Abstract
BACKGROUND: Phantom limb pain (PLP) is a debilitating condition leading to the experience of pain in a limb that has been amputated. Pharmacological interventions have been proposed to prevent chronic PLP. However, results of these interventions are still controversial. This systematic review and meta-analysis clarifies the effectiveness of preemptive pharmacological interventions in prevention of chronic phantom pain by evaluating incidence and intensity of PLP, residual limb pain (RLP), quality of life (QoL), depression, and anxiety. METHODS: We systematically searched the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases for published randomized clinical trials with the outcomes of incidence and intensity for PLP, RLP, QoL, depression, and anxiety in amputation candidates due to any reason. We used the Risk of Bias tool (ROB2) to assess the quality of evidence. Relative risks and mean differences were calculated by a fixed-effects model, and sensitivity analysis was conducted post-hoc for risk of bias. We presented the results using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tables. RESULTS: Overall, 20 studies were found to address outcomes of interest at 6 months or longer. In 18 studies, intervention was planned for lower limb amputations. Peripheral vascular disease was the most studied cause for amputation. Intervention showed a mean reduction of 0.63 (0.10- 1.15) in 6-month intensity of PLP with low certainty of evidence. Evidence for Ketamine, Gabapentin, Valproic Acid, Calcitonin, Amide local anesthetics such as bupivacaine via epidural and perineural catheters did not support reduction in PLP. CONCLUSION: Imprecision due to small sample sizes, inadequate blinding, and publication bias downgraded the quality of evidence in this clinical scenario. Overall, preemptive perioperative pharmacological interventions do not seem to prevent phantom pain or stump pain compared with conventional perioperative pain control methods. Further robust studies are required for the effectiveness of Memantine in the prevention of chronic PLP.