Description

Rationale: In the Netherlands, approximately 3300 lower extremity amputations (sacroiliac to forefoot) are performed each year. In current amputation practice, the nerves are simply cut, without employing any nerve surgical techniques to prevent the development of chronic pain due to neuroma formation. Around 61% of these patients develop postamputation pain (PAP). PAP is a severe lifelong disabling condition profoundly affecting quality of life.

Microsurgical nerve handling can prevent the formation of a painful neuroma and its sequelae. In recent years, targeted muscle reinnervation (TMR) has been the most frequently studied technique with promising results. TMR prevents neuroma formation by rerouting a cut mixed nerve end to a functional motor nerve.

The expected benefit of the implementation of TMR during amputation surgery is a significant reduction in the incidence of PAP. Prevention of this chronic pain syndrome will lead to a significant improvement in quality of life, participation in family life and society, and reduction of health-related costs for thousands of amputation patients every year. To achieve this, a transformation of nerve handling during amputation is needed.

Objective: To compare postamputation pain (phantom limb pain and residual limb pain) one year postoperatively in patients who received a lower extremity amputation (LEA) with standard nerve handling (neurectomy) versus those who received TMR.

Study design: A national, multicenter, randomized, sham-controlled superiority trial, comparing standard neurectomy with TMR in amputations of the lower extremities.

Study population: Patients between 18 and 75 years old, scheduled for an LEA (transfemoral to transtibial) as a primary or secondary sequela of vascular disease.

Intervention: Patients with an LEA are randomized into standard neurectomy or TMR. TMR in short: each transected nerve is identified after amputation and is dissected proximally for length. A nerve stimulator is used to identify functional motor nerve branches. Near the point where the motor branch enters the muscle, the motor nerve branch is transected, and an end-to-end coaptation is performed with a nearby amputated nerve.

Main study parameters: The mean difference in pain scores for phantom limb pain and residual limb pain one year postoperatively. Pain is measured for 30 consecutive days (Pain Diary) on the 11-point (0-10) numerical rating scale (NRS) and according to the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Behavior and Interference Questionnaire Short Forms (7a and 8a, respectively).

Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: The additional risks of performing TMR during amputation are negligible. TMR can be performed at any level of the lower extremities with a standardized technique. For TMR to be possible, in upper leg amputations, an additional incision (ca 10 centimetres) has to be made on the dorsal side of the leg, medial tot the sartorius muscle. In our experience this will not result in more postoperative pain or difficulty in sitting. To properly blind study participants this additional incision for upper leg amputations must also be superficially performed in the control group. Another factor that will differ from current standards is that the procedure will take 30 to 90 minutes longer. The extra time investment will depend on technical aspects related to the level of amputation and surgeon experience. Although an increase in surgical time of this length is associated with a slightly higher risk of infection, studies have not found more complications in patients undergoing acute TMR compared to those receiving standard care. The burden of the study is minimal, as participation only requires patients to fill out multiple online questionnaires at five evaluation moments (at 2 weeks, and at 3, 6, 9, and 12 months). Prophylactic TMR results in a reduction of the chance to develop PAP. The risks and the burden for patients are negligible.