Short-term effects of neuromuscular blockade on global and regional lung mechanics, oxygenation and ventilation in pediatric acute hypoxemic respiratory failure

Background: Neuromuscular blockade (NMB) has been shown to improve outcome in acute respiratory distress syndrome (ARDS) in adults, challenging maintaining spontaneous breathing when there is severe lung injury. We tested in a prospective physiological study the hypothesis that continuous administration of NMB agents in mechanically ventilated children with severe acute hypoxemic respiratory failure (AHRF) improves the oxygenation index without a redistribution of tidal volume VT toward non-dependent lung zones. Methods: Oxygenation index, PaO2/FiO(2) ratio, lung mechanics (plateau pressure, mean airway pressure, respiratory system compliance and resistance), hemodynamics (heart rate, central venous and arterial blood pressures), oxygenation [ oxygenation index (OI), PaO2/FiO(2) and SpO(2)/FiO(2)], ventilation (physiological dead space-to-VT ratio) and electrical impedance tomography measured changes in end-expiratory lung volume (EELV), and VT distribution was measured before and 15 min after the start of continuous infusion of rocuronium 1 mg/kg. Patients were ventilated in a time-cycled, pressure-limited mode with pre-set VT. All ventilator settings were not changed during the study. Results: Twenty-two patients were studied (N = 18 met the criteria for pediatric ARDS). Median age (25-75 interquartile range) was 15 (7.8-77.5) weeks. Pulmonary pathology was present in 77.3%. The median lung injury score was 9 (8-10). The overall median CoV and regional lung filling characteristics were not affected by NMB, indicating no ventilation shift toward the non-dependent lung zones. Regional analysis showed a homogeneous time course of lung inflation during inspiration, indicating no tendency to atelectasis after the introduction of NMB. NMB decreased the mean airway pressure (p = 0.039) and OI (p = 0.039) in all patients. There were no significant changes in lung mechanics, hemodynamics and EELV. Subgroup analysis showed that OI decreased (p = 0.01) and PaO2/FiO(2) increased (p = 0.02) in patients with moderate or severe PARDS. Conclusions: NMB resulted in an improved oxygenation index in pediatric patients with AHRF. Distribution of VT and regional lung filling characteristics were not affected

Monitoring and regulation of supported breathing in Intensive Care

This thesis describes several chapters related to monitoring and regulation of breathing. The main goal is to provide better insight in the interaction between spontaneous breathing and mechanical ventilatory support. In chapter 2 we investigated the effect of metabolic alkalosis on the ventilatory response. To analyze whether speckle tracking ultrasound can be used to noninvasively quantify diaphragm contractility, in chapter 3 this technique is used in healthy subjects undergoing a randomized stepwise threshold loading protocol. Chapters 4, 5 and 6 of this thesis focus on the interaction between the two parallel systems involved in providing adequate ventilation: the patient and more specific its upper airway, and the ventilator. We studied this interaction in patients with an acute exacerbation of COPD during noninvasive ventilation

Breathing pattern characterization in patients with respiratory and cardiac failure

El objetivo principal de la tesis es estudiar los patrones respiratorios de pacientes en proceso de extubación y pacientes con insuficiencia cardiaca crónica (CHF), a partirde la señal de flujo respiratorio. La información obtenida de este estudio puede contribuir a la comprensión de los procesos fisiológicos subyacentes,y ayudar en el diagnóstico de estos pacientes. Uno de los problemas más desafiantes en unidades de cuidados intensivos es elproceso de desconexión de pacientes asistidos mediante ventilación mecánica. Más del 10% de pacientes que se extuban tienen que ser reintubados antes de 48 horas. Una prueba fallida puede ocasionar distrés cardiopulmonar y una mayor tasa de mortalidad. Se caracterizó el patrón respiratorio y la interacción dinámica entre la frecuenciacardiaca y frecuencia respiratoria, para obtener índices no invasivos que proporcionen una mayor información en el proceso de destete y mejorar el éxito de la desconexión.Las señales de flujo respiratorio y electrocardiográfica utilizadas en este estudio fueron obtenidas durante 30 minutos aplicando la prueba de tubo en T. Se compararon94 pacientes que tuvieron éxito en el proceso de extubación (GE), 39 pacientes que fracasaron en la prueba al mantener la respiración espontánea (GF), y 21 pacientes quesuperaron la prueba con éxito y fueron extubados, pero antes de 48 horas tuvieron que ser reintubados (GR). El patrón respiratorio se caracterizó a partir de las series temporales. Se aplicó la dinámica simbólica conjunta a las series correspondientes a las frecuencias cardiaca y respiratoria, para describir las interacciones cardiorrespiratoria de estos pacientes. Técnicas de "clustering", ecualización del histograma, clasificación mediante máquinasde soporte vectorial (SVM) y técnicas de validación permitieron seleccionar el conjunto de características más relevantes. Se propuso una nueva métrica B (índice de equilibrio) para la optimización de la clasificación con muestras desbalanceadas. Basado en este nuevo índice, aplicando SVM, se seleccionaron las mejores características que mantenían el mejor equilibrio entre sensibilidad y especificidad en todas las clasificaciones. El mejor resultado se obtuvo considerando conjuntamente la precisión y el valor de B, con una clasificación del 80% entre los grupos GE y GF, con 6 características. Clasificando GE vs. el resto de los pacientes, el mejor resultado se obtuvo con 9 características, con 81%. Clasificando GR vs. GE y GR vs. el resto de pacientes la precisión fue del 83% y 81% con 9 y 10 características, respectivamente. La tasa de mortalidad en pacientes con CHF es alta y la estratificación de estospacientes en función del riesgo es uno de los principales retos de la cardiología contemporánea. Estos pacientes a menudo desarrollan patrones de respiraciónperiódica (PB) incluyendo la respiración de Cheyne-Stokes (CSR) y respiración periódica sin apnea. La respiración periódica en estos pacientes se ha asociadocon una mayor mortalidad, especialmente en pacientes con CSR. Por lo tanto, el estudio de estos patrones respiratorios podría servir como un marcador de riesgo y proporcionar una mayor información sobre el estado fisiopatológico de pacientes con CHF. Se pretende identificar la condición de los pacientes con CHFde forma no invasiva mediante la caracterización y clasificación de patrones respiratorios con PBy respiración no periódica (nPB), y patrón de sujetos sanos, a partir registros de 15minutos de la señal de flujo respiratorio. Se caracterizó el patrón respiratorio mediante un estudio tiempo-frecuencia estacionario y no estacionario, de la envolvente de la señal de flujo respiratorio. Parámetros relacionados con la potencia espectral de la envolvente de la señal presentaron losmejores resultados en la clasificación de sujetos sanos y pacientes con CHF con CSR, PB y nPB. Las curvas ROC validan los resultados obtenidos. Se aplicó la "correntropy" para una caracterización tiempo-frecuencia mas completa del patrón respiratorio de pacientes con CHF. La "corretronpy" considera los momentos estadísticos de orden superior, siendo más robusta frente a los "outliers". Con la densidad espectral de correntropy (CSD) tanto la frecuencia de modulación como la dela respiración se representan en su posición real en el eje frecuencial. Los pacientes con PB y nPB, presentan diferentesgrados de periodicidad en función de su condición, mientras que los sujetos sanos no tienen periodicidad marcada. Con único parámetro se obtuvieron resultados del 88.9% clasificando pacientes PB vs. nPB, 95.2% para CHF vs. sanos, 94.4% para nPB vs. sanos.The main objective of this thesis is to study andcharacterize breathing patterns through the respiratory flow signal applied to patients on weaning trials from mechanicalventilation and patients with chronic heart failure (CHF). The aim is to contribute to theunderstanding of the underlying physiological processes and to help in the diagnosis of these patients. One of the most challenging problems in intensive care units is still the process ofdiscontinuing mechanical ventilation, as over 10% of patients who undergo successfulT-tube trials have to be reintubated in less than 48 hours. A failed weaning trial mayinduce cardiopulmonary distress and carries a higher mortality rate. We characterize therespiratory pattern and the dynamic interaction between heart rate and breathing rate toobtain noninvasive indices that provide enhanced information about the weaningprocess and improve the weaning outcome. This is achieved through a comparison of 94 patients with successful trials (GS), 39patients who fail to maintain spontaneous breathing (GF), and 21 patients who successfully maintain spontaneous breathing and are extubated, but require thereinstitution of mechanical ventilation in less than 48 hours because they are unable tobreathe (GR). The ECG and the respiratory flow signals used in this study were acquired during T-tube tests and last 30 minute. The respiratory pattern was characterized by means of a number of respiratory timeseries. Joint symbolic dynamics applied to time series of heart rate and respiratoryfrequency was used to describe the cardiorespiratory interactions of patients during theweaning trial process. Clustering, histogram equalization, support vector machines-based classification (SVM) and validation techniques enabled the selection of the bestsubset of input features. We defined a new optimization metric for unbalanced classification problems, andestablished a new SVM feature selection method, based on this balance index B. The proposed B-based SVM feature selection provided a better balance between sensitivityand specificity in all classifications. The best classification result was obtained with SVM feature selection based on bothaccuracy and the balance index, which classified GS and GFwith an accuracy of 80%, considering 6 features. Classifying GS versus the rest of patients, the best result wasobtained with 9 features, 81%, and the accuracy classifying GR versus GS, and GR versus the rest of the patients was 83% and 81% with 9 and 10 features, respectively.The mortality rate in CHF patients remains high and risk stratification in these patients isstill one of the major challenges of contemporary cardiology. Patients with CHF oftendevelop periodic breathing patterns including Cheyne-Stokes respiration (CSR) and periodic breathing without apnea. Periodic breathing in CHF patients is associated withincreased mortality, especially in CSR patients. Therefore it could serve as a risk markerand can provide enhanced information about thepathophysiological condition of CHF patients. The main goal of this research was to identify CHF patients' condition noninvasively bycharacterizing and classifying respiratory flow patterns from patients with PB and nPBand healthy subjects by using 15-minute long respiratory flow signals. The respiratory pattern was characterized by a stationary and a nonstationary time-frequency study through the envelope of the respiratory flow signal. Power-related parameters achieved the best results in all of the classifications involving healthy subjects and CHF patients with CSR, PB and nPB and the ROC curves validated theresults obtained for the identification of different respiratory patterns. We investigated the use of correntropy for the spectral characterization of respiratory patterns in CHF patients. The correntropy function accounts for higher-order moments and is robust to outliers. Due to the former property, the respiratory and modulationfrequencies appear at their actual locations along the frequency axis in the correntropy spectral density (CSD). The best results were achieved with correntropy and CSD-related parameters that characterized the power in the modulation and respiration discriminant bands, definedas a frequency interval centred on the modulation and respiration frequency peaks,respectively. All patients, i.e. both PB and nPB, exhibit various degrees of periodicitydepending on their condition, whereas healthy subjects have no pronounced periodicity.This fact led to excellent results classifying PB and nPB patients 88.9%, CHF versushealthy 95.2%, and nPB versus healthy 94.4% with only one parameter.Postprint (published version

The (human) respiratory rate at rest

All schoolchildren know how often they breathe, but even experts don't know exactly why. The aim of this publication is to develop a model of the resting spontaneous breathing rate using physiological, physical and mathematical methods with the aid of the principle that evolution pushes physiology in a direction that is as economical as possible. The respiratory rate then follows from an equation with the parameters CO2-production rate of the organism, resistance, static compliance and dead space of the lungs, the inspiration duration: expiration duration - ratio and the end-expiratory CO2 fraction. The derivation requires exclusively secondary school mathematics. Using the example of an adult human or a newborn child, data from the literature then result in normal values for their breathing rate at rest. The reason for the higher respiratory rate of a newborn human compared to an adult is the relatively high CO2-production rate together with the comparatively low compliance of the lungs. A side result is the fact that the common alveolar pressure throughout the lungs and the common time constant is a consequence of the economical principle as well. Since the above parameters are not human-specific, there is no reason to assume that the above equation could not also be applicable to many animals breathing through lungs within a thorax, especially mammals. Not only physiology and biology, but also medicine, could benefit: Applicability is being discussed in pulmonary function diagnostics, including pathophysiology. However, the present publication only claims to be a theoretical concept for the spontaneous quiet breathing rate. In the absence of comparable animal data, this publication is intended to encourage further scientific tests.Comment: 41 pages, 6 figures, 4 table

Modeling, Simulation, And Visualization Of 3d Lung Dynamics

Medical simulation has facilitated the understanding of complex biological phenomenon through its inherent explanatory power. It is a critical component for planning clinical interventions and analyzing its effect on a human subject. The success of medical simulation is evidenced by the fact that over one third of all medical schools in the United States augment their teaching curricula using patient simulators. Medical simulators present combat medics and emergency providers with video-based descriptions of patient symptoms along with step-by-step instructions on clinical procedures that alleviate the patient\u27s condition. Recent advances in clinical imaging technology have led to an effective medical visualization by coupling medical simulations with patient-specific anatomical models and their physically and physiologically realistic organ deformation. 3D physically-based deformable lung models obtained from a human subject are tools for representing regional lung structure and function analysis. Static imaging techniques such as Magnetic Resonance Imaging (MRI), Chest x-rays, and Computed Tomography (CT) are conventionally used to estimate the extent of pulmonary disease and to establish available courses for clinical intervention. The predictive accuracy and evaluative strength of the static imaging techniques may be augmented by improved computer technologies and graphical rendering techniques that can transform these static images into dynamic representations of subject specific organ deformations. By creating physically based 3D simulation and visualization, 3D deformable models obtained from subject-specific lung images will better represent lung structure and function. Variations in overall lung deformations may indicate tissue pathologies, thus 3D visualization of functioning lungs may also provide a visual tool to current diagnostic methods. The feasibility of medical visualization using static 3D lungs as an effective tool for endotracheal intubation was previously shown using Augmented Reality (AR) based techniques in one of the several research efforts at the Optical Diagnostics and Applications Laboratory (ODALAB). This research effort also shed light on the potential usage of coupling such medical visualization with dynamic 3D lungs. The purpose of this dissertation is to develop 3D deformable lung models, which are developed from subject-specific high resolution CT data and can be visualized using the AR based environment. A review of the literature illustrates that the techniques for modeling real-time 3D lung dynamics can be roughly grouped into two categories: Geometrically-based and Physically-based. Additional classifications would include considering a 3D lung model as either a volumetric or surface model, modeling the lungs as either a single-compartment or a multi-compartment, modeling either the air-blood interaction or the air-blood-tissue interaction, and considering either a normal or pathophysical behavior of lungs. Validating the simulated lung dynamics is a complex problem and has been previously approached by tracking a set of landmarks on the CT images. An area that needs to be explored is the relationship between the choice of the deformation method for the 3D lung dynamics and its visualization framework. Constraints on the choice of the deformation method and the 3D model resolution arise from the visualization framework. Such constraints of our interest are the real-time requirement and the level of interaction required with the 3D lung models. The work presented here discusses a framework that facilitates a physics-based and physiology-based deformation of a single-compartment surface lung model that maintains the frame-rate requirements of the visualization system. The framework presented here is part of several research efforts at ODALab for developing an AR based medical visualization framework. The framework consists of 3 components, (i) modeling the Pressure-Volume (PV) relation, (ii) modeling the lung deformation using a Green\u27s function based deformation operator, and (iii) optimizing the deformation using state-of-art Graphics Processing Units (GPU). The validation of the results obtained in the first two modeling steps is also discussed for normal human subjects. Disease states such as Pneumothorax and lung tumors are modeled using the proposed deformation method. Additionally, a method to synchronize the instantiations of the deformation across a network is also discussed

Hot-thermistor spirometry for the artificial ventilation of infants

Bibliography: leaves 230-245.This thesis describes equipment and techniques which were developed for use in monitoring mechanical aspects of artificial ventilation and optimising ventilation procedures. A strong emphasis is placed on the clinical applicability of the techniques and clinical applications are discussed. A new temperature-compensated hot-thermistor anemometer/spirometer was developed because the wide variety of spirometers described previously for-measuring respiratory volumes •and volume flow rates were unsatisfactory for routine use in monitoring infant ventilation. The principles of hot-thermistor spirometry were investigated both theoretically and experimental.ly to develop new temperature-compensation techniques and to predict the effect of gas composition changes on spirometer celebration. New electronic circuits were developed which greatly simplify the construction of temperature-compensated hot- thermistor anemometers and extend the dynamic range off low rates that can be measured

Physiology-based Mathematical Models for the Intensive Care Unit: Application to Mechanical Ventilation

This work takes us a step closer to realizing personalized medicine, complementing empirical and heuristic way in which clinicians typically work. This thesis presents mechanistic models of physiology. These models, given continuous signals from a patient, can be fine-tuned via parameter estimation methods so that the model's outputs match the patient's. We thus obtain a virtual patient mimicking the patient at hand. Therapeutic scenarios can then be applied and optimal diagnosis and therapy can thus be attained. As such, personalized medicine can then be achieved without resorting to costly genetics. In particular we have developed a novel comprehensive mathematical model of the cardiopulmonary system that includes cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control. Validity of the model was proven by the excellent agreement with real patient data, under normo-physiological as well as hypercapnic and hypoxic conditions, taken from literature. As a concrete example, a submodel of the lung mechanics was fine-tuned using real patient data and personalized respiratory parameters (resistance, R_rs, and compliance, C_rs) were estimated continually. This allows us to compute the patient's effort (Work of Breathing), continuously and more importantly noninvasively. Finally, the use of Bayesian estimation techniques, which allow incorporation of population studies and prior information about model's parameters, was proposed in the contest of patient-specific physiological models. A Bayesian Maximum a Posteriori Probability (MAP) estimator was implemented and applied to a case-study of respiratory mechanics. Its superiority against the classical Least Squares method was proven in data-poor conditions using both simulated and real animal data. This thesis can serve as a platform for a plethora of applications for cardiopulmonary personalized medicine

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 182, July 1978

This bibliography lists 165 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1978

A Systems Engineering Approach to Modeling and Analysis of Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by airflow limitation. This study develops a systems engineering framework for representing important mechanistic details of COPD in a model of the cardio-respiratory system. In this model, we present the cardio-respiratory system as an integrated biological control system responsible for regulating breathing. Four engineering control system components are considered: sensor, controller, actuator, and the process itself. Knowledge of human anatomy and physiology is used to develop appropriate mechanistic mathematical models for each component. Following a systematic analysis of the computational model, we identify three physiological parameters associated with reproducing clinical manifestations of COPD - changes in the forced expiratory volume (FEV), lung volumes, and pulmonary hypertension. We quantify the changes in these parameters (airway resistance, lung elastance, and pulmonary resistance) as the ones that result in a systemic response that is diagnostic of COPD. A multivariate analysis reveals that the changes in airway resistance have a broad impact on the human cardio-respiratory system, and that the pulmonary circuit is stressed beyond normal under hypoxic environments in most COPD patients.Comment: 25 pages, 15 figure