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Carbogen

Carbogen, originally developed by Ladislas Meduna in 1921 as a mixture with higher carbon dioxide content for psychiatric applications, is a medical gas mixture composed of 95–98% oxygen and 2–5% carbon dioxide, administered by inhalation to enhance tissue oxygenation and reduce hypoxia in various clinical contexts.^[1]^[2]^[3] The use of carbon dioxide-oxygen mixtures dates back to the 1920s, when they were employed to treat carbon monoxide poisoning by stimulating respiration and improving oxygen delivery.^[4] Modern applications of carbogen evolved from preclinical studies conducted over half a century ago, focusing on its potential to counteract tumor hypoxia and augment radiotherapy efficacy.^[3] By inducing vasodilation through elevated carbon dioxide levels, carbogen stabilizes blood flow and increases partial pressure of oxygen (pO₂) in hypoxic tissues, making it a valuable adjunct in oncology.^[3] In cancer treatment, carbogen serves as a radiosensitizer, particularly when combined with nicotinamide in regimens like ARCON (accelerated radiotherapy with carbogen and nicotinamide), which has shown improved survival in phase III trials for bladder and laryngeal cancers.^[3] For prostate cancer, studies such as the PROCON trial demonstrate its feasibility in enhancing tumor oxygenation during radiotherapy, with preclinical data indicating a significant reduction in hypoxia markers like R₂* values by up to 21.6%.^[3] Beyond oncology, carbogen is utilized in otology for sudden sensorineural hearing loss (SHL), where daily inhalation for five days increases inner ear blood flow and oxygen saturation, achieving recovery rates of 67.9% in clinical studies compared to lower rates with steroids alone.^[5] Additional applications include assessing cerebrovascular reactivity in neuroimaging via gas-challenge protocols, where carbogen provides a hypercapnic stimulus alternative to CO₂ in air for measuring vascular responses.^[6] In experimental settings, it has been used in noise-induced hearing protection models, underscoring its broad utility in improving oxygenation across medical disciplines.^[7]

History

Psychiatric Development by Ladislas Meduna

Mixtures of carbon dioxide and oxygen, known as carbogen, were first used medically in the 1920s to treat carbon monoxide poisoning by stimulating respiration and improving oxygen delivery.^[8] Ladislas Meduna, a Hungarian psychiatrist and neuropathologist born in 1896, developed an early interest in biological approaches to mental illness during his training at the University of Budapest, where he earned his medical degree in 1921.^[9] By the early 1930s, while working as a neuropathologist, Meduna formulated a groundbreaking theory positing a biological antagonism between schizophrenia and epilepsy. Through histological examinations of postmortem brain tissue, he observed proliferation of glial cells—particularly oligodendroglia and microglia—in the brains of individuals with schizophrenia, interpreting this as a pathological "glial reaction" that disrupted neuronal function.^[10] In contrast, brains from epileptic patients who died during status epilepticus showed marked destruction or reduction of these glial elements, alongside heightened neuronal activity, leading Meduna to hypothesize that inducing epileptic-like states could counteract the glial overactivity in schizophrenia.^[11] Building on this theoretical foundation, Meduna pioneered convulsive therapies in the mid-1930s, initially using intramuscular camphor oil to induce seizures in schizophrenic patients, followed by the more reliable convulsant pentylenetetrazol (Metrazol).^[12] These efforts marked a shift toward physiological interventions in psychiatry, but by the 1940s, after emigrating to the United States in 1940 amid World War II and joining the University of Illinois College of Medicine in 1943, Meduna extended his research to non-convulsive methods.^[9] Seeking milder ways to alter brain physiology without full seizures, he experimented with gas inhalation to produce controlled physiological changes, adapting existing carbogen mixtures into a specific high-CO₂ variant (30% carbon dioxide (CO₂) and 70% oxygen (O₂)), known as Meduna's mixture—a formulation distinct from the low-CO₂ carbogen (2–5% CO₂) used in contemporary medical applications.^[2]^[3] Meduna's formal introduction of his mixture occurred with the publication of his seminal book, Carbon Dioxide Therapy: A Neurophysiological Treatment of Nervous Disorders, in 1950 by Charles C. Thomas Publisher.^[13] In this work, he detailed over 100 cases of psychoneuroses and psychosomatic disorders treated via inhalation of the mixture, emphasizing its role in provoking therapeutic altered states. The initial rationale centered on inducing hypercapnia—a state of elevated CO₂ levels in the blood—to stimulate respiratory drive, alter cerebral pH, and modulate neural excitability, thereby providing relief from psychiatric symptoms without the risks of pharmacological convulsions.^[14] This approach reflected Meduna's ongoing commitment to neurophysiological interventions rooted in his glial-neuronal antagonism theory, positioning his mixture as a safer adjunct to his earlier convulsive methods.^[9]

Early Psychiatric Applications

Carbogen inhalation therapy gained prominence in psychiatric practice during the 1940s and 1950s as a method to induce altered states of consciousness for treating schizophrenia, anxiety, and neuroses.^[2] Pioneered by Ladislas Meduna after his emigration to the United States, the treatment involved patients breathing the gas mixture—typically Meduna's mixture (30% carbon dioxide and 70% oxygen), though concentrations could vary from 1.5% to 50% depending on the clinical goal—for 20 to 30 breaths, often leading to rapid unconsciousness and convulsions within 1 to 3 minutes.^[2] This approach facilitated cathartic abreaction, allowing patients to access repressed emotions and transition into psychedelic-like experiences that Meduna believed could alleviate psychotic symptoms and neurotic patterns.^[2] The therapy was frequently integrated with other convulsive treatments, serving as a non-electrical precursor to electroconvulsive therapy (ECT), which had been introduced in 1938.^[2] In sessions, the mixture induced physiological changes that mimicked seizure states, promoting therapeutic insights without invasive procedures.^[2] Meduna documented numerous case studies in his seminal 1950 monograph, where patients described vivid sensory phenomena, such as perceptions of "bright light like the sun" or out-of-body sensations, alongside emotional releases that contributed to symptom relief in conditions like obsessive-compulsive disorder and severe anxiety.^[2] For instance, one patient reported a horrifying preconvulsive terror followed by profound catharsis, illustrating the mixture's role in desensitizing individuals to intense psychological distress.^[2] By the mid-1950s, carbogen therapy had spread across Europe and the United States, becoming a widely accepted somatic intervention among psychiatrists before its eventual decline in favor of more effective pharmacological options.^[2] This dissemination included explorations by early psychedelic researchers, such as Humphry Osmond, who encountered the technique through networks involving figures like Al Hubbard and integrated similar inhalation methods into preparatory phases of hallucinogen-assisted psychotherapy. Meduna's work laid foundational groundwork for understanding gas-induced altered states in mental health, influencing subsequent convulsive and psychedelic approaches despite the therapy's limitations in long-term efficacy.^[2]

Composition

Gas Mixtures

Carbogen is defined as a binary gas mixture composed exclusively of oxygen (O₂) and carbon dioxide (CO₂), without inclusion of any other gases. The original formulation, developed by Ladislas Meduna in the 1930s for psychiatric applications, consisted of approximately 30% CO₂ and 70% O₂.^[2] This composition was selected to induce rapid physiological responses during therapy sessions.^[15] In contemporary medical practice, a prevalent variant employs 95% O₂ and 5% CO₂, particularly for enhancing tissue oxygenation in treatments such as radiotherapy adjuncts.^[16] CO₂ concentrations in carbogen mixtures generally span 1.5% to 50%, tailored to the therapeutic objective—higher levels to elicit hallucinogenic effects in psychotherapy, and lower levels to support oxygenation in applications like oncology.^[2] Under medical gas regulations, carbogen is classified as a non-flammable, oxidizing, and potential asphyxiant gas, requiring handling in compliance with standards for compressed medical gases.^[16]^[17]

Preparation and Variations

Carbogen is prepared by blending medical-grade oxygen (O₂) and carbon dioxide (CO₂), both meeting United States Pharmacopeia (USP) standards for purity, in high-pressure cylinders by specialized gas manufacturers such as Westair Gases & Equipment or Industrial Source.^[18]^[19] This mixing process ensures precise ratios while adhering to USP monograph requirements for medical gases, which limit impurities like moisture, non-volatile residues, and oxidizing substances to maintain therapeutic safety and efficacy. Delivery systems typically involve pre-mixed cylinders equipped with demand-flow regulators to provide controlled inhalation rates, often via face masks or nasal cannulas in clinical settings; these regulators adjust gas flow based on patient demand to prevent over-pressurization and ensure consistent delivery.^[18] While on-site gas mixing using automated blenders is possible in research facilities for custom blends from bulk USP-grade sources, medical applications predominantly rely on factory-pre-mixed cylinders to guarantee uniformity and compliance.^[20] Variations in carbogen composition are tailored to specific clinical needs, with the standard mixture being 95% O₂ and 5% CO₂ for general medical uses like radiosensitization in oncology.^[19] Lower CO₂ concentrations, such as 2-5%, are employed in oncology to enhance tumor oxygenation during radiotherapy without excessive respiratory stimulation, as demonstrated in studies showing improved pO₂ levels with 98% O₂/2% CO₂.^[21] In contrast, historical psychiatric applications used higher CO₂ levels, notably Meduna's mixture of 70% O₂/30% CO₂, to induce altered states for therapeutic purposes.^[15] Experimental variations, like 98% O₂/2% CO₂, have been tested for tolerability and oxygenation benefits in tumor models. Quality control for carbogen involves rigorous testing at production to detect contaminants such as hydrocarbons, nitrogen, or argon, ensuring levels below USP limits (e.g., purity not less than 99.0% for both oxygen and carbon dioxide, with carbon monoxide not more than 10 ppm and other specific impurities such as carbon dioxide in oxygen not more than 300 ppm). Stability during storage is maintained in cylinders under controlled conditions, typically at ambient temperatures below 52°C and away from ignition sources, with periodic validation confirming no degradation or separation of gas components over shelf life.^[18]

Mechanism of Action

Respiratory and Cardiovascular Effects

Inhalation of carbogen induces mild hypercapnia by elevating arterial partial pressure of carbon dioxide (PaCO₂), which stimulates peripheral chemoreceptors in the carotid and aortic bodies as well as central chemoreceptors in the medulla oblongata, prompting an increase in respiratory rate and tidal volume to facilitate CO₂ elimination.^[22] Inhalation of standard carbogen mixtures (95% O₂ and 5% CO₂) typically increases minute ventilation in healthy individuals due to CO₂-driven stimulation, though responses can vary, with some studies reporting reductions in respiratory rate due to the interplay between CO₂ stimulation and oxygen-induced suppression of hypoxic drive.^[23]^[24] The hypercapnia from carbogen promotes vasodilation through direct relaxation of vascular smooth muscle and acidification of the extracellular environment, enhancing cerebral and peripheral blood flow in responsive vascular beds. This improves tissue perfusion without significant changes in systemic arterial blood pressure in most cases.^[25] In ocular and retinal circulations, for instance, carbogen breathing has been shown to increase blood velocity and flow, demonstrating the widespread vasodilatory impact.^[26] Enhanced oxygenation occurs as the high oxygen partial pressure (PaO₂) in carbogen, often exceeding 400 mmHg, directly counters tissue hypoxia by saturating hemoglobin near 100%. Concurrently, the Bohr effect—wherein elevated CO₂ and resultant acidosis decrease hemoglobin's oxygen affinity—shifts the oxygen-hemoglobin dissociation curve to the right, promoting greater oxygen unloading in peripheral tissues.^[27] Cardiovascular responses include tachycardia and modest elevations in blood pressure driven by sympathetic nervous system activation from hypercapnic chemoreceptor signaling, with heart rate increases of about 8-10 beats per minute and systolic/diastolic pressure rises of similar magnitude observed during inhalation.^[26] These changes reflect heightened sympathoadrenal activity, boosting cardiac output while maintaining overall hemodynamic stability.^[22] Effects typically peak within 1-2 minutes of onset and subside 5-10 minutes after discontinuation, aligning with the rapid pharmacokinetics of inhaled gases.^[28]

Neurological Impacts

Carbogen inhalation enhances cerebral blood flow and oxygen delivery to neural tissues, thereby mitigating hypoxia in brain regions susceptible to ischemic stress. The mixture's 5% carbon dioxide component induces vasodilation in cerebral arterioles, counteracting the vasoconstrictive effects of hyperoxia and resulting in net increases in blood flow.^[29] This improved perfusion supports neuronal metabolism, particularly in hypoperfused regions, as demonstrated in patients with occlusive carotid artery disease where carbogen boosted oxygen transport without exacerbating ischemia.^[30] The elevated CO2 levels in carbogen cause respiratory acidosis, lowering extracellular pH in the brain and directly modulating neuronal excitability. Acidosis inhibits voltage-gated sodium channels, such as NaV1.2 in pyramidal neuron axon initial segments, reducing action potential firing and overall cortical hyperactivity.^[31] This pH shift also promotes enhanced release of inhibitory neurotransmitters like GABA, further dampening excitatory signaling and contributing to anticonvulsant effects observed in experimental seizure models.^[32] Inhalation of carbogen's CO2 component activates central chemoreceptors, evoking a perception of suffocation that elicits acute panic-like neural responses involving the amygdala and brainstem fear circuits. This triggers sympathetic activation and heightened vigilance, mimicking endogenous alarm states that can facilitate emotional processing in neural pathways.^[33] At concentrations around 5% CO2, such responses are reliably induced, as evidenced by increased anxiety and autonomic arousal in controlled human studies.^[34] In patients with occlusive carotid artery disease, carbogen inhalation acutely increases cerebral blood flow and oxygen transport to hypoperfused brain tissue.^[30]

Psychiatric Uses

Psychedelic Therapy Techniques

Carbogen inhalation emerged as a key technique in psychedelic therapy during the 1950s and 1960s, primarily to induce rapid altered states of consciousness for accessing repressed emotions and facilitating abreaction in psychotherapy. Pioneered by Hungarian psychiatrist Ladislas J. Meduna, the method utilized a gas mixture of 30% carbon dioxide and 70% oxygen, administered to patients with neuroses, anxiety, and other psychiatric conditions to promote cathartic release and psychological insight. This approach was integrated into broader psychotherapeutic practices, including as an adjunct to LSD-assisted sessions, where it served to acclimate patients to ego-dissolving experiences before fuller psychedelic immersion.^[2]^[9]^[35] Sessions followed a structured protocol beginning with pre-inhalation preparation, during which the therapist established rapport, outlined potential sensations such as suffocation or euphoria, and positioned the patient supine for safety and comfort. The inhalation phase then involved delivering the carbogen mixture via a face mask connected to a pressurized cylinder, typically requiring 20-30 breaths over 1-3 minutes to reach peak effects, including vivid hallucinations, out-of-body perceptions, and emotional surges, all under close therapist supervision to manage intensity.^[2]^[9] Throughout the peak effects, which lasted 5-10 minutes, patients were encouraged to verbalize emerging unconscious material—such as traumatic memories or repressed impulses—to integrate it immediately with ongoing talk therapy, thereby desensitizing emotional blocks and fostering therapeutic breakthroughs. Following the dissipation of acute effects, the session concluded with an integration discussion, where the therapist and patient reviewed insights, processed residual emotions, and connected experiences to daily life challenges. This verbalization and reflection were central to Meduna's framework, drawing on abreactive principles to purge psychological tensions.^[2]^[9] In historical applications, Meduna conducted thousands of such sessions in the 1950s, administering treatments three times weekly to build cumulative therapeutic effects, while researchers like Myron Stolaroff at the Institute for Advanced Study employed carbogen in the 1960s to prepare participants for LSD therapy, enhancing overall session efficacy by simulating profound altered states without prolonged commitment. These techniques relied on hypercapnia-induced neurological shifts to mimic hallucinogenic states, temporarily disrupting normal cortical inhibition.^[35]^[9]

Historical Outcomes and Decline

Early studies in the 1950s reported successes with carbogen inhalation in psychiatric treatment, particularly for schizophrenia, where symptom reduction was observed in a significant proportion of cases through facilitation of abreaction and altered states that allowed for emotional release. In neuroses, carbogen was noted for promoting catharsis, suggesting its utility in alleviating anxiety and neurotic patterns by inducing rapid psychological insights. These outcomes were attributed to the gas mixture's ability to trigger non-ordinary states of consciousness, enabling patients to access repressed material under therapeutic guidance.^[36] Despite initial enthusiasm, carbogen therapy faced notable limitations, including inconsistent results across patients and a risk of inducing panic or adverse emotional reactions during inhalation, which could exacerbate symptoms in vulnerable individuals. The absence of randomized controlled trials further undermined its credibility, as early claims of efficacy were largely anecdotal or based on open-label observations without rigorous controls, leading to skepticism in the psychiatric community.^[37] The decline of carbogen in psychiatric practice accelerated in the 1950s with the advent of antipsychotic medications like chlorpromazine, which offered more reliable symptom management for schizophrenia and reduced the need for inhalation-based interventions.^[38] This shift toward pharmacological therapies, coupled with increasing regulatory scrutiny on substances inducing altered states amid the broader crackdown on psychedelics, contributed to its fall from favor, as safer, pill-based options became standard. Carbogen's legacy endures in modern breathwork practices, influencing techniques like holotropic breathwork developed by Stanislav Grof, which draws on similar principles of non-drug-induced altered states for self-exploration and therapy.^[39] Grof's approach, created as an alternative to psychedelic sessions, echoes Meduna's use of carbogen to facilitate cathartic experiences without pharmacological agents.^[40]

Medical Applications

Oncology Treatments

Carbogen, a gas mixture consisting of 95% oxygen and 5% carbon dioxide, is inhaled during radiotherapy sessions to act as a radiosensitizer by enhancing tumor oxygenation. This approach targets hypoxic regions within tumors, where low oxygen levels contribute to radioresistance, thereby increasing the efficacy of radiation in killing cancer cells.^[41]^[42] Tumor hypoxia is a significant resistance factor observed in 50-60% of solid tumors, limiting the effectiveness of standard radiotherapy by reducing the production of radiation-induced DNA-damaging free radicals. By promoting vasodilation and improving blood flow through the CO2 component while delivering high oxygen levels, carbogen helps overcome this hypoxia, reoxygenating tumor tissues and restoring radiosensitivity.^[43]^[44] A key application of carbogen in oncology is the ARCON regimen, which combines accelerated radiotherapy with carbogen inhalation and nicotinamide administration to address both acute and chronic hypoxia. In a phase III randomized trial involving patients with T2-T4 laryngeal cancer, ARCON did not significantly improve 5-year local control rates compared to accelerated radiotherapy alone (79% versus 78%, p=0.80) but showed improved regional control (93% versus 86%, p=0.04), with no increase in severe late toxicity.^[45] In bladder cancer, the BCON phase III trial demonstrated that adding carbogen and nicotinamide to radiotherapy improved 5-year overall survival from 41% to 50% (HR 0.79, 95% CI 0.64-0.98, p=0.04), with sustained benefits confirmed in the 2021 10-year update.^[46] Clinical evidence from translational studies in the 2000s supports carbogen's oxygenation benefits; for instance, in prostate cancer patients, BOLD MRI imaging during carbogen breathing demonstrated a mean 21.6% reduction in R₂* values, indicating a substantial increase in tumor oxygenation levels. Similar enhancements have been observed in other solid tumors, providing rationale for its radiosensitizing potential.^[47] As of 2025, carbogen remains investigational for oncology, particularly in head and neck cancers, where it continues to be explored in clinical trials as an adjunct to radiotherapy rather than standard care, with ongoing research focusing on optimizing hypoxic modification strategies.^[48]

Otolaryngology and Ophthalmology Uses

Carbogen, consisting of 95% oxygen and 5% carbon dioxide, is utilized in otolaryngology for the treatment of sudden sensorineural hearing loss (SSHL), an acute condition involving rapid deterioration of hearing due to impaired inner ear blood flow. The mixture is inhaled to enhance cochlear oxygenation, with the carbon dioxide component inducing vasodilation to improve microcirculation in the labyrinth.^[49] This approach aims to mitigate ischemic damage in the cochlea, particularly when initiated promptly after symptom onset. Clinical trials from the 2000s onward have evaluated carbogen's efficacy, often in combination with steroids or lipo-prostaglandin E1 (lipo-PGE1). A 2010 prospective study found that combined steroid, carbogen inhalation, and lipo-PGE1 therapy yielded superior hearing recovery compared to steroids alone or other regimens in patients with idiopathic SSHL, with notable improvements in pure-tone average thresholds.^[50] Similarly, a 2012 randomized trial reported overall recovery rates of 67.9% in the carbogen-plus-steroid group versus 52.3% in the steroid-only group, suggesting a 10-20% relative improvement attributable to carbogen's circulatory effects when added to standard care.^[5] These findings position carbogen as an adjunctive option, though a 2002 systematic review of three comparative studies concluded it offers no significant advantage over placebo for hearing recovery in SSHL.^[51] Administration typically occurs via normobaric inhalation in acute hospital settings, ideally within 24 hours of onset, with sessions lasting 20-30 minutes multiple times daily for several days.^[52] In ophthalmology, carbogen serves as an emergency intervention for central retinal artery occlusion (CRAO), a vision-threatening ischemic event caused by emboli or thrombosis blocking retinal blood supply. Inhalation promotes vasodilation to facilitate reperfusion of hypoxic retinal tissue, potentially preserving photoreceptor function if applied early.^[53] Protocols generally involve 10-15 minute sessions of normobaric or hyperbaric delivery, repeated over hours to days in the initial 24-hour window post-onset, often alongside ocular massage or pressure-lowering agents.^[54] Evidence for carbogen in CRAO remains limited and mixed, with 2000s-era investigations, including combinations with anterior chamber paracentesis, showing minimal visual acuity gains in controlled trials.^[55] It is recommended in some guidelines as a low-risk, noninvasive measure but is not considered first-line due to inconsistent outcomes.^[56] Meta-analyses of acute CRAO therapies up to 2020 report partial visual restoration in approximately 40-50% of cases across various interventions, though carbogen-specific data highlight modest benefits in uncontrolled series, such as improved acuity in about 35% of treated patients.^[57]

Other Clinical Applications

Carbogen, typically a 95% oxygen and 5% carbon dioxide mixture, is employed in in vitro neuroscience studies to perfuse artificial cerebrospinal fluid (aCSF) in brain slice preparations, thereby maintaining physiological pH levels around 7.4 and ensuring adequate tissue oxygenation during electrophysiological recordings and imaging.^[58] This approach enhances the viability of acute brain slices by mitigating hypoxia-induced metabolic stress, allowing for prolonged experimental durations in models of neuronal activity and synaptic function.^[59] Such applications are standard in basic research settings, where carbogen bubbling prevents acidosis and supports network-level analyses without systemic influences.^[60] In investigational contexts, carbogen has been explored for its potential to improve post-stroke oxygenation in animal models of cerebral ischemia, particularly through hyperoxic challenges that enhance cerebral blood flow and oxygen delivery to ischemic penumbras.^[61] Preliminary studies from the 2010s demonstrated that carbogen inhalation could modulate vessel size and blood oxygenation level-dependent signals in rodent stroke models, suggesting a supportive role in recovery by reducing hypoxic damage, though translation to clinical settings remains exploratory.^[62] These findings highlight carbogen's utility in preclinical simulations of transient ischemia, where it aids in assessing metabolic responses without direct therapeutic intent.^[63] Beyond neuroscience, carbogen serves as a tool in biological assays evaluating oxygen and CO2 flux dynamics, particularly for assessing tissue viability under controlled hypoxic conditions.^[64] In such experiments, varying carbogen concentrations simulate physiological gas exchanges, enabling quantification of metabolic rates and cell survival in organotypic cultures, which informs broader studies on perfusion-dependent processes.^[65] Carbogen has seen rare adjunctive use in migraine therapy, where its vasodilatory effects—induced by CO2-mediated cerebral vessel dilation—may alleviate acute symptoms by improving hypoperfused brain tissue oxygenation.^[66] Historically, it was investigated for preventing altitude sickness through enhanced oxygen uptake and acid-base balance during high-altitude exposure, though this application has largely been supplanted by other interventions.^[67] Despite these niche roles, evidence for carbogen's broader clinical applications remains limited, with few human trials conducted in the 2020s and most uses confined to supportive, experimental frameworks in research laboratories.^[68] Core benefits stem from its ability to optimize tissue oxygenation, underscoring its value in controlled settings rather than routine patient care.^[69]

Safety and Side Effects

Common Adverse Reactions

Common adverse reactions to carbogen inhalation stem from the physiological effects of mild hypercapnia induced by the carbon dioxide component, typically manifesting as short-term symptoms that resolve rapidly upon cessation. Dizziness, headache, and nausea are frequently reported, arising from elevated CO2 levels affecting cerebral blood flow and acid-base balance.^[70] In psychiatric applications, particularly with higher CO2 concentrations (e.g., 5-7.5%) used for induction, patients may experience anxiety, panic attacks, or hallucinations, which are more prevalent in individuals with underlying anxiety disorders.^[71] Cardiovascular responses include elevated heart rate due to chemoreceptor stimulation.^[72] At elevated CO2 levels beyond standard 5% formulations, paresthesia and tinnitus can emerge as sensory disturbances linked to intensified hypercapnic acidosis.^[73] Mild effects are generally reported across clinical uses, resolving within minutes post-inhalation without long-term sequelae. In clinical trials, such as ARCON regimens for cancers, carbogen has been well-tolerated with no significant toxicity.^[52]

Contraindications and Precautions

Carbogen inhalation is contraindicated in conditions exacerbated by hypercapnia, such as severe chronic obstructive pulmonary disease (COPD) or recent myocardial infarction, as the CO2 component can worsen respiratory acidosis or induce cardiovascular stress through increased heart rate and respiration.^[70] Use with caution in asthma or pregnancy due to risks of bronchospasm or potential fetal effects from maternal hypercapnia.^[70] Precautions for safe use involve initiating therapy with low CO2 concentrations (e.g., 2-5%) to assess tolerance, avoiding administration in unsupervised environments to monitor for acute reactions, and obtaining informed consent highlighting possible disorienting effects.^[18] The U.S. Food and Drug Administration (FDA) classifies Carbogen as an investigational medical gas for most therapeutic applications beyond basic respiratory stimulation, mandating administration under direct medical supervision by qualified practitioners.^[52] To mitigate risks, protocols emphasize gradual exposure starting at short durations (e.g., 5-10 minutes) with immediate availability of emergency oxygen and resuscitation equipment.^[74]

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In addition to the inhalation of carbon dioxide, injections of apomorphine (14) or the barbiturate sodium amytal (15) interrupted catatonic stupors in ...
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In 1966, Hanns Hippius, a German researcher, was asked to continue the trials on humans by Wander. The results confirmed that clozapine was an effective ...
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Jan 22, 2008 · Meduna began researching carbogen therapy in 1943 and over the course of his career conducted more than 15,000 carbogen "treatments".1 His ...
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Definition of carbogen - NCI Dictionary of Cancer Terms
It may increase the amount of oxygen in cancer cells, which may make them easier to kill with radiation therapy. Carbogen is a type of radiosensitizing agent.Missing: oncology | Show results with:oncology
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Middle dose rate irradiation in combination with carbogen inhalation ...
Purpose: Carbogen increases the radiation response of tumors and reduced dose rate irradiation spares the damage of normal tissues.
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Hypoxia in Solid Tumors: How Low Oxygenation Impacts the “Six Rs ...
Sep 2, 2021 · In this sense, hypoxic regions are considered to be present in about 50% of solid tumors, and hypoxia is one of the most studied causes of ...
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ARCON: a novel biology-based approach in radiotherapy - The Lancet
ARCON (accelerated radiotherapy with carbogen and nicotinamide) is a new therapeutic strategy that combines radiation treatment modifications, with the aim of ...<|control11|><|separator|>
[45]
results of a phase III randomized trial - PubMed
May 20, 2012 · A randomized trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen inhalation and nicotinamide (ARCON) in laryngeal cancer.Missing: regimen | Show results with:regimen
[46]
Carbogen breathing increases prostate cancer oxygenation
The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen ...
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Preclinical and clinical advances to overcome hypoxia in ... - Nature
Jul 13, 2024 · Breathing carbogen before and during irradiation increases the dissolved oxygen in the plasma and reduced chronic hypoxia, while nicotinamide ...<|control11|><|separator|>
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Effects of Carbogen on Cochlear Blood Flow and Hearing Function ...
Carbogen refers to mixed gases that contain 5% CO2 and 95% oxygen (O2), which was described as a treatment for sudden hearing loss by Fisch et al. (5). Despite ...
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Effect of steroid, carbogen inhalation, and lipoprostaglandin E1 ...
Conclusion: Steroid, lipo-PGE(1), and carbogen inhalation therapy was more effective than the other treatment modalities studied for patients with ISSNHL.Missing: ophthalmology evidence 2000s
[50]
Is carbogen gas effective in the treatment of sudden sensorineural ...
Aug 7, 2003 · - We identified three comparative studies that evaluate the effectiveness of carbogen gas in the treatment of sudden sensorineural hearing loss.
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Carbogen Inhalation Therapy - Medical Clinical Policy Bulletins
These include plasma expanders, anti-platelet agents, anti-coagulants, vasodilators, and carbogen gas (5 % carbon dioxide and 95 % oxygen). It has been ...Missing: modern composition<|control11|><|separator|>
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Central Retinal Artery Occlusion (CRAO) Treatment & Management
Sep 23, 2024 · Some of the noninvasive treatments include ocular massage, hyperbaric oxygen (HBO) therapy, carbogen inhalation therapy, intraocular pressure reduction.Medical Care · Hyperbaric Medicine · Inpatient Care
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Diagnosis and Management of Central Retinal Artery Occlusion
Aug 1, 2017 · Table 1: Treatment Options for CRAO ; Inhalation of carbogen, Vasodilation to increase blood oxygen content ; Sublingual isosorbide dinitrate ...
[54]
Efficacy of anterior chamber paracentesis and Carbogen in treating ...
The data suggest that anterior chamber paracentesis and Carbogen therapy offer little benefit for treating acute nonarteritic CRAO.
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In Vitro Wedge Slice Prep for Neuronal Circuit Connectivity
Aug 18, 2020 · We developed a modified brain slice to mimic in vivo ... Maintain oxygenation and pH of solution by bubbling continuously with carbogen throughout ...
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Easy Cost-Effective Acute Brain Slice Incubation System
Jan 15, 2022 · Easy to build cost-effective acute brain slice incubation system for parallel analysis of multiple treatment conditions ... Carbogen was injected ...
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Oxygen metabolism in acute ischemic stroke - Sage Journals
Aug 9, 2017 · These results demonstrate that not only do OEF and CMRO2 respond consistently with the reported results during carbogen challenges, but that ...
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Vessel size imaging reveals pathological changes of microvessel ...
Jochimsen et al (2010) assessed venous VSI in healthy human brains with the administration of carbogen by measuring the induced blood oxygenation level- ...
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Applications of Nitroimidazole In Vivo Hypoxia Imaging in Ischemic ...
May 1, 2008 · Influence of tumour volume and carbogen breathing. Acta Oncol. 2002 ... cerebral blood flow and hypoxia in an animal stroke model. Magn ...
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Effect of Oxygen Concentration on Viability and Metabolism in ... - NIH
Four oxygen treatments were tested and validated by an in-line oxygen electrode: (1) 95:5 oxygen:carbon dioxide (carbogen), (2) 75:20:5 nitrogen:oxygen ...
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Effect of Hyperoxia and Hypercapnia on Tissue Oxygen and ...
Gas challenges (100% O2, 10% CO2, and carbogen [90% O2+10% CO2]) interleaved with room air was delivered to rabbits to investigate their effect on tissue ...Missing: assays viability
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Treatment of acute migraine by a partial rebreathing device
Aug 22, 2018 · ... migraine pain is caused by cerebral vasodilation. Rather than the ... Improvement of brain tissue oxygenation by inhalation of carbogen.
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Supplemental CO 2 improves oxygen saturation, oxygen tension ...
Jul 29, 2020 · At altitude, decreased atmospheric partial pressure of oxygen (PO2) ... Improvement of brain tissue oxygenation by inhalation of carbogen.Missing: prevention | Show results with:prevention
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Inspired and expired gas concentrations in man during carbogen ...
Carbogen is a mixture of 5% carbon dioxide (C02) and 95% oxygen (O2). Its medical use was first developed in the 1930's and in recent years interest has been ...
[68]
Exercise facilitates post-stroke recovery through mitigation ... - Nature
Oct 8, 2025 · The pH of the ACSF was adjusted to 7.35 by introducing carbogen gas (95% O2 and 5% CO2). The recording process involved patching the soma of ...<|separator|>
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Hypercapnea - StatPearls - NCBI Bookshelf
Patients may present with complaints of flushed skin, lethargy, inability to focus, mild headaches, disorientation, dizziness, shortness of breath, dyspnea on ...
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Carbon Dioxide—Induced Anxiety: Behavioral, Physiologic, and ...
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The effects of breathing 5% CO2 on human cardiovascular ...
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Carbon Dioxide Narcosis - StatPearls - NCBI Bookshelf
Carbon dioxide (CO 2 ) narcosis is a condition that develops when excessive CO 2 is present in the bloodstream, leading to a depressed level of consciousness.
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Carbogen - DailyMed
WARNING: Administration of Oxygen-Carbon Dioxide Mixtures may be hazardous or contraindicated. effects and the precautions to be taken. WARNING: HIGH PRESSURE ...