Efficacy and safety of epidural, continuous perineural infusion and adjuvant analgesics for acute postoperative pain after major limb amputation - a systematic review

Background and aims: Treatment of pain following major limb amputations is often a clinical challenge in a patient population consisting mainly of elderly with underlying diseases. Literature on management of acute post-amputation pain is scarce. We performed a systematic review on this topic to evaluate the efficacy and safety of analgesic interventions for acute pain following major limb amputation. Methods: A literature search was performed in PubMed, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews using the following key words: [(amputation) AND (pain OR analgesi* OR pain relief)] AND (acute OR postoperative). Randomized controlled studies (RCTs) and observational studies investigating treatment of acute pain following major amputations for any indication (peripheral vascular disease, malignant disease, trauma) were included. The review was performed according to the standards described in the PRISMA statement. The Cochrane quality assessment tool was used to evaluate the risk of bias in the RCTs. Results: Nineteen studies with total of 949 patients were included. The studies were generally small and heterogeneous on outcomes, study designs and quality. There were 16 studies on epidural or continuous perineural analgesia CPI). Based on five RCTs (n = 268) and two observational studies (n = 49), epidural analgesia decreased the intensity of acute stump pain as compared to systemic analgesics, during the first 24 h after the operation. Based on one study epidural analgesia caused more adverse effects like sedation, nausea and motor block than continuous perineural local anesthetic infusion. Based on one RCT (n = 21) and eight observational studies (n = 501) CPI seemed to decrease opioid consumption as compared to systemic analgesics only, on the first three postoperative days, and was well tolerated. Only three trials investigated systemic analgesics (oral memantine, oral gabapentine, iv ketamine). Ketamine did not decrease acute pain or opioid consumption after amputation as compared to other systemic analgesics. Gabapentin did not decrease acute pain when combined to epidural analgesia as compared to epidural analgesia and opioid treatment, and caused adverse effects. Conclusions: The main finding of this systematic review is that evidence regarding pain management after major limb amputation is very limited. Epidural analgesia may be effective, but firm evidence is lacking. Epidural causes more adverse effects than CPI. The results on efficacy of CPI are indecisive. The data on adjuvant medications combined to epidural analgesia or CPI is limited. Studies on efficacy and adverse effects of systemic analgesics for amputation pain, especially concentrating on elderly patients, are needed.