Topical nitroglycerin is associated with a reduced mastectomy skin flap necrosis-systematic review and meta-analysis

The flap necrosis rate remains high despite the advancement of technology in daily practices. Several randomized trials of topical Nitroglycerin (NTG) have shown promise in reducing flap necrosis. We aim to evaluate the efficacy and safety of topical NTG in preventing flap failure based on existing databases.

We searched through PubMed, EuropePMC, EBSCOhost, Cochrane CENTRAL database, Clinicaltrials.gov, and hand sampling for "flap survival", "topical nitroglycerin", and "flap perfusion".

With a total of 6947 patients from 3 RCT and 2 retrospective cohorts, NTG was shown to prevent flap failure in mastectomy flaps by NTG with an OR 0.23 [0.10, 0.53]; p < 0.001), I² 73%. Upon sensitivity analysis to reduce heterogeneity, the OR was 0.17 [0.07, 0.40]; p < 0.001, I² 52%. Upon subgroup analysis of RCT, the OR was 0.17 [0.10, 0.30]; p < 0.001, I² 50%. Newer studies subgroup had OR 0.48 [0.33, 0.70]; p<0.001; I² 46. Upon subgroup analysis of single application only, the OR for flap necrosis was 0.36 [0.18, 0.73]; p = 0.005, I² 67% and subgroup analysis repeated application had an OR of 0.05 [0.01, 0.21]; p < 0.001, I² 14%.

Nitroglycerin seemed to be an ideal agent to increase the chance of flap survival in mastectomy flaps. It has an excellent safety profile, hence, is suitable for empiric use. More randomized controlled trials comparing different regiments and other preparations are needed to conclude whether repeated application at a low dose is most effective, and whether the success is reproducible on other types of flaps.