The Latest in Critical Care, 1/8/23 (Issue #24)
The transfusion issue: Reducing wasted blood, red cell transfusion in MI, updated transfusion guidelines
Cumulatively, daily labs on hospitalized patients deplete substantial volumes of blood, almost all of which is wasted. The 4 to 6 mL of blood drawn per standard tube is a legacy of older equipment: modern testing machines only need <0.5 mL per sample, and the rest is discarded. More blood is drawn and discarded the next day, and the next, and the next—wasting about a unit of whole blood per week from each patient in the ICU.
By one estimate, 25 million liters (6.6 million gallons) of blood are wasted in this fashion, every year—enough to fill about 700 railroad tanker cars with blood, or about four times the total amount of blood transfused annually.
Smaller-volume blood collection tubes are widely available at equivalent cost and are compatible with standard blood analyzers. They have a less-powerful vacuum that removes about half as much blood per tube. But apparently, few centers use them, because … well, no one can give a good reason why.
In one of those “how has this not been done already?” trials, the hypothesis was tested: would removing less blood result in more blood remaining inside patients, thus requiring less blood to be transfused into them?
Twenty-five ICUs in Canada were switched to small-volume blood collection tubes at randomly assigned times (a so-called stepped-wedge cluster design) from 2019-2021. (Rollout was delayed by several months at many centers during the Covid-19 pandemic, creating protocol deviations to be dealt with later.) Over 21,000 patients were included and analyzed.
After conversion to smaller-volume tubes, there were an absolute (and statistically significant) 9.84 fewer units RBC transfused per 100 patients, relative to the standard-volume tube epochs.
(This was among all patients, in what they termed their secondary analysis. In the primary analysis which excluded the ~6,000 delayed-rollout Covid-19 patients, there were 7.24 fewer units transfused per 100 patients, which did not reach significance.)
The individual patient-level effects were very small. Smaller-volume tubes mitigated the decline in hemoglobin from blood draws by only about 0.1 g/dL per patient.
Stepped-wedge designs require adjustment for confounding by time, because temporal trends could be responsible for any observed effect; there was no such confounding detected. There was no significant increase in inadequate samples for analysis after the change to smaller volume tubes.
Although effects were small in individual patients, those milliliters really added up. Over the two years studied, 30,000 patients may have been spared the transfusion of 1,500 units of blood.
The current situation may seem bizarre, callous and a bit macabre—and it is!—and it’s hard to figure out who’s in the best position to change it (other than the U.S. government). No stakeholder feels pain by continuing the status quo. The Red Cross funds a large portion of its operations through its ~$2 billion transfusion business, and would seem to be unlikely to advocate for reducing its size.
Health systems shouldn’t be expected to take the lead; most will need to be regulated or otherwise herded into making any change (such as through a new quality measure for judicious transfusion or reduced blood wastage, or a regulation mandating small volume tubes).
The societies overseeing blood transfusion and laboratory medicine have reportedly been waiting to issue guidance toward smaller tubes until more data (like this study) became available.
Individual patients don’t seem to be harmed by excessive blood draws—and they usually aren’t, tangibly; the risk and costs occur on a population/systems level. Harm to individual patients from avoidable transfusion certainly must occur regularly in hospitals, but is subtle. Transfusion harms are usually clinically inapparent, showing up in data sets as slightly worsened outcomes among a few more of the transfused, as compared to the not-transfused.
The situation is a watered-down version of the philosopher Derek Parfit’s “Harmless Torturers” problem — in which a thousand torturers each press a button that causes a minuscule amount of damage, but together sum into something truly harmful. How to consider individual moral responsibility in such situations, i.e. the problem of imperceptible harms, represents a dilemma.
Phlebotomy is not torture (and neither is ordering daily labs). But wasting such vast quantities of patients’ blood, and the blood collected at great expense from altruistic donors, seems unacceptable. If it’s really this easy to cut the waste by 50%, shouldn’t we be doing it already? Read in JAMA
In randomized trials totaling over 21,000 patients, restricting red blood cell transfusion until hemoglobin fell below 7 or 8 g/dL in acutely ill, hemodynamically stable patients (as compared to transfusing below 9 or 10 g/dL) resulted in a 50% reduction in blood transfused, without apparent harm.
In critically ill patients, the 1999 TRICC trial established 7 g/dL as a generally accepted threshold for red cell transfusion in most ICU patients.
Above those thresholds, the less blood transfused, the better, it seems.
Controversy has persisted, though, as to ideal transfusion thresholds in patients with cardiovascular disease, particularly active myocardial ischemia. Does increasing oxygen delivery to ischemic myocardium outweigh any harms of volume loading and immunogenicity from the transfused blood? Three randomized trials showed inconsistent results; the largest suggested restricting transfusion to Hb<8 g/dL in acute MI appeared safe, but that non-inferiority trial with a wide confidence interval was far from conclusive.
In a follow-up to that study, investigators randomized 3506 patients with acute myocardial infarction (ST- or non-ST-elevation MI) and anemia to either a liberal transfusion threshold (hemoglobin less than 10 g/dL) or a restrictive threshold (permitted at Hb < 8 g/dL, strongly recommended at Hb < 7 g/dL). Over 140 centers in United States, Canada, Australia, New Zealand, France, and Brazil participated.
There were almost no exclusion criteria, resulting in a real-world, chronically ill patient population with high rates of prior MI, current systolic heart failure and chronic kidney disease (11% on dialysis). Almost half were women and more than 20% self-identified as other than white.
After 30 days, the liberal transfusion patients received more than three times as much blood (~4300 units, an average of 2.5 units transfused per patient) than the restrictive patients (~1200 units, average 0.7 per patient).
Much blood was spared. But was there harm? The results were not reassuring:
Recurrent myocardial infarction or death, the composite primary outcome (~17% in restrictive, 14.5% in liberal)
Death (~10% in restrictive, ~8% in liberal)
Recurrent MI (8.5% in restrictive, ~7% in liberal)
Cardiac death (5.5% in restrictive, ~3% in liberal)
These confidence intervals generally included 1.0, but just barely, suggesting harm. A very rough estimate would be a number needed to harm of about 50 by restricting transfusion in acute MI.
There was no increased rate of heart failure symptoms among the liberally-transfused. As the trial was unblinded, attendings’ knowledge of intervention assignment probably created differences in care.
I predict the MINT trial will enshrine the usual practice of more-liberal red blood cell transfusion in patients with active myocardial ischemia and anemia. It’s hard to imagine a larger trial being performed, given the strength of signal here; it would be expensive, unlikely to repudiate MINT, and ethically questionable. Read in NEJM
The Association for the Advancement of Blood and Biotherapies (formerly called the American Association of Blood Banks) issued newly updated guidelines on red cell transfusion in hospitalized patients.
More than 45 randomized trials were considered, including more than a dozen since their last guideline update several years ago.
AABB recommended transfusion be restricted (in hospitalized hemodynamically stable patients) until hemoglobin is less than 7 g/dL: a strong recommendation on moderate quality evidence.
They advised a higher threshold of 7.5 g/dL for cardiac surgery patients, 8 g/dL for orthopedic surgery, and 8 g/dL for patients with chronic cardiovascular conditions.
They declined to advise on thresholds for transfusion during acute myocardial infarction.
For hemodynamically stable, acutely ill children who are critically ill or at risk for progressing to critical illness, a transfusion threshold of 7 g/dL was advised—also a strong recommendation on evidence considered moderate quality.
Some children with congenital heart disease and other conditions should be transfused to higher targets, they advised.
AABB stated its transfusion recommendations are intended only for the management of patients without hemoglobinopathies (sickle cell disease, thalassemia, et al), many of whom require episodic transfusions according to other clinical criteria. Read in JAMA
Jon and colleagues ask:
“What is fluid tolerance? What is fluid responsiveness? With Doppler ultrasound measures (e.g., VExUS, VTI) there is growing interest in characterizing these phenomena. But what are they and more specifically, how do they relate to each other? In this brief commentary in Critical Care Explorations, we propose that the Frank-Starling relationship and the venerable Diamond-Forrester classification are useful roadmaps.”