Using intra-breath oscillometry in obesity hypoventilation syndrome to detect tidal expiratory flow limitation: a potential marker to optimize CPAP therapy.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy has profound effects in obesity hypoventilation syndrome (OHS). Current therapy initiation focuses on upper airway patency rather than the assessment of altered respiratory mechanics due to increased extrapulmonary mechanical load. METHODS: We aimed to examine the viability of intra-breath oscillometry in optimizing CPAP therapy for OHS. We performed intra-breath oscillometry at 10 Hz in the sitting and supine positions, followed by measurements at increasing CPAP levels (none-5-10-15-20 cmH2O) in awake OHS patients. We plotted intra-breath resistance and reactance (Xrs) values against flow (V') and volume (V) to identify tidal expiratory flow limitation (tEFL). RESULTS: Thirty-five patients (65.7% male) completed the study. We found a characteristic looping of the Xrs vs V' plot in all patients in the supine position revealing tEFL: Xrs fell with decreasing flow at end-expiration. Intra-breath variables representing expiratory decrease of Xrs became more negative in the supine position [end-expiratory Xrs (mean ± SD): -1.9 ± 1.8 cmH2O·s·L- 1 sitting vs. -4.2 ± 2.2 cmH2O·s·L- 1 supine; difference between end-expiratory and end-inspiratory Xrs: -1.3 ± 1.7 cmH2O·s·L- 1 sitting vs. -3.6 ± 2.0 cmH2O·s·L- 1 supine, p < 0.001]. Increasing CPAP altered expiratory Xrs values and loop areas, suggesting diminished tEFL (p < 0.001). 'Optimal CPAP' value (able to cease tEFL) was 14.8 ± 4.1 cmH2O in our cohort, close to the long-term support average of 13.01(± 2.97) cmH2O but not correlated. We found no correlation between forced spirometry values, patient characteristics, apnea-hypopnea index and intra-breath oscillometry variables. CONCLUSIONS: tEFL, worsened by the supine position, can be diminished by stepwise CPAP application in most patients. Intra-breath oscillometry is a viable method to detect tEFL during CPAP initiation in OHS patients and tEFL is a possible target for optimizing therapy in OHS patients.

Exploring red cell distribution width as a biomarker for treatment efficacy in home mechanical ventilation.

BACKGROUND: With the growing practice of home mechanical ventilation, there is a need to identify biological markers for adequate follow-up. Red cell distribution width (RDW) is a promising candidate because it is convenient, objective and may reflect treatment effect over a long period of time. The aim of this study was to explore the possible role of RDW as a marker for home mechanical ventilation in real-life, unselected chronic respiratory patient populations. METHODS: First, we identified characteristic RDW values for mixed case, unselected chronic respiratory failure and home mechanical ventilated patients through retrospective review within our institutional database. Next, we conducted a prospective observational study to identify RDW changes during the first six months of optimized home mechanical ventilation treatment. Adult patients starting home mechanical ventilation were included. Factors affecting RDW change during the first 6 months of treatment were analysed. RESULTS: RDW was elevated in both chronic respiratory failure and home mechanical ventilation patients compared to healthy individuals in the retrospective review. In the prospective study of 70 patients, we found that 55.4% of patients starting home mechanical ventilation have abnormal RDW values which are reduced from 14.7 (IQR = 13.2-16.2)% to 13.5 (IQR = 13.1-14.6)% during the first 6 months of HMV treatment (p < 0.001). RDW improvement correlates with improvement in self-reported health-related quality of life and sleepiness scale scores, as well as physical functional status during the same time frame. RDW proved to be a comparable marker to other parameters traditionally used to evaluate treatment efficacy. CONCLUSIONS: RDW is elevated in chronic respiratory failure patients and is significantly reduced in the first six months of optimized home mechanical ventilation. Although further research is needed to verify if RDW change reflects outcome and how comorbidities influence RDW values, our results suggest that RDW is a promising marker of home mechanical ventilation efficacy. Trial registration This study was approved by and registered at the ethics committee of Semmelweis University (TUKEB 250/2017 and TUKEB 250-1/2017, 20th of December 2017 and 1st of October 2019).

Home mechanical ventilation: quality of life patterns after six months of treatment.

BACKGROUND: It has been shown that home mechanical ventilation improves quality of life, but it has not been widely studied which particular patient groups benefit the most from starting this type of therapy. The purpose of this prospective observational study was to evaluate quality of life change patterns 6 months after initiation of home mechanical ventilation in patients suffering from chronic respiratory failure using patient reported outcomes. METHODS: We enrolled 74 chronic respiratory failure patients starting invasive or noninvasive home mechanical ventilation through the Semmelweis University Home Mechanical Ventilation Program. Quality of life was evaluated at baseline and at 6 months after initiation of home mechanical ventilation using the Severe Respiratory Insufficiency Questionnaire. RESULTS: Overall quality of life showed 10.5% improvement 6 months after initiation of home mechanical ventilation (p < 0.001). The greatest improvement was observed in Respiratory complaint (20.4%, p = 0.015), Sleep and attendant symptoms (19.3%, p < 0.001), and Anxiety related subscales (14.4%, p < 0.001). Interface (invasive versus noninvasive ventilation) was not associated with improvement in quality of life (p = 0.660). Severely impaired patients showed the greatest improvement (CC = -0.328, p < 0.001). Initial diagnosis contributed to the observed change (p = 0.025), with chronic obstructive pulmonary disease and obesity hypoventilation syndrome patients showing the greatest improvement, while amyotrophic lateral sclerosis patients showed no improvement in quality of life. We found that patients who were started on long term ventilation in an acute setting, required oxygen supplementation and had low baseline quality of life, showed the most improvement during the six-month study period. CONCLUSIONS: Our study highlights the profound effect of home mechanical ventilation on quality of life in chronic respiratory failure patients that is indifferent of ventilation interface but is dependent on initial diagnosis and some baseline characteristics, like acute initiation, oxygen supplementation need and baseline quality of life. TRIAL REGISTRATION: This study was approved by and registered at the ethics committee of Semmelweis University (SE TUKEB 251/2017; 20th of December, 2017).

Validation of the Hungarian version of the SRI Questionnaire.

BACKGROUND: Home mechanical ventilation is a reliable treatment for patients suffering from chronic respiratory failure, improving survival and quality of life. Prevalence has been increasing worldwide as a result of evolving technical possibilities, telemedicine and improving national guidelines. Projects to establish a national guideline and registry for patients treated with home mechanical ventilation are currently under way in Hungary and our aim was to validate a quality of life questionnaire suited for evaluation and follow up in this specific patient group. The Severe Respiratory Insufficiency Questionnaire (SRI) is a quality of life tool designed to evaluate patients receiving home mechanical ventilation and has been validated both in patient groups receiving invasive and noninvasive ventilation. METHODS: The Hungarian version of the SRI was created using the translation-backtranslation method, which was then tested for validity, viability and reliability in a cohort involving patients from three centers, receiving long-term home mechanical ventilation for chronic respiratory failure through an invasive or noninvasive interface. Patient data was collected (demographic data, lung function test, arterial blood gas, ventilation settings) and quality of life was measured with the previously validated SF-36 and newly created Hungarian SRI Questionnaires at two time points. RESULTS: One hundred four patients receiving home mechanical ventilation were enrolled. The time to complete the SRI Questionnaire was 8.6 (±3.1) minutes, 69.2% questionnaires were self-administered. Exploratory factor analysis explained 73.8% of the variance of the questionnaire, but resulted in 13 scales. We found correlations between the SRI subscale scores to corresponding scales of the previously validated general quality of life survey SF-36. The Cronbach alpha coefficient was 0.928 for the Summary Scale of the SRI Questionnaire, proving high internal consistency. Reproducibility was high for most scales, resulting in a high overall correlation for the summary score (0.877, p < 0.001). CONCLUSIONS: The Hungarian version of the SRI Questionnaire is a viable, valid, reliable and reproduceable quality of life tool applicable for patients treated with home mechanical ventilation.

National survey: current prevalence and characteristics of home mechanical ventilation in Hungary.

BACKGROUND: Home mechanical ventilation is an established treatment for chronic respiratory failure resulting in improved survival and quality of life. Technological advancement, evolving health care reimbursement systems and newly implemented national guidelines result in increased utilization worldwide. Prevalence shows great geographical variations and data on East-Central European practice has been scarce to date. The aim of the current study was to evaluate prevalence and characteristics of home mechanical ventilation in Hungary. METHODS: We conducted a nationwide study using an online survey focusing on patients receiving ventilatory support at home. The survey focused on characterization of the site (affiliation, type), experience with home mechanical ventilation, number of patients treated, indication for home mechanical ventilation (disease type), description of home mechanical ventilation (invasive/noninvasive, ventilation hours, duration of ventilation) and description of the care provided (type of follow up visits, hospitalization need, reimbursement). RESULTS: Our survey uncovered a total of 384 patients amounting to a prevalence of 3.9/100,000 in Hungary. 10.4% of patients received invasive, while 89.6% received noninvasive ventilation. The most frequent diagnosis was central hypopnea syndromes (60%), while pulmonary (20%), neuromuscular (11%) and chest wall disorders (7%) were less frequent indications. Daily ventilation need was less than 8 h in 74.2%, between 8 and 16 h in 15.4% and more than 16 h in 10.4% of patients reported. When comparing sites with a limited (< 50 patients) versus substantial (> 50 patients) case number, we found the former had significantly higher ratio of neuromuscular conditions, were more likely to ventilate invasively, with more than 16 h/day ventilation need and were more likely to provide home visits and readmit patients (p < 0,001). CONCLUSIONS: Our results show a reasonable current estimate and characterization of home mechanical ventilation practice in Hungary. Although a growing practice can be assumed, current prevalence is still markedly reduced compared to international data reported, the duality of current data hinting to a possible gap in diagnosis and care for more dependent patients. This points to the importance of establishing home mechanical ventilation centers, where increased experience will enable state of the art care to more dependent patients as well, increasing overall prevalence.

[Use of noninvasive ventilation in critically ill patients]. / Nem invazív lélegeztetés alkalmazása kritikus állapotú betegekben.

INTRODUCTION: The use of noninvasive ventilation has increased worldwide. Its mortality reducing benefit has been shown in several different conditions compared to invasive ventilation. Common counterarguments against the technique are its increased technical and caregiver requirements and increased mortality associated with treatment failure. AIM: The aim of our work was to describe our experiences with noninvasive ventilation in the intensive care unit. METHOD: We reviewed patient data from the Respiratory Intensive Care unit of Semmelweis University operated from 2014 to 2016. Statistical analysis was performed by Mann-Whitney U test and Z-test; odds ratio was calculated with χ-square test. RESULTS: Out of the 301 patients analyzed, 147 received noninvasive ventilation. Noninvasive failure rate was 24.5%. The highest failure rate was associated with immunodeficiency associated pneumonia, interstitial lung disease and pneumonia (71.4%, 33.3% and 31.6%), while noninvasive ventilation was the most successful in cardiogenic pulmonary edema and hypercapnic respiratory failure (0 and 16.7% failure rate). Treatment failure was associated with significantly higher mortality (33.3%) compared to patients initially ventilated invasively (24.5%) and patients successfully treated with noninvasive ventilation (3.6%), resulting in a 2.65-fold mortality increase in invasively ventilated patients (OR = 2.65, 95% CI = 1.305-5.374, p = 0.009), and a 13.33-fold mortality increase in noninvasive failure patients (OR = 13.33; 95% CI 3.278-54.238; p<0.001). Outcome scores did not predict noninvasive failure. CONCLUSION: Noninvasive ventilation is a widely used, effective treatment mode which can improve the outcome in certain diseases compared to invasive ventilation. Noninvasive ventilation in incorrect indications could, however, lead to increased failure rates and mortality. Orv Hetil. 2018; 159(45): 1831-1837.

Prevalence of suspected obesity hypoventilation syndrome in Hungarian Intensive Care Units during the COVID-19 pandemic.

INTRODUCTION: The symptoms of obesity hypoventilation syndrome (OHS) may be present for years with concomitant progressive comorbidities, and the condition is frequently diagnosed late as a result of acute-on-chronic hypercapnic respiratory failure. Although some data exist on intensive care unit (ICU) prevalence, mortality and morbidity of OHS, little is known about the ICU mortality of these chronic respiratory failure patients during the COVID-19 pandemic. METHODS: We performed a cross-sectional observational study in five Hungarian Intensive Care Units for 4 months during the COVID-19 pandemic. All ICU patients were screened for OHS risk factors by treating physicians. Risk factors were defined as obesity (body mass index [BMI] ≥ 30 kg/m2 ) and at least one of the following: Epworth Sleepiness Score ≥ 6; symptoms of right heart failure; daytime or night-time hypoxemia; presence of loud snoring; witnessed apnoea. We calculated prevalence, mortality and factors associated with unfavourable outcome. RESULTS: A total of 904 ICU patients were screened for OHS risk factors. Overall 79 (8.74 ± 5.53%) patients were reported to have met the criteria for suspected OHS with a mortality rate of 40.5%; 69% (54 patients) of the cohort displayed at least 3 symptoms related to OHS before their acute illness. COVID-19 infection was associated with higher mortality in OHS-suspected patients, independently of actual BMI. CONCLUSION: Despite the increased risk of obese patients, suspected OHS did not show higher prevalence than expected during the COVID-19 pandemic in critically ill patients. COVID-19 infection however was a risk for mortality in these patients, independent of actual BMI.

Implementation of a Comprehensive Testing Protocol for a Rapidly Manufactured Mechanical Ventilator.

Introduction: The COVID-19 pandemic highlighted that surges in critical care demand can overwhelm existing healthcare infrastructures, most evident in the acute shortage of mechanical ventilators across the globe. Despite efforts to encourage urgent authorization of newly developed emergency ventilators, the currently available testing protocols are not internationally accepted, standardized and none address testing in clinical settings. The aim of this study was to compile and perform a comprehensive clinical testing protocol for a newly developed emergency ventilator. Methods: Using previously available guidance, we compiled a sequential testing protocol with a: 1. preclinical, 2. safety testing, 3. clinician usability test and 4. clinical stage involving respiratory failure patients. The protocol was then tested on the Luca ventilator, a mechanical ventilator capable of sophisticated ventilator settings rapidly developed specifically in response to the COVID-19 pandemic. Results: During the pre-clinical/safety stages, the ventilator produced pressure and volume changes deemed acceptable by the Rapidly Manufactured Ventilator System guideline. Furthermore, our protocol allowed the identification of a number of issues that were easily resolved with minor software adjustments. Usability was excellent (overall System Usability Scale score = 90.5). Clinical testing revealed that a sampling frame of 15 critically ill patients was sufficiently powered to detect any significant, clinically relevant differences between the Luca ventilator and a standard ICU ventilator. Conclusions: The ventilator was accurate, reliable, safe, and user-friendly. The implementation of a comprehensive, standardized pre-clinical/clinical testing protocol is feasible, potentially enabling the safe and timely emergency authorization of rapidly developed mechanical ventilators crucial in pandemic situations.

Introducción: La pandemia de COVID-19 ha puesto de manifiesto que las sobrecargas en los cuidados intensivos pueden desbordar las infraestructuras sanitarias existentes, que fue evidente en la escasez inmediata de respiradores mecánicos observada en todo el mundo. A pesar de las tentativas de alentar la autorización urgente de respiradores de emergencia recién desarrollados, los protocolos de ensayos existentes no están aceptados en todo el mundo, no están normalizados y ninguno trata los ensayos en entornos clínicos. El objetivo de este estudio fue recopilar y ejecutar un protocolo de ensayos clínicos exhaustivo para un respirador de emergencia recién desarrollado. Métodos: Aplicando las directrices previas recopilamos un protocolo secuencial de ensayos con: 1. estudio preclínico, 2. estudio de seguridad, 3. ensayo de operabilidad por los facultativos y 4. fase clínica con participación de pacientes con insuficiencia respiratoria. Se analizó el protocolo con el respirador Luca, un respirador mecánico con configuraciones sofisticadas desarrollado rápida y específicamente para responder a la pandemia de la COVID-19. Resultados: Durante las fases preclínicas/de seguridad, los cambios de presión y volumen que produjo el respirador se consideraron aceptables, según la directriz Rapidly Manufactured Ventilator System. Asimismo, nuestro protocolo permitió identificar varios problemas que se resolvieron fácilmente con mínimos ajustes de software. La operabilidad resultó excelente (puntuación total de la escala de operabilidad del sistema = 90,5). Los ensayos clínicos revelaron que una muestra de 15 pacientes graves presentaba suficiente potencia estadística para detectar todas las diferencias significativas de interés clínico entre el respirador Luca y uno de Unidad de Cuidados Intensivos ordinario. Conclusiones: El respirador resultó exacto, fiable, seguro y fácil de usar. La implantación de un protocolo de ensayos preclínicos y clínicos exhaustivo y normalizado es factible y puede habilitar la autorización de emergencia oportuna de respiradores mecánicos de desarrollo rápido, cruciales en situaciones pandémicas.