Does Size Matter in Drawing Blood?

• 40% of patients admitted to intensive care units (ICUs) require transfusion, more than half given “in the absence of active bleeding.”
• Critically ill patients typically have multiple 6 mL vials of blood drawn daily, and our typical laboratory equipment usually requires less than 10% of that volume to provide accurate results.

Blood tubes used to draw samples from pediatric patients are much smaller, and I have often wondered, as both physician and patient, why these tubes were not used preferentially for adults. I was not alone in my thinking, and some have suggested that the multiple blood samples taken from patients in critical condition resulted in losing about a unit of blood every eight days. Could the 90% of wasted blood in those standard tubes be a source of “substantial iatrogenic (caused by medical treatment) blood loss” necessitating transfusion?

Stepped Wedge Trials

In search of an answer, researchers reporting in a new study used a stepped wedge trial design where blood draws were transitioned from large to smaller volumes. This is a pragmatic, real-world clinical trial of delivered care that is especially useful when, in the researchers' words, there is “a high likelihood of benefit and low risk of harm.” Clusters of patients, or in this instance, those in specific ICUs, are randomly and sequentially moved from control to intervention until all the ICUs and their patients were exposed to the treatment variable, in this instance, the use of smaller tubes to gather blood samples.

There is no blinding to the intervention, a typical source of bias, but one, in this particular study is hard to believe would matter. Additionally, as more ICUs (the clusters) were exposed towards the end of the intervention, underlying temporal trends, care changes over the course of the study, might bias outcomes. This was a concern in this study because of COVID admissions. The researchers decided to pause the transition to smaller vials for several months to allow the COVID wave to pass through and not further bias the data.

Results

The study involved 25 ICUs in Canada with 27,411 patients staying in the ICU for more than 48 hours – the hope being that this inclusion requirement of a lengthier stay would allow the impact of larger and smaller blood draws to be identified. The primary population studied included 21,201 patients without COVID; the secondary population included those patients with COVID again staying in the ICU for 48 hours or more. The findings include:

• 30% of each population were transfused 28,549 units in the primary group and 35,687 in the larger secondary population.
• The number of transfusions and reductions in hemoglobin did not differ significantly, clinically or statistically, in the transition from larger to smaller volume blood draws. There was a smaller rate of transfusion and decreases in hemoglobin in the larger secondary population that included those patients with COVID.
• The use of smaller tubes did not reduce the efficacy of blood testing. Only 0.02% of the larger tubes had insufficient blood for analysis, and 0.03% in the smaller tubes after the change.

The researchers concluded there was

“a possible small reduction in RBC transfusion and ICU-related decrease in hemoglobin with transitioning to small volume tubes. Importantly, we showed no adverse effect on laboratory testing measured as specimen insufficiency, the most important potential harm associated with use of small volume tubes.”

Those restrained conclusions are limited by an essential missing component in the study: the variance in the need for transfusion amongst patients. You get a sense of this from the inclusion of the 6,000⁺ COVID patients in the secondary population. With a lesser need for transfusion than patients undergoing cardiovascular surgery or trauma care, the small effect of using smaller volume blood draws begins to become apparent. How you might construct a study to increase the sensitivity to such a slight difference is unclear, and some might say that given such a small impact of smaller volume blood draws, why bother at all?

Another variable the researchers freely acknowledged was not controlled was the individual hospital and physician criteria for transfusion. The 30-year-old with no cardiovascular disease may tolerate a lower oxygen capacity from a lowered hemoglobin than a 60-year-old with known heart disease currently being treated with supplemental oxygen where a hemoglobin boost would be beneficial. That same 60-year-old with the additional co-morbidity of kidney failure and the inability to urinate away excess fluid from the transfusion might not tolerate the needed transfusion without undergoing dialysis to remove excess fluid. The complexity of medical decision-making and care is simplified in studies that utilize protocols, another factor that makes the results of clinical trials, even as grounded in real-time care as this one, difficult to fully translate and apply in the real world.

Source: Small-Volume Blood Collection Tubes to Reduce Transfusions in Intensive Care The STRATUS Randomized Clinical Trial JAMA DOI:10.1001/jama.2023.20820