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Hyperbaric Oxygen Therapy in Sinonasal Disease: Mechanisms, Clinical Evidence, and Multidisciplinary Perspectives on Invasive Fungal Rhinosinusitis and Post-Radiotherapy Injury

A peer-reviewed version of this preprint was published in:
Sinusitis 2026, 10(2), 21. https://doi.org/10.3390/sinusitis10020021

Submitted:

02 July 2026

Posted:

03 July 2026

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Abstract
Background. Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen at supra-atmospheric pressure, producing tissue hyperoxygenation, enhanced phagocytic killing, neoangiogenesis, and immunomodulation. Although HBOT is well established in head-and-neck practice, its specific role in sinonasal disease remains poorly systematised. Objective. To reappraise the rationale, evidence, and practical implementation of HBOT in two cardinal sinonasal indications—acute invasive fungal rhinosinusitis (AIFRS) and post-radiotherapy sinonasal damage—through a rhinology-centred, multidisciplinary lens. Methods. Narrative review of articles published in PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library between 1 January 1980 and 31 March 2026, conducted following the SANRA framework and combining MeSH terms for HBOT with sinonasal, mucormycosis, osteoradionecrosis, and skull-base keywords. Results. In AIFRS, HBOT addresses the angioinvasive ischaemic core, restores oxidative neutrophil killing, and potentiates amphotericin B; observational data—including the recent COVID-19-associated mucormycosis (CAM) experience—suggest a survival benefit when HBOT is added early to surgical and antifungal therapy. In post-radiotherapy injury, HBOT reverses Marx's hypoxic–hypocellular–hypovascular triad, supporting healing of osteoradionecrosis (maxillary and skull-base), soft-tissue radionecrosis, and reconstructive procedures in the irradiated bed. Sinus barotrauma, the most frequent rhinological complication, is largely preventable with structured pre-treatment ENT assessment. Conclusions. HBOT is a mechanistically well-founded, well-tolerated adjunct with a favourable safety profile when delivered by a multidisciplinary team. Sinonasal-specific prospective registries and pragmatic randomised trials are urgently needed.
Keywords: 
hyperbaric oxygen therapy
;  
rhinosinusitis
;  
radionecrosis
;  
invasive fungal rhinosinusitis
;  
mucormycosis
;  
osteoradionecrosis
;  
paranasal sinuses
;  
skull base
;  
sinus barotrauma
Subject: 
Medicine and Pharmacology  -   Otolaryngology

1. Introduction

The paranasal sinuses and anterior skull base occupy a peculiar position in head-and-neck pathology: their three-dimensional anatomy, proximity to the orbit and intracranial cavity, and reliance on a delicate mucosal microcirculation make them inherently vulnerable to two major insults—aggressive infection in the immunocompromised host and radiation-induced injury after treatment of sinonasal or nasopharyngeal malignancy. In both, the unifying pathophysiological mechanism is a critically hypoxic tissue microenvironment in which antimicrobial therapy and surgical débridement, however aggressive, are frequently insufficient if oxygenation is not restored.
Hyperbaric oxygen therapy (HBOT)—the intermittent administration of 100% oxygen at 2.0–2.8 atmospheres absolute (ATA)—directly targets this hypoxic niche. The Undersea and Hyperbaric Medical Society (UHMS) currently recognises 14 indications, several of which intersect head-and-neck practice, including necrotising soft-tissue infections, refractory osteomyelitis, compromised grafts and flaps, and delayed radiation injury [1,2]. Yet, despite this broad endorsement, the application of HBOT to sinonasal disease has received surprisingly little dedicated rhinological attention: the literature is fragmented across case reports, retrospective series, and reviews focused on the wider head-and-neck region. This is particularly regrettable for two conditions—acute invasive fungal rhinosinusitis (AIFRS) and post-radiotherapy sinonasal damage—which carry persistently high morbidity and mortality despite advances in pharmacotherapy and reconstructive surgery, and which frequently affect critically ill patients posing formidable safety challenges within the pressurised environment.
The present narrative review aims to fill this gap by offering a rhinology-focused synthesis of the current evidence. We first delineate the molecular, cellular and pharmacokinetic underpinnings of HBOT within the sinonasal microenvironment; we then provide a critical appraisal of its two principal rhinological applications — acute invasive fungal rhinosinusitis (AIFRS) and post-radiotherapy sinonasal injury — and discuss sinus barotrauma as the most clinically relevant HBOT-specific complication. A concise overview of related head-and-neck indications is also provided. Finally, we translate these data into practical multidisciplinary recommendations and outline priorities for future research.

2. Methods

This narrative review was conducted following the Scale for the Assessment of Narrative Review Articles (SANRA) framework. We searched PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library from 1 January 1980 to 31 March 2026, using combinations of the following terms: "hyperbaric oxygen" OR "HBOT" AND ("sinonasal" OR "paranasal sinuses" OR "rhinosinusitis" OR "mucormycosis" OR "invasive fungal sinusitis" OR "osteoradionecrosis" OR "skull base" OR "radionecrosis" OR "barotrauma" OR "COVID-19-associated mucormycosis"). Original studies, systematic reviews, narrative reviews, society guidelines, and selected case series of educational value were considered. Non-English articles were included when an English abstract was available and the methodology was judged adequate. Reference lists of pivotal papers were screened manually for additional sources. Conference abstracts and unpublished data were excluded. Two authors (D.S.P., L.L.V.) independently selected the references; disagreements were resolved by consensus with a third author (M.S.).

3. Mechanisms of Action Relevant to Sinonasal Disease

The therapeutic effects of HBOT can be grouped into four overlapping domains: hyperoxygenation and oxygen-gradient restoration, potentiation of host antimicrobial defences, stimulation of neoangiogenesis and tissue repair, and modulation of inflammation. Pharmacokinetic interactions with concomitantly administered drugs are summarised in Table 1, and the integrated mechanistic framework is presented in Table 2.

3.1. Hyperoxygenation and Restoration of the Oxygen Gradient

At 1 ATA, breathing air yields an arterial pO2 (PaO2) of approximately 100 mmHg and tissue pO2 of 40–60 mmHg in well-perfused organs. In ischaemic or irradiated tissue, values fall below 10–20 mmHg—a threshold at which fibroblast proliferation, collagen synthesis, and leukocyte killing are severely impaired [3]. At 2.4 ATA on 100% O2, PaO2 rises to ~1800 mmHg and tissue pO2 may exceed 300 mmHg even in poorly vascularised regions, because the dissolved-oxygen fraction (Henry's law) becomes the dominant delivery mechanism, independent of haemoglobin [4]. This is critical in AIFRS and osteoradionecrosis (ORN), where small-vessel thrombosis or obliteration renders haemoglobin-dependent delivery inadequate. The intermittent tissue pO2 peaks produced by daily sessions re-establish the oxygen gradient that drives angiogenic sprouting and fibroblast migration [5].

3.2. Potentiation of Host Antimicrobial Defences

Polymorphonuclear leukocyte (PMN) bactericidal activity is critically oxygen-dependent: the respiratory burst, generating superoxide (O2−), hydrogen peroxide (H2O2), and hypochlorous acid (HOCl) via NADPH oxidase, requires molecular oxygen as substrate. In hypoxic tissue, this burst is attenuated up to 50-fold, rendering phagocytes functionally impotent despite adequate numbers [6]. HBOT restores—and supranormally enhances—PMN killing capacity, an effect persisting for several hours after the session [7]. This is particularly relevant to AIFRS, in which neutropenia, corticosteroid-induced dysfunction, or diabetic ketoacidosis-related acidosis impair phagocytic competence. Elevated tissue oxygen also inhibits anaerobes within necrotic foci that may harbour secondary bacterial superinfection [8].

3.3. Neoangiogenesis and Tissue Repair

The pro-angiogenic effect of HBOT depends on cyclical alternation between hyperoxia (during sessions) and relative hypoxia (between sessions) [9]. Hyperoxia upregulates VEGF in macrophages, mobilises endothelial progenitor cells via a nitric-oxide-dependent pathway, and increases local PDGF and FGF [10,11]. Over 20–40 daily sessions, this produces a measurable increase in vascular density—a phenomenon histologically demonstrated in irradiated mandibular bone (Marx model) [12]. Collagen maturation is also oxygen-dependent: prolyl and lysyl hydroxylase require molecular oxygen for the cross-linking that confers tensile strength [13]. These effects are pertinent to healing of post-débridement cavities and recovery of irradiated mucosa.

3.4. Modulation of Inflammation

HBOT exerts a dual, context-dependent effect. Acutely, it inhibits neutrophil β2-integrin (CD18)-mediated endothelial adherence, attenuating ischaemia–reperfusion injury [14], and downregulates TNF-α, IL-1β, and IL-6 while upregulating IL-10 [15]. In chronic-wound settings—such as the irradiated sinus—it promotes M2-macrophage polarisation and growth-factor release [16]. This balance is valuable in the sinonasal environment, where thin mucosa overlying bone is susceptible to both undertreatment (persistent infection) and overtreatment (excessive fibrosis).

3.5. Biofilm Disruption

Finally, emerging evidence indicates that HBOT can enhance antibiotic penetration and bactericidal activity against biofilm-forming organisms [17]. Although still investigational, this mechanism is of potential interest in refractory chronic rhinosinusitis—the condition at the core of everyday rhinological practice—and represents a logical, currently under-explored bridge between the indications reviewed here and routine sinonasal disease.
Table 1. Pharmacokinetic considerations under hyperbaric conditions.
Table 1. Pharmacokinetic considerations under hyperbaric conditions.
Drug Class Hyperbaric Implication
Amphotericin B Fungicidal activity partly mediated by reactive oxygen species; supra-additive effect with HBOT plausible in AIFRS [18,19].
Aminoglycosides and fluoroquinolones Bactericidal activity oxygen-dependent and potentiated by HBOT.
Metronidazole Requires low-redox environment; theoretical attenuation under hyperoxia, not clinically demonstrated [20].
Volatile anaesthetics MAC unchanged at 2.0–2.8 ATA, but vaporisers must be hyperbaric-validated; total intravenous anaesthesia (TIVA) is preferred [21].
Propofol, midazolam, opioids Pharmacokinetics substantially preserved; mild slowing of redistribution due to hyperoxia-induced ~10–15% reduction in cardiac output [22].
Table 2. Mechanistic effects of HBOT relevant to sinonasal pathology.
Table 2. Mechanistic effects of HBOT relevant to sinonasal pathology.
Mechanism Cellular/molecular basis Relevance to AIFRS Relevance to post-RT injury Refs.
Tissue hyperoxygenation Henry's law: dissolved O2 becomes principal delivery vector Restores O2 to peri-necrotic penumbra distal to thrombosed vessels Reverses chronic hypoxia of irradiated tissue [3,4]
Phagocyte oxidative burst NADPH-oxidase reactivation Restores PMN fungicidal killing in DKA/neutropenia Reduces secondary infection of necrotic foci [6,7]
Neoangiogenesis VEGF↑, EPC mobilisation, PDGF/FGF Revascularises debrided cavity Rebuilds capillary density (Marx model) [9,10,11,12]
Collagen maturation Prolyl/lysyl hydroxylase O2-dependent Supports post-surgical healing Enables stable mucosal regeneration [13]
Immunomodulation ↓CD18 adhesion; ↓TNF-α/IL-1β/IL-6; ↑IL-10; M2 polarisation Limits bystander damage during reperfusion Promotes constructive remodelling [14,15,16]
Antimicrobial synergy ROS-mediated potentiation of amphotericin B and aminoglycosides Supra-additive with liposomal amphotericin B Adjunctive in superinfected ORN [18,19]

4. HBOT in Acute Invasive Fungal Rhinosinusitis

4.1. Clinical Significance and Pathophysiological Rationale

AIFRS is a fulminant, life-threatening infection characterised by rapid fungal invasion of mucosa, submucosa, bone, and vasculature, with propensity for orbital and intracranial extension. It occurs almost exclusively in immunocompromised hosts—uncontrolled diabetes (especially in ketoacidosis), haematological malignancy, prolonged neutropenia, transplantation, and high-dose corticosteroid therapy [23]. The principal pathogens are Mucorales (Rhizopus, Mucor, Rhizomucor, Lichtheimia) and Aspergillus spp. Despite advances in antifungal pharmacotherapy and endoscopic surgery, mortality remains 20–80% [24,25], and survivors often suffer severe functional and aesthetic morbidity.
The pathogenesis is dominated by angioinvasion: hyphae penetrate vessel walls, proliferate, and cause thrombosis with downstream infarction, with fungal elements such as Rhizopus oryzae further amplifying chemotactic and inflammatory cascades within the necrotic core [26,27]. This generates a vicious cycle—ischaemic necrosis impairs host defence and antifungal delivery, while expanding devitalised tissue fuels further fungal growth.
HBOT intervenes at multiple points: it bypasses thrombosed vasculature via dissolved oxygen, restoring oxygenation of the peri-necrotic penumbra [28]; it restores neutrophil oxidative burst, particularly relevant in DKA where acidosis and hyperglycaemia independently impair PMN function [6]; it potentiates amphotericin B fungicidal activity [18]; and it stimulates revascularisation of the debrided cavity. In vitro and clinical observations also suggest a direct inhibitory effect on Mucorales and Aspergillus species, although its quantitative contribution remains uncertain [29].

4.2. COVID-19-Associated Mucormycosis (CAM)

The SARS-CoV-2 pandemic produced an unprecedented surge of AIFRS, particularly in India during the 2021 second wave ("black fungus") [30]. The convergence of uncontrolled diabetes, high-dose corticosteroids, lymphopenia, and possible iron dysregulation created ideal conditions for Mucorales infection, with rhinocerebral involvement predominating [31]. Several Indian centres reported adjunctive HBOT in CAM with apparent survival benefit and reduced surgical extent [32,33]; despite their retrospective design, these reports represent the largest collective experience to date and have reinvigorated interest in HBOT for AIFRS.

4.3. Staging and Treatment Algorithm

Several staging systems exist. Honavar's classification of rhino-orbito-cerebral mucormycosis (ROCM) divides disease into stage 1 (nasal only), 2 (sinonasal ± unilateral orbit), 3 (bilateral orbit/CNS), and 4 (disseminated) [34]; the Plowes-Hernández TNM-style system and the Cornely EQUAL score offer additional frameworks [35,36]. A pragmatic approach considers HBOT as standard adjunct in stages 1–2, case-by-case in stage 3, and generally not indicated in stage 4 [37].

4.4. Clinical Evidence

The evidence base is entirely observational; no randomised controlled trial (RCT) has been performed, and the rarity and acuity of AIFRS make such a trial logistically and ethically challenging. The principal series are summarised in Table 3. While the consistent direction of findings supports an adjunctive role, the level of evidence remains low (Level 3–4), with confounding by indication a major limitation: patients sufficiently stable to tolerate chamber pressurisation may have an inherently better prognosis.

4.5. Treatment Protocol and Surgical Integration

Typical adjunctive protocol: 2.0–2.5 ATA, 90 minutes O2 breathing, daily, for 20–40 sessions, started within 24–48 h of the first débridement, with reassessment by serial endoscopy and contrast-enhanced MRI every 7–10 days [41]. HBOT must not delay initial surgery; between débridements, it stabilises the peri-necrotic zone and may allow more conservative subsequent resections. Some authors advocate a pre-operative session on the morning of repeat débridement to enhance intraoperative tissue discrimination and reduce bleeding [42]. Concurrent systemic antifungal therapy (liposomal amphotericin B 5–10 mg/kg/day, transitioning to posaconazole or isavuconazole) is maintained throughout, consistent with current ECMM/MSGERC global-guideline recommendations [19,43].

4.6. The Critically Ill AIFRS Patient: A Multidisciplinary, Intensive-Care Perspective

A substantial proportion of AIFRS patients considered for HBOT are critically ill—in diabetic ketoacidosis with haemodynamic instability, profoundly neutropenic with concurrent sepsis, or in the early post-transplant period. Far from contraindicating treatment, this scenario is precisely where the multidisciplinary model demonstrates its value: from the intensivist's standpoint, the organ support routinely delivered in the ICU can be reproduced inside the hyperbaric chamber. The hyperbaric-medicine anaesthesiologist assumes responsibility for pre-session stabilisation, mechanical ventilation under pressure (requiring hyperbaric-validated ventilators, tidal volumes recalculated according to Boyle's law, and continuous capnography), invasive haemodynamic monitoring, glycaemic control with hyperbaric-validated point-of-care devices, and the management of intra-chamber emergencies such as oxygen-toxicity seizures, tension pneumothorax, and cardiac arrest [44,45,46,47,48,49,50,51,52,53]. The corresponding technical protocols are detailed in Supplementary Material S1. The practical message for the rhinologist is therefore a reassuring one: where intensive-care expertise is embedded within the hyperbaric facility, even mechanically ventilated, haemodynamically supported AIFRS patients can safely receive adjunctive HBOT, and critical illness per se should not be regarded as a barrier to referral.
Paediatric disease deserves specific mention. AIFRS in children—predominantly in the setting of haematological malignancy, post-transplantation, and primary immunodeficiency—follows the same biological principles, but HBOT protocols require adaptation: lower target pressures (typically 2.0–2.2 ATA), shorter sessions (60–90 minutes), and, where feasible, multiplace chambers allowing the presence of a parent or specialist nurse. Published experience with adjunctive HBOT in paediatric AIFRS is limited to case reports; close collaboration between paediatric oncology, rhinology, and hyperbaric medicine is essential, and an individualised risk–benefit assessment is mandatory.

4.7. Chronic Invasive and Granulomatous Forms

Chronic invasive (CIFS) and chronic granulomatous (CGFS) fungal sinusitis—the latter frequently caused by Aspergillus flavus in immunocompetent hosts in South Asia and the Middle East [54]—involve slower tissue invasion. The role of HBOT in these forms has not been specifically studied, but the pro-angiogenic and reparative rationale suggests potential benefit in refractory cases; this is a clear gap warranting future investigation.
In practice, HBOT in AIFRS is best conceived not as a salvage measure but as an early adjunct—initiated within 24–48 h of the first débridement and reserved primarily for stages 1–2—with the multidisciplinary team enabling its safe use even in the critically ill.

5. HBOT in Post-Radiotherapy Sinonasal Damage

5.1. Spectrum of Radiation-Induced Sinonasal Injury

Radiotherapy (RT) is central to the treatment of paranasal sinus, nasal cavity, and nasopharyngeal malignancies. Despite advances in IMRT and proton-beam therapy, sinonasal tissues frequently lie within high-dose volumes [55]. Late effects—appearing months to years post-RT—include mucosal atrophy, refractory chronic rhinosinusitis, osteoradionecrosis (ORN) of the maxilla, palate, sphenoid, or skull base, soft-tissue radionecrosis (STRN) with fistula formation, skull-base necrosis with potential CSF leak, and cranial neuropathy [56,57].
The pathophysiology is captured by Marx's "three-H" paradigm: tissue is hypoxic, hypocellular, and hypovascular as a consequence of endarteritis obliterans [58,59]. Once ORN/STRN is established, the cycle is self-perpetuating, since damaged vasculature cannot meet the metabolic demand created by inflammation.

5.2. Osteoradionecrosis of the Maxilla and Skull Base

Maxillary ORN occurs in 2–10% of patients after RT for sinonasal/nasopharyngeal malignancy and is challenging because of thin bony walls and proximity to orbit and skull base [60]. Skull-base ORN (SBORN), involving sphenoid, clivus, or petrous apex, is a feared complication of RT for nasopharyngeal carcinoma and clival chordoma, presenting with headache, cranial neuropathies (most often abducens palsy), CSF rhinorrhoea, or secondary infection [61]. The Notani classification, originally developed for mandibular disease, has been adapted to other craniofacial sites and remains useful for stratifying treatment intensity according to extent of bony involvement and radiation dose [62].
The UHMS recognises delayed radiation injury of bone as a covered HBOT indication (Level 2 evidence) [63]. While the strongest data pertain to mandibular ORN (Marx RCT, 1985 [64]), the pathophysiology is identical in the maxilla and skull base. The Marx protocol—30 pre-operative + 10 post-operative sessions at 2.4 ATA, 90 minutes daily—has been applied to maxillary and skull-base ORN with resolution or improvement in 50–80% of patients [65,66].

5.3. Soft-Tissue Radionecrosis and Chronic Radiation-Induced Sinusitis

Beyond bony necrosis, RT causes chronic non-healing ulceration, mucosal atrophy with persistent crusting, oroantral or oronasal fistulae, and a debilitating chronic rhinosinusitis with thick secretions, bacterial superinfection, and progressive obstruction [67]. Standard treatments often disappoint because they do not address tissue hypoxia. STRN is a separate UHMS-approved HBOT indication, supported by the RCT (Teguh et al., 2009) demonstrating quality-of-life improvements in irradiated head-and-neck survivors [68]. Although not sinonasal-specific, the same pro-angiogenic and reparative mechanisms apply. HBOT is particularly valuable as pre-conditioning before planned procedures in the irradiated field—endoscopic sinus surgery, oroantral fistula repair, skull-base reconstruction—reducing wound breakdown and ORN exacerbation [69].

5.4. Post-Radiation CSF Leak and Skull-Base Defects

CSF rhinorrhoea from skull-base necrosis carries a high risk of ascending meningitis. Endoscopic repair with vascularised flaps (nasoseptal, pericranial) is the preferred approach but flap viability is jeopardised by the irradiated bed. Case series describe HBOT both pre- and post-operatively (typically 20 + 10 sessions) with encouraging outcomes [70,71]; the mechanistic rationale is strong and warrants formal study.

5.5. Evidence and Controversies

Sinonasal-specific data remain limited to case series and retrospective analyses. The ORN96 trial (Annane et al., 2004) reported no benefit in mandibular ORN and was terminated early [72], but has been heavily critiqued for protocol deviations, an unusually high control-arm spontaneous resolution, and inadequate baseline staging; its findings have not been replicated [73]. More recently, the HOPON trial in irradiated mandible (Shaw et al., 2019) provided contemporary RCT data on prophylactic HBOT before dentoalveolar surgery, with prespecified endpoints addressing several methodological criticisms of earlier studies [74]. The broader literature, including the Marx RCT and large retrospective series, continues to support HBOT for established ORN and prophylaxis before surgery in the irradiated field. The risk-benefit profile of a non-invasive, well-tolerated therapy is favourable, particularly given the paucity of alternatives.
For the rhinologist, the key point is that established sinonasal ORN/STRN, and procedures planned in the irradiated field, are the settings in which HBOT—whether therapeutic or as pre-surgical conditioning—offers the most favourable risk–benefit balance, given the paucity of effective alternatives.

6. Sinus Barotrauma: An HBOT-Specific Rhinological Complication

6.1. Pathophysiology and Risk Factors

Sinus barotrauma is the most common otorhinolaryngological complication of HBOT, affecting 2–9% of patients—mild forms likely under-reported [75]. It results from failure of pressure equilibration between sinus cavity and chamber during compression. Obstruction of the ostium (mucosal oedema, polyps, septal deviation, secretions) generates relative intra-sinusal negative pressure, with mucosal engorgement, submucosal haemorrhage, and—in severe cases—haematoma or wall fracture [76]. The frontal and maxillary sinuses are most often involved, given their tortuous drainage. Pre-existing chronic rhinosinusitis, polyposis, and significant septal deviation are key risk factors. This pattern is mirrored in real-world practice: in a recent Italian national multicentre prospective study, difficulty with pressure equalisation was the leading cause of session interruption and the principal non-serious adverse event, with no serious adverse events recorded across the cohort [77].

6.2. Prevention and Management

Prevention starts with structured rhinological assessment before initiating HBOT, ideally including screening nasal endoscopy and CT in patients with sinonasal symptoms [78]. Modifiable risk factors should be addressed before or concurrently with HBOT. Topical nasal corticosteroids and oxymetazoline 15–30 minutes before each session reduce ostial oedema; slower compression rates allow more time for equilibration. A modified Weissman/Teed-style severity grading guides management (Table 4).
Adapted from [79]. Liaison between the rhinologist (anatomical and pathological assessment) and the hyperbaric-medicine anaesthesiologist (compression/decompression profile) is essential.
Because sinus barotrauma is the only sinonasal complication caused by HBOT itself, it is also the most preventable: structured pre-treatment rhinological assessment, pharmacological optimisation of ostial patency, and a slower compression profile remove most of the risk before the first session.

7. HBOT in Other Head-and-Neck Indications: Brief Overview

Several other head-and-neck indications share the mechanistic framework outlined in Section 3 and are regularly encountered by the same multidisciplinary team that manages sinonasal disease; they are summarised here to situate the sinonasal applications within their broader clinical context. Mandibular ORN is the prototypical and most extensively studied indication—directly relevant to the maxillary and skull-base disease discussed above—supported by the Marx RCT [64] and large case series with resolution rates of 50–90% [80]; the prophylactic 20+10 protocol reduces post-extraction ORN in the irradiated mandible from ~30% to <5% [81]. Laryngeal chondroradionecrosis responds to HBOT in 50–60% of cases, potentially avoiding laryngectomy [82,83], and radiation-induced xerostomia is supported by Level 1 evidence from the trial by Teguh et al. [68]. Of particular pathophysiological kinship with AIFRS is malignant otitis externa, in which adjunctive HBOT improves cure rates in refractory cases [84,85]. Sudden sensorineural hearing loss features in the AAO-HNS guideline as salvage therapy when initiated within two weeks of onset [86,87]; and compromised grafts or flaps in irradiated fields benefit from both pre-conditioning and salvage HBOT [88,89]—a consideration directly applicable to sinonasal and skull-base reconstruction.

8. Practical Considerations for the Multidisciplinary Team

8.1. Patient Selection and Referral Timing

In AIFRS, referral should be initiated at the time of diagnosis and first débridement, not after failure of standard therapy. In post-RT injury, HBOT should be considered for established refractory ORN/STRN, before surgery in the irradiated field (prophylactic protocol), or when post-surgical wound healing is failing. Formal hyperbaric-medicine anaesthesiology consultation confirms candidacy and identifies contraindications.

8.2. Contraindications and Precautions

These are summarised in Table 5. The anaesthesiologist must weigh contraindications against severity: in life-threatening AIFRS, a relative contraindication may be accepted with precautions; in elective post-RT sinusitis, the same may tip the balance against treatment.

8.3. Treatment Protocols

Standard protocols are summarised in Table 6. Critically ill patients requiring continuous monitoring, mechanical ventilation, or vasopressor infusions should be treated in multiplace chambers to allow attendant care.

8.4. Oxygen Toxicity: Practical Surveillance

CNS oxygen toxicity (Paul Bert effect) presents as a generalised tonic-clonic seizure, with incidence ~1–3 per 10,000 patient-sessions at 2.0–2.4 ATA [90,91,92]. Prodromal symptoms—captured by the VENTID-C mnemonic (Vision, Ears/tinnitus, Nausea, Twitching, Irritability, Dizziness, Convulsions) [92]—should be recognised by all chamber staff. Management consists of immediate removal of the O2 source (hood/mask switch to air in multiplace; controlled decompression in monoplace), benzodiazepines if persistent (midazolam 2–5 mg IV or 5–10 mg IM), and airway protection [93,94,95]. Pulmonary toxicity (Lorrain Smith effect) is cumulative: weekly spirometry (FVC, FEV1) is recommended for prolonged courses (>20–30 sessions); a >10% FVC decline warrants reduced frequency or rest days [49]. Reversible myopia affects up to 20% of patients on extended courses and resolves over weeks to months [96,97]. Detailed protocols for ventilated patients, intra-chamber emergencies, and pharmacokinetic considerations are provided in Supplementary Material S1.

8.5. Pre-HBOT Rhinological Checklist

A structured pre-HBOT rhinological evaluation reduces the incidence of sinus barotrauma and identifies modifiable risk factors. Recommended elements: (i) targeted history (chronic rhinosinusitis, polyposis, previous sinonasal surgery, allergic rhinitis, ability to perform Valsalva); (ii) anterior rhinoscopy and flexible nasal endoscopy; (iii) sinus CT in symptomatic patients or those with prior pathology; (iv) optimisation of sinus drainage (intranasal corticosteroids ± oral antibiotics if indicated); (v) shared treatment plan including topical decongestant pre-medication and adapted compression rate.

8.6. The Hyperbaric Anaesthesiologist and the Rhinologist: A Structured Interface

In many European systems, hyperbaric units are directed by anaesthesiologist-intensivists, who act as the "conductors" of each session: pre-session clearance, selection of the treatment table, supervision of compression and decompression, management of intra-chamber emergencies, and post-session evaluation [53]. For the rhinologist, this means that responsibility for safe delivery is shared rather than delegated. The rhinologist contributes the anatomical, endoscopic, and surgical assessment and defines the therapeutic target; the hyperbaric anaesthesiologist governs the physiological conduct of the session and the safety of the critically ill patient under pressure. This relationship is best formalised through joint planning meetings, shared progress notes, and predefined adverse-event communication pathways—mirroring the surgeon–anaesthesiologist dyad of the operating theatre, and equally indispensable to a safe outcome. This model reflects real-world Italian practice: in a recent national multicentre prospective study of hyperbaric oxygen therapy, certified anaesthesiologist-intensivists constituted the medical staff of most participating centres, underscoring the central role of intensive-care competence in the safe delivery of HBOT [77].

8.7. Logistical and Cost Considerations

HBOT is time-intensive (~2 hours per session) and demands daily attendance over several weeks. Facility availability is uneven and reimbursement requires prior authorisation in most jurisdictions; the administrative burden should not be underestimated [98].

8.8. Limitations of the Available Evidence

Several caveats temper the recommendations advanced in this review. First, no randomised controlled trial has tested HBOT against sinonasal-specific endpoints; the AIFRS evidence base is entirely observational (Level 3–4), with confounding by indication an unavoidable concern. Second, the post-radiotherapy literature is dominated by mandibular ORN, and extrapolation to maxillary, sphenoid, and skull-base ORN—although mechanistically reasonable—has not been formally validated. Third, HBOT protocols vary considerably in pressure, session duration, and total number of sessions, hampering meta-analytic synthesis. Fourth, reporting bias is likely, with preferential publication of successful series and probable under-reporting of complications. Fifth, paediatric data are sparse, and HBOT parameters in children require dedicated protocols. Sixth, this is a narrative—not systematic—review; selection of references reflects authors’ judgement rather than a pre-specified inclusion algorithm, and grey literature was not searched. Seventh, the bulk of CAM evidence originates from a single geographical and temporal context (the 2021 Indian wave), limiting external validity to other epidemiological settings.

9. Conclusions and Future Directions

HBOT occupies a mechanistically coherent place in the management of two of the most challenging sinonasal conditions encountered in modern rhinology. In AIFRS, it targets the ischaemic core of angioinvasive disease, restores phagocytic competence, and augments antifungal pharmacotherapy. In post-RT injury, it reverses the hypoxic–hypocellular–hypovascular triad underlying ORN and STRN. Across both indications, the available evidence—although predominantly observational—is consistent and biologically plausible.
Three messages emerge for the practising rhinologist. First, early referral matters: HBOT in AIFRS appears most effective when initiated within 24–48 hours of the first débridement, not as a salvage measure. Second, multidisciplinary integration is essential: the rhinologist contributes anatomical, surgical, and endoscopic expertise; the hyperbaric-medicine anaesthesiologist ensures safe delivery, particularly in critically ill, ventilated, or metabolically deranged patients. Third, sinus barotrauma—the only sinonasal complication directly caused by HBOT itself—is largely preventable through structured pre-treatment rhinological assessment.
Priorities for future research are concrete and achievable: (i) prospective multicentre AIFRS/CAM registries embedded in the ECMM/EQUAL networks; (ii) pragmatic, pre-registered RCTs of adjunctive HBOT in AIFRS with hard, sinonasal-specific endpoints (e.g., orbital exenteration-free survival, time to negative endoscopic biopsy, 30- and 90-day all-cause mortality); (iii) prospective pre-surgical HBOT studies in the irradiated sinonasal field, using endoscopic scoring, transcutaneous oximetry, and validated patient-reported outcomes such as the SNOT-22 [99]; (iv) translational work on HBOT–antifungal pharmacodynamic interactions in models of rhinocerebral mucormycosis; (v) cost-effectiveness analyses anchored to real-world reimbursement scenarios; and (vi) jointly authored, standardised rhinology–anaesthesiology intra-chamber critical-care protocols. Until such data emerge, HBOT should be regarded as a mechanistically justified, well-tolerated adjunct—deployed selectively, early, and within a structured rhinology–hyperbaric medicine collaboration.

Author Contributions

Conceptualization, D.S.P. and M.S.; methodology, D.S.P., L.L.V. and A.M.; literature search and data curation, D.S.P., L.L.V., A.M., M.L. and A.C.; writing—original draft preparation, D.S.P., L.L.V., A.M. and M.L.; writing—review and editing, all authors; visualisation, C.M.T., F.P., E.P., P.T. and E.L.G.; supervision, M.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable (narrative review).

Conflicts of Interest

The authors declare no conflict of interest.

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Table 3. Summary of clinical evidence for adjunctive HBOT in AIFRS.
Table 3. Summary of clinical evidence for adjunctive HBOT in AIFRS.
Author/year Design N Pathogen HBOT protocol Outcome LoE
Ferguson et al. 1988 [38] Retrospective case series 6 Mucorales 2.0–2.5 ATA, daily Improved survival vs historical controls 4
Couch et al. 1988 [39] Case series 2 Mucorales 2.0–2.5 ATA, daily 2/2 survived (both disease-free at 21 months) 4
Garcia-Covarrubias et al. 2004 [40] Literature review + cases 28 Mucorales Variable Favourable survival, especially if early 4
LoE, Level of Evidence (Oxford CEBM).
Table 4. Severity grading and management of HBOT-induced sinus barotrauma.
Table 4. Severity grading and management of HBOT-induced sinus barotrauma.
Grade Clinical/imaging findings Management HBOT continuation
1 (mild) Transient facial pain; no imaging changes Topical decongestants; analgesia Continue, slower compression
2 (moderate) Persistent pain; mucosal thickening/opacification on imaging Short oral steroid course; optimise drainage Temporary pause; resume after improvement
3 (severe) Haemosinus; orbital symptoms Suspend HBOT; rhinological assessment ± endoscopic sinus surgery Resume only after surgical drainage
Table 5. Contraindications and precautions for HBOT in sinonasal patients.
Table 5. Contraindications and precautions for HBOT in sinonasal patients.
Category Item Rationale
Absolute Untreated pneumothorax Risk of fatal tension pneumothorax during decompression
Concurrent bleomycin Risk of fatal pulmonary fibrosis
Active cisplatin/doxorubicin Enhanced organ toxicity
Relative Uncontrolled seizure disorder CNS O2 toxicity risk
Severe congestive heart failure Pulmonary oedema risk (hyperoxic vasoconstriction)
Severe claustrophobia Manageable with anxiolytic premedication
URI/active sinonasal inflammation Sinus barotrauma risk
Fever > 38.5 °C Lowered seizure threshold
Prior thoracic radiation Pulmonary barotrauma/O2 toxicity risk
Sinonasal-specific Significant septal deviation, nasal polyposis, ostial obstruction Sinus barotrauma — address before/during HBOT
Otitis media with effusion Impaired Eustachian tube equalisation; high risk of middle-ear barotrauma during compression — myringotomy ± tympanostomy tube placement recommended before initiating HBOT
Recent endoscopic sinus surgery (< 2 weeks) Fresh mucosal flaps, unhealed osteotomies and intracavitary packing predispose to surgical emphysema, epistaxis and disruption of healing under pressure changes; defer HBOT until ≥ 2 weeks post-op or until endoscopic confirmation of mucosal sealing
Table 6. HBOT protocols by sinonasal indication.
Table 6. HBOT protocols by sinonasal indication.
Indication Pressure (ATA) Session length (min O2) Frequency Total sessions Comments
AIFRS (acute) 2.0–2.5 90 Daily (or BID severe) 20–40 Start within 24–48 h of first débridement
Established sinonasal ORN 2.4 90 Daily 30 + 10 (Marx) Surgery between pre- and post-op blocks
STRN of paranasal sinuses 2.0–2.4 90 Daily 30–40 Combine with topical/systemic therapy
Pre-surgical conditioning (irradiated field) 2.4 90 Daily 20 + 10 Prophylactic ("Marx") regimen
Post-RT CSF leak repair 2.4 90 Daily 20 + 10 Around endoscopic flap repair
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