Hyperbaric oxygen therapy in Plastic Surgery practice: case series and literature overview

Abstract

Hyperbaric oxygen therapy (HBOT) is the use of 100% oxygen at pressures more than atmospheric. Several approved applications and indications exist for HBOT in the literature. Non-healing wounds, such as diabetic and vascular insufficiency ulcers, have 1 Clinic of Plastic and Reconstructive Surgery, Department of Neurosciences, University Hospital of Padova, Padova, Italy 2 Department of Physiology, University of Padova, Padova, Italy Corresponding author: Ilaria Tocco-Tussardi, e-mail: ilaria.toccotussardi@gmail.com © Copyright 2019, CIC Edizioni Internazionali, Romabeen a major area of application, and the use of HBOT as an adjunct has been approved by several studies and trials. HBOT is also indicated for acute soft tissue infections like clostridial myonecrosis, necrotising soft tissue infections, as also for traumatic wounds, crush injury, compartment syndrome, and compromised skin grafts and flaps. Another major area of application of HBOT is radiation-induced wounds. With increasing availability of chambers and studies proving the benefits of use, HBOT should be considered as an essential part of the overall management strategy for plastic surgeons.

Full text

257
Introduction
Hyperbaric oxygen therapy (HBOT) is defined
as breathing pure (100%) oxygen while under in-
creased absolute atmospheric pressure (ATA). The
first record of use of air at raised ambient pressure
for the treatment of illnesses can be traced back to
1662, when the British clergyman Henshaw devel-
oped an airtight chamber (the domicilium) in which
the atmosphere could be compressed and decom-
pressed using oxygen bellows and valves; but it was
not until the 19th century that the first successful
employment was achieved by Benke and Shaw with
resolution of decompression sickness (1).
The era of modern-generation hyperbaric cham-
bers begins in 1955, when Churchill-Davidson et al.
began to use oxygen therapy in a hyperbaric cham-
ber to treat radiotherapy-induced damage in cancer
patients. After encouraging reports, there was an up-
surge in the number of chambers and applications;
however, reports of use of HBOT without sound ra-
tionale (e.g. as anti-aging treatment) led to calls for
better regulation during the 1960s (1, 2).
The Undersea and Hyperbaric Medical Society
(UHMS) was established in 1967 with the rationale
of giving HBOT a full professional status in terms of
regulation, staffing, training, and certification.
UHMS acts as the primary scientific body for
HBOT in the USA and provides with a list of emer-
gent and non-emergent applications proved by rea-
sonable scientific evidence or clinical experience (3).
These indications had also been subsequently sup-
ported by the British Hyperbaric Association (4).
Most recently, the 2016 European consensus confer-
ence recommended HBOT for some additional con-
ditions based on sufficient evidence in the form of
expert consensus opinion (5).
The generic application of HBOT is in clinical
conditions characterized by an imbalance between
the oxygen request and supply. HBOT is adminis-
G Chir Vol. 40 - n. 4 - pp. 257-275
July-August 2019 review
Hyperbaric oxygen therapy in Plastic Surgery practice:
case series and literature overview
F. BASSETTO1, G. BOSCO2, T. BRAMBULLO1, E. KOHLSCHEEN1,
I. TOCCO-TUSSARDI1, V. VINDIGNI1, C. TIENGO1
SUMMARY: Hyperbaric oxygen therapy in Plastic Surgery
practice: case series and literature overview.
F. BASSETTO, G. BOSCO, T. BRAMBULLO, E. KOHLSCHEEN, I. TOC-
CO-TUSSARDI, V. VINDIGNI, C. TIENGO
Hyperbaric oxygen therapy (HBOT) is the use of 100% oxygen
at pressures more than atmospheric. Several approved applications
and indications exist for HBOT in the literature. Non-healing
wounds, such as diabetic and vascular insufficiency ulcers, have
1 Clinic of Plastic and Reconstructive Surgery, Department of Neurosciences,
University Hospital of Padova, Padova, Italy
2 Department of Physiology, University of Padova, Padova, Italy
Corresponding author: Ilaria Tocco-Tussardi,
e-mail: ilaria.toccotussardi@gmail.com
© Copyright 2019, CIC Edizioni Internazionali, Roma
been a major area of application, and the use of HBOT as an
adjunct has been approved by several studies and trials. HBOT is
also indicated for acute soft tissue infections like clostridial myone-
crosis, necrotising soft tissue infections, as also for traumatic
wounds, crush injury, compartment syndrome, and compromised
skin grafts and flaps. Another major area of application of HBOT
is radiation-induced wounds. With increasing availability of cham-
bers and studies proving the benefits of use, HBOT should be con-
sidered as an essential part of the overall management strategy for
plastic surgeons.
KEY WORDS: Application - Guidelines - Hyperbaric medicine - Hyperbaric oxygen therapy - Indication - Plastic reconstructive surgery.
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F. Bassetto et al.
tered inside chambers that are pressurized using air
or oxygen to pressures more than atmospheric.
Broadly, there are two types of chambers: multi-
place, which can hold more than one patient; and
monoplace chambers, designed to cater for a single
patient. Administration, commonly referred to as a
“compression”, involves pressurization between 2.0
and 3.0 ATA and the average duration of therapy is
60-90 min. Number of therapies may vary from 3 to
5 for acute conditions to 50-60 for radiation illness-
es. Treatments are administered once or twice a day.
Overall, the modality of administration is highly
variable, depending not only on the clinical indica-
tion, but also on the patient’s conditions.
HBOT mechanisms of action
In normobaric conditions, we live at 1 ATA of
pressure measured at the sea level, meaning that
downward pressure exerted on a body equals the
weight of the atmosphere above a body. Commonly,
the atmospheric pressure is measured in millimetres
of mercury, where 1 ATA is equal to 760 mm Hg,
1.101 bar, 14.7 psi, 760 torr, or 10 m of seawater.
The physics behind HBOT lies within the ideal
gas laws, Boyle and Henry laws. Boyle law states that
the absolute pressure exerted by a given mass of gas
is inversely proportional to the volume it occupies
(if the temperature and amount of gas remain un-
changed):
PV=k
and Henry law states that the amount of dissolved
gas is proportional to its partial pressure in the gas
phase:
C=kPgas
The application of Boyle law is seen in many as-
pects of HBOT. This can be useful with embolic
phenomena such as decompression sickness or arte-
rial gas embolism, as the volume of a bubble decreas-
es directly in proportion to increasing pressure. On
the other hand, Henry law accounts for the increase
in oxygen dissolved in the plasma by increasing the
atmospheric pressure in the chamber. Thus, the dis-
solved plasma oxygen concentration of 0.3 ml/dL at
1 ATA increases to 1.5 ml/dL upon administration
of 100% oxygen, while hyperbaric oxygen delivered
at 3 ATA yields a dissolved oxygen content of 6
ml/dL. The raise in the partial pressure of oxygen in
the blood, and subsequently in tissues, has been
shown to have many downstream biological effects:
•Neovascularization: regional angiogenic stimuli
influence the efficiency of new blood vessel
growth by local endothelial cells (termed angio-
genesis); and they stimulate the recruitment and
differentiation of circulating stem/progenitor
cells (SPCs) to form vessels de novo in a process
termed vasculogenesis (6-11). HBOT has effects
on both these processes, as an effect of an in-
creased oxygen gradient between the centre and
periphery of the wound. In an in vivo mouse
model and in an experimental wound, HBOT
directly promoted neovascularization in a dose-
dependent manner, which peaked at 2.5 ATA.
The Authors postulated the cyclic nature of
HBOT facilitates the process since neovascular-
ization requires collagen to form microvessel
tubes, with procollagen forming during periods
of hypoxia, and collagen export and maturation
occurring during hyperoxic periods (12).
Vascular endothelial growth factor (VEGF) and
angiopoietin, as well as stromal derived factor-1
(SDF-1) influence SPCs homing to wounds and
SPCs differentiation to endothelial cells (13, 14).
Synthesis of VEGF has been shown to be in-
creased in wounds by HBO: in a rat model,
HBOT applied at 2.1 ATA twice per day for 7
days significantly increased VEGF within
wounds (15). HBO also stimulates synthesis of
basic fibroblast growth factor (bFGF) and trans-
forming growth factor β1 by human dermal fi-
broblasts (16), angiopoietin-2 by human umbili-
cal vein endothelial cells (17), bFGF and hepato-
cyte growth factor in ischemic limbs (18), and it
up-regulates platelet derived growth factor recep-
tor in wounds (19).
•Reduction of inflammation: an early event asso-
ciated with post-ischemic tissue reperfusion is
the adherence of circulating neutrophils to vascu-
lar endothelium by β2 integrins and extravasa-
tion from capillaries, leading to what is known as
‘ischemia-reperfusion injury’ (20). When ani-
mals or humans are exposed to HBO at 2.8 to
3.0 ATA for at least 45 minutes, the ability of
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Hyperbaric oxygen therapy in Plastic Surgery practice
circulating neutrophils to adhere to target tissues
is temporarily inhibited, as part of a general re-
sponse, protecting endothelium, reducing its
porosity, and hence reducing interstitial edema
(20-23). In animal models, HBO-mediated inhi-
bition of neutrophil β2 integrin adhesion has
been shown to ameliorate reperfusion injuries of
brain, heart, lung, liver, skeletal muscle and in-
testine, as well as smoke-induced lung injury and
encephalopathy due to carbon monoxide poison-
ing (11, 24-31).
•Control of infection: HBOT may promote the
efficiency of leukocytes to kill pathogens by
phagocytosis. Phagocytosis requires large quanti-
ties of oxygen to form reactive species such as free
radicals, to inactivate pathogens within phago-
somes. This mechanism is blunted in a hypoxic
environment: HBOT increases the generation of
oxygen free radicals, which oxidize proteins and
membrane lipids, damage DNA, and inhibit bac-
terial metabolic functions (32). Superoxide dis-
mutase, catalase, and glutathione reductase keep
the formation of these radicals in check until the
oxygen load overwhelms the enzymes, leading to
the detrimental effects on cell membranes, pro-
teins, and enzymes (32, 33). In a rabbit experi-
mental model of osteomyelitis, Staphylococcus au-
reus inoculum decreases after exposure to hyper-
oxia (150 mm Hg) (34). This suggests HBOT
could help the host to overcome infection within
hypoxic soft tissue and bone. Control of anaero-
bic organisms is also achieved by HBOT by sup-
pression of clostridial α-toxin production in gas
gangrene (34, 35). Moreover, the efficacy of an-
tibiotics has been reported to improve in the hy-
perbaric environment: the activity of aminogly-
cosides and antimetabolite agents such as
trimethoprim, sulfamethoxazole, and sulfasoxa-
zole all showed an increase in effectiveness with
high oxygen tensions (36, 37).
•Promotion of wound healing: animal trials have
documented wound healing benefits of HBO
(38-40). The basis for its efficacy continues to be
investigated and appears to be a combination of
systemic events as well as local alterations within
the wound margin. In the early wound repair
phase, fibroblasts repopulate and proliferate
within the wound bed. There is evidence that
HBOT facilitates this process. Fibroblasts prolif-
eration increases in a dose-dependent manner be-
tween 1.0 and 2.5 ATA. This occurs for both
normal and diabetic skin fibroblasts (34).
Fibroblasts participate in wound repair by syn-
thesis of collagen. Procollagen is formed in a hypox-
ic environment. However, maturation of collagen
requires oxygen: HBOT promotes polymerization
and cross-linking of collagen in a dose-dependent
manner. This process involves proline hydroxyla-
tion: proline hydroxylase uses oxygen as a substrate
and is maximally active at 225 mm Hg and higher
(34).
Extracellular matrix formation is closely linked
to neovascularization and it is another oxygen-de-
pendent process (12). Enhanced collagen synthesis
and cross-linking by HBO2 have been described,
but whether changes are linked to the oxygen-de-
pendence of fibroblast hydroxylases, alteration in
balance of wound growth factors, metalloproteinases
and/or inhibitors of metalloproteases, is as yet un-
clear (12, 41).
HBOT in plastic surgery
HBOT and plastic surgery are tightly connected:
a large number of conditions treated by this surgical
specialty are eligible to benefit from HBO as adjunct
treatment. In 2015, the Italian Undersea and Hy-
perbaric Medicine Society updated its current indi-
cations for HBOT (42). Applications related to plas-
tic surgery are several (Table 1) and discussed below.
Acute soft tissue infections (clostridial myositis and
myonecrosis, necrotizing soft tissue infections)
HBOT, combined with antibiotics and surgical
removal of dead tissue, is an effective treatment for
severe soft tissue infections.
Clostridial myositis and myonecrosis (gas gangrene).
Gas gangrene is a fulminating, soft-tissue infection
with gram-positive anaerobic bacilli of the species
Clostridium, notably Cl. perfringens. The skin, sub-
cutaneous fat and muscle may all be affected. The
majority of cases are the consequence of contamina-
tion of traumatic wounds, where the initial cause of
necrosis is not the microorganism itself, but the fact
that tissue damage has resulted in locally hypoxic tis-
sue, so allowing Clostridium to thrive (43). Bacteria
then produce the α-toxin, which causes the necrosis.
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F. Bassetto et al.
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Hyperbaric oxygen therapy in Plastic Surgery practice
TABLE 2 - MANGLED EXTREMITY SCORING SCALE. ADAPTED FROM JOHANSEN ET AL. (117).
A. Skeletal/Soft tissue Injury
1. Low energy (stab, simple fracture), low velocity (gunshot wound)
2. Medium energy (open or multiple fractures)
3. High energy (close range gunshot wound, crush injury)
4. Very high energy (above + gross contamination, avulsion)
B. Limb Ischemia (double time if ischemia time > 6 h)
0. Perfusion normal
1. Pulse reduced/absent – perfusion still present
2. No pulse, paresis, dimished capillary refill
3. Cool, paralyzed, insensate, numb
C. Shock
0. Systolic blood pressure always >90 mmHg
1. Hypotension transiently
2. Persistent hypotension
D. Age
1. <30
2. 30-50
3. >50
TABLE 3 - HBOT THERAPY FOR FRACTURED CRUSH INJURY (GUSTILO CLASSIFICATION). ADAPTED FROM GUSTILO
ET AL. (118).
!
Use of HBOT and Host Status
Type
Characteristic
Infection
Rate
Amputation
Rate
Normal Host Impaired Host
Compromised
Host
I
Small (<1 cm)
laceration, from
inside out
Almost nil
0 No No Yes
II
Laceration, with
minimal soft
tissue injury
3%
0 No Yes Yes
III-A
Crush with
adequate soft
tissue coverage
<10% 0 No Yes Yes
III-B
Crush with
extensive soft
tissue injury,
insufficient to
cover bone
52% 16% Yes Yes Yes
III-C
Crush with
major vascular
injury
42% 42% Yes Yes Yes
!
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F. Bassetto et al.
The toxin is not only hemolytic but also has phos-
pholipase activity, with consequent activation of
inflammatory pathways causing increased vascular
permeability. This results in edema of the affected
tissues, which in turn contributes to hypoxia, so fa-
cilitating the further multiplication of the bacteria
(44).
Appropriate surgical management with antibiotic
therapy should constitute the first line of manage-
ment. At tissue oxygen tensions in excess of
250mmHg, α-toxin production is halted within
minutes of commencing hyperbaric oxygen therapy
(28, 45). The combination of HBOT and surgery
has been demonstrated to be synergistic in reducing
both mortality and morbidity, since the need for ex-
tensive debridement and amputation is significantly
reduced, with viable and non-viable tissue being
more strongly demarcated, thus making possible
more accurate tissue debridement (46). It has there-
fore been proposed that, where there is close contact
between surgical and hyperbaric facilities, the initial
surgical management should be limited to fascioto-
my, with debridement of necrotic tissue performed
later, after treatment with hyperbaric oxygen thera-
py (47). The extent of ablation might be reduced if
early HBO treatment is used to halt progression of
the infection.
Necrotizing soft tissue infections (NSTIs). NSTIs
are a rare spectrum of rapidly progressive infections
that are highly destructive of skin, fascia, and sur-
rounding tissue, with approximately 500 to 1500
cases reported annually in the US (48). Despite ag-
gressive therapy, including emergent surgical de-
bridement and broad-spectrum antibiotic use, mor-
tality remains as high as 76% in some series (48-51).
The literature surrounding the use of HBOT in
STIs is mixed. The majority support the use of ad-
junctive HBOT to reduce mortality in NSTIs. Sev-
eral case series and retrospective cohort studies re-
port lower than expected mortality relative to pub-
lished mortality rates from earlier series of NSTI pa-
tients treated with surgery and antibiotics alone (52-
54). On the other hand, other studies have reported
that use of HBO appears to provide no mortality
benefit and may be associated with increased mor-
bidity (e.g. increase in the number of operative de-
bridements needed) (55-57). A recent retrospective
analysis on the topic concluded that no statistically
TABLE 4 - CIERNY-MADER STAGING SYSTEM. ADAPTED FROM CIERNY ET AL. (116).
Anatomic Type
Stage 1: Medullary osteomyelitis
Stage 2: Superficial osteomyelitis
Stage 3: Localized osteomyelitis
Stage 4: Diffuse osteomyelitis
Physiologic class
A host: Normal host
B host
Systemic compromise (Bs)*
Local compromise (Bl)*
Systemic and local compromise (Bls)*
C host: Treatment worse than the disease
Systemic or local factors that affect immune surveillance, metabolism, and local vascularity
Systemic (Bs)
Malnutrition
Renal or hepatic failure
Diabetes mellitus
Chronic hypoxia
Immune disease
Malignancy
Extremes of age
Immunosuppression or neuropathy
Immune deficiency
Local (Bl)
Chronic lymphedema
Venous stasis
Major-vessel compromise
Arteritis
Extensive scarring
Radiation fibrosis
Small-vessel disease
Complete loss of sensation
Tobacco abuse
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Hyperbaric oxygen therapy in Plastic Surgery practice
significant differences in mortality or amputation
rate could be found between patients who under-
went HBO treatment and those who did not (58).
Nonetheless, the Authors agreed that given the the-
oretical advantages of HBO, it should be considered
as an adjunctive therapy in NSTI patients who have
been surgically debrided and medically optimized.
Crush injuries - severed fractures
HBO can be used as adjunctive therapy for trau-
ma patients with crush injury, compartment syn-
drome, and acute traumatic peripheral ischemia (59,
60). The rationale is the need to counter the effects
of tissue hypoxia arising as a direct consequence of
vascular injury and as a secondary consequence of
trauma and infection. The unifying factors among
these various conditions include a self-perpetuating
cycle of ischemia, edema, and injury gradient (20).
Crush injury/Compartment syndrome. Three as-
pects of a diffuse crushing injury contribute to the
development of compartment syndrome: (1) tissue
destruction, (2) type of tissue involved, and (3) gra-
dient of injury. Tissue is destroyed at the site of in-
jury: the extent of this destruction depends on the
acceleration/deceleration force applied to the tissue.
The goal of therapy is to limit the spread of injury
(59-61). The rationale for using HBO in crush in-
jury and compartment syndrome has been outlined
as follows:
1. Vasoconstriction: vasoconstriction occurs as a
protective reaction to hyperoxia. A 20% reduc-
tion in blood flow lessens extravasation of fluid
and thus edema, with reduced collapse of capil-
laries. The net effect is an increase in oxygenation
to the tissues, with improvement in microcircula-
tion (60).
2. Cellular function: with enhanced oxygenation at
the injury zone, host factors related to healing
and infection control come into play. Tissue oxy-
gen levels less than 30 mm Hg inhibit fibroblast
proliferation, which in turn inhibits neovascular-
ization and repair (see above) (34, 38-40).
3. Inhibition of infection (see above) (32-27).
4. Mitigation of reperfusion injury (see above) (20-
31).
Severed fractures. HBOT effect on bone tissue has
been heavily investigated and reported in the litera-
ture. Basset demonstrated that cultures of multi-po-
tent mesenchymal cells can differentiate into bone
or cartilage depending on the oxygen tension (62).
At increased oxygen tension with compression, there
was an enhancement of bone formation, whereas re-
duced oxygen tension produced cartilaginous cells
and tissues. These mesenchymal cells are found
within the perivascular zone. Trueta demonstrated
that pericytes from blood vessels act as osteoprogen-
itor cells (63). These pericytes are considered undif-
ferentiated mesenchymal cells, which have the ca-
pacity to differentiate into various connective tissue
forming cell types, including bone-forming os-
teoblasts. According to Hulth et al., vascularity is es-
sential in the healing of all tissues except for cartilage
(64). Jan et al. showed enhanced healing of supra-
critical sized defects with HBOT even in the absence
of bone grafts or bone substitutes (65, 66). Muho-
nen et al. investigated the effect of HBOT on the os-
teoblastic activity and angiogenesis in both irradiat-
ed and non-irradiated rabbit model subjected to
mandibular distraction osteogenesis procedure.
They found that HBO increased the osteoblastic ac-
tivity in the irradiated rabbit model but not to the
same level as in the non-irradiated controls (67).
Compromised flaps of grafts
HBOT is used on occasion to treat compromised
flaps and grafts, where there is decreased perfusion
or hypoxia, a practice supported also by the Guide-
lines from UHMS (3, 68-70). HBO can help maxi-
mize the viability of the compromised tissue thereby
reducing the need for re-grafting or repeat flap pro-
cedures. A published prospective, blinded clinical
trial showed that administration of HBO prior to
and for three days following skin grafting led to a
significant 29% improvement in graft survival (71).
A problem with this trial, however, is that the suc-
cess in the control arm of the study was markedly
less that one would expect in current practice. As
previously emphasized, support for use of HBO in
flap/graft compromise comes from quite a number
of studies (70, 72-75) but more work is needed.
Chronic refractory osteomyelitis
Refractory osteomyelitis is defined as a chronic
osteomyelitis that persists (≥ 6 weeks) or recurs after
appropriate interventions have been performed or
where acute osteomyelitis has not responded to ac-
cepted management techniques. The pathophysiolo-
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F. Bassetto et al.
gy of chronic osteomyelitis is characterized by both
acute and chronic sources of ischemia. The hypoth-
esis that raising oxygen tension within the soft tissue
and bone can enhance the treatment of chronic os-
teomyelitis stems from lines of evidence similar to
those that exist in the many other conditions for
which HBOT has been applied (76-78). HBOT has
been shown to be effective in acutely reducing tissue
edema, lowering intra-compartmental pressures and
ameliorating the detrimental effects of inflammatory
reactions; over the longer term, HBOT can be used
to promote new collagen formation and capillary an-
giogenesis in both hypoxic bone and surrounding
tissues; and this neovascularization works to counter
the less easily reversible consequences of os-
teomyelitis, such as surgical trauma, tissue scarring
and nutrient blood vessel occlusion. By creating a
sustained increase in the arterial perfusion of previ-
ously hypoxic bone and soft tissues, HBOT can re-
duce the susceptibility of these tissues to recurrent
infection and necrosis. Although high-quality clini-
cal trials may not be available, several retrospective
reports have been published in the recent literature
(79-84). Despite the inherent weaknesses of these
studies, they do suggest great potential for HBOT in
the treatment of chronic osteomyelitis. In most cas-
es, the best clinical results are obtained when HBOT
is administered in conjunction with culture-directed
antibiotics and scheduled to begin soon after thor-
ough surgical debridement.
Chronic non-healing wounds (non-diabetic and
diabetic)
The hypoxic nature of all wounds has been
demonstrated, and the hypoxia, when pathologically
increased, correlates with impaired wound healing
and increased rates of wound infection. HBOT has
been increasingly utilized in an adjunctive role in
many of these scenarios including venous ulcers,
pressure ulcers, diabetic foot ulcers, coinciding with
optimized patient and local wound care (85-95).
Patients with wounds that fall within a category
defined as potentially appropriate for adjunctive
HBOT should be evaluated for likelihood of bene-
fit. Hypoxia (i.e. wound PO2 < 40 mmHg) general-
ly best defines wounds appropriate for HBOT or
rather, lack of hypoxia (i.e. wound PO2 >40-50
mmHg) defines wounds potentially not appropriate
for HBOT. Breathing 100% oxygen at 1 ATA or
under hyperbaric conditions can improve the accu-
racy of transcutaneous oximetry (PtcO2) measure-
ment in predicting successful healing with adjunc-
tive hyperbaric oxygen treatment. The following
conclusions were drawn from a study of 1144 dia-
betic foot ulcer patients who underwent adjunctive
hyperbaric oxygen treatment in support of wound
healing or limb salvage (96). PtcO2 measured on air
at sea level defines the degree of periwound hypoxia
but has almost no value in predicting benefit with
subsequent hyperbaric oxygen treatment. These
measurements are more useful in predicting who
will fail to heal without hyperbaric oxygen treat-
ment. PtcO2 values below 35 mmHg obtained
while breathing 100% oxygen at sea level are associ-
ated with a 41% failure rate of subsequent hyperbar-
ic oxygen treatment while values obtained greater
than 35 mmHg were associated with a 69% likeli-
hood of a beneficial response. PtcO2 values meas-
ured during hyperbaric oxygen treatment exceeding
a cutoff value of 200 mmHg were 74% reliable in
predicting wound healing improvement or limb sal-
vage as the result of a therapeutic course of hyper-
baric oxygen. This positive predictive value is con-
sistent with those reported by others in both arterial
insufficiency and diabetic lower extremity wounds
(97, 98). Lack of an increase in PtcO2 to >100
mmHg appears to be an appropriate cut-off for pre-
dicting failure to heal, at least in ischemic diabetic
foot ulcers. This requirement for achieving supra-
physiologic wound oxygen concentration lends sup-
port to the argument that restoration of wound nor-
moxia is not the primary mechanism of action of
HBOT in healing hypoxic wounds. The failure rate
for <100 mmHg is not 100%, however, so that it is
not unreasonable to give a trial of HBOT (10-15
treatments) to such patients for whom the alterna-
tive is amputation (99).
Radiation injuries
Radiation complications are fortunately fairly rare,
with most radiation oncologists willing to accept a 5%
serious complication rate when treating with curative
intent. HBO has been applied as a therapy for delayed
radiation injury for more than 30 years, and soft-tissue
and bony necrosis is one of the entities included as an
approved indication in the Hyperbaric Oxygen era-
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Hyperbaric oxygen therapy in Plastic Surgery practice
py Committee Report of the UHMS (100-106). In
the U.S., third-party insurance entities will frequently
reimburse for this application, but often a formal ap-
peal will be required to obtain payment. In informal
surveys of practitioners at continuing medical educa-
tion meetings on HBO, it was consistently found that
between one third and one half of US patients are
treated for delayed radiation injuries (unpublished da-
ta). A recent comment on the topic by Feldeimer stat-
ed that ‘Hyperbaric oxygen is a very safe therapy; its
serious complications occur in fractions of a percent-
age point. It is not uncommon for patients to have
myopic visual changes, but these are usually tempo-
rary. Treatments with HBO2 are expensive, but much
less so than some of the newer cancer therapies, in-
cluding intensity-modulated radiation therapy and the
newer chemotherapy agents and marrow growth fac-
tors’ (107). Because a consistent cause and manifesta-
tion of radiation injury is vascular obliteration and
stromal fibrosis, the known impact of hyperbaric oxy-
gen in stimulating neovascularization is an obvious
and important mechanism whereby hyperbaric oxygen
is effective in radiation injury.
HBOT report of treatment
The University Hospital of Padova is a public
1,400-bed tertiary care facility located in the north-
ern-eastern Italy. It serves a population of approxi-
mately 1,000,000 inhabitants. In 2016-17, there
were 110,380 urgent care records, and more than
60,000 patients were hospitalized. Among multiple
services, the facility contains a state-of-the-art Hy-
perbaric Medicine Centre with dual chambers for
capacity of 24 patients. From January 2006 to De-
cember 2015, the Clinic of Plastic Surgery of the
Hospital referred 184 patients (≥18-years of age) to
the Hyperbaric Medicine Centre (mean of 18.9±7.7
per year) (Figure 1). The population was male pre-
dominant (M=140) of mean age of 47±17 years.
Reasons for referral to HBO treatment are shown in
Figure 2. More than half of patients (N=97, 52.7%)
required HBO treatment for severed injuries of the
upper or lower extremity (N=64 injuries of the low-
er extremity; N=33 injuries of the upper extremity)
(Figures 3, 4 show sequential pictures of patients
managed for complex injuries of the upper and low-
Figure 1 - Number of plastic surgery patients referred to the Hyperbaric Medicine Centre per year from January 2006 to December
2015.
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F. Bassetto et al.
Figure 2 - Reasons for referral to HBO therapy for the patient population.
Figure 3 - Age: 27-year old. Gender: M. Indication for HBOT: High-pressure injection injury to the upper arm with subsequent soft tis-
sue necrosis and high risk for acute infection. A, B) Clinical presentation at admission (7 days after injury) as referral from a secon-
dary-care facility, where he had been treated with decompression fasciotomies, broad-spectrum empiric antibiotic therapy, and local
wound care. The patient was immediately started on daily HBO treatment sessions (<24 hours from admission). C) Surgical debride-
ment (sharp debridement) and wound coverage with cadaveric donor skin (post-injury day 17). D) New surgical debridement and
wound coverage with artificial dermal substitute on the palm and autologous skin graft on the forearm (post-injury day 39). The der-
mal substitute required revision and re-application 34 days after the procedure. E) Final wound coverage with autologous skin graft
on the palm (post-injury day 96). F) Ten-month follow-up. Total number of treatment sessions: 19.
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Hyperbaric oxygen therapy in Plastic Surgery practice
er arm, respectively). The second most common rea-
son for referral was acute soft tissue infections
(N=38, 20.6%, of which N= 5 necrotizing fasciitis).
The patient population was treated with HBO
per protocol according to the most recent Guide-
lines from Italian Undersea and Hyperbaric Medi-
cine Society (42) (Table 1). Patients underwent a
mean of 12.6±8.0 HBO treatment sessions (Figure
5). HBOT was begun a mean of 2.7±3.1 days after
admission and continued until healing/resolution
was completed. There were no adverse effects related
to HBO treatment in our series.
Discussion
Our experience confirms the usefulness of HBO
as auxiliary treatment for many plastic surgical con-
Figure 4 - Age: 16-year old. Gender: F.
Indication for HBOT: Crush injury to the
lower arm with degloving injury of the
foot and high risk for soft tissue necro-
sis and acute infection. A, B) Clinical
presentation at admission. C) After ur-
gent surgical debridement. The patient
was immediately started on daily HBO
treatment sessions (<48 hours from ad-
mission), broad-spectrum empiric anti-
biotic therapy, and local wound care. C)
Surgical debridement (sharp debride-
ment) and wound coverage with cadave-
ric donor skin (post-injury day 20). D)
Clinical status at post-injury day 67. The
patient required a new surgical debride-
ment. E) Fresh bleeding tissue after de-
bridement. F) Application of single-layer
artificial dermal substitute. G) Coverage
of the dermal substitute with autologous
skin graft. H) One-year follow-up. Total
number of treatment sessions: 15.
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F. Bassetto et al.
ditions and the low incidence of complications.
However, the timing and start of the treatment
seems to impact on the final outcome. A previously
published case series from our group (108) showed
that amongst 33 patients affected by complex in-
juries of the upper arm and who were treated with a
mean of 12.3 HBO treatment sessions per patient,
the only two secondary amputations were performed
in patients who underwent the first HBO session
more than 48 hours after the injury. Moreover, a
late start of HBO therapy was also associated with a
significantly higher infection rate (15.4% vs 57.1%
in patients receiving the first session within and after
the first 48 hours from the injury, respectively). Da-
ta on surgical procedures from the case series also
highlighted how the number of patients requiring
highly complex reconstructions (pedicled and/or
free flaps) was lower in the group receiving HBOT
earlier (15.4% vs 85.6%). Therefore, Authors postu-
lated that an early (<48 hours from admission) start
of HBOT could be associated with a reduction in
treatment costs by reducing surgical time, length of
hospital stay, number of dressing changes and
amount of dressing material (including advanced
products). Also, the patient could be referred to
physical and occupational therapy earlier, limiting
lost workdays and reducing social costs. The study
was certainly limited by the small patient population
and absence of randomization, but it could provide
the cue for further research focusing on the timing
and start of HBO therapy.
Although thermal burns have not been men-
tioned as one of the indications for HBO by the Ital-
ian Undersea and Hyperbaric Medicine Society, five
patients from our population were treated for this
condition. Universal consensus on the issue is still
lacking (109), but clinical results show HBOT re-
duces capillary stasis and limits the increase in size of
the coagulation zone, thus assisting in tissue preser-
vation. This mechanism might be of particular value
in the case of burns in aesthetically or functionally
important zones (face, hands, perineum) or with del-
icate vascularization (cartilaginous - ears, nose). In a
prospective study on burn patients, Hart et al. found
that HBOT treated patients required 2.2 ml/kg/%
total body surface area (TBSA) of fluids as opposed
to 3.4 ml/kg/% TBSA in the control group (110).
The hypothesized mechanisms of action involves a
vasoconstriction induced by hyperoxia, resulting in
reduced plasma exudation while preserving and en-
hancing tissue oxygenation. The reduction in edema
and fluid loss is responsible for a reduction in the
amount of fluids required for resuscitation. Further,
HBOT may exert beneficial effects by its anti-sludg-
Figure 5 - Mean HBO treatment sessions per patient per year.
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Hyperbaric oxygen therapy in Plastic Surgery practice
ing effect in the microcirculation and prevention of
injury by oxygen free radicals (109). Finally, HBOT
in the later stages of management of burns may be
useful by its antibacterial action (thus reducing sep-
sis) and by improved take of skin grafts. UHMS ap-
proves the use of HBO for thermal burns in the most
recently published guidelines (3).
Dangers, side effects and contraindications
HBOT is generally considered safe and with few
side effects. The most common problem is barotrau-
mas of the middle ear. Patients are taught autoinfla-
tion techniques and sometimes decongestants are
used. If necessary, grommets can be inserted. In
emergency treatments in unconscious patients,
myringotomy is performed. Prolonged exposure to
high-pressure oxygen can cause two potentially seri-
ous side-effects: seizures and pulmonary oxygen tox-
icity. Both of these are very rare, as safe therapeutic
limits have been developed over time. Oxygen toxi-
city seizures are not inherently harmful, and air
breathing intervals during HBO therapy are factored
into treatment regimens and prophylactic vitamin E
is administered to further minimize the risk. Careful
history is taken and prophylactic treatment is given
in those with specific risk factors; e.g. those with his-
tory of seizures, fever, acidosis, or low blood sugar.
Claustrophobia may be a problem with some pa-
tients, and it is reduced by having an attendant in-
side the chamber (multiplace) or beside it (mono-
place). Mild sedatives are sometimes indicated. Pa-
tients are expected to stop smoking for the entire
course of HBO therapy. The vasoconstrictive effects
of nicotine may interfere with angiogenesis, and
raised carbon monoxide levels reduce the full benefit
of oxygenation (111, 112).
The only absolute contra-indications are an un-
treated pneumothorax and certain anticancer drugs,
i.e. doxorubicin, bleomycin and cis-platinum, as
HBO significantly increases their cytotoxicity. Rela-
tive contra-indications include acute viral URTI’s,
sinusitis, bullous pulmonary disease, history of
spontaneous pneumothorax and congenital sphero-
cytosis. Consultation with a physician trained in hy-
perbaric medicine is important, both for evaluating
the indication for HBO therapy and for addressing
any possible contraindications (111, 112, 119).
Conclusions
HBOT was started as a treatment modality for
management of decompression sickness and, with the
passage of time, its scope has gradually increased to
include numerous indications. While there has been
substantial advancement of the field in recent years,
more work is required to establish the place of HBOT
in 21st century medicine. Investigation of fundamen-
tal mechanisms is still needed, and better patient se-
lection criteria would improve cost-efficacy.
Declarations
Ethics approval and consent to participate
The need for approval was waived.
Consent for publication
Acquired.
Availability of data and material
The datasets used and/or analysed during the
current study are available from the corresponding
Author on reasonable request.
Funding
Not applicable.
Competing interests
The Authors declare that they have no compet-
ing interests.
Authors’ contributions
Dr. Bassetto substantially contributed to the
conception and design of the article. Dr. Vindigni
contributed to the conception and design of the ar-
ticle and critically revised the content. Dr. Tocco-
Tussardi acquired and analysed the clinical data,
contributed to the conception and design of the ar-
ticle. Dr. Brambullo and Tiengo contributed to the
present work by interpreting the data. All Authors
read and approved the final manuscript.
Acknowledgments
The Authors would like to thank Dr. Elena
Pescarini and Dr. Gabriela Spanikova for skillful as-
sistance in data collection.
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F. Bassetto et al.
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