Introduction

Hyperbaric oxygen therapy (HBOT) exposes the body to a pressurized environment of at least 1.4 atmospheres absolute (ATA) with 100% oxygen inspiration.[1] Selecting an appropriate treatment plan requires balancing risks and benefits.[2] Although HBOT is generally well tolerated, candidates, especially those with chronic medical conditions, must be evaluated carefully before treatment begins.

Function

Absolute Contraindications

The only absolute contraindication to HBOT is untreated pneumothorax. Placing a patient in a chamber and altering ambient pressure can trigger life-threatening tension pneumothorax during ascent. Patients with pneumothorax should receive appropriate treatment, such as thoracostomy tube insertion, before undergoing HBOT.

Relative Contraindications

Certain conditions were previously considered absolute contraindications to HBOT, but evolving evidence now supports their reclassification as relative contraindications. These conditions include the following:

• Concurrent doxorubicin use and HBOT can increase the risk of doxorubicin-mediated cardiotoxicity. However, the risk can be mitigated by discontinuing doxorubicin at least 24 hours before HBOT, allowing treatment while minimizing potential adverse effects.
• Treatment with bleomycin, known to cause interstitial pneumonitis and fibrosis, was previously considered an absolute contraindication for HBOT due to studies suggesting an increased risk of adverse effects with supplemental oxygen. However, recent research indicates that many patients can safely undergo HBOT, particularly if drug exposure occurred more than 6 months prior. A pretreatment evaluation, including a physical examination, radiography, blood gas analysis, and spirometry, is necessary to assess HBOT safety.
• Disulfiram inhibits superoxide dismutase, increasing the risk of oxygen toxicity, which can present with seizures and pulmonary complications. To minimize this risk, the medication should be discontinued before HBOT, allowing for adequate clearance. Careful monitoring for early signs of toxicity and adjusting oxygen exposure parameters may further enhance patient safety.
• Cisplatin use is a relative contraindication due to the drug's potential to impair wound healing, which may reduce HBOT's effectiveness for treating wounds and late radiation effects. However, no evidence suggests an increased risk or severity of side effects with cisplatin, and its use remains acceptable in emergent HBOT applications.
• Mafenide increases local carbon dioxide production, potentially leading to acidosis. Removing the medication before HBOT can enhance safety. No significant adverse effects have been well documented from concurrent use of this medication.[3]

A number of conditions have traditionally been regarded as relative contraindications to HBOT, necessitating a thorough evaluation of individual risk factors and potential benefits to determine whether proceeding with this intervention is appropriate. These conditions include the following:

• Chronic obstructive pulmonary disease is a relative contraindication to HBOT due to the risk of hypercarbia. Increased oxygen levels can lead to oxygen-induced hypoventilation and exacerbate ventilation/perfusion (V/Q) mismatch.
• Asthma may cause air trapping and pulmonary barotrauma. Similarly, asymptomatic pulmonary blebs, bullae, and pulmonary sequestrations identified on imaging are relative contraindications due to the risk of air trapping leading to pneumothorax.[4]
• Implanted devices should be pressure-tested to ensure functionality in a high-pressure environment. Most withstand 100 feet of seawater (4 ATA), but manufacturer confirmation is advisable. While no cases of an internal cardiac defibrillator triggering a fire in the hyperbaric chamber have been reported, disabling the device during treatment may be considered if the dysrhythmia risk is acceptable. Emergent treatment with HBOT may still be reasonable for patients with implanted defibrillators, as ex vivo data support its safety.[5]
• Epidural pain pumps may malfunction or deform under pressure. Contacting the manufacturer is essential to determine device-specific pressure limitations.
• Pregnancy has traditionally been considered a relative contraindication due to unknown fetal effects. However, recent studies suggest that HBOT may be beneficial in specific cases, such as carbon monoxide poisoning. Given the high affinity of fetal hemoglobin for oxygen and carbon monoxide, HBOT can improve fetal outcomes in cases of severe maternal hypoxia, such as in carbon monoxide poisoning.
• High fever or epilepsy can lower the seizure threshold, increasing the likelihood of oxygen toxicity. The risk of HBOT-induced seizures in patients with a seizure history or recent brain surgery remains uncertain. Antiepileptic medications and fever management can help mitigate this risk.
• Difficulty equalizing ear or sinus pressure due to prior surgery, radiation, or an acute upper respiratory infection can lead to pain or barotrauma. A history of ear conditions requiring surgery, such as otosclerosis, may also present challenges. Patients with nasal congestion or mild difficulty clearing their ears may benefit from phenylephrine nasal spray. If ineffective or if a significant history of ear disease is present, tympanostomy tubes should be placed before initiating HBOT.
• Eustachian tube dysfunction increases the risk of tympanic membrane barotrauma. Pressure equalization training or tympanostomy tube placement is recommended before HBOT in affected patients.
• Claustrophobia may be a contraindication depending on severity, response to anxiolytics, and chamber size. In extreme cases, this condition may even be an absolute contraindication if the patient poses a risk to themselves or the chamber operator.
• A history of eye surgery may contraindicate HBOT if any air or gas remains trapped in the eye, as pressure changes could cause expansion or contraction, leading to ocular damage.
• A history of thoracic surgery can elevate the risk of atelectasis and pneumothorax during HBOT, necessitating a thorough pretreatment evaluation.
• A history of spontaneous pneumothorax is a relative contraindication and requires further assessment before initiating HBOT.[6]
• Active upper respiratory tract and severe sinus infections increase the risk of sinus and inner ear barotrauma, potentially leading to complications and significant discomfort. Similarly, uncontrolled high fevers (>39°C) are a relative contraindication and warrant clinical evaluation to determine the underlying infection.
• Asymptomatic pulmonary lesions identified on chest radiographs should be assessed before proceeding with HBOT.
• A history of optic neuritis or sudden blindness has traditionally been regarded as a relative contraindication. However, limited studies have evaluated HBOT in these patients. Notably, HBOT has demonstrated therapeutic benefits for various ophthalmologic conditions, including radiation-induced optic neuritis, central retinal artery occlusion, retinal vein occlusion, and macular edema. Clinical evaluation is necessary to assess potential risks and benefits in patients with a history of ocular pathology.
• Insulin-dependent diabetes mellitus and acute hypoglycemia are considered relative contraindications due to the risk of therapy-induced hypoglycemia. However, point-of-care glucose monitoring and frequent nursing assessment often allow for the safe administration of HBOT in patients with diabetes mellitus.
• Nicotine and caffeine use are contraindicated before HBOT, as the vasoconstrictive effects of these agents reduce treatment efficacy. Illicit vasoconstricting agents, such as cocaine and amphetamines, are also contraindicated for the same reason.
• Congenital spherocytosis has been considered a potential contraindication due to the risk of hemolysis from increased oxygen partial pressure. However, reports indicate that some patients with this hematologic condition have undergone HBOT without complications.
• Perilymph fistulas, which result from inner ear barotrauma, can cause vestibular symptoms, such as vertigo. HBOT may exacerbate these symptoms by forcing gas into the cochlea.[7] To prevent complications, the condition must be carefully assessed before treatment. Vestibular symptoms should be monitored during HBOT, adjusting pressure changes as needed.
• HBOT may trigger the reactivation of tuberculosis. To identify latent tuberculosis, high-risk patients should undergo the tuberculin skin test or interferon γ release assay before HBOT.[8]

Exposure to HBOT-related oxidative stress may have significant implications for ocular diseases, such as age-related macular degeneration and keratoconus. These conditions should be carefully evaluated when assessing the risks and benefits of treatment.[9] In glaucoma cases, elevated oxygen concentrations in the aqueous humor may increase the risk of trabecular meshwork damage, particularly when the anterior ocular surface is directly exposed to hyperbaric oxygen in a hood or monoplace chamber. Mask delivery of HBOT may provide a safer alternative.[10]

Active Cancer: Not a Contraindication

Active cancer was once hypothesized to be a contraindication to HBOT due to concerns that HBOT may stimulate vascular endothelial growth factor (VEGF) release and promote tumor progression. However, differences in tumor growth cycles compared to wound healing, along with a literature review, indicate a net neutral effect on gene expression related to cancer progression.

Issues of Concern

Hyperbaric Oxygen: A Driver of Cancer Progression? 

Due to HBOT’s ability to stimulate the regeneration of chronically injured tissue, concerns have been raised about whether increased oxygen delivery could promote cancer growth, particularly in solid tumors with large hypoxic regions. Many HBOT candidates have a prior history of cancer or are actively battling malignancy. However, the concern over accelerating tumor progression remains largely theoretical. Substantial evidence indicates that HBOT has little to no effect on cancer progression.[11][12] On the contrary, the treatment may even serve as a beneficial adjunct to chemotherapy, immunotherapy, and radiation therapy.[13][14] Notably, hypoxia is increasingly recognized as a driver rather than an inhibitor of malignant progression.[15]

Apprehension about HBOT stimulating cancer progression has existed for decades, fueled in part by isolated case reports describing patients with rapid tumor progression following treatment.[16] However, these reports fail to establish a causative link between HBOT and malignancy. In contrast, most studies demonstrate that HBOT has minimal to no impact on cancer growth and progression.[17][18] A deeper understanding of tumor hypoxia at the molecular and physiological levels further supports these findings.

As mentioned, instead of inhibiting cancer growth, hypoxia is increasingly recognized as a driver of cancer progression and is considered by some to be a hallmark of tumor biology.[19] Growing solid tumors outpace their blood supply, creating areas of hypoxia. To survive, tumor cells release angiogenic signals that stimulate new blood vessel formation.

Cancer cells differ markedly from normal cells. Mutations in cancer cells lead to the upregulation of angiogenic factors, resulting in a disorganized and defective vascular network that further exacerbates intratumor hypoxia.[20] Additionally, the rapid proliferation of tumor cells and blood vessels disrupts the basement membrane, increasing the risk of invasion and metastasis. Tumor hypoxia is associated with more aggressive malignant behavior and reduced survival across multiple cancer types.[21]

Under normal physiologic conditions, oxygen inhibits neovascularization by promoting the degradation of hypoxia-inducible factor (HIF) proteins. In hypoxic environments, however, this degradation is suppressed, allowing HIF proteins to bind to VEGF DNA and enhance protein translation. This dysregulation makes hypoxia a potent stimulus for angiogenesis. In some cancers, such as neuroblastoma, mutations in HIF proteins are central to tumor pathogenesis.[22]

In addition to dysregulated angiogenesis, hypoxic tumor cells adapt metabolically to survive in low-oxygen conditions. Tumor cells preferentially rely on anaerobic glucose metabolism, a phenomenon known as the Warburg effect. Hypoxia amplifies this effect by upregulating glucose transporters and depriving cells of the oxygen required for normal cellular respiration. Higher levels of HIF have also been shown to enhance the Warburg effect.[23] These anaerobic metabolic adaptations contribute to tumor metastasis, immune evasion, and decreased efficacy of certain chemotherapy drugs, collectively driving cancer progression and aggressiveness.

Hypoxia and increased anaerobic respiration also lead to elevated production of reactive oxygen species (ROS), imposing additional stress on tumor cells. In response, tumors upregulate antioxidant defense mechanisms, enhancing resistance to therapy. Additionally, chronic ROS exposure induces persistent DNA damage, promoting mutational heterogeneity and selecting cells that evade apoptosis, further supporting tumor survival and progression.

Hyperbaric oxygen therapy in malignancy

The above mechanisms demonstrate the profound impact that hypoxia has on tumor cells. However, HBOT counteracts these hypoxia-driven processes rather than facilitating cancer growth. Increased oxygen delivery to hypoxic tumor cells enhances HIF protein degradation, leading to decreased VEGF expression and reducing angiogenic signaling.[24] Due to inherent tumor biology, HBOT exposure does not stimulate angiogenesis.

Several in vitro and clinical studies support this conclusion. In a murine model, 4 weeks of HBOT resulted in no significant changes in tumor vascularity, tumor mass, or Ki-67 expression compared to an untreated control group. In humans, HBOT has been investigated as a pretreatment for chemotherapy, with clinical trials similarly demonstrating no alterations in tumor volume or vascularity as measured by magnetic resonance imaging.

HBOT alone is ineffective against cancer. However, this intervention has been explored as an adjunct to radiation and chemotherapy, potentially enhancing treatment efficacy by increasing oxygen availability and promoting the generation of cytotoxic ROS. Additionally, emerging evidence suggests that HBOT may modulate immune responses, improving the efficacy of immunotherapy.[25] These potential applications remain under investigation, and a comprehensive review of ongoing research is beyond the scope of this discussion.

Conclusions on hyperbaric oxygen therapy and cancer

We echo a clinical observation first noted by Feldmeier et al in 2003: HBOT does not accelerate the healing of normal wounds.[26] Oxygen alone, regardless of concentration, does not enhance cellular growth or division. The benefits of HBOT in wound healing stem from its ability to stimulate angiogenesis, recruit stem cells, and activate other slower-acting mechanisms. The tumor microenvironment differs significantly from that of a chronic, nonhealing wound. In tumors, angiogenesis is a response to excessive, dysregulated growth rather than impaired cellular proliferation. As a result, HBOT has little to no impact on tumor progression.

Although the role of HBOT as an adjunct to cancer therapy remains under investigation, many individuals undergoing cancer treatment develop chronic, nonhealing wounds. HBOT has demonstrated significant benefits for conditions such as radiation cystitis and osteoradionecrosis of the jaw. However, concerns about HBOT accelerating tumor growth or reactivating dormant malignancies often lead to denial of treatment for patients. Based on the evidence presented, the risk of HBOT promoting cancer growth is largely theoretical, while the potential benefits for these patients outweigh this minimal risk.

Heart Failure and Hyperbaric Oxygen Therapy

HBOT induces diffuse vasoconstriction, increasing cardiac afterload while simultaneously reducing cardiac output. Consequently, a history of heart failure, particularly with reduced ejection fraction, is considered a relative contraindication. However, clinical evidence suggests that HBOT can be safely administered with appropriate optimization of heart failure management, including diuretics and fluid restriction.[27]

Clinical Significance

HBOT is used for both emergent and elective interventions. The primary emergent indication is decompression sickness from gas embolism and decompression illness. The treatment is also used for the acute management of carbon monoxide toxicity, chronic refractory osteomyelitis, radiation injuries to soft tissue, and clostridial myonecrosis, though the quality of evidence supporting these applications varies. HBOT has also been used for necrotizing wounds, retinal artery occlusion, and acute trauma, but clear efficacy for these conditions remains uncertain. In some cases, HBOT serves as an adjuvant for conditions unresponsive to conventional treatment methods alone.[28]

Additional research indicates that patients recovering from head and neck tumors after radiation and surgical intervention may experience progressive fibrosis of soft tissue within the jaw. Studies suggest that individuals who receive coadministered HBOT experience better outcomes than those who do not, supporting the referral of irradiated head and neck cancer patients to HBOT centers. Physicians should coordinate this effort with planned surgeries to optimize tissue healing.[29] Delayed radiation sequelae from treatments for neurologic, gynecologic, urologic, and colorectal cancers have also demonstrated responsiveness to concurrent HBOT.[30][31]

HBOT has also been used to treat severe anemia when transfusions are either refused (such as by observant Jehovah’s Witnesses) or cannot be safely performed.[32] This application is supported by basic science research and corroborated in clinical cases.

One of the main drawbacks of this treatment method is the relative lack of access. A national shortage of HBOT centers in the United States limits this intervention's availability and hinders further research into its role as a mainstay therapy.

Enhancing Healthcare Team Outcomes

HBOT indications should be carefully assessed against potential contraindications to ensure that the expected benefits outweigh the associated risks.[33] Interprofessional collaboration is essential for evaluating contraindications and determining whether HBOT is appropriately indicated. HBOT is used in both emergent and elective settings. Thus, the roles of healthcare professionals vary significantly. In emergencies, earlier initiation is associated with improved outcomes.[34] While emergency physicians typically make the final decision regarding emergent HBOT, nurses, radiologists, emergency medical personnel, and pharmacists play key roles in identifying contraindications.

Emergency medical personnel are responsible for obtaining the initial history, which may reveal indications for emergent HBOT, such as a diving injury or carbon monoxide toxicity. Radiology staff must assess prior imaging for abnormalities, such as pulmonary nodules, that could contraindicate elective HBOT. In emergent cases, radiologists play a critical role in ruling out tension pneumothorax, the only absolute contraindication to HBOT.

Pharmacists and pharmacy staff are essential in reviewing a patient’s medication regimen to ensure that HBOT can be safely administered alongside medical interventions, such as cancer chemotherapy. Nurses play a key role in monitoring patients for adverse reactions and ensuring their safety and well-being throughout HBOT treatment.

For elective HBOT, primary care providers must assess medical conditions that could serve as relative contraindications, including claustrophobia, upper respiratory infections, diabetes, eustachian tube malformations, and chronic respiratory diseases. Ongoing evaluation of comorbidities is necessary to mitigate potential risks associated with HBOT.

The Oxford Centre for Evidence-Based Medicine (CEBM) has established evidence levels for HBOT based on specific conditions, including gas embolism, radiation injury treatment, and refractory osteomyelitis.[35][36][37] This framework allows clinicians to make informed decisions about the use of HBOT, ensuring that it is applied appropriately based on the quality of evidence available for each condition.