End-tidal Carbon Monoxide Levels Research Articles

Neonatal hyperbilirubinemia management: Clinical assessment of bilirubin production

The predominant cause of elevated total/plasma bilirubin (TB) levels is from an increase in bilirubin production primarily because of ongoing hemolysis. If undiagnosed or untreated, the risk for developing extreme neonatal hyperbilirubinemia and possibly bilirubin-induced neurological dysfunction (BIND) is increased. Since carbon monoxide (CO) and bilirubin are produced in equimolar amounts during the heme catabolic process, measurements of end-tidal CO levels, corrected for ambient CO (ETCOc) can be used as a direct indicator of ongoing hemolysis. A newly developed point-of-care ETCOc device has been shown to be a useful for identifying hemolysis-associated hyperbilirubinemia in newborns. This review summarizes the biology of bilirubin production, the clinical utility of a novel device to identify neonates undergoing hemolysis, and a brief introduction on the use of ETCOc measurements in a cohort of neonates in China.

Comparison of End Tidal Carbon Monoxide Levels between Conventional Cigarette, Electronic Cigarette and Heated Tobacco Product among Asiatic Smokers

Background Electronic nicotine delivery systems (ENDS) and heated tobacco products (HTPs) are noncombustible tobacco products which have been found to generate aerosols containing lower levels of Harmful and Potentially Harmful Constituents (HPHCs) in comparison to conventional cigarettes. Objective: This quasi experimental study measured and compared the end tidal carbon monoxide (eCO) levels of participants after use of ENDS, HTPs and conventional cigarettes. Methods: In total 45 smokers, each smoking at least 10 conventional cigarettes per day for 5 years participated in the study. Based on their preference, participants used only one of the tobacco products (ENDS, HTPs, or conventional cigarette) and were briefed about the product use based on manufacturer’s instructions. The eCO levels were obtained at baseline, followed by 5, 10, 15, 30 and 45 min respectively after the product use. Results: There was significant increase in eCO levels for conventional cigarettes as compared to other modes. Peak eCO levels of 20.2 ± 0.86 ppm, 8.8 ± 1.56 ppm and 6.0 ± 1.36 ppm was achieved at 30 min, 15 min and 10 min for conventional cigarettes, ENDS and HTPs respectively. However, the levels were significantly lower in ENDS and HTPs. Conclusion: Even though ENDS and HTPs may have produced significantly lower eCO than conventional cigarettes, the significantly increasing levels over time from baseline which was not shown before is a cause of concern. As of now, their use as an alternate to cigarettes needs to be considered under regulatory framework.

Early End-Tidal Carbon Monoxide Levels, Patency of the Ductus Arteriosus and Regional Cerebral Oxygenation in Preterm Infants

Background: Carbon monoxide (CO), a relaxant regulator of muscle tone and marker of oxidative stress and inflammation, can be measured in exhaled air by determination of end-tidal CO corrected for CO in ambient air (ETCOc). Objective: Increased endogenous production of CO may influence patency of the ductus arteriosus, cerebral perfusion and, subsequently, cerebral oxygenation. The aim was to study the relation between early ETCOc levels, hemodynamically significant patent ductus arteriosus (hsPDA) and cerebral oxygenation (rScO₂) in preterm infants <32 weeks' gestational age and determine predictive values of ETCOc for hsPDA. Methods: ETCOc was measured in 91 infants within the first 24 h after birth. A hsPDA was diagnosed according to echocardiographic indices. In 78/91 infants, rScO₂ was monitored with near-infrared spectroscopy to assess cerebral oxygenation. Results: ETCOc values were significantly higher in infants who subsequently developed hsPDA (2.3 ± 0.7 ppm) vs. no-hsPDA (1.7 ± 0.6 ppm), p < 0.001. With a cut-off value of 2.5 ppm, positive and negative predictive values of ETCOc for hsPDA were 55 and 88%, respectively. rScO₂ values were not different between the two groups (64 ± 1 vs. 65 ± 3%, NS). Conclusions: The higher ETCOc values in hsPDA infants early after birth reflect the early relaxant state of ductal muscular tone. ETCOc <2.5 ppm within 24 h after birth may predict the subsequent absence of hsPDA. ETCOc showed no correlation with cerebral oxygenation in both groups.

Early end-tidal carbon monoxide levels and neurodevelopmental outcome at 3 years 6 months of age in preterm infants

Increased end-tidal carbon monoxide (ETCOc) and cytokines in preterm infants are related to bronchopulmonary dysplasia and intraventricular haemorrhages. The aim was to study the predictive value of ETCOc and cytokine levels for long-term outcome. This study comprised 105 very preterm infants (57 males, 48 females; gestational age range 25 wks 5d-31 wks 4d; birthweight 610-2100 g) who were admitted to a neonatal intensive care unit between 1 February and 31 December 2002. ETCOc, plasma tumour necrosis factor alpha (TNF-α) and interleukins (IL) 6 and 8, and malondialdehyde (MDA, a marker of lipid peroxidation), were measured at days 1, 3, and 5 of life and related to outcome at 3 years 6 months of age (Griffiths Mental Developmental Scales). Of the 105 infants, 69 were eligible for follow-up (37 males; 32 females; bronchopulmonary dysplasia, n = 12). ETCOc at 0 to 24 hours was higher in infants with adverse outcome (Griffiths developmental quotient <85, n = 15) compared with favourable outcome (2.7SD 0.7 vs 2.0SD 0.5; p < 0.05). MDA and cytokines did not differ between groups. Regression analysis with bootstrapping of independent variables (gestational age, birthweight, ETCOc, TNF-α, IL-6, IL-8, and bronchopulmonary dysplasia) showed that ETCOc was the only parameter that correlated with outcome. The sensitivity and negative predictive value of ETCOc for adverse outcome were 93% and 85% respectively. Adverse neurodevelopmental outcome is associated with increased endogenous carbon monoxide. ETCOc less than 2.0 ppm during the first day indicates a favourable outcome.

Prediction of bronchopulmonary dysplasia

ObjectiveTo determine whether elevation of a biological marker of inflammation would be a better predictor of bronchopulmonary dysplasia (BPD) development than lung function measurement results.DesignProspective study.SettingTertiary neonatal intensive care unit.Patients78...

Cardiopulmonary Bypass Increases Endogenous Carbon Monoxide Production

Endogenous carbon monoxide (CO) production results from heme metabolism catalyzed by heme oxygenase (HO) enzymes of which HO-1 is inducible by oxidative stress. Cardiopulmonary bypass provokes oxidative stress associated with systemic and pulmonary inflammatory responses. Therefore, the authors hypothesized that cardiopulmonary bypass is associated with an increase in endogenous carbon monoxide production. A prospective, observational study. A cardiothoracic operating room. Forty patients undergoing cardiac surgery with cardiopulmonary bypass. None. End-tidal CO levels and arterial carboxyhemoglobin concentrations were measured before and after cardiopulmonary bypass. End-tidal CO concentrations and carboxyhemoglobin levels were increased significantly after cardiopulmonary bypass as compared with prebypass values (median [interquartile range]: end-tidal CO levels: 33 [20-42] ppm v 22 [16-32] ppm, p < 0.01; carboxyhemoglobin 1.3% [1.0%-1.3%] v 0.9% [0.6%-1.0%], p < 0.01). To exclude that the observed increases were caused by CO accumulation during CPB, the authors also assessed carboxyhemoglobin concentrations in the arterial and venous limb of the oxygenator, indicating that CO is eliminated across the membrane oxygenator during CPB. Cardiac surgery with cardiopulmonary bypass is associated with an increase in endogenous CO production.

End-tidal Carbon Monoxide Levels in Prematurely Born Infants Developing Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is associated with an early inflammatory response that persists after the first week of life. Inflammatory mediators can induce hemoxygenase-1 with a consequent increase in carbon monoxide (CO) production. End-tidal CO (ETCO) levels would be elevated in infants developing BPD. Serial measurements of ETCO levels were attempted on d 3, 5, 7, 14, 21, and 28 in 50 prematurely born infants (median gestational age 29 wk). Fourteen infants developed BPD [oxygen dependent beyond 36 wk post-menstrual age (PMA)] and had higher ETCO levels compared with the rest of the cohort on d 7, 14, 21, and 28. On d 14, the mean (SD) ETCO levels of the BPD group were 3.19 (1.11) ppm and 1.43 (0.61) ppm in the non-BPD group (p<0.001). An ETCO level on d 14>2.15 ppm had a sensitivity of 80% and specificity of 92% in predicting oxygen dependency at 36 wk PMA. Measurement of ETCO levels in prematurely born infants may be useful in the prediction of BPD.

The Contribution of Hemolysis to Early Jaundice in Normal Newborns

Neonatal jaundice is the result of an imbalance between bilirubin production and elimination, and our objective was to clarify the contribution of an increase in bilirubin production to hyperbilirubinemia in newborns. We measured the end-tidal carbon monoxide concentration corrected for ambient carbon monoxide concentration in 108 jaundiced newborns (total serum bilirubin level >75th percentile) and 164 control newborns in our well-infant nursery, for the first 4 days after birth. Mean end-tidal carbon monoxide levels decreased in the control infants in the first 4 days but increased in the hyperbilirubinemic group. The differences between the jaundiced and nonjaundiced infants were statistically significant on all days. Before hospital discharge, most infants with bilirubin levels >75th percentile are producing significantly more bilirubin than those with lower bilirubin levels. Because the ability of newborns to conjugate bilirubin is significantly impaired in the first few days, even a small increase in the rate of production can contribute to the development of hyperbilirubinemia. These data suggest that increased heme catabolism is an important mechanism responsible for hyperbilirubinemia in the first 4 days after birth.

Computed tomography and pulmonary function abnormalities in sickle cell disease

The aim of this study was to determine whether patients with sickle cell disease (SCD) in steady state had pulmonary abnormalities seen on high-resolution computed tomography (HRCT) and whether any abnormalities correlated with contemporaneously diagnosed lung function abnormalities. A subsidiary question was whether the results of a noninvasive measure of haemolysis (end-tidal carbon monoxide (ETCO) levels) correlated with pulmonary function abnormalities. Thirty three patients with SCD, median (range) age 36 yrs (17-67 yrs) were examined. The degree of lobar volume loss and ground-glass opacification and prominence of central vessels on HRCT were quantitatively assessed. Pulmonary function was assessed by measurements of lung volumes, spirometry, gas transfer and oxygen saturation. ETCO levels were measured using an end-tidal CO monitor. Forced expiratory volume in one second (FEV1), forced vital capacity and total lung capacity significantly correlated with HRCT findings, particularly lobar volume loss. ETCO levels significantly negatively correlated with FEV1, vital capacity measured using a plethysmograph, specific airway conductance and arterial oxygen saturation measured by pulse oxymetry. In conclusion, the present results suggest that high-resolution computed tomography noninvasive assessment of haemolysis might be useful to identify sickle cell disease patients with respiratory function impairment.

Effects of Inspiratory Oxygen Concentration on Endtidal Carbon Monoxide Concentration

Carbon monoxide (CO) is eliminated mainly via the lungs so that exhaled carbon monoxide concentration reflects endogenous production. In this context, we studied the effects of inspiratory oxygen concentration and endotracheal intubation on endtidal CO concentrations. In patients undergoing general anaesthesia, endtidal CO concentrations were measured while breathing room air, oxygen as well as after induction of general anaesthesia and endotracheal intubation. To exclude time-dependent effects, patients were assigned to two groups. Patients in group 1 (n = 20) were preoxygenated for 5 minutes, whereas patients in group 2 (n = 20) were preoxygenated for 10 minutes. We also studied the effects of different inspiratory oxygen concentrations in volunteers (n = 20) breathing room air, 50% and 100% oxygen. Breathing oxygen for 5 minutes increased endtidal carbon monoxide concentrations in all patients (in group 1 from 7.6+/-4.9 to 12.6+/- 5.0 ppm, p < 0.001; in group 2 from 7.1+/-6.1 to 16.4 +/- 8.6 ppm, p < 0.001). No further change of CO concentration was detected after 10 minutes of preoxygenation (16.4 +/- 9.0 vs. 16.4 +/- 8.6 ppm, p > 0.05). Endtidal CO values however significantly increased with induction of anaesthesia and endotracheal intubation (in group 1 to 21.5 +/- 6.3 ppm, p < 0.001, in group 2 to 26.1 +/- 13.1 ppm, p < 0.001). In volunteers, mean endtidal CO values increased from 10.7 +/-5.9 to 14.8+/-7.3 ppm after breathing 50% oxygen for 3 minutes (p < 0.001). Breathing pure oxygen had no additional effect on endtidal CO values (16.0 +/- 6.0 ppm, p > 0.05). Endtidal carbon monoxide levels are influenced by inspiratory oxygen concentrations. Induction of anaesthesia and endotracheal intubation further increases endtidal CO concentrations beyond the effects attributable to preoxygenation alone.

Lung Function and High Resolution Computed Tomography in Sickle Cell Disease.

Adults with sickle cell disease (SCD) may develop sickle chronic lung disease which appears to be a complication of chronic hemolysis and repeated episodes of pulmonary vaso-occlusion. Pulmonary function tests have usually been used to document the severity of lung disease in SCD, but some patients cannot successfully undertake such examinations. Recently, high resolution computed tomography (HRCT) has been shown to be of value in the evaluation of patients with diffuse lung diseases. Assessment of lung disease in SCD by HRCT, however, has not been fully explored. The study sets out to investigate the relationship of any pulmonary function abnormalities in adults with SCD to a non-invasive measure of hemolysis and findings on HRCT. The study population consisted of 33 Hb SS subjects (12 males) with a median age of 36 (range 17–67) years, median height of 167 (range 53–188) cm, and median weight of 69 (range 52–92) kg.Pulmonary function was assessed by measurements of lung volumes, spirometry, gas transfer and oxygen saturation, and hemolysis by measurement of end-tidal carbon monoxide (ETCO). The degree of a lobar volume loss and ground glass opacification and prominence of central vessels on HRCT were quantitatively assessed.There was a wide variation in the lung function of the cohort. Nine patients had a restrictive lung function abnormality, five an obstructive abnormality and four a mixed restrictive/obstructive abnormality. Twenty-seven of the patients completed assessment of ETCO levels. ETCO levels correlated positively with bilirubin levels (rs=0.66, p=0.0002) and the absolute reticulocyte count (rs=0.70, p=0.0002), and negatively with hemoglobin (rs=−0.51, p=0.008). ETCO levels negatively correlated with FEV1 (p=0.006), VCpleth (p=0.006), sGaw (p=0.04) and SpO2 (p=0.007). A reticular pattern, lobar volume loss and prominent central vessels were the three most common abnormalities on HRCT. FEV1 (p<0.05), FVC (p<0.005) and TLC (p=0.008) correlated with HRCT findings, particularly lobar volume loss. Lobar volume loss, prominent central vessels and a reticular pattern/ground glass opacification were all present on HRCT in 12 of 18 subjects with a restrictive, obstructive or mixed defect.Our results suggest that non-invasive assessment of hemolysis and/or HRCT examination might facilitate identification of SCD patients with respiratory function impairment. More of the patients had abnormalities on HRCT than on lung function testing, which suggests that HRCT is a more sensitive detector of respiratory abnormalities than lung function testing. This hypothesis merits testing by serially assessing SCD patients to determine if those with only HRCT abnormalities subsequently develop lung function abnormalities.

Exhaled carbon monoxide levels in children with sickle cell disease

It is important to measure the rate of haemolysis in patients with sickle cell disease (SCD) to identify aplastic crises and indirectly assess the rate of vaso-occlusion and sequestration. The aim of this study was to assess whether end-tidal carbon monoxide (ETCOc) levels in children with sickle cell disease (SCD) could be measured reproducibly, reflected haemolysis and whether they were elevated compared to those of similarly aged, ethnic matched children without SCD (controls). ETCOc levels were measured non-invasively in 87 SCD children (age range 2.3-17.6 years) and 26 age and ethnic origin matched healthy controls using an electro-chemical sensor. The within- and between- occasion reproducibilities were assessed in ten and 15 SCD children respectively. ETCOc levels of 15 SCD children undergoing regular transfusions were related to carboxyhaemoglobin, haemoglobin and bilirubin levels. The within and between occasions' mean intrasubject coefficients of reproducibility were 5% and 18% respectively. Positive correlations were found between the ETCOc and carboxyhaemoglobin ( P =0.007) and bilirubin ( P =0.02) levels, and a significant negative correlation between the ETCOc and haemoglobin ( P =0.0002) levels. The mean and SD ETCOc levels of the SCD children (4.9 ppm; SD 1.7 ppm) were significantly higher than that of the controls (mean 1.3 ppm; SD 0.4 ppm) (difference between means 3.60; 95% C.I. 2.93-4.28; P <0.0001). These results suggest that measurement of end-tidal carbon monoxide levels is a reliable and useful method to monitor haemolysis in children with sickle cell disease.

End tidal carbon monoxide levels are lower in women with gestational hypertension and pre-eclampsia.

The possible role of heme oxygenase and its byproduct carbon monoxide (CO) in the regulation of blood pressure is under investigation. The aim of this study was to compare end tidal breath CO (ETCO) levels in women with gestational hypertension (GH) or pre-eclampsia to the levels in healthy pregnant and nonpregnant women. We prospectively performed ETCO measurements corrected for ambient CO (ETCOc) in two medical centers (Stanford, CA and Cleveland, OH). A Natus CO-Stat End Tidal Breath Analyzer (Natus Medical Inc., San Carlos, CA) was used. The study group included a convenience sample of 31 women with GH/pre-eclampsia (PE). Control groups included 46 nonpregnant healthy women, 44 first-trimester and 48 third-trimester pregnant healthy women. Mean+/-SD ETCOc measurements were significantly lower in the GH/PE group compared to first-trimester (p=0.004) and third-trimester (p=0.001) normotensive pregnant and nonpregnant women (p=0.002) (1.36+/-0.30 vs 1.76+/-0.47, 1.72+/-0.42 and 1.78+/-0.54 ppm, respectively). The ETCOc values were < or =1.6 ppm in 89% of GH/PE women compared with, respectively, only 45, 54, and 46% of nonpregnant, first- and third-trimester normotensive pregnant women (p<0.05). ETCO measurements were not influenced by maternal age, parity, ethnicity, body mass index, gestational age or presence of household smokers. In the two centers, the controls had a similar mean ETCOc and the differences found remained significant when results for each center were analyzed separately. ETCOc levels were found to be significantly lower in women with GH/PE. Further investigation is required to determine if the lower CO levels reflect a deficient compensatory response to the increase in blood pressure or whether these are primary changes of significance to our understanding of the pathogenesis of GH/PE.

Evaluation of the Direct Antiglobulin (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

First, to determine the sensitivity, specificity, and positive predictive value (PPV) of the direct antiglobulin test (DAT) for significant hemolysis in the neonate, as referenced to end-tidal carbon monoxide, the criterion standard for estimating the rate of hemolysis; and second, to evaluate the predictive value of the two procedures for significant jaundice. Consecutive term newborns admitted to the nursery of an inner-city university hospital over a 15-week period. DAT screening by the Blood Bank was performed on all. End-tidal carbon monoxide levels were obtained at 12+/-6 and at 24+/-6 hours of age. Infants of nonsmoking mothers whose 12-hour exhaled carbon monoxide level was > or = 95th percentile were defined as having significant hemolysis. n=660; DAT was positive in 23 (3.5%). Using the 12-hour end-tidal carbon monoxide > or = 3.2 microl/l (> or = 95th percentile) as reference (n=499 nonsmokers), the sensitivity of the DAT was 38.5% (10 of 26) and specificity 98.5% (466 of 473) for the detection of significant hemolysis. The PPV of the DAT for significant hemolysis at 12 hours was 58.8% (10 of 17). For significant jaundice the PPV of end-tidal carbon monoxide was greater than that for DAT (65.4% vs 52.9%), although not statistically so (p=0.25). The negative predictive values were similar. DAT fails to identify over half of the cases of significant hemolysis that are diagnosed by end-tidal carbon monoxide. A neonate with a positive DAT has about a 59% chance of having significant hemolysis. End-tidal carbon monoxide may also provide a more sensitive index for predicting significant jaundice.

Serum bilirubin levels at 72 hours by selected characteristics in breastfed and formula‐fed term infants delivered by cesarean section

The present multicenter study analysed the relative impact of maternal and infant factors on serum bilirubin levels at 72 +/- 12 h in exclusively breastfed vs formula-fed term infants. End-tidal carbon monoxide levels corrected for ambient air (ETCOc), an index of bilirubin production, were measured in exclusively breastfed (B = 66) or formula-fed (F = 210) term infants at 2-8 h of age. Inclusion criteria included cesarean section to ensure a 3 d hospitalization, birthweight > or = 2,500 g, gestational age >37 wk and absence of any illness. The ETCOc for B infants and F infants did not differ significantly (1.3 +/- 0.7 ppm vs 1.3 +/- 0.8 ppm). The serum bilirubin level at 72 +/- 12 h was significantly higher in B infants than in F infants (8.5 +/- 3.4mg dl(-1) vs 6.7 +/- 3.4mg dl(-1) p < 0.001), as was the percentage weight loss from birthweight. Serum bilirubin levels were significantly higher in infants who were male, who did not have meconium-stained amniotic fluid, and in those whose mothers were insulin-dependent diabetics or hypertensive. There was no difference between groups in the need for phototherapy or exchange transfusion. Although higher bilirubin levels were observed in group B at 72 +/- 12 h compared with group F, this finding was not of clinical or therapeutic consequence in this study. The lack of difference in ETCOc between the groups may be a factor of the timing of ETCOc measurement in this study, or may suggest that early increased bilirubin production is not a significant contributor to jaundice observed in exclusively breastfed infants. Key words: bilirubin, breastfeeding, jaundice