ROCKVILLE, Maryland—The chondrolysis risk reported by MSKreport.com last March has triggered an FDA demand for label warnings by makers of intra-articular infusion pumps (“pain pumps”) and also by makers of the local anesthetics that have been used with these devices. The firms have 30 days to submit proposed new labeling to the agency.

The regulatory action is expected to affect many of the hundreds of lawsuits now pending against makers of the pumps, including Stryker, I-Flow, Donjoy and Breg.

The FDA's November 13, 2009, “dear doctor” letter cites 35 reports of chondrylosis in patients given continuous intra-articular infusions of local anesthetics with elastomeric infusion devices to control post-surgical pain. The strongly-worded letter emphasizes, “...both the local anesthetics and the elastomeric infusion devices —or any other type of device used for intra-articular infusions—are not approved or cleared by the FDA for continuous intra-articular infusion.”

“The significance of this injury to otherwise healthy young adults warrants notification to health care professionals,” the agency said.

The median age of the affected patients was 25 years, with an age range of 16-58 years. Six of the reports involved pediatric patients between 16 and 18 years. In almost all of the reported cases (34/35 or 97%), the location of chondrolysis was in the shoulder joint. The remaining report involved the knee joint.

Off-label use for local anesthetics and for pumps

In the reported cases, local anesthetics (with and without epinephrine) given for post-surgical pain had been infused for extended periods of time (48 to 72 hours) directly into the intra-articular space using an elastomeric pump. Chondrolysis was diagnosed within a median of 8.5 months after the infusion, but joint pain, stiffness, and loss of motion had been reported as early as the second month after infusion.

Almost all of cases occurred following shoulder surgeries, and more than half of the patients required additional surgery, including joint replacement in some cases.

However, the FDA also points out, “It is important to note that single intra-articular injections of local anesthetics in orthopedic procedures have been used for many years without any reported occurrence of chondrolysis.”

The FDA emphasizes that approved uses for local anesthetics do not include continuous intra-articular postoperative infusions or use of infusion devices, such as elastomeric pumps and that no infusion devices have been cleared for use in intra-articular infusion of local anesthetics.

Half of patients required more surgery

Of 35 reports of chondrolysis (primarily in the shoulder) occurring in patients administered continuous intra-articular infusions of local anesthetics with elastomeric infusion devices were reported to the FDA's Adverse Event Reporting System (AERS), 32 (91%) had received bupivacaine (with or without epinephrine) as an intra-articular infusion after having undergone arthroscopic and other surgical procedures; 2 had received ropivacaine in addition to bupivacaine; and 2 had received bupivacaine as a single injection along with an intra-articular infusion of lidocaine. The most commonly reported infusion site was the glenohumeral (glenoid) space (46%).

Half of the bupivacaine-associated AERS reports included the dose administered, with 10 of 16 patients receiving 500mg over 48 hours or 250mg/day. According to the FDA, “While this daily intra-articular dose was within the maximum dose listed in the drug label (400mg/day), it is important to note that this maximum labeled daily dose was determined for the approved uses and not for off-label uses such as continuous intra-articular infusions with elastomeric infusion devices.” The FDA later received four additional reports of chondrolysis.

More pain for Stryker

The manufacturer mentioned most often in the case reports were Stryker (n=11); other manufacturers mentioned in the reports were I-flow, Donjoy and Breg (n=14 combined).

The FDA letter adds to ongoing pain for Stryker. The company, its former president, and 3 current sales managers were indicted October 28 by the US Department of Justice for illegal promotion of medical devices used in invasive spinal and long bone surgeries.