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Clinical Policy Bulletin:
Carbogen Inhalation Therapy
Number: 0428


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).

  • Central retinal artery occlusion
  • 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.

Cugati et al (2013) stated that central retinal artery occlusion (CRAO) is an ocular emergency and is the ocular analog of cerebral stroke.  It results in profound, usually monocular vision loss, and is associated with significant functional morbidity.  The risk factors for CRAO are the same atherosclerotic risk factors as for stroke and heart disease.  As such, individuals with CRAO may be at risk of ischemic end organ damage such as a cerebral stroke.  Therefore, the management of CRAO is not only to restore vision, but at the same time to manage risk factors that may lead to other vascular conditions.  There are a number of therapies that has been used in the treatment of CRAO in the past.  These include carbogen inhalation, acetazolamide infusion, ocular massage and paracentesis, as well as various vasodilators such as intravenous glyceryl trinitrate.  None of these "standard agents" had been shown to alter the natural history of disease definitively.  There has been recent interest shown in the use of thrombolytic therapy, delivered either intravenously or intra-arterially by direct catheterization of the ophthalmic artery.  While a number of observational series have shown that the recovery of vision can be quite dramatic, 2 recent randomized controlled trials have not demonstrated efficacy.  On the contrary, intra-arterial delivery of thrombolytic may result in an increased risk of intra-cranial and systemic hemorrhage, while the intravenous use of tissue plasminogen activator was not shown to be effective within 24 hrs of symptom onset.  Nevertheless, both of these studies have shown one thing in common, and that is for treatment to be effective in CRAO, it must be deployed within a short time window, probably within 6 hrs of symptom onset.  Therefore, while CRAO is a disease that does not have a treatment, nevertheless it needs to follow the same principles of treatment as any other vascular end organ ischemic disease.  That is, to attempt to re-perfuse ischemic tissue as quickly as possible and to institute secondary prevention early.

Furthermore, an UpToDate review on “Central and branch retinal artery occlusion” (Hedges, 2013) states that “A mixture of 95 percent oxygen and 5 percent carbon dioxide (Carbogen) can be provided in an attempt to induce vasodilation and improve oxygenation.  However, this is difficult to obtain in most hospitals on an urgent basis, and published reports are not supportive of its efficacy”.

CPT Codes / HCPCS Codes / ICD-9 Codes
There is no specific code for carbogen inhalation therapy:
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
345.00 - 345.91 Epilepsy and recurrent seizures
362.31 Central retinal artery occlusion
388.2 Sudden hearing loss, unspecified
430 - 438.9 Cerebrovascular disease
997.02 Iatrogenic cerebrovascular infarction or hemorrhage

The above policy is based on the following references:
  1. Edamatsu H, Hasegawa M, Oku T, et al. Treatment of sudden deafness: Carbon dioxide and oxygen inhalation and steroids. Clin Otolaryngol. 1985;10:69-72.
  2. Thurman M, Amedee RG. Sudden sensorineural hearing loss: Etiologies and treatments. J La State Med Soc. 1998;150(5):200-203.
  3. Schweinfurth JM, Cacace AT, Parnes SM. Clinical applications of otoacoustic emissions in sudden hearing loss. Laryngoscope. 1997;107(11 Pt 1):1457-1463.
  4. Stokroos RJ, Albers FW. Therapy of idiopathic sudden sensorineural hearing loss. A review of the literature. Acta Otorhinolaryngol Belg. 1996;50(1):77-84.
  5. Schweinfurth JM, Parnes SM, Very M. Current concepts in the diagnosis and treatment of sudden sensorineural hearing loss. Eur Arch Otorhinolaryngol. 1996;253(3):117-121.
  6. Rahko T, Kotti V. Comparison of carbogen inhalation and intravenous heparin infusion therapies in idiopathic sudden sensorineural hearing loss. Acta Otolaryngol Suppl. 1997;529:86-87.
  7. Kallinen J, Laurikainen E, Laippala P, Grenman R. Sudden deafness: A comparison of anticoagulant therapy and carbogen inhalation therapy. Ann Otol Rhinol Laryngol. 1997;106(1):22-26.
  8. Harris JP, Ruckenstein MJ. Sudden sensorineural hearing loss, perilymph fistula, and autoimmune inner ear disease. In: Otolaryngology. Head and Neck Surgery. 15th ed. JJ Ballenger, JB Snow, Jr. eds. Philadelphia, PA: Williams & Wilkins; 1996; Ch. 55:1109-1118.
  9. Hender K. Is carbogen gas effective in the treatment of sudden sensorineural hearing loss? Evidence Centre Evidence Report. Clayton, VIC: Centre for Clinical Effectiveness (CCE); 2000.
  10. Cinamon U, Bendet E, Kronenberg J. Steroids, carbogen or placebo for sudden hearing loss: A prospective double-blind study. Eur Arch Otorhinolaryngol. 2001;258(9):477-480.
  11. Hender KM, Anderson JN, Vallance NA, et al. Carbogen gas for treatment of sudden deafness. EBM in Action. Med J Austral. 2002;176(7):387-388.
  12. Joachims HZ, Segal J, Golz A, et al. Antioxidants in treatment of idiopathic sudden hearing loss. Otol Neurotol. 2003;24(4):572-575.
  13. Agarwal L, Pothier DD. Vasodilators and vasoactive substances for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev. 2009;(4):CD003422.
  14. Ashkanian M, Gjedde A, Mouridsen K, et al. Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease: Increased oxygen transport to hypoperfused brain. Brain Res. 2009;1304:90-95.
  15. Kim MG, Jung YG, Eun YG. Effect of steroid, carbogen inhalation, and lipoprostaglandin E(1) combination therapy for sudden sensorineural hearing loss. Am J Otolaryngol. 2011;32(2):91-95.
  16. Tolner EA, Hochman DW, Hassinen P, et al. Five percent CO₂is a potent, fast-acting inhalation anticonvulsant. Epilepsia. 2011;52(1):104-114.
  17. Cugati S, Varma DD, Chen CS, Lee AW. Treatment options for central retinal artery occlusion. Curr Treat Options Neurol. 2013;15(1):63-77.
  18. Hedges TR, III. Central and branch retinal artery occlusion. Last reviewed March 2013. UpToDate Inc. Waltham, MA.

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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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