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Case. 28y male involved in an industrial accident Sustained significant injuries to right lower leg, femur and ?hemipelvis Prolonged extrication “tons of blood” at the scene. Case 1. Looks very unwell with ++ ongoing bleeding GCS E3 V4 M5 (12) Temp 34.7 HR 160 BP 77/50 manual RR 30 - PowerPoint PPT PresentationTRANSCRIPT
CaseCase 28y male involved in an industrial 28y male involved in an industrial
accidentaccident
Sustained significant injuries to right Sustained significant injuries to right lower leg, femur and ?hemipelvislower leg, femur and ?hemipelvis
Prolonged extrication “tons of blood” Prolonged extrication “tons of blood” at the sceneat the scene
Case 1Case 1 Looks very unwell with ++ ongoing Looks very unwell with ++ ongoing
bleedingbleeding– GCS E3 V4 M5 (12)GCS E3 V4 M5 (12)– Temp 34.7Temp 34.7– HR 160HR 160– BP 77/50 manualBP 77/50 manual– RR 30RR 30– SaOSaO22 97% 10L by mask 97% 10L by mask
What is your initial management?What is your initial management?
CaseCase What other investigations?What other investigations?
Who are you going to call?Who are you going to call?
Surgery and IR are held up for 30minSurgery and IR are held up for 30min
Is there anything else we can do?Is there anything else we can do?
Massive transfusion Massive transfusion (all bleeding stops…)(all bleeding stops…)
Grand RoundsGrand RoundsOct 2Oct 2ndnd 2008 2008
Kristian HechtKristian HechtPGY-3 CCFP-EMPGY-3 CCFP-EM
ObjectivesObjectives Define massive transfusionDefine massive transfusion Review complications of massive Review complications of massive
transfusiontransfusion Review FMC’s Massive Transfusion Review FMC’s Massive Transfusion
ProtocolProtocol Review literature supporting the MTPReview literature supporting the MTP Review adjunctive therapies in Review adjunctive therapies in
massive hemorrhagemassive hemorrhage
BackgroundBackground First attempted blood transfusion First attempted blood transfusion
was in 1492 after Pope Innocent VIII was in 1492 after Pope Innocent VIII became comatosebecame comatose
Blood from 3 aides was instilled into Blood from 3 aides was instilled into the Pope’s mouththe Pope’s mouth
All 4 diedAll 4 died
BackgroundBackground In 1600’s many animal-to-human In 1600’s many animal-to-human
transfusions attemptedtransfusions attempted– These were later banned due to high These were later banned due to high
mortalitymortality The first documented successful The first documented successful
transfusion was between two dogs in transfusion was between two dogs in 16671667
The first documented human-to-human The first documented human-to-human transfusion was in 1818 by Dr. James transfusion was in 1818 by Dr. James Blundell a British obstetricianBlundell a British obstetrician
BackgroundBackground Hemorrhage is the second leading Hemorrhage is the second leading
cause of death in traumacause of death in trauma
CNS injury is 1CNS injury is 1stst
May require massive transfusionMay require massive transfusion
BackgroundBackground Massive transfusion (MT):Massive transfusion (MT):
– >10U pRBC’s in 24h>10U pRBC’s in 24h– Replacement of 50% blood volume in 3hReplacement of 50% blood volume in 3h– 4U pRBC in 4h with ongoing major bleeding4U pRBC in 4h with ongoing major bleeding– Replacement with blood loss >150mL/minReplacement with blood loss >150mL/min
Required in only 1% of civilian trauma ptsRequired in only 1% of civilian trauma pts
Mortality rates are between 20 – 50% in Mortality rates are between 20 – 50% in those requiring massive transfusionthose requiring massive transfusion
Complications of MTComplications of MT Acute hemolytic transfusion reactionsAcute hemolytic transfusion reactions Hyperkalemia Hyperkalemia Acidosis Acidosis HypothermiaHypothermia HypocalcemiaHypocalcemia CoagulopathyCoagulopathy All more common and/or severe with All more common and/or severe with
increasing number of units transfusedincreasing number of units transfused
Acute hemolytic reactionsAcute hemolytic reactions Most often due to ABO incompatible Most often due to ABO incompatible
RBC’s or plasma (clerical error, lab error RBC’s or plasma (clerical error, lab error etc)etc)
Rarely seen with unmatched O+ Rarely seen with unmatched O+ pRBC’spRBC’s
Occasionally with unmatched type Occasionally with unmatched type specific pRBC’sspecific pRBC’s
Commonly with unmatched type Commonly with unmatched type specific specific whole bloodwhole blood
HyperkalemiaHyperkalemia Storage of pRBC’s results in cell lysis Storage of pRBC’s results in cell lysis
and increased extracellular [Kand increased extracellular [K++]]
12 mEq/L at 7d12 mEq/L at 7d
32 mEq/L at 21d32 mEq/L at 21d
HyperkalemiaHyperkalemia Inconsequential if infused slowlyInconsequential if infused slowly KK++ is shifted to intracellular space is shifted to intracellular space
and later eliminatedand later eliminated If large amounts of pRBC’s infused If large amounts of pRBC’s infused
through a central line a large amount through a central line a large amount of Kof K++ is delivered directly to the RA is delivered directly to the RA– Potentially resulting in…Potentially resulting in…
HyperkalemiaHyperkalemia If encountered treat as per medical If encountered treat as per medical
hyperkalemiahyperkalemia May be prevented by using May be prevented by using
peripheral venous accessperipheral venous access Use of fresh blood (<14d) may Use of fresh blood (<14d) may
decrease incidencedecrease incidence
HypothermiaHypothermia Traumatized pts are at risk for Traumatized pts are at risk for
significant hypothermia due to significant hypothermia due to environmental and surgical exposureenvironmental and surgical exposure
pRBC’s are stored at 4pRBC’s are stored at 4°°C and will C and will cause rapid hypothermia if not put cause rapid hypothermia if not put through warmerthrough warmer
Hypothermia is an independent risk Hypothermia is an independent risk factor for mortality in traumafactor for mortality in trauma
HypothermiaHypothermia Physiologic effects:Physiologic effects:
– Decreased contractilityDecreased contractility– Cardiac dysrhythmia Cardiac dysrhythmia – CoagulopathyCoagulopathy
HypothermiaHypothermia TreatmentTreatment
– Drapes/blanketsDrapes/blankets– Warmed IV fluidsWarmed IV fluids– Warm humidified OWarm humidified O22
– External rewaming (hot air blankets, External rewaming (hot air blankets, etc)etc)
– Internal rewarming (peritoneal/pleural Internal rewarming (peritoneal/pleural lavage)lavage)
HypocalcemiaHypocalcemia Citrate is used as an anticoagulant in Citrate is used as an anticoagulant in
all blood productsall blood products Citrate binds ionized calcium and Citrate binds ionized calcium and
inhibits calcium-dependent coagulationinhibits calcium-dependent coagulation Higher concentrations in FFP and PltsHigher concentrations in FFP and Plts Usually inconsequential due to rapid Usually inconsequential due to rapid
hepatic metabolismhepatic metabolism May become significant with poor May become significant with poor
circulation and/or large amountscirculation and/or large amounts
HypocalcemiaHypocalcemia TetanyTetany QT prolongationQT prolongation Decreased myocardial contractilityDecreased myocardial contractility HypotensionHypotension Exacerbation of concomitant Exacerbation of concomitant
hyperkalemiahyperkalemia Coagulopathy (occurs at very low Coagulopathy (occurs at very low
[Ca[Ca2+2+])])
HypocalcemiaHypocalcemia TreatmentTreatment Correct shockCorrect shock
Decrease rate of blood product Decrease rate of blood product infusioninfusion
IV CaClIV CaCl2 2 1g slowly1g slowly
AcidosisAcidosis In hemorrhagic shock metabolic In hemorrhagic shock metabolic
acidosis results from poor perfusion acidosis results from poor perfusion and subsequent lactate productionand subsequent lactate production
Stored pRBC’s pH Stored pRBC’s pH 6.876.87 at 21dat 21d
Metabolism of exogenous acid may Metabolism of exogenous acid may be decreased due to poor circulation be decreased due to poor circulation or rapid/large amountor rapid/large amount
AcidosisAcidosis Causes other electrolyte Causes other electrolyte
disturbances (hyper Kdisturbances (hyper K++))
Independent risk factor for Independent risk factor for coagulopathycoagulopathy
Activity of factor VIIa decreases by Activity of factor VIIa decreases by 90%90% when pH drops from 7.4 to 7.0 when pH drops from 7.4 to 7.0
AcidosisAcidosis TreatmentTreatment
– Correction of volume status and Correction of volume status and restoration of tissue perfusion restoration of tissue perfusion
– Use fresh blood products if possibleUse fresh blood products if possible
– Addition of HCOAddition of HCO33-- is ineffective is ineffective
Stored blood productsStored blood products pH 6.87pH 6.87 [K[K++] 32 mEq/L] 32 mEq/L 44°C°C citratecitrate
CoagulopathyCoagulopathy ClinicallyClinically
– Oozing from IV sites, wounds and Oozing from IV sites, wounds and uninjured mucosauninjured mucosa
Lab values can correlate poorly with Lab values can correlate poorly with coagulopathycoagulopathy– PT abnormal in 97%PT abnormal in 97%– aPTT abnormal in 70%aPTT abnormal in 70%
CoagulopathyCoagulopathy Often present on admission esp. with Often present on admission esp. with
CNS and penetrating traumaCNS and penetrating trauma Correlated with increased mortalityCorrelated with increased mortality Often leads to further bleeding and Often leads to further bleeding and
ongoing need for volume ongoing need for volume resuscitationresuscitation
Leads to further worsening of Leads to further worsening of physiologic derrangmentsphysiologic derrangments
Ongoing hemorrhage
Volume replacement
Blood products
Shock acidosis
Coagulopathy
Hyopthermia Hemodilution
Bloody vicious cycle
Hypothermia
Hemodilution Consumptivecoagulation
Derangedmetabolism
Acidosis
Coagulopathy
Hypothermia
Hemodilution Consumptivecoagulation
Derangedmetabolism
Acidosis
Coagulopathy
Normal clottingNormal clotting
Local coagulation at wound
Exposure of tissue factor
Activation of clotting cascade
Tissue injury
Consumptive and Intravascular Consumptive and Intravascular CoagulationCoagulation
Systemic release of thromboplastin
Systemic endothelial damage
Widespread intravascular coagulation
Massive soft tissue damage, long bone fractures, CNS injury
Dilutional CoagulopathyDilutional Coagulopathy Results from loss of whole blood and Results from loss of whole blood and
replacement of factor and platelet-replacement of factor and platelet-poor fluidspoor fluids
ATLS 3:1 replacement of blood loss ATLS 3:1 replacement of blood loss with crystalloidwith crystalloid
Also in shock, fluid shifts from the Also in shock, fluid shifts from the extracellular to vascular space, extracellular to vascular space, worsening hemodilutionworsening hemodilution
Dilutional CoagulopathyDilutional Coagulopathy First described in 1954First described in 1954 Commonly occurred in those receiving Commonly occurred in those receiving
>10U of stored whole blood (up to 78%)>10U of stored whole blood (up to 78%)– Related to stored platelet dysfunction and Related to stored platelet dysfunction and
factor V and VIII deficiencyfactor V and VIII deficiency
1970’s: modified whole blood1970’s: modified whole blood– Platelets removedPlatelets removed– Thromobcytopenia related coagulopathyThromobcytopenia related coagulopathy
Dilutional CoagulopathyDilutional Coagulopathy 1980’s: fractionated component 1980’s: fractionated component
transfusiontransfusion– Implemented to reduce infectious disease Implemented to reduce infectious disease
transmission and conserve scarce blood transmission and conserve scarce blood productsproducts
Diluted coagulation factorsDiluted coagulation factors Transfusion of components based on Transfusion of components based on lab parameterslab parameters (hgb>70, plt >30, (hgb>70, plt >30,
INR>1.5)INR>1.5)
Dilutional CoagulopathyDilutional Coagulopathy Traditionally FFP transfusion started after Traditionally FFP transfusion started after
1 blood volume and/or INR>1.51 blood volume and/or INR>1.5
Recommendations based on mathematical Recommendations based on mathematical models in elective surgical patientsmodels in elective surgical patients
Drawbacks to previous recommendationsDrawbacks to previous recommendations– Mathematical models invalid in trauma ptsMathematical models invalid in trauma pts– Relied on lab studiesRelied on lab studies
Difficult to use clinicallyDifficult to use clinically– Inadequate responseInadequate response
FFPFFP One unit contains:One unit contains:
– 0.5g fibrinogen0.5g fibrinogen– All other coagulation factors in All other coagulation factors in
physiologic concentrationsphysiologic concentrations– Will raise factors by 3–5%Will raise factors by 3–5%Contains the most citrate of all blood Contains the most citrate of all blood
productsproducts
Slow paradigm shift to factor replacement Slow paradigm shift to factor replacement beforebefore the development of coagulopathy the development of coagulopathy
Now trending to replacement of Now trending to replacement of RBC:plasma:platelets at 1:1:1 ratiosRBC:plasma:platelets at 1:1:1 ratios
Ongoing hemorrhage
Shock acidosis
Coagulopathy
Hyopthermia Hemodilution
CrystalloidBlood
products
Bloody vicious cycle
Massive Transfusion Massive Transfusion ProtocolProtocol
Implemented in June 2008 as a pilotImplemented in June 2008 as a pilot
Developed by Trauma Services in Developed by Trauma Services in conjunction with ER, ICU, OR, conjunction with ER, ICU, OR, Transfusion Medicine and Canadian Transfusion Medicine and Canadian Blood servicesBlood services
Massive Transfusion Massive Transfusion ProtocolProtocol
Has been activated ~40 timesHas been activated ~40 times– Mostly trauma ptsMostly trauma pts– Some OR cases and GI bleeds Some OR cases and GI bleeds – Currently in a ‘trial phase’Currently in a ‘trial phase’
Currently evaluating: time to MTP pack Currently evaluating: time to MTP pack arrival, trauma severity score, type of arrival, trauma severity score, type of injury and final ratio of blood productsinjury and final ratio of blood products
2 Protocol based on varying levels of evidence and expert consensus
MTPMTP Cinat et al. examined FFP:RBC ratios Cinat et al. examined FFP:RBC ratios
in civilian trauma in civilian trauma Arch Surg 1999; 134:964-968Arch Surg 1999; 134:964-968
Survivors had avg ratio 1:1.8Survivors had avg ratio 1:1.8
Nonsurvivors had avg ratio 1:2.5Nonsurvivors had avg ratio 1:2.5
Retropsective study involving 246 combat-Retropsective study involving 246 combat-related trauma patients in Iraq requiring related trauma patients in Iraq requiring >10U pRBC’s between 2003 and 2005>10U pRBC’s between 2003 and 2005
Compared mortality relative to the ratio of Compared mortality relative to the ratio of plasma:RBC transfusedplasma:RBC transfused
LimitationsLimitations Retrospective study Retrospective study Young healthy patient populationYoung healthy patient population Mostly penetrating traumaMostly penetrating trauma Unclear how groups were allocated Unclear how groups were allocated
to receive different ratiosto receive different ratios Low ratio group were slightly sicker Low ratio group were slightly sicker
at presentationat presentation
Recommended anticipating transfusion Recommended anticipating transfusion needs of severely injured trauma ptsneeds of severely injured trauma pts
Emphasized preventing coagulopathy Emphasized preventing coagulopathy with early* FFP, cryoprecipitate and with early* FFP, cryoprecipitate and plateletsplatelets
**before 1 blood volume and/or signs of before 1 blood volume and/or signs of coagulopathycoagulopathy
MTPMTP May have implications on blood May have implications on blood
supplysupply Will necessitate the availability of Will necessitate the availability of
FFP on relatively short noticeFFP on relatively short notice– Some blood banks in trauma centers Some blood banks in trauma centers
keep stock of thawed FFP, refrigerated keep stock of thawed FFP, refrigerated for 5dfor 5d
– This fresh refrigerated plasma has 20% This fresh refrigerated plasma has 20% less factor activityless factor activity
PlateletsPlatelets
PlateletsPlatelets Traditionally transfused if <50x10Traditionally transfused if <50x1099/L/L Johansson et alJohansson et al. . showed increased showed increased
survival in AAA patients who received survival in AAA patients who received platelet transfusions to keep platelet transfusions to keep >100x10>100x1099/L /L
Cosgriff et al. MT patientsCosgriff et al. MT patients– Survivors had plt:RBC of 1:1.3Survivors had plt:RBC of 1:1.3– Non-survivors had plt:RBC of 1:2Non-survivors had plt:RBC of 1:2
MTPMTP Transfusion of pRBC’s, plasma and Transfusion of pRBC’s, plasma and
platelets in a 1:1:1 ratio results in a platelets in a 1:1:1 ratio results in a solution that has:solution that has:– Hematocrit 30%Hematocrit 30%– Coagulation factors 60%Coagulation factors 60%– Platelets 80 x10Platelets 80 x1099/L/L
Mimics whole blood proportionsMimics whole blood proportions Whole blood out Whole blood out whole blood in whole blood in
Other therapiesOther therapies Cryoprecipitate 15mL/UCryoprecipitate 15mL/U
– 100U factor VIII100U factor VIII– 250mg fibrinogen250mg fibrinogen– Also vWF, factor XIII and fibronectinAlso vWF, factor XIII and fibronectin
Given in doses of 6-10UGiven in doses of 6-10U Indicated when fibrinogen <1g/L with Indicated when fibrinogen <1g/L with
ongoing bleedingongoing bleeding Not currently indicated during early Not currently indicated during early
transfusiontransfusion
Recombinant factor VIIaRecombinant factor VIIa Potent procoagulantPotent procoagulant Showed great promise in treatment Showed great promise in treatment
of refractory massive hemorrhageof refractory massive hemorrhageDecreased transfusion utilization and improved Decreased transfusion utilization and improved outcome associated with the use of recombinant outcome associated with the use of recombinant factor viia as an adjunct in trauma factor viia as an adjunct in trauma Kenneth D. Boffard, Brian Warren, Philip Iau, et alKenneth D. Boffard, Brian Warren, Philip Iau, et al
rFVIIarFVIIa Now emerging literature has made this Now emerging literature has made this
“last ditch” treatment more controversial“last ditch” treatment more controversial
May not be any added survival benefitMay not be any added survival benefit
May have increased thrombosis riskMay have increased thrombosis risk Thomas et al. J Trauma 2007
– thrombosis risk of 9.4% in pts receiving rFVIIa
Efficacy and Safety of Recombinant Activated Factor Efficacy and Safety of Recombinant Activated Factor VII to Control Bleeding in Nonhemophiliac Patients: A VII to Control Bleeding in Nonhemophiliac Patients: A Review of 17 Randomized Controlled Trials Review of 17 Randomized Controlled Trials
Ann Thorac SurgAnn Thorac Surg 2008;86:1038-1048 2008;86:1038-1048
““generalized use of rFVIIa to prevent or to control bleeding in generalized use of rFVIIa to prevent or to control bleeding in nonhemophiliac patients can not be recommended” nonhemophiliac patients can not be recommended”
Comprehensive Canadian Review of the Off-Label Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Use of Recombinant Activated Factor VII in Cardiac SurgerySurgery
Circulation 2008; 118:331-338Circulation 2008; 118:331-338
““rFVIIa is associated with reduced blood product transfusions rFVIIa is associated with reduced blood product transfusions and … does not appear to be associated with increased or and … does not appear to be associated with increased or decreased complication ratesdecreased complication rates””
FibrinolyticsFibrinolytics Hyperfibrinolysis contributes to Hyperfibrinolysis contributes to
coagulopathycoagulopathy Antifibrinolytics bind Antifibrinolytics bind
plasminogen/tPA and reduce plasminogen/tPA and reduce fibrinolysisfibrinolysis– Aprotinin Aprotinin – Serine protease– Serine protease– Aminocaproic acidAminocaproic acid– Tranexamic acidTranexamic acid
Lysine proteases
AprotininAprotinin– Cochrane review showed no evidence Cochrane review showed no evidence
supporting routine usesupporting routine use
Tranexamic acidTranexamic acid Aminocaproic acidAminocaproic acid
– Cochrane: no adequate studies to assess Cochrane: no adequate studies to assess benefit in traumabenefit in trauma
CRASH-2: tranexamic acid Vs. PlaceboCRASH-2: tranexamic acid Vs. Placebo
FibrinolyticsFibrinolytics
SummarySummary Massive transfusion is uncommon in Massive transfusion is uncommon in
civilian traumacivilian trauma MT has several preventable complicationsMT has several preventable complications ““Early” coagulation factor replacement Early” coagulation factor replacement
with FFP may result in lower mortality due with FFP may result in lower mortality due to ongoing hemorrhageto ongoing hemorrhage
No current indications for factor VIIaNo current indications for factor VIIa No current indications for antifibrinolyticsNo current indications for antifibrinolytics
ReferencesReferences Massive transfusion and nonsurgical
hemostatic agents Crit Care Med 2008 Vol. 36, No. 7 (Suppl.)
Black Hawk Down: The evolution of resuscitation strategies in massive traumatic hemorrhage Critical care 2008 12:305
Rosen Tintinalli
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