A Single Postoperative Application of Nitroglycerin
Ointment Does Not Increase Survival of Cutaneous Flaps
and Grafts
Cary L. Dunn, MD,* David G. Brodland, MD,* Robert D. Griego, MD,†
Michael J. Huether, MD,‡ Michael J. Fazio, MD,§ and John A. Zitelli, MD*
*Shadyside Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, †Scottsdale, Arizona,
‡Tucson, Arizona, and §Sacramento, California
background. Nitroglycerin is a vasodilator that has been re-
ported to improve cutaneous flap and graft survival. It has not
been tested in controlled studies.
objective. We designed our study to test the effectiveness of a
single postoperative application of nitroglycerin on flap and
graft survival.
methods. Eighty-eight surgical repairs received topical nitro-
glycerin and 85 received control ointment (polysporin). Treat-
ment sites were evaluated on postoperative day 7 and assigned
a percentage of surface area survival.
CUTANEOUS FLAP AND graft necrosis is an adverse
event that can lead to a negative cosmetic outcome, in-
fection, and reoperation. Skin flap failure has been at-
tributed to multiple factors, including arteriovenous
blood shunting, decreased arterial flow, and venous
sludging.1 Nitroglycerin (NTG) is a potent topical va-
sodilator that increases local blood flow by dilating
arteries and veins without altering the ratio of pre- to
postcapillary resistance.2 It has been assumed that by
increasing local blood flow, postoperative nitroglyc-
erin use will lead to enhanced skin flap survival.
Several investigators evaluated the effect of topical
NTG on skin flap survival, with mixed results. In ani-
mal models, Rohrich et al.3 and Davis et al.4 found
that frequent postoperative application of topical NTG
prevented skin necrosis. Lehman et al.5 reported simi-
lar findings in human neonates following neurosurgi-
cal procedures. Fan and Jinli6 reported that a single
application of NTG prevented skin flap necrosis in
women following radical breast cancer resection. Scheuer
and Hanna7 found that NTG enhanced blood flow to
distal flap skin (by fluorescein flow analysis) in humans,
C.L. Dunn, MD, D.G. Brodland, MD, R.D. Griego, MD, M.J.
Huether, MD, M.J. Fazio, MD, and J.A. Zitelli, MD have indicated no
significant interest with commercial supporters.
Address correspondence and reprint requests to: Cary L. Dunn, MD,
2032 Hawthorne St., Sarasota, FL 34239.
© 2000 by the American Society for Dermatologic Surgery, Inc. • Published by Blackwell Science, Inc.
ISSN: 1076-0512/00/$15.00/0 • Dermatol Surg 2000;26:425–427
results. There was no significant difference in the complica-
tion rate of flaps and grafts treated with nitroglycerin (12.5%)
compared with those treated with control ointment (8.4%)
(P ⫽ .244). Subset analysis of flaps as a group and grafts as a
group were not meaningful because the complication rates were
so low.
conclusion. There is no survival increase of flaps and
grafts treated with a single application of nitroglycerin oint-
ment.
and that flap necrosis was less likely in children under-
going meatoplasty/glanduloplasty when treated with a
single postoperative application of NTG. However,
not all studies confirm the utility of NTG in skin flap
preservation. Nichter et al.8 found that daily applica-
tion of NTG slow release pads offered no greater flap
survival than controls.
We designed our study to test the efficacy of a sin-
gle immediate postoperative application of topical
NTG 2% ointment to skin flaps and grafts. We chose
this regimen for several reasons. First, a single postop-
erative application of topical NTG has been reported
to be effective in skin flap preservation in published
reports. Second, serial application (every 6 hours) of
NTG to flaps and grafts would change our own stan-
dard postoperative wound care regimen, which in-
volves continual wound occlusion (sterile dressing) for
7 days. Third, NTG ointment was chosen over NTG
patches because we were concerned that adhesive
patches might injure the sutured edge of flaps and
grafts when removed.
Materials and Methods
All patients enrolled in the study were adults in the immedi-
ate postoperative period following Mohs micrographic sur-
gical excision of cutaneous malignancies. Only wounds re-
paired with flaps or grafts were enrolled in the study. The
426 dunn et al.: nitroglycerin ointment Dermatol Surg 26:5:May 2000

Table 1. Table 3. Graft Complications

Nitroglycerin Control Nitroglycerin Control

Closures (n ⫽ 88) (n ⫽ 85)
Epidermal necrosis 10 2
FTSG 67 62 ⬎25% necrosis 0 1
STSG 4 2 ⬎50% necrosis 0 1
Transposition 7 8 Total necrosis 1 0
Bilobe 4 6 Overall graft complications 11/71 (15.5%) 4/64 (6.2%)
A-T advancement 2 0
Island pedicle 4 7

ence in the complication rate for wounds treated with

patients were required to return 1 week after surgery for
evaluation of their surgical site. At the 1-week postoperative
evaluation, we inspected the grafts/flaps for signs of failure
(necrosis, color changes suggestive of nonviability). We de-
clared a pink or skin-toned repair to be viable and did not
reevaluate these patients other than per our usual protocol.
If at the 1-week postoperative evaluation we found any flap/
graft to be at risk for failure (purple, black, or partially ne-
crotic), we reevaluated the patient on the third postopera-
tive week. The 3-week postoperative evaluation served as
the final evaluation, and at that point we assigned a percent-
age survival value to the flap/graft.
A total of 168 patients with 173 tumors were enrolled in
four separate clinics that specialize in Mohs micrographic
surgery and surgical reconstruction. We randomly assigned
patients in a double-blind fashion to receive either topical
NTG 2% ointment (less than 1 cm strip) or the same
amount of control ointment (polysporin). The ointments
were applied immediately following surgical reconstruction
of wounds created by the removal of cutaneous malignan-
cies by Mohs micrographic surgery.
Results
Eighty-eight wounds received NTG ointment and 85
received control ointment. The distribution of wound
closure type is shown in Table 1.
The overall complication rate of any kind for flaps
and grafts was low (18/173 ⫽ 10.4%). Surgical re-
pairs treated with NTG had a complication rate of
12.5% and repairs treated with polysporin had a com-
plication rate of 8.2% (Table 2). There was no differ-
Table 2. Total Flap and Graft Complications
Nitroglycerin Control
(n ⫽ 88) (n ⫽ 85)
NTG compared to control ointment (P ⫽ .36) (Table 2).
Skin grafts did not benefit from topical application
of NTG. Eleven of the 71 grafts treated with NTG de-
veloped complications, as did 4 of the 64 grafts
treated with polysporin. Due to the small number of
complications occurring in grafts, the normal approxi-
mation may be inaccurate. With this in mind, the two
proportions were compared and there appears to be
no significant difference (P ⫽ .088 at 95% CI) (Table 3).
The sample size for flaps treated with each oint-
ment is too small to perform meaningful tests. In our
study, there were no complications in the NTG group
and only three instances of tip necrosis in the control
group (Table 4).
Discussion
In our study, a single postoperative application of
NTG was no more effective than control ointment in
preventing flap and graft complications. There are sev-
eral possible explanations for NTG’s ineffectiveness in
our study. Since NTG’s effect as a vasodilator is short
lived (less than 24 hours), it may be that the single ap-
plication of NTG does not enhance blood flow to the
area surrounding FTSGs at a time when it would be
helpful. Since our practice is to bolster all grafts with
tie-over dressings, we would not be able to apply
NTG directly to the graft on a frequent basis postop-
eratively. It might be worth testing the more frequent
(every 6 hours) application of NTG to the area sur-
rounding the bolster in future studies.
Skin flap complication rate was low overall. Total
flap failure did not occur in our study. The relatively
minor complication of tip necrosis occurred only in
controls. Because the number of cases with complica-
tions was so low, it is not reasonable to attribute the
complications to the type of ointment employed. There

Epidermal necrosis 10 2
⬎25% necrosis 0 1 Table 4. Flap Complications
⬎50% necrosis 0 1
Nitroglycerin Control
Total necrosis 1 0
Tip necrosis 0 3 Tip necrosis 0 3
Total complications 11 7 All other complications 0 0
Dermatol Surg 26:5:May 2000
is no statistically significant difference between flap
complications when NTG is compared to control. Be-
cause the complication rate with small facial skin flaps
is so low, only very large sample groups would allow
detection of an effective preventive treatment.
In summary, we found no benefit in the use of NTG
to prevent complications in facial flap and graft sur-
gery. Further studies may need to focus on high-risk
patients since the overall complication rate in unse-
lected patients is so low. Smokers, for example, may
have a higher complication rate than other patients
and could be selectively tested.
References
1. Kerrigan CL. Skin flap failure: pathophysiology. Plast Reconstr Surg
1983;72:766–74.
Commentary
The complication rate for grafts and local flaps in dermatologic
surgery is low, which makes studies of methods to further de-
crease this rate difficult. This study is an important effort to eval-
uate a possible method of increasing flap and graft survival in der-
matologic surgery. Unfortunately it finds no benefit in the use of
topical nitroglycerin ointment in this setting. This overall analysis
is made by including both flaps and grafts as a single group, pro-
ducing an aggregate that yields no significant difference in com-
plication rates. Although this conclusion is supportable, subgroup
analysis points to a possible short-term detrimental effect (epider-
mal necrosis in 10 of 71 with NTG versus 2 of 64 for the control)
with the treatment of grafts with nitroglycerin ointment and a
possible benefit with regards to tip necrosis (0 of 19 with NTG
dunn et al.: nitroglycerin ointment 427
2. Needelman P, Corr PB, Johnson EM. Drugs used for the treatment
of angina: organic nitrates, calcium channel blockers, and beta-
adrenergic antagonists. In: Gilman AG, et al., eds. The Pharmaco-
logical Basis for Therapeutics, 7th ed. New York: MacMillan, 1985;
806–26.
3. Rohrich RJ, Cherry GW, Spira M. Enhancement of skin-flap sur-
vival using nitroglycerine ointment. Plast Reconstr Surg 1984;76:
943–48.
4. Davis RE, Wachholz JH, et al. Comparison of topical anti-ischemic
agents in the salvage of failing random-pattern skin flaps in rats.
Arch Facial Plast Surg 1999;1:27–32.
5. Lehman RAW, Page RB, et al. Technical note: use of nitroglycerin
ointment after precarious neurosurgical wound closure. Neurosur-
gery 1985;16:701–2.
6. Fan Z, Jinli H. Preventing necrosis of the skin flaps with nitroglycer-
ine after radical resection for breast cancer. J Surg Oncol 1993;53:
210.
7. Scheuer S, Hanna MK. Effect of nitroglycerine ointment on penile
skin flap survival in hypospadias repair. Urology 1986;28:438–40.
8. Nichter LS, Sobieski BA, Edgerton MT. Efficacy of topical nitroglyc-
erine for random-pattern skin-flap salvage. Plast Reconstr Surg
1985;75:847–52.
versus 3 of 21 for the control) in the treatment of flaps with nitro-
glycerin ointment. However, by the authors’ analysis, neither of
these suggestions is statistically supportable. This study should
not lead us to abandon the search for topical medications, includ-
ing nitroglycerin ointment, which might help decrease complica-
tion rates or to embrace the use of a medication which appears to
have a numerical benefit in certain circumstances, though not sta-
tistically significant. Rather we should heed the advice of the au-
thors and design additional studies that include larger numbers of
patients or select patients with a higher risk of complications.
Thomas Stasko, MD
Nashville, Tennessee