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\begin{document}

\title{Hyperbaric oxygen therapy as adjuvant therapy for odontogenic
necrotizing myositis: case report}



\author[1]{Andrea Neville Cracchiolo}%
\author[1]{Daniela Maria Palma}%
\author[1]{Marco Palmeri}%
\author[1]{Fabio Genco}%
\author[1]{Rosalia Lo Bue}%
\author[1]{Diego Tantillo}%
\author[1]{Andrea Braconi}%
\author[1]{Claudio Caramanna}%
\author[1]{Luigi Solazzo}%
\affil[1]{Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Civico Di Cristina Benfratelli}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\begin{abstract}
Necrotizing soft tissue infections (NSTIs) are life-threatening
conditions burdened with high mortality. They're often associated to a
poor prognosis if early diagnosis and prompt treatment is not warranted.
Treatment is always medical, often surgical and sometimes with
hyperbaric oxygen.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Necrotizing soft tissue infections (NSTIs) are life-threatening
conditions firstly described by Wilson in 1952. He portrayed a rare
infection characterized by bacteria-induced necrosis of the subcutaneous
tissue and fascia {[}1{]} with mortality from 6\% to 80\% {[}2{]} . The
infection travels along planes and later can potentially involve deeper
muscles with resultant myositis and myonecrosis.

The etiology is based on mono or polymicrobial infection and most
frequently arises from odontogenic infections {[}3{]}. Nowadays the
management is based on a rapid and aggressive surgical treatment with
removal of the necrotic tissue along with broad spectrum antibiotic
therapy. Some facilities have also included hyperbaric oxygen therapy
(HBOT) {[}4{]}. The Italian Society of Undersea and Hyperbaric Medicine
(SIMSI) is withheld the Italian authority on the indications for HBOT.
In the 2nd edition of their guidelines HBOT was also recommended as
adjuvant therapy in NSTIs {[}5{]}. Despite this, HBOT is not usually
used as a standard of care in these patients and this happens for
several reasons: not all hospitals are equipped with a hyperbaric
medicine service, a high percentage of doctors do not know the
usefulness of HBOT and its possible use in these conditions and
well-controlled, randomized, clinical trials demonstrating a
statistically significant benefit of HBOT are lacking and consequently
its use as an adjunctive therapy for NSTIs remains controversial{[}6{]}.
Besides transfer to a hospital equipped with HBOT, we should never delay
emergency surgical intervention.

We report the case of a young patient affected by NSTI resulting from
dental infection and complicated by necrotizing myositis of right
pectoral muscle treated with standard of care plus HBOT as adjuvant
therapy.

\textbf{Case report}

A 37 years old man was admitted to our maxillo facial surgery department
with a two weeks history of dental pain under treatment with antibiotic
therapy at home. During this time, after extraction of the lower right
third molar, there was a progressive swelling of the submandibular and
laterocervical region showing tense and painful skin and progressive
involvement of the right upper thoracic region. The patient did not
report any pathologies in his past medical history. On admission he was
conscious and cooperating, his body temperature was 37,5\selectlanguage{ngerman}°C, blood
pressure 110/60 mmHg, heart rate 94 b.p.m., oxygen saturation on room
air 98\% with no signs of respiratory exertion. Physical examination
revealed swelling of the latero-cervical region with involvement of the
right pectoral region where the skin appeared tense, burning and painful
on palpation (fig 1). Our examination of the oral cavity revealed a poor
oral hygiene condition with inflammation of the gingival mucosa and leak
of purulent material in the gingival fornix . The computed tomography
(CT) scan of the head, neck and thorax with contrast was performed and
revealed locules of gas and ill-defined low attenuation in the cervical
area and in the thigh chest muscle, highly suspicious for a gas-forming
infection (figure 2-3).

Routine laboratory report as follow: white blood cell count 15.230 mm3,
Hb 14,5 gr/dl, CPK 414 U/L, CRP 150 mg/L, PCT 0.94. The day after
admission the pain and swelling increased and he developed dysaesthesia
on the right upper thoracic zone. A compartment syndrome due to
infection was diagnosed, thus patient was urgently carried on operating
room where underwent to extensive surgical debridement of right pectoral
area. The operating field showed interstitial ``dishwater-like'' fluid
and discolored poor contractile muscles, with pockets of necrosis and
pus. The tissues were irrigated with 10 L of saline and based on advice
with infectious disease empiric antibiotic therapy was started with
piperacilline-tazobactam 4,5 gr ev/4 die and daptomycin 8 mg/kg/day ev.
Blood cultures were performed pre-operatively with a sterile peripheral
vein technique and during surgery cultures were taken from the surgical
site. After surgery patient was extubated and the day after he started
HBOT as adjunctive therapy in the treatment of NSTIs and myositis. The
HBOT treatment consisted in two dives with 100\% oxygen in a pressure
chamber 2,8 atmospheres absolute within the first two days, and then
daily for a total of 16 session. Clinical improvement was observed after
third day of HBOT and three weeks after admission patient was discharged
at home in good health (figure 4).

\textbf{Discussion}

NSTIs are infectious diseases burdened with high mortality that spreads
through the fascial planes and leads to connective tissue necrosis.
NSTIs may occur as a complication of a variety of surgical procedures or
medical conditions and it may also be idiopathic, as in scrotal or
penile necrotizing fasciitis.The prevalence is higher in males and in
patients aged 45 to 64 years. Physical findings may not be commensurate
with the degree of patient discomfort. Early in the disease course, the
patient may look misleading well; unfortunately, this may interfere with
early detection, which is the cornerstone to a favorable outcome. As
reported by our previous work{[}7{]}, the sites from which NSTIs may
originate in the cervical district are represented in order of frequency
by:

odontogenic infection, peritonsillar abscess and sinusitis.

According to the depth of tissue infection and necrosis, NSTs can be
classified into three forms which involve the dermis and subcutaneous
tissue for necrotizing cellulitis, the fascia for necrotizing fasciitis,
and the muscle layer with the intact overlying skin for necrotizing
myositis {[}8{]} .

Cervical fascia is the fibrous tissue that divides structures of the
neck and is divided into superficial and deep layers. The superficial
layer of the deep cervical fascia envelops parotid and submandibular
glands and it is the external border of the odontogenic infections of
the neck {[}9{]}. Most of these infections originate from the second or
third mandibular teeth infection or extraction. The roots of the second
and third molars can extend up to the submandibular space and through
this path the infections of this site can spread through the cervical
fascia to the lateral pharyngeal space, involve the retropharyngeal
space and track into the anterior or to the posterior mediastinal region
with the clinical picture of mediastinitis {[}10{]}. The infection can
be monomicrobial or polymicrobial. The most frequently isolated
organisms in NSTI include viridans group streptococci, S. aureus,
peptostreptococci, Bacteroides spp., Prevotella spp. and
Fusobacterium{[}11{]}

Antibiotic therapy must be started early, must be empirical and wide
spectrum in the early stages, subsequently tailored on the basis of the
results obtained from cultural tests performed on biological material.
Furthermore, in the choice of drugs used, other variables should be
carefully considered, such as the risk factors for multidrug-resistant
microorganisms. Finally, a further key point consists is the rapid
antibiotic steward ship which must be based on clinical evidence and
bio-humoral markers. Serum procalcitonin has been proposed as a
biomarker capable of guiding the response to antibiotic therapy,
allowing a rapid de-escalation. Normal serum procalcitonin concentration
in a healthy individual is \textless{}0.05 ng/mL. Patients with
procalcitonin concentration of \textless{}0.5 ng/mL are unlikely to have
sepsis. However, this concentration does not exclude infection, because
localized infections like cervical NSTI without systemic signs are still
possible{[}12{]} . Regrettably, with high frequency, antibiotic therapy
is started on an empirical basis without providing for targeted culture
samples and subsequently followed superficially.

Cervical NSTIs uncommonly gets complicated with the involvement of
muscles but when that happens, as happened in our patient, a theatre of
necrotizing myositis occurs. Necrotizing myositis is a surgical
emergency. It may presents without changes in the skin thus it is under
appreciated and diagnosis is often delayed {[}13{]} . In our patient the
entry route was through dental infection and this is in accordance with
a literature review published by Pellis et al {[}14{]} , wich
highlighted how the teeth are the main (65\%) responsible cause of NSTIs
of the cervical region. In our case infection, luckily did not involve
the deep cervical fascial planes, but spread along the superficial
planes and affect the subcutaneous skin and muscles of the right upper
thoracic region, as evidenced by the images.

HBOT has been proposed as an adjunctive therapy for patients with
NSTIs{[}15{]} . In HBOT, patients breathes 100\% oxygen for a specified
period of time in a pressurized chamber at pressure higher than
atmospheric pressure at sea level. It causes increased blood and oxygen
content in hypoxic tissues and this increased oxygen availability is
responsible for multiple effects as antimicrobial activity on both
aerobic and anaerobic bacteria thereby demonstrating the bactericidal
and bacteriostatic effects due to enhanced mobility and bacteriophagic
activity of leukocytes. Parts of the antimicrobial effects of HBOT are
believed to result of both formation of reactive oxygen species
(ROS){[}16{]} and synergistic effects with some antibiotics {[}17{]}

On top HBOT promotes granulation tissue formation due to fibroblast
proliferation and collagen synthesis, and improves microcirculation due
to edema reduction{[}18{]} .The increase in O2 tension produced by HBOT,
which persists for several hours after therapy, is responsible for
angiogenic properties of HBOT {[}19{]} Hyperbaric O2 causes reduced
platelet aggregation, improved tissue microcirculation, and diminished
metabolic disturbances. These properties along with increased dissolved
O2 in plasma lead to better oxygenation of hypoxic tissue, where red
blood cells cannot reach.{[}20{]}

The hyperbaric treatment of our patient was conducted on the basis of
the SIMSI guidelines {[}5{]}: in the first 3 days, we adopted the
maximum oxygen dosage at 2.8 ATA (284 kPa), twice day. From the 4th day:
treatments become daily with sessions at 2.5 ATA (253 kPa). The duration
of each session was 80 minutes and the treatment was continued until the
infection is considered to be overcome.

Absolute contraindications to HBOT are represented by non-drained
pneumothorax, PaO2 / FiO2 ratio \textless{}200 assessed by blood gas
analysis, seizures, claustrophobia and psychotic pictures in rupture.
Our patient had none of these, he showed good compliance with the method
with a good response to treatment from the third day of HBOT.

\textbf{Conclusion}

HBOT should be added to surgical treatment and antibiotics for all NSTIs
patients if there is no contraindications. Prompt HBOT could be useful
for preventing mortal complications and for reducing costs, associated
with the management of these patients, through a shorter length of stay
and a reduction in relapses.

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