IF THEY RE BLEEDING, GIVE EM BLOOD. Gary J. Merlotti, M.D. Department of Surgery University of Illinois at Chicago

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1 IF THEY RE BLEEDING, GIVE EM BLOOD Gary J. Merlotti, M.D. Department of Surgery University of Illinois at Chicago

2 Review data supporting massive transfusion protocols Review actual protocols to determine optimal regimen Determine if history will repeat itself!

3 With any hypotensive patient, 4 units of type-specific RBC are delivered ASAP 4 units of crossmatched RBC kept available at all times For each 4 units RBC infused, 2 units FFP infused For each 10 units RBC infused, 1 pack (10 pooled units) platelets given Cook County Hospital, 1979!!!!

4 Abandoned in early 1980 s At 4 units, only 2% of patients were coagulopathic At 10 units, only 25% were coagulopathic 50% of coagulopathies were clinically insignificant Protocol became FFP/platelets for nonsurgical hemorrhage or laboratory evidence of coagulopathy

5 Next 25 years Resuscitation based on large volumes of lactated Ringers solution Critical volume deficit in INTERSTITIUM!!

6 Next 25 years Blood for oxygen carrying capacity only Given when inadequate response to crystalloid Transfusion of red blood cells and products was comparatively late

7 Next 25 years Fresh frozen plasma given for clinical coagulopathy and guided by lab studies Platelets/cryoprecipitate given when plasma failed to stop bleeding

8 Plasma is not administered routinely by a preset formula after RBC transfusion. Sabiston Textbook of Surgery 18 th Edition, 2006

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10 RATIONALE Coagulopathy occurs very early after injury More rapid availability of products reduces coagulopathic hemorrhage Reduces incidence and severity of lactic acidosis that contributes to non-surgical hemorrhage

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12 246 military casualties Low ratio group (FFP:RBC=1:8) mortality of 65% Medium ratio group (FFP:RBC=1:2.5) mortality of 34% High ratio group (FFP:RBC=1:1.4) mortality of 19% Used mostly whole blood! Borgman,, JOT Oct, 2007.

13 133 patients receiving >10 units RBC/24 hours Mortality actually lowest with FFP:RBC = 1:2 Variables predicting mortality Units RBC transfused/6 hours 6 hours >1.5 Temp <34 degrees Age >55

14 Complex relationship between coagulopathy and mortality Kashuk,, JOT, Aug, 2008.

15 135 patients receiving >10 units RBC/24 hours Mortality when FFP:RBC = 1:1 was 26% Mortality when FFP:RBC = 1:4 was 87.5% Additional 626 patients that received < 10 units Mortality 11.8% vs. 21.2% favoring 1:1 ratio Duchesne, JOT, Aug, 2008

16 73 patients compared to 84 historical controls MTP resulted in Higher FFP:RBC Significantly < RBC transfusion total 34% vs. 55% mortality advantage Dente, JOT, June, 2009

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18 These studies concentrated only on FFP:RBC ratios and evaluated only survival advantage Ignores end organ dysfunction

19 Multicenter trial Compared mortality if FFP:RBC is < or > 1: patients not randomized Early (<24 hour) mortality significantly lower with high ratio (3.9% vs. 12.8%) Not sustained beyond 24 hours Sperry, JOT, Nov, 2008

20 Higher risk of ARDS in high FFP:RBC group (47.1% vs. 24.0%) Higher risk of infectious complications in high FFP:RBC group (58.4% vs. 43.2%) Trend toward higher risk of MOF in high FFP:RBS group Sperry, JOT, Nov, 2008

21 125 patients compared with historical controls prior to MTP 30 day survival higher in MTP group (56.8% vs. 37.6%) Amount of blood products slightly lower in MTP group

22 MTP group with significantly LOWER risk of the following complications Sepsis (19.8% vs. 10.0%) VAP (39.0% vs. 27.2%) Abdominal compartment syndrome (9.9% vs. 0%) MOF (37.2% vs. 15.6%) Cotton, JOT, Jan, 2009

23 134 patients receiving > 10 units RBC Split into high group (>1:2) and low group (<1:2) FFP:RBC Mortality 63% lower for high group Groups transition as time passes When timing accounted for there was no survival advantage Snyder, JOT, Feb, 2009

24 40 patients after MTP implemented compared to historical control FFP:RBC = 1:1.8 in BOTH groups Time to first product reduced from 115 minutes to 71 minutes Mortality reduced from 45% to 19% Riskin,, JACS, Aug, 2009

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26 WHAT DOES IT ALL MEAN?

27 MTP leads to earlier institution of blood product administration In majority of studies this led to decreased overall utilization More prompt correction of coagulopathy Clear association between number of RBC and infectious complications that should be improved

28 MTP was accompanied by a reduction in crystalloid administered LR thought to adversely impact WBC function Limited resuscitation means lower incidence of abdominal compartment syndrome (?lower risk of end organ dysfunction) Resuscitation endpoints remain poorly defined?interstitial fluid deficit

29 MTP leads to overutilization of blood bank resources?degree?cost?can we accurately predict who does need the aggressive FFP/platelet/cryo infusion to start it early?

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31 Studies that need to be done Prospective, randomized trial with preset FFP:RBC infusion vs. RBC infusion with FFP as indicated by clinical setting Current studies mostly use historical controls Mobilization of blood bank improved with MTP More rapid infusion may explain apparent advantage

32 Studies that need to be done Prospective, randomized trial MTP + crystalloid to standard endpoints vs. limited endpoints Urine output of 1 cc/kg vs. 0.5 cc/kg Complete resolution of acidosis vs. resolution to acceptable level Eliminate variable blood product resuscitation as confounder on the effects of limited resuscitation

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34 Studies that need to be done Assess the impact of MTP on brain injuries Higher incidence of early coagulopathy Reduced fluid requirement to reach endpoints may be beneficial or detrimental to secondary brain injury Should limited endpoints be used with TBI

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36 Summary Massive transfusion protocols remain poorly defined Rapid mobilization of the blood bank is an advantage in resuscitating critically injured patients Unknown if there is an exact ratio of products that should be used

37 Summary There is much more work to be done We all need to do it!