ST LOUIS (MD Consult) - On November 13, 2009, the US Food and Drug Administration (FDA) announced that it has reviewed 35 reports of chondrolysis in patients who had received continuous intraarticular infusions of certain local anesthetics. The process of chondrolysis results in the necrosis and destruction of cartilage.

Most of these events occurred in otherwise healthy young adults. The median age of the affected patients was 25 years, with an age range of 16 to 58 years. Six of the reports involved pediatric patients between the ages of 16 and 18 years.

The local anesthetics were given (with and without epinephrine) for the purpose of postoperative pain control, and were infused for extended periods of time (48 to 72 hours) directly into the intraarticular space using an elastomeric pump. The anesthetics named in the reports include bupivacaine, chloroprocaine, lidocaine, mepivacaine, procaine, and ropivacaine.

Chondrolysis was diagnosed within a median of 8.5 months after the infusion. Almost all of the reported cases of chondrolysis (97%) occurred after shoulder surgeries. Thirty-two (91%) of these patients received bupivacaine (with or without epinephrine). Joint pain, stiffness, and loss of motion were reported as early as the second month after receiving the infusion. In more than half of these reports, the patients required additional surgery, including arthroscopy or arthroplasty.

It is not known which specific factor or combination of factors contributed to the development of chondrolysis in these cases. The infused local anesthetic drugs, the device materials, and/or other sources may have resulted in the development of chondrolysis. The FDA pointed out that single intraarticular injections of local anesthetics for orthopedic procedures have been used for many years without any reported occurrence of chondrolysis.

Local anesthetics are approved as injections for the production of local or regional anesthesia or analgesia. The approved drug labels for local anesthetics do not include an indication for continuous intraarticular postoperative infusions or use of infusion devices, such as elastomeric pumps. The FDA has not cleared any infusion devices with an indication for use in intraarticular infusion of local anesthetics.

Health care professionals are encouraged to follow the instructions for use of elastomeric infusion devices and to not use these devices for continuous intraarticular infusion of local anesthetics after orthopedic surgery.

Because of these reports, the FDA is requiring the drug manufacturers to update their product labels to warn health care professionals about this potential serious adverse effect. In addition, the FDA will be requiring manufacturers of pumps that may be used to infuse local anesthetics, including elastomeric infusion devices, to carry similar warnings for their products.

 

圣路易斯(MD Consult)——2009年11月13日，美国食品药品管理局(FDA)宣布已对35份部分局麻药关节腔内持续输注致软骨溶解的报告进行了分析。软骨溶解的过程可导致软骨坏死和软骨破坏。

 

大部分不良事件都发生在除目标疾病外身体健康的年轻成人中。出现了该不良事件的患者的中位年龄为25岁，年龄范围在16～58岁之间。其中6份报告涉及年龄在16～18岁之间的患儿。

 

在这些不良事件报告中，使用局麻药(加或不加肾上腺素)的目的是用于术后镇痛，通过弹性泵将局麻药直接输入关节腔内，且输注时间较长(48～72h)。报告涉及的局麻药包括布比卡因、氯普鲁卡因、利多卡因、甲哌卡因、普鲁卡因和罗哌卡因。

 

软骨溶解的确诊时间是在输注后大约8.5个月(中位值)。几乎报告的所有软骨溶解病例(97%)都出现在肩关节术后。其中32名 (91%)患者都接受的是布比卡因(加或不加肾上腺素)给药。早在输注后第2个月就有报告称出现了关节疼痛、僵硬和活动受限。半数以上的患者都需要再次手术，包括关节镜检查或关节成形术。

 

对于这些病例，目前尚不清楚是哪种特定因素或是几种因素共同作用导致了软骨溶解。所输注的局麻药、仪器材料和/或其他原因都可能导致软骨溶解的出现。FDA指出，采用局麻药单剂关节腔内注射以控制骨科术后疼痛，这种做法已沿用多年，目前尚无软骨溶解的报告。

 

局麻药注射剂是获准用于局部或区域麻醉或镇痛。已核准的局麻药产品标签并未提及术后关节腔内持续输注的适应证，也没有建议采用任何输液装置，如弹性泵。FDA尚未明确指出局麻药用于关节腔内输注时应采用哪种输液装置。

 

建议医务人员遵照弹性输液装置的使用说明，避免将这类装置用于骨科术后局麻药的关节腔内持续输注。

 

鉴于这些不良事件报告，FDA要求药品生产商更新其产品标签，警示医务人员这一潜在的严重不良反应。此外，FDA还将要求包括弹性输液装置在内的可能用于局麻药输注的输液泵生产商也在其产品标签上注明类似的警告。