Understanding Central Nervous System Effects, Pulmonary Exposure, Risk Factors, Prevention, and Emergency Response
Oxygen is essential to human metabolism, but it also behaves like a medication. Its physiologic effects depend on the concentration delivered, the surrounding pressure, the duration of exposure, and the individual patient’s susceptibility.
During hyperbaric oxygen therapy, or HBOT, a patient breathes oxygen at an ambient pressure greater than normal atmospheric pressure. This produces oxygen partial pressures that cannot be reached by breathing supplemental oxygen at sea level alone.
The resulting hyperoxia is responsible for many of HBOT’s therapeutic effects. It increases dissolved plasma oxygen, supports oxygen-dependent immune activity, influences vascular signaling, and improves diffusion into selected hypoxic tissues. The same exposure can become toxic when the oxygen dose exceeds the capacity of cellular antioxidant systems.
Modern clinical protocols are designed to remain within established therapeutic limits. Serious oxygen toxicity is uncommon during medically supervised HBOT, but every hyperbaric team must understand how to recognize, prevent, and manage it.
Oxygen Toxicity Is a Dose-Dependent Effect
Oxygen toxicity is not an allergy to oxygen. It is a dose-related cellular response to elevated oxygen partial pressure.
The oxygen dose delivered during HBOT is influenced by:
- Treatment pressure
- Oxygen concentration
- Duration of each oxygen-breathing period
- Length and frequency of air breaks
- Number of treatments
- Interval between treatments
- Patient-specific physiologic factors
A higher pressure increases the partial pressure of oxygen delivered to the lungs. Longer uninterrupted exposure increases the time during which tissues are exposed to that pressure. Repeated sessions increase cumulative exposure, particularly in the lungs and ocular tissues.
The two principal clinical patterns are:
- Central nervous system oxygen toxicity, which is generally associated with shorter exposure to high oxygen partial pressures and may culminate in a seizure
- Pulmonary oxygen toxicity, which is more closely associated with prolonged or cumulative oxygen exposure and may cause respiratory irritation or reduced lung function
These patterns overlap, but they occur on different exposure timelines. Acute central nervous system effects can develop within a single treatment, while clinically significant pulmonary toxicity is more often associated with longer or unusually intensive oxygen schedules. (PubMed)
Reactive Oxygen Species and Cellular Injury
Normal oxygen metabolism produces reactive oxygen species, including superoxide and hydrogen peroxide. These molecules are not inherently harmful. At controlled levels, they participate in cell signaling, immune function, vascular regulation, and adaptation to physiologic stress.
Cells protect themselves through antioxidant systems such as superoxide dismutase, catalase, glutathione, and other enzymatic and nonenzymatic defenses.
Hyperbaric exposure increases the generation of reactive oxygen and nitrogen species. When production temporarily exceeds the ability of antioxidant systems to neutralize them, oxidative stress can affect cell membranes, proteins, enzymes, mitochondria, and signaling pathways.
In the central nervous system, this imbalance may alter neuronal excitability and inhibitory signaling. In the lungs, repeated oxidative injury may affect the alveolar-capillary membrane and pulmonary epithelium. The precise sequence leading from therapeutic hyperoxia to clinical toxicity remains incompletely understood and varies among patients. (PubMed)
This biologic variability explains why oxygen toxicity cannot be predicted from pressure and exposure time alone. Two patients receiving the same protocol may not have the same response, and an individual patient’s tolerance may vary from one day to another.
Central Nervous System Oxygen Toxicity
Central nervous system oxygen toxicity, often abbreviated as CNS oxygen toxicity, is the most dramatic acute oxygen-related complication of HBOT.
Its most recognizable manifestation is a generalized tonic-clonic seizure. These events are uncommon during standard clinical protocols and are usually self-limited after the patient is removed from oxygen exposure. They still require immediate, coordinated management because the chamber environment limits access and introduces additional airway and pressure-related concerns.
Possible warning symptoms include:
- Visual changes, such as narrowing of the visual field or unusual lights
- Ringing in the ears or other auditory changes
- Nausea
- Facial, lip, or limb twitching
- Irritability, agitation, confusion, or unusual behavior
- Dizziness
- Tingling sensations
- A sense of apprehension
- Generalized seizure
These symptoms are sometimes organized into the mnemonic VENTID-C: visual changes, ear symptoms, nausea, twitching, irritability, dizziness, and convulsion.
The mnemonic is useful for staff education, but it should not create false reassurance. Warning symptoms are inconsistent, and a seizure may occur without a recognizable prodrome. (NCBI)
Not every seizure occurring inside a hyperbaric chamber is caused by oxygen toxicity. Hypoglycemia, fever, medication effects, withdrawal, intracranial disease, carbon monoxide poisoning, and a preexisting seizure disorder may produce similar events. Published case reports describe seizure-like episodes during HBOT that were ultimately attributed to causes other than CNS oxygen toxicity. (PubMed)
A post-event evaluation should therefore investigate alternative or contributing causes rather than automatically labeling every chamber seizure as an oxygen reaction.
How Common Are Oxygen Toxicity Seizures?
Reported seizure rates vary according to treatment pressure, oxygen duration, air-break practices, patient population, indication, and how events are classified.
Large clinical series consistently indicate that seizures are uncommon. One review of more than 80,000 treatments reported two seizures, or approximately 2.4 events per 100,000 treatments. Another analysis of 62,614 sessions identified seven seizures from all causes, with only one considered clearly attributable to oxygen toxicity. (PubMed)
A larger study examining more than 180,000 treatments found a seizure frequency of 3.9 per 10,000 treatments before the introduction of a five-minute air break and 1.2 per 10,000 treatments afterward. Differences between studies illustrate how protocol design and event classification affect reported incidence. (PubMed)
Patients should be informed that the risk exists, but it should be presented in proportion. For most appropriately screened patients receiving standard clinical protocols, a CNS oxygen toxicity seizure is a rare event.
Factors That May Lower the Seizure Threshold
The strongest treatment-related risk factors are increased oxygen partial pressure and longer uninterrupted oxygen exposure. Other physiologic or clinical conditions may reduce an individual patient’s tolerance.
Potential contributors include:
- Fever
- Hypoglycemia
- Hypercapnia or carbon dioxide retention
- Significant respiratory obstruction
- Uncontrolled seizure disorder
- Acute brain injury
- Alcohol or sedative withdrawal
- Stimulant or recreational drug exposure
- Certain medications that influence seizure threshold
- Severe physiologic stress
- Prolonged or repeated high-pressure oxygen exposure
Carbon dioxide is particularly relevant because it increases cerebral blood flow and may increase oxygen delivery to the brain. A patient who is hypoventilating, retaining carbon dioxide, exercising under pressure, or breathing through excessive apparatus resistance may theoretically reach a toxic cerebral oxygen exposure more quickly.
The Undersea and Hyperbaric Medical Society notes that fever, low blood glucose, medications, and underlying disease processes may lower the threshold for oxygen toxicity in some patients. These factors should be assessed clinically, but they are not precise predictors of who will experience a seizure. (UHMS)
A history of seizures is generally treated as a relative consideration rather than an automatic exclusion. The hyperbaric physician should review seizure control, medication adherence, recent events, metabolic abnormalities, fever, and the urgency of the HBOT indication.
Responding to a Seizure Under Pressure
A seizure during HBOT requires an immediate but controlled response.
The first action is to discontinue oxygen exposure. In a multiplace chamber, the patient’s oxygen mask or hood is removed so the patient breathes the chamber’s compressed-air atmosphere. In a monoplace chamber, air may be supplied through the designated breathing system when the chamber design and protocol permit.
The treatment team should then:
- Protect the patient from striking the chamber or equipment
- Maintain the airway as safely as possible
- Avoid placing objects in the patient’s mouth
- Observe breathing and circulation
- Prepare for suction, airway support, or emergency medication if needed
- Check glucose and assess other possible causes after the event
- Follow the facility’s emergency protocol and physician direction
The chamber should not be rapidly decompressed during an active generalized convulsion. A convulsing patient may briefly hold their breath or have an obstructed airway. Expanding pulmonary gas during decompression could create an additional risk of pulmonary barotrauma. Hyperbaric nursing guidance advises waiting for the convulsion to stop and spontaneous respiration to return before beginning controlled decompression. (UHMS)
Once oxygen exposure is stopped, an oxygen toxicity seizure commonly resolves without anticonvulsant medication. Medication may still be required when seizure activity is prolonged, recurrent, or suspected to have another cause.
The patient should receive a full medical assessment before any decision is made about resuming HBOT. A treatment may later continue at a reduced pressure, with shorter oxygen periods, additional air breaks, or after correction of a contributing factor. The decision depends on the indication, event severity, and expected benefit of continued therapy.
Pulmonary Oxygen Toxicity
The lungs are continuously exposed to the inspired treatment gas, making them an important site of cumulative oxygen effects.
Pulmonary oxygen toxicity begins with oxidative irritation of the respiratory epithelium and alveolar-capillary interface. With sufficient exposure, patients may develop:
- Dry cough
- Substernal burning or discomfort
- Chest tightness
- Pain with deep inspiration
- Shortness of breath
- Reduced exercise tolerance
- A measurable decline in vital capacity
More advanced pulmonary injury is uncommon in routine outpatient HBOT. It is more relevant during prolonged treatment tables, repeated emergency treatments, intensive diving exposures, critical-care oxygen therapy, or other situations involving a high cumulative oxygen dose.
A 2023 longitudinal study evaluated patients receiving 100 percent oxygen at 2.0 to 2.4 ATA for 90 minutes, five days per week. Investigators found no significant changes in measured pulmonary function after 20, 40, or 60 treatments, including among patients with preexisting respiratory disease. These findings support the pulmonary safety of commonly used modern protocols while not eliminating the need to evaluate new respiratory symptoms. (PubMed)
Patients who develop persistent cough, chest discomfort, new dyspnea, or an unexplained change in respiratory function should be reassessed. The treatment pressure, exposure time, cumulative dose, pulmonary history, and alternative diagnoses should be reviewed.
Pulmonary Disease and Oxygen Toxicity Are Not the Same Risk
Pulmonary oxygen toxicity should be distinguished from pulmonary barotrauma.
Oxygen toxicity is caused by the biochemical effects of elevated oxygen exposure. Pulmonary barotrauma is caused by the expansion or compression of gas within the lungs during pressure changes.
A patient with airway obstruction, bullous disease, pulmonary air trapping, or a history of spontaneous pneumothorax may be at increased risk for pressure-related injury during decompression. This does not necessarily mean the patient has an increased biochemical susceptibility to pulmonary oxygen toxicity.
The risks can overlap in the same patient, but they require different screening and preventive strategies. UHMS guidance identifies significant air trapping, airway obstruction, and previous spontaneous pneumothorax as concerns requiring a careful benefit-risk assessment before HBOT. (UHMS)
An untreated pneumothorax remains a major contraindication because trapped pleural gas may expand during decompression.
Ocular Effects of Repeated Oxygen Exposure
Repeated HBOT may produce temporary changes in the eye, most commonly a myopic shift. Patients may notice blurred distance vision while near vision remains stable or improves.
This change is associated with oxygen-related alterations in the crystalline lens rather than injury to the retina or optic nerve in routine treatment. It often develops gradually during a multweek course and usually improves after treatments are completed.
Very prolonged cumulative exposure has also been associated with cataract development or progression. These effects are distinct from acute CNS oxygen toxicity but remain part of the broader discussion of cumulative oxygen dose. (Mayo Clinic)
Patients should report sudden visual loss, eye pain, flashes, floaters, or major visual-field changes promptly. These findings should not be assumed to represent the expected temporary refractive shift.
Air Breaks and Oxygen Toxicity Prevention
An air break is a planned interval during which the patient stops breathing oxygen but remains at treatment pressure.
In a multiplace chamber, the patient generally removes the oxygen mask or hood and breathes the compressed-air chamber atmosphere. In a monoplace chamber, air is delivered through an approved breathing system.
Air breaks are used to interrupt continuous oxygen exposure and reduce the likelihood of central nervous system and pulmonary oxygen toxicity. They are commonly included in protocols delivered above 2 ATA or when treatment duration and patient risk justify them. (UHMS)
The large retrospective study involving more than 180,000 sessions found that introduction of a five-minute air break was associated with a significant reduction in seizure frequency. Because the study was observational, it cannot prove that the air break alone caused the reduction, but it supports their practical role in clinical protocols. (PubMed)
An air break does not eliminate all risk. A seizure can still occur after an air break or during a protocol that has been tolerated previously. The complete oxygen dose and the patient’s current clinical condition remain important.
Treatment Protocols Are Designed Around Oxygen Dose
Hyperbaric protocols intentionally control pressure and exposure duration. A standard treatment may divide the oxygen dose into several breathing periods separated by air breaks rather than providing one uninterrupted exposure.
Risk-reduction strategies may include:
- Selecting the lowest effective treatment pressure for the indication
- Limiting uninterrupted oxygen-breathing periods
- Incorporating scheduled air breaks
- Avoiding unnecessary extension of treatment time
- Reassessing unusually intensive or twice-daily schedules
- Reviewing medications and recent clinical changes
- Correcting fever or hypoglycemia before treatment
- Monitoring patients continuously
- Adjusting future treatments after suspected toxicity
More oxygen does not automatically produce a better clinical outcome. Increasing pressure or duration may increase toxicity risk without increasing therapeutic benefit.
Protocols should be selected for the diagnosis rather than copied from another indication. A treatment table used for decompression illness or arterial gas embolism may involve a different exposure pattern from a routine wound or radiation-injury protocol.
Pre-Treatment Screening Reduces Avoidable Risk
Screening should occur before the treatment course and continue before every session.
The clinical team should review:
- New fever or infection symptoms
- Recent seizure activity
- Medication additions or interruptions
- Alcohol, sedative, or stimulant withdrawal
- Blood glucose when clinically indicated
- Changes in respiratory status
- New confusion, weakness, or neurologic symptoms
- Sleep deprivation or severe physiologic stress
- Previous difficulty tolerating oxygen exposure
- Recent treatment interruptions or adverse events
A stable patient can develop a new risk factor during a long treatment course. A respiratory infection, medication change, poor oral intake, or loss of glucose control may alter the safety of that day’s treatment.
Patients should be encouraged to report symptoms honestly. They should not feel that mentioning nausea, twitching, visual changes, or anxiety will be interpreted as failure to cooperate.
Continuous Observation Is Essential
Oxygen toxicity cannot be prevented through screening alone. Staff must observe the patient throughout compression, oxygen breathing, air breaks, and decompression.
Observation should include:
- Facial movement and twitching
- Behavior and mental status
- Communication ability
- Respiratory pattern
- Reports of nausea, dizziness, or visual change
- Oxygen-delivery system performance
- Glucose-related symptoms
- Changes in monitoring data when physiologic monitoring is used
In a monoplace chamber, observation and communication occur through the transparent chamber wall and intercommunication system. In a multiplace chamber, an inside attendant may provide direct assessment while communicating with the chamber operator and attending clinician.
The FDA advises facilities to monitor and supervise patients throughout treatment, maintain trained staff, follow manufacturer instructions, and perform the required equipment maintenance and safety checks. (U.S. Food and Drug Administration)
Patient Counseling Should Be Accurate and Reassuring
Patients deserve a clear explanation of oxygen toxicity without language that creates unnecessary fear.
They should understand that:
- Oxygen is being delivered at a controlled medical dose.
- Serious oxygen toxicity is uncommon during standard clinical HBOT.
- Staff monitor continuously for early symptoms.
- Air breaks may be used to reduce uninterrupted oxygen exposure.
- A seizure is possible but rare.
- New cough, chest discomfort, visual changes, twitching, nausea, or unusual sensations should be reported immediately.
- Treatment can be stopped or modified when a safety concern develops.
Patients should also be told that a previous uneventful session does not guarantee that every later treatment will feel identical. Daily communication remains important throughout the course.
Oxygen toxicity represents the point at which the therapeutic oxygen dose exceeds an individual tissue’s tolerance. In clinical hyperbaric medicine, that risk is managed through appropriate pressure selection, limited exposure periods, air breaks, patient screening, continuous observation, and rehearsed emergency procedures.
The objective is not to avoid oxygen’s biologic effects. Those effects are the reason HBOT is prescribed. The objective is to deliver enough oxygen to achieve the intended clinical response while remaining within a carefully controlled safety range.
