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Wang AS, Armstrong EJ, Armstrong AW.

Corticosteroids and wound healing: clinical
considerations in the perioperative period

ARTICLE in AMERICAN JOURNAL OF SURGERY · JUNE 2013

Impact Factor: 2.29 · DOI: 10.1016/j.amjsurg.2012.11.018 · Source: PubMed

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The American Journal of Surgery (2013) -, -–-

Corticosteroids and wound healing: clinical considerations

in the perioperative period
Audrey S. Wang, M.D.a,*, Ehrin J. Armstrong, M.D., M.Sc.b,
April W. Armstrong, M.D., M.P.H.a

a
Department of Dermatology, University of California, Davis, 3301 C Street, Suite 1400, Sacramento, CA 95816;
b
Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, 4860 Y Street,
Suite 2820, Sacramento, CA 95817

KEYWORDS: Abstract
Corticosteroids; BACKGROUND: Determining whether systemic corticosteroids impair wound healing is a clinically
Wound healing; relevant topic that has important management implications.
Perioperative METHODS: We reviewed literature on the effects of corticosteroids on wound healing from animal
and human studies searching MEDLINE from 1949 to 2011.
RESULTS: Some animal studies show a 30% reduction in wound tensile strength with perioperative
corticosteroids at 15 to 40 mg/kg/day. The preponderance of human literature found that high-dose cor-
ticosteroid administration for ,10 days has no clinically important effect on wound healing. In patients
taking chronic corticosteroids for at least 30 days before surgery, their rates of wound complications
may be increased 2 to 5 times compared with those not taking corticosteroids. Complication rates
may vary depending on dose and duration of steroid use, comorbidities, and types of surgery.
CONCLUSIONS: Acute, high-dose systemic corticosteroid use likely has no clinically significant
effect on wound healing, whereas chronic systemic steroids may impair wound healing in susceptible
individuals.
Ó 2013 Elsevier Inc. All rights reserved.

The effects of corticosteroids on wound healing have
been a topic of great interest among surgeons, internists, and
dermatologists. Within the past century, pivotal discoveries
in the mechanisms of wound healing have enhanced our
understanding of the molecular interactions between corti-
costeroids and cutaneous wounds.1–11 These basic science
discoveries, coupled with findings from clinical studies,
have highlighted several important considerations regarding
This work was not supported by any funding sources. The authors
declare no conflicts of interest.
* Corresponding author.
E-mail address: audrey.wang@ucdmc.ucdavis.edu
Manuscript received June 25, 2012; revised manuscript November 1,
2012
perioperative corticosteroid administration, namely, dosing,
chronicity, and timing relative to surgery.
In 1949, Hench et al12 revolutionized the treatment
of rheumatologic patients when they reported dramatic
improvement of rheumatoid arthritis symptoms in pati-
ents treated with 50 to 100 mg of 17-hydroxy-11-
dehydrocorticosterone daily. The following year, they
were awarded the Nobel Prize in Medicine for this ‘‘medi-
cal miracle.’’ Since then, systemic corticosteroids have
been used to treat various inflammatory conditions, includ-
ing rheumatoid arthritis, temporal arteritis, gout, and in-
flammatory bowel disease, which may require surgical
management.
Importantly, the initial report from Hench et al12 did not
describe wound healing concerns, but subsequent clinical

0002-9610/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjsurg.2012.11.018
2 The American Journal of Surgery, Vol -, No -, - 2013
reports noted potential adverse effects of corticosteroids on
wound healing.13 Later studies in animal models also
showed corticosteroid-induced wound healing impairment
at high doses.14–27 Thus, when patients on systemic cortico-
steroids require surgical procedures, concerns may arise re-
garding postoperative wound complications.
This article reviews the three aspects of the effects of
corticosteroids on wound healing. First, the mechanisms of
normal wound healing will be summarized, followed by an
overview of the molecular interactions between corticoste-
roids and the wound healing process in the context of a
cutaneous wound. Second, data regarding the effects of
corticosteroids on wound healing in animal models and
humans will be presented. Finally, dosing, chronicity, and
timing of corticosteroid administration relative to surgery
will be discussed.
Corticosteroid structure and function
Corticosteroids are lipophilic molecules derived from
the endogenous hormone cortisol that diffuse into cells,
then bind to and activate glucocorticoid receptors (GRs).
Activated GRs dimerize and diffuse into the nucleus, where
they drive or inhibit gene transcription by binding to gluco-
corticoid response elements present in the promoter re-
gions of target genes. Structural alterations of the cortisol
backbone result in corticosteroids with varying tissue distri-
bution, rate of hepatic metabolism, and affinity for the GR.28
Molecular mechanisms of corticosteroids and
their effects on wound healing
Corticosteroids have been shown to affect all major steps
of the wound healing process,29,30 which is somewhat arbi-
trarily divided into 3 phases: inflammatory, proliferative,
and remodeling. In reality, these 3 phases overlap signifi-
cantly, and signaling cascades initiated in 1 phase influence
cell growth and differentiation in later phases.31
Inflammatory phase. Immediately after wounding, plate-
lets and the coagulation cascade initiate primary and
secondary hemostasis. During primary hemostasis, platelets
release numerous cytokines, including transforming growth
factor-ß (TGF-ß), which trigger the subsequent production
of additional growth factors, such as basic fibroblast growth
factor 2, from nearby cells. The fibrin mesh scaffold
established during secondary hemostasis acts as a reservoir
for growth factors and provides a matrix for future tissue
deposition.32 In addition, cellular membrane-bound recep-
tors, such as intercellular adhesion molecule 1 (ICAM-1), fa-
cilitate recruitment of inflammatory cells.33 Within minutes
of injury, neutrophils arrive.34 Then, over the course of 2 to 3
days, macrophages become predominant.9 Treatment with
the corticosteroid dexamethasone decreases the expression
of cytokines, including TGF-b1, platelet-derived growth
factor, tumor necrosis factor, and interleukin-1a in wounded
tissue and may thereby decrease the chemotactic and mito-
genic stimulus for other inflammatory cells.1,8 Dexametha-
sone also downregulates endothelial cell expression of
intercellular adhesion molecule 1 (ICAM-1) in culture and
in healing colonic anastomoses, resulting in attenuated gran-
ulocyte adhesion and migration.4,11 Consistent with this
finding, high-dose corticosteroids reduce the extent of mac-
rophage infiltration into the wound.9
Proliferative phase. Platelets and macrophages from the
inflammatory phase establish the growth factor and cyto-
kine milieu that drives angiogenesis, fibroplasia, and re-
epithelialization during the proliferative phase.32 Following
construction of the framework of extracellular matrix and
new blood vessels, epithelial cells from the basal layer
migrate across the basal lamina.35,36 Re-epithelialization,
stimulated by keratinocyte growth factor (KGF),37 is also
dependent upon plasmin and matrix metalloproteinases to
digest the leading edge of the fibrin clot.38 Corticosteroids
reduce TGF-ß levels and mesenchymal cell expression of
keratinocyte growth factor (KGF), which attenuates fibro-
blast proliferation5 and impairs wound re-epithelialization.2
Remodeling phase. During remodeling, the wound un-
dergoes contraction and alters its collagen expression
pattern. Myofibroblasts facilitate wound contraction via
TGF-ß1 stimulation.39,40 Collagen remodeling requires col-
lagen digestion and a switch from type III collagen in the
wound to type I collagen.3,10 Animal studies suggest that
corticosteroids impair collagen turnover,3,10 disrupt der-
mal–epidermal junctional interactions,7 and decrease the
tensile strength of cutaneous wounds by reducing collagen
accumulation.6,41
Notably, the mechanisms described above occur in the
setting of acute wound healing, but corticosteroids have
systemic and possibly indirect effects as well, which are
less well understood. Insights into these processes could
promise new therapeutics, including steroids that retain
anti-inflammatory properties but have minimal adverse
effects on wound healing.
Clinical effects of corticosteroids on wound
healing
In the same year that Hench et al12 described their
‘‘medical miracle,’’ Ragan et al13 documented impaired
wound healing in 3 of 8 rheumatoid arthritis patients treated
with 25 U/day of adrenocorticotropic hormone (roughly
equivalent to 75 mg/day of prednisone). Specifically, these
patients developed a nonhealing biopsy site, a nonhealing
episiotomy site and decubitus ulcer, and nonhealing abscess
drainage sites. In 2 of these patients, the wounds quickly
granulated within 4 days of discontinuing adrenocorticotro-
pic hormone treatment. These findings led to subsequent
studies to better evaluate the effects of corticosteroids on
wound healing. Below, data from animal models, patients
with Cushing syndrome, and clinical studies are reviewed.
A.S. Wang et al. Corticosteroids and wound healing 3

Effect of corticosteroid dose on wound healing
A number of animal studies have quantified the effects
of high-dose corticosteroids on wound tensile strength and
anastomotic bursting pressures (Table 1).14–27 Comparing
these animal studies as a group is challenging because of
differences in methodology, internal controls, and measure-
ment of wound strength. Overall, these studies converge on
an approximately 30% reduction in wound tensile strength
at cortisone doses of 15 to 40 mg/kg/day, equivalent to ap-
proximately 200 to 560 mg/day of prednisone in a 70-kg
person (Table 1), but these results cannot be generalized
to other species. For example, cortisone dramatically de-
creases wound tensile strength in rats but has no effect at
equivalent doses in guinea pigs.42 Indeed, human studies
should ultimately provide evidence for clinical decision
making.
Patients with Cushing syndrome are chronically exposed
to excess adrenocorticoids and provide the closest human
correlate to these animal studies. Compared with a healthy
human population, 5 patients with Cushing syndrome dem-
onstrated a 40% reduction in cutaneous wound tensile
strength.43,44 Notably, 1 patient’s tensile strength improved
after adrenal resection. These findings suggest that cortico-
steroid excess may adversely affect wound healing in hu-
mans; however, these patients are chronically exposed to
high doses of cortisol, whereas in clinical practice, the doses
are usually smaller and may be given on an acute or chronic
basis. Additionally, although a retrospective case series
described increased wound complication rates in patients
with Cushing syndrome, the absolute risk appeared to be
small, even with open procedures requiring large incisions.45
Furthermore, wound disruption or dehiscence, rather than
wound tensile strength, should be considered more clinically
relevant outcome measures.
Effect of chronicity of corticosteroid
administration on wound healing
Since the duration of systemic corticosteroid exposure
may affect wound healing, the effects of acute and chronic
corticosteroid administration are compared below for
various indications.
Acute administration. The inflammatory response that
occurs shortly after myocardial infarction is analogous to
creation of an acute wound that heals over the course of
days to weeks; thus, limiting the extent of postinfarct
inflammation may improve subsequent outcomes. Initial
studies performed in the 1960s and 1970s yielded conflict-
ing results. Some studies suggested as much as a 50%
mortality reduction with high-dose cortisone,46–48 while
others suggested no benefit on mortality or an increase in
myocardial infarction (MI) extent and higher risk of ven-
tricular aneurysm.9,49–51 In all of these studies in which in-
itiation of treatment ranged from within 6 to 72 hours after
symptom onset, a large dose of prednisone (.100 mg/day)
for at least 10 days was required for a therapeutic or toxic
effect. In 2003, a meta-analysis of high-dose corticosteroids
at the time of myocardial infarction (MI) suggested a slight
decrease in mortality associated with high-dose corticoste-
roids, but the result was statistically insignificant when con-
sidering randomized controlled trials only.52 More recently,
a Cochrane review of 54 randomized studies concluded that
prophylactic corticosteroids in adult cardiac surgery pa-
tients provide no mortality benefit.53 Importantly, the

Table 1 Effect of acute corticosteroid administration on wound tensile strength in animals

Study (Ref) Animal Drug Dose (mg/kg/day) Wound type Outcome measure Change (%)
Howes et al, 1950 21
Rat C 40 I TS 238
Findlay & Howes, 195218 Rabbit C 1.5 I TS 0
Meadows & Prudden, 195324 Rat C 4, 20, 100 I BD 230, 236, 265
Pearce et al, 196025 Rat C 20 I TS 245
Hinshaw et al, 196120 Rabbit C 12.5 I BD 0
Sandberg, 196427 Rat C 40 I TS 230
Ehrlich & Hunt, 196817 Rat C 25 I TS 230
McNamara et al, 196923 Rat Dex 6 I TS 0
Dostal & Gamelli, 199016 Mouse Dex 16 I TS 259
Dostal & Gamelli, 199016 Mouse C 400 I TS 268
Dostal & Gamelli, 199016 Mouse MP 80 I TS 0
Aszodi & Ponsky, 198414 Rat C 5 A BP 224
Cali et al, 199315 Rat C 5 A BP 0
Mastboom et al, 199122 Rat MP 2.5, 10 A BP 0, 0
Phillips et al, 199226 Rabbit Dex .1 A BP 246
Furst et al, 199419 Rat C 15 A BP 233
In all of these studies, animals were given corticosteroids within 1 week prior to surgery and then daily after surgery until the time of outcome
measure determination. In each case, the outcome measure was determined within 7 days after wounding.
A 5 anastomosis; BD 5 balloon disruption; BP 5 bursting pressure; C 5 cortisone; Dex 5 dexamethasone; I 5 incision; MP 5 methylprednisolone;
TS 5 tensile strength.
4 The American Journal of Surgery, Vol -, No -, - 2013

authors noted no significant increase in postoperative infec-
tion or impairment of wound healing.
Likewise, patients with suspected temporal arteritis may
receive corticosteroids (usually 40 to 60 mg/day of predni-
sone) shortly before undergoing temporal artery biopsy. In a
large case series of patients with suspected temporal arteri-
tis, 237 individuals underwent 250 temporal artery biop-
sies.54 Corticosteroids were given to 178 (75%) of these
patients preoperatively, with a mean preoperative duration
of 7.3 6 2.0 days. There were no biopsy-related complica-
tions.54 More recently, Younge et al55 reviewed the records
of 1,113 patients who underwent temporal artery biopsy
for suspected temporal arteritis. Twenty percent of these
patients were on corticosteroid therapy at the time of the
procedure, but none experienced serious complications.55
Other case series in the literature have not reported the com-
plication rate, if any, of temporal artery biopsy and its rela-
tionship to preoperative prednisone administration.
To date, only 1 randomized, double-blind, placebo-
controlled trial has addressed the effects of acute, preop-
erative corticosteroid administration on cutaneous wound
healing.56 In this study of 24 patients, a single dose of 30
mg/kg methylprednisolone or placebo was administered
intravenously 90 minutes prior to colon resection. Among
the 12 patients in the treatment group, only 1 patient devel-
oped a wound dehiscence, while 2 patients in the placebo
group developed a dehiscence. No wound infections oc-
curred in the treatment group, but 1 infection required
surgical debridement in the placebo group. For direct tissue
evaluation, a small subcutaneous wound was created on
each patient’s upper arm. Proline levels in the collagen
and the amount of collagen accumulation within the wou-
nds over 10 postoperative days were evaluated. The authors
found no difference between the treatment and control
groups.56 This study suggests that acute, high-dose steroid
administration does not significantly affect wound healing,
as measured by both clinical and biochemical parameters.
Perioperative ‘‘stress dosing’’ with physiologic or supra-
physiologic levels of corticosteroids in patients on chronic
corticosteroids is beyond the scope of this article and has
been reviewed recently elsewhere.57,58 It is worth noting,
however, that these reviews did not report an increased
risk of wound dehiscence or infection.
Taken together, these data, although limited, suggest that
acute, high-dose corticosteroid administration for less than
10 days has no clinically important effect on wound healing.
Chronic administration. Only a few human studies have
quantified the risks of corticosteroid-induced wound com-
plications in surgical practice (Table 2).59–62 These studies
found that rates of wound complications may be increased
2- to 5-fold in patients taking corticosteroids compared
with those not on corticosteroids; however, since the major-
ity of the studies were uncontrolled and retrospective, it is
difficult to determine whether the complications were con-
founded by other factors.

Table 2 Effect of chronic corticosteroid administration on wound healing in humans

Equivalent dose Wound complication
Study (Ref) N (mg/day of prednisone) Duration rate (control %)
Numerous Diseases
Green, 196561 38 10.8 6 7 1 day–13 mo 29 (NR)
Engquist et al, 197460 100 18 pts: ,10 19 pts: ,1 yr 44 (22)
74 pts: .10 73 pts: .1 yr
Reding et al, 199062 55 51 (15–480) 18 mo 13 (2)
Rheumatoid Arthritis
Popert & Davis, 195868 15 12.4 6 3 25 6 16 mo 20
Garner et al, 197365 100 2.5–15 Variable 71 (25)
Escalante & Beardmore, 199566 204 6.4 6 2.2 NR 15.9
Jain et al, 200267 30 8.8 (4.25–20) NR 3.3 (9.5)
Inflammatory Bowel Disease
Price, 196874 80 NR NR 15 (40)
Knudsen et al, 197672 41 .40 NR; .2 mo 66 (27)
Allsop & Lee, 197869 162 .20 NR 31
Post et al, 199173 265 NR NR; preoperative 19 (7)*
Ziv et al, 199675 361 169 pts: .20 NR; .1 mo 8 (6)
192 pts: ,20 12 (6)
Bruewer et al, 200370 219 73 pts: .20 NR 18 (11)
146 pts: ,20 NR 12 (11)
N is the number of patients or the number of operations from each study in the experimental group. Dose is adjusted for equivalent doses of
prednisone (1 5 1 mg/day prednisone). Duration refers to the number of months that patients took corticosteroids preoperatively. Wound complication
rate is defined as disruption, persistent drainage, dehiscence, infection, or wound failure. In cases where no control group was included, there are no
parenthetical numbers provided. *Indicates there was a statistically significant difference in complication rates between the experimental and control
groups.
NR 5 not reported; pts 5 patients.
A.S. Wang et al. Corticosteroids and wound healing
Similarly, a recent retrospective study reviewed the
National Surgical Quality Improvement Program public
use files from 2005 to 2008 to evaluate the adverse effects
of preoperative corticosteroid use.63 The authors found that
of the 635,265 patients identified in the database, the
20,434 patients (3.2%) who were treated with chronic par-
enteral or oral corticosteroids for at least 30 days prior to
surgery had a significant increase in rates of superficial
and deep surgical site infections (from 2.9% to 5% and
from 0.8% to 1.8%, respectively) with steroid use. They
also reported a 2- to 3-fold increase in wound dehiscence
and a 4-fold increase in mortality associated with preoper-
ative corticosteroid use63; however, the authors were unable
to specify the dose or duration of corticosteroid use and the
underlying condition that required corticosteroid therapy,
which may have contributed to the increased complication
rates. In addition, they did not identify the types of surgery
performed or address whether corticosteroids were contin-
ued postoperatively.
The orthopaedic literature has also provided a few
studies regarding wound healing in patients with rheuma-
toid arthritis (RA; Table 2). Poss et al64 retrospectively
found that RA patients have a 2- to 3-fold greater risk of
infection and wound complications after joint replacement
compared with patients with osteoarthritis undergoing sim-
ilar procedures. A larger study of 100 RA patients sug-
gested that patients taking corticosteroids for more than 3
years had statistically significantly delayed wound healing
after surgery compared with those taking corticosteroids
for fewer than 3 years.65 Additionally, in a retrospective
study of 204 RA patients who underwent joint surgery,
the authors noted a dose-dependent trend toward increased
complication rates associated with corticosteroid adminis-
tration, but the differences were not statistically signifi-
cant.66 Similarly, during 30 hand and wrist procedures in
18 patients taking an average of 8.8 mg/day of prednisone,
only 1 wound dehiscence occurred; there were no other
wound complications in the steroid-treated group.67 In con-
trast, another report of 15 RA patients undergoing surgery
while taking cortisone (at doses equivalent to 12.5 to 20
mg/day of prednisone for between 2 weeks and 57 months)
described no significant corticosteroid effect on wound
healing, except in a few cases associated with overt signs
of hypercortisolism.68 Altogether, corticosteroid adminis-
tration appears to increase the risk of wound complications
in RA patients, but not all data have been statistically sig-
nificant. Furthermore, because these studies were not ran-
domized, it is unclear whether the increased risk is
related to intrinsic disease activity, restrictions on postoper-
ative mobility, the effects of other medications used for RA,
or corticosteroid effects alone.
In patients with inflammatory bowel disease, retrospec-
tive clinical studies have also reported conflicting results
(Table 2).69–75 Some studies showed no significant increase
in postoperative wound complications,70,72,75 while others
reported greater risk of wound infection,76 anastomotic leak-
age,71 intra-abdominal abscesses,73 and sepsis77 associated
5
with preoperative corticosteroids. For example, chronic
corticosteroid use was associated with a greater than 3-fold
increased infection rate in patients with inflammatory bowel
disease undergoing bowel resection, with even higher in-
fection rates occurring at doses of prednisone greater than
40 mg/day.76 In addition, some studies have suggested that
corticosteroid administration in patients with concomitant
intestinal abscesses greatly increases the risk of postopera-
tive morbidity.73,77
Although patients with primary nonmalignant dermato-
logic diseases do not typically undergo surgical procedures
for their skin conditions, some have chronic wounds that
present significant treatment challenges. Pyoderma gangre-
nosum is an uncommon neutrophilic dermatosis character-
ized by tender ulcers, often on the lower extremities or at
sites of trauma, with bluish undermined borders and
surrounding erythema. These lesions may develop in asso-
ciation with systemic diseases, such as inflammatory bowel
disease, rheumatologic disease, or hematologic malignan-
cies, but approximately 25% to 50% of cases are idio-
pathic.78 The treatment of choice for this condition is
systemic corticosteroids (0.5 to 2 mg/kg per dose, generally
40 to 60 mg/day) for at least 4 to 6 weeks, sometimes re-
quiring multiple courses because of recurrence. For refrac-
tory disease, high-dose intravenous methylprednisolone
(1,000 mg/day) has been used for pulse therapy. Topical
corticosteroids (such as high-potency clobetasol propionate
0.05%) and intralesional corticosteroids are also considered
options, although there is some concern for pathergy with
the latter.79 In these cases, suppression of the underlying in-
flammatory process with corticosteroids facilitates ulcer
healing. Surgical treatment, such as debridement, would
exacerbate the condition.
Perhaps the most convincing evidence regarding the
effects of chronic, high-dose corticosteroids on wound
healing is the previously cited example of Cushing syn-
drome.43,80 These effects are similar to those that Ragan
et al13 observed. Granted, both are examples of high-dose
and chronic exposure, whereas the key clinical question is
the effect of low-dose but chronic corticosteroids.
Altogether, the clinical data discussed above suggest
that preoperative corticosteroid treatment of at least 30
days, particularly at prednisone doses of 40 mg/day or
greater, may increase wound complication rates by up to 2
to 5 times compared with patients not on corticosteroids.
Some patients, such as those with RA, may be more
susceptible to wound complications as well. Nevertheless,
corticosteroids still play a significant role in facilitating
wound healing in other conditions, such as pyoderma
gangrenosum.
Effect of timing of corticosteroid administration
on wound healing
Postoperative timing of administration may be critical,
as in the case of a patient who develops an acute flare
6 The American Journal of Surgery, Vol -, No -, - 2013
of gout postoperatively and requires corticosteroids for
alleviation of pain. Animal studies have suggested that
corticosteroids have no effect on wound tensile strength if
administered 3 or more days after wounding.27 If given in
large doses, however, postoperative corticosteroids could
cause immunosuppression and predispose to infection,
which in turn contributes to mechanical complications of
wound healing. To our knowledge, no clinical studies
have compared the differential effects of corticosteroids
on wound healing when given before versus after surgery.
Summary
To better manage patients on corticosteroids, the optimal
dose and duration that will minimize the adverse effects on
wound healing while still adequately treating the underly-
ing condition need to be determined. If the dose and
chronicity are defined in relation to hypothalamic–pitui-
tary–adrenal axis suppression, then administration lasting
less than 5 days could be considered ‘‘acute,’’ and doses
greater than 10 mg/day for more than 1 week might be
considered ‘‘chronic.’’81 Although it is not clear whether
hypothalamic–pituitary–adrenal suppression is in any way
related to altered wound healing, these numbers estimate
the endogenous levels of corticosteroids produced under
physiologic conditions. Any dose lower than these values
is unlikely to have pharmacologic effects. Regarding timing
of administration, animal studies have shown that cortico-
steroids given at least 3 days after wounding have no effect
on wound healing.27 Altogether, these findings suggest that
there are no contraindications to prescribing a short course
of corticosteroids (eg, 5 mg/day of prednisone for 5 to 10
days), for example, to a postoperative patient suffering
from an acute flare of gout if initiated at least 3 days after
surgery. Certainly, large prospective, randomized, con-
trolled trials are needed to fully address this issue.
Establishing an optimal corticosteroid dose and duration
is challenging for several reasons. First, the mechanisms
whereby corticosteroids impair wound healing are incom-
pletely understood. In particular, impairment of wound
healing associated with chronic corticosteroid use and in
patients with Cushing syndrome underscores the need to
better understand the systemic and indirect effects of
corticosteroids. Additionally, different corticosteroids may
have varying tissue concentrations or affinity for the
molecular targets that influence wound healing. Moreover,
dosing and duration should also be tailored toward the
individual patient with attention to the underlying condition
requiring corticosteroids and any comorbidities. Smaller
procedures, such as temporal artery biopsies, are expected
to have lower wound complication rates than larger proce-
dures, such as bowel resection with anastomotic recon-
struction. Thus, the type of surgery and the patient’s clinical
status would likely further influence considerations for
perioperative corticosteroids and alter the overall risk of
wound complications.
Conclusions
More than 50 years after their miraculous introduction to
clinical medicine, corticosteroids are still commonly used
and effective therapies for numerous inflammatory disor-
ders. Although wound disruptions have occurred in patients
taking corticosteroids, in clinical practice, treatment doses
are generally below the level required for dramatic inhibi-
tion of wound healing. In the absence of large prospective
randomized controlled studies, this question remains in-
completely answered.
Now, corticosteroid research is moving toward dissoci-
ating the anti-inflammatory effects of corticosteroids from
their numerous side effects with the development of so-
called selective glucocorticoid receptor modulators.28,82
Some reports have suggested that methylprednisolone
may have less effect on wound healing than other cortico-
steroids,16 but these results require confirmation.
Several strategies have also emerged to mitigate the
effects of corticosteroids on wound healing. These ap-
proaches include local administration of vitamin A and
cytokine modulation.83 For decades, vitamin A has been
known to reverse the effects of corticosteroids on wound
healing in animals; this approach is sometimes used in hu-
mans but has never been validated in a controlled study of
wound complication rates.17,84–86 Additionally, cytokine
modulation, such as with the use of TGF-ß, may be an ex-
citing mechanism for counteracting corticosteroid effects
on wound healing but requires further investigation.87,88
Overall, corticosteroids have been and will likely con-
tinue to be essential components of our pharmacologic
armamentarium. Therefore, until more data become avail-
able to guide clinical practice, appropriate preoperative
patient counseling about the potential risks of impaired
wound healing would be prudent.
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