Targeted Muscle Reinnervation at the Time of Major Limb Amputation Reduces Long-Term Use and Dependence for Opioid Analgesic Therapy: A Multicenter Propensity-Matched Study.

Objective: To evaluate the impact of primary targeted muscle reinnervation (TMR) performed at the time of major limb amputation on long-term opioid use, opioid dependence, and neuropathic pain medication use compared to standard amputation.

Summary background data: Postoperative pain following major limb amputation is common, often leading to prolonged opioid use, dependence, and neuropathic pain. TMR, a surgical technique that redirects amputated nerves into motor targets, has been proposed as a method to reduce pain-related complications, but prior studies are limited by small sample sizes, single-center experiences, and insufficient follow-up data. This study utilizes a multicenter database to assess long-term outcomes of TMR compared to standard amputation.

Methods: A multicenter query was conducted using the TriNetX Research Network to identify patients undergoing major limb amputation with or without TMR over 20 years. Propensity score matching was used to create comparable cohorts for analysis. Primary outcomes included opioid use, opioid dependence, neuropathic pain medication use, and stump-related complications, evaluated from 90 days to 3 years postoperatively.

Results: Among 43,890 patients, those undergoing primary TMR (n=644) had significantly lower risks of opioid use (RR=0.72; 95%CI [0.60, 0.86], P<0.001) and opioid dependence (RR=0.50; 95%CI [0.27, 0.92], P=0.023) compared to matched controls undergoing standard amputation (n=644). In the ischemia subgroup, TMR patients had a 41% lower risk of opioid use (RR=0.59; 95%CI [0.42, 0.83], P=0.002). No differences in neuropathic pain medication use or stump-related complications were observed between cohorts. Time-course analysis demonstrated persistent reductions in opioid use among TMR patients at all intervals from 3 months to 3 years.

Conclusions: Primary TMR at the time of major limb amputation significantly reduces long-term opioid use and dependence, particularly in patients with limb-threatening ischemia, without increasing the risk of stump-related complications. These findings support the broader adoption of TMR to improve postoperative outcomes in amputees.