1. RBC transfusions in critically ill patients TMR Journal Club March 1, 2007 Maggie Constantine

2. RBC transfusions in critically ill patients Background RBC transfusion relationship to mortality morbidity infection

3. RBC transfusions in critically ill patients Background – RCTs Liberal vs Restrictive RBC Strategies StudySetting# patients30-Day Mortality – Liberal [%(n)] 30-Day Mortality – Restrictive [%(n)] Topley et al., 1956Trauma22 Blair et al., 1986GI bleed508.3 (2)0 (0) Fortune et al., 1987Trauma, acute hemorrhage 25 Johnson et al., 1992CVS38 Hebert et al., 1995ICU6925 (9)24 (8) Bush et al., 1997Vascular Surgery998 (4) Carson et al., 1998Ortho (hip #)842.4 (1) Hebert et al., 1999ICU83823.3 (98)18.7 (78) Bracey et al., 1999Cardiac Surgery4282.7 (6)1.4 (3) Lotke et al., 1999Ortho (knee)127 Grover et al., 2006Vascular Surgery260 McIntyre et al., 2006Trauma (head)671317

4. RBC transfusions in critically ill patients Background - TRICC P=0.10 NEJM 1999; 340(6)

5. RBC transfusions in critically ill patients Background – TRICC – CVD Subgroup Analysis Crit Care Med 2001

6. RBC transfusions in critically ill patients Background - ABC Difference in Mortality by Number of Units Transfused P Value <.01 JAMA 2002; 288 (12)

7. RBC transfusions in critically ill patients Background - CRIT Crit Care Med 2004;32(1)

8. RBC transfusions in critically ill patients Background - CRIT P<0.001 Crit Care Med 2004;32(1)

9. RBC transfusions in critically ill patients Background – Nosocomial infections Recent literature Link between RBC transfusion and development of nosocomial infections in a variety of ICU patients ABC Newsletter Feb 16, 2007 – Gould et al., Am J Crit Care 2007;16:3948. “According to the available data, transfusion of packed red blood cells should be reserved only for situations in which clear physiological indicators of transfusions are present.” StudyStudy typeSetting# patientsResults Leal-Noval et., 2001Case control (SPI)CSICU738RBC transfusion of 4 or more units assoc with SPI Taylor et al., 2001Retro cohortMSICU1717Higher NI rate in transfused (p<.005). Dose response seen. Shorr et al., 2004Secondary analysis of CRIT trial Variety of ICUs5000Higher rate of RBC transfusion in VAP (p<.0001)

10. RBC transfusions in critically ill patients Article review Crit Care Med 2006;34(9): 2303-2308. Prior retrospective study – Project Impact (PI) ? Association between nosocomial infections, mortality and length of stay with RBC transfusions

11. RBC transfusions in critically ill patients Article review Are the results of study valid? Prospective observational cohort >/18 years – 50% random sample of all ICU patients  N=428 transfused vs 1657 nontransfused  Decision to transfuse made by treating physician Single center med/surgical ICU August 2001 to June 2003 Primary objectives  Development of infections  Compare rates of infectious complications between cohorts Secondary objective  “whether patients in the transfused group remained at higher risk of NI when stratified by the patients’ probability of survival.” - ? Post hoc

12. RBC transfusions in critically ill patients Article review Cohorts similar? NO Significantly, transfused cohort was Older Had lower MPM-0 scores Different admitting diagnoses Exposures and outcomes measured in the same way for both cohorts? POSSIBLY Exposure opportunity not equal amongst cohorts Unclear if “senior critical care nurses” blinded to transfusion Standard definition of NI

13. RBC transfusions in critically ill patients Article review Was follow-up sufficient? YES “throughout the patients’ ICU stay.” Temporal relationship correct? UNCLEAR NI included if occurring during ICU stay AND absent on admission But unclear if infection occurred AFTER RBC transfusion Dose-response gradient? YES “for every unit increase in RBCs transfused, the risk of NI increased 9.7%”

14. RBC transfusions in critically ill patients Article review Dose-response gradient? YES Rate of NI 14.3% “post-transfusion” vs. 5.8% in non- transfused (p<0.0001) “for every unit increase in RBCs transfused, the risk of NI increased 9.7%”

15. RBC transfusions in critically ill patients Article review Relative risk of NI with transfusion = 2.74 Related to illness severity at baseline? Adjusted for POS NI rate still significantly higher in transfused group (p<.0001) Patients with better prognosis – higher risk of NI if transfused 95% CI taken from Odds ratio Very close to 1 NINo NI Transfused61367 Not transfused 961561

16. RBC transfusions in critically ill patients Article review Secondary analysis Transfused patients (NI vs. No NI) No significant difference in age of RBC (NI vs. No NI) No effect of RBC age on rate of NI (NI vs. No NI) No significant difference in LR status of RBC (NI vs. No NI) Significantly higher mortality rate patients (21.8% vs. 10.2%, p<.0001) Significantly longer IUC stay (p<.0001)

17. RBC transfusions in critically ill patients Article review Implications for my practice? Medical / surgical ICU Adult No suspected or actual infection on admission Magnitude of risk? RR = 2.7 AR increase = 8.5% For every 12 patients transfused – one will develop NI Should I attempt to stop exposure? YES, BUT PERHAPS FOR OTHER REASONS Prospective cohort – hypothesis generating – possible RCT Strength of RBC transfusion to NI is clearly established

18. RBC transfusions in critically ill patients TMR Journal Club March 1, 2007 Maggie Constantine Comments? Questions?