Efficacy and safety of topical nitroglycerin in the prevention of mastectomy flap necrosis: a systematic review and meta-analysis

Abstract

Flap necrosis is a common complication after mastectomy, and nitroglycerin (NTG) ointment has been used successfully to treat it. However, it is not clear whether topical NTG can completely prevent the occurrence of flap necrosis after breast cancer surgery, and it is also unclear whether this treatment may cause side effects. Three randomized controlled trials (RCTs) and two retrospective cohort studies (RCSs) were included in our investigation. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We found that NTG significantly reduced the rates of mastectomy flap necrosis, full-thickness flap necrosis, and debridement as well as the rate of early complications other than flap necrosis. However, there was no significant difference in drug-related adverse reactions, explantation, superficial flap necrosis, infection, hematoma or seroma between the NTG and placebo groups. Flap-related complications are extremely common after breast surgery, among them, flap necrosis is the most serious and leads to a poor prognosis. In the literature, the reported rates of mastectomy flap necrosis (MFN) range from 5% to 30% 1-9. The rate may continue to rise as nipple-sparing mastectomy and immediate breast reconstruction (IBR) become more prevalent in young breast cancer patients, although there is some evidence that the risks of flap necrosis and implant failure are higher in IBR than in mastectomy alone 10. Nitroglycerin (NTG) effectively increases local blood flow by dilating arteries and veins without altering the ratio of precapillary to postcapillary resistance. Many studies have shown that NTG treatment may improve the survival of random-pattern skin flaps by increasing local blood flow 11-13. Nonetheless, not all studies confirm the utility of NTG in skin flap preservation. Several scholars have found that daily application of NTG slow-release pads offer no greater flap survival than a control treatment 14-17. Furthermore, some of the side effects of NTG may limit its use. However, Ricci has argued that NTG is safe and effective and does not increase the occurrence of side effects 18. Given the lack of consensus on the use of NTG to prevent MFN, the purpose of this meta-analysis is to determine the efficacy and safety of NTG for the prevention of MFN. Debridement is an important solution to skin flap necrosis, but it causes psychological and physical trauma to patients. Further attention should be paid to the debridement rate after mastectomy, especially after IBR, in which circumstances it may cause the tissue expander/implant to be lost. Unfortunately, some studies have suggested that NTG cannot reduce the rate of debridement after IBR 19-21. Hence, another purpose of this article is to determine whether NTG can reduce the flap debridement rate after mastectomy.

Systematic Review of Patient Safety and Quality Improvement Initiatives in Breast Reconstruction

“…Our review also showed the potential for nitroglycerin to increase flap survival while decreasing skin flap necrosis. These results are similar to previous studies looking at nitroglycerin on skin flaps, including a meta-analysis by Wang and colleagues 65 that reveals a reduction in rates of flap necrosis. Finally, in keeping with the large body of anesthesia literature, 66 we found that nerve blocks were an effective approach to reducing postoperative pain.…”

Topical Dimethyl Sulfoxide for Congested Nipple–areolar Complexes in Breast Surgery: A Pilot Study

“…Topical NTG has been well studied in the prevention of mastectomy flap necrosis, with a recent meta-analysis showing that NTG significantly improved rates of full-thickness flap necrosis over placebo, but did not prevent superficial flap necrosis (ie, congestion). 4 The studies included in that meta-analysis tested NTG as a preventative measure administered to all patients following mastectomy, not as an intervention for threatened flaps. Dent et al studied the use of NTG in the treatment of 65 cases of NAC ischemia following nipple-sparing mastectomy, reporting a 100% or 71% salvage rate for partial-thickness or full-thickness ischemia, respectively.…”

Experimental study of the effects of nitroglycerin, botulinum toxin A, and clopidogrel on bipedicled superficial inferior epigastric artery flap survival

“…Nitroglycerin effectively causes vasodilatation by releasing nitric oxide leading to vascular smooth muscle relaxation and increased tissue perfusion with a main action on the veins, hence increasing the salvage response of the skin flaps 35 , 36 . Another known desirable effect is that nitroglycerin exerts an antithrombotic action 37 .…”

“…It is known that nitroglycerin ointment has a potent local vasodilator effect and increases the local blood flow that could potentially improve flap survival, although it is not popularly used for preventing skin flap necrosis, possibly due to the lack of effect shown in some studies 6 , 7 . However, others have shown desirable results on flap survival in both humans and animals 8 – 10 .…”