Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

BACKGROUND: Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. RESULTS: Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. CONCLUSION: We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

High Flow Nasal Cannula compared to Continuous Positive Airway Pressure: a bench and physiological study.

High-flow nasal cannula (HFNC) is extensively used for acute respiratory failure. However, questions remain regarding its physiological effects. We explored 1) whether HFNC produced similar effects to continuous positive airway pressure (CPAP); 2) possible explanations of respiratory rate changes; 3) the effects of mouth opening. Two studies were conducted: a bench study using a manikin's head with lungs connected to a breathing simulator while delivering HFNC flow rates from 0 to 60L/min; a physiological cross-over study in 10 healthy volunteers receiving HFNC (20 to 60L/min) with the mouth open or closed and CPAP 4cmH2O delivered through face-mask. Nasopharyngeal and esophageal pressures were measured; tidal volume and flow were estimated using calibrated electrical impedance tomography. In the bench study, nasopharyngeal pressure at end-expiration reached 4cmH2O with HFNC at 60L/min, while tidal volume decreased with increasing flow. In volunteers with HFNC at 60L/min, nasopharyngeal pressure reached 6.8cmH2O with mouth closed and 0.8cmH2O with mouth open; p<0.001. When increasing HFNC flow, respiratory rate decreased by lengthening expiratory time, tidal volume did not change, and effort decreased (pressure-time product of the respiratory muscles); at 40L/min, effort was equivalent between CPAP and HFNC40L/min and became lower at 60L/min (p=0.045). During HFNC with mouth closed, and not during CPAP, resistance to breathing was increased, mostly during expiration. In conclusion, mouth closure during HFNC induces a positive nasopharyngeal pressure proportional to flow rate and an increase in expiratory resistance that might explain the prolonged expiration and reduction in respiratory rate and effort, and contribute to physiological benefits.

Non-invasive phrenic nerve stimulation to avoid ventilator-induced diaphragm dysfunction in critical care.

BACKGROUND: Diaphragm muscle atrophy during mechanical ventilation begins within 24 h and progresses rapidly with significant clinical consequences. Electrical stimulation of the phrenic nerves using invasive electrodes has shown promise in maintaining diaphragm condition by inducing intermittent diaphragm muscle contraction. However, the widespread application of these methods may be limited by their risks as well as the technical and environmental requirements of placement and care. Non-invasive stimulation would offer a valuable alternative method to maintain diaphragm health while overcoming these limitations. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. Respiratory pressure and flow, diaphragm electromyography and mechanomyography, and ultrasound visualization were used to assess the diaphragmatic response to stimulation. The electrode positions and stimulation parameters were systematically varied in order to investigate the influence of these parameters on the ability to induce diaphragm contraction with non-invasive stimulation. RESULTS: We demonstrate that non-invasive capture of the phrenic nerve is feasible using surface electrodes without the application of pressure, and characterize the stimulation parameters required to achieve therapeutic diaphragm contractions in healthy volunteers. We show that an optimal electrode position for phrenic nerve capture can be identified and that this position does not vary as head orientation is changed. The stimulation parameters required to produce a diaphragm response at this site are characterized and we show that burst stimulation above the activation threshold reliably produces diaphragm contractions sufficient to drive an inspired volume of over 600 ml, indicating the ability to produce significant diaphragmatic work using non-invasive stimulation. CONCLUSION: This opens the possibility of non-invasive systems, requiring minimal specialist skills to set up, for maintaining diaphragm function in the intensive care setting.

Impact of Reverse Triggering Dyssynchrony during Lung-Protective Ventilation on Diaphragm Function: An Experimental Model.

Rationale: Reverse triggering dyssynchrony (RT) is a patient-ventilator interaction where a respiratory muscle contraction is triggered by a passive mechanical insufflation. Its impact on diaphragm structure and function is unknown. Objectives: To establish an animal model of RT with lung injury receiving lung-protective ventilation and to assess its impact on the structure and function of the diaphragm. Methods: Lung injury was induced by surfactant depletion and high-stress ventilation in 32 ventilated pigs. Animals were allocated to receive passive mechanical ventilation (Vt: 10 ml/kg; respiratory rate [RR]: 30-35 breaths/min; n = 8) or a more lung-protective strategy (Vt: 6-8 ml/kg; n = 24) with adjustments in RR to facilitate the occurrence of RT for 3 hours. Diaphragm function (transdiaphragmatic pressure [Pdi] during phrenic nerve stimulation [force/frequency curve]) and structure (biopsies) were assessed. The impact of RT on diaphragm function was analyzed according to the breathing effort assessed by the pressure-time product. Measurements and Main Results: Compared with passive ventilation, the protective ventilation group with RT received significantly lower Vt (7 vs. 10 ml/kg) and higher RR (45 vs. 31 breaths/min). An entrainment pattern of 1:1 was the most frequently occurring in 83% of the animals. Breathing effort induced by RT was highly variable across animals. RT with the lowest tercile of breathing effort was associated with 23% higher twitch Pdi compared with passive ventilation, whereas RT with high breathing effort was associated with a 10% lower twitch Pdi and a higher proportion of abnormal muscle fibers. Conclusions: In a reproducible animal model of RT with variable levels of breathing effort and entrainment patterns, RT with high effort is associated with impaired diaphragm function, whereas RT with low effort is associated with preserved diaphragm force.

Acute lung injury secondary to hydrochloric acid instillation induces small airway hyperresponsiveness.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure characterized by altered lung mechanics and poor oxygenation. Bronchial hyperresponsiveness has been reported in ARDS survivors and animal models of acute lung injury. Whether this hyperreactivity occurs at the small airways or not is unknown. OBJECTIVE: To determine ex-vivo small airway reactivity in a rat model of acute lung injury (ALI) by hydrochloric acid (HCl) instillation. METHODS: Twelve anesthetized rats were connected to mechanical ventilation for 4-hour, and randomly allocated to either ALI group (HCl intratracheal instillation; n=6) or Sham (intratracheal instillation of 0.9% NaCl; n=6). Oxygenation was assessed by arterial blood gases. After euthanasia, tissue samples from the right lung were harvested for histologic analysis and wet-dry weight ratio assessment. Precision cut lung slice technique (100-200 µm diameter) was applied in the left lung to evaluate ex vivo small airway constriction in response to histamine and carbachol stimulation, using phase-contrast video microscopy. RESULTS: Rats from the ALI group exhibited hypoxemia, worse histologic lung injury, and increased lung wet-dry weight ratio as compared with the sham group. The bronchoconstrictor responsiveness was significantly higher in the ALI group, both for carbachol (maximal contraction of 84.5±2.5% versus 61.4±4.2% in the Sham group, P<0.05), and for histamine (maximal contraction of 78.6±5.3% versus 49.6±5.3% in the Sham group, P<0.05). CONCLUSION: In an animal model of acute lung injury secondary to HCL instillation, small airway hyperresponsiveness to carbachol and histamine is present. These results may provide further insight into the pathophysiology of ARDS.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation.

BACKGROUND: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. METHODS: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. RESULTS: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. CONCLUSIONS: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients.

BACKGROUND: In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity. METHODS: Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering. RESULTS: Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0-50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering. CONCLUSION: Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity. Trial Registration ClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

Disfunción Diafragmática en Ventilación Mecánica: Evaluación e Implicancias Clínicas / Diaphragmatic Dysfunction in Mechanical Ventilation: Evaluation and Clinical Implications

La debilidad diafragmática es un problema relevante en pacientes admitidos a la unidad de cuidados intensivos (UCI). Su presencia ha sido asociada a mayor tiempo en ventilación mecánica, weaning dificultoso, mayor riesgo de readmisión hospitalaria y mayor mortalidad. Las causas de esta debilidad son múltiples incluyendo factores relacionados a la severidad de la enfermedad, las intervenciones en la UCI y el uso de ventilación mecánica, termino conocido como miotrauma. Se han propuesto cuatro diferentes mecanismos de miotrauma relacionados a la sobre asistencia ventilatoria, baja asistencia ventilatoria, ocurrencia de contracciones diafragmáticas excéntricas y efecto de la presión espiratoria al final de espiración. Una adecuada evaluación y monitoreo de la función diafragmática es, por lo tanto, un aspecto clave que debe ser realizado al lado de la cama del paciente. La prueba de referencia para medir la función del diafragma es la presión transdiafragmática calculada como la diferencia entre la presión gástrica y presión esofágica. Adicionalmente, otras técnicas disponibles para la evaluación de la función del diafragma corresponden a la ecografía y la medición de la actividad eléctrica. Desde un punto de vista clínico, basado en la evidencia sobre disfunción diafragmática en los pacientes ventilados mecánicamente, uno de los principales desafíos actuales es poder buscar estrategias ventilatorias que incorporen protección diafragmática mientras se mantiene una ventilación protectora pulmonar. En este sentido, favorecer un nivel de esfuerzo inspiratorio adecuado junto con optimizar la interacción entre el paciente y el ventilador constituyen los principales objetivos de una ventilación diafragmática protectora.

Diaphragm weakness is a relevant problem in patients admitted to the intensive care unit (ICU). Its presence has been associated with prolonged mechanical ventilation, difficult weaning, higher risk of hospital readmission, and higher mortality. The causes of this weakness are multiple, including factors related to the severity of the disease, ICU interventions and the use of mechanical ventilation, a term known as myotrauma. Four different mechanisms of myotrauma have been proposed: 1. Ventilator over-assistance; 2. Ventilator under-assistance: 3. Eccentric diaphragm contractions: and 4. Excessive end-expiratory shortening by high PEEP. An adequate evaluation and monitoring of diaphragmatic function is, therefore, a key aspect that must be performed at the patient's bedside. The gold standard for measuring diaphragm function is transdiaphragmatic pressure calculated as the difference between gastric pressure and esophageal pressure. Furthermore, other techniques available for the evaluation of diaphragm function correspond to ultrasound and the measurement of its electrical activity. From a clinical point of view, based on diaphragmatic dysfunction evidence in mechanically ventilated patients, the main current challenge consists in applying ventilatory strategies that incorporate diaphragmatic protection while maintaining lung protective ventilation. In this sense, favoring an adequate level of inspiratory effort together with optimizing the interaction between the patient and the ventilator are the main objectives of diaphragm protective ventilation.

Low Spontaneous Breathing Effort during Extracorporeal Membrane Oxygenation in a Porcine Model of Severe Acute Respiratory Distress Syndrome.

BACKGROUND: A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. METHODS: Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. RESULTS: Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. CONCLUSIONS: In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.

Simple Wireless Impedance Pneumography System for Unobtrusive Sensing of Respiration.

This extended paper presents the development and implementation at a prototype level of a wireless, low-cost system for the measurement of the electrical bioimpedance of the chest with two channels using the AD5933 in a bipolar electrode configuration to measure impedance pneumography. The measurement device works for impedance measurements ranging from 1 Ω to 1800 Ω. Fifteen volunteers were measured with the prototype. We found that the left hemithorax has higher impedance compared to the right hemithorax, and the acquired signal presents the phases of the respiratory cycle with variations between 1 Ω, in normal breathing, to 6 Ω in maximum inhalation events. The system can measure the respiratory cycle variations simultaneously in both hemithorax with a mean error of -0.18 ± 1.42 BPM (breaths per minute) in the right hemithorax and -0.52 ± 1.31 BPM for the left hemithorax, constituting a useful device for the breathing rate calculation and possible screening applications.

Early rise in central venous pressure during a spontaneous breathing trial: A promising test to identify patients at high risk of weaning failure?

BACKGROUND: The spontaneous breathing trial (SBT) assesses the risk of weaning failure by evaluating some physiological responses to the massive venous return increase imposed by discontinuing positive pressure ventilation. This trial can be very demanding for some critically ill patients, inducing excessive physical and cardiovascular stress, including muscle fatigue, heart ischemia and eventually cardiac dysfunction. Extubation failure with emergency reintubation is a serious adverse consequence of a failed weaning process. Some data suggest that as many as 50% of patients that fail weaning do so because of cardiac dysfunction. Unfortunately, monitoring cardiovascular function at the time of the SBT is complex. The aim of our study was to explore if central venous pressure (CVP) changes were related to weaning failure after starting an SBT. We hypothesized that an early rise on CVP could signal a cardiac failure when handling a massive increase on venous return following a discontinuation of positive pressure ventilation. This CVP rise could identify a subset of patients at high risk for extubation failure. METHODS: Two-hundred and four mechanically ventilated patients in whom an SBT was decided were subjected to a monitoring protocol that included blinded assessment of CVP at baseline, and at 2 minutes after starting the trial (CVP-test). Weaning failure was defined as reintubation within 48-hours following extubation. Comparisons between two parametric or non-parametric variables were performed with student T test or Mann Whitney U test, respectively. A logistic multivariate regression was performed to determine the predictive value on extubation failure of usual clinical variables and CVP at 2-min after starting the SBT. RESULTS: One-hundred and sixty-five patients were extubated after the SBT, 11 of whom were reintubated within 48h. Absolute CVP values at 2-minutes, and the change from baseline (dCVP) were significantly higher in patients with extubation failure as compared to those successfully weaned. dCVP was an early predictor for reintubation (OR: 1.70 [1.31,2.19], p<0.001). CONCLUSIONS: An early rise in CVP after starting an SBT was associated with an increased risk of extubation failure. This might represent a warning signal not captured by usual SBT monitoring and could have relevant clinical implications.

Estrategia metodológica para enseñar innovación en estudiantes de cinesiología / A methodological strategy to teach innovation in Kinesiology students

Introducción: Se realiza una adaptación del design thinking para enseñar innovación a estudiantes de cinesiología. Sujetos y métodos: Se utiliza un diseño cuasiexperimental con pre y postest y dos grupos de tratamiento evaluados con un cuestionario que mide la percepción de capacidad en habilidades para innovar. Resultados: Se obtuvieron diferencias significativas en ambos grupos con aumento en el postest. Conclusiones: La estrategia muestra un efecto importante sobre la calidad de los proyectos, la percepción de dominio y de capacidad para innovar

Introduction: This paper do an adaptation of design thinking methodology to teach innovation to Kinesiology students. Subjects and methods: It use a quasi-experimental design with pre and post-test, and two treatment groups evaluated with a questionnaire that measures capacity in innovation skills perception. Results: Shows statistically significant differences between the groups with an increase in the post-test. Conclusions: The strategy shows an important effect in the project quality, the domain perception and the perceived capacity to innovate

Cardiovascular Action of Insulin in Health and Disease: Endothelial L-Arginine Transport and Cardiac Voltage-Dependent Potassium Channels.

Impairment of insulin signaling on diabetes mellitus has been related to cardiovascular dysfunction, heart failure, and sudden death. In human endothelium, cationic amino acid transporter 1 (hCAT-1) is related to the synthesis of nitric oxide (NO) and insulin has a vascular effect in endothelial cells through a signaling pathway that involves increases in hCAT-1 expression and L-arginine transport. This mechanism is disrupted in diabetes, a phenomenon potentiated by excessive accumulation of reactive oxygen species (ROS), which contribute to lower availability of NO and endothelial dysfunction. On the other hand, electrical remodeling in cardiomyocytes is considered a key factor in heart failure progression associated to diabetes mellitus. This generates a challenge to understand the specific role of insulin and the pathways involved in cardiac function. Studies on isolated mammalian cardiomyocytes have shown prolongated action potential in ventricular repolarization phase that produces a long QT interval, which is well explained by attenuation in the repolarizing potassium currents in cardiac ventricles. Impaired insulin signaling causes specific changes in these currents, such a decrease amplitude of the transient outward K(+) (Ito) and the ultra-rapid delayed rectifier (IKur) currents where, together, a reduction of mRNA and protein expression levels of α-subunits (Ito, fast; Kv 4.2 and IKs; Kv 1.5) or ß-subunits (KChIP2 and MiRP) of K(+) channels involved in these currents in a MAPK mediated pathway process have been described. These results support the hypothesis that lack of insulin signaling can produce an abnormal repolarization in cardiomyocytes. Furthermore, the arrhythmogenic potential due to reduced Ito current can contribute to an increase in the incidence of sudden death in heart failure. This review aims to show, based on pathophysiological models, the regulatory function that would have insulin in vascular system and in cardiac electrophysiology.