Monthly Journal article review: Vimmi Kang PGY 2 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.

Enrolled patients in Canada between November 1994 and November 1997 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 Scores range from 0 to 24

Outcome measures Primary outcome Secondary 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