TRICC

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Hebert PC, et al. "A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care". The New England Journal of Medicine. 1999. 340(6):409-417.
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Clinical Question

Among critically ill patients, how does a restrictive transfusion strategy (hemoglobin goal of 7-9 g/dL) compare with a liberal transfusion strategy (hemoglobin goal of 10-12 g/dL) in decreasing mortality?

Bottom Line

In critically ill patients, restrictive transfusion (Hgb >7 g/dL) is associated with better survival compared to liberal strategy (Hgb >10).

Major Points

The Transfusion Requirements in Critical Care (TRICC) trial randomized 838 patients admitted to the ICU without evidence of active bleeding to a restrictive transfusion strategy (transfusion to maintain hemoglobin >7 g/dL) versus a liberal strategy (transfusion to maintain hemoglobin ≥10 g/dL). The study enrolled patients who were euvolemic after initial fluid resuscitation. There was adequate separation between the two groups, with an average hemoglobin 8.5 vs. 10.7 g/dL, respectively. The restrictive transfusion strategy was associated with decreased rates of in-hospital mortality compared to those seen with the liberal transfusion strategy. This benefit was most prominent among the less critically ill patients (APACHE II score ≤20) and <55 years old. However, in the restrictive arm, there was a trend towards improved outcomes in patients with active cardiac ischemia.

TRICC's results were met favorably among blood bank specialists and other guardians of the red blood cell supply,[1] but many questioned the external validity of the study. In particular, some criticisms included that only 13% of patients screened were ultimately randomized, that the study's results were unlikely to apply to patients at high altitude, and that red cell transfusions should not be restricted among patients with traumatic brain injury.[2]

Before the publication of TRICC, ICU patients were routinely transfused for hemoglobin <10 g/dL. Modern practice guidelines[3] now recommend a Hgb transfusion goal of 7-9 g/dL, except in choice patients. A large non-blinded, randomized trial, Transfusion Strategies for Acute Upper Gastrointestinal Bleeding (2013) studied restrictive versus liberal transfusion strategies in patients with upper GI bleeding, a group that was notably excluded from TRICC. It found a similar reduction in mortality with restrictive transfusion goals. More recently, the 2014 TRISS trial[4] found no difference 90 day all-cause mortality for Hgb transfusion goals of 7 vs. 9 g/dL in patients with septic shock.

Guidelines

Surviving Sepsis Campaign severe sepsis and septic shock (2016, adapted)[5]

  • RBC transfusion only when Hgb is <7 g/dL unless extenuating circumstances (e.g., MI, severe hypoxemia, hemorrhage; strong recommendation, moderate quality of evidence)

Design

  • Multicenter, non-blinded, parallel-group, randomized, controlled trial
  • N=838 critically ill patients with anemia
    • Restrictive strategy (n=418)
    • Liberal strategy (n=420)
  • Setting: 22 tertiary care and 3 community ICUs in Canada
  • Enrollment: 1994-1997 (terminated early due to low enrollment)
  • Primary outcome: 30-day mortality

Population

Inclusion Criteria

  • Expected ICU stay ≥24 hours
  • Hemoglobin concentration of no more than 9.0 g/dL within 72 hours after the ICU admission
  • Clinically euvolemic after fluid resuscitation

Exclusion Criteria

  • Age <16 years
  • Inability to receive blood products
  • Active blood loss at enrollment
  • Chronic anemia
  • Pregnancy
  • Brain death
  • Expected death within 24 hours
  • Attendings questioning whether to withhold or withdraw treatment
  • Admission after a routine cardiac procedure

Interventions

Randomly assigned to restrictive (hemoglobin 7-9 g/dL) or liberal (hemoglobin 10-12 g/dL) strategy

Outcomes

Comparisons are restrictive vs. liberal strategy.

Primary Outcomes

30-day mortality
18.7% vs. 23.3% (ARR 4.7%; P=0.11)

Secondary Outcomes

Inpatient mortality
22.2% vs. 28.1% (ARR 5.8%; P=0.05)
ICU mortality
13.9% vs. 16.2% (ARR 2.3%; P=0.29)
60-day mortality
22.7% vs. 26.5% (ARR 3.7%; P=0.23)
Multiple-organ dysfunction score
3.2 vs. 4.2 (P=0.04)
Change in organ dysfunction from baseline
3.2 vs. 4.2 (P=0.04)

Subgroup Analysis

Significant survival benefit when adjusted for
APACHE II ≤20
Age <55 years
No difference in survival when adjusted for
Cardiac disease
Severe infections or septic shock
Trauma

Adverse Events

ICU cardiac events
13.2% vs. 21% (ARR 7.8%; P<0.01)

Criticisms

  • Reduced enrollment of patients with cardiac disease decreases the generalizability of the results
  • May not apply to patients at high altitudes[6]
  • No subgroup analysis in those with brain injury[6]
  • Only 13% of those screened were randomized in the trial, potentially harming external validity[6]

Funding

Funding from Medical Research Council of Canada and an unrestricted grant from Bayer.

Further Reading

  1. Goodnough LT, et al. "Transfusion Medicine — Blood Transfusion." N Engl J Med. 1999; 340:438-447.
  2. Ely EW, Bernard GR. "Transfusions in Critically Ill Patients" N Engl J Med. 1999; 340:467-468
  3. Cite error: Invalid <ref> tag; no text was provided for refs named ssc
  4. Holst LB, et al. "Lower versus higher hemoglobin threshold for transfusion in septic shock." The New England Journal of Medicine. ePublished 2014-10-01. Accessed 2014-10-01.
  5. Rhodes A, et al. "Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016." Critical Care Medicine. 2017;45(3)1-67.
  6. 6.0 6.1 6.2 NEJM Letters to the Editor