Assessing breathing effort by barometric whole-body plethysmography and its relationship with prognosis in client-owned cats with respiratory distress.

BACKGROUND: Cats in respiratory distress have limited tolerance for manipulation, hindering clinical monitoring. Minute volume (MV) can be utilized to rate dyspnea in humans, but its relationship with respiratory distress in cats remains poorly investigated. HYPOTHESIS: Cats with respiratory distress will show higher MV per kg body weight (MV/BW) than normal cats, and the MV/BW increase will correlate with survival. ANIMALS: Fifty-two cats with respiratory distress from lung parenchymal disease, pleural space disease, lower airway obstruction (LAO), or upper airway obstruction were recruited since 2014. METHODS: This is a prospective observational study. Study cats were placed in a transparent chamber, allowing clinicians to easily observe their breathing status and record ventilation using barometric whole-body plethysmography (BWBP). Ventilatory variables of the 52 cats were compared with those of 14 historic control cats. Follow-up data, including disease category, clinical outcomes, and survival, were prospectively collected. RESULTS: Cats in respiratory distress demonstrated significantly higher MV/BW (397 mL/kg; range, 158-1240) than normal cats (269 mL/kg; range, 168-389; P < .001). Among the etiologies, cats with LAO, parenchymal, and pleural space disease exhibited higher-than-normal MV/BW trends. A cutoff value of 373 mL/kg (1.4-fold increase) indicated abnormally increased breathing efforts (sensitivity, 67%; specificity, 93%). MV/BW was independently associated with increased cardiorespiratory mortality in cats with respiratory distress (adjusted hazard ratio 1.17, 95% confidence interval [CI] 1.02-1.35; P = .03). CONCLUSIONS AND CLINICAL IMPORTANCE: Breathing efforts in cats can be noninvasively quantified using BWBP. Measurement of MV/BW could serve as a prognostic index for monitoring cats experiencing respiratory distress.

LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis.

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.

Quantifiable features of a tidal breathing phenotype in dogs with severe bronchomalacia diagnosed by bronchoscopy.

Dynamic lower airway obstruction is the primary component of canine bronchomalacia, but the ventilatory function remains underinvestigated. This prospective study analyzed tidal breathing characteristics in 28 dogs, comprising 14 with severe bronchomalacia diagnosed by bronchoscopy versus 14 without respiratory disease. Spirometry was conducted in all dogs. Bronchoscopy with bronchoalveolar lavage or brush under anesthesia was performed in 14 dogs with cough and expiratory effort. Severe bronchomalacia was defined by the severity of collapse and total number of bronchi affected. Ventilatory characteristics were compared between groups. Results revealed that dogs with severe bronchomalacia had lower minute volume (218 vs 338 mL/kg, p = .039) and greater expiratory-to-inspiratory time ratio (1.55 vs 1.35, p = .01) compared to control dogs. The tidal breathing pattern of dogs with bronchomalacia was different from that of normal dogs, and the pattern differed from the concave or flat expiratory curves typical of lower airway obstruction. Compared to control dogs, dogs with severe bronchomalacia had a significantly prolonged low-flow expiratory phase (p < .001) on the flow-time plot and a more exponential shape of the expiratory curve (p < .001) on the volume-time plot. Flow-time index ExpLF/Te (>0.14) and volume-time index Vt-AUCexp (≤31%) had a high ROC-AUC (1.00, 95% confidence interval 0.88 to 1.00) in predicting severe bronchomalacia. In conclusion, the tidal breathing pattern identified here indicates abnormal and complicated ventilatory mechanics in dogs with severe bronchomalacia. The role of this pulmonary functional phenotype should be investigated for disease progression and therapeutic monitoring in canine bronchomalacia.

Automatic tube compensation for liberation from prolonged mechanical ventilation in tracheostomized patients: A retrospective analysis.

BACKGROUND: To analyze the predictability of an automatic tube compensation (ATC) screening test compared with the conventional direct liberation test performed before continuous oxygen support for MV liberation. METHODS: This retrospective study analyzed tracheostomized patients with prolonged MV in a weaning unit of a medical center in Taiwan. In March 2020, a four-day ATC test to screen patient eligibility for ventilator liberation was implemented, intended to replace the direct liberation test. We compared the predictive accuracy of these two screening methods on the relevant outcomes in the two years before and one year after the implementation of this policy. RESULTS: Of the 403 cases, 246 (61%) and 157 (39%) received direct liberation and ATC screening tests, respectively. These two groups had similar outcomes: successful weaning upon leaving the Respiratory Care Center (RCC), success on day 100 of MV, success at hospital discharge, and in-hospital survival. Receiver operating characteristic curve analysis showed that the ATC screening test had better predictive ability than the direct liberation test for RCC weaning, discharge weaning, 100-day weaning, and in-hospital survival. CONCLUSION: This closed-circuit ATC screening test before ventilator liberation is a feasible and valuable method for screening PMV patients undergoing ventilator liberation in the pandemic era. Its predictability for a comparison with the open-circuit oxygen test requires further investigation.

Impact of ventilator settings during venovenous extracorporeal membrane oxygenation on clinical outcomes in influenza-associated acute respiratory distress syndrome: a multicenter retrospective cohort study.

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown. Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes. Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs. 12 breaths/min, p = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p = 0.034). Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population.

Safety and efficacy of vacuum bottle plus catheter for drainage of iatrogenic pneumothorax.

BACKGROUND: Iatrogenic pneumothorax is common after thoracic procedures. For patients with pneumothorax larger than 15%, simple aspiration is suggested. Although vacuum bottle plus non-tunneled catheter drainage has been performed in many institutions, its safety and efficacy remain to be assessed. METHODS: Through this prospective cohort study (NCT03724721), we evaluated the safety and efficacy of vacuum bottle plus non-tunneled catheter drainage. Patients older than 20 years old who developed post-procedural pneumothorax were enrolled. A non-tunneled catheter was placed at the intersection of the midclavicular line and the second intercostal space. A 3-way stopcock, a drainage set, and a digital pressure gauge were connected. The stopcock was manipulated to connect the pleural space to the pressure gauge for measurement of end-expiration intrapleural pressure or to the vacuum bottle for air drainage. The rate of successful drainage, the end-expiration intrapleural pressure before, during, and after the procedure and the duration of hospitalization were recorded. RESULTS: From August 2018 to February 2020, 21 patients underwent vacuum bottle plus catheter drainage (intervention group) and 31 patients received conservative treatment (control group). The end-expiration intrapleural pressure of all patients remained less than - 20 cmH2O during drainage. No procedure related complication was observed. Large pneumothorax (≥ 15%) was associated with higher risk of persistent air leak (Odds ratio 12, 95% CI 1.2-569.7). Vacuum bottle assisted air drainage yielded shorter event-free duration than that of conservative treatment (2 days vs 5 days [interquartile range 1-4 days vs 3-7 days], p < .05). Vacuum bottle assisted air drainage also help identifying patients with persistent pneumothorax and necessitate the subsequent management. The event-free duration of persistent air leak in the intervention group was also comparable with that of conservative treatment (5 days vs 5 days [interquartile range 5-8 days vs 3-7 days], p = .45). CONCLUSIONS: Vacuum bottle plus catheter drainage of iatrogenic pneumothorax is a safe and efficient procedure. It may be considered as an alternative management of stable post-procedural pneumothorax with size larger than 15%. Trial registration The study protocol was approved by the Research Ethics Committee of National Taiwan University Hospital (No. 201805105DINA) on 6th August, 2018. The first participant was enrolled on 23rd August, 2018 after Research Ethics Committee approval. This clinical trial complete registration at U.S. National Library of Medicine clinicaltrials.gov with identifier NCT03724721 and URL: https://clinicaltrials.gov/ct2/show/NCT03724721 on 30th October, 2018.

Influence of concurrent lower respiratory tract disease on point-of-care lung ultrasound in small-breed dogs with myxomatous mitral valve disease.

BACKGROUND: Small-breed dogs commonly have concurrent myxomatous mitral valve disease (MMVD) and lower respiratory tract disease (LRTD). HYPOTHESIS: Small-breed dogs with preclinical MMVD and concurrent LRTD have more B-lines on point-of-care lung ultrasound (POC-LUS) compared to dogs without concurrent LRTD and are prone to misdiagnose as cardiogenic pulmonary edema (CPE). ANIMALS: A total of 114 small-breed dogs with preclinical MMVD. METHODS: A prospective study was conducted, in which POC-LUS was obtained and the number of B-lines was calculated by a single clinician using the Veterinary Bedside Lung Ultrasound Examination protocol. The presence/absence of LRTD was assessed by clinicians blinded to the POC-LUS results. RESULTS: Fifty and 64 dogs were in ACVIM stage B1 and B2, respectively. The presence of LRTD was prevalent in 74.6% (85/114) of small-breed dogs with preclinical MMVD. When a previously reported criterion for CPE diagnosis (≥2 sites with >3 B-lines/site) was applied, false-positive results were observed in 15.8% (18/114) of dogs with preclinical MMVD. The summated number of B-lines (3 vs. 1, P = .003), as well as the false-positive rate (20% vs 3%, P = .04), were significantly higher in dogs with LRTD compared with dogs without LRTD. Multivariable logistic regression showed the presence of abnormalities other than B-line on POC-LUS (eg, thickened pleura or consolidation) could predict false-positive results (odds ratio = 3.75, 95% confidence intervals 1.12-12.54; P = .03) after adjustment for other clinical and echocardiographic factors. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent LRTD and abnormalities other than B-lines should be considered in the interpretation of POC-LUS in MMVD dogs.

The application of ultrasound shear wave elastography in the prediction of paradoxical upgrading reaction in tuberculous lymphadenitis. a pilot study.

BACKGROUND: Paradoxical upgrading reaction (PUR) indicates the unanticipated deterioration during therapy in patients with tuberculous lymphadenitis. We investigated the diagnostic performance of the ultrasonography and shear wave elastography (SWE) in predicting the therapeutic response of peripheral tuberculous lymphadenitis. METHODS: A prospective observational study was conducted from December 2017 to August 2020. Participants diagnosed with peripheral tuberculous lymphadenitis were included for a longitudinal follow-up utilizing ultrasonography with two-dimensional SWE to record sonographic features and the maximum elasticity value (Emax). We defined PUR as the development of any worsening symptoms of the pre-existing lymphadenitis within one month after the previous ultrasonography. RESULTS: A total of 108 sonographic and SWE examinations were performed in 20 enrollees (75% woman), and their mean ( ± standard deviation) age was 49.6 ( ± 22.7) years. The area under the receiver operating characteristic curve of Emax to predict the next-month PUR was 0.906 at the cut-point of 85 kPa, with an accuracy of 87.0%, a sensitivity of 81.1% and a specificity of 87.9%. Multivariate analysis indicated that Emax > 85 kPa (OR: 24.85, 95% CI: 4.01-154.08, p < 0.001), Emax increment rate >2 kPa/month (OR: 15.14, 95% CI: 4.24-54.06, p < 0.001), and heterogeneous echogenicity (OR: 4.37, 95% CI: 1.16-16.43, p = 0.029) were independent sonographic predictors for PUR in the coming month. CONCLUSION: A high and non-declining Emax level and heterogeneous echogenicity were associated with the next-month PUR of tuberculous lymphadenitis. Ultrasonography with SWE may be a potential radiologic marker to predict the therapeutic response of tuberculous lymphadenitis.

Inspiratory muscle activation during inspiratory muscle training in patients with COPD.

BACKGROUND AND OBJECTIVES: The main target of inspiratory muscle training (IMT) is to improve diaphragm function in patients with COPD who have inspiratory muscle weakness. Ventilatory demand is already increased during quiet breathing in patients with COPD, and whether threshold load imposed by IMT would active more accessory muscle remained to be determined. The purpose of this study was to examine diaphragm and sternocleidomastoid (SCM) activation during IMT with intensities of 30% and 50% maximal inspiratory pressure (PImax). METHODS: Patients with COPD and a PImax lower than 60 cmH2O were recruited for the study. Surface electromyography (EMG) was used to measure diaphragm and SCM activation, and group-based trajectory modeling (GBTM) was used to identify activation patterns during IMT. The generalized estimating equation (GEE) was then used to detect differences of variables between various breathing tasks. Statistical significance was established at p < 0.05. RESULTS: A total of 30 patients with COPD participated in this study. All patients demonstrated significant increases in diaphragm and SCM activation during 30% and 50% PImax of IMT than during quiet breathing (all p < 0.001). Diaphragm demonstrated two distinct patterns in response to IMT: low activation (n = 8) and high activation (n = 22) group using GBTM analysis. CONCLUSION: Diaphragm and SCM were substantially activated during IMT in patients with COPD who had inspiratory muscle weakness. Regardless of whether diaphragm activation was high or low, SCM was activated to a greater extent in response to IMT.

End-Expiratory Lung Volumes During Spontaneous Breathing Trials in Tracheostomized Subjects on Prolonged Mechanical Ventilation.

BACKGROUND: The role of end-expiratory lung volume (EELV) during a spontaneous breathing trial (SBT) in patients who were tracheostomized and on prolonged mechanical ventilation is unclear. This study aimed to assess EELV during a 60-min SBT and its correlation with weaning success. METHODS: Enrolled subjects admitted to a weaning unit were measured for EELV and relevant parameters before and after the SBT. RESULTS: Of the 44 enrolled subjects, 29 (66%) were successfully liberated, defined as not needing mechanical ventilation for 5 d. The success group had fewer subjects with chronic kidney disease (41% vs 73%, P = .044), stronger mean ± SD maximum inspiratory pressure (41.6 ± 10.4 vs 34.1 ± 7.1 cm H2O; P = .02) and mean ± SD maximum expiratory pressure (46.9 ± 11.7 vs 35.3 ± 16.9 cm H2O; P = .01) versus the failure group. Toward the end of the SBT, the success group had a significant increase in the mean ± SD EELV (before vs after: 1,278 ± 744 vs 1,493 ± 867 mL; P = .040) and a decrease in the mean ± SD rapid shallow breathing index (83.8 ± 39.4 vs 66.3 ± 29.4; P = .02), whereas there were no significant changes in these 2 parameters in the failure group. The Cox regression analysis showed that, at the beginning of SBT, a greater difference between EELV with a PEEP of 0 cm H2O and with a PEEP of 5 cm H2O was significantly correlated to a higher likelihood of weaning success. Toward the end of the SBT, a greater EELV level at a PEEP of 0 cm H2O was also correlated with weaning success. Also, the greater difference of EELV at a PEEP of 0 cm H2O between the beginning and the end of the SBT was also correlated with a shorter duration to weaning success. CONCLUSIONS: The change in EELV during a 60-min SBT may be of prognostic value for liberation from prolonged mechanical ventilation in patients who had a tracheostomy. Our findings suggest a model to understand the underlying mechanism of failure of liberation from mechanical ventilation in these patients.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. METHODS: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. RESULTS: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia. CONCLUSION: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Application of transthoracic shear-wave ultrasound elastography in lung lesions.

INTRODUCTION: Tissue stiffness information may help in the diagnosis of lung lesions. This study aimed to investigate and validate the application of transthoracic two-dimensional shear-wave ultrasound elastography in differentiating malignant from benign subpleural lung lesions. METHODS: This study involved one retrospective observational derivation cohort from January 2016 to December 2017 and one prospective observational validation cohort from December 2017 to December 2019. The inclusion criterion was radiographic evidence of pulmonary lesions. The patients were categorised into air bronchogram and hypoechoic groups based on B-mode grayscale images. The elasticity of subpleural lung lesions with acceptable shear-wave propagation was measured. Diagnoses were made on the basis of pathology, microbiological studies or following up the clinical course for at least 6 months. RESULTS: A total of 354 patients were included. Among the 121 patients in the derivation cohort, a receiver operating characteristic curve was constructed and the cut-off point to differentiate benign from malignant lesions was 65 kPa with a Youden index of 0.60 and an accuracy of 84.3%. Among the 233 patients in the validation cohort, the diagnostic performance was maintained, with a Youden index of 0.65 and an accuracy of 86.7%. Upon applying the cut-off point to the air bronchogram group, the Youden index was 0.70 and the accuracy was 85.0%. CONCLUSIONS: This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy.

A Strategy to Treat COVID-19 Disease With Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Preclinical Pharmacokinetic Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen causing the coronavirus disease 2019 (COVID-19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti-inflammatory drug, has been shown to inhibit SARS-CoV-2 infection in vitro and tested in clinical studies. However, achievement of lung concentrations predicted to have in vivo antiviral efficacy might not be possible with the currently proposed oral dosing regimens. Further, high cumulative doses of HCQ raise concerns of systemic toxicity, including cardiotoxicity. Here, we describe a preclinical study to investigate the pharmacokinetics (PKs) of a novel formulation of liposomal HCQ administered by intratracheal (IT) instillation in Sprague-Dawley rats. Compared with unformulated HCQ administered intravenously, liposomal HCQ showed higher (~ 30-fold) lung exposure, longer (~ 2.5-fold) half-life in lungs, but lower blood exposure with ~ 20% of peak plasma concentration (Cmax ) and 74% of area under the curve from 0 to 72 hours (AUC0-72 ) and lower heart exposure with 23% of Cmax and 58% of AUC0-24 (normalized for dose). Similar results were observed relative to IT administration of unformulated HCQ. These PKs result in an animal model that demonstrated the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID-19.

Kinetics of oxygen uptake during unassisted breathing trials in prolonged mechanical ventilation: a prospective pilot study.

Few studies have investigated the measurement of oxygen uptake ([Formula: see text]O2) in tracheostomized patients undergoing unassisted breathing trials (UBTs) for liberation from mechanical ventilation (MV). Using an open-circuit, breath-to-breath method, we continuously measured [Formula: see text]O2 and relevant parameters during 120-min UBTs via a T-tube in 49 tracheostomized patients with prolonged MV, and calculated mean values in the first and last 5-min periods. Forty-one (84%) patients successfully completed the UBTs. The median [Formula: see text]O2 increased significantly (from 235.8 to 298.2 ml/min; P = 0.025) in the failure group, but there was no significant change in the success group (from 223.1 to 221.6 ml/min; P = 0.505). In multivariate logistic regression analysis, an increase in [Formula: see text]O2 > 17% from the beginning period (odds ratio [OR] 0.084; 95% confidence interval [CI] 0.012-0.600; P = 0.014) and a peak inspiratory pressure greater than - 30 cmH2O (OR 11.083; 95% CI 1.117-109.944; P = 0.04) were significantly associated with the success of 120-min UBT. A refined prediction model combining heart rate, energy expenditure, end-tidal CO2 and oxygen equivalent showed a modest increase in the area under the receiver operating characteristic curve of 0.788 (P = 0.578) and lower Akaike information criterion score of 41.83 compared to the traditional prediction model including heart rate and respiratory rate for achieving 48 h of unassisted breathing. Our findings show the potential of monitoring [Formula: see text]O2 in the final phase of weaning in tracheostomized patients with prolonged MV.

Improving patient safety during intrahospital transportation of mechanically ventilated patients with critical illness.

AIM: Intrahospital transportation (IHT) of patients under mechanical ventilation (MV) significantly increases the risk of patient harm. A structured process performed by a well-prepared team with adequate communication among team members plays a vital role in enhancing patient safety during transportation. DESIGN AND IMPLEMENTATION: We conducted this quality improvement programme at the intensive care units of a university-affiliated medical centre, focusing on the care of patients under MV who received IHT for CT or MRI examinations. With the interventions based on the analysis finding of the IHT process by healthcare failure mode and effects analysis, we developed and implemented strategies to improve this process, including standardisation of the transportation process, enhancing equipment maintenance and strengthening the teamwork among the transportation teammates. In a subsequent cycle, we developed and implemented a new process with the practice of reminder-assisted briefing. The reminders were printed on cards with mnemonics including 'VITAL' (Vital signs, Infusions, Tubes, Alarms and Leave) attached to the transportation monitors for the intensive care unit nurses, 'STOP' (Secretions, Tubes, Oxygen and Power) attached to the transportation ventilators for the respiratory therapists and 'STOP' (Speak-out, Tubes, Others and Position) attached to the examination equipment for the radiology technicians. We compared the incidence of adverse events and completeness and correctness of the tasks deemed to be essential for effective teamwork before and after implementing the programme. RESULTS: The implementation of the programme significantly reduced the number and incidence of adverse events (1.08% vs 0.23%, p=0.01). Audits also showed improved teamwork during transportation as the team members showed increased completeness and correctness of the essential IHT tasks (80.8% vs 96.5%, p<0.001). CONCLUSION: The implementation of reminder-assisted briefings significantly enhanced patient safety and teamwork behaviours during the IHT of mechanically ventilated patients with critical illness.

Association of weaning preparedness with extubation outcome of mechanically ventilated patients in medical intensive care units: a retrospective analysis.

BACKGROUND: Assessment of preparedness of weaning has been recommended before extubation for mechanically ventilated patients. We aimed to understand the association of a structured assessment of weaning preparedness with successful liberation. METHODS: We retrospectively investigated patients with acute respiratory failure who experienced an extubation trial at the medical intensive care units of a medical center and compared the demographic and clinical characteristics between those patients with successful and failed extubation. A composite score to assess the preparedness of weaning, the WEANSNOW score, was generated consisting of eight components, including Weaning parameters, Endotracheal tube, Arterial blood gas analysis, Nutrition, Secretions, Neuromuscular-affecting agents, Obstructive airway problems and Wakefulness. The prognostic ability of the WEANSNOW score for extubation was then analyzed. RESULTS: Of the 205 patients included, 138 (67.3%) patients had successful extubation. Compared with the failure group, the success group had a significantly shorter duration of MV before the weaning attempt (11.2 ± 11.6 vs. 31.7 ± 26.2 days, p < 0.001), more with congestive heart failure (42.0% vs. 25.4%, p = 0.020), and had different distribution of the types of acute respiratory failure (p = 0.037). The failure group also had a higher WEANSNOW score (1.22 ± 0.85 vs. 0.51 ± 0.71, p < 0.001) and worse Rapid Shallow Breathing Index (93.9 ± 63.8 vs. 56.3 ± 35.1, p < 0.001). Multivariate logistic regression analysis showed that a WEANSNOW Score = 1 or higher (OR = 2.880 (95% CI [1.291-6.426]), p = 0.010) and intubation duration >21 days (OR = 7.752 (95% CI [3.560-16.879]), p < 0.001) were independently associated with an increased probability of extubation failure. CONCLUSION: Assessing the pre-extubation status of intubated patients in a checklist-based approach using the WEANSNOW score might provide valuable insights into extubation failure in patients in a medical ICU for acute respiratory failure. Further prospective studies are warranted to elucidate the practice of assessing weaning preparedness.

Maximal expiratory pressure is associated with reinstitution of mechanical ventilation after successful unassisted breathing trials in tracheostomized patients with prolonged mechanical ventilation.

OBJECTIVE: Reinstitution of mechanical ventilation (MV) for tracheostomized patients after successful weaning may occur as the care setting changes from critical care to general care. We aimed to investigate the occurrence, consequence and associated factors of MV reinstitution. METHODS: We analyzed the clinical data and physiological measurements of tracheostomized patients with prolonged MV discharged from the weaning unit to general wards after successful weaning to compare between those with and without in-hospital MV reinstitution within 60 days. RESULTS: Of 454 patients successfully weaned, 116 (25.6%) reinstituted MV at general wards within 60 days; at hospital discharge, 42 (36.2%) of them were eventually liberated from MV, 51 (44.0%) remained MV dependent, and 33 (28.4%) died. Of the 338 patients without reinstitution within 60 days, only 3 (0.9%) were later reinstituted with MV before discharge (on day 67, 89 and 136 at general wards, respectively), and 322 (95.2%) were successfully weaned again at discharge, while 13 (3.8%) died. Patients with MV reinstitution had a significantly lower level of maximal expiratory pressure (PEmax) before unassisted breathing trial compared to those without reinstitution. Multivariable Cox regression analysis showed fever at RCC discharge (hazard ratio [HR] 14.00, 95% confidence interval [CI] 3.2-61.9) chronic obstructive pulmonary disease (HR 2.37, 95% CI 1.34-4.18), renal replacement therapy at the ICU (HR 2.29, 95% CI 1.50-3.49) and extubation failure before tracheostomy (HR 1.76, 95% CI 1.18-2.63) were associated with increased risks of reinstitution, while PEmax > 30 cmH2O (HR 0.51, 95% CI 0.35-0.76) was associated with a decreased risk of reinstitution. CONCLUSIONS: The reinstitution of MV at the general ward is significant, with poor outcomes. The PEmax measured before unassisted breathing trial was significantly associated with the risk of reinstituting MV at the general wards.

In Vitro Evaluation of Aerosol Performance and Delivery Efficiency During Mechanical Ventilation Between Soft Mist Inhaler and Pressurized Metered-Dose Inhaler.

BACKGROUND: Soft mist inhalers (SMIs) generate aerosols with a smaller particle size than pressurized metered-dose inhalers (pMDIs). However, the whole-span particle size distribution (PSD) of SMIs and the optimal delivery method of SMIs during mechanical ventilation have not been fully investigated. This study aimed to measure the PSD of the SMI alone and the SMI coupled to an inhalation aid (eg, a spacer, a valved holding chamber), as well as the delivery efficiency of SMI in different actuation timings and circuit positions during mechanical ventilation. As a suitable comparison, the pMDI was chosen for the same measurement. METHODS: SMIs (2.5 µg/actuation of tiotropium) were compared with pMDIs (100 µg/actuation of salbutamol). A microorifice uniform deposit impactor was utilized for the particle sizing of drug aerosols generated by inhalers alone, inhalers with a spacer, and inhalers with a valved holding chamber. To optimize the delivery efficiency of both inhalers during mechanical ventilation, the operating parameters included the circuit positions and actuation timings in the ventilator circuit. Particle sizes and inhaled doses were measured with an optical particle sizer and filters used to collect and quantify the drug, respectively. RESULTS: The SMI generated a smaller mass medium aerodynamic diameter (MMAD) than that from the pMDI. The extrafine-particle fraction (EFPF, < 1 µm) of the SMI was significantly higher than that of the pMDI. With the use of either inhalation aid, the MMAD of both inhalers decreased, and both inhalers with inhalation aid showed significant increases in EFPF. During mechanical ventilation, the optimum way to deliver the SMI and pMDI was at 15 cm from the Y-piece and actuated at the end of expiration and the onset of inspiration, respectively. CONCLUSIONS: The SMI with an inhalation aid showed marginal improvement on the PSD. The inhaler type, actuation timing, and position within the circuit also played important roles in delivery efficiency during mechanical ventilation.

Dynamic Changes in Prognosis with Elapsed Time on Ventilators among Mechanically Ventilated Patients.

Rationale: Previous outcome studies of mechanical ventilation usually adopted a static timeframe to observe the outcome and reported prognosis from the standpoint of the first ventilator day. However, patients and their families may repeatedly inquire about prognosis over time after the initiation of mechanical ventilation.Objectives: We aimed to describe dynamic changes in prognosis according to the elapsed time on a ventilator among mechanically ventilated patients.Methods: For this cohort study we used the entire population dataset of Taiwan's National Health Insurance database. We enrolled adults who newly received invasive mechanical ventilation for at least two consecutive days between March 1, 2010, and August 31, 2011. For every single ventilator day after the initiation of mechanical ventilation, we estimated the cumulative probabilities of weaning success and death in the subsequent 90 days.Results: A total of 162,200 episodes of respiratory failure requiring invasive mechanical ventilation were included. The median age of the subjects was 72 years (interquartile range 57-81 yr) and the median follow-up time was 250 days (interquartile range 30-463 d). The probability curve of weaning success against the time on ventilation showed a unidirectionally decreasing trend, with a relatively sharp slope in the initial 2 months. The probabilities of weaning success in 90 days after the 2nd, 7th, 21st, and 60th ventilator days were 68.3% (95% confidence interval [CI], 68.1-68.5%), 62.6% (95% CI, 62.2-62.9%), 46.3% (95% CI, 45.8-46.8%), and 21.0% (95% CI, 20.3-21.8%), respectively. In contrast, the death curve showed an initial increase and then a decreasing trend after the 19th ventilator day. We also reported tailored prognosis information according to the age, sex, and ventilator day of a mechanically ventilated patient.Conclusions: This study provides ventilator-day-specific prognosis information obtained from a large cohort of unselected patients on invasive mechanical ventilation. The probability of weaning success decreased with the elapsed time on mechanical ventilation, and the decline was particularly remarkable in the first 2 months of ventilatory support.