Objective: To evaluate the impact of N-acetyl-cysteine (NAC) on amputation stump perfusion and healing in patients with critical limb-threatening ischemia (CLTI). Background: Patients with CLTI are at increased risk of poor amputation site healing leading to increased procedure-associated morbidity. Methods: In a pilot, double-blind, placebo-controlled, randomized controlled trial, patients with CLTI undergoing major elective lower extremity amputation were randomized 1:1 to intravenous NAC (1200 mg twice-daily) or placebo for up to 5 days postoperatively. Primary outcomes were change in stump perfusion at postoperative day 3 (POD3) and POD5, and healing at POD30. Stumps were serially evaluated for wound healing, and tissue perfusion was evaluated using noninvasive laser-assisted fluorescent angiography. Results: Thirty-three patients were randomized to NAC (n = 16) or placebo (n = 17). Thirty-one patients were eligible for intent-to-treat analysis (NAC14; placebo17). Twenty patients (NAC7; placebo13) had amputation stump perfusion defects at POD0 and were considered high-risk for poor healing. Intent-to-treat analysis revealed no significant differences between treatment groups. Subgroup analysis of high-risk patients revealed differences in stump perfusion defect size (NAC–0.53-fold, placebo +0.71–fold; 95% confidence interval -2.11 to–0.35; P < 0.05) and healing (NAC [100%], placebo [46%]; P < 0.01) between study treatments. Conclusions: Postoperative NAC administration may improve amputation stump perfusion and healing in patients with CLTI and tissue perfusion defects at the time of amputation. Intraoperative laser-assisted fluorescent angiogra-phy may help surgeons identify high-risk patients with stump perfusion defects and provide early adjunctive interventions. Future studies can further explore the therapeutic benefits of NAC in the healing and perfusion of other surgical operative sites in high-risk individuals.

Original languageEnglish
Pages (from-to)E302-E310
JournalAnnals of surgery
Issue number5
StatePublished - Nov 1 2022


  • Amputation
  • Critical limb threatening ischemia
  • N-acetyl-cysteine
  • Surgical healing
  • Tissue perfusion


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