Background. Adequate pain management is mandatory for patients' early rehabilitation and improvement of outcome after total knee arthroplasty (TKA). Conventional pain management, consisted of mainly opioids, has some adverse effects such as dizziness and nausea. Motor blockade occasionally resulted from epidural analgesics. A novel multimodal analgesic strategy with peripheral nerve block, peri-articular injection (PAI) and intravenous patient controlled analgesia (IVPCA) were utilized for our patients receiving TKA. In this study, we compared the clinical efficacy and adverse effects in the group of multimodal analgesia (MA) or epidural analgesia alone. Methods. One hundred and eighteen patients undergoing TKA with spinal anesthesia were enrolled. Patients of TKA received either our protocol of multimodal analgesia or patient controlled epidural analgesia (PCEA) alone. MA included ultrasound guided nerve block in femoral and obturator nerves before spinal anesthesia, and PAI mixed with NSAID, morphine, ropivacaine and epinephrine, as well as IVPCA after surgeries. The analgesic effect with numeric rating scale (NRS) and occurrence of adverse effects, including motor blockade, numbness, postoperative nausea/vomiting (PONV), and dizziness were recorded for all patients. Results. Thirty-one patients received MA, and eighty-seven patients received PCEA. No significant difference of NRS in MA and PCEA group within 24 hours after surgery either in rest (0.2 ± 1 compared with 0.22 ± 0.98; p = 0.930) or motion (0.40 ± 1.56 compared with 0.31± 1.23; p = 0.764). MA group sustained lesser motor blockade than PCEA (6.45% compared with 22.98%; p = 0.028) beyond 24 hours after surgery. The occurrence of numbness is lower in MA group (18.52%) compared with PCEA group(43.33%) (p=0.031). No statistic difference of PONV and dizziness is noted between two groups. However, there is a trend that lesser PONV and dizziness occurred in MA group than PCEA group. Conclusion. TKA patients receiving either MA or PCEA have adequate analgesic efficacy after surgeries. MA group has a lower incidence of motor blockade and PONV than PCEA. This multimodal analgesia proposed here has shown patients' safety and improved pain control after TKA, decreased narcotics use and their associated side effects. Besides, lesser motor blockade and adequate pain relief may encourage patient's early rehabilitation

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