
Christensen RD, Malleske DT, Lambert DK, Baer VL, Prchal JT, Denson LE, Gerday E, Weaver Lewis KA, Shepherd JG. Measuring End-Tidal Carbon Monoxide of Jaundiced Neonates in the Birth Hospital to Identify Those with Hemolysis. Neonatology. 2016;109(1):1-5.

Non-invasive Detection of Hemolysis: Changing the Jaundice Management Paradigm
At the 2015 joint European Neonatology Society (jENS) Meeting in Budapest, Hungary, a distinguished faculty discussed jaundice management and the role of the CoSense® ETCO Monitor in the non-invasive detection of hemolysis.
CoSense End-Tidal Carbon Monoxide Monitor
- Identification of neonatal haemolysis: An approach to predischarge management of neonatal hyperbilirubinemia
Bhutani VK, et al. Acta Paediatr. 2016 May; 105(5):e189-94.DESIGN Prospective POPULATION & SAMPLE SIZE Newborns, ≥ 35 weeks gestational age (GA), n=79 OBJECTIVE Report predischarge ETCOc ranges to guide clinical management of hyperbilirubimia KEY FINDINGS Elevated ETCOc level (>1.5ppm) and/or excessive rate of TB rise (0.2mg/dL/h) may identify infants most at risk
Confirms previous reports that pre-discharge measurements of TB together with ETCO can be used as an index of increased bilirubin loads due to hemolysisARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/26802319 - End-Tidal Carbon Monoxide as an Indicator of the Hemolytic Rate
Christensen RD, et al. Mol Dis. 2015;54(3):292-6.DESIGN Prospective; Prospective Controlled POPULATION & SAMPLE SIZE Newborns, ≥ 37 weeks gestational age (GA), n=30; Neonates & children with hemolytic disorders, n=40 OBJECTIVE Assess the feasibility of ETCO measurements and determine if there is a significant difference in ETCO values between hemolyzers and non-hemolyzers KEY FINDINGS ETCO1 values of the subjects with known hemolysis were higher than the age-matched healthy controls (p<0.0001)
Neonates with hemolytic conditions can be recognized using CoSense and be targeted for rigorous follow-up/treatmentARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/26802319 - Evaluation of a New End-Tidal Carbon Monoxide Monitor From the Bench to the Bedside
Castillo Cuadrado ME, Bhutani VK, Aby JL, Vreman HJ, Wong RJ, Stevenson DK. Acta Paediatr. 2015 Jun;104(6):e279-82.DESIGN Bench Testing / Prospective Clinical Study POPULATION & SAMPLE SIZE Newborns, ≥ 30 weeks gestational age (GA), n=83 OBJECTIVE Evaluate the accuracy of CoSense versus blood carboxyhemoglobin (COHb), the “gold standard” for detecting hemolysis KEY FINDINGS Strong linear correction (r=.93) between ETCO and COHb
CoSense can identify the presence of hemolysis in infants
CoSense is accurate, precise, and can be used as a reliable measurement of bilirubin productionARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/25640053 - Point-of-Care End-Tidal Carbon Monoxide Reflects Severity of Hemolysis in Sickle Cell Anemia
Lal A, Patterson L, Goldrich A, Marsh A. Pediatr Blood Cancer. 2015 May;62(5):912-4.DESIGN Prospective Controlled POPULATION & SAMPLE SIZE Children (5-14) with and without SCA, n=33 OBJECTIVE Evaluate the ability of CoSense to detect hemolysis in patients with a known hemolytic condition KEY FINDINGS ETCO values 5-fold higher in SCA subjects than controls
ETCO values correlated with reticulocytes and bilirubinARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/25683629 - Exhaled End-Tidal Carbon Monoxide Testing for Hemolysis in Neonates with Significant Hyperbilirubinemia and Positive Direct Anti-Globulin Test
Du L, Zou P, Chen L, Bhutani V. Poster presentation at Pediatrics Academic Societies Meeting, May 6, 2014.DESIGN Prospective POPULATION & SAMPLE SIZE Neonates with significant HB (SHB), n=56 OBJECTIVE Test CoSense‘s ability to detect hemolysis in neonates with SHB. KEY FINDINGS CoSense provided similar information as invasive blood tests (DAT, retic count, hematocrit and bilirubin), confirming feasibility of detecting hemolysis using a simple breath test
End-Tidal Carbon Monoxide
- Bilirubin Production and Hour-Specific Bilirubin Levels
Bhutani VK, et al. J Perinatol. 2015:1-4. E-pub ahead of print.DESIGN Post Hoc Analysis POPULATION & SAMPLE SIZE Newborns ≥ 35 weeks GA, n=793 OBJECTIVE Characterize the roles of increased bilirubin production and impaired bilirubin elimination to the development of HB. KEY FINDINGS Increased bilirubin production in ~80%, 42%, and 32% infants in high-, intermediate-, and low-risk TB zones, respectively
Pre-discharge assessment of risk with ETCOARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/25880796 - State-of-the-Art: End-Tidal Carbon Monoxide and Hemolysis
Tidmarsh GF, et al. J Perinatol. 2014;34:577-581.DESIGN Systematic Review POPULATION & SAMPLE SIZE N/A OBJECTIVE Describe ETCO & its application in identifying infants at risk for developing hyperbilirubinemia (HB) associated with hemolysis KEY FINDINGS Elevated levels of ETCO have been correlated with hemolysis in newborns suggesting that accurate, rapid analysis of ETCO may provide a useful tool for identifying newborns with HB requiring greater attention ARTICLE LINK http://www.nature.com/jp/journal/v34/n8/full/jp201466a.html - Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation
Subcommittee on Hyperbilirubinemia. Pediatrics. 2004;114(1):297-316.DESIGN Guideline POPULATION & SAMPLE SIZE N/A OBJECTIVE Provide guidance on how to manage HB in newborns ≥ 35 weeks of gestation KEY FINDINGS Standard lab tests for hemolysis are frequently unhelpful
ETCO confirms the presence or absence of hemolysis and is the only clinical test that provides a direct measurement of bilirubin productionARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/15231951
Hemolysis & Risk
- Interaction of Hemolysis and Hyperbilirubinemia on Neurodevelopmental Outcomes in the Collaborative Perinatal Project (CPP)
Kuzniewicz M, Newman TB. Pediatrics. 2009;123(3):1045-1050.DESIGN Retrospective POPULATION & SAMPLE SIZE Newborns ≥ 36 weeks GA, n=54,795 OBJECTIVE Reanalyze data from the CPP to investigate whether bilirubin is more neurotoxic in newborns with a positive DAT (used as a surrogate for hemolysis) KEY FINDINGS There is an association between TSB levels ≥ 25 mg/dL, a positive DAT, and lower IQ scores
Supports AAP recommendation to treat at a lower level of jaundice with a positive DAT
Reinforces findings of Newman et al. NEJM. 2006;354(18).ARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/19255038 - Early End-Tidal Carbon Monoxide Levels and Neurodevelopmental Outcome at 3 Years 6 Months of Age in Preterm Infants
Blok CA, et al. Dev Med Child Neurol. 2011;53(12):1113-1118.DESIGN Prospective Observational POPULATION & SAMPLE SIZE Preterm infants ≤ 32 weeks GA, n=105 OBJECTIVE Evaluate the predictive value of ETCO and cytokine levels for long-term outcome KEY FINDINGS ETCO <2.0 ppm in the first 24 hours of life is high predictive of a favorable neurodevelopmental outcome at 3.5 years
Majority of children with an ETCO >2.0 ppm in the first 24 hours of life had adverse neurodevelopmental outcomesARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/21933176 - Neonatal Hemolysis and Risk of Bilirubin-Induced Neurologic Dysfunction
Wong RJ, Stevenson DK. Semin Fetal Neonat M. 2015;20(1):26-30.DESIGN Systematic Review POPULATION & SAMPLE SIZE N/A OBJECTIVE Describe the causes of neonatal hemolysis and the risk of BIND associated with neonates with hemolytic disease KEY FINDINGS Severe HB in newborns can be caused by hemolysis, which results from a number of different conditions
Infants with hemolytic disease are at greater risk of developing bilirubin-induced neurotoxicity and BINDARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/25560401 - Causes of Hemolysis in Neonates with Extreme Hyperbilirubinemia
Christensen RD, et al. J Perinatol. 2014;34(8):616-619.DESIGN Retrospective POPULATION & SAMPLE SIZE Neonates with bilirubin ≥ 25 mg/dL, n=12 OBJECTIVE Evaluate a quality improvement process to diagnose hemolytic conditions in neonates with HB. KEY FINDINGS Many of the cases of extreme HB have an underlying basis involving hemolysis
Inherited conditions such as hereditary spherocytosis and G6PD deficiency can be missed in neonatesARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/24762414 - The Contribution of Hemolysis to Early Jaundice in Normal Newborns
Maisels MJ, Kring E. Pediatrics. 2006;118(1):276-279.DESIGN Prospective Controlled POPULATION & SAMPLE SIZE Newborns, n=272 OBJECTIVE Clarify the contribution of an increase in bilirubin production in HB in newborns KEY FINDINGS Hemolysis is an important mechanism responsible for HB in the first 4 days of life ARTICLE LINK http://www.ncbi.nlm.nih.gov/pubmed/16818575