Transfusion literature summaries

Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care.

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Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. Erratum in: N Engl J Med 1999 Apr1;340(13):1056. PubMed PMID: 9971864.


In patients with a critical illness does a restrictive transfusion strategy (to lớn a target of 70 – 90 g/L, transfusion trigger


TYPE OF STUDY

Multi centre randomised controlled trial (22 tertiary level và 3 ‘community’ ICUs in Canada)Computer randomised using permuted blocks of 4 or 6, và stratified by center APACHE score of >15 and 15 or lessNon-blinded

POPULATION

Inclusion criteria:Expected to stay in ICU > 24 hoursHb concentration of 90 g/L or less within 72 hours of admission to lớn ICUConsidered lớn be euvolaemic following initial treatment by ICU teamExclusion criteria:Age Inability to lớn receive sầu blood productsActive sầu bleeding at time of enrolment (evidence of ongoing blood loss và a decrease in Hb concentration of 30 g/L in the preceding 12 hours OR a requirement for at least 3 units of packed RBCs in the same period)Chronic anaemiaPregnancyBrain deathImminent death (Consideration of withdrawal of treatment/DNR orderAdmission for a routine cardiac surgical procedurePrevious transfusionEnrolment in other study

INTERVENTIONS/ COMPARISONS

Restrictive sầu transfusion strategy (lớn a target of Hb 70 – 90 g/L, transfusion trigger Hb Liberal transfusion strategy (to target of Hb 100 – 120 g/L, transfusion trigger Hb

OUTCOMES

Average daily Hb concentrations differed significantlyRestrictive sầu 85 +/- 7 g/L, Liberal 107 +/- 7 g/LNumber of units of RBCs transfused was significantly reduced (RRR 0.54) in the restrictive sầu group (2.6 +/- 4.1 units) compared with the liberal group (5.6 +/- 5.3 units) (p Primary outcomerate of death from all causes at 30 daysNo significant differenceRestrictive sầu 18.7%, Liberal 23.3% (95%CI -0.84 – 10.2%, p = 0.11)Secondary outcomesMortality rates during hospitalisation were lower in the restrictive sầu group, but there was no difference in ICU mortality or 60 day mortalityinpatient 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)There were slightly lower adjusted multiple-organ dsyfunction scores in the restrictive sầu group (10.7 +/- 7.5 vs 11.8 +/- 7.7; p=0.03)Subgroup analysesWhen analysed by sub-group baseline characteristics remained similar between treatment armsNo differences in survival when adjusted for:traumacardiac diseasesevere infections or septic shockThere was lower mortality in the restrictive group for these a priori determined subgroups:APACHE II ≤20: 8.7% vs 16.1% (95% CI 1.0% – 13.6%, p = 0.03)Age

Adjusted multiple-organ dysfunction scores were statistically significantly lower in the restrictive sầu group. compared with the liberal group, in the APACHE Adverse cardiac events (e.g. cardiac ischaemia, pulmonary oedema, cardiac arrest) were more comtháng in the liberal group: 13.2% vs. 21% (ARR 7.8%; PAll of the liberal group received blood transfusion, whereas 33% of the restrictive group did not receive transfusion


Commentary

This is a landmark practice-changing classic of ICU research, but it is not without its flaws.The study raised concerns about the harms of blood transfusion and questioned the presumed benefit of increasing oxygen delivery – at least by transfusion – in the critically ill.Practice guidelines today generally tư vấn a transfusion trigger of Hb 70 g/L in critically ill patients as a result, except for selected patient subgroups (e.g. cardiac patients)Subsequent studies have supported similar targets in patients with upper GI haemorrhage và septic shockThere is considerable controversy about the optimal Hb target in individual ICU patients và there are concerns over the external validity & power of the TRICC trial

Strengths

Randomised, multicentre controlled trialAppropriately chosen primary/secondary outcomesPower nguồn calculation performed, but…calculated to detect a 5% difference in 30d mortalitytarget sample kích thước of 16đôi mươi patients was determined by an interlặng analysis suggesting a higher than expected mortality ratesee criticisms belowused intention lớn treat analysisRelevant population group (i.e. APACHEII scores consistent with critical illness)Comparable healthcare setting lớn the Australian settingHighlighted how a simple, inexpensive to institute intervention could significantly reduce costs & lead lớn apparently superior patient outcomes

Criticisms

The total number of patients enrolled (n=838) resulted in the study being underpowered & thus prone to lớn type II errorOnly ~12.9% of total assessed patients were enrolled in the trial, with a large number of them being excluded due to physician refusal (selection bias)APACHE II score subgroup stratification was altered after the fact (This study may have sầu been subject to lớn practice misalignmenta survey by Hebert et al (1998) showed that standard practice was not khổng lồ transfuse patients to lớn Hb >100 g/L & most clinicians would use a target higher than 70 g/L in patients with ischaemic heart disease. Allocation of these patients khổng lồ the corresponding treatment arms might have been expected to lớn cause harm.External validity is limited by the following:Exclusion of patients following cardiac surgery removed a large population of critically ill patients that may require significant volumes of blood và blood products – this is markedly different to the Alfred ICU populationThe study not include long-stay ICU patients who required transfusion later (i.e. onmix of anaemia had to lớn occur within 72 hours)There was a significant difference in the percentage of patients with cardiovascular disease between those excluded from the trial and those enrolled (20% vs 26% respectively) – excluded pateints also tended to lớn be older – decreasing ability to lớn apply results across a broader population297 patients were excluded for having had a transfusion prior to lớn ICU that increased their Hb to lớn >90 g/L – may reduce applicability khổng lồ certain patient groups who may receive frequent or be at high likelihood of transfusionStudy conducted prior lớn routine use of leucodepleted PRBCs in Canadomain authority – would repeating the trial with leucodepleted PRBCs diminish the significant differences?


The TRICC study is a landmark trial that supports the use of a restrictive transfusion strategy targeting Hb> 70 g/L in ICU patients. However, the optimal Hb target in different patient subgroups (e.g. cardiac disease) remains uncertain.Concerns remain over the external validity of the study and the fact that it was underpowered.

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Tagged chris nickson, Hebert et al 1998, kent lavery, liberal, red blood cell transfusion, restrictive, TRICC trial Post navigation
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