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UHM 2018, V ol. 45, N o.

2 – HBO 2 F REQUENCY FOR COMPROMISED FLAPS

Research Report
Random flap survival with hyperbaric oxygen:
daily versus twice-daily treatments
Rachel Weber MD; Andrew Silver MD; Shelley J. Williams MS; Linda Stephenson MS;
Phillip C. Usera MD; Fan Zhang MS; Honglin Tian PhD; Wei Yang MD, PD; Wei Z Wang MD;
Xin Hua Fang MT; William A Zamboni MD; Richard Baynosa MD
UNLV School of Medicine, Division of Plastic Surgery, Las Vegas, Nevada, U.S.

CORRESPONDING AUTHOR: Richard C. Baynosa MD – richard.baynosa@unlv.edu


_________________________________________________________________________________________________________________________________________________________________

ABSTRACT Introduction
Plastic surgeons are often faced with the problem of
Purpose: Hyperbaric oxygen (HBO2) therapy is used to
a compromised flap. Due to tenuous blood supplies,
improve the survival of compromised flaps. Compromised flaps
random pattern flaps can become compromised and
are complications encountered postsurgically, or in traumatic
may be prone to necrosis, especially distally. While
degloving or avulsion injuries. Failed flaps lead to persistence
postsurgical etiologies of such flaps may be multifac-
of the defect, requirement of another donor site, and psycho-
social sequelae. Although evidence of the benefit of HBO2 torial, including random ischemia, arterial insuffi-
therapy is significant, there is no consensus on the optimal ciency or venous insufficiency, they are also common
treatment regimen. The purpose of this study is to examine in traumatic degloving and avulsion-type injuries.
whether twice-daily treatments (BID HBO2) provide additional Failed flaps have significant clinical implications in-
benefit compared to daily treatments (QD HBO 2) in a rat cluding flap loss, persistence of the original defect,
compromised random flap model. requirement of another donor site with associated
Method: A rat random flap model was used with subjects morbidity, as well as psychosocial sequelae. Thus,
divided into three groups: 1) control group; 2) QD HBO 2; and interventions that improve the survival of compromised
3) BID HBO 2, where HBO 2 was performed with 100% oxygen at flaps are of great value.
2.5 atmospheres absolute/ATA (253 kPa) for 90 minutes. Hyperbaric oxygen (HBO2) therapy is a useful tool
After 10 days, areas of flap necrosis were measured and that has been used as an adjunct to increase the survival
biopsies were taken for histologic analysis. Statistical analysis of compromised flaps [1]. Via Henry’s law, increased
was performed using ANOVA and paired t-tests. A P-value oxygen is dissolved in the plasma that can then diffuse
<0.05 was considered significant. to ischemic tissues [2,3]. Normally, the amount of
Result: Both treatment groups had significantly increased oxygen dissolved in the plasma is insignificant, but
mean flap survival compared to controls (P<0.05). There HBO2 therapy increases the amount of plasma oxygen
was no significant difference in flap survival between the tenfold which is enough to become physiologically
QD and BID groups. Capillary proliferation in the QD group adequate to preserve ischemic tissues [1]. In addition,
was increased compared with controls. it prevents ischemic injury by interfering with neutrophil
Conclusion: Both QD and BID HBO 2 protocols can sig- adherence [4] and by decreasing inflammation, edema
nificantly decrease random flap necrosis. However, the results and apoptosis [3,5,6,7]. Although it does increase reactive
of this study suggest there is no additional benefit gained with oxygen species, it also upregulates pathways that pro-
BID treatments. Clinical studies are warranted to confirm tect against oxidative stress [8]. Finally, it stimulates
these findings and assist in formalization of protocols for neovascularization, improves blood flow, and leads to
the use of HBO2 in treating compromised random flaps. vasodilation [9,10].

_______________________________________________________________________________________________________________________
KEYWORDS: HBO2 therapy; compromised flap; random flap survival; random flap necrosis; neovascularization

Copyright © 2018 Undersea & Hyperbaric Medical Society, Inc. 157


UHM 2018, V ol. 45, N o. 2 – HBO 2 F REQUENCY FOR COMPROMISED FLAPS

Multiple studies have shown that hyperbaric oxygen • Group 2: flap elevated, HBO2 for 90 minutes daily
treatment leads to a significant increase in flap survival (QD HBO2);
ranging from 18%-51% in animal models. However, the • Group 3: flap elevated, HBO2 for 90 minutes
treatment regimen varies widely anywhere from one to every 12 hours (BID HBO2).
six treatments/day, with treatments lasting one to six
hours at 2-3 atmospheres absolute/ATA (203-304 kPa) Surgical procedure: Design of a random pattern
pressure [11]. In human patients, HBO2 is admin- flap model
istered 90-120 minutes one to three times daily. The Rats were placed in the prone position. The dorsum
regimen is mainly determined by clinician judgment was shaved and a caudally based modification of the
[12,13]. However, there is no true standard, as the effec- McFarlane flap was designed (Figure 1). The landmarks
tive frequency of treatments has not been tested. were the iliac crests and the spine. The base of the flap
Although hyperbaric oxygen therapy is relatively safe, was located 1cm cranial to the iliac crests and extended
it does have some risks, with some being extremely rare. a length of 9cm. There was a width of 1.5cm on both
Otic barotrauma, seizures, myopia and nuclear cata- sides of the spine, which created a 9x3 cm flap. The
racts have all been reported. Patients often experience flap was incised and elevated above the deep fascia to
confinement anxiety [14,28]. In addition, a regimen con- include skin, subcutaneous fat and the panniculus
sisting of multiple treatments per day is inconvenient carnosus. The axial deep circumflex iliac vessels were
and may lead to patient non-compliance. cauterized to make the flap pattern random. The flap
In light of these issues, the goal of this study is to de- was then sutured back in place using continuous
termine an evidence-based frequency of treatments 4-0 monofilament sutures. Postoperatively the animals
in a hyperbaric regimen. Our aim is to see if there is a were returned to their cages.
difference in flap survival between daily and twice- As this flap modification had not yet been evaluated
daily hyperbaric oxygen treatments in a rat model of in our lab, it was first tested in eight control animals to
a compromised random pattern flap. ensure a pattern of necrosis comparable with previously
tested random pattern flaps. All experimental rats had
Methods the operative procedure performed by the same surgeon
The experimental protocol was approved by IACUC (RW) to minimize variability. All experimental rats were
and guidelines for the care and use of laboratory placed in the chamber for the HBO2 treatment less
animals were followed. All procedures were carried than one hour from completion of the surgery.
out under intraperitoneal dexmedetomidine/ketamine
anesthesia. Surgical procedures were carried out with HBO2 treatments
sterile technique. A power calculation was performed HBO2 was administered in a chamber manufactured by
to determine the minimum sample size in each group Dixie Manufacturing company (Baltimore, Maryland)
to obtain an 80% chance of detecting a statistically (Model 20, 1,500 psi chamber) that is 54 inches long
significant effect given an alpha level of P<0.05, with an inside diameter of 20 inches. 100% oxygen
and this was calculated to be 15 animals per group. was infused at one end of the chamber while ex-
This power calculation was included to minimize the pired carbon dioxide (CO2) exited an exhaust system
chance of Type II error. at the other end. Prior to pressurization the chamber
was flushed with 100% O2 until oxygen concentration
Subjects and groups reached 100% as measured with calibrated oximeter.
Forty-five male Sprague-Dawley rats (270 – 422g) were Pressure was then raised to 2.5 ATA. Immediately post-
used in this study. Rats were housed individually in stan- operatively and no longer than one hour after surgery,
dard conditions with rat chow and water ad libitum. four animals at a time were placed in the chamber for
The rats were ear-notched for identification and 90-minute treatments. After treatments the animals
divided into three groups (N=15 per group): were returned to their cages. In Group 2, treatments
• Group 1: Controls – flap elevated, no HBO2; were continued every 24 hours for 10 days. In Group 3,
treatments were carried out every 12 hours for 10 days.

158 Weber R; Silver A; Williams SJ, et al.


UHM 2018, V ol. 45, N o. 2 – HBo 2 F REQUENCY FoR CoMPRoMIsED FlAPs

FIGURe 1.
Modified
McFarlane
flap design necrosis

viable tissue
with capillary
proliferation
muscular
layer

FIGURe 2. Histological analysis of random skin flap specimen.


Magnification at 40x (hematoxylin and eosin stain).

Samples collected blinded to the different groups. The H&E slide of each
On postoperative day 10, the animals were sedated with specimen was evaluated for necrosis and capillary
intraperitoneal dexmedetomidine and ketamine. The counts (Figure 2). Histologic necrosis was measured
dorsum of each rat was shaved. The flap was outlined as the proportion of specimen thickness with non-
and divided into equal 3cm-long proximal, middle and viable, avascular coagulative necrosis, excluding the
distal segments. The demarcated necrotic tissue was thickness attributed to serum crust formation. Capillary
outlined. Pictures were taken of each subject at a counts were determined by counting the number in
constant distance. The flaps were then re-raised and 10 high-power fields at 40 x (Cap/hpf ).
0.75cm x 0.75cm full-thickness tissue samples were
taken from the middle and distal zones of the flap Statistical analysis
to serve as representative samples of the entire flap Gross necrotic area, histologic area of necrosis, and
section and placed in 10% buffered formalin. After capillary counts were each analyzed using both ANOVA
samples were collected, the animals were euthanized (analysis of variance) and paired t-test to assess for
by pneumothorax while under anesthesia. differences among and between groups. A P-value <0.05
was considered statistically significant. All data were
Percentage of necrotic area expressed as a mean and standard error. Analysis was
Photographs of the entire flap area from postoperative conducted using Statistical Analysis System (version 9.3)
day 10 were used to calculate the area of flap necrosis software.
using Sigma Scan Pro (version 5.0) software. The digi-
tal photos were pixelated by the software, and the dark RESULTS
areas defined as areas of flap necrosis were divided Percentage of necrotic area
by the area of the entire flap by the software to On postoperative day 10 the areas of necrosis were
determine the percentage gross flap necrosis. Mean flap clearly demarcated as dark, rigid, non-bleeding tissue,
necrosis of each group was calculated. mostly in the distal aspect of the flap (Figure 3). This
was in contrast with surviving skin which was pink,
Histology soft and bled when cut. The mean percentage of flap
Tissue samples were fixed in 10% buffered formalin, necrosis in HBO2 treatment groups 2 and 3 (40.6 ± 1.8
embedded in paraffin, sectioned in 4µm slices and and 40.2 ± 2.1%) were significantly less than the con-
stained with hematoxylin and eosin (H&E). They trol group (48.5 ± 1.7)% (ANOVA P<0.05), but did not
were sent for analysis to a board-certified pathologist differ significantly between the two groups (Figure 4).

Weber R; Silver A; Williams SJ, et al. 159


UHM 2018, V ol. 45, N o. 2 – HBo 2 F REQUENCY FoR CoMPRoMIsED FlAPs

60

50

40

percent necrosis
30

20

10

0
control 1 x HBO2 2 x HBO2

FIGURe 3. Comparison of percent necrosis on random skin flaps between groups


Data are expressed as mean ± standard error P<0.05
Control vs. treatment groups (aNOVa)

control daily/QD HbO2 bID HbO2


(57% necrosis) (38% necrosis) (41% necrosis)

MeaN: control – 48.5% necrosis; daily/QD HbO2 – 40.6% necrosis; bID HbO2 – 40.2% necrosis

FIGURe 4. Representative photos of each of the three rat groups

Histologic analysis 0.54, and 2.7 ± 0.58 Cap/hpf in the control, QD HBO2,
Specimens taken from the distal third of the flap had and BID HBO2 groups respectively. Although ANOVA
the greatest amount of histologic necrosis, with 72.7 ± only approached a difference among groups (ANOVA
7.5, 66.5 ± 7.5, and 61.7 ± 9.3 % in the control, QD HBO2 P= 0.06), paired t-test did show a statistically significant
and BID HBO2 groups respectively (Table 1). ANOVA difference between the control and once-daily HBO2
and paired t-tests showed no statistically significant group (P=0.04). No difference was seen between BID
difference between the groups. Specimens from the HBO2 and control (Table 2). Capillary counts of 2.8 ±
middle third had less necrosis, with an average of 10 ± 0.31, 2.5 ± 0.36, and 2.9 ± 0.31 per hpf in the control,
3.8, 12.7 ± 6.5, 5.1 ± 2.7% necrosis, again with no sig- QD HBO2, and BID HBO2 respectively did not
nificant difference among groups (Table 1). differ among groups in specimens taken from the
Specimens from the distal third had 2.0 ± 0.49, 3.5 ± middle third of the flap (Table 2).

160 Weber R; Silver A; Williams SJ, et al.


UHM 2018, V ol. 45, N o. 2 – HBO 2 F REQUENCY FOR COMPROMISED FLAPS

____________________________________________________________________________________________________________

Treatment specimens from specimens from


Group distal third of skin flap middle third of skin flap
____________________________________________________________________________________________________________

mean ± standard error mean ± standard error


____________________________________________________________________________________________________________

Control 72.7 ± 7.5 10 ± 3.8


____________________________________________________________________________________________________________

QD HBO2 66.5 ± 7.5 12.7 ± 6.5


____________________________________________________________________________________________________________

BID HBO2 61.7 ± 9.3 5.1 ± 2.7


____________________________________________________________________________________________________________

Table 1. Comparison of histologic necrosis on specimens obtained from skin flap.


No significant difference between groups (ANOVA and paired t-test).

____________________________________________________________________________________________________________

Treatment specimens from specimens from


Group distal third of skin flap middle third of skin flap
____________________________________________________________________________________________________________

mean ± standard error mean ± standard error


____________________________________________________________________________________________________________

Control 2.0 ± 0.49 2.8 ± 0.31


____________________________________________________________________________________________________________

QD HBO2 3.5 ± 0.54 2.5 ± 0.36


____________________________________________________________________________________________________________

BID HBO2 2.7 ± 0.58 2.9 ± 0.31


____________________________________________________________________________________________________________

Table 2. Comparison of capillary count per high-powered field (Cap/hpf) on specimens


obtained from skin flap. P<0.05 Control vs. QD HBO2 in distal third of skin flap (paired t-test).

Random flap model all differences in complete survival between the controls
The random flap model created by cauterizing the flap’s and the two groups. There was no significant difference
axial vessels was first tested in eight animals of the in the flap survival between the treatment groups.
control group. The modification involved transection of The study was designed to directly compare these two
the deep circumflex iliac vessels to completely ensure the regimens, as they are currently the most common in
random flap pattern and revealed an equivalent pattern clinical practice. Since both of these regimens are used
of necrosis (mean of 48%) which was comparable to the effectively, we expected no difference between the two.
classic flap designs. In studying efficacy of hyperbaric oxygen treatment
of compromised flaps, multiple studies have used
Discussion once-daily treatments with varying success. Studies
Our findings suggest that a daily HBO2 regimen is as by Zhang [15] and Selcuk [16] used once-daily hyper-
effective as twice-daily HBO2 in improving the sur- baric treatments in their studies on dorsal rat flaps.
vival of compromised random flaps, with a statistically Both noted a significant increase in survival of HBO2-
significant improvement in the percent necrosis com- treated flaps. Arturson and Khana [17] treated rat
pared to the control random flap group. Although there dorsal flaps with both daily and twice-daily HBO2 treat-
were no histological differences in necrosis of the distal ments. There was a significant increase in flap survival
and middle thirds of the flaps for any of the groups, it is with both treatment regimens; however there were other
important to note that these were tissue biopsies that varying factors, and treatment frequencies were not
were representative of their sections of the flap and compared directly. In opposition, studies by da Rocha
confirmed the representative areas of necrosis for these and Stewart using once-daily HBO2 therapy alone failed
respective sections. The mean percentage of flap necro- to show an improvement in HBO2 only treated flaps
sis evaluates the entire flap area to determine the over- that was statistically significant [18,19]. A retrospective

Weber R; Silver A; Williams SJ, et al. 161


UHM 2018, V ol. 45, N o. 2 – HBO 2 F REQUENCY FOR COMPROMISED FLAPS

clinical review was performed by Larson and colleagues not usually seen until very prolonged exposure to HBO2.
[13] on 15 patients who received HBO2 for failing Another hypothesis is that being moved and confined in
reconstructive flaps, 14 of whom received once-daily the chamber more often increases psychological stress
treatments. Of these 15 flaps, 73% were salvaged. Thus and causes detrimental effects on wound healing similar
the literature has generally supported the effective- to those seen by Padgett in restrained mice [24]. It is
ness of a once-daily regimen, but no studies have com- important to emphasize that this study focused solely
pared a once-daily regimen with a twice-daily regimen. on a compromised random flap model. The results and
In addition to these studies with once-daily treat- conclusions found in this study cannot and should not
ments, others employed a multitude of different regi- be extrapolated to other types of flap compromise (i.e.,
mens. Friedman [11] performed a review of the ischemia-reperfusion), other flap types (i.e., axial or free
hyperbaric treatment literature that made clear the very flaps), or to any grafts in general. It is highly possible
diverse treatment regimens. Although the most com- that BID dosing in other situations (ischemia-reperfu-
mon regimen was twice-daily treatments, the range sion or compromised grafts) would have a significant
was from one to six at 2 to 3 ATA. Some regimens were difference and improvement with BID dosing.
defined by a set number of treatments with air breaks This study supports a once-daily treatment hyper-
in between in the first 24 to 48 hours postoperatively. baric oxygen regimen for compromised random flaps.
Still others used a de-escalating regimen. Jurell [20] used Currently, the most common clinical regimen for com-
different frequencies of treatment, but finding a difference promised grafts and flaps is 90 minutes twice a day and
between them was not a primary endpoint and was not is determined by clinician preference [12,13]. As alluded
commented on. Although most studies did demonstrate to previously, the decision for BID dosing may be related
a benefit, the regimens were so varied that conclusions to the etiology of the flap compromise or the presence of
on optimal treatment frequency are difficult to draw. a compromised graft as opposed to a random flap.
The reason why twice-daily therapy is not more However, there would be multiple advantages to once-
effective than once-daily therapy may be inferenced daily therapy. Cost of treatment would decrease with
from the capillary count data. Only the group exposed to decreased frequency. Because of the occurrence of con-
once-daily therapy had greater capillary proliferation finement anxiety, many patients would desire less fre-
than the control. One hypothesis for this difference is the quent treatments. In addition, the simpler, more con-
action of hypoxia-inducible factor 1 (HIF-1), a protein venient treatment schedule would hopefully lead to
that promotes the expression of vascular endothelial an increase in patient compliance. Larson [13] found
growth factor (VEGF) and subsequent neovascular- a significant association between flap survival and the
ization. HIF-1 is typically induced by hypoxia or free amount of the prescribed treatment completed, which
radicals and has been shown to be stabilized in tissue serves as an impetus to devise a regimen that will
undergoing HBO2 therapy. However, for several hours increase patient compliance. Lastly, otic barotrauma,
following HBO2 its levels are initially low, presumably seizures and ocular disturbances have been associated
due to the high tissue levels of oxygen. HIF-1 levels later with HBO2 [14,29]. Decreasing the number of treat-
begin to rise, possibly by the effect of free radicals ments may have the potential to decrease these risks.
produced by HBO2 treatment [21]. BID HBO2 may As expected, the use of HBO2 to increase random
suppress HIF-1 too frequently, leading to decreased pattern flap survival was supported in this study. Both
vascularization compared to the group exposed to HBO2 treatment groups had less necrosis of the distal aspect
less frequently. of the flap than the control group, which did not undergo
Other theories for why BID HBO2 was not more ben- HBO2 treatment. The increase in survival in flap length
eficial are multiple. There may be a parabolic effect where was in the same range as that demonstrated in other
the benefits of increasing hyperbaric oxygen therapy are studies. This is important, as the distal survival of a
countered by the growing harmful effects with increased random pattern flap is usually most crucial to maintain
dosing. Direct harm from HBO2 in the form of breathing closure of a defect.
difficulties or increased reactive oxygen species tox- The model used in this study was supported as an
icity is possible [22,23]; however, harmful effects are appropriate representation of a random pattern flap.

162 Weber R; Silver A; Williams SJ, et al.


UHM 2018, V ol. 45, N o. 2 – HBO 2 FREQUENCY FOR COMPROMISED F LAPS

An average of 48% of the flap areas became necrotic tiated that will still provide benefit to the flap needs
distally. This was within the range seen in other rat ran- to be elucidated. Similarly, in this study treatments
dom flap models, which has been reported as 22%- were carried on for 10 days but the flaps appeared
52% [25-28]. This flap was designed so that it could demarcated earlier in the course. This leads to a question
serve as an axial flap if the vessels were not cauterized, of what the optimal duration of treatment is. Finally,
thus allowing an easy direct comparison between axial treatment regimens will need to be studied in a
and random pattern flaps in future studies. human population to ensure clinical validity.

LIMITATIONS Conclusion
The main limitation of this study is that it is a rat model Our study supported the effectiveness of a once-daily
of a random pattern flap. It is possible that the results hyperbaric oxygen treatment regimen to increase survival
in the rat model will not apply to humans. Nonethe- of a compromised flap in a rat model. There was no
less, this study does give us data to support clinical benefit to twice-daily therapy. This is an important
testing of the regimen. In addition, it is a highly repro- step toward the creation of an evidence-based treatment
ducible model that may be used in subsequent studies. regimen for HBO2 that will maximize cost-effectiveness,
This study opened several avenues for further research. patient compliance, and safety.
n
In this protocol, HBO2 was started immediately after
the flaps were created. However, in a clinical scenario, Source of support: University of Nevada School of Medicine
the fact that a flap is compromised may not be noticed Surgery Departmental Grant
immediately postoperatively or post-injury. Thus the Conflict of interest statement: None of the authors have any
window of opportunity in which treatments may be ini- relevant conflict of interest to declare.

_____________________________________________________________________________________________________________________________________________________________________

REFERENCES

1. Baynosa RC, Zamboni WA. Compromised grafts and flaps. In: 7. Vidigal J, José Fagundes D, De Jesus Simões M, Oshima CT,
TS Neuman & SR Thom, Eds. Physiology and Medicine of Hyper- Odashiro AN, Santos Simões R, Negrini Fagundes AT, Taha MO,
baric Oxygen Therapy. Philadelphia, PA: Saunders/Elsevier; 2008: Montero EF. Effect of different periods of hyperbaric oxygen on
373-395. ischemia-reperfusion injury of rat skeletal muscle. Microsurgery.
2. Kranke P, Bennet M, Martyn-St James M, Schnabel A, Debus SE. 2007; 27(4): 252-257.
Hyperbaric oxygen therapy for chronic wounds. Review. Cochrane 8. Thom SR. Hyperbaric oxygen: its mechanisms and efficacy.
Database Syst Rev (2012): 4:CD004123. Plast Reconstr Surg. 2011 Jan; 127 Suppl 1:131S-141S.
3. Da Rocha FP, Fagundes DJ, Rivoire HC, Rech FV, Almeida MW, 9. Ulkür E, Karagoz H, Ergun O, Celikoz B, Yildiz S, Yildirim S.
Pires JA. Immunohistochemical expression of apoptosis and VEGF The effect of hyperbaric oxygen therapy on the delay procedure.
expression on random skin flaps in rats treated with hyperbaric Plast Reconstr Surg. 2007 Jan; 119(1) :86-94.
oxygen and N-acetylcysteine. Undersea Hyperb Med. 2011 May- 10. Meltzer T, Myers B. The effect of hyperbaric oxygen on the
Jun; 38(3): 167-174. bursting strength and rate of vascularization of skin wounds in
4. Khiabani KT, Bellister SA, Skaggs SS, Stephenson LL, Nataraj C, the rat. Am Surg. 1986 Dec; 52(12): 659-662.
Wang WZ, Zamboni WA. Reperfusion-induced neutrophil CD18 11. Friedman HI, Fitzmaurice M, Lefaivre JF, Vecchiolla T,
polarization: effect of hyperbaric oxygen. J Surg Res. 2008 Nov; Clarke D. An evidence-based appraisal of the use of hyperbaric
150(1):11-16. oxygen on flaps and grafts. Plast Reconstr Surg. 2006 Jun; 117
5 . Zhang Q, Chang Q, Cox RA, Gong X, Gould LJ. Hyperbaric (7 Suppl):175S-190S.
oxygen attenuates apoptosis and decreases inflammation in an 12. Baynosa RC, Zamboni WA. The effect of hyperbaric oxygen
ischemic wound model. J Invest Dermatol. 2008 Aug; 128(8): on compromised grafts and flaps. Undersea Hyperb Med. 2012
2102-2112. Jul-Aug; 39(4): 857-865.
6. Nylander G, Lewis D, Nordström H, Larsson J. Reduction of 13. Larson JV, Steensma EA, Flikkema RM, Norman EM. The
postischemic edema with hyperbaric oxygen. Plast Reconstr Surg. application of hyperbaric oxygen therapy in the management of
1985 Oct; 76(4): 596-603. compromised flaps. Undersea Hyperb Med. 2013 Nov-Dec; 40(6):
499-504.

Weber R; Silver A; Williams SJ, et al. 163


UHM 2018, V ol. 45, N o. 2 – HBO 2 F REQUENCY FOR COMPROMISED FLAPS

14. Plafki C, Peters P, Almeling M, Welslau W, Busch R. 22. Jurell G, Kaijser L. The influence of varying pressure and du-
Complications and side effects of hyperbaric oxygen therapy. ration of treatment with hyperbaric oxygen on the survival of skin
Aviat Space Environ Med. 2000 Feb; 71(2): 119-124. flaps. An experimental study. Scand J Plast Reconstr Surg. 1973;
15. Zhang T, Gong W, Li Z, Yang S, Zhang K, Yin D, Xu P, Jia T. 7(1): 25-8.
Efficacy of hyperbaric oxygen on survival of random pattern skin 23. Narkowicz CK, Vial JH, McCartney PW. Hyperbaric oxygen
flap in diabetic rats. Undersea Hyperb Med. 2007 Sep-Oct; 34(5): therapy increases free radical levels in the blood of humans. Free
335-339. Radic Res Commun. 1993;19(2):71-80.
16. Selcuk CT, Kuvat SV, Bozkurt M, Yasar Z, Gülsün N, Ilgezdi S, 24. Padgett DA, Marucha PT, Sheridan JF. Restraint stress slows
Ula M, Ozalp B. The effect of hyperbaric oxygen therapy on the cutaneous wound healing in mice. Brain Behav Immun. 1998
survival of random pattern skin flaps in nicotine-treated rats. Mar;12(1):64-73
J Plast Reconstr Aesthet Surg. 2012 Apr; 65(4):489-493. 25. McFarlane RM, Deyoung G, Henry RA. The design of a pedicle
17. Arturson G, Khanna NN. The effects of hyperbaric oxygen, flap in the rat to study necrosis and its prevention. Plast Reconstr
dimethyl sulfide and Complamin on the survival of experimental Surg. 1965 Feb; 35:177-182.
skin flaps. Scand J Plast Reconstr Surg. 1970; 4(1): 8-10. 26. Adamson JE, Horton CE, Crawford HH, Ayers WT Jr. The ef-
18. da Rocha FP, Fagundes DJ, Pires JA, da Rocha FS. Effects of fects of dimethyl sulfoxide on the experimental pedicle flap: a pre-
hyperbaric oxygen and N-acetylcysteine in survival of random liminary report. Plast Reconstr Surg. 1966 Feb; 37(2): 105-110.
pattern skin flaps in rats. Indian J Plast Surg. 2012 Sep; 45(3): 27. Yang D, Morris SF. An extended dorsal island skin flap with
453-458. multiple vascular territories in the rat: A new skin flap model.
19. Stewart RJ, Moore T, Bennett B, Easton M, Newton GW, J Surg Res. 1999 Dec; 87(2):164-170.
Yamaguchi KT. Effect of free-radical scavengers and hyperbaric 28. Hurn IL, Fisher JC, Arganese T, Rudolph R. Standardization of
oxygen on random-pattern skin flaps. Arch Surg. 1994 Sep; the dorsal rat flap model. Ann Plast Surg. 1983 Sep;11(3): 210-213.
129(9): 982-987 29. Jokinen-Gordon H, Barry RC, Watson B, Covington DS. A retro-
20. Jurell G, Kaijser L. The influence of varying pressure and du- spective analysis of adverse events in hyperbaric oxygen therapy
ration of treatment with hyperbaric oxygen on the survival of skin (2012-2015): lessons learned from 1.5 million treatments.
flaps. An experimental study. Scand J Plast Reconstr Surg. 1973; Adv Skin Wound Care. 2017 Mar; 30(3): 125-129.
7(1): 25-28. ✦
21. Sunkari VG, Lind F, Botusan IR, Kashif A, Liu ZJ, Ylä-Herttuala
S, Brismar K, Velazquez O, Catrina SB. Hyperbaric oxygen therapy
activates hypoxia-inducible factor 1 (HIF-1), which contributes to
improved wound healing in diabetic mice. Wound Repair Regen.
2015 Jan-Feb; 23(1): 98-110.

164 Weber R; Silver A; Williams SJ, et al.

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