Download Corticosteroids and wound healing

The American Journal of Surgery (2013) 206, 410-417
Review
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;
Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, 4860 Y Street,
Suite 2820, Sacramento, CA 95817
b
KEYWORDS:
Corticosteroids;
Wound healing;
Perioperative
Abstract
BACKGROUND: Determining whether systemic corticosteroids impair wound healing is a clinically
relevant topic that has important management implications.
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 corticosteroid 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 corticosteroids 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: [email protected]
Manuscript received June 25, 2012; revised manuscript November 1,
2012
0002-9610/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjsurg.2012.11.018
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 patients treated with 50 to 100 mg of 17-hydroxy-11dehydrocorticosterone daily. The following year, they
were awarded the Nobel Prize in Medicine for this ‘‘medical miracle.’’ Since then, systemic corticosteroids have
been used to treat various inflammatory conditions, including rheumatoid arthritis, temporal arteritis, gout, and inflammatory bowel disease, which may require surgical
management.
Importantly, the initial report from Hench et al12 did not
describe wound healing concerns, but subsequent clinical
A.S. Wang et al.
Corticosteroids and wound healing
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 corticosteroids require surgical procedures, concerns may arise regarding 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 corticosteroids 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 glucocorticoid response elements present in the promoter regions of target genes. Structural alterations of the cortisol
backbone result in corticosteroids with varying tissue distribution, 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 arbitrarily divided into 3 phases: inflammatory, proliferative,
and remodeling. In reality, these 3 phases overlap significantly, and signaling cascades initiated in 1 phase influence
cell growth and differentiation in later phases.31
Inflammatory phase. Immediately after wounding, platelets 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 receptors, such as intercellular adhesion molecule 1 (ICAM-1), facilitate 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
411
tissue and may thereby decrease the chemotactic and mitogenic stimulus for other inflammatory cells.1,8 Dexamethasone also downregulates endothelial cell expression of
intercellular adhesion molecule 1 (ICAM-1) in culture and
in healing colonic anastomoses, resulting in attenuated granulocyte adhesion and migration.4,11 Consistent with this
finding, high-dose corticosteroids reduce the extent of macrophage infiltration into the wound.9
Proliferative phase. Platelets and macrophages from the
inflammatory phase establish the growth factor and cytokine milieu that drives angiogenesis, fibroplasia, and reepithelialization 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 fibroblast proliferation5 and impairs wound re-epithelialization.2
Remodeling phase. During remodeling, the wound undergoes contraction and alters its collagen expression
pattern. Myofibroblasts facilitate wound contraction via
TGF-ß1 stimulation.39,40 Collagen remodeling requires collagen 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 dermal–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 adrenocorticotropic 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.
412
The American Journal of Surgery, Vol 206, No 3, September 2013
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 measurement 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 approximately 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 decreases 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 demonstrated a 40% reduction in cutaneous wound tensile
strength.43,44 Notably, 1 patient’s tensile strength improved
after adrenal resection. These findings suggest that corticosteroid excess may adversely affect wound healing in humans; 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
Table 1
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 conflicting 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 ventricular aneurysm.9,49–51 In all of these studies in which initiation 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 corticosteroids, but the result was statistically insignificant when considering randomized controlled trials only.52 More recently,
a Cochrane review of 54 randomized studies concluded that
prophylactic corticosteroids in adult cardiac surgery patients provide no mortality benefit.53 Importantly, the
Effect of acute corticosteroid administration on wound tensile strength in animals
Study (Ref)
21
Howes et al, 1950
Findlay & Howes, 195218
Meadows & Prudden, 195324
Pearce et al, 196025
Hinshaw et al, 196120
Sandberg, 196427
Ehrlich & Hunt, 196817
McNamara et al, 196923
Dostal & Gamelli, 199016
Dostal & Gamelli, 199016
Dostal & Gamelli, 199016
Aszodi & Ponsky, 198414
Cali et al, 199315
Mastboom et al, 199122
Phillips et al, 199226
Furst et al, 199419
Animal
Drug
Dose (mg/kg/day)
Wound type
Outcome measure
Change (%)
Rat
Rabbit
Rat
Rat
Rabbit
Rat
Rat
Rat
Mouse
Mouse
Mouse
Rat
Rat
Rat
Rabbit
Rat
C
C
C
C
C
C
C
Dex
Dex
C
MP
C
C
MP
Dex
C
40
1.5
4, 20, 100
20
12.5
40
25
6
16
400
80
5
5
2.5, 10
.1
15
I
I
I
I
I
I
I
I
I
I
I
A
A
A
A
A
TS
TS
BD
TS
BD
TS
TS
TS
TS
TS
TS
BP
BP
BP
BP
BP
238
0
230, 236, 265
245
0
230
230
0
259
268
0
224
0
0, 0
246
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.
A.S. Wang et al.
Corticosteroids and wound healing
authors noted no significant increase in postoperative infection or impairment of wound healing.
Likewise, patients with suspected temporal arteritis may
receive corticosteroids (usually 40 to 60 mg/day of prednisone) shortly before undergoing temporal artery biopsy. In a
large case series of patients with suspected temporal arteritis, 237 individuals underwent 250 temporal artery biopsies.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 complications.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 complication rate, if any, of temporal artery biopsy and its relationship to preoperative prednisone administration.
To date, only 1 randomized, double-blind, placebocontrolled trial has addressed the effects of acute, preoperative 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 developed a wound dehiscence, while 2 patients in the placebo
group developed a dehiscence. No wound infections occurred in the treatment group, but 1 infection required
Table 2
413
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 wounds 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 supraphysiologic 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 complications 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 majority of the studies were uncontrolled and retrospective, it is
difficult to determine whether the complications were confounded by other factors.
Effect of chronic corticosteroid administration on wound healing in humans
Equivalent dose
(mg/day of prednisone)
Duration
55
10.8 6 7
18 pts: ,10
74 pts: .10
51 (15–480)
1 day–13 mo
19 pts: ,1 yr
73 pts: .1 yr
18 mo
13 (2)
15
100
204
30
12.4 6 3
2.5–15
6.4 6 2.2
8.8 (4.25–20)
25 6 16 mo
Variable
NR
NR
20
71 (25)
15.9
3.3 (9.5)
80
41
162
265
361
NR
.40
.20
NR
169 pts: .20
192 pts: ,20
73 pts: .20
146 pts: ,20
NR
NR; .2 mo
NR
NR; preoperative
NR; .1 mo
15 (40)
66 (27)
31
19 (7)*
8 (6)
12 (6)
18 (11)
12 (11)
Study (Ref)
N
Numerous Diseases
Green, 196561
Engquist et al, 197460
38
100
Reding et al, 199062
Rheumatoid Arthritis
Popert & Davis, 195868
Garner et al, 197365
Escalante & Beardmore, 199566
Jain et al, 200267
Inflammatory Bowel Disease
Price, 196874
Knudsen et al, 197672
Allsop & Lee, 197869
Post et al, 199173
Ziv et al, 199675
Bruewer et al, 200370
219
NR
NR
Wound complication
rate (control %)
29 (NR)
44 (22)
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.
414
The American Journal of Surgery, Vol 206, No 3, September 2013
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 parenteral 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 preoperative 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 continued postoperatively.
The orthopaedic literature has also provided a few
studies regarding wound healing in patients with rheumatoid 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 similar procedures. A larger study of 100 RA patients suggested 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 administration, but the differences were not statistically significant.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 contrast, 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 administration appears to increase the risk of wound complications
in RA patients, but not all data have been statistically significant. Furthermore, because these studies were not randomized, it is unclear whether the increased risk is
related to intrinsic disease activity, restrictions on postoperative mobility, the effects of other medications used for RA,
or corticosteroid effects alone.
In patients with inflammatory bowel disease, retrospective 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 leakage,71 intra-abdominal abscesses,73 and sepsis77 associated
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 infection 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 postoperative morbidity.73,77
Although patients with primary nonmalignant dermatologic diseases do not typically undergo surgical procedures
for their skin conditions, some have chronic wounds that
present significant treatment challenges. Pyoderma gangrenosum is an uncommon neutrophilic dermatosis characterized 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 association with systemic diseases, such as inflammatory bowel
disease, rheumatologic disease, or hematologic malignancies, but approximately 25% to 50% of cases are idiopathic.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 requiring multiple courses because of recurrence. For refractory 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 inflammatory 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 syndrome.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
A.S. Wang et al.
Corticosteroids and wound healing
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 underlying condition need to be determined. If the dose and
chronicity are defined in relation to hypothalamic–pituitary–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 corticosteroids 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, controlled 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 incompletely 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 procedures, such as bowel resection with anastomotic reconstruction. 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.
415
Conclusions
More than 50 years after their miraculous introduction to
clinical medicine, corticosteroids are still commonly used
and effective therapies for numerous inflammatory disorders. Although wound disruptions have occurred in patients
taking corticosteroids, in clinical practice, treatment doses
are generally below the level required for dramatic inhibition of wound healing. In the absence of large prospective
randomized controlled studies, this question remains incompletely answered.
Now, corticosteroid research is moving toward dissociating the anti-inflammatory effects of corticosteroids from
their numerous side effects with the development of socalled selective glucocorticoid receptor modulators.28,82
Some reports have suggested that methylprednisolone
may have less effect on wound healing than other corticosteroids,16 but these results require confirmation.
Several strategies have also emerged to mitigate the
effects of corticosteroids on wound healing. These approaches 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 humans 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 exciting mechanism for counteracting corticosteroid effects
on wound healing but requires further investigation.87,88
Overall, corticosteroids have been and will likely continue to be essential components of our pharmacologic
armamentarium. Therefore, until more data become available to guide clinical practice, appropriate preoperative
patient counseling about the potential risks of impaired
wound healing would be prudent.
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