Despite initial concerns about the drug’s effect on kidney function, a Georgia research team has concluded that desmopressin (DDAVP) can be used in cardiac surgery without special concerns for safety. The team’s pilot study concluded that although desmopressin causes statistically significant increases in creatinine, these are not associated with an increased incidence in relevant side effects.
Meanwhile, a Toronto clinician recommended caution with off-label administration of the agent in the absence of very specific indications.
“We have a cardiothoracic surgeon who almost always uses DDAVP in his patients after CABG [coronary artery bypass graft] surgery or valve replacement,” said Vikas Kumar, MD, assistant professor of anesthesiology and perioperative medicine at Augusta University, in Georgia. “We had read in the literature that it can cause increases in creatinine and renal insufficiency, so we wondered what kinds of effects it was having on his patients. And the only way to find out was to do a study of our own to see what it shows.”
Increased Kidney Dysfunction?
Desmopressin—a synthetic analog of vasopressin—promotes both antidiuretic properties and an ability to increase factor VIII and von Willebrand factor levels without vasoconstriction. These properties, however, may come at the cost of increased perioperative kidney dysfunction and water retention, which in turn may lead to more ventilator days.
To help shed some light on this potential relationship, Dr. Kumar and his colleagues analyzed data from 116 patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) at the institution between April and December 2013. Patients were excluded if they had risk factors that predisposed them to renal injury and pulmonary complications, including diabetes, lung and renal disease, anemia, CPB time and heart failure.
A total of 58 patients received intraoperative desmopressin to minimize postoperative bleeding. The study’s primary end point was acute kidney injury (AKI), as assessed according to the Acute Kidney Injury Network’s definition. Secondary end points were ventilator days and ICU length of stay. “We only administer desmopressin once, either in the operating room or at the end of the surgery when the patient is coming off bypass,” he explained.
Despite these differences, patients proved similar with respect to secondary end points. Patients not receiving desmopressin had an average of 1.5 ventilator days, compared with 2.3 days for those receiving desmopressin (P=0.20). ICU length of stay was 6.8 days for controls and 6.3 days for desmopressin patients (P=0.38).
Effects Not Clinically Significant
“We were thinking that patients who received desmopressin might have more urinary retention, which may subsequently increase ventilator days and cause more postoperative pulmonary congestion,” he said in an interview with Anesthesiology News. “But surprisingly, we didn’t see any.”
Although the study’s outcomes may have proved somewhat unexpected to the researchers, the rise in creatinine among patients who received desmopressin was not. “The creatinine increase was not really surprising to us,” he added. “What’s more, it was only a transient rise, and it came back to normal in a couple of days.
“Furthermore, the differences in renal function that we found between the control and desmopressin groups were statistically significant, but we believe they’re not clinically significant,” he said. “That was certainly our initial concern: We began the study by thinking that we should not use desmopressin regularly. But when we finished the study, our opinions had changed substantially.”
As such, it was easy for the researchers to recommend the use of desmopressin in these procedures, particularly when excessive bleeding is suspected. “Although it’s difficult to generalize, we see that in cardiac surgery there is some component of platelet dysfunction and patients can start to ooze postoperatively,” he said. “Many times they get aspirin or clopidogrel preoperatively, which also increases the tendency for excessive intraoperative or postoperative bleeding.
“So based on our experience, if the patient has an increased chance of bleeding—whether it’s because of platelet dysfunction, preoperative aspirin or prolonged bypass time—I would say that we should use desmopressin, since it’s a benign drug and does not cause a significant increase in bleeding postoperatively, and may decrease blood transfusion.” Nevertheless, the investigators recognized the need for a larger, prospective study to shed more light on the effects of desmopressin in patients undergoing cardiac surgery.
… But Mixed Findings Warrant Caution
David Orlov, MD, found the results of the study interesting, but also noted that the subject warrants a randomized controlled trial. “Given the retrospective, observational nature of the study, it would be interesting to see how the investigators adjusted for baseline group differences between DDAVP recipients and controls,” said the staff anesthesiologist in Toronto General Hospital’s Department of Anesthesiology and Pain Management.
Nevertheless, Dr. Orlov agreed that the administration of desmopressin is unlikely to worsen post-CPB bleeding. “However,” he noted, “the primary goal of its administration should be to reduce post-CPB bleeding, an effect that has been hotly debated and controversial. Although some older meta-analyses have reported mild reductions in perioperative blood loss after DDAVP administration, overall results have been inconsistent.
“Indeed, the largest and most contemporary randomized controlled trial examining desmopressin use after cardiac surgery in bleeding patients who were all administered antifibrinolytic agents was stopped prematurely for futility of treatment [Acta Anaesthesiol Scand 2016;60:892-900],” Dr. Orlov continued. “Moreover, recent research from our center [J Cardiothorac Vasc Anesth2017;31:883-895] has supported this limited evidence of hemostatic benefit from DDAVP administration alongside the identification of increased rates of its utilization following implementation of point-of-care hemostatic testing.
“In all,” Dr. Orlov said, “I would recommend caution with off-label administration of DDAVP in contemporary cardiac anesthesia practice in the absence of very specific indications, given the potential for increased use and associated cost—despite limited evidence of benefit.”