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Long-Lasting Analgesia with Liposomal Bupivacaine

Carlson, Robert H.

doi: 10.1097/01.COT.0000466404.48815.12


MIAMI BEACH—One of the main causes of chronic pain after breast surgery is inadequate management prior to surgery. That was the word from Valerie Lemaine, MD, Assistant Professor of Plastic Surgery and Vice Chair for Research at Mayo Clinic College of Medicine, speaking here at the Miami Breast Cancer Conference, discussing her experience treating pain preoperatively using a relatively new anesthetic, liposomal-encased bupivacaine.

At Mayo, she said, the drug has been used for patients undergoing mastectomy, lumpectomy, autologous and implant-based reconstruction, and cosmetic procedures. The maximum tolerated dose is significantly higher compared with what is possible with bupivacaine hydrochloride. The newer drug also appears to help decrease opioid requirements, and if used in place of paravertebral block, there is a cost savings.

The effects of this long-acting agent have been reported to last up to 96 hours after surgery, she said. Liposomal bupivacaine was approved by the Food and Drug Administration in 2011, for single-dose application to the surgical site by injection to produce postoperative analgesia.

A show of hands in the audience of approximately 800, the majority of whom were physicians, indicated, however, that very few had experience with the drug.

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‘Not Unlike a Pomegranate’

Postoperative pain is common, Lemaine said, with the highest percentage incidence reported in amputees— 57 to 62 percent. Among patients undergoing breast surgery, 27 to 48 percent report postoperative pain.

Liposomal-encased bupivacaine is an amide-type local anesthetic delivered by gradual release through multivesicular liposomal technology. Lemaine likened the molecule of liposomal bupivacaine to a pomegranate, with a lipid membrane as the outer shell, and inner lipid membranes containing the drug.



Particles of the anesthetic are released when there is erosion and reorganization of the lipid membranes. “Pharmacokinetics demonstrate that plasma levels of liposomal bupivacaine can persist for up to 96 hours, although in my personal experience I've seen more of a 72-hour difference,” Lemaine said.

The experience of microsurgical breast reconstruction patients is a good example of liposomal bupivacaine's efficacy, she noted. These patients stay in the hospital for three to four days so the degree of pain control is apparent. “Not until about day three do they start taking a little more oral medication to control their pain,” if liposomal bupivacaine was administered before surgery.

The drug's first peak is early on, a few hours post-surgery, but the main peak level is at about 30 to 40 hours, she said.

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Dilute with Preservative-Free Normal Saline Only

The drug is packaged in a 20-cc vial and is diluted with preservative-free normal saline: “The drug can be diluted with up to 220 cc of saline, for a total dilution of 260 cc, although I occasionally will inject it undiluted,” she said.

Lemaine emphasized that the product must be injected within four hours of preparation: “I've had very motivated circulating nurses who would prepare it at the beginning of a free-flap procedure, and then 12 hours later the product has to be wasted. It's important to communicate this with your team.”

She said it is not recommended to dilute the product with anything but preservative-free saline. Using anything else, such as water or a hypotonic agent, will disrupt the liposomes so more liposomal bupivacaine is released at the same time, and there is a higher risk of toxicity.

Lemaine said she injects into the substance of the pectoralis major muscle after the fascia has been partially removed. She makes decisions on administration on a case-by-case basis—for example, for a recent case of a mastectomy for a woman with D-cup breasts, Lemaine planned a 50-cc injection per breast.

“I don't do this with all mastectomies, but with patients who have very large breasts I would likely increase the dilution.”

Be cautious about using liposomal bupivacaine with other local anesthetic agents such as lidocaine, she said. Administering the two together locally may cause immediate release of liposomal bupivacaine from liposomes.

If both drugs are used, she said lidocaine may be used first, but administration of liposomal bupivacaine must follow administration of lidocaine after a delay of 20 minutes or longer.

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Liposomal Bupivacaine vs. Paravertebral Block

Lemaine said the practice at Mayo had been to perform paravertebral blocks for all patients undergoing mastectomy and immediate breast reconstruction with a tissue expander (but not free flaps). “We had a good experience with microsurgical breast reconstruction using bupivacaine and we thought it might also be useful in tissue expansion reconstruction.”

She shared the unpublished, retrospective data analyzed this year by Abdelsattar and colleagues, comparing local injection of liposomal bupivacaine versus regional paravertebral block. Half of the patients received liposomal bupivacaine, the others paravertebral block, but none received both.

“In the liposomal bupivacaine group, we saw reduced use of opioid in the recovery room,” she said. “That was surprising—it seems a bit early, and I am not sure that is linked to the liposomal bupivacaine.”

Also in this retrospective study, fewer patients receiving liposomal bupivacaine required antiemetics postoperatively. “That is not a finding consistent in all studies, but in our study we were able to find a small difference,” she said.

There were lower day-of-surgery pain scores with liposomal bupivacaine, and a longer time until patients requested their first opioid.

Another consideration is that paravertebral block takes more time. “That's a source of frustration for plastic surgeons at Mayo, who are the last ones to operate on the patient, and we would like to go home a little bit earlier sometimes,” she said. “Doing a paravertebral block can add up to 45 minutes to the first case of the day because it has to be done in the operating room.

She said plastic surgeons were enthusiastic about using liposomal bupivacaine, “and our wonderful breast surgeons were willing to try it.”

A point in favor of liposomal bupivacaine is that with paravertebral block there is a low but significant incidence of pneumothorax, a complication that may require chest tubes—“It's rare, but when it happens it is usually on very slender patients,” Lemaine said.

She noted that in two years of experience she has found the new drug to be safe, although she added that there is a learning curve—“So if you start using it, don't be discouraged.

“It is important for our patients that they live pain-free after surgery,” Lemaine concluded.

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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