1 Transfusion Medicine Journal Club Omar Al Suhaibani 24 th March,2009

2  Transfusion therapy is common in trauma patients.  Transfusion of PRBCs, platelets, and fresh frozen plasma are all associated with the development of ARDS in trauma patients.  Massive transfusion (more than 10 units of PRBCs within a 12- to 48-h interval) has been identified as a risk factor for ARDS in trauma patients.

3  Massive transfusion is defined as 10 or more RBC units in a 24 hour period  Massive transfusion occurs in up to 15% of civilian trauma patients  Massive transfusion is associated with a mortality rate of 20-50%  Most patients requiring massive transfusion die within 6 hours of admission

4  American-European Consensus Conference definition for ARDS: - bilateral infiltrates on chest radiograph - a PaO2/FIO2 ratio less than a pulmonary artery occlusion pressure of less than 18 mmHg or no clinical evidence of left atrial hypertension.  Acute lung injury (ALI) is a less severe form of ARDS defined by PaO2/FIO2 ratio less than 300 mmHg (within 6 h).

5  Causal relationship between transfusion products and ARDS.  Host reactions to antigranulocyte antibodies.  Interactions between non-specific systemic inflammatory mediators such as interleukin 8 and tumor necrosis factor.  Depressed immune responses leading to a higher risk of infection

6  Neutrophils isolated from trauma patients receiving PRBCs demonstrate neutrophil priming as per measured increase in surface expression of CD11b/CD18 receptor sites, superoxide production and elastase release all of which may predispose to ALI and ARDS.  Cryoprecipitate and FFP have the highest rate of antibodies and are more associated with both TRALI and ARDS compared to PRBCs.

7  Observational prospective cohort.  688 patients with sepsis, trauma, aspiration, and hypertransfusion.  PRBC transfusion was associated with ARDS (aOR 1.52, 95% CI , p=.05)  PRBC transfusion was associated with increased mortality in ARDS (aOR 1.10 per unit transfused; 95% CI ) with a significant dose-dependant response (p=.02)

8  Prospective cohort study.  102 consecutive patients with severe trauma.  Patients devided into 3 groups on the basis of total number of PRBC units received in the first 24 h.  0-5 units of PRBC = 21% ARDS  6-10 units of PRBC = 31% ARDS  Greater than 10 units of PRBC =57% ARDS

9  Retrospective study.  103 patients received multiple transfusions (more than 6 units of PRBC) in the first 24 h.  Total amount of transfusion in the first 24 h was 14.0+/- 6.8 U in the ARDS patients and 10.6+/- 7.3 U in other patients (p=0.17)  ARDS in massively transfused patients was less related to poly-transfusion than to other factors related to circulatory shock, poly- trauma or thoracic trauma.

10  Single-center retrospective cohort study.  841 consecutive critically ill patients.  298 patients (35%) received blood transfusion.  ALI/ARDS more likely to develop in patients received FFP (OR, 2.48; 95% CI, ) and platelet transfusions (OR, 3.89; 95% CI, ) than those who only received PRBCs (OR,1.39; 95% CI, ).

11 Anesthesiology 2009; 110:351–60 Early Packed Red Blood Cell Transfusion and Acute Respiratory Distress Syndrome after Trauma Onuma Chaiwat, M.D., John D. Lang, M.D., Monica S. Vavilala, M.D., Jin Wang, Ph.D., Ellen J. MacKenzie, Ph.D., Gregory J. Jurkovich, M.D., Frederick P. Rivara, M.D.

12  Data from National Study on Cost and Outcomes of Trauma (NSCOT)  Multicenter prospective cohort study  Injured patients treated in 18 trauma centers and 51 large non-trauma centers in 14 states across the United States  18 month period July 1, Nov.30, 2002

13  Inclusion criteria: - patients of age - at least one injury of Abbreviated Injury Scale score of 3 or greater  Patients were excluded if: - no vital signs - pronounced dead within 30 min of arrival - had injury occurring more than 24 h before hospital arrival - major burns - primary diagnosis of hip fracture (65 yrs of age or older) - spoke neither English nor Spanish - non-US residents - incarcerated or homeless at the time of injury

14  14,070 patients were included.  Main exposure : number of units of PRBCs received within the first 24 h of presenting to hospital and this was analyzed both as continuous variable and categorized into four groups : 0, 1-5, 6-10, and >10.  Outcomes were the development of ARDS and in-hospital mortality.  Diagnosis of ARDS was made by primary physicians according to the American- European Consensus Conference definition.

15  Sequential regression imputation method was used to perform the multiple imputations of missing values.  Associations among patient characteristics and ARDS and PRBCs transfusion units was determined by using chi-square statistics and t-test for categorical and continuous variables, respectively.  Adjusted logistic regression method was developed to determine which characteristics were independently associated with ARDS.  Multivariate weighted logistic regression models were used to determine the effect of PRBC transfusion on ARDS and in-hospital mortality.

16  Abbreviated Injury Scale (AIS) is an anatomical scoring system.  first introduced in  Injuries are ranked on a scale of 1 to 6, with 1 being minor, 5 severe, and 6 a non- survivable injury.

17  Injury Severity Score (ISS) is an anatomical scoring system that provides an overall score for patients with multiple injuries.  Each injury is assigned an AIS and is allocated to one of six body regions (Head, Face, Chest, Abdomen, Extremities (including Pelvis), External).  The 3 most severely injured body regions have their score squared and added together to produce the ISS score.  The ISS score takes values from 0 to 75.  The New Injury Severity Score (NISS) is calculated as the sum of the squares of the top three scores regardless of body region.

18  Patients were primarily males (68.5%)  Blunt trauma (86.6%)  Non-Hispanic whites (60.2%)  Average age was 43.3  Mean injury severity score of 29.9

19  ARDS developed in 521 patients (4.6%)  Total of 331 (63.5%) received early PRBCs transfusion  Prevalence of ARDS increased with higher units of early PRBCs transfusion

20  Clinical predictors for ARDS in the final logistic regression model.  Mean NISS, thoracic injury, poly-trauma, pneumonia, and receiving more than 5 units of FFP and 6-10 units of PRBCs.

21 Risk Factor Odds Ratio (95% CI) Age, yr 1.02 ( ) NISS 1.02 ( ) Thoracic injury 1.57 ( ) Pneumonia 7.52 ( ) Poly-trauma 2.77 ( ) PRBC transfusion units 0 Ref ( ) ( ) > ( ) FFP transfusion units 0 Ref ( ) > ( )

22  Two multivariate logistic regression analyses were performed.  Effects of PRBC units transfused in initial 24 h after hospital admission categorized into four groups, group 1 as a reference group  Greater risk for developing ARDS if pts received more than 5 units of PRBCs

23  PRBC units transfused during the first 24 h categorized as continuous variable when controlling for all confounding variables.  Effect of PRBCs transfused during first 24 h remained significant for ARDS (adjusted odds ratio 1.06, 95% CI ).  6% higher risk of ARDS for additional unit of PRBCs transfused.

24 ARDS, aOR (95% CI)In-hospital death, aOR (95% CI) PRBC units ( ) 1.13 ( ) ( )* 1.52 ( ) > ( )* 0.93 ( ) * P< 0.05; Referent group = 0 PRBC units aOR = adjusted odds ratio

25  Timing of ARDS onset.  Separation between ARDS and TRALI.  Leukoreduction of PRBCs??  Gender of donors.  Age of transfused PRBCs.

26  “ early PRBCs transfusion is an independent risk factor for ARDS in trauma patients, and each unit of PRBCs transfused increases the risk of ARDS by 6%.”  Conservative PRBC transfusion strategies early after trauma may need to be considered as part of early goal-directed therapy protocols.

27 “ Future randomized clinical trials will be necessary to confirm the important results of Chaiwat et al. so that the use of less blood products during the initial resuscitation of trauma victims actually decreases the risk of developing ARDS. Less may actually be more.” Benson et al, Anesthesiology 2009; 110:216–7

28  Are the results of this study valid? - Prospective cohort study with retrospective analyses. - Multicenter large sample size study. - Incomplete or missing data. - No trauma transfusion protocols. - Outcomes were not measured in the same way. - Follow-up not sufficiently complete.

29  Are the results of this study valid? - Patients not treated equally. - Patients were not similar to begin with

30  Are the results of this study important? - Yes, each unit of PRBC transfused in the first 24 h increase the risk of ARDS by 6%.  Are these results applicable to our patients? - Yes  Should I attempt to stop the exposure? - Alternatives?? - Maybe review the ratio of plasma to PRBC. - RCT is necessary but challenging.

31 THANK YOU