A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Children with prolonged mechanical ventilation after cardiac surgery have a higher risk for poor outcome due to a variety of ventilator‐associated morbidities. It therefore becomes essential to identify these children at higher risk of prolonged mechanical ventilation as well as find methods to identify children ready to be extubated as early as possible to avoid these complications. One physiological variable, the pulmonary dead space fraction (VD/VT), has been suggested as a possible indicator of prolonged mechanical ventilation. VD/VT essentially measures the amount of ventilated air that is unable to participate in gas exchange. Can VD/VT be used successfully in children undergoing cardiac surgery to identify those at risk for prolonged mechanical ventilation and identify those ready for extubation? Retrospective chart review of 461 patients at Phoenix Children’s Hospital in the Pediatric Cardiac Intensive Care Unit since the initiation of standard application of the Philips NM3 monitors in October 2013 through December 2014. From the 461 patients screened, only 99 patients met all the inclusion criteria. These 99 patients consisted of 29 patients with balanced single ventricle physiology and 61 patients with two ventricle physiology. Initial postoperative and pre‐extubation VD/VT values correlated with length of mechanical ventilation for patients with two ventricle physiology but not for patients with single ventricle physiology. Additionally, pre‐extubation VD/VT values of greater than 0.5 indicated higher rates of extubation failure in two ventricle patients. Conclusion: For children with two ventricle physiology undergoing cardiac surgery, VD/VT should be used clinically to estimate the length of mechanical ventilation for these children. VD/VT should also be checked in these patients before attempting to extubate. If VD/VT is found to be higher than 0.5, extubation should not be attempted since the patient is at a much higher risk for extubation failure.

The majority of patients with chronic obstructive pulmonary disease (COPD) have milder airway obstruction and are not diagnosed in a timely fashion. Nevertheless, these patients are largely under-studied; this, despite new evidence of increased morbidity and mortality in this sub-population. Recent studies have highlighted the increased ventilatory requirements and abnormalities in respiratory mechanics as important features to explain the relatively reduced exercise tolerance and greater exertional dyspnea in these patients. However, it remains uncertain whether such abnormal mechanical factors actually limit exercise capacity in mild COPD. Accordingly, the objective of this study was to determine whether ventilatory constraints represent a primary factor in exercise limitation and increased dyspnea in this patient group. To determine the role of mechanical factors in exercise limitation in mild COPD, we selectively loaded the respiratory system by adding dead space (DS) to the breathing circuit. We compared ventilation, breathing pattern, operating lung volumes, and dyspnea intensity during incremental cycle exercise in 20 patients with GOLD stage I COPD (post-bronchodilator FEV1/FVC=61±5%, and FEV1=95±11% predicted; mean±SD) and 20 healthy age-, sex- and BMI-matched subjects under two conditions, in randomized order: unloaded control (CTRL) or ventilatory stimulation by 600mL of an added DS. Compared to the CTRL condition, both healthy and COPD participants had small decreases in peak work rate and no significant increase in peak ventilation with the added DS. At the highest equivalent work rate of 60 watts, DS caused a smaller increase in tidal volume (VT) in COPD compared with healthy subjects (+0.26±0.29 vs. +0.56±0.22 L respectively, p<0.01) with a correspondingly greater increase in dyspnea intensity (+1.8±1.8 vs. +0.2±0.6 Borg units, respectively, p<0.0001). At peak exercise, COPD patients failed to significantly increase VT, reflecting the fact that end-inspiratory lung volume (EILV) could not increase with DS vs. CTRL (5.25±0.91 vs. 5.16±0.84 L, respectively, p=0.41). This contrasts the results in health where EILV increased with DS vs. CTRL (5.40±1.01 vs. 5.13±0.90 L, respectively, p<0.05). We conclude that the lower exercise performance in mild COPD, compared with health, is explained by critical respiratory mechanical constraints which limit further increases in ventilation to support a higher metabolic load. / Thesis (Master, Physiology) -- Queen's University, 2012-09-28 12:04:50.507

<p>The recognition that supportive mechanical ventilation can also damage the lung, the so called ventilation induced lung injury (VILI), has revived the more than 40 year long debate on the optimal level of PEEP to be used. It is established that the prevention of VILI improves patient outcome and that PEEP exerts protective effects by preventing unstable diseased alveoli from collapsing. Therefore, the term “open lung PEEP” (OL-PEEP) has been introduced as the end-expiratory pressure that keeps the lung open after its collapse has been eliminated by an active lung recruitment manoeuvre. The determination of such an optimal level of PEEP under clinical circumstances is difficult and remains to be investigated.</p><p>The aim of this study was to investigate the usefulness of breath by breath monitoring of dynamic compliance (Cdyn) as a clinical means to identify OL-PEEP at the bedside and to demonstrate the improvement in lung function resulting from its application.</p><p>In a porcine lung lavage model of acute lung injury PEEP at maximum Cdyn during a decremental PEEP trial after full lung recruitment was related to the onset of lung collapse and OL-PEEP could be found 2 cmH₂O above this level Ventilation at OL-PEEP was associated with improved gas exchange, efficiency of ventilation, lung mechanics and less than 5% collapse on CT scans. In addition, dead space, especially its portion related to alveolar gas changed characteristically during recruitment, PEEP titration and collapse thereby helping to identify OL-PEEP.</p><p>The beneficial effects of OL-PEEP on lung function and mechanics was demonstrated in a porcine model of VILI. OL-PEEP improved lung function and mechanics when compared to lower or higher levels prior to or after lung recruitment. By using electrical impedance tomography it could be shown that PEEPs within the range of 14 to 22 cmH₂O resulted in a similar redistribution of both ventilation and perfusion to the dorsal regions of the lung. OL-PEEP resulted in the best regional and global matching of ventilation and perfusion explaining the drastic improvements in gas exchange. Also regional compliance was greatly improved in the lower half of the lung as compared to all other situations.</p><p>In ARDS patients OL-PEEP could be identified applying the same protocol. The physiological changes described could now be reproduced and maintained during a four hours study ventilation period in real patients at four study centres.</p><p>In conclusion, the usefulness of dynamic compliance for identifying open lung PEEP during a decremental PEEP trial was demonstrated under experimental and clinical conditions. This PEEP should then be used as an essential part of any lung protective ventilation strategy. The impact of ventilating ARDS patients according to the principles described in these studies on outcome are currently being evaluated in an international randomized controlled trial.</p>

The recognition that supportive mechanical ventilation can also damage the lung, the so called ventilation induced lung injury (VILI), has revived the more than 40 year long debate on the optimal level of PEEP to be used. It is established that the prevention of VILI improves patient outcome and that PEEP exerts protective effects by preventing unstable diseased alveoli from collapsing. Therefore, the term “open lung PEEP” (OL-PEEP) has been introduced as the end-expiratory pressure that keeps the lung open after its collapse has been eliminated by an active lung recruitment manoeuvre. The determination of such an optimal level of PEEP under clinical circumstances is difficult and remains to be investigated. The aim of this study was to investigate the usefulness of breath by breath monitoring of dynamic compliance (Cdyn) as a clinical means to identify OL-PEEP at the bedside and to demonstrate the improvement in lung function resulting from its application. In a porcine lung lavage model of acute lung injury PEEP at maximum Cdyn during a decremental PEEP trial after full lung recruitment was related to the onset of lung collapse and OL-PEEP could be found 2 cmH2O above this level Ventilation at OL-PEEP was associated with improved gas exchange, efficiency of ventilation, lung mechanics and less than 5% collapse on CT scans. In addition, dead space, especially its portion related to alveolar gas changed characteristically during recruitment, PEEP titration and collapse thereby helping to identify OL-PEEP. The beneficial effects of OL-PEEP on lung function and mechanics was demonstrated in a porcine model of VILI. OL-PEEP improved lung function and mechanics when compared to lower or higher levels prior to or after lung recruitment. By using electrical impedance tomography it could be shown that PEEPs within the range of 14 to 22 cmH2O resulted in a similar redistribution of both ventilation and perfusion to the dorsal regions of the lung. OL-PEEP resulted in the best regional and global matching of ventilation and perfusion explaining the drastic improvements in gas exchange. Also regional compliance was greatly improved in the lower half of the lung as compared to all other situations. In ARDS patients OL-PEEP could be identified applying the same protocol. The physiological changes described could now be reproduced and maintained during a four hours study ventilation period in real patients at four study centres. In conclusion, the usefulness of dynamic compliance for identifying open lung PEEP during a decremental PEEP trial was demonstrated under experimental and clinical conditions. This PEEP should then be used as an essential part of any lung protective ventilation strategy. The impact of ventilating ARDS patients according to the principles described in these studies on outcome are currently being evaluated in an international randomized controlled trial.

There are limited methods of assessing pulmonary function in horses at rest. In this study, we developed clinical techniques to measure gas exchange efficiency in horses. These techniques were then used to evaluate horses with varying degrees of lower respiratory disease. Three groups of horses (Group 1: asymptomatic, n=6; Group 2: symptomatic only with rebreathing, n=11; Group 3: symptomatic at rest, n=9) were selected based on physical exam, transtracheal aspirate, and thoracic radiographs. Blood samples were obtained from the transverse facial artery and jugular vein. Maximal end-tidal CO₂ tension (E_TCO₂) was measured by an infrared capnograph through a facemask. Alveolar O, tension, alveolar dead space fraction (V_DB/V_T), and physiologic shunt fraction (Q_S/Q_T) were calculated using standard formulas. Horses with both mild and severe signs of lower respiratory disease had significant (p<0.05) differences in gas exchange indices at rest compared to asymptomatic horses. Albuterol was administered to seven of the Group 2 horses from a metered-dose inhaler through an equine facemask at a dose of 90 μg per 100 kg. Blood samples and tidal gas samples were obtained 15 minutes post-treatment, and Q_S/Q_T and (V_DB/V_T) were calculated. Albuterol caused significant (p<0.05) hypoxemia 15 minutes following inhaled administration. This was accompanied by a significant increase in Q_S/Q_T, suggesting that the hypoxemia was due to increases in which the ratios of ventilation to perfusion were decreased. / Master of Science

Nasal high flow (NHF) therapy is a recent form of non-invasive respiratory support for patients suffering from respiratory distress that supplies high flows of heated and humidified air, oxygen or a mix via a nasal cannula. A number of in vivo studies have proven its effectiveness at improving blood oxygenation; however, its mechanisms of action remain widely unproven. Two proposed mechanisms of action, the CO2 washout of anatomic dead space and the production of positive airway pressure, are investigated in this thesis for the use of the Fisher & Paykel Healthcare Ltd (FPH) Optiflow™ adult nasal cannula through a range of experiments. Five anatomically correct upper airway models produced from computed tomography (CT) scan data via 3D printing were employed during in vitro experiments and two live subjects participated in in vivo measurements. The human respiratory system was faithfully replicated for CO2 washout experiments with physiological CO2 diffusion into the lung replicated by a constant flow of CO2 into the lung pump. In vivo measurement of a natural breathing flow pattern was scaled to an average population tidal volume and respiratory rate for in vitro use. In vitro measurements of static pressure during natural breathing found similar flow resistances across the nasal passage for inspiratory and expiratory flow directions; however, across the entire upper airway greater resistance was seen for inspiration. Introduction of NHF therapy produced significant increases in all mean and peak airway pressures within the upper airway with a flow rate of 30 LPM fulfilling the inspiratory work requirements presented by the upper airway resistance. In vivo and in vitro hot wire anemometry measurements at the exterior nares indicated low velocity and turbulence intensity flows at peak inspiration and a high velocity jet with high turbulence during peak expiration. At natural breathing an in vitro anterior-posterior velopharynx traverse captured low turbulence intensities during peak inspiration and high turbulence intensities during peak expiration. Introduction of NHF therapy had little influence on the turbulence intensity profile of peak expiration yet did cause significant increases in the turbulence intensities during peak inspiration. Measurements of the CO2 concentration near the lung volume over many breath cycles were used to find time-averaged CO2 concentrations. For the standard airway model an average CO2 concentration of 4.88 ± 0.07 %V/V was determined during natural breathing. Implementation of increasing levels of NHF therapy generated significant washout of CO2 reducing this average concentration to a minimum of 3.81 ± 0.11 %V/V at a flow rate of 80 LPM. It was determined that airway geometry significantly affected the efficacy of the NHF therapy though CO2 washout was observed in all five airway models.

In this thesis a method for determining optimal dead space in an axial-type expander is developed. The axial-type expander in question is for use in a steam engine, a environmental friendly and fuel-agnostic alternative to the ICE-engine. Optimal dead space is of importance as an increase in the dead space lowers the efficiency of the engine, however, is needed to ensure operation of expander as the piston could otherwise collide with the expander chamber top surface. The model for determining the optimal dead space in this thesis is based on vectorial tolerance models used for kinematic assemblies, and include the effect of thermal expansion, clearances at joints, manufacturing tolerances and deformations. With resulting tolerances and safety factors, a safe position of the expansion chamber top surface can then be established by Monte Carlo analysis. With input of design variables and the effect from factors mentioned and their effect on the minimal safe distance is calculated using the model in this thesis. From numerical analysis, the factors having the most contribution on the dead space are concluded to be thermal expansion of piston and piston rod, dimensional manufacturing tolerances of piston and piston rod, clearance at ball joints, axial clearance at shaft and bending of Z-shaft. / I detta examensarbete har en metod för att bestämma det optimala avståndet mellan kolv och expansionskammarens högsta yta tagits fram. Axial-kolvmotorn avses för bruk i en ångmotor, ett miljövänligt alternativ till bensin och dieselmotorer som kan drivas med många drivmedel, t.ex. biomassa. Att bestämma detta optimala avstånd är viktigt eftersom en ökning i detta avstånd minskar motorns effektivitet. Dock behövs ett visst avstånd för att säkerställa att ingen kontakt mellan de två ytorna sker under drift. Modellen framtagen i detta examensarbete baserar sig på tolerans analys-modeller med vektorer som används för mekanismer under rörelse. I denna modell inkluderas effekten av termisk expansion, glapp i kontakt mellan komponenter, tillverkningstoleranser och deformationer på kolvens rörelse. Med hjälp av resulterande toleranser och säkerhetsfaktorer kan genom Monte Carlo simulationer ett optimalt avstånd mellan kolv och expansionkammaren bestämmas. Genom inmatning av designvariabler och undersökta effekter kunde genom numerisk analys konstateras att de viktigaste parametrarna att undersöka med störst effekt på axial-kolvmotorn var termisk expansion av kolv och kolvstång, dimensionella toleranser av kolv och kolvstång, glapp i kul-kontakter, axial rörelsefrihet vid kulled och böjning av Z-axel.

A frequency response tracer technique was used to study the hydraulic properties of a laboratory flow through reactor with variations in reactor size, flow rate and applied mixing. At any one set of conditions the reactor was studied over a range of input sine wave frequencies. Theoretical models consisting of in-series networks of completely mixed segments, plug flow segments, and dead space allowances were developed to approximate the experimental findings. / Thesis / Master of Engineering (ME)

Orientadores: Jose Dirceu Ribeiro, Marcos Tadeu Nolasco da Silva / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T18:07:20Z (GMT). No. of bitstreams: 1 AlmeidaJunior_ArmandoAugusto_M.pdf: 4431376 bytes, checksum: 1942765ed1a5dc73ed3bc9e4f73a54af (MD5) Previous issue date: 2006 / Resumo: Técnicas de monitorização da função respiratória são recursos importantes no diagnóstico e seguimento das doenças pulmonares em pacientes em ventilação mecânica invasiva (VMI). O presente estudo propiciou a realização de dois trabalhos com os seguintes objetivos: 1)Avaliar a associação entre tempo de VMI, variáveis antropométricas, clínicas e de função pulmonar, precocemente, em lactentes com insuficiência respiratória aguda (IRA) por bronquiolite viral aguda (BVA) em VMI, e a evolução temporal das variáveis significativamente correlacionadas; 2) Avaliar a associação entre a relação VD/VT e variáveis da função pulmonar, precocemente medidas nestes lactentes. Métodos: Realizou-se um estudo clinico, do tipo coorte prospectivo com 29 lactentes em VMI por IRA com diagnóstico clínico de BVA, admitidos na Unidade de Terapia Intensiva Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas no período de abril de 2001 a abril de 2004. Todos os pacientes tiveram os valores de mecânica pulmonar e capnografia medidos com aparelho CO2SMO Plus. Resultados: 1) O tempo de VMI apresentou correlação positiva, medida pela correlação de Spearman (rs), significativa com a PaCO2 (rs= 0,45, p= 0,01) e com o índice de ventilação (rs= 0,51, p= 0,005), e negativa com o pH (rs= -0,40, p= 0,03). Índice de ventilação com valor de 37, avaliado do primeiro ao quinto dia, foi associado a risco progressivamente aumentado de tempo de VMI maior que sete dias (OR= 4,2 no primeiro dia a 15,71 no quarto dia). 2) As seguintes variáveis mostraram uma associação significante com VD/VT: PaO2 (rs=-0.63, p < 0.001), PaO2/FiO2 (rs= -0.56, p= 0.002), PaO2/PAO2 (rs= -0.46, p = 0.012), P(A-a)O2/PaO2 (rs= -0.46, p= 0.012), PaCO2 (rs= 0.51, p= 0.005), VCO2 (rs= -0,69, p < 0,001), índice de oxigenação (rs= -0.48, p= 0.009), índice de ventilação (rs= -0.53, p= 0.003). Encontrou-se associação estatisticamnete significativa entre um aumento do VD/VT e a gravidade da lesão pulmonar definida por PaO2/FiO2 < 200 (p= 0.03, Mann-Whitney). Conclusões: 1) Índice ventilatório, PaCO2 e pH, precocemente medidos, foram associados com tempo prolongado em ventilação mecânica, refletindo a gravidade do distúrbio ventilatório e necessidade de suporte. 2) VD/VT associou-se fortemente com variáveis que representam a relação ventilação/perfusão. A correlação negativa com as variáveis de oxigenação arterial, índice de oxigenação e índice ventilatório sugere associação entre VD/VT e a gravidade da injúria pulmonar / Abstract: Respiratory function monitoring techniques are important in the diagnosis ant follow-up of pulmonary diseases in patients on invasive mechanical ventilation (IMV). The present study comprehended two trials with the following objectives: 1) To evaluate the association between time on mechanical ventilation and anthropometric data, clinical and pulmonary function variables, measured early, in infants on IMV with acute respiratory failure due to acute viral bronchiolitis (AVB), and the temporal progression of variables with significant correlations. 2) To evaluate the association between dead space/tidal volume ratio (VD/VT) and pulmonary function variables early evaluated in infants on IMV with acute respiratory failure due to AVB. Methods: A prospective cohort study was done, enrolling 29 infants on IMV with AVB, admitted to the Pediatric Intensive Care Unit of the State University of Campinas Hospital, from April, 2001 to April, 2004. All patients had pulmonary mechanics and capnography values measured with the Co2SMO Plus device. Results: 1) Time on mechanical ventilation showed a significant positive correlation, calculated using Spearman's correlation coefficient (rs), with PaCO2 (rs= 0.45, p= 0.01) and ventilation index (rs= 0.51, p= 0.005), and a negative correlation with pH (rs= -0.40, p= 0.03). A ventilation index of 37, measured between day one and day five, was associated with a progressively increased risk of more than 7 days on mechanical ventilation (OR= 4.2 on the first day to 15.71 on the fourth day). 2) The following variables showed a statistically significant association with VD/VT: PaO2 (rs= -0.63, p < 0.001), PaO2/FiO2 (rs= -0.56, p= 0.002), PaO2/PAO2 (rs= -0.46, p= 0.012), P(A-a)O2/PaO2 (rs= -0.46, p= 0.012), PaCO2 (rs= 0.51, p= 0.005), VCO2 for breath (rs= -0,69, p < 0,001), oxygenation index (rs= -0.48, p= 0.009), ventilation index (rs= -0.53, p= 0.003). A statistically significant association was found between increased VD/VT and severity of lung injury, defined as PaO2/FiO2 < 200 (p= 0.03, Mann-Whitney). Conclusions: 1) Ventilation index, PaCO2 and pH, measured early, were associated with prolonged mechanical ventilation, reflecting the ventilatory disturbance severity and the need of mechanical respiratory support. 2) VD/VT has a strong association with variables which represent ventilation/perfusion relationship. The negative correlation with arterial oxigenation variables, oxygenation index and ventilatory index suggests an association between VD/VT and severity of lung injury / Mestrado / Pediatria / Mestre em Saude da Criança e do Adolescente

Background: This work presents a generalized technique to estimate pulmonary ventilation-to-volume (v/V) distributions using the multiple-breath nitrogen washout, in which both tidal volume (VT) and the end-expiratory lung volume (EELV) are allowed to vary during the maneuver. In addition, the volume of the series dead space (vd), unlike the classical model, is considered a common series unit connected to a set of parallel alveolar units. Methods: The numerical solution for simulated data, either error-free or with the N2 measurement contaminated with the addition of Gaussian random noise of 3 or 5 % standard deviation was tested under several conditions in a computational model constituted by 50 alveolar units with unimodal and bimodal distributions of v/V. Non-negative least squares regression with Tikhonov regularization was employed for parameter retrieval. The solution was obtained with either unconstrained or constrained (VT, EELV and vd) conditions. The Tikhonov gain was fixed or estimated and a weighting matrix (WM) was considered. The quality of estimation was evaluated by the sum of the squared errors (SSE) (between reference and recovered distributions) and by the deviations of the first three moments calculated for both distributions. Additionally, a shape classification method was tested to identify the solution as unimodal or bimodal, by counting the number of shape agreements after 1000 repetitions. Results: The accuracy of the results showed a high dependence on the noise amplitude. The best algorithm for SSE and moments included the constrained and the WM solvers, whereas shape agreement improved without WM, resulting in 97.2 % for unimodal and 90.0 % for bimodal distributions in the highest noise condition. Conclusions: In conclusion this generalized method was able to identify v/V distributions from a lung model with a common series dead space even with variable VT. Although limitations remain in presence of experimental noise, appropriate combination of processing steps were also found to reduce estimation errors.