transfusion triggers: going beyond the tricc · pdf filehistorical rbc transfusion trigger...

Transfusion triggers: Going beyond the TRICC trial

Paul Hebert MD MHSc

University of Ottawa Centre for Transfusion Research, Ottawa Health Research Institute and the Ottawa Hospital

Historical RBC transfusion trigger

Historical RBC transfusion trigger

Lundy. Surg Gynecol Obstet 1954; 74: 1011

“This condition, owing to the lowered oxygen carrying capacity of the blood interferes with the adequate transportation of oxygen to the tissues. When the concentration of hemoglobin is less than 8-10 gm per 100 cc of whole blood it is wise to give blood transfusion

Study design: Multicentre RCTSetting: 25 ICUs across CanadaStudy Population: Included Hgb< 90 g/l within 72 hrs

and excluded patients with active blood loss (30 g/l decrease or >3 unit transfusion in 12 hrs)

Intervention: 70 g/L vs 100 g/L hemoglobin triggerOutcomes: 30 day all-cause mortality and organ failure

Study Design

Hebert et al. NEJM 321: 151-156, 1999

Hemoglobin over time

0 5 10 15 20 25 30

Time (Days)

0102030405060708090

100110120

Hem

oglo

bin

(g/L

)

Liberal strategy

Restrictive strategy

p<0.01

Hebert et al. NEJM 321: 151-156, 1999

Hemoglobin over time

0 5 10 15 20 25 30

Time (Days)

0102030405060708090

100110120

Hem

oglo

bin

(g/L

)

Liberal strategy


p<0.01

Hebert et al. NEJM 321: 151-156, 1999

2.6 units

5.4 units

Survival of all patients over 30 days

0 5 10 15 20 25 30

Time (Days)

50

60

70

80

90

100

Sur

viva

l (%

)


Liberal strategy

p=0.10

Hebert et al. NEJM 321: 151-156, 1999

Survival of all patients over 30 days

0 5 10 15 20 25 30

Time (Days)

50

60

70

80

90

100

Sur

viva

l (%

)


Liberal strategy

p=0.10

Hebert et al. NEJM 321: 151-156, 1999

18.7%

23.3%

RBC transfusion cause harm?

RBC transfusion cause harm?

• Are findings consistent within study?• Do findings agree with other studies?• Are findings generalizable to other patient

groups?

Spurious result or true finding?

Observational studies of RBC transfusions

Marik and Corwin, CCM 2008;36:2667

Can we trust these studies?

Can we trust these studies?

Inferences weakened due to:• Logic of transfusions always being harmful??• Retrospective studies - limited data collection• Minimal adjustment for confounding factors• Timing of RBCs unknown• Trigger unknown…admission hematocrit/nadir

hematocritMain culprit: “Confounding by Indication”• higher acuity → more aggressive care

RCTs of Red Cell Transfusion Triggers Author Year N Setting Hgb trigger (g/dL)

Topley 1956 22 Trauma 11.3 vs 15.6

Blair 1986 50 GI Bleed 2 U vs 8U

Fortune 1987 25 Trauma 10.0 vs 13.0

Weisel 1992 27 CABG 10.0 vs 12.0

Johnson 1992 39 CABG 8.3 vs 10.7

Hebert 1995 69 ICU 7.0 -9.0 vs 10.0 -12.0

Bush 1997 99 Vascular 9.0 vs 10.0

Carson 1998 84 Hip Fx 10.0 vs symptoms

Bracey 1999 428 CABG 8.0 vs.9.0/symptoms

Hebert 1999 838 ICU 7.0 vs 10.0

Carson. Trans Med Reviews 2002

Does a Restrictive strategy decrease all cause mortality?

Carson., Hebert, Careless 2011

Other major RCTs of

Purpose: To determine if a restrictive red cell

transfusion strategy will reduce red cell exposure without worsening organ dysfunction in pediatric critical care patients.

Lacroix. NEJM 2007; 356: 1609.

TRIPICU studyStudy design: Multicentre RCTSetting: 19 ICUs in Canada, EuropeStudy Population: Age 3 days – 14 yrs and hb < 95

g/L within 7 days of PICU admission. Stable, no acute blood loss and no cardiac disease

Intervention:Restrictive (70 g/L) vs. liberal (95 g/L) hemoglobin trigger

Outcomes: Death, new or progressive multiorgan dysfunction.

Lacroix. NEJM 2007; 356: 1609.

TRIPICU – Hemoglobin levels

Lacroix. NEJM 2007; 356: 1609.

4.00

6.75

9.50

12.25

15.00

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Low

est H

b (g

/dL)

Length of stay post-randomization (day)

RestrictiveLiberal

Average Hb : 87±4.0 vs. 108±5.0 g/L (δ: 21±2.0).

TRIPICU - Outcomes

Restrictive group Liberal group

Total # of patients 320 317

Non-transfused (n)174

(54.4%)7

(2.2%)

No. of transfusions 301 542

New or progressive MODS (n) 38 39

New or progressive MODS (%) 11.9(95% CI 8.5-15.9)

12.3(95% CI 8.9-16.4)

Lacroix. NEJM 2007; 356: 1609.

Generalizabilty

TRICCsepsis

cardiac

medical

surgeryoncology

Study Patients: 263 patients with EARLY sepsis and septic shockSetting: Single Centre study conducted in large city hospitalStudy design: open-labeled randomized trialIntervention: Early Goal-directed therapy using ScvO2 guided

care vs standard of careOutcome: in-hospital mortality and other mortality rates

Rivers et al NEJM 2001;345:1368Courtesy of E Rivers

Rivers et al NEJM 2001;345:1368

Did transfusions help?

Courtesy of E Rivers

Outcome Control Treatment RR (95% C.I.) P-value

In-hospital 46.5 30.5 0.58 (0.38-0.87) 0.009

28-day Mortality 49.2 33.3 0.58 (0.39 – 0.87) 0.01

60-day Mortality 56.9 44.3 0.67 (0.46-0.96) 0.03


Mortality Rates in 263 Septic Shock Patients

Outcome Control Treatment RR (95% C.I.) P-value

In-hospital 46.5 30.5 0.58 (0.38-0.87) 0.009

28-day Mortality 49.2 33.3 0.58 (0.39 – 0.87) 0.01

60-day Mortality 56.9 44.3 0.67 (0.46-0.96) 0.03


Cardiovascular Disease

Patients with ischemic heart disease (n=257)

Patients with cardiovascular diseases (n=357)

Hebert et al. NEJM 321: 151-156, 1999

Complications during the ICU Stay

Effect of anemia on mortality in cardiac disease

1.00

4.04

7.08

10.12

13.16

16.20

6 7 8 9 10 11 12+

Odd

s R

atio

Preoperative Hgb (g/dl)

Healthy (No IHD) Ischemic Heart Disease

P=0.03

Carson JL, et al. Lancet 1996;348:1055-60.

• Retrospective cohort of patients who refuse blood transfusion

• CVD definition - History of MI, angina, CHF, or PVD.

• 1,958 patients age 18 or older.• Undergo surgical procedure in OR.• Outcome-30-day mortality or morbidity.

Adjusted OR of death in transfused versus not transfused patients

Hct OR (95% CI)*

*Wu. NEJM 2001; 345: 1230.

RBCs Kill

RBCs save lives

Copyright restrictions may apply.

Rao, S. V. et al. JAMA 2004;292:1555-1562.

Nadir Hematocrit, % Adjusted OR 95% CI __________________________________________

35 291.64 10.28-8273.85

30 168.64 7.49-3797.69

25 1.13 0.70-1.82 20 1.59 0.95-2.66 __________________________________________

RiskofDeathin24,112transfusedversus

non-transfusedfrom3RCTs

Functional outcomes in cardiovascular patients undergoing surgical hip fracture repair (FOCUS)

Design: Multicentre RCT in 47 North American centresStudy Population: 2016 hip fracture patients undergoing

surgical repair with a Hb < 100 g/L within 3 days fo surgeryIntervention:• Liberal Strategy: transfusion trigger of 100 g/L• Restrictive Strategy: transfusion for symptomatic anemia Outcomes:• Primary: functional recovery (ability to walk 10 feet without

human assistance 60 days post-op)• Long term survival, nursing home placement, post-op

complications (MI and infection)

Carson. Transfusion 2006; 46 2192

FOCUS study

• Results yet to be published• Lower pre-transfusion hemoglobin with

symptomatic transfusions (79 g/L vs 92 g/L)• Early report: No difference in mortality and

cardiac outcomes

Carson. AABB & ASH Annual Meetings 2009

Overall recommendations

• Adopt a transfusion threshold of 70 g/L and maintain critically ill children and adults between 70 and 90 g/L

• Transfuse one RBC unit at a time.• Patients with acute coronary syndrome and

septic shock may benefit from Hb> 80 g/L • Further trials are especially focused on patients

with cardiac disease• For peri-operative care await results of FOCUS

study soon to be published

transfusion triggers: going beyond the tricc · pdf filehistorical rbc transfusion trigger...

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