National Drug Shortage Affects TKA Practice Standards and Outcomes

Author: Michael DePeau-Wilson

Anesthesiology News

The effects of a nationwide shortage of hyperbaric bupivacaine in 2018 led to changes in clinical practice, including an increased use of intrathecal adjuvants, and increases in minor adverse events in total knee arthroplasty (TKA) cases, according to a single-institution study.

The shortage also provided the opportunity for a team of anesthesiologists and health-system pharmacists to test their clinical protocols around TKA and the effectiveness of isobaric bupivacaine, their second-choice anesthetic for TKA, as a replacement.

Edward Mariano, MD, MAS, the chief of anesthesiology and the perioperative care service at the VA Palo Alto Health Care System, in California, was one of the primary investigators of the study. He said the team saw the shortage as a unique opportunity to learn more about their practices and how they were handling the sudden crisis of being without their first-choice anesthetic drug. In his words, it was a natural experiment and one that his team believes they must be prepared for again.

“Unfortunately, it’s going to be an experiment that gets repeated,” said Dr. Mariano, who is a member of the editorial advisory board of Anesthesiology News. “Whether it’s hyperbaric bupivacaine or another local anesthetic or another analgesic drug, we’re going to be facing drug shortages for the near future, [and] for the rest of our careers perhaps.”

Facing the Adversity

Once Dr. Mariano and his team made the decision to study the difference in outcomes between the two protocols, they collected data from 123 TKA cases. Of those, 14 cases were excluded, leaving 109 cases that were divided into a control group (n=55) and a shortage group (n=54). The control group included cases from three months before the shortage of hyperbaric bupivacaine (Table 1).

The use of spinal anesthesia was slightly different, with 80% (44/55) of the control group receiving it compared with 68% (37/54) of the shortage group (P=0.170). The most common replacement for the unavailable hyperbaric bupivacaine was isobaric bupivacaine.

In addition, 88% (30/34) of the shortage group was given at least one intrathecal adjuvant, either fentanyl or epinephrine, or both, compared with just 54% (19/35) in the control group (P=0.003). The research was presented at the 2019 annual meeting of the American Society of Regional Anesthesia and Pain Medicine (abstract 6847).

The study found that the shortage group experienced more nausea and vomiting as well as other minor adverse events in the PACU (Table 2). But the most important change the study revealed, according to Dr. Mariano, was that the shortage changed the clinical practice of the anesthesiologists.

“What our study shows is that behavior does change [and] that you have to adapt,” he said. “You have to change your practice.”

Dr. Mariano added he was also encouraged by the team’s ability to respond to the adversity presented by the shortage.

“The fact that we were able to continue to maintain that first-choice anesthetic [spinal] to an acceptable rate, which was not statistically different than from our pre-shortage rate, I think is important,” he said.

Shortly after the study period ended, Dr. Mariano reported that the shortage of hyperbaric bupivacaine ended in their institution, and the rates of adjuvant use and minor adverse events returned to pre-shortage levels as practice resumed with the original, first-choice anesthetic.

Preparing for the Next Shortage

One of the major lessons for the VA Palo Alto team, Dr. Mariano said, was that hyperbaric bupivacaine is their first-choice anesthetic for a reason. The evidence for hyperbaric use over isobaric—which produces a longer duration than desired—has been found in previous studies, and that preference for hyperbaric was proven to be an important factor for the team’s standards of practice (Anesth Analg 2017;125[5]:1627-1637).

The team also realized the need for better communication about the hospital supply of key drugs used in their standard practice. It was a point that Dr. Mariano said was reinforced throughout the experience of working during the shortage and when the final numbers were analyzed for this study.

In the end, the most important finding was that the shortage had many unintended effects on typical clinical practice for the team and that secondary options during shortages are not ideal for providing the best possible care. A goal for the future is to be as aware as possible of potential shortages and to be prepared.

“[We] will continue to try to avoid adverse events, if possible,” Dr. Mariano said. “Although knowing from the evidence that it’s not exactly a one-for-one trade in terms of the way that this spinal anesthetic sets up and how long it lasts. But there is evidence now from our own experience that there are definitely some side effects associated with trying to do multimodal intrathecal anesthesia.”

Those lessons will serve to prepare Dr. Mariano and his team for the next shortage that could already be on the horizon.