Author: Michael Vlessides
Common hospital policies that mandate the administration of packed red blood cells (PRBCs) through a dedicated IV catheter may be overly cautious, according to the results of a new study. These policies assume detrimental effects on erythrocyte integrity when crystalloids and certain medications are coadministered.
Researchers at the University of Alabama at Birmingham and Johns Hopkins University found that five minutes of incubation of PRBCs with isotonic crystalloids or catecholamines did not deleteriously alter PRBC hemolysis, membrane deformability or aggregation. The trial also found that coincubation with 5% dextrose in water likely increases hemolysis, while propofol may promote hemolysis.
“Many hospital policies mandate that packed red blood cells be delivered in a dedicated IV catheter so that no other medications or infusions can be delivered through that IV,” said Domagoj Mladinov, MD, an assistant professor of critical care medicine and thoracic anesthesia at the University of Alabama at Birmingham. “And while this might sound like a trivial problem, it can actually be an issue in patients with multiple comorbidities, in whom we sometimes need to put central venous catheters.
“So we wanted to examine the basis of such hospital policies,” he added. Liberating institutions from these requirements would decrease the need for obtaining additional central venous access in a number of critically ill patients, potentially decreasing resource utilization, procedure-related complications and patient discomfort.
No Difference in Hemolysis
Led by senior investigator Jeffrey M. Dodd-o, MD, PhD, an associate professor of anesthesiology and critical care medicine at the Johns Hopkins University, in Baltimore, the researchers incubated human donor PRBCs for five minutes at room temperature with either crystalloid solutions (multiple electrolytes injection [Plasma-Lyte A, Baxter], 0.9% sodium chloride, 5% dextrose in water [D5W]) or medications (epinephrine, norepinephrine, dopamine, propofol). Each donor’s fresh frozen plasma served as a control.
“We selected these medications because they’re typically administered as prolonged infusions to patients in the ICU,” Dr. Mladinov said.
Erythrocyte integrity was assessed through blood smears, potassium concentration, heme degradation products, deformability and aggregation.
“The next question was in what ratio would we mix the packed red blood cells and those infusions,” Dr. Mladinov said. “We did that at a ratio of 6 to 1: 6 mL of packed red blood cells to 1 mL of the crystalloids or medications. Those were arbitrarily selected parameters, but we feel they are reasonable, and they reflect our real practice.”
As Dr. Mladinov reported at the 2019 annual meeting of the International Anesthesia Research Society (abstract C013), D5W was the only crystalloid found to cause a significant increase in hemolysis, through elevated free hemoglobin and potassium. No statistically significant difference in hemolysis was observed with any of the tested medications.
“The next thing we looked at was potassium levels,” Dr. Mladinov said. “Again, as expected, we saw an increase in potassium levels with D5W, confirming the increased hemolysis in that sample.” The researchers also observed increased potassium levels in propofol samples.
A similar effect was seen with all medications except propofol, although none reached statistical significance. “All of those medications are suspended in normal saline, which may have added to the dilution effect,” Dr. Mladinov explained.
Of note, propofol caused a relative increase in erythrocyte aggregation. However, this change did not reach statistical significance.
Isotonic Crystalloids and Catecholamines
Finally, analysis of red blood cell membrane deformability once again revealed a statistically significant increase with D5W relative to the other crystalloids. Although no statistically significant effects of the medications were observed with respect to deformability, a decreased trend in elasticity index was found with dopamine.
“And as we know,” Dr. Mladinov said, “an increase in deformability is associated with a shorter life span of erythrocytes.”
These findings, the researchers said, demonstrate that incubating PRBCs for five minutes with isotonic crystalloids or catecholamines does not deleteriously alter erythrocyte integrity. Hypotonic solutions such as D5W—as well as medications mixed in such solutions—likely increase cell lysis, whereas propofol may lead to increased PRBC lysis and aggregation.
“Our study suggests that coadministration of normal saline, Plasma-Lyte, epinephrine and norepinephrine together with packed red blood cells would be a safe practice,” Dr. Mladinov said. “On the other hand, we showed that coadministering the D5W would not be a good idea.
“We are hoping that the results of this study might work their way into relevant guidelines of major societies and then, ultimately, could potentially be reflected in changes in hospital policies, because liberation from this restriction of infusing medications or crystalloids with packed red blood cells might decrease resource utilization, decrease risk to the patient, decrease comorbidities, and naturally improve patient outcomes.”
Hilary P. Grocott, MD, a professor of anesthesiology, perioperative and pain medicine, and surgery at the University of Manitoba in Winnipeg, agreed that the trial disrupts commonly held notions regarding the administration of PRBCs. “This study is a good example of how dogmatic practices should always be questioned as to what comprises the evidence base surrounding them,” Dr. Grocott said.
“Paraphrasing the noted British economist John Maynard Keynes, when the data changes, be prepared to change your mind,” she added.