Aetna considers carbogen inhalation therapy for the treatment of the following indications experimental and investigational because the effectiveness of this treatment has not been established by the peer-reviewed medical literature (not an all inclusive list).

• Seizures
• Stroke
• Sudden hearing loss.

Sudden hearing loss (SHL) is defined as sensorineural hearing loss of 30 decibels or more in 3 contiguous frequencies that develops in less than 3 days.  In most patients with SHL, hearing loss occurs within much less than 3 days.  Although a number of disease processes can produce similar hearing loss, true SHL is idiopathic in nature.  Males and females are evenly affected by SHL, and either ear is equally vulnerable.  The hearing loss is unilateral in about 90 % of patients.  In some patients, the profound loss in hearing may lessen, and in some cases, completely recover over a period of days or weeks.  Currently, there is no definitive practice guideline for the treatment of SHL.  Steroid therapy appears to be the only medical treatment proven to have a significant beneficial effect in selected patients with idiopathic SHL.

Various agents designed to enhance cochlear circulation and oxygenation have been advocated for the treatment of SHL.  These include plasma expanders, anti-platelet agents, anti-coagulants, vasodilators, and carbogen gas (5 % carbon dioxide and 95 % oxygen).  It has been suggested that carbogen inhalation therapy is effective in treating patients with high-frequency-sloping (from pure-tone audiogram) hearing impairment.  However, clinical studies of carbogen inhalation therapy have demonstrated no improvement in rates of recovery from SHL than the rate of spontaneous recovery.  A systematic review of the evidence of the use of carbogen gas for treatment of sudden deafness (Hender et al, 2002) concluded that “it is reasonably safe to conclude that carbogen gas inhalation is no more effective than heparin or 'standard care' in patients with idiopathic sudden sensorineural hearing loss”.

Ashkanian et al (2009) stated that hyperoxic therapy for cerebral ischemia reduces cerebral blood flow (CBF) principally from the vasoconstrictive effect of oxygen on cerebral arterioles.  Based on a recent study in normal volunteers, these researchers claim that the vasodilatory effect of carbon dioxide predominates when 5 % CO(2) is added to inhaled oxygen (the mixture known as carbogen).  These investigators measured CBF by positron emission tomography (PET) during inhalation of test gases (O(2), carbogen, and atmospheric air) in healthy volunteers (n = 10) and in patients with occlusive carotid artery disease (n = 6).  Statistical comparisons by an additive ANOVA model showed that carbogen significantly increased CBF by 7.51 + or - 1.62 ml/100 g/min while oxygen tended to reduce it by -3.22 + or - 1.62 ml/100 g/min.  A separate analysis of the hemisphere contralateral to the hypo-perfused hemisphere showed that carbogen significantly increased CBF by 8.90 + or - 2.81 ml/100 g/min whereas oxygen inhalation produced no reliable change in CBF (-1.15 + or - 2.81 ml/100 g/min).  In both patients and controls, carbogen was as efficient as oxygen in increasing Sa(O2) or PaO(2) values.  The findings of this study demonstrated that concomitant increases of CBF and Sa(O2) are readily obtained with carbogen, while oxygen increases only Sa(O2).  Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone.  The authors concluded that further studies with more subjects are, however, needed to investigate the applicability of carbogen for long-term inhalation and to assess its therapeutic benefits in acute stroke patients.

Tolner et al (2011) examined if inhaling 5 % CO(2) can be used to suppress seizures in epilepsy patients.  The effect of CO(2) on cortical epileptic activity accompanying behavioral seizures was studied in rats and non-human primates, and based on these data, preliminary tests were carried out in humans.  In freely moving rats, cortical afterdischarges paralleled by myoclonic convulsions were evoked by sensorimotor cortex stimulation.  Five percent CO(2) was applied for 5 mins, 3 mins before stimulation.  In macaque monkeys, hypercarbia was induced by hypoventilation while seizure activity was electrically or chemically evoked in the sensorimotor cortex.  A total of 7 patients with drug-resistant partial epilepsy were examined with video-electroencephalography and received 5 % CO(2) in medical carbogen shortly after electrographic seizure onset.  In rats, 5 % CO(2) strongly suppressed cortical afterdischarges, by approximately 75 %, whereas responses to single-pulse stimulation were reduced by about 15 %.  In macaques, increasing pCO(2) from 37 mm Hg to 44 - 45 mm Hg (corresponding to inhalation of 5 % CO(2) or less) suppressed stimulation-induced cortical afterdischarges by about 70 % and single, bicuculline-induced epileptiform spikes by approximately 25 %.  In a pilot trial carried out in 7 patients, a rapid termination of electrographic seizures was observed despite the fact that the application of 5 % CO(2) was started after seizure generalization.  The authors concluded that 5 % CO(2) has a fast and potent anti-convulsant action.  The present data suggested that medical carbogen with 5 % CO(2) can be used for acute treatment to suppress seizures in epilepsy patients.  The findings of this small, pilot study need to be validated by well-designed studies.