No Difference in Early Analgesia Between Liposomal Bupivacaine Injection and Intrathecal Morphine After TKA

Background Opioid analgesics have been a standard modality for postoperative pain management after total knee arthroplasty (TKA) but are also associated with increased risk of nausea, pruritus, vomiting, respiratory depression, prolonged ileus, and cognitive dysfunction. There is still a need for a method of anesthesia that can deliver effective long-term postoperative pain relief without incurring the high cost and health burden of opioids and nerve blocks.

Questions/purposes (1) Is liposomal bupivacaine-based periarticular injection (PAI) more effective than morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA? (2) Do patients treated with liposomal bupivacaine-based PAI experience fewer opioid-related adverse events compared with patients treated with morphine-based spinal anesthesia or ropivacaine-based PAI in controlling postoperative pain after TKA?

Methods This multicenter, blind trial randomized 119 patients undergoing TKA with spinal anesthesia to receive spinal anesthesia plus periarticular injection with liposomal bupivacaine (40 patients), spinal anesthesia with bupivacaine plus intrathecal morphine (41 patients) but no liposomal bupivacaine injection, or spinal anesthesia with bupivacaine (38 patients) and no liposomal bupivacaine injection. The two groups that did not receive periarticular liposomal bupivacaine did receive periarticular injection with ropivacaine, and all three groups had ketorolac (30 mg) plus epinephrine (1:1000) in the periarticular injections. Patients in all three groups received identical perioperative multimodal analgesic and antiemetic drugs. All patients were analyzed in the group to which they were randomized and no patients were lost to followup. The primary study endpoints were visual analog score (VAS) for pain and narcotic use during postoperative day 1. Secondary endpoints included side effects associated with narcotic administration during the hospital stay.

Results Mean VAS pain in the liposomal bupivacaine PAI group was lower than that for the ropivacaine PAI group at 6 hours (1.8 ± 2.1 versus 3.3 ± 2.3, p = 0.005, mean difference: 1.5, 95% confidence interval [CI], 0.5-2.5) and 12 hours (1.5 ± 2.0 versus 3.3 ± 2.4, p < 0.001, mean difference: 1.8, 95% CI, 0.8-2.8) after surgery. The morphine spinal group had lower pain compared with the liposomal bupivacaine PAI group at 6 hours (0.9 ± 1.8 versus 1.8 ± 2.1, p = 0.035, mean difference: 1.0, 95% CI, 0.1-1.8), but there was no difference at 12 hours (0.8 ± 1.5 versus 1.5 ± 2.0, p = 0.086, mean difference: 0.7, 95% CI, −0.1 to 1.5). The magnitude of the differences at 6 and 12 hours are near the lower end of minimal clinically important differences reported in the literature, and thus the improvement shown in this study may only represent a small clinical improvement. Both the liposomal bupivacaine group (13% [five of 40]) and the ropivacaine group (5% [two of 38]) had fewer incidents of itching (pruritus) than the spinal morphine group (38% [15 of 41]) (p = 0.001).

Conclusions This prospective multicenter three-arm blind randomized controlled trial showed potentially improved pain control at 6 and 12 hours in the liposomal bupivacaine and intrathecal morphine groups compared with the ropivacaine group at the cost of much higher incidences of pruritus (itching) in the intrathecal morphine group. Based on these results, we prefer the use of PAI with liposomal bupivacaine as an alternative to spinal anesthesia with intrathecal morphine as a result of similar postoperative pain control and the potential for reducing adverse events.

Level of Evidence Level I, therapeutic study.