Pre‐operative sciatic nerve block vs postoperative surgeon‐placed perineural stump catheter for prevention of phantom limb pain after below‐knee amputation

Phantom limb pain after major lower limb amputation occurs in up to 80% of patients. Around 60 treatments for phantom limb pain have been described, yet there remain few data to support optimal treatment or prevention [1]. In major limb amputation, nerve structures are transfected directly at the time of surgery, providing an anatomical target for intervention. Chemically blocking nerve structures before surgical transection could prevent peripheral pain input to the central nervous system, possibly circumventing the establishment of phantom limb pain. The uncontrolled study by Borghi et al. suggested sciatic nerve blockade before, and for a median of 30 days following lower limb amputation, may be associated with reduced phantom limb pain [2]. Ilfeld et al. showed in patients with established phantom limb pain, peripheral nerve blockade for 6 days reduced pain at 4 weeks and 6 months [3]. This single tertiary centre study aimed to determine whether pre- and postoperative regional analgesia (sciatic nerve block before surgery with a continuous sciatic nerve infusion for 5 days following surgery) reduces phantom limb pain following below-knee amputation, compared with a post-amputation surgically sited perineural sciatic catheter (continuous nerve sheath infusion for 5 days). The study was prospectively registered, with ethical and local approvals. Consecutive vascular patients for below-knee amputations were recruited and allocated randomly (1:1 fashion, concealed envelopes) by an independent investigator. The intervention group received a pre-operative sciatic nerve block (with 30 ml of bupivacaine 0.25%) and a continuous peripheral sciatic nerve catheter placed before surgery, with an infusion rate of 6–10 ml.h-1 bupivacaine 0.25% for 5 days. The control group had a postoperative perineural sciatic catheter placed following limb amputation, before wound closure. The block was established (with 30 ml of bupivacaine 0.25%) and the subsequent infusion was 3–5 ml.h-1 bupivacaine 0.5% for 5 days. The infusion regime enabled a low-volume infusion and provided an equivalent milligram dose of a local anaesthetic to both groups. The primary outcome measures were phantom limb pain at 5 days, 6- and 12 months following surgery, assessed using an adapted questionnaire from previous research in phantom limb pain outcomes [4]. Secondary outcomes were opioid consumption in oral morphine equivalents and mean pain scores (NRS) over the first 5 postoperative days. An a priori power calculation was conducted. This geographical region had a 70% incidence of phantom limb pain [4]. A 35% absolute risk reduction in phantom limb pain was determined as clinically significant. Whilst 30 patients in each group would be required (α 0.05 and β 0.8), due to high 1-year mortality in this patient population, a target of 40 patients per group was set. Mann–Whitney U, chi-squared tests or Student's t-test were used for statistical analysis with significance set at p < 0.05. Statistical analysis was completed in R (R Foundation for Statistical Computing, Vienna, Austria). Eighty participants were recruited (40 in each group, online Supporting Information Figure S1). Patient characteristics are summarised in Table 1. There was no difference in the incidence of phantom limb pain at 5 days (control 47.5% vs. intervention 40%), 6 months (42.5% vs. 47.5%) or 12 months (35.0% vs. 36.5%) (Fig. 1). Median (IQR [range]) postoperative oral morphine equivalents consumed were not different between groups (control 177.5 (23.8–347.5[0–1810]) mg vs. intervention 60.0 (17.2–432.5[0–1400])) mg. Pain scores (NRS) were lower in the intervention compared with the control group 4 h following surgery (control: 3 (0–5.8 [0–10]) vs. intervention: 0 (0–1 [0–9]); adjusted p = 0.03). There were no differences in pain scores between groups at other time-points in the first 48 h. The total amount of local anaesthetic delivered by catheters was comparable between groups (control mean (SD) 2132.3 mg (644.4 mg) vs. intervention 1899.5 mg (881.6 mg)) bupivacaine equivalents. The duration of local anaesthetic infusion (control mean (SD) 97.8 h (23.5 h) vs. intervention 98.5 h (34.5 h)) and patient-controlled analgesia use (control median (IQR [range]) 44.5 h (18.0–85.2[0–183]) vs. intervention 39.5 h (13.8–69.5[0–236])) did not differ between groups. Eight patients underwent subsequent above-knee amputations of the same leg for progression (control 5 (12.5%) vs. intervention 3 (7.5%)), all of whom died during study follow-up. During the trial 19 (23.8%) patients died within 12 months (control 10 (25.0%) vs. intervention: 9 (22.5%)), five during the index admission, nine between discharge and 6 months, and five between 6- and 12 months. While some effect of the pre-operative sciatic nerve is possible, as this is a small study, our results demonstrate that pre-operative peripheral nerve blockade does not cause a decrease in the incidence of phantom limb pain at 5 days, 6 or 12 months after below-knee amputation. Although no differences in long-term analgesic outcomes were detected, a pre-operative sciatica nerve block may have short-term analgesic advantages. The study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ACTRN12613000227796). No external funding or competing interests declared. Figure S1. CONSORT diagram of patient recruitment. Figure S2. Analgesic requirements between groups based on (A) intra-operative oral morphine equivalent doses; (B) postoperative patient-controlled analgesia oral morphine equivalent doses; and (C) local anaesthetic doses delivered via nerve catheters. Figure S3. Pain scores (NRS) after surgery. 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