RBC transfusions in critically ill patients

TMR Journal Club

March 1, 2007

Maggie Constantine

RBC transfusions in critically ill patientsBackground

RBC transfusion relationship to mortality morbidity

infection

RBC transfusions in critically ill patientsBackground – RCTs Liberal vs Restrictive RBC Strategies

Study Setting # patients 30-Day Mortality – Liberal [%(n)]

30-Day Mortality – Restrictive [%(n)]

Topley et al., 1956 Trauma 22

Blair et al., 1986 GI bleed 50 8.3 (2) 0 (0)

Fortune et al., 1987 Trauma, acute hemorrhage

25

Johnson et al., 1992 CVS 38

Hebert et al., 1995 ICU 69 25 (9) 24 (8)

Bush et al., 1997 Vascular Surgery 99 8 (4) 8 (4)

Carson et al., 1998 Ortho (hip #) 84 2.4 (1) 2.4 (1)

Hebert et al., 1999 ICU 838 23.3 (98) 18.7 (78)

Bracey et al., 1999 Cardiac Surgery 428 2.7 (6) 1.4 (3)

Lotke et al., 1999 Ortho (knee) 127

Grover et al., 2006 Vascular Surgery 260

McIntyre et al., 2006 Trauma (head) 67 13 17

RBC transfusions in critically ill patientsBackground - TRICC

P=0.10

NEJM 1999; 340(6)

RBC transfusions in critically ill patientsBackground – TRICC – CVD Subgroup Analysis

Crit Care Med 2001

RBC transfusions in critically ill patientsBackground - ABC

Difference in Mortality by Number of Units Transfused

Units Transfused #

Survived (n=2422)

Died (n=614)

0 1896 85.1 14.91 157 84.1 15.92 377 79.6 20.43 157 70.7 29.34 130 69.2 30.8

>4 319 55.2 44.8

P Value

<.01

JAMA 2002; 288 (12)

RBC transfusions in critically ill patientsBackground - CRIT

Reason for Transfusion

% of Transfusions

Low hemoglobin 90Active bleeding 24

Ischemia 3Increased

cardiac output 2Surgical

procedure 19Hemodynamic

instability 21Clinical

condition 26

Crit Care Med 2004;32(1)

RBC transfusions in critically ill patientsBackground - CRIT

P<0.001

Crit Care Med 2004;32(1)

RBC transfusions in critically ill patientsBackground – 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.”

Study Study type Setting # patients Results

Leal-Noval et ., 2001 Case control (SPI) CSICU 738 RBC transfusion of 4 or more units assoc with SPI

Taylor et al., 2001 Retro cohort MSICU 1717 Higher NI rate in transfused (p<.005). Dose response seen.

Shorr et al., 2004 Secondary analysis of CRIT trial

Variety of ICUs 5000 Higher rate of RBC transfusion in VAP (p<.0001)

RBC transfusions in critically ill patientsArticle 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

RBC transfusions in critically ill patientsArticle 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

RBC transfusions in critically ill patientsArticle 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

RBC transfusions in critically ill patientsArticle 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%”

RBC transfusions in critically ill patientsArticle 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%”

RBC transfusions in critically ill patientsArticle 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

NI No NI

Transfused 61 367

Not transfused

96 1561

RBC transfusions in critically ill patientsArticle 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)

RBC transfusions in critically ill patientsArticle 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

RBC transfusions in critically ill patients

TMR Journal Club

March 1, 2007

Maggie Constantine

Comments? Questions?