Research Paper Title

The Impact of Surgical Amputation and Valproic Acid on Pain and Functional Trajectory: Results from the Veterans Integrated Pain Evaluation Research (VIPER) Randomized, Double-Blinded Placebo-Controlled Trial.

Background

To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery.

Methods

A multi-centre, randomised, double-blind, placebo-controlled trial in academic, military, and veteran medical centres. One hundred twenty-eight patients undergoing amputation or amputation revision surgery at Duke University Hospital, Walter Reed National Military Medical Centre, or the Durham Veterans Affairs Medical Centre for either medical disease or trauma.

Patients were randomised to placebo or valproic acid for the duration of hospitalisation and treated with multimodal analgesic care, including regional anaesthetic blockade.

Primary outcome was the proportion of patients with chronic pain at three months (average numeric pain score intensity of 3/10 or greater). Secondary outcomes included functional trajectories (assessed with the Brief Pain Inventory short form and the Defense and Veterans Pain Rating Scale).

Results

The overall rate of chronic pain was 68.2% in the 107 patients who completed the end point assessment. There was no significant effect of perioperative valproic acid administration, with a rate of 65.45% (N = 36) in the treatment group and a rate of 71.15% (N = 37) in the placebo group.

Overall, pain scores decreased from baseline to follow-up (median = -2 on the numeric pain scale). Patients additionally experienced improvements in self-perceived function.

Conclusions

The rate of chronic pain after amputation surgery is not significantly improved with the perioperative administration of valproic acid. In this cohort treated with multi-modal perioperative analgesia and regional anaesthetic blockade, we observed improvements in both pain severity and function.

Reference

Buchheit, T., Hsia, H.J., Cooter, M., Shortell, C., Kent, M., McDuffie, M., Shaw, A., Buckenmaier, C.T. & Van de Ven, T. (2019) The Impact of Surgical Amputation and Valproic Acid on Pain and Functional Trajectory: Results from the Veterans Integrated Pain Evaluation Research (VIPER) Randomized, Double-Blinded Placebo-Controlled Trial. Pain Medicine (Malden, Mass.). pii: pnz067. doi: 10.1093/pm/pnz067. [Epub ahead of print].