Doctor of Philosophy

dissertationFunctional residual capacity (FRC) is the gas volume remaining in the lung following a normal expiration. The size of the FRC may be compromised as result of many pathophysiologic factors, including anesthesia, obesity, acute lung injury, and acute respiratory distress syndrome. Without sufficient FRC volume, both blood oxygenation and carbon dioxide excretion are limited, leading to hypoxemia, carbon dioxide retention, and possible morbidity and mortality. Clinicians have long recognized the potential for improved care from FRC measurement availability, and researchers have been looking for an effective means of bedside FRC assessment during mechanical ventilation for decades. FRC measurement is useful, for example, for guiding ventilation management to improve gas exchange for patients with reduced FRC. Traditional methods of FRC measurement have been valuable for researching disease progression and monitoring ambulatory patients, but are impractical at the bedside. Recent research has proposed better bedside utility through volume-based methods such as nitrogen or oxygen wash-in/ washout to help address the need for FRC measurement. However, the proposed volume-based methods give lower measurement precision during ventilation with spontaneous effort or high airway pressure. Furthermore, these volume-based systems cannot be used with circle breathing systems which are commonly found in the operating room. Thus, the need remains for automated, accurate bedside FRC measurement systems that can be used in the intensive care unit and the operating room during many modes of ventilation, including controlled, assisted, spontaneous and mixed. This dissertation describes the development, clinical feasibility testing and clinical accuracy assessment of two novel bedside models for FRC measurement that use tracer gas washin/washout. The first model, called the modified multiple breath nitrogen washout model, makes use of end-tidal gas measurements to measure FRC. Using endtidal measurements instead of volume reduces errors from signal synchronization. The second model, which is called the partial rebreathing carbon dioxide model, allows FRC measurement during fixed inspired oxygen concentration, making FRC measurement possible in the operating room, where circle breathing systems are common. Both FRC measurement methods demonstrate good accuracy, are compatible with any ventilator brand and can easily be moved from patient to patient for bedside measurement

Breathfinding: A Wireless Network that Monitors and Locates Breathing in a Home

This paper explores using RSS measurements on many links in a wireless network to estimate the breathing rate of a person, and the location where the breathing is occurring, in a home, while the person is sitting, laying down, standing, or sleeping. The main challenge in breathing rate estimation is that "motion interference", i.e., movements other than a person's breathing, generally cause larger changes in RSS than inhalation and exhalation. We develop a method to estimate breathing rate despite motion interference, and demonstrate its performance during multiple short (3-7 minute) tests and during a longer 66 minute test. Further, for the same experiments, we show the location of the breathing person can be estimated, to within about 2 m average error in a 56 square meter apartment. Being able to locate a breathing person who is not otherwise moving, without calibration, is important for applications in search and rescue, health care, and security

Measurement of Functional Residual Capacity of the Lung by Nitrogen Washout/Wash-in in Mechanically Ventilated ICU Patients

Background: We evaluated the functionality, feasibility of use at the bedside and repeatability of subsequent Functional Residual Capacity (FRC) measurements in mechanically ventilated ICU patients using a new system. The newly developed system had previously been assessed for accuracy in spontaneously breathing human volunteers. Materials and Methods: We measured the FRC of the lungs of 20 mechanically ventilated ICU patients using the nitrogen washout/wash-in technique. Duplicate measures in each of the patients were analyzed for repeatability. Results: The squared correlation coefficient for the linear regression between repeated measurements was r2=0.92 (n=39); y=0.99x +0.03. the bias +/- Standard Deviation was -0.009 +/- 0.212 L (-0.4 +/- 8.9%). The Limits of agreement (mean +/- 2*SD) were between -0.42 and 0.41 L (-17.9 to 17.1%). Conclusion: These results indicate FRC measurement is repeatable within a clinically acceptable range. This method compares favorably with other methods recently reported in the literature. This system could possibly be used in space to monitor lung volume, especially as it relates to pulmonary disease in weightlessness

Evaluation of a CO2 Partial Rebreathing-Based Functional Residual Capacity Measurement Method for Mechanically Ventilated Patients

There is a need for an automated bedside functional residual capacity (FRC) measurement method that can continually monitor both the size and a change in size of a patient’s lung volume during mechanical ventilation without the use of bulky equipment, expensive tracer gases or step increases in inspired oxygen fraction. We developed a CO2 rebreathing method for FRC measurement that simply requires data from a volumetric capnometer (partial pressure of end-tidal carbon dioxide (PetCO2) and volume of CO2 eliminated (VCO2) for the measurement. This study was designed to assess the accuracy, precision and repeatability of the proposed FRC measurement system during stable ventilation. Methods: Accuracy and precision of measurements were assessed by comparing the CO2 rebreathing FRC values to the gold standard, body plethysmography, in nine spontaneously breathing volunteers. Repeatability was assessed by comparing subsequent measurements in nine intensive care patients whose lungs were under mechanical ventilation. The accuracy and precision of the CO2 FRC measurement during mechanical ventilation were then compared to the reference method, modified multiple breath nitrogen washout, in the same ICU patients. Results: Compared to body plethysmography, the accuracy (mean bias) of the CO2 method was -0.085 L and precision (1 standard deviation) was 0.033 L (-2.3 ± 9.2% of body plethysmography). The accuracy in the mechanically ventilated patients was -0.055 L and precision was 0.336 L (-2.6% ± 17.5% of nitrogen washout). The difference between repeated FRC measurements in the ICU patients was 0.020 ± 0.42 L (mean ± standard deviation) (1.1 ± 23.4 %). Conclusions: The CO2 rebreathing method for FRC measurement provides acceptable accuracy and repeatability compared to existing methods during ventilation with mechanical ventilation. Further study of the CO2 rebreathing method is needed

Measurement of Functional Residual Capacity of the Lung by Nitrogen Washout, Carbon Dioxide Rebreathing and Body Plethysmography in Healthy Volunteers

Background: We measured Functional Residual Capacity (FRC) of the lungs with three methods in healthy volunteers. The three techniques included a CO2 partial rebreathing technique, nitrogen washout technique, and the reference technique for ambulatory patients, body plethysmography. Materials and Methods: After granting consent to an IRB-approved protocol, each of the 20 healthy volunteers participated in FRC measurement by three methods, including body plethysmography, carbon dioxide (CO2) rebreathing, and nitrogen washout. Gas concentration and volume data were collected from the distal side of a mouthpiece during spontaneous ventilation for the washout and rebreathing measurements. The FRC was measured twice with a nitrogen washout measurement technique and then signals from five partial CO2 rebreathing measurement cycles were collected. Finally, the nitrogen washout FRC measurements were repeated twice. We compared the average CO2 rebreathing FRC measurements and the average nitrogen washout FRC measurements to the body plethysmography FRC measurements for each subject through statistical methods of linear regression analysis and Bland-Altman Analysis. Results: The squared correlation coefficient for the linear regression between nitrogen washout and body plethysmography measurements was r2 = 0.91 (n = 35). The bias +/- Standard Deviation was 0.054 +/- 0.373 L Conclusion: These results indicate FRC measurement by nitrogen washout correlate well with the body plethysmography reference standard in ambulatory, spontaneously breathing subjects. This method could possibly be used in space to monitor lung function

Anatomic Dead Space Cannot Be Predicted by Body Weight

Anatomic, airway, or tracheal, dead space is the part of the tidal volume that does not participate in gas exchange. Knowledge of the size of the dead space is important for proper mechanical ventilation, especially if small tidal volumes are used. Respiratory and medical textbooks state that anatomic dead space can be estimated from the patient’s body weight. Specifically, these references suggest dead space can be predicted using a relationship of one milliliter per pound of body weight. Using a volumetric capnography monitor that incorporates on-airway flow and CO2 monitoring (NICO2, Respironics, Wallingford CT), anatomic dead space can be automatically and directly measured using Fowler’s method in which dead space equals the exhaled volume up to the point when CO2 rises above a threshold [4]. We retrospectively analyzed data collected in 58 (43 male, 15 female) patients to assess the accuracy of weight-based estimation of anatomic dead space. It appears that the average anatomic dead space roughly corresponds to the average body weight for the overall population; however, the poor correlation between individual patient weight and dead space contradicts the suggestion that dead space can be estimated from body weight

Measurement of Functional Residual Capacity of the Lung Before and During Acute Lung Injury

Background: We measured Functional Residual Capacity (FRC) of the lungs with a CO2 partial rebreathing technique, first in a mechanical lung analog, and then in mechanically ventilated animals before, during, and subsequent to an acute lung injury induced by oleic acid. We compared the FRC from partial CO2 rebreathing with those of a nitrogen washout reference method. Materials and Methods: Using an approved animal protocol, general anesthesia was induced and maintained with propofol in six swine (38.8-50.8 kg). In both the mechanical lung analog and the animals, a partial CO2 rebreathing monitor (NICO2, Respironics Inc., Wallingford, CT) was placed in the breathing circuit between the endotracheal tube and the Y-piece. The partial CO2 rebreathing signal obtained from this monitor was used to calculate FRC. FRC was also measured with a nitrogen washout measurement technique. In the animals, we collected data from healthy lungs and then subsequent to a lung injury that simulated the conditions of ARDS/ALI which was created by intravenously infusing 0.09 mL/kg of oleic acid over a 15-minute period. At each stage of the experiment, the positive end-expiratory pressure (PEEP) was set to 0, 5, 10, and 15 mmHg H2O. At each PEEP level, we compared the average of three FRC measurements from CO2 rebreathing to the average of three nitrogen washout reference measurements. Results: The correlation coefficient for the linear regression between CO2 rebreathing and nitrogen washout measurements in the animals was r2= 0.89 (n = 50). The average error of the CO2 washout system was -87 mL with limits of agreement (LOA) ± 263 mL. In the mechanical lung, the average error in the FRC measured by the CO2 wash-in system was 37 mL with LOA ± 103 mL, which was equivalent to 1.7% of the true FRC. The correlation coefficient was r2= 0.96. Conclusion: These results indicate FRC measurement by CO2 rebreathing can reliably detect a decrease in FRC during lung injury and can reflect the response of the FRC to treatment with PEEP

Detecting Adverse Respiratory Effects of Anesthetics and Opiod Analgesics in the Postoperative Period

The underlying problem for two of the three most common patterns of unexpected hospital deaths (PUHD) is hypoventilation1. Current methods of post-operative respiratory monitoring give delayed signals and have a high false positive rate leading nurses to ignore alarms. We hypothesize there exists a combination of low cost sensors which are capable of providing real time feedback and alarms regarding obstructive sleep apnea and ventilatory depression. Such a monitor would be useful during space travel when monitoring personnel are limited following an injury or if astronauts were to be sedated during extended travel. Methods:Twenty-Six subjects will be recruited to participate in a study of the effects of Propofol and Remifentanil. Throughout the day, these patients will be exposed to varying levels of both drugs simultaneously via target controlled infusions. These patients will be attached to breathing and oxygen monitors including chest bands, pulse oximeters, nasal pressure sensors, CO2 capnography, breathing microphones, and thermistors. The patients are then observed for types of apnea or ventilatory depression. Results: The study is currently ongoing however preliminary analyses of the data indicate multiple low cost sensors are capable of detecting breathing as well as obstructive events and apnea. Conclusion: Using only a combination of low cost sensors, we can provide real time respiratory event data to nurses and practitioners

Detecting Adverse Respiratory Events: A Comparison of the Effectiveness of Modern Respiratory Sensors

The underlying problem for two of the three most common patterns of unexpected hospital deaths (PUHD) is hypoventilation1. Current methods of post-operative respiratory monitoring give delayed signals and have a high false positive rate leading nurses to ignore alarms. We hypothesize there exists a combination of low cost sensors which are capable of providing real time feedback and alarms regarding obstructive sleep apnea and ventilatory depression. Such a monitor would be useful during space travel when monitoring personnel are limited following an injury or if astronauts were to be sedated during extended travel. Methods: Twenty-six subjects were recruited to participate in a study of the effects of Propofol and Remifentanil. Throughout the day, these patients were exposed to varying levels of both drugs simultaneously via target controlled infusions. These patients were attached to breathing and oxygen monitors including chest bands, pulse oximeters, nasal pressure sensors, C02 capnography, breathing microphones, and thermistors. The patients were then observed for types of apnea or ventilatory depression. Results: The study is currently ongoing however preliminary analyses of the data indicate multiple low cost sensors are capable of detecting breathing as well as obstructive events and apnea. Conclusion: Using only a combination of low cost sensors, we can provide real time respiratory event data to nurses and practitioners

Measurement of the Respiratory Functional Residual Capacity on an Artificial Lung System

Decreases in functional residual capacity (FRC), the residual respiratory volume following an expiration, are associated with the application of anesthesia and supine body positioning, both common in the ICU. We are developing two non-invasive methods of measuring the FRC on patients under mechanical ventilation. FRC increases are typically accomplished by increasing the Positive End Expiratory Pressure (PEEP) until the arterial O2 content is saturated; however, increased PEEP may also cause a decrease in cardiac output due to the increased thoracic cavity pressure, resulting in a net decreased O2 delivery. Measurement of the FRC will be useful in optimizing the application of PEEP to maximize O2 delivery. FRC determination as a function of PEEP was made on a test lung using a partial CO2 rebreathing method and an N2 washout method in order to compare their accuracy. The CO2 rebreathing method uses Fick’s principle along with a perturbation of gas concentrations initiated by partial rebreathing. The N2 washout method also utilizes Fick’s principle, but creates the perturbation through an increase in inspired O2 concentration. Preliminary FRC measurements were made using the NICO2 system which includes a pneumotachograph for volumetric measurements and a CAPNOSTATTM sensor for CO2 concentration measurement. Although both methods correlated to measured FRC volumes in the test lung, the N2 washout method resulted in greater precision and less variability, most likely due to the greater magnitude of perturbation that is made and the use of data from multiple breaths. Both methods will require further bench testing to verify their accuracy within typical ranges of mechanical ventilation variables, followed by en vivo studies in order to characterize any inherent physiologic implications and to determine repeatability