Laird Harrison

March 14, 2014

NEW ORLEANS — The extended-release formulation of the local anesthetic bupivacaine is just as effective as a femoral nerve block for relieving pain after total knee replacement surgery, new research shows.

"These patients have essentially no pain," said lead investigator Roger Emerson Jr., MD, a private practice orthopedic surgeon in Plano, Texas. "It's the most incredible thing I've seen in my life," he told Medscape Medical News.

Patients treated with extended-release bupivacaine also used less narcotic rescue medication, spent less time in the hospital, and had fewer falls than those treated with femoral nerve block. And their care cost less.

Dr. Emerson and his colleague, John Barrington, MD, from the Texas Center for Joint Replacement in Plano, presented results from 2 cohorts of patients treated with extended-release bupivacaine here at the American Academy of Orthopaedic Surgeons 2014 Annual Meeting.

To address the extreme pain experienced by patients after total knee replacement surgery, physicians commonly use a multimodal approach. This can consist of a femoral nerve catheter and pump with other parenteral and oral analgesics. Patients frequently suffer from adverse reactions to narcotics with these cocktails, said Dr. Emerson.

These patients have essentially no pain. It's the most incredible thing I've seen in my life.

The regular formulation of bupivacaine relieves pain for only about 6 to 8 hours; however, a new delivery system for bupivacaine (Exparel, Pacira), in which injected liposomes release the drug slowly, relieves pain for 72 hours, he explained.

The researchers conducted 2 retrospective analyses of patients treated with this system.

The first analysis compared 2 groups of consecutive patients who underwent total knee replacement; 1000 were treated with bupivacaine extended-release liposome injection and 1000 were not.

The extended-release bupivacaine cut the number of falls from 10 to 2 and saved $1246 per patient. The elimination of the catheter and pump is a big reason for the cost reduction, Dr. Barrington told Medscape Medical News. Pain rated on a visual analog scale was equivalent in the 2 groups.

Extended-Release Bupivacaine vs Femoral Block

In the second analysis, pain management was randomly assigned after knee replacement surgery; 36 patients received extended-release bupivacaine and 36 received femoral nerve block.

All patients got the same preoperative mix of analgesics.

Patients treated with the femoral nerve block also received a bolus and infusion of ropivacaine; the dose was adjusted by nursing and physical therapy staff and was terminated on the day of discharge. In addition, these patients got a routine combination of oxycodone, hydrocodone, gabapentin, and ketorolac. As rescue medication, they received hydromorphone.

In the bupivacaine group, an intraoperative extended-release liposome injection of bupivacaine 266 mg was administered at the end of surgery. Routine medications in this group were meloxicam, tramadol, acetaminophen, and gabapentin. As rescue medication, these patients received hydromorphone and hydrocodone.

More pain was reported with the femoral nerve block than with the bupivacaine, but the difference was not statistically significant.

There was, however, a significant difference in narcotic rescue medication; patients treated with femoral nerve block used twice as much as those treated with bupivacaine.

Table. Pain Management Outcomes

Outcome Extended-Release Bupivacaine Femoral Nerve Block P Value
Average 5-day pain score 1.82 2.29 .09
Narcotic doses used, n 7.47 14.25 <.001
Narcotic amount used (mg) 82.2 176.6 <.001


There were no adverse reactions to the extended-release bupivacaine, Dr. Emerson reported. Some of his patients experienced drop foot, but he said he attributes that to too much of the drug being injected laterally.

The results stimulated a lively discussion during an electronic poster tour.

Extended-release bupivacaine "has been an absolute game-changer as far as the control of pain," said Charles Lowry Barnes, MD, professor of orthopedics at the University of Arkansas in Little Rock. He has also been using this formulation for knee replacement patients.

The development of a system to deliver anesthetics over a longer period of time could be useful for other drugs and other procedures, noted Michael Ivanitsky, MD, an orthopedic surgeon in private practice in Coquille, Oregon.

However, he said he is reserving judgment on this specific therapy. "There needs to be other studies," he told Medscape Medical News. "It's an interesting and probably useful development, but I'm not going to change my practice based on 1 study."

Dr. Barrington and Dr. Emerson report that they are paid consultants to Pacira Pharmaceuticals, the maker of extended-release bupivacaine. Dr. Ivanitsky has disclosed no relevant financial relationships.

American Academy of Orthopaedic Surgeons (AAOS) 2014 Annual Meeting: Abstract P124 presented March 11, 2014; Abstract 675 presented March 14, 2013.


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