The New England Journal of Medicine: A Multicenter, Randomized, Controlled

Clinical Trial of Transfusion Requirements in Critical Care

Monthly Journal article review:

Vimmi Kang PGY 2

Importance

Transfusions are a necessary part of managing critical patients. Different views of when to transfuse in regards to risks versus

benefits– Microcirculatory and immunosuppressive complications of red cell

transfusions– Concern about supply and safety of blood– Two recent studies suggested that anemia increases risk of death

in patients with cardiac disease and in critical ill patients Prompted the routine use of transfusion in hgb>10g/dL

Optimal transfusion practice for various types of critically ill patients with anemia has not been established

Background

To determine whether a restrictive strategy of red cell transfusion and a liberal strategy produced equivalent results in critically ill patients.

Rates of death from all causes at 30 days and the severity of organ dysfunction was compared between the two groups.

Study was published in 1999 Enrolled patients in Canada between November 1994 and November 1997 Exclusion criteria

– Age less than 16yrs– Inability to receive blood products– Active blood loss at the time of enrollment

Requirement of >3prbc OR Decrease in hgb by 3 in the preceding 12 hours

– Chronic anemia (hgb <9) At least one occasion more than 1 month prior to hospital admission

– Pregnancy– Brain death or imminent death (within 24hrs)– Question on the part of attending physicians whether to withhold or withdraw ongoing

treatment– Admission after a routine cardiac procedure

Method

Enrolled 838 critically ill patients with euvolemia after initial treatment, with hemoglobin conc of less than 9 g/dL within 72 hours of admission to the ICU

418 of those were randomly assigned to the restrictive group

420 patients to the liberal group

Restrictive Strategy of transfusion

RBC were transfused if hemoglobin concentration dropped <7.0g/dL

Hemoglobin concentration was maintained at 7 to 9 g/dL

Liberal Strategy of red cell transfusion

Transfusion was given if hemoglobin concentrations fell below 10g/dL

Hemoglobin concentrations were maintained at 10 to 12 g/dL

Base Line Characteristics of the Study Patients

Hgb was measured after each unit of transfusion

APACHE II– Assessed on the day of admission to the ICU– Scores range from 0 to 71

MODS– Assessed on the day of admission to the ICU– Scores range from 0 to 24

Outcome measures

Primary outcome – Death from all causes in 30 days

Secondary outcome– 60 day rates of death– Mortality rates during ICU stay– Mortality rated during hospitialization– Measures of organ failure and dysfunction

Outcomes

Results

30 day mortality between the two groups were similar– 18.7% vs 23.3%– Exceptions

Rates were significantly lower in the restrictive group among patients who had a score <20 in Acute Physiology and Chronic Health Evaluation II

– 8.7% vs 16.1% Among patient less than 55yrs of age

– 5.7% vs 13% But not among patients with significant cardiac disease

– 20.5% vs 22.9% Mortality rate during hospitalization was significantly lower in

the restrictive strategy group– 22.2% vs 28.1%

Cardiac events, primarily pulmonary edema and Myocardial infarction were more frequent in the liberal-strategy group than in the restrictive strategy group during ICU stay

Conclusions

Restrictive strategy of red cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients with the possible exception of patients with acute myocardial infarction and unstable angina

critique

Hypothesis: oxygen delivery should be increased or maintained at high levels to minimize the effects of tissue hypoxis caused by disease processes that interfere with oxygen delivery or the body ability to extract oxygen

– Many randomized, controlled clinical trials addressed this hypothesis

– Trials did not make inferences on the optimal strategy for red cell transfusion

Results from previous studies were not correlated with this study

– “Increasing severity of anemia was associated with a disproportionate increase in mortality rates among patients with ischemic heart disease”

However with this study, it did not show increase in mortality or adverse outcomes in patients with cardiac disease under the restrictive transfusion group when compared to the liberal group

Greater proportion of patients that ‘refused’ to be included this study were of the cardiac disease category

– Attending physicians– Can affect generalization of the results, especially myocardial infarction

and angina Not enough data to make any generalization

Did not adhere to the liberal vs restrictive strategy once patient was transferred out of ICU– What affect does that have on the secondary

outcomes