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End-Tidal Carbon Monoxide Measurement (ETCOc)

Policy Number: MP-196

Latest Review Date: August 2021

Category:  Laboratory                                                            

Policy Grade:  Active Policy but no longer scheduled for regular literature reviews and updates.


End-Tidal Carbon Monoxide measurement as an index of bilirubin production and/or hemolysis is considered investigational.


The measurement of ETCOc corrected for background carbon monoxide (CO) in the breath represents a new technology that is said to detect the rate of hemolysis and/or assist in the tracking of hemolytic conditions.  The technology is said to also measure end-tidal carbon dioxide (ETCO2) and respiratory rate simultaneously.  The test is non-invasive, does not require the cooperation of the patient, and the results are available immediately.

The catabolism of hemoglobin (Hgb) results in the equimolar formation of CO and Bilirubin.  ETCOc is an indicator of the rate of hemolysis and bilirubin production.  Elevation of breath CO may be indicative of pathological process in the newborn.

Administration of the test involves placement of a catheter into a patient’s nostril, secured to the lip with tape; insertion of filter cartridge to analyzer port; and sampling of patient’s breath with background air check for base levels.  An elevated ETCOc is said to indicate that the infant is at high risk for development of hyperbilirubinemia.  The cause of the hemolysis should be identified, appropriate treatment should be initiated, and the patient should be monitored closely.

Jaundice is probably the most common medical issue in newborns, affecting 60% to 70% of children within the first week of life.  It is one of the most common diagnoses for readmission of newborns.  Although all babies have levels higher than adults do, neonatal hyperbilirubinemia is considered when total serum bilirubin (TSB) level is >5 mg/dL.  Bilirubin is formed from the breakdown of hemoglobin and hemoproteins.  There is equimolar production of carbon monoxide (which is exhaled) and bilirubin (which is excreted in the GI tract).  Bilirubin excess occurs due to overproduction, decreased conjugation, or impaired excretion/increased reabsorption. 

The examining clinician who notices jaundice or scleral icterus often first detects hyperbilirubinemia.  Jaundice typically begins in the face and spreads to the chest and the extremities.  Visual examination (largely dependent on experience, skin tone, and lighting) may not be reliable.  Jaundice within the first 24 hours is pathologic and requires immediate evaluation and therapy.  More typically, jaundice appears on day of life 2 to 4 and is often idiopathic.

The diagnosis of hyperbilirubinemia is based on TSB.  Transcutaneous bilimeters offer advantages in ease, cost, and comfort to the patient.  The newer models may not be as dependent on skin pigmentation, which is the biggest obstacle in using these devices.  End tidal carbon monoxide levels is said to help assess for increased production of bilirubin, but this method has not been shown to be clinically superior to hour-specific bilirubin levels in the prediction of hyperbilirubinemia. 


The most recent update with literature review covers the period through August 10, 2021.

Summary of Evidence

While measurement of end-tidal carbon monoxide levels, an index of bilirubin production can provide information about the presence or absence of hemolysis, additional research is needed to quantify the risks, benefits, and costs of these measurements.  Until such information is available, the American Association of Pediatrics practice guidelines represent a good approach for most infants.


End-tidal carbon monoxide levels, ETCOc, hyperbilirubinemia, serum bilirubin, bilirubin, hemolysis, jaundice, transcutaneous bilimeters

Approved by Governing Bodies:

Not applicable.


Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity. Special benefit consideration may apply.  Refer to member’s benefit plan.


CPT codes:


Unlisted chemistry procedure



Carbon monoxide, expired gas analysis (e.g., ETCOc/hemolysis breath test) (Code deleted effective January 1, 2009)


  1. Akera, C. and Ro, S. Medical concerns in the neonatal period, Clin Fam Pract 2003;5(2):265-86.
  2. American Academy of Pediatrics. Management of hyperbilirubinemia in the healthy term newborn, Pediatrics 1994;94(4):1-15. available at (accessed 7/1/04)
  3. Bahr TM, Shakib JH, Stipelman CH, Kawamoto K, Lauer S, Christensen RD. Improvement Initiative: End-Tidal Carbon Monoxide Measurement in Newborns Receiving Phototherapy. J Pediatr. 2021 Jul 11:S0022-3476(21)00673-9. doi: 10.1016/j.jpeds.2021.07.008. Epub ahead of print.
  4. Herschel, M. Evaluation of the direct antiglobin (coombs’) test for identifying newborns at risk for hemolysis as determined by end-tidal carbon monoxide concentration (ETCOc); and comparison of the Coombs’ test with ETCOc for detecting significant jaundice, J Perinatol 2002;22(5):341-7.
  5. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  6. Javier, M.C. Corrected end-tidal carbon monoxide closely correlates with the corrected reticulocyte count in coombs’ test-positive term neonates, Pediatrics 2003;112(6):1333-7.
  7. Johnson, L.H., Bhutani,V.K., and Brown, A.K. System-based approach to management of neonatal jaundice and prevention of kernicterus, J Pediatr 2002;140(4):396-403.
  8. Krediet TG, Cirkel GA, et al.  End-tidal carbon monoxide measurements in infant respiratory distress syndrome.  Acta Paediatr 2006; 95(9): 1075-1082.
  9. Maisels, M.J., Baltz, R.D., Bhutani, V.K., and et al. Neonatal Jaundice and kernicterus, Pediatrics 2001;108(3):763-5.
  10. May C, Patel S, Peacock J, et al.  End-tidal carbon monoxide levels in prematurely born infants developing bronchopulmonary dysplasia.  Pediatr Res 2007; 61(4): 474-478.
  11. Okuyama, H. End-tidal carbon monoxide is predictive for neonatal non-hemolytic hyperbilirubinemia, Pediatr Int 2001;43(4):275-8.
  12. Stevenson, D.K. Prediction of hyperbilirubinemia in near-term and term infants, Pediatrics 2001;108(1):31-9.
  13. Stevenson, D.K. Prediction of hyperbilirubinemia in near-term and term infants, J Perinatol 2001;21 Suppl 1:S63-72.
  14. U.S. Preventive Services Task Force (USPSTF).  Screening of infants for hyperbilirubinemia to prevent chronic bilirubin encephalopathy. Agency for Healthcare Research and Quality, October 2009,


Medical Policy Group, August 2004 (4)

Medical Policy Administration Committee, September 2004

Available for comment September 7-October 21, 2004

Medical Policy Group, August 2006 (1)

Medical Policy Group, August 2008 (1)

Medical Policy Group, August 2010 (1) Key points updated

Medical Policy Group, September 2012 (3): Active Policy but no longer scheduled for regular literature reviews and updates.

Medical Policy Group, July 2019 (3): 2019 Updates to Key Points. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy.

Medical Policy Group, August 2021 (5): Updates to Key Points, and References. Policy statement updated to remove “not medically necessary,” no change to policy intent. Reviewed by consensus. There is no new published peer-reviewed literature available that would alter the coverage statement in this policy.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.


This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.


Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.