Blood Management Year in Review – Part II
This is Part II (see Part I) of a blog based upon my Blood Management University® year-end webinar by the same title, where I tried to hit the high points of the transfusion medicine literature.
Transfusion in Critical Care Patients
In general, critical care physicians have been very supportive of conservative transfusion practice since they started the “less is more” bandwagon with the landmark TRICC trial. There was additional information published this year regarding transfusion practice in patients on mechanical ventilation and patients with sepsis. Prior to the TRICC trial, it was commonly believed that blood transfusions were useful to help wean patients from the ventilator, with the assumption that transfusions helped improve oxygen delivery. After the TRICC trial showed a conservative approach to transfusion was at least as effective and possibly superior to a liberal strategy of transfusion in ICU patients1, a number of “post hoc” analyses were done to try and derive information about subgroups of patients within the study. An analysis of 713 patients in the TRICC trial who were on mechanical ventilation demonstrated no differences in ventilator weaning between the restrictive and liberal group, with 82% of the patients in the restrictive group considered successfully weaned and extubated for at least 24 hours, compared with 78% for the liberal group2. Based upon that analysis, the Society of Critical Care Medicine transfusion guidelines state that “RBC transfusion should not be considered as a method to facilitate weaning from mechanical ventilation”3. Published this year was a pilot randomized controlled trial (RCT) designed to prospectively study this issue4. The trial included 100 patients of age ≥ 55 years requiring ≥ 4 days of mechanical ventilation in the ICU, randomized to a restrictive (Hb 7.0 mg/dL) or liberal (Hb 9.0) transfusion strategy for 14 days or the remainder of ICU stay, whichever was longest. As expected, 22% fewer patients in the restrictive group were transfused and they received a median of 1 fewer RBC unit. With regards to outcomes, there were no major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications between groups, emphasizing the lack of benefit of liberal transfusions for ventilator weaning. There was also a trend towards higher mortality at 180 days in the liberal group, but it was not statistically significant. A larger RCT is now being planned to confirm these findings.
An update to the “Surviving Sepsis” guidelines was published this year that had a significant change to transfusion recommendations for these patients. The genesis of the Surviving Sepsis guidelines was a 2001 article by Rivers et al “Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock”5 where the EGDT group had a dramatically lower mortality rate compared to conventional therapy (31% vs. 47%). Part of the EGDT protocol called for an RBC target of 10 g/dL in the first 6 hours of resuscitation if the patient had a ScvO2 < 70% in order to increase tissue oxygenation. This part of the protocol has received some criticism as the protocol was developed before the TRICC trial, and the study was not designed or powered to look at the independent effect of this transfusion strategy. The latest Surviving Sepsis update now essentially aligns the transfusion protocol with the TRICC trial guidance while acknowledging the contrast to the original EGDT protocol:
“Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances (myocardial ischemia/ IHD, severe hypoxemia, acute hemorrhage) we recommend that RBC transfusion occur only when hemoglobin decreases to < 7.0 g/dL to target a hemoglobin concentration of 7.0-9.0 g/dL in adults”6.
Transfusion in Patients with Cardiac Disease
The final group to review regarding transfusion practice updates is arguably the most controversial, patients with active cardiac disease. Patients with acute coronary syndromes (MI, unstable angina) were listed as a possible exception to the restrictive transfusion recommendation in the TRICC trial because very few ACS patients were enrolled in the trial, along with the reasonable presumption that ACS patients require higher transfusion thresholds to augmented oxygen delivery. Surprisingly, the Cardiology literature over the past decade has been leaning towards more conservative practice because of a growing number of observational studies showing higher morbidity and mortality in ACS patients who are transfused. Most of these studies come from FDA trials for ACS therapies, which were not designed to evaluate transfusion therapy but contain large amounts of patient data that can be statistically analyzed. A meta-analysis of 10 observational studies that included 203,665 patients with ACS concluded that transfusion vs. no transfusion increased all-cause mortality by almost 300% (18.2% vs 10.2%, OR 2.91, p= 0.001), with an absolute increase in mortality of 12%7. Transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Transfusion was also associated with a 200% increase in myocardial infarction (OR 2.04; P=.03). These conclusions are counter to the presumption that transfusions reduce both MI and mortality rates in patients with ACS, but consistent with the growing body of evidence showing the proinflammatory and procoagulant properties of stored blood8. Based upon studies such as this, the European Society of Cardiologist and the Society of Critical Care Medicine have both recommended a transfusion threshold of 8 g/dL for ACS patients9,3.
While the “less is more” bandwagon is gaining supporters among Cardiologists, a recently published pilot trial has renewed the controversy. The Myocardial Ischemia and Transfusion (MINT) trial enrolled 110 patients with ACS, or patients with stable coronary artery disease undergoing cardiac catheterization, who were randomized to a liberal transfusion strategy (Hb < 10.0 g/dL) vs. a restrictive strategy (Hb < 8.0 g/dL, or transfuse for symptoms related to anemia at any Hb)10. The results of this small RCT were different from the previously mentioned observational trials in that there was a trend towards better composite outcomes (death/ MI unscheduled revascularization at 30 days) in the liberal group compared to the restrictive group ( 10.9% vs. 25.9%) which bordered on statistical significance (p = .054). The discussion section of the article included the caution: “While our results are provocative, the pilot trial was not designed to enroll enough patients to answer the transfusion dilemma currently facing clinicians in practice.”