb
Value <7 <9 < 10 < 11 < 12 < -10 < -6 < -2 < 100 < 120 > 120
Score 8 6 4 3 2 4 3 1 4 1 2 3 3 6 1
Base Excess SBP HR
Free uid on abdom. ultrasound
Femur or open/disloc. Fracture Pelvic Fracture with blood loss Male patient
TASH: Patients
all patients primary cases with data about RBC transfusion

HR
17,200
13,436
412 936 1,112 1,245 (3%) (7%) (8%) (9%)
completeness of predictor variables (patients with missing data)
BP AIS Hb BE
6,622 (49%)
patients with complete data
6,044
Incidence of mass transfusion: 13,9% (n=841)
TASH vs average number of RBC

30 40
Average no. of RBC
20
10
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
TASH score
Development data set: n=4527
Clinical Problem Acute Coagulopathy Acute Management TASH-Score RBC : FFP

Percentage with mass transfusion
TASH vs Percentage of patients with Mass Transfusions

100% 90%
Coagulation Support Conclusion
80%
70%
60%
50%
40%
30%
20%
10%
0% 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
TASH score
TASH
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
0,7 1,0 1,3 1,8 2,4 3,2 4,3 5,7 7,6 10,0 13,0 16,8 21,4 26,9 33,2 40,1 47,5 55,0 62,2 69,0 75,0 80,2 84,6 88,1 90,9 93,1 94,8 96,1 97,1
PMT
Probability PMT for Mass derived from TASH

Logistic function: P = 1 / [ 1 + exp ( 4.9 - 0.3 * TASH ) ]
100
Probability of MT (%)
90 80 70 60 50 40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
TASH Score
The TASH score is a simple method for quickly predicting need of mass transfusion It can be calculated within the first 10 minutes after admission
RBC : FFP ratio: Does it matter?

Evidence from Military Settings

(Borgman M et al., J Trauma 2007; 63: 805)
!US Military hospital Iraq 2003-2005 !Patients fullling denition for massive transfusion (> 10 RBC units) !246 patients (94% penetrating injury) !Grouped according to RBC to FFP transfusion ratio
RBC : FFP Ratio Groups

80
60 Mortality in (%)
40
20
Low (8:1)
Medium (2,5:1) RBC : FFP ratio groups
High (1,4:1)
Borgman et al., J Trauma 2007; 63: 805
High ratio groups died not from hemorrhage !

100 80 Mortality in (%) 60 40 20
Low (8:1)
Medium (2,5:1)
High (1,4:1)
Hemorrhage (%) 95,2 Sepsis (%) 5 MOF (%) 0 Airway (%) 0 CNS (%) 2,5 Time to death (hrs) (%) 2(1-4)
78 6 11 6 0 2(2-16)
37 19 13 8 23 38(4-155)
Borgman et al., J Trauma 2007; 63: 805
RBC to Plasma Ratios Transfused during Massive Transfusion are Associated with Mortality in Severe Multiply Injury: Data from the German Trauma Registry
< 24 hours (p<0,0001) In-hospital (overall; p<0,0004)
n = 409
Maegele et al., Vox Saguinis 2008; submitted
Transfusion Packages: A Pro-Active Approach

for massive / life-threatening bleedings 5 RBCs + 5 FFPs + PCs, resulting in a haematocrit - 30%, factor concentration > 30% and a platelet count -80 x 109/L administered consecutively until heamostasis is secured
Johansson et al., Transfusion 2007; 47:593-598
Package Approach in rAAA

(ruptured abdominal aortic aneurysm)
Prospective intervention (n=55; 12 months) > 2 PCs at start of surgery and 2 PCs during reperfusion, FFPs administered in a 1:1 ratio with RBCs from start of surgery versus Retrospective control (n=93; 24 months) > transfused according to exsisting guidelines
(ASA Task Force on Blood Component Therapy, Anesthesiology 1996; 84:732-747)
Conclusions: 1. Transfusion packages maintain haemostatic competence despite life-threatening bleedings 2. Transfusion packages + real time monitoring helped to reduce mortality with > 30% in the massively bleeding patients
Johansson et al., Transfusion 2007; 47:593-598
Algorithm of the bleeding trauma patient

Massive Bleeding
Control of bleeding source via surgery/embolism Blood products Reversal of anticoagulation
Bleeding stopped
On-going massive Bleeding
No further Treatment
????
Coagulation Support for Bleeding Complications

Adjunctive treatment options ! Antibrinolytics > aprotinin, tranexamic acid, e-aminocaproic acid
Coagulation factor substitution ! Fibrinogen, cryoprecipitates ! Prothrombin complex concentrate (PCC) ! AT III ! rFVIIa
Adjunctive Treatment Options

Antibrinolytic Agents: Recommendation R23
We suggest that antibrinolytic agents be considered in the treatment of the bleeding trauma patient. Suggested dosages: " Tranexamic acid 10-15 mg/kg followed by an infusion of 1-5 mg/kg/h " e-aminocaproic acid 100-150 mg/kg followed by 15 mg/kg/h " Aprotinin 2 million KIU (after a test dose) immediately followed by 500,000 KIU/h in an i.v.-infusion Antibrinolytic therapy should be stopped once bleeding has been adequately controlled. (Grade 2C)
Spahn et al., Crit Care 2007; 11:R17
A large randomised controlled trial among trauma patients with signicant haemorrhage, of the effects of antibrinolytic treatment on death and transfusion requirement (PI T. Coats/ Leicester (UK)) ! Largest clinical trial in traumatic hemorrhage ! Aims to recruit 20,000 patients world-wide ! Expected to be completed in December 2009 ! Already 6,500 patients included
Information: www.crash2.lshtm.ac.uk/CRASH2_Scientic.ppt
Coagulation Factor Substitution

Fibrinogen or Cryoprecipitate: Recommendation R22
We recommend treatment with brinogen concentrate or cryoprecipitate if signicant bleeding is accompanied by a plasma brinogen level < 1 g/l. We suggest an initial brinogen concentrate dose of 3-5 or 50 mg/kg of cryoprecipitate approximately equivalent to 15-20 units in a 70 kg adult. Repeated dose should be guided by laboratory assessment of brinogen levels. (Grade 1C)
Fibrinogen to Treat Coagulopathy

Objective:
To determine whether brinogen is useful in reversing dilutional coagulopathy after severe haemorrhage and administration of colloids
Methods:
# 14 pigs with a 65% exchange of blood versus gelatin for dilutional coagulopathy after standardized liver injury (uncontrolled bleed) # Treatment with 250 mg/kg brinogen (Cave: supratherapeutic dose!) versus normal saline # Sequential blood sampling for ROTEM, standard coagulation tests # Electron microscopy of blood clots, and documentation of blood loss
Results:
! Replacing 65% of estimated blood volume with gelatin resulted in dilutional coagulopathy ! Fibrinogen improved clot formation and reduced blood loss signicantly
Fries et al., Br J Anaesth 2005; 95: 172-177
Fibrinogen to Treat Coagulopathy

Electron Microscopy for Blood Clot Formation
Normal Clot
Diluted Clot
Diluted Clot after Fibrinogen administration

Fries et al., Br J Anaesth 2005; 95: 172-177
Prothrombin Complex Concentrate (PCC)

! Contains factors II, V, VII, IX, X ! Recommended if rapid correction of aquired coagulation factor is needed ! Often used incorrectly as rst-line bleeding treatment ! Prolonged use and concurrent treatment with antibrinolytics should be avoided > risk of thrombembolic events!
Collen and Lijnen, Blood 1991; 78: 3114-3127 Menzebach et al., Eur J Anesthesiol 2003; 20: 764-770 Royston, Int Anesthesiol Clin 1995; 33: 155-179 Staudinger et al., Int Care Med 1999; 25: 1105-1110
Rationale for Prothrombin Complex Concentrate (PCC)

! PCC has been used to control bleeding in haemophilia patients or to reverse effect of oral anticoagulant agents ! Despite its common use, there is no clear indication for prothrombin complex concentrate (PCC) use in bleeding nonhaemophilia patients ! No clinical randomised studies have been conducted to date to determine whether administration of PCC improves clinical outcome in severely bleeding trauma patients
Practice guidelines for blood component therapy. Anesthesiology 1996; 84: 732-747 Kessler, J Thromb Haemost 2006; 4: 963-966
Prothrombin Complex Concentrate (PCC)
Prothrombin Complex Concentrate (PCC): Recommendation R25
Antithrombin III
Antithrombin III: Recommendation R26
Antithrombin III
Antithrombin III: Recommendation R26
rFVIIa
Tissue factor (TF)/FVIIa, or TF/rFVIIa interaction, is necessary to initiatiate haemostasis
The thrombin burst leads to the formation of a stable clot
At pharmacological concentrations rFVIIa directly activates FX on the surface of locally activated platelets. This activation will initiate the thrombin burst independently of FVIII and FIX. This step is independent of Tissue Factor (TF).
rFVIIa: RBC requirements during 48 hours after rst dose of trial drug
Two randomized, placebo-controlled, double-blind trials simultaneously 1. Blunt trauma 2. Penetrating trauma Goal: To evaluate the efcacy and safety of rFVIIa as adjunctive for bleeding control in severe blunt or penetrating trauma Methods: Randomisation into 1. rFVIIa (200, 100, and 100 microg/kg) 2. Placebo First dose after 8th RBC unit, then after 1 and 3 hrs Primary Endpoint: RBC units transfused within 48 hours after 1st dose
Boffard et al., J Trauma 2005; 59: 8-18
rFVIIa: RBC requirements during 48 hours after rst dose of trial drug
301 Patients randomised Blunt Trauma n = 143 (69v/74pla) RBC
estimated reduction of 2.6 units (p = 0.02)
Penetrating Trauma n = 134 (70v/64pla) RBC

estimated reduction of 1.0 units (p = 0.10)
Massive Transfusion
14% vs. 33% of patients (p = 0.03)
Massive Transfusion
7% vs. 19% of patients (p = 0.08)
rFVIIa: 30 d Incidence of MOF, ARDS and Death, ITT-population

Blunt Trauma
4 0 Incidence in (%)
n=22
Penetrating Trauma
4 0
n=17
3 0 p=0,03 2 0 1 0
n=12 n=9 n=5 n=3
3 0 2 0 1 0
n=18 n=17
n=7 n=5 n=4 n=2
MOF Placebo rFVIIa
ARDS
Death
MOF
ARDS
Death
rFVIIa: Effect on Mortality in Combatrelated Casualties with Severe Trauma and Massive Transfusion
Objective: To determine whether rFVIIa decreased mortality in combat casualties with severe trauma and massive transfusion and its association with thrombembolic events p=0,12 Methods: Mortality n=29/37 # Retrospective analysis from combat 8 database 0 # Combat victims (ISS > 15), MT p=0,03 (>10 RBC/24 hrs) in combat support n=8/14 6 n=38/75 hospital Baghdad/Iraq between 0 12/2003 and 10/2005 p=0,01
Mortality (%)
Results: 124 patients 49 with rFVIIa 75 no rFVIIa no differences in ISS, Labs and vital signs differences in blood pressure and temperature no differences in thrombotic events
4 0 2 0
n=26/75 n=15/49
n=7/49
24 hours
rFVIIa Placebo
30 days
from hemorrhage
Spinella et al., J Trauma 2008; 64: 268-293
rFVIIa
rFVIIa: Recommendation R24
We suggest that the use of rFVIIa be considered if major bleeding in blunt trauma persists despite standard attempts to control bleeding an best practice use of blood components. We suggest an initial dose of 200 microgramm/kg followed by two 100 microgramm/kg doses administered at 1 and 3 hours following the rst dose. (Grade 2C)
Conclusions (I)
! There is a high frequency of established coagulopathy in multiply injury upon ER admission. ! The presence of early post-traumatic coagulopathy is associated with > injury severity > negative outcome ! The TASH-Score presents a simple scoring system to predict the need for massive blood transfusion in severe trauma patients. ! The TASH-Score can be calculated within the rst 10 minutes after ER admission.
Conclusions (II)
Goal for Resuscitation - Early

! Expedite control of hemorrhage. ! Limit crystalloid infusion > consider vasopressors early! ! Maintain blood pressure 80-100 mmHg systolic! ! Give blood products early and often: 1:1:1 ! Frequent laboratory studies! ! Deep anesthesia!
Conclusions (III)
Key Goals for the Management of critical bleeding in the Trauma Patient > 8 Steps to Support Coagulation
1. 2. 3. 4. 5. 6. 7. 8. Achieve normothermia Achieve normal pH Achieve normal Ca2++ Treat with FFP, if PT or aPTT abnormal Treat with platelets, if < 80 x 109 Treat with Fibrinogen, if < 1g/l Treat with Antibrinolytics, if hyperbrinolysis Treat with rFVIIa, if all else fails Plt > 50x109, Fg > 1g/l,
Hct >24, pH > 7,2
Modied from Spahn D, Roissaint R, Br J Anaesth 2005; 95(2): 130-139 Hct=21-24% PT,aPTT > 1,5x normal Fg=1,0g litre-1 Plt<80x109 litre-1
RBC, red blood cells; FFP, fresh frozen plasma; PCC, prothrombin complex concentrate; Fg, brinogen; Plt, platelets; Hct, haematocrit; PT, prothrombin time; aPTT, activated partial thromboplastin time.
Do you still remember our patient?

He successfully resumed his hobby after hospital discharge!
6th Congress of the International Federation of Shock Societies
&
31st Annual Conference on Shock
&
7th International Conference on Complexity in Acute Illness (ICCAI)
June 28 July 2, 2008 Cologne, Germany
&
Translational Research From the Bedside to the Bench and Back
Congress President E. A. M. Neugebauer University of Witten/Herdecke
www.shock2008-cologne.org

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Clinical Problem Acute Coagulopathy Acute Management TASH-Score RBC : FFP Coagulation Support Conclusion

Management of Critical Bleeding in Multiple Trauma

Motor cycle accident

Free intraabdominal uid

Polytrauma management=Coagulation management

12 RBCs + 11 FFPs + 1 PC + 500.000 IE Aprotinin + 2g Fibrinogen

Intensive Care Unit (ICI 166)

Quick > 90% and PTT < 40sec

Intensive Care Unit (ICI 166)

axial rotation cont

Intensive Care Unit (ICI 166)

End axial rotation and alternating prone/supine 1350 degrees

axial rotation cont

Intensive Care Unit (ICI 166)

Pulmonary Function 6 months after trauma normal!

FVC (best): Forcierte Vitalkapazitt

Trauma (i.e. pulmonary injury)

Coaguloathy is also known as > microvascular hemorrhage or > non-surgical bleeding

Development of Traumatic Coagulopathy: Key Factors

Tissue trauma + consumption Tissue trauma + hyperbrinolysis

> hard to break <

Injury Blood with loss multifocal bleeding

Fibrinolysis Triad of malfunction

Consumption of Clotting factors

hypothermia, acidosis, hypocalcemia

Traumatic Coagulopathy: The Lethal Triad

! Coagulopathy ! Acidosis ! Hypothermia

Ferrara et al., Am J Surg 1990; 160: 515

Traumatic Coagulopathy: The Lethal Triad

Meng et al., J Trauma 2003; 55:886-891

Probability of Life-Threatening Coagulopathy Increases with Shock, Hypothermia and Acidosis

ISS = Injury Severity Score SBP = Systolic Blood Pressure

Clinical Problem Acute Coagulopathy Acute Management TASH-Score RBC : FFP

Bleeding is the Major Cause of Death in Trauma

Mortality < 48 hours after Trauma in (%)

Sauaia et al., J Trauma 1995; 38: 185-193

The Incidence of Acute Post-Traumatic Coagulopathy upon ER Admission

Trauma Patients in (%)

Brohi J Trauma 2003 n=1,088

MacLeod J Trauma 2003 n=10,790

Maegele Injury 2007 n=8,724

Brohi Ann Surg 2007 n=208

Rugeri J Th Hem 2007 n=88

Acute Post-Traumatic Coagulopathy: Data from the German Trauma Registry

Screening criteria: Denitions:

Data analysis: Statistics:

Acute Post-Traumatic Coagulopathy: Data from the German Trauma Registry

Acute Post-Traumatic Coagulopathy: Data from the German Trauma Registry

In-hospital Mortality (overall)

The Clinical Signicance of Acute PostTraumatic Coagulopathy : Mortality

Brohi J Trauma 2003 n=1,088

MacLeod J Trauma 2003 n=10,790

Maegele Injury 2007 n=8,724

Brohi Ann Surg 2007 n=208

Clinical Problem Acute Coagulopathy Acute Management

Abnormal Coagulation upon ER Admission: Predictor for Outcome

TASH-Score RBC : FFP Coagulation Support Conclusion

0,00 10 20 30 Analysis of Time (days) 10 20 30

MacLeod et al., J Trauma 2003; 55: 39-44

Prothrombin Time is a Predictor for Survival after Major Trauma

What can we do: How is Shock Treated?

Principles: !Identify and eliminate trigger ! ! Restore normal physiology !

Hemorrhage: Control the bleeding

Chest, Abdomen, Retroperitoneum, Long Bones,Vacular Injury