peter mazolewski, md, facs ltcol usar cynosure summit may 21, 2012 peter mazolewski, md, facs ltcol...

Peter Mazolewski, MD, FACSLtCol USAR

Cynosure SummitMay 21, 2012

Peter Mazolewski, MD, FACSLtCol USAR

Cynosure SummitMay 21, 2012

Blood ManagementThe Impact of Blood Transfusions on

Surgical Outcomes

DisclosuresDisclosures

• NO pharmacy

• Paid consultant for Strategic Healthcare Group– Comprehensive Provider for Blood

Management Consultation

• NO pharmacy

• Paid consultant for Strategic Healthcare Group– Comprehensive Provider for Blood

Management Consultation

2

What is Blood Management?What is Blood Management?

• Blood Management is evidence-based transfusion practices which result in safe and efficient use of blood products

• Why Blood Management?– Inappropriate and excessive transfusions– No formal blood management training for clinicians– Measurable risks associated with EACH transfusion– Judicious use of blood reduces patient complications– Blood is a limited resource

• Blood Management is evidence-based transfusion practices which result in safe and efficient use of blood products

• Why Blood Management?– Inappropriate and excessive transfusions– No formal blood management training for clinicians– Measurable risks associated with EACH transfusion– Judicious use of blood reduces patient complications– Blood is a limited resource

4

What We Have Learned is Not What We Now KnowWhat We Have Learned is Not What We Now Know

risk

BENEFIT

• What we learned in residency and medical school is far different than what the present literature states

risk

BENEFIT

• What we learned in residency and medical school is far different than what the present literature states

5

Current Understanding of Transfusion PracticesCurrent Understanding of Transfusion Practices

RISK benefit

In most clinical situations in which we are administering blood, the risk of transfusion far exceeds the benefit of transfusion

RISK benefit

In most clinical situations in which we are administering blood, the risk of transfusion far exceeds the benefit of transfusion

6

Patient PopulationsPatient Populations

• Hemodynamically stable patients with blood component deficiencies, i.e. anemia, low platelets, abnormally elevated INR

• Acutely injured trauma patients with immediate life threatening hemorrhage– Consider GI hemorrhage which is life threatening– Consider Post operative life threatening bleeding– Consider person with unresponsive lactic acidosis

• Hemodynamically stable patients with blood component deficiencies, i.e. anemia, low platelets, abnormally elevated INR

• Acutely injured trauma patients with immediate life threatening hemorrhage– Consider GI hemorrhage which is life threatening– Consider Post operative life threatening bleeding– Consider person with unresponsive lactic acidosis

7

Changing Dogma Creates ConfusionChanging Dogma Creates Confusion

Two developing dogmas which are different than what we had learned previously:

– Hemodynamic stable anemic pts even with cardiac disease:

OBSERVE

– Acutely bleeding trauma: EARLY RESUSCITATION with BLOOD COMPONENTS

• Then turn off after resuscitation

Two developing dogmas which are different than what we had learned previously:

– Hemodynamic stable anemic pts even with cardiac disease:

OBSERVE

– Acutely bleeding trauma: EARLY RESUSCITATION with BLOOD COMPONENTS

• Then turn off after resuscitation

8

How Can We Make a Change?How Can We Make a Change?• Medicine is always changing—not only at

periphery, but also at its core• Treatment with blood is only one example• Other examples

– Hyperventilation in Head Injury– B-blockade in CHF– Hormonal Replacement Therapy– Radiation Therapy in Breast Cancer??

• But this particular change is going to be difficult

• Medicine is always changing—not only at periphery, but also at its core

• Treatment with blood is only one example• Other examples

– Hyperventilation in Head Injury– B-blockade in CHF– Hormonal Replacement Therapy– Radiation Therapy in Breast Cancer??

• But this particular change is going to be difficult

9

Why Difficult to Change?Why Difficult to Change?

• Crosses all specialties and all doctors who were taught the same thing:

risk

BENEFIT

• Crosses all specialties and all doctors who were taught the same thing:

risk

BENEFIT

10

Risks (Historical)Risks (Historical)

• Primary Infectious (vs. secondary)– Viral (HBV, HCV, and HIV)– Bacterial (plts, 1:1000 – 1:2000)

• Transfusion Reactions– Fever, Flushing– Tachycardia– Aggressive Immune response that is life threatening

(RARE)• Perception of “Episodic” Risk

– Few and far between– Clinicians have not taken seriously--in the sense that

the benefit always outweighs these episodic rare complications

• Primary Infectious (vs. secondary)– Viral (HBV, HCV, and HIV)– Bacterial (plts, 1:1000 – 1:2000)

• Transfusion Reactions– Fever, Flushing– Tachycardia– Aggressive Immune response that is life threatening

(RARE)• Perception of “Episodic” Risk

– Few and far between– Clinicians have not taken seriously--in the sense that

the benefit always outweighs these episodic rare complications

11

Risks (Current)Risks (Current)

• TRIM (Transfusion Related ImmunoModulation)– Immunosuppression

• Secondary Infection– Pneumonia, wound site infections, central line sepsis, etc

• Reduced Survival in Cancer?*• Increased ICU and Hospital length of stay

– Immunostimulation?• TRALI (Transfusion Related Acute Lung Injury)• ARDS, MODS• Late Mortality, most notably from cardiac literature

– Vs. Early Mortality which may be also mechanical in nature (plugging, acute pathophysiology)

– Dose Response Pattern (as opposed to episodic)• Each transfusion carries a measurable insult• Insults increase with number of transfusions • Also dose-dependent with respect to storage time







12

*Vamvakas EC. Transfusion 1996.

Benefit (Historical)Benefit (Historical)

• Enhanced Oxygen Delivery

• Improved overall Morbidity and Mortality

• Prevent Cardiac morbidity (angina and MI)

• Enhanced Oxygen Delivery

• Improved overall Morbidity and Mortality

• Prevent Cardiac morbidity (angina and MI)

13

Paradoxical RealityParadoxical Reality

• While O2 delivery (DO2) is increased, tissue oxygen consumption (VO2)either stays the same or worsens*

– VO2 independent of D02

• “RBC STORAGE LESION” (This is NOT fresh BLOOD!!!)– Loss of 2,3 DPG which shifts Oxy-hgb curve making it difficult to unload oxygen in the

tissues– Discoid RBC now spherical, broken (rheologic properties)^– Increased RBC clumping and aggregation– Decoupling of NO-Hgb** (free Hgb scavenges also NO)– Pro-Inflammatory Nature of Stored Blood

– Which is pro thrombotic in nature

» Increase 3-6fold PAI after 35 days, increased ADP which stimulates platelets, Nitric Oxide inhibits platelet activation

• While O2 delivery (DO2) is increased, tissue oxygen consumption (VO2)either stays the same or worsens*

– VO2 independent of D02

• “RBC STORAGE LESION” (This is NOT fresh BLOOD!!!)– Loss of 2,3 DPG which shifts Oxy-hgb curve making it difficult to unload oxygen in the

tissues– Discoid RBC now spherical, broken (rheologic properties)^– Increased RBC clumping and aggregation– Decoupling of NO-Hgb** (free Hgb scavenges also NO)– Pro-Inflammatory Nature of Stored Blood

– Which is pro thrombotic in nature

» Increase 3-6fold PAI after 35 days, increased ADP which stimulates platelets, Nitric Oxide inhibits platelet activation

*Tsai et al, Transfusion 2004^Almac et al, Best Pract Res Clin Anesth 2007**Crawford et al. Blood 2006. Reynolds et, Proc Natl Acad Sci 2007

Quality Issues: Storage Defects and Microvascular PerfusionQuality Issues: Storage Defects and Microvascular Perfusion

Decreased 2,3- DPG, ADPBuild-up of cytokines, free

Hgb, K+, debris (BRMs) 1,2

Poor deformability3

Decreased 2,3- DPG, ADPBuild-up of cytokines, free

Hgb, K+, debris (BRMs) 1,2

Poor deformability3

15

0

50

100

150

200

Day 1 Day 10 Day 20 Day 30 Day 40

Con

cent

ratio

n (p

g/m

l)

IL-1

IL-8

IL-6 **

*

*

**

1 Kristiansson- ActaAnesthScand 1996;402 Fransen- Chest 1999;1163 Hovav- Transfusion 1999; 39

3

Stored PRBCs

behave in this manner!

Anemic patients with NL RBCs can

at least behave in

these ways

Schechter, Gladwin, NEJM April 10, 2003

Tissue oxygenation after Transfusion In TraumaTissue oxygenation after Transfusion In Trauma

18Kiraly. J Trauma. July 2009

Blood Transfusion VideoBlood Transfusion Video

CYTOSC~1.MPGCYTOSC~1.MPG CYTOSC~4.MPG


• Enhanced Oxygen Consumption (NO!!!)

• Improved overall Morbidity and Mortality– Trauma is exception with MTP (Massive

Transfusion Protocol)

• Less Cardiac Events

• Enhanced Oxygen Consumption (NO!!!)

• Improved overall Morbidity and Mortality– Trauma is exception with MTP (Massive

Transfusion Protocol)

• Less Cardiac Events

20

Current Risk/Benefit RatioCurrent Risk/Benefit Ratio

RISK

BENEFIT

RISK

BENEFIT

21

Risks (Current)Risks (Current)













22

*Vamvakas EC. Transfusion 1996.

Immunosuppression of PRBCs

Immunosuppression of PRBCs

Effect of blood transfusions on subsequent kidney transplants.

Opelz G, Sengar DP, Mickey MR, Terasaki PI. Transplant Proc 1973; 5:253-9

Opelz reevaluated again in 1997 (prospective randomized) with modern immunosuppressive therapy and still found a significant impact of PRBC transfusion on renal allograft acceptance

Effect of blood transfusions on subsequent kidney transplants.

Opelz G, Sengar DP, Mickey MR, Terasaki PI. Transplant Proc 1973; 5:253-9

Opelz reevaluated again in 1997 (prospective randomized) with modern immunosuppressive therapy and still found a significant impact of PRBC transfusion on renal allograft acceptance

Did this Information Initiate Quality Controls in Blood Banking?Did this Information Initiate Quality Controls in Blood Banking?

• I argue “NO.” (With respects to immunomodulation)• The only current measure of “quality” with regards to RBC

transfusion is if 70% of the RBCs survive in the circulation at 24hrs post transfusion. (Developed in 1940’s)

• Except for leukoreduction (which is not universal),there has been no attempt to diminish or to measure cellular debris or mediators

• Therefore it is not surprising that we see a multitude of complications as a result of PRBC transfusions.

• I argue “NO.” (With respects to immunomodulation)• The only current measure of “quality” with regards to RBC

transfusion is if 70% of the RBCs survive in the circulation at 24hrs post transfusion. (Developed in 1940’s)

• Except for leukoreduction (which is not universal),there has been no attempt to diminish or to measure cellular debris or mediators

• Therefore it is not surprising that we see a multitude of complications as a result of PRBC transfusions.

24

25

Infection and Transfusion in Surgical ProceduresInfection and Transfusion in Surgical Procedures

No Transfusion Transfusion * Significant in Multivariate Analysis

Ed

na

Tri

ulz

i

Jen

sen

Jen

sen

Vig

nal

Mu

rph

y

05

10

1520

25

3035

40

Inci

den

ce o

f In

fect

ion

(%

)

N=868

N=589

N=197 N=343N=267

N=238

N=109

**

**

*

Tar

tter

CardiacSpinalTraumaColorectal

Adapted from: Despotis G.

• 4892 Patients at initial ICU admission

• 1518 mechanically ventilated >48hrs

• VAP in 20.5%

• Multivariate Analysis transfusion independently increased risk for VAP

• OR 1.89

• 4892 Patients at initial ICU admission

• 1518 mechanically ventilated >48hrs

• VAP in 20.5%

• Multivariate Analysis transfusion independently increased risk for VAP

• OR 1.8926

Transfusion and Nosocomial InfectionsTransfusion and Nosocomial Infections

1

1.2

1.4

1.6

1.8

1 2 3 4 5+

Adj

uste

d ha

zard

rat

io

serious bacterialinfection

pneumonia

1

1.2

1.4

1.6

1.8

1 2 3 4 5+

Adj

uste

d ha

zard

rat

io

serious bacterialinfection

pneumonia

27Carson et al, Transfusion 1999;39

n=9598

Units Transfused

2.5

78

12.5

14

6

10 10

1617

12

1718

21

22.5

0

5

10

15

20

25

0 1-2 3-4 5-6 >6

Day

s

VentTimeICUStayHospitalStay

n = 576

Units Transfused

Transfusion and Length of StayTransfusion and Length of Stay

28Shapiro et al, J Trauma 2003;55

Quality Issues: Duration of Blood Storage and OutcomesQuality Issues: Duration of Blood Storage and Outcomes

29

In H

osp

ital M

ort

ality A

RF

LO

S

1 Basran et al- Anesth Analg 2006;1032 Koch et al- NEJM 2008;358

30

Transfusion Requirements in Critical Care (TRICC) Study

Transfusion Requirements in Critical Care (TRICC) Study

OutcomesRestrictive

<7 g/dl

Liberal <10 g/dl

p-Value

Overall 30-day Mortality 18.7% 23.3% p=0.11

Pts < 55 years old 5.7% 13.0% p=0.02

APACHE II score ≤20 8.7% 16.1% p=0.03

Cardiac Disease 20.5% 22.9% p=0.69

In-hospital mortality 22.2% 28.1% p=0.05

Is Anemia beneficial??Is Anemia beneficial??

• Yes it is.• Anemia lessens viscosity and therefore lessens

resistance.• Diminished venous resistance results in improved

venous return.• Diminished arterial resistance results in lower SVR.• Together both these mechanisms result in a

significantly higher cardiac output.

• Yes it is.• Anemia lessens viscosity and therefore lessens

resistance.• Diminished venous resistance results in improved

venous return.• Diminished arterial resistance results in lower SVR.• Together both these mechanisms result in a

significantly higher cardiac output.

31

Tsai, et al. Transf Apher Sci. 2010 August.

CRIT StudyCRIT Study

• 2004, 284 ICUs, 4892 Pts in prospective, observational cohert

• Transfusion was an independent predictor of ICU length of stay, increased complications, and increased mortality (1.65 adjusted mortality ratio) with propensity scoring (1059 pts transfused to 1059 matched no transfusion)

• 65% pts received transfusions with hgb>8.0 gm/dl

• <10% pts received transfusions with hgb<7.0 gm/dl

• 2004, 284 ICUs, 4892 Pts in prospective, observational cohert

• Transfusion was an independent predictor of ICU length of stay, increased complications, and increased mortality (1.65 adjusted mortality ratio) with propensity scoring (1059 pts transfused to 1059 matched no transfusion)

• 65% pts received transfusions with hgb>8.0 gm/dl

• <10% pts received transfusions with hgb<7.0 gm/dl

Corwin et al. Crit Care Med. 2004. Vol 3, No 1

Transfusion and Mortality in Trauma (Pre MTP era)Transfusion and Mortality in Trauma (Pre MTP era)

33

Malone et al. J Trauma. May 2003

NSQIP Data (adjusted odds ratio) NSQIP Data (adjusted odds ratio)

0 PRBC 1PRBCS 2PRBCS

# pts 120,389 1,343 1,903

SSI Reference 1.02 1.25

UTIReference

1.12 1.04

Pneumonia Reference1.24 1.25

Sepsis or Septic Shock

Reference1.29 1.5

Mortality <30 days

Reference1.32 1.38

Bernard AC, et al. jamcollsurg 2008

Surgical Outcomes: one unit transfusionSurgical Outcomes: one unit transfusion

35Ferrarris, et al. Arch Surg. 2012;147:49-55


• Enhanced Oxygen Delivery (NO!!!)

• Improved overall Morbidity and Mortality (NO!!!)– Because we are transfusing too many

patients where there is simply no benefit. If there is a benefit, we cannot see it.

– Overall, trend for outcomes is significantly worse

– Trauma is exception with MTP (Massive Transfusion Protocol)

Less Cardiac Events




– Overall, trend for outcomes is significantly worse


Less Cardiac Events 36


RISKbenefit

RISKbenefit

37

Blood Transfusion & Percutaneous Coronary Intervention

39Doyle,et al. JACC. 2009. Vol 53

Cardiac Surgery and Blood Transfusion

Cardiac Surgery and Blood Transfusion

• Northern New England Cardiovascular Disease Study Group

• 8 Centers evaluated 9079 consecutive patients between 2001-2004

• Cox Proportional Hazard and Propensity Analysis• 3254 patients exposed to one or two units PRBCs

and compared to those who had none• 16% increased mortality out to 6mos

• Surgenor et al. Cardiovascular Anesthesiology. 2009

• Northern New England Cardiovascular Disease Study Group

• 8 Centers evaluated 9079 consecutive patients between 2001-2004

• Cox Proportional Hazard and Propensity Analysis• 3254 patients exposed to one or two units PRBCs

and compared to those who had none• 16% increased mortality out to 6mos

• Surgenor et al. Cardiovascular Anesthesiology. 2009

42

TRACSTRACS

• Prospective Randomized Trial in Cardiac Elective Surgery• JAMA Oct 13, 2010• Compared Liberal (>10gm/dl) and Restrictive (>8gm/dl) strategies

in Blood Management• 250pt each arm• 78% (liberal) vs 47% (restrictive) pts transfused• No difference in outcomes• When looking at those transfused, independent risk factor for

clinical complications or death @ 30days (HR for each add’l unit 1.2)

• Avoid transfusion solely to correct low hgb

• Prospective Randomized Trial in Cardiac Elective Surgery• JAMA Oct 13, 2010• Compared Liberal (>10gm/dl) and Restrictive (>8gm/dl) strategies

in Blood Management• 250pt each arm• 78% (liberal) vs 47% (restrictive) pts transfused• No difference in outcomes• When looking at those transfused, independent risk factor for

clinical complications or death @ 30days (HR for each add’l unit 1.2)

• Avoid transfusion solely to correct low hgb

FOCUS TrialFOCUS Trial

• 2016 high risk cardiovascular pts undergoing hip fracture surgery prospectively randomized into a restrictive vs. liberal transfusion policy

• Restrictive 8gm/dl and symptomatic• Liberal 10gm/dl• Median Age 82• Non-inferiority study

• 2016 high risk cardiovascular pts undergoing hip fracture surgery prospectively randomized into a restrictive vs. liberal transfusion policy

• Restrictive 8gm/dl and symptomatic• Liberal 10gm/dl• Median Age 82• Non-inferiority study

Carson, et al. NEJM. Dec 2011. 44

FOCUS Trial—RESULTSFOCUS Trial—RESULTS

• Primary Outcome: inability to walk 10ft unassisted at 60d and mortality– 34.7% restrictive and 35.2% liberal

• All other secondary measures of morbidity did not reach statistical significance (trend towards restrictive group)– Very similar percentages seen in other high powered

observational studies using propensity scoring.

• 65% less blood used in restrictive group• 97% of patients transfused in liberal group

• Primary Outcome: inability to walk 10ft unassisted at 60d and mortality– 34.7% restrictive and 35.2% liberal

• All other secondary measures of morbidity did not reach statistical significance (trend towards restrictive group)– Very similar percentages seen in other high powered

observational studies using propensity scoring.

• 65% less blood used in restrictive group• 97% of patients transfused in liberal group

45

RBC Transfusion in CVT Surgery and Quality of Life

RBC Transfusion in CVT Surgery and Quality of Life

• Patient’s perspective• RBC and Component transfusion therapy and

functional health-related Quality of Life• 7321/12536 pts over 4yr period (1995-99)

completed self administered DASI preop and postop (6-12mos)

• Regression analysis showed that postoperative functional status after CVT surgery was incrementally worse with more PRCs and platelets transfused

• Patient’s perspective• RBC and Component transfusion therapy and

functional health-related Quality of Life• 7321/12536 pts over 4yr period (1995-99)

completed self administered DASI preop and postop (6-12mos)

• Regression analysis showed that postoperative functional status after CVT surgery was incrementally worse with more PRCs and platelets transfused

Kock, et al. Soc Th Surg. 2006

Benefit (Historical)Benefit (Historical)• Enhanced Oxygen Delivery (NO!!!)




• Less Cardiac Events (NO!!!)– Actually more!!!





• Less Cardiac Events (NO!!!)– Actually more!!!

48


RISKbenefit

RISKbenefit

49

Difficult DilemmaDifficult Dilemma

• Anemia and acute coronary events carry a high mortality

• However, transfusion has not been shown to confer a benefit or improvement in survival

• IN FACT, many studies show that patients do worse with transfusion

• What to do?• This data should provide enough comfort for

clinicians NOT to feel need to transfuse in anemic hemodynamically stable patients with cardiac disease

• Anemia and acute coronary events carry a high mortality

• However, transfusion has not been shown to confer a benefit or improvement in survival

• IN FACT, many studies show that patients do worse with transfusion

• What to do?• This data should provide enough comfort for

clinicians NOT to feel need to transfuse in anemic hemodynamically stable patients with cardiac disease

Is Hgb 7.0 the trigger? Is Hgb 7.0 the trigger?

It is “the trigger to CONSIDER” transfusion…..

TASK FORCE-EAST AND ACCM

TASK FORCE-EAST AND ACCM

• NO “TRANFUSION TRIGGER” based on hgb level• Critically ill patients, HD stable anemia, except possibly those w/acute

myocardial ischemia, a “restrictive” strategy (hgb < 7gm/dl) is equally as effective as a “liberal” strategy (hgb < 10gm/dl) LEVEL I evidence

• In critically ill pts on the ventilator, the above also holds true. LEVEL II• In resuscitated, critically ill trauma pts, the above holds true. LEVEL II• In critically ill patients with stable cardiac disease, the above holds true.

LEVEL II. (very important: prevention of ischemia not supported by literature)

• RBC transfusions should be given as single unit. LEVEL II• RBC transfusions should not be considered as an absolute method to

improve tissue oxygen consumption in critically ill. LEVEL II

• Napolitano Crit Care Med. Dec 2009.

• NO “TRANFUSION TRIGGER” based on hgb level• Critically ill patients, HD stable anemia, except possibly those w/acute

myocardial ischemia, a “restrictive” strategy (hgb < 7gm/dl) is equally as effective as a “liberal” strategy (hgb < 10gm/dl) LEVEL I evidence

• In critically ill pts on the ventilator, the above also holds true. LEVEL II• In resuscitated, critically ill trauma pts, the above holds true. LEVEL II• In critically ill patients with stable cardiac disease, the above holds true.

LEVEL II. (very important: prevention of ischemia not supported by literature)

• RBC transfusions should be given as single unit. LEVEL II• RBC transfusions should not be considered as an absolute method to

improve tissue oxygen consumption in critically ill. LEVEL II

• Napolitano Crit Care Med. Dec 2009.

Indicators for Considering RBC Transfusion (in absence of bleeding) Indicators for Considering RBC Transfusion (in absence of bleeding)

Normovolemic anemia (Hgb≤7) WITH signs or symptoms of inadequate oxygen delivery

Normovolemic anemia (Hgb≤7) WITH signs or symptoms of inadequate oxygen delivery

Napolitano et al. Critical Care Medicine 2009;37:3124-3157

Pape, A., et al: Blood Transfus 7:250-8, 2009

What are signs or symptoms of What are signs or symptoms of inadequate oxygen delivery?inadequate oxygen delivery?

SignsSigns1.1. ScvOScvO22 < 70% [nl=80%] < 70% [nl=80%]

(central line)(central line)

2.2. SvOSvO22 < 65% [nl=75%] (PA < 65% [nl=75%] (PA catheter)catheter)

3.3. Low cerebral or tissue Low cerebral or tissue oximetryoximetry

4.4. Base deficit – ABGBase deficit – ABG

5.5. Lactic acidosis - labLactic acidosis - lab

6.6. ST changes - EKGST changes - EKG

7.7. ↓ ↓ LV contractility by trans LV contractility by trans esoph echoesoph echo

SYMPTOMSSYMPTOMS1.1. Mental status Mental status

alterationalteration2.2. DyspneaDyspnea3.3. Chest painChest pain4.4. New arrhythmiasNew arrhythmias5.5. Tachycardia Tachycardia

(VERY RELATIVE)(VERY RELATIVE)-Main Provider -Main Provider

ExcuseExcuse

Napolitano et al. Critical Care Medicine 2009;37:3124-3157

Pape, A., et al: Blood Transfus 7:250-8, 2009

How Can we immediately improve the situation?

How Can we immediately improve the situation?

• If we follow transfusion guidelines published by large societies (and remove less blood), we will transfuse far less blood (>50%) than currently given.

• This will diminish the need to store blood for 42 days and perhaps we can survive with a smaller pool of blood which is younger, fresher, and significantly safer (goal < 21days).

• In addition, we need to improve our science regarding blood banking which ameliorates the effects of the “storage lesion.”

• If we follow transfusion guidelines published by large societies (and remove less blood), we will transfuse far less blood (>50%) than currently given.

• This will diminish the need to store blood for 42 days and perhaps we can survive with a smaller pool of blood which is younger, fresher, and significantly safer (goal < 21days).

• In addition, we need to improve our science regarding blood banking which ameliorates the effects of the “storage lesion.”

57

Benefits (Current)Benefits (Current)

• Survival?

– Trauma. Yes, emerging in the setting of a Massive Transfusion Protocol

• 1:1:1 ratio (FFP:RBC:Plts) • But data emerging that 1:1:1 is resulting in excessive MODS

without survival benefit• 1:2-3 Ratio considered optimal by some at this time…but

literature quickly evolving• Evidence indicates that in the setting of MTP, less blood is used

on each pt during an entire hospitalization.

Dente, et al. J of Trauma, 2009

• Survival?

– Trauma. Yes, emerging in the setting of a Massive Transfusion Protocol

• 1:1:1 ratio (FFP:RBC:Plts) • But data emerging that 1:1:1 is resulting in excessive MODS

without survival benefit• 1:2-3 Ratio considered optimal by some at this time…but

literature quickly evolving• Evidence indicates that in the setting of MTP, less blood is used

on each pt during an entire hospitalization.

Dente, et al. J of Trauma, 2009

58

Massive Transfusion (MTP) Improves Survival

Massive Transfusion (MTP) Improves Survival

• Instituted a MTP in 1:1:1 ratio PRBC:FFP:PLTS• Prospective Non Randomized (“Unethical”)• No faculty turnover and no other significant changes

in treatment • Compared Pre-MTP with MTP• 73 MTP vs 84 similar pre-MTP patients• 24hr mort: 17% vs 36%, MTP vs Pre-MTP• 30day mort: 34% vs 55%• Early deaths from coagulopathic bleeding: 4/13

MTP, 21/31 Pre-MTP

• Instituted a MTP in 1:1:1 ratio PRBC:FFP:PLTS• Prospective Non Randomized (“Unethical”)• No faculty turnover and no other significant changes

in treatment • Compared Pre-MTP with MTP• 73 MTP vs 84 similar pre-MTP patients• 24hr mort: 17% vs 36%, MTP vs Pre-MTP• 30day mort: 34% vs 55%• Early deaths from coagulopathic bleeding: 4/13

MTP, 21/31 Pre-MTP59 Dente, et al. J of Trauma. 2009

MTP Questions RemainMTP Questions Remain• Optimal ratios of blood component resuscitation?

• Trying to mimic military experience of fresh whole blood

• Vanderbilt experience 3:2 PRBC:FFP, 5:1 PRBC:Plts showed survival experience

• No dose dependent survival beyond these ratios

• Grady 1:1and 2:1for both FFP and Plts; showed similar survival advantage for pts who received 2:1 and 3:1

• Late effects of excessive blood leading to later mortality? MODS, ARDS, Infection, etc

• Call it early and diminish amount of uncrossmatched blood

• Turn it off immediately and institute restrictive approach (<7gm hgb/dl) to blood component therapy

• Optimal ratios of blood component resuscitation?

• Trying to mimic military experience of fresh whole blood

• Vanderbilt experience 3:2 PRBC:FFP, 5:1 PRBC:Plts showed survival experience

• No dose dependent survival beyond these ratios

• Grady 1:1and 2:1for both FFP and Plts; showed similar survival advantage for pts who received 2:1 and 3:1

• Late effects of excessive blood leading to later mortality? MODS, ARDS, Infection, etc

• Call it early and diminish amount of uncrossmatched blood

• Turn it off immediately and institute restrictive approach (<7gm hgb/dl) to blood component therapy

60


RISKbenefit

RISKbenefit

61

THANK YOUTHANK YOU

Correcting Coagulopathy– PlasmaWhy do we transfuse?

Correcting Coagulopathy– PlasmaWhy do we transfuse?

• Replace volume and coagulation factors during massive transfusion

• Prevent further or future bleeding in patients undergoing invasive procedures

• Reverse Coumadin therapy in patients with or without bleeding

• Address isolated coagulation factor abnormalities

• Replace volume and coagulation factors during massive transfusion

• Prevent further or future bleeding in patients undergoing invasive procedures

• Reverse Coumadin therapy in patients with or without bleeding

• Address isolated coagulation factor abnormalities

63

INR and FFPINR and FFP

• INR Established to monitor Coumadin effectiveness• Estimated INR of FFP is 1.3 – 1.7 (mean about 1.4)• Deitcher showed INR 1.3 – 1.9 mean factor:

– FII 31-65%– FV 40-70%– FVII 22-60%– All levels consistent with adequate concentrations for

hemostasis

• Makes sense since “therapeutic” INR is at least 2.5 or 3.0 INR

• INR Established to monitor Coumadin effectiveness• Estimated INR of FFP is 1.3 – 1.7 (mean about 1.4)• Deitcher showed INR 1.3 – 1.9 mean factor:

– FII 31-65%– FV 40-70%– FVII 22-60%– All levels consistent with adequate concentrations for

hemostasis

• Makes sense since “therapeutic” INR is at least 2.5 or 3.0 INR

Understanding Derivation of INRUnderstanding Derivation of INR

• Most thromboplastins in use in the US prior to 2000, had an ISI of greater than 2.0

• Based on this understanding, equivalent INRs pre-2000 and post-2000 was 1.5 = 2.25

• This certainly fits with the literature and clinically

• Most thromboplastins in use in the US prior to 2000, had an ISI of greater than 2.0

• Based on this understanding, equivalent INRs pre-2000 and post-2000 was 1.5 = 2.25

• This certainly fits with the literature and clinically

Tavares, et al. Transfusion April 2011;51:754-761

FFP Effect on INRFFP Effect on INR

• Holland and Brooks– INR change = .37 (pretransfusion INR) - 0.47– INR > 1.7 before transfusion

• 50% of patients showed improvement in INR after FFP transfusion

– INR 1.3 – 1.6• Supportive treatment of underlying medical condition lowers

PT the same as FFP

• Holland and Brooks– INR change = .37 (pretransfusion INR) - 0.47– INR > 1.7 before transfusion

• 50% of patients showed improvement in INR after FFP transfusion

– INR 1.3 – 1.6• Supportive treatment of underlying medical condition lowers

PT the same as FFP

FFP Effect on INRFFP Effect on INR

• Abdel-Wahab, prospective transfusions in patients with INR 1.1 – 1.85– 324 plasma units given– 121 patients– Less than 1% normalization of INR– 15% corrected only half way to normal– No retrospective correlational to bleeding

• Abdel-Wahab, prospective transfusions in patients with INR 1.1 – 1.85– 324 plasma units given– 121 patients– Less than 1% normalization of INR– 15% corrected only half way to normal– No retrospective correlational to bleeding

INR and bleeding CVT SurgeryINR and bleeding CVT Surgery

• Pawan, et al– Cardiac Surgical Literature– 4 groups based on INR: <1.5, 1.5-2.0, 2.0-

2.5,>2.5• No evidence of increased bleeding in group 2 pts,

i.e. those with INR 1.5-2.0

• Pawan, et al– Cardiac Surgical Literature– 4 groups based on INR: <1.5, 1.5-2.0, 2.0-

2.5,>2.5• No evidence of increased bleeding in group 2 pts,

i.e. those with INR 1.5-2.0

Roger Williams Hospital Providence RI

Roger Williams Hospital Providence RI

• With the concept that 2.0 INR is the “new” 1.5, they built an evidence based program around this transfusion “threshold.”

• Dropped their FFP usage 80%!!!!• Not one reported adverse event attributed to

bleeding or lack of use of FFP to prevent bleeding

• Inpatient Mortality decreased over this time period---cause and effect?????

• With the concept that 2.0 INR is the “new” 1.5, they built an evidence based program around this transfusion “threshold.”

• Dropped their FFP usage 80%!!!!• Not one reported adverse event attributed to

bleeding or lack of use of FFP to prevent bleeding

• Inpatient Mortality decreased over this time period---cause and effect?????

peter mazolewski, md, facs ltcol usar cynosure summit may 21, 2012 peter mazolewski, md, facs ltcol...

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