Continuing Education Activity

Hyperbaric oxygen therapy (HBOT) involves administering 100% oxygen at pressures above 1.4 ATA and is being explored as an adjunctive treatment for intracranial abscesses, including cerebral abscesses and subdural and epidural empyema. These abscesses develop during life-threatening infections, resulting in localized pus collections within the cranial cavity. Although the incidence is up to 1.3 per 100,000 individuals, intracranial abscesses occur more frequently in high-risk populations, such as patients with HIV/AIDS.

Surgical aspiration or evacuation combined with antibiotics remains the standard treatment for intracranial abscesses. However, HBOT has shown promise as a valuable adjunct in certain cases. A retrospective cohort study found that patients receiving HBOT experienced lower morbidity, fewer reoperations, and a higher likelihood of returning to baseline function compared to those treated with standard therapy alone. Treatment duration varies based on clinical response and imaging findings, with reports averaging 14 sessions. Although HBOT has antimicrobial benefits through reactive oxygen species, neurological sequelae remain a challenge, underscoring the need for effective adjunctive therapies. This activity highlights the potential of HBOT in enhancing outcomes for patients with intracranial abscesses through effective collaboration among healthcare providers.

Objectives:

• Identify the indications for hyperbaric oxygen therapy as an adjunctive treatment in patients with intracranial abscesses.

• Implement evidence-based protocols for administering hyperbaric oxygen therapy, including appropriate pressure settings and session durations based on clinical guidelines.

• Apply knowledge of the physiological mechanisms by which hyperbaric oxygen therapy enhances antibiotic efficacy and immune function in the context of intracranial infections.

• Collaborate with the interprofessional healthcare team to develop individualized treatment plans incorporating hyperbaric oxygen therapy and standard management strategies.

Introduction

The first hyperbaric chamber was constructed in 1662 by Nathaniel Henshaw, a British clergyman. Over the years, various hyperbaric devices were used to treat different ailments, with varying degrees of success until 1955. Until then, the use of hyperbaric methods had minimal scientific support. The clinical application of hyperbaric oxygen therapy (HBOT) began in 1955 when Churchill-Davidson and colleagues explored its potential to enhance the effects of radiation therapy in cancer patients.[1]

HBOT is a therapeutic modality that delivers 100% oxygen in a chamber or environment pressurized to more than 1.4 atmospheres absolute (ATA). The antimicrobial effects of HBOT are partly attributed to generating reactive oxygen species. HBOT is being explored as an adjunctive treatment for various conditions, including intracranial abscesses, with common examples being cerebral abscesses and subdural and epidural empyema. Please see StatPearls' companion resources, "Brain Abscess," "Subdural Empyema," and "Epidural Abscess," for more information about these clinical conditions.

Intracranial Abscess

An intracranial abscess is a localized, encapsulated collection of pus within the cranial cavity. While brain abscesses are relatively rare, occurring in only 0.3 to 1.3 per 100,000 individuals, their incidence is significantly higher among high-risk patients, particularly those with HIV infection or AIDS.[2][3][4]

Etiology and pathogenesis: The development of an intracranial abscess involves several mechanisms, as mentioned below.

• Direct spread: This occurs when an initial infection spreads contiguously into adjacent tissues, such as the sinuses, ears, mastoid air cells, or teeth, affecting up to 60% of patients.
• Hematogenous seeding: Infectious agents can reach the brain via the bloodstream, often leading to multiple abscesses.
• Cranial trauma: Penetrating head injuries can provide a direct route for microorganisms to enter the skull.

Streptococcus and Staphylococcus species are the most common bacterial causes of brain abscesses, with viridans group streptococci (VGS) and Staphylococcus aureus being the most prevalent. Anaerobes are also commonly found in brain abscesses, originating from the normal oral flora. When determining the cause of an infection, it is essential to consider the patient's immune status. Bacterial abscesses are typically observed in immunocompetent individuals, whereas immunocompromised patients may be infected by various organisms, including fungi.[5]

Factors Contributing to Improved Outcomes

Although brain abscesses are a rare condition, mortality rates remain high among affected patients. However, the prognosis for these individuals has significantly improved compared to historical data. A systematic review and meta-analysis revealed that over the past 6 decades, the case fatality rate has decreased from 40% to 10%, while the proportion of patients achieving full recovery has increased from 33% to 70%.[6] Additionally, a study of 289 patients with pyogenic brain abscesses treated between 1999 and 2006 reported a mortality rate as low as 2.7%.[7]

Several factors, as mentioned below, have contributed to this positive trend.

• Computed tomography: The advent of computed tomography (CT) imaging has significantly improved outcomes by enabling faster diagnoses and facilitating less invasive, more precise neurosurgical interventions, such as stereotactic aspiration. One retrospective study showed a reduction in mortality from 40% to 20% within the first decade following the introduction of CT.
• Neurosurgical techniques: Advancements in neurosurgical procedures and the precision offered by CT-guided interventions have improved abscess drainage and reduced complications.
• Antimicrobial therapy: The development of more effective antibiotics has been crucial for controlling infections.

Anatomy and Physiology

Principles Governing Oxygen Delivery in Hyperbaric Oxygen Therapy

The theoretical framework and clinical effectiveness of HBOT are based on the principles of increased oxygen delivery, which is governed by the physical laws below.

• Dalton's law: This law of partial pressures states that the total pressure of a gas mixture equals the sum of the partial pressures of each component gas. Dalton's law explains how variations in pressure or gas concentration influence the partial pressure of a specific gas within the mixture.
• Henry's law: According to this law, the concentration of a gas dissolved in a liquid is directly proportional to its partial pressure and solubility. This law underlies the increased oxygen levels dissolved in blood during HBOT.

Oxygen Delivery During Hyperbaric Oxygen Therapy

The effectiveness of HBOT in enhancing oxygen delivery to tissues relies on several fundamental principles of gas transport and diffusion, as mentioned below.

• Normal conditions: Under typical conditions, hemoglobin carries the majority of oxygen, with only a small amount (3 mL/L) dissolved in plasma.
• 100% oxygen: When breathing 100% oxygen, the dissolved oxygen level increases to 15 mL/L.
• HBOT at 2.5 ATA: Dissolves 60 mL/L of oxygen to support resting tissue metabolism without relying on hemoglobin-bound oxygen.
• Diffusion: Oxygen reaches cells through diffusion, which is influenced by the distance from capillaries and local oxygen levels.
• HBOT and diffusion: The increased PO₂ at the capillary extends the diffusion distance 3-fold.

Proposed Mechanisms of Action for Hyperbaric Oxygen Therapy in Treating Intracranial Abscesses

HBOT is being explored as an adjunctive treatment for intracranial abscesses, with several proposed mechanisms of action, as mentioned below.

• Reduction of perifocal brain swelling: HBOT can cause vasoconstriction and decreased cerebral blood flow, which may help reduce edema and intracranial pressure associated with brain abscesses.
• Inhibition of anaerobic organisms: Many intracranial abscesses involve anaerobic bacteria. The high-oxygen environment created by HBOT is detrimental to the growth and survival of these organisms.
• Enhancement of neutrophil function: HBOT has been shown to increase the oxygen-dependent killing mechanisms of neutrophils, which are the key immune cell subtypes involved in fighting infection. This enhanced phagocytosis may aid in clearing the infecting organisms.
• Treatment of concomitant skull osteomyelitis: In cases where the infection has spread to the skull bone, HBOT can facilitate treatment by increasing oxygen delivery to the affected area and promoting healing.

Indications

According to the Undersea and Hyperbaric Medical Society (UHMS), adjunct HBOT should be considered for the treatment of intracranial abscesses in the following situations:

• Compromised host
• Multiple abscesses
• Abscesses in a deep or dominant location
• Patients for whom surgery is contraindicated
• Patients who are poor surgical candidates
• Patients who deteriorate or show no response to standard surgical and antibiotic therapies

Contraindications

Absolute Contraindications

Untreated pneumothorax: This is the only absolute contraindication to HBOT. A pneumothorax occurs when air becomes trapped in the pleural space, and the increased pressure during HBOT can cause it to expand dangerously, leading to tension pneumothorax and potentially life-threatening complications.

Relative Contraindications

Claustrophobia: The enclosed environment of the hyperbaric chamber can trigger anxiety or panic attacks in individuals with claustrophobia.

Obstructive lung disease: Conditions such as chronic obstructive pulmonary disease can impair gas exchange and increase the risk of complications during HBOT.

Asymptomatic pulmonary blebs: These small air pockets in the lungs can rupture under increased pressure, potentially leading to pneumothorax.

Upper respiratory or sinus infections: Pressure changes during HBOT can worsen symptoms or cause ear and sinus barotrauma.

Recent ear or thoracic surgery: Healing tissues may be more susceptible to pressure changes and barotrauma.

Uncontrolled seizures: HBOT may potentially lower the seizure threshold in some individuals.

Relative contraindications do not automatically exclude the use of HBOT. Each patient should be evaluated individually, weighing the potential benefits against the risks in consultation with a qualified healthcare professional. In some cases, appropriate management or modifications may enable patients with relative contraindications to safely undergo HBOT.

Equipment

HBOT is administered in a chamber where the patient is placed. There are 2 types of chambers, as mentioned below.[8]

• Monoplace chamber: The patient inhales pressurized 100% oxygen directly in this chamber.
• Multiplace chamber: Multiple patients inhale pressurized 100% oxygen indirectly through a head hood, mask, or endotracheal tube in this setup.

Technique or Treatment

Recommended Protocol

The UHMS offers guidelines for administering HBOT in cases of intracranial abscesses, which are mentioned below.

• Pressure: The recommended pressure ranges from 2.0 to 2.5 ATA.
• Oxygen administration duration: Each treatment session lasts 60 to 90 minutes.
• Frequency: Depending on the patient's clinical condition, treatments may be administered once or twice daily.

Duration of Therapy

Although definitive guidelines for the optimal number of HBOT sessions for intracranial abscesses do not exist, the largest case series reported an average of 14 sessions in patients without osteomyelitis. The duration of therapy should be individualized based on the below-mentioned criteria.[9][10][11]

• Radiological findings: Serial imaging studies (eg, CT or magnetic resonance imaging [MRI] scans) can be used to monitor the size and resolution of the abscess.
• Clinical response: Improvement in neurological symptoms and signs can help guide treatment decisions.

Complications

Barotrauma

• Middle ear barotrauma: This is the most frequent complication, particularly in patients undergoing multiple treatments. This arises due to pressure differences between the middle ear and the hyperbaric chamber. Symptoms may include ear pain, tympanic membrane rupture, and even hearing loss.
• Sinus barotrauma: This is the second most common complication, often affecting individuals with preexisting conditions such as upper respiratory infections or allergic rhinitis. This complication typically manifests as sinus pain and congestion.

Pulmonary Complications

• Pulmonary oxygen toxicity: This condition may develop with multiple treatments, causing chest tightness due to lung irritation from extended exposure to high oxygen concentrations.
• Pulmonary barotrauma: This is a rare but severe complication caused by pressure changes that damage lung tissue, potentially leading to pneumothorax or pneumomediastinum.[12]

Central Nervous System Oxygen Toxicity

• Seizures: Seizures are a rare but serious complication, with an incidence of only one seizure reported per 62,614 hyperbaric sessions involving 2334 patients. The risk increases with prolonged exposure (over 90–120 min) or when pressures exceed 2.8 ATA.
• Management: If a seizure occurs, the oxygen concentration should be immediately reduced, and anticonvulsant medications may be administered as needed.[13]

Clinical Significance

Limitations of Conventional Therapy and Need for Adjunctive Treatment

Despite advancements in reducing mortality rates, significant challenges persist in managing intracranial abscesses. Neurologic sequelae are common, with some being severe enough to impact patients' social and professional lives. This underscores the urgent need for more effective and conservative treatment strategies.

Antibiotic treatment for intracranial abscesses has various limitations, as mentioned below.

• Limited penetration: Antibiotics may not readily cross the blood-brain barrier, ischemic tissues, or the abscess capsule.
• Hypoxic and acidic environment: The local environment within an abscess can significantly reduce the effectiveness of antibiotics.
• Impaired immune function: Hypoxia within the abscess can impair white blood cell phagocytic function, thereby diminishing the antimicrobial effects of antibiotics.

Potential Benefits of Hyperbaric Oxygen Therapy

HBOT helps overcome the limitations of conventional treatment through several physiological mechanisms, as listed below.

• Correction of tissue hypoxia: Increased oxygen delivery improves tissue oxygenation, alleviating the hypoxic environment within the abscess.
• Direct antimicrobial effects: HBOT exerts bacteriostatic and bactericidal effects, particularly against anaerobic organisms.
• Enhanced antibiotic efficacy: Improved tissue oxygenation can enhance antibiotic penetration and effectiveness within infected tissues.
• Enhanced immune function: HBOT can improve neutrophil-mediated phagocytosis, thereby strengthening the immune response against infections.
• Reduced brain swelling: The vasoconstrictive and dose-dependent anti-inflammatory effects of HBOT can help reduce edema and intracranial pressure.

Evidence for Hyperbaric Oxygen Therapy Efficacy

Although data remain limited, a recent retrospective cohort study showed promising results with adjuvant HBOT in treating intracranial abscesses. Patients receiving HBOT showed lower morbidity, decreased reoperation rates, and a higher likelihood of returning to their premorbid functional state compared to those receiving standard therapy alone.[3]

HBOT offers potentially valuable adjunctive therapy for intracranial abscesses, overcoming the limitations of conventional treatment and offering additional benefits. Although further research is required, the available limited evidence supports its use in specific clinical scenarios.

Enhancing Healthcare Team Outcomes

The primary treatment for intracranial abscesses usually involves a combination of the below-mentioned criteria.

• Antibiotics: Targeted antibiotic therapy is crucial for controlling the infection. The choice of antibiotics depends on the suspected or identified causative organisms.
• Drainage: Surgical drainage or aspiration of the abscess is often necessary to remove the purulent material and reduce intracranial pressure. Various techniques can be used, including stereotactic aspiration, open craniotomy, or endoscopic drainage.

HBOT is being explored as an adjunctive therapy for intracranial abscesses, and key considerations are mentioned below.[14]

• First-line treatment: HBOT is not intended as the primary therapy but should be used alongside standard antibiotic and surgical management.
• Unstable patients: HBOT is generally not recommended for individuals with unstable vital signs or those in need of urgent surgical intervention.
• Replacement for antibiotics: HBOT serves as a complementary therapy (adjunct) to enhance antibiotic effectiveness, not as a substitute for antibiotic treatment.
• Potential risks: HBOT carries risks such as barotrauma and oxygen toxicity, which require careful monitoring and management.

However, HBOT shows significant potential as an adjunctive therapy, supported by its physiological benefits and evidence from case reports and series.[15][16]

Nursing, Allied Health, and Interprofessional Team Monitoring

The management of intracranial abscesses necessitates a collaborative approach involving an interprofessional healthcare team, which includes neurosurgeons, infectious disease specialists, neurologists, neurocritical care nurses, radiologists, pharmacists, and rehabilitation specialists.