Botulinum Toxin A and B Improve Perfusion, Increase Flap Survival, Cause Vasodilation, and Prevent Thrombosis: A Systematic Review and Meta-analysis of Controlled Animal Studies

Abstract

Background: A systematic review and meta-analysis of case-control animal model studies will help clarify the vascular effects of botulinum toxin (BTX). Methods: Preferred Reporting Items of Systematic reviews and Meta-Analyses guidelines were used to identify all animal case-control studies published before September 13, 2020, evaluating the vascular effects of BTX. Primary parameters included the following: perfusion, flap survival, arterial and venous dilation, and arterial and venous thrombosis. Results: Thirty-six studies with 1032 animals met the systematic review inclusion criteria. Twenty-nine studies had quantifiable data for statistical analysis. Statistically significant increases in perfusion with BTX over saline were detected within 1 day and sustained up to 8 weeks. The following represent weighted mean data from the meta-analysis. The administration of BTX has a 26% increase in both random pattern and pedicled flap survival area over controls. Botulinum toxin causes vasodilation. Botulinum toxin increases vessel diameter in arteries by 40% and in veins by 46% compared with saline controls. The administration of BTX reduces thrombosis by 85% in arteries and by 79% in veins compared with saline controls. Vascular effects were consistent across both BTX-A and BTX-B serotypes, multiple animal species, and various doses. No clear relationships between vascular effects and BTX pretreatment time were identified. Conclusions: Perivascular BTX administration intraoperatively or as a chemical delay pretreatment several days before surgery in multiple animal species and models shows multiple changes to the vascular system. Extrapolation of lessons learned from this systematic review and meta-analysis of animal models could expand research and clinical use of BTX in human vascular disease and surgery.