Effect of ventilation on breath hydrogen measurements

Measurement of hydrogen (H2) in expired air by interval sampling after oral administration of carbohydrate detects sugar malabsorption. Standard breath H2 tests require comparison of H2 concentrations in expired air samples obtained immediately before and after delivery of a test substrate. Comparison of interval samples assumes that minute ventilation (VE) remains constant unless H2 is independent of VE. Because healthy individuals have variable VE, we determined how H2 is influenced by changes in VE. H2 concentration was studied at different ventilatory rates in eight healthy adults. It varied inversely with VE in all subjects. We also compared the effect of changes in VE on the relationship between H2 and carbon dioxide (CO2) concentrations in expired air samples. At constant VE, the relationship between H2 and CO2 was linear (r = 0.95, P less than 0.001). As VE changed, the relationship between H2 and CO2 became nonlinear. Changes in VE altered methane concentrations in expired air samples from two subjects in a manner comparable to the effect on H2. These results demonstrate that breath H2 concentrations vary with ventilatory rate. Under conditions where frequent changes in VE are likely, independent measures for ensuring constant VE over sampling times are necessary. Use of CO2 as an internal standard to normalize H2 values to an alveolar concentration is appropriate only under conditions of constant VE.     

Estimation of IgM in cerebrospinal fluid by enzyme immunoassay

We have compared a nasopharyngeal catheter method for breath sampling and a valved collection device. Sample quality was assessed by simultaneous oxygen measurement and reproducibility was checked by the analysis of 50 pairs of samples from four premature neonates.Both collection methods produced samples of highly variable quality suggesting a variable mixture of alveolar and non-alveolar air as well as differences in expired oxygen levels between babies. The mean oxygen levels were similar for both sampling techniques. Linear regression analysis of paired hydrogen results showed a highly significant correlation coefficient r = 0.73. This was improved markedly to r = 0.94 by normalization of hydrogen values based on observed oxygen levels, and so supports the earlier article by Robb and Davidson [1].All breath hydrogen analyses require a measure of sample quality. Reproducible results and meaningful changes in hydrogen concentration in breath samples can only be achieved by correction according to sample quality. Correction to a common oxygen value should allow quantitative comparisons between patients. Samples were best collected from neonates by the nasopharyngeal catheter method, which least disturbed the patient, allowed multiple sample collection and gave lower oxygen and higher hydrogen values where large differences between pairs occurred.     

Monitoring pulmonary function with superimposed pulmonary gas exchange curves from standard analyzers

Objective.A repetitive graphic display of the single breath pulmonary function can indicate changes in cardiac and pulmonary physiology brought on by clinical events. Parallel advances in computer technology and monitoring make real-time, single breath pulmonary function clinically practicable. We describe a system built from a commercially available airway gas monitor and off the shelf computer and data-acquisition hardware. Methods.Analog data for gas flow rate, O₂, and CO₂ concentrations are introduced into a computer through an analog-to-digital conversion board. Oxygen uptake (VO₂) and carbon dioxide output (VCO₂) are calculated for each breath. Inspired minus expired concentrations for O₂ and CO₂ are displayed simultaneously with the expired gas flow rate curve for each breath. Dead-space and alveolar ventilation are calculated for each breath and readily appreciated from the display. Results.Graphs illustrating the function of the system are presented for the following clinical scenarios; upper airway obstruction, bronchospasm, bronchopleural fistula, pulmonary perfusion changes and inadequate oxygen delivery. Conclusions.This paper describes a real-time, single breath pulmonary monitoring system that displays three parameters graphed against time: expired flow rate, oxygen uptake and carbon dioxide production. This system allows for early and rapid recognition of treatable conditions that may lead to adverse events without any additional patient measurements or invasive procedures. Monitoring systems similar to the one described in this paper may lead to a higher level of patient safety without any additional patient risk.     

Hydrogen breath test in the diagnosis of lactose malabsorption: accuracy of new versus conventional criteria

Increased hydrogen excretion in the breath after carbohydrate ingestion, an expression of carbohydrate malabsorption, represents the pathophysiologic basis of the hydrogen breath test, a simple, noninvasive, reproducible test for the diagnosis of this condition. Few data are available concerning the breath hydrogen response that most accurately identifies carbohydrate malabsorption. In this article we report our application for the first time in clinical practice of 2 recently described, more accurate criteria for the diagnosis of lactose malabsorption (ie, breath hydrogen excretion value > 6 parts per million (ppm) 6 hours after carbohydrate load and a sum greater than 15 ppm for the breath hydrogen values obtained 5, 6, and 7 hours after carbohydrate load). On 3 separate days, we subjected 84 consecutive patients with functional or organic gastrointestinal disease to measurement of hydrogen excretion in the breath after the administration of lactose to test for lactose malabsorption; after the administration of lactulose as a means of ruling out false-negative results resulting from hydrogen-nonproducer status; and after the administration of a nonabsorbable electrolyte solution as a means of ruling out false-positive results caused by the mixing of intestinal content and release of preformed hydrogen trapped in the feces. According to the conventional criterion, 51% of the subjects proved to be lactose malabsorbers. Positive results were obtained with the use of the 6th-hour criterion in 76% of patients, and positive results were found in 80% when the sum of the excretion at hours 5, 6, and 7 was used as the criterion (P < .05 for both comparisons). Ten of 21 and 11 of 25, respectively, showed intolerance symptoms. It was therefore possible for us to diagnose lactose malabsorption in 24% and 27% of patients, respectively, who tested negative according to the conventional criterion. The conventional criterion must be abandoned and these new criteria adopted.     

Measurement of carbon monoxide in simulated expired breath

BACKGROUND: Environmental carbon dioxide (CO) detectors used as an early warning method have been adapted to measure CO concentration in expired breath. This technique has been validated in smokers with relatively low CO concentrations, but its applicability to poisoning has not been demonstrated. OBJECTIVE: To compare the reliability of toxicologically significant CO measurements performed using a portable CO detector with those obtained using infrared spectrometry, the standard method for blood CO concentration determination. DESIGN: Experimental study with a CO detector and infrared spectrometer. A balloon simulated respiratory movements and an expired breath. Balloon gas mixtures contained CO, in one of 21 different concentrations from 100 to 600 parts per million (ppm) in air. CO concentration was measured directly with the portable CO detector and two gas samples obtained at the beginning and end of the simulated expired breath were diluted, with validation, for spectrometric measures. MAIN OUTCOME MEASURES: Portable CO detector concentrations were compared with the mean value of the reference method. Simple linear regression was performed using ANOVA to evaluate the parallel between the model with the reference method. RESULTS: Portable CO detector concentration measurements were perfectly linear (R2=0.989, P<10(-3)) over a concentration range of 46-645 ppm. The difference from the reference plot was significant (P<0.01). CONCLUSION: Given the linearity of the measurements, the underestimation by the portable CO detector at higher concentrations can be corrected mathematically. A portable CO detector should measure CO in expired breath efficiently and reliably.     

Methodological aspects of breath hydrogen (H2) analysis. Evaluation of a H2 monitor and interpretation of the breath H2 test

The reliability of end-expiratory hydrogen (H2) breath tests were assessed and the significance of some important pitfalls were studied, using a compact, rapid H2-monitor with electrochemical cells. The H2 response was shown to be linear and stable. The reproducibility of the breath collection technique was determined in 20 patients following ingestion of lactulose. The increment between consecutive means of duplicate samples indicative of a significant rise of H2 concentration never exceeded 10 p.p.m., the mean coefficient of variation of the duplicate samples was below 5%. Fasting H2 levels were studied in 10 healthy adults during a 4-month period and they showed very marked inter- and intra-individual variability (16% above 40 p.p.m.). Initial peaks (early, short-lived H2 rises unrelated to carbohydrate malabsorption) were identified in 25% of the breath tests (in 4% above 20 p.p.m). It is concluded that the technique used for interval sampling of end-expiratory breath samples for H2 concentration gives reliable results. The biological significance of H2 concentration increments can only be evaluated if the limitations of the technical procedures and the individual ability to produce H2 is known.     

Limitations of the triolein breath test.

Patients being investigated for intestinal absorptive capacity were classified as normals or malabsorbers on the basis of three fat absorption tests. Malabsorbers were further classified as mild, moderate, severe or gross according to severity of malabsorption. Using this classification system the triolein breath test was evaluated in 53 patients. Seventeen patients were excluded because their graph of percentage breath [14C]carbon dioxide versus time was exponential indicating that the peak [14C]-carbon dioxide may be occurring later than the six hour duration of the test. The sensitivity and specificity of the triolein breath test were found to be 100% and 96%, respectively and moderate correlations with the individual fat absorption tests were found. However, the breath test was limited in its capacity to predict the severity of malabsorption. Carbon dioxide output was also measured in order to determine the applicability of using an assumed value. The respiratory quotient and variability of results were high in nineteen patients indicating possible hyperventilation. In 32 patients with reproducible results and normal respiratory quotients the average carbon dioxide output was 8.66 mmol/kg per hour with a wide range of 5-12.4 mmol/kg per hour. Consequently the use of an assumed carbon dioxide output can introduce considerable errors in the triolein breath test. This study highlights drawbacks of the triolein breath test, particularly problems in using an assumed carbon dioxide output for its calculation, its inability to predict the severity of malabsorption and the nature of the dietary load used.     

End-tidal carbon dioxide as a measure of arterial carbon dioxide during intermittent mandatory ventilation

To determine if end-tidal carbon dioxide tension (PetCO₂) is a clinically reliable indicator of arterial carbon dioxide tension (PaCO₂) under conditions of heterogeneous tidal volumes and ventilation-perfusion inequality, we examined the expiratory gases of 25 postcardiotomy patients being weaned from ventilator support with intermittent mandatory ventilation. Using a computerized system that automatically sampled airway flow, pressure, and expired carbon dioxide tension, we were able to distinguish spontaneous ventilatory efforts from mechanical ventilatory efforts. ThePetCO₂ values varied widely from breath to breath, and the arterial to end-tidal carbon dioxide tension gradient was appreciably altered during the course of several hours. About two-thirds of the time, thePetCO₂ of spontaneous breaths was greater than that of ventilator breaths during the same 70-second sample period. The most accurate indicator of PaCO₂ was the maximalPetCO₂ value in each sample period, the correlation coefficient being 0.768 (P < 0.001) and the arterial to end-tidal gradient being 4.24 ± 4.42 mm Hg (P < 0.01 compared with all other measures). When all values from an 8-minute period were averaged, stability was significantly improved without sacrificing accuracy. We conclude that monitoring the maximalPetCO₂, independent of breathing pattern, provides a clinically useful indicator of PaCO₂ in postcardiotomy patients receiving intermittent mandatory ventilation.     

Influence of sodium fluoride on the stability of human blood samples and blood gas measurements

OBJECTIVE: This study aimed to reduce the analytical error associated with measuring oxygen and carbon dioxide partial pressures as well as the pH in arterial blood samples an hour after sample collection. The standard blood sample preparation procedure involving sample cooling down to 0 degrees C is known to have several drawbacks. Therefore, another approach using NaF at room temperature as an inhibitor of metabolic reactions was introduced. DESIGN AND METHODS: Arterial heparin blood samples from six volunteers were distributed over 104 single capillaries prepared with different concentrations of NaF. The capillaries were filled simultaneously and under the same conditions with blood samples, and the blood gas parameters of each sample were measured. Changes in pO2, pCO2, and pH during storage were evaluated with the aid of t test statistics. RESULTS: During the storage period under investigation, fluctuations of the carbon dioxide partial pressure and the pH were low, whereas there was a significant (P < 0.01) decrease of the oxygen partial pressure. This was observed at all NaF concentrations. Depending on the addition of NaF, a significant baseline shift for the time-resolved pH and pCO2 values could be observed. Whereas the partial pressure of carbon dioxide and the pH could be kept stable by adding a defined amount of NaF, the partial pressure of oxygen decreased significantly over 70 min. CONCLUSIONS: The proposed new method can be practically applied to a comparative blood gas study, significantly reducing the blood sample volume required. The application of analytical grade NaF is an improvement compared to previous work because a pH decrease could not be observed.     

Computer application for respiratory data processing in closed circuit anesthesia

Summary A computerized respiratory monitor system for closed circuit anesthesia is described. The system consists of a mass spectrometer, a hot-wire respiratory flow meter, a microcomputer, a central display and a recorder. Respiratory parameters obtained by the computerized system include O₂ consumption, carbon dioxide production, expiratory minute volume and respiratory rate. Using this system, closed circuit anesthesia was used in eleven surgical patients. Breath by breath value of carbon dioxide production stayed within the normal range during the procedure, though that of oxygen consumption varied markedly. This system allows anesthesiologists to detect, breath by breath, optimal gas flow and metabolic requirement during the closed circuit anesthesia.Closed circuit anesthesia is being used with increasing frequency in recent years. The patient's condition must be monitored continuously during the closed circuit anesthesia to maintain optimal depth of anesthesia and to prevent hypoxia or hypercarbia; however, monitoring of the respiratory gas exchange is difficult. We have developed a computerized respiratory monitor system for the closed circuit anesthesia.     

Predicting sulfur solubility in hydrogen sulfide,carbon dioxide,and methane with an improved thermodynamic model

During development of high sulfur-content natural gas fields, gaseous sulfur is likely to precipitate and deposit in the reservoir and transmission pipelines owing to changes in the temperature, pressure, and gas components. It is important to accurately predict the elemental sulfur solubility in hydrogen sulfide, carbon dioxide, and methane because these are the three main components of high-sulfur-content natural gas. The binary interaction coefficients between sulfur and hydrogen sulfide, carbon dioxide, and methane are the key parameters for predicting the sulfur solubility with a thermodynamic model. In this work, we show that the binary interaction coefficients are not constant, but temperature dependent. Three-parameter temperature-dependent equations for the binary interaction coefficients between sulfur and solvents are proposed. The corresponding regression equations for calculating the binary interaction coefficients between sulfur and hydrogen sulfide, carbon dioxide, and methane are obtained using experimental sulfur solubility data. The average relative errors of the sulfur solubility predicted using the experimental data in hydrogen sulfide, carbon dioxide, and methane using the thermodynamic model with the improved binary interaction coefficients are 6.30%, 1.69%, and 4.34%, and the average absolute relative errors are 7.90%, 13.12%, and 14.98%, respectively. Comparing the improved binary interaction coefficients with four other sets of reported values shows that the solubility values predicted by the thermodynamic model with improved binary interaction coefficients fit the experimental data better.

The binary interaction coefficients between sulfur and H₂S, CO₂ or CH₄ are not constant, but temperature dependent. Three-parameter temperature-dependent equations for the binary interaction coefficients between sulfur and solvents are proposed.     

Breath biomarkers in diagnosis of pulmonary diseases

Breath analysis provides a convenient and simple alternative to traditional specimen testing in clinical laboratory diagnosis. As such, substantial research has been devoted to the analysis and identification of breath biomarkers. Development of new analytes enhances the desirability of breath analysis especially for patients who monitor daily biochemical parameters. Elucidating the physiologic significance of volatile substances in breath is essential for clinical use. This review describes the use of breath biomarkers in diagnosis of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), lung cancer, as well as other pulmonary diseases. A number of breath biomarkers in lung pathophysiology will be described including nitric oxide (NO), carbon monoxide (CO), hydrogen peroxide (H(2)O(2)) and other hydrocarbons.     

The daytime breath hydrogen profile: technical aspects and normal pattern

A method is described for breath sampling which can be used for breath hydrogen estimations not only in clinical practice, but also at home. Sampling of end-expiratory air is performed using a 10-ml syringe with a side hole. The samples are transferred to 3-ml vacuum tubes, which can be stored and mailed without significant loss of hydrogen. The hydrogen concentration is estimated gas chromatographically using 0.4 ml of sampled air. This method was used to assess the breath hydrogen pattern under normal circumstances: the daytime breath hydrogen profile. Fourteen children sampled their breath at 30-min intervals during one full day, and recorded diet and activity. The normal daytime breath hydrogen profile showed a typical pattern. Morning values were low, but the evening values were markedly increased in half of the children. These patterns differed markedly from those registered in three children with carbohydrate malabsorption. The daytime breath hydrogen profile, which is easy to perform and applicable at home, might provide valuable additional information in the investigation of children with suspected carbohydrate malabsorption.     

Technique for gas-chromatographic measurement of volatile alkanes from single-breath samples

For detection of small quantities of alkanes that are present in expired breath, these gases have hitherto been concentrated, either by passing large volumes of breath through a liquid-nitrogen-cooled precolumn or by use of a closed collection system. Here, we describe a technique for analyzing small volumes of gas from single-breath samples from humans, in which no precolumn is required. Results are linearly related to sample concentrations of ethane, propane, butane, and pentane in the range 0 to 13 nmol per liter of air (r = 0.999). Within-run coefficients of variation were less than 15%. Breath samples could be stored for as long as 10 h without loss of the alkanes. We also report alkane concentrations in samples of alveolar gas and total breath collected from normal subjects. This technique appears to be well suited for measuring alkane concentrations in single-breath samples.     

Evaluation of a non-invasive method for the measurement of metabolic rate in humans

Measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) can be used to calculate energy expenditure. Such data are useful in the nutritional management of a variety of pathological conditions. This study is an evaluation in vitro and in vivo of the mating of a canopy and a Beckman metabolic measurement cart 1 (MMC). The canopy allows for the collection of expired gases without facial attachments. Studies in vitro demonstrated the necessity of calibrating the CO2 analyser at the concentrations used in such a system (0.50-0.80% CO2). Measurements of VO2 were within + 12% to -8% of predicted values, and when calibrated at 0.50% and 0.75% CO2, measurements of VCO2 were within + 2% and -7% of predicted values. The studies in vivo revealed that VO2 and VCO2 were within +/- 11% of the values obtained by using a canopy-spirometer-computer system. The MMC plus canopy may provide an alternative method for the clinical measurement of VO2 and VCO2, especially in subjects unable to tolerate a tight-fitting mask for prolonged periods.     

Detection of Carbon Monoxide Production as a Result of the Interaction of Five Volatile Anesthetics and Desiccated Sodalime with an Electrochemical Carbon Monoxide Sensor in an Anesthetic Circuit Compared to Gas Chromatography

OBJECTIVES: There is a continuing risk of production of toxic levels of carbon monoxide (CO) as a result of interaction of volatile anesthetics and desiccated strong base carbon dioxide absorbents like soda lime. The aim of this study is to establish the reliability of detection of CO levels by an electrochemical carbon monoxide sensor compared to gas chromatography. METHODS: Completely desiccated sodalime was conducted through a circle anesthesia system connected to an artificial lung. For different rates of CO production, a low flow anesthesia with a oxygen/nitrous oxide mixture was maintained using five volatile anesthetics. For quantification of CO production, a portable gas chromatograph (GC) was connected to this setup, as well as a Bedfont EC40 electrochemical carbon monoxide sensor (ES) with a claimed reliable sensitivity of 0-200 parts per million (ppm) and a maximum detection range of more than 5500 ppm. To assess the agreement between the GC and ES measurements the intra class correlation coefficient (ICC) and the 95% limits of agreement were calculated. Bland and Altman scatterplots were made to visualize the difference between measurements. RESULTS: For concentrations up to 200 ppm, no significant differences between the GC and ES mean CO measurements were found in the halothane experiments. However CO was not accurately measured at every moment during these experiments by the ES. For concentrations above 200 ppm the results of the two instruments differed significantly. The ES malfunctioned when exposed to sevoflurane and desiccated sodalime. CONCLUSIONS: From these data we conclude that the ES can only be used as an indicator of CO production. When this sensor is used with sevoflurane and desiccated sodalime it is not capable of normal operation. The use of a strong base free carbon dioxide absorbent is therefore recommended.     

The Technicon RA-1000 evaluated for measuring sodium, potassium, chloride, and carbon dioxide

We evaluated the Technicon RA-1000 "random-access" analyzer for the measurements of sodium, potassium, and carbon dioxide by an indirect potentiometric method (ion-selective electrode) and for chloride by a colorimetric method (mercuric thiocyanate). For various concentrations of control materials the total precision (CV) ranged from 0.9 to 1.2% for sodium, 1.1 to 1.3% for potassium, 1.0 to 1.2% for chloride, and 2.8 to 3.8% for carbon dioxide. The system demonstrated acceptable performance in linearity and carryover. Patients' results from the RA-1000 correlated well with those from the Beckman ASTRA-8. In a study on potential interferences, we found that high concentrations of salicylate and bromide significantly affected measurements of carbon dioxide and chloride, respectively. The RA-1000 requires only 30 microL of sample for all four tests and it offers a high throughout (30 specimens analyzed for the four tests in 25 min). This precise, easy-to-use, random-access analyzer requires minimal maintenance.     

Carbon dioxide tensions in physiological salt solutions: direct measurements

Carbon dioxide tensions were measured directly in organ baths and a tonometer aerated in parallel with 6 different gas mixtures of O2 and CO2, 3 gas flows, 3 equilibration periods, and 3 bicarbonate concentrations. The measured partial pressure of carbon dioxide differed systematically from expected values, probably due to errors in the carbon dioxide measurement system. In conclusion, carbon dioxide equilibrates with the bubbling gas in the baths as well as in the tonometer to an almost perfect equilibration.     

A new method for measurement of gas exchange during anaesthesia using an extractable marker gas

A new method for the measurement of pulmonary gas exchange during inhalational anaesthesia is described which measures fresh gas and exhaust gas flows using carbon dioxide as an extractable marker gas. The theoretical precision of the method was compared by Monte Carlo modelling with other approaches which use marker gas dilution. A system was constructed for automated measurement of uptake of oxygen, nitrous oxide, volatile anaesthetic agent and elimination of carbon dioxide by an anaesthetized patient. The accuracy and precision of the method was tested in vitro on a lung gas exchange simulator, by comparison with simultaneous measurements made using nitrogen as marker gas and the Haldane transformation. Good agreement was obtained for measurement of simulated uptake or elimination of all gases studied over a physiologically realistic range of values. Mean bias for oxygen and nitrous oxide uptake was 0.003 l min(-1), for isoflurane 0.0001 l min(-1) and for carbon dioxide 0.001 l min(-1). Limits of agreement lay within 10% of the mean uptake rate for nitrous oxide, within 5% for oxygen and isoflurane and within 1% for carbon dioxide. The extractable marker gas method allows accurate and continuous measurement of gas exchange in an anaesthetic breathing system with any inspired gas mixture.     

Occupational exposure during nitric oxided inhalational therapy in a pediatric intensive care setting

Objective To determine the amount of occupational exposure to nitric oxide (NO) and nitrogen dioxide (NO₂) during NO inhalational therapy.Design In a standard pediatric intensive care room, 800 ppm NO was delivered to a high-frequency oscillator and mixed with 100% O₂ to obtain 20 ppm NO in the inspiratory gas flow. NO and NO₂ concentrations in room air were measured using a chemiluminescence analyzer. Air samples were taken from a height of 150 cm at a horizontal distance of 65 cm from the ventilator in a nonventilated and in a well-ventilated room with and without an expiratory gas exhaust under normal intensive care environmental conditions.Setting Pediatric intensive care unit in a university children's hospital.Mesaurements and results Maximal concentrations of NO and NO₂ were reached after 4 h NO use. Without exhaust, in a nonventilated room, environmental NO and NO₂ concentration rose to a maximum of 0.462 and 0.064 ppm, respectively. With the use of an expiratory gas exhaust, NO and NO₂ concentrations were 0.176 and 0.042 ppm, respectively. With normal air-conditioning, these values were 0.075 and 0.034 ppm, respectively, without the use of an expiratory gas exhaust. With expiratory gas exhaust added to normal air-conditioning, values for NO and NO₂ were 0.035 and 0.030 ppm, respectively.Conclusions The use of 20 ppm NO, even under minimal room ventilation conditions, did not lead to room air levels of NO or NO₂ that should be considered toxic to adjacent intensive care patients or staff. Slight increases in NO and NO₂ concentrations were measurable but remained within occupational safety limits. The use of an exhaust system and normal room ventilation lowers NO and NO₂ concentrations further to almost background levels.