OBJECTIVE: To clarify the mechanistic basis for the success or failure of noninvasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF).
METHODS: We created digital twins based on mechanistic computational models of individual patients with AHRF.
METHODS: Interdisciplinary Collaboration in Systems Medicine Research Network.
METHODS: We used individual patient data from 30 moderate-to-severe AHRF patients who had failed high-flow nasal cannula (HFNC) therapy and subsequently underwent a trial of NIV.
METHODS: Using the digital twins, we evaluated lung mechanics, quantified the separate contributions of external support and patient respiratory effort to lung injury indices, and investigated their relative impact on NIV success or failure.
RESULTS: In digital twins of patients who successfully completed/failed NIV, after 2 hours of the trial the mean (sd) of the change in total lung stress was -10.9 (6.2)/-0.35 (3.38) cm H2O, mechanical power -13.4 (12.2)/-1.0 (5.4) J/min, and total lung strain 0.02 (0.24)/0.16 (0.30). In the digital twins, positive end-expiratory pressure (PEEP) produced by HFNC was similar to that set during NIV. In digital twins of patients who failed NIV vs. those who succeeded, intrinsic PEEP was 3.5 (0.6) vs. 2.3 (0.8) cm H2O, inspiratory pressure support was 8.3 (5.9) vs. 22.3 (7.2) cm H2O, and tidal volume was 10.9 (1.2) vs. 9.4 (1.8) mL/kg. In digital twins, successful NIV increased respiratory system compliance +25.0 (16.4) mL/cm H2O, lowered inspiratory muscle pressure -9.7 (9.6) cm H2O, and reduced the contribution of patient spontaneous breathing to total driving pressure by 57.0%.
CONCLUSIONS: In digital twins of AHRF patients, successful NIV improved lung mechanics, lowering respiratory effort and indices associated with lung injury. NIV failed in patients for whom only low levels of positive inspiratory pressure support could be applied without risking patient self-inflicted lung injury due to excessive tidal volumes.

OBJECTIVE: Patients with acute respiratory failure often require mechanical ventilation to reduce the work of breathing and improve gas exchange; however, this may exacerbate lung injury. Protective ventilation strategies, characterized by low tidal volumes (≤ 8mL/kg of predicted body weight) and limited plateau pressure below 30cmH2O, have shown improved outcomes in patients with acute respiratory distress syndrome. However, in the transition to spontaneous ventilation, it can be challenging to maintain tidal volume within protective levels, and it is unclear whether low tidal volumes during spontaneous ventilation impact patient outcomes. We developed a study protocol to estimate the prevalence of low tidal volume ventilation in the first 24 hours of spontaneous ventilation in patients with hypoxemic acute respiratory failure and its association with ventilator-free days and survival.
METHODS: We designed a multicenter, multinational, cohort study with a 28-day follow-up that will include patients with acute respiratory failure, defined as a partial oxygen pressure/fraction of inspired oxygen ratio < 300mmHg, in transition to spontaneous ventilation in intensive care units in Latin America.
RESULTS: We plan to include 422 patients in ten countries. The primary outcomes are the prevalence of low tidal volume in the first 24 hours of spontaneous ventilation and ventilator-free days on day 28. The secondary outcomes are intensive care unit and hospital mortality, incidence of asynchrony and return to controlled ventilation and sedation.
CONCLUSIONS: In this study, we will assess the prevalence of low tidal volume during spontaneous ventilation and its association with clinical outcomes, which can inform clinical practice and future clinical trials.

Background: A non-invasive ventilation (NIV) mask has been designed to deliver NIV with expiratory washout (EW) to improve efficacy of ventilation by optimizing clearance of expired gases from the anatomic dead-space. This study compared the performance and comfort of a novel investigational mask with EW with a conventional mask during NIV therapy.Methods: In this pilot cross-over study, participants with severe stable chronic obstructive pulmonary disease (COPD) attended a single visit to receive bi-level NIV through two masks; the investigational mask with EW, and a conventional mask. The order of mask use was randomly allocated, and each mask was used for 60-minutes with a 30-to-60-minute washout in between. The primary outcome was transcutaneous carbon dioxide (PtCO2) at 60 minutes. Other physiologic and NIV device variables were also assessed.Results: The mean difference [95% CI] in the PtCO2 between the investigational and conventional masks at 60 minutes, adjusted for baseline, was -0.74 mmHg [-2.81 to 1.33, P=0.45]. The investigational mask with EW elicited a lower tidal volume (-128.7 mL [-190.0 to -67.3], P<0.001) and minute ventilation (-2.28 L·min-1 [-3.12 to -1.43], P<0.001), and a higher leak (7.96 L·min-1 [4.39 to 11.54], P<0.001), than the conventional mask. There were no significant differences in other physiological responses or ratings of dyspnoea or comfort.Conclusions: NIV therapy delivered using a novel mask with EW was similarly effective at reducing PtCO2, while the delivered tidal volume and minute ventilation were significantly lower, when compared to a conventional mask in participants with severe COPD.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 μg/kg and especially at 120 μg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

BACKGROUND: Adaptive pressure control-continuous mandatory ventilation (APC-CMV) is a frequently utilized ventilator mode in ICU settings. This analysis compared APC-CMV and traditional volume control-continuous mandatory ventilation (VC-CMV) mode, describing factors associated with initiation, maintenance, and changes in settings of each mode.
METHODS: We analyzed ventilator data from a retrospective electronic health record data set collected as part of a quality improvement project in a single academic ICU. The majority ventilator mode was defined as the mode comprising the highest proportion of mechanical ventilation time. Multivariable logistic regression was used to identify variables associated with initial and majority APC-CMV or VC-CMV modes. Wilcoxon rank-sum tests were used to compare ventilator setting changes/d and sedation as a function of APC-CMV and VC-CMV majority modes.
RESULTS: Among 1,213 subjects initiated on mechanical ventilation from January 2013-March 2017, 68% and 24% were initiated on APC-CMV and VC-CMV, respectively, which composed 62% and 21% of the majority ventilator modes. Age, sex, race, and ethnicity were not associated with the initial or majority APC-CMV or VC-CMV modes. Subjects initiated on APC-CMV spent 88% of the mechanical ventilation time on APC-CMV mode. Compared to VC-CMV, subjects with APC-CMV majority mode experienced more ventilator setting changes/d (1.1 vs 0.8, P < .001). There were no significant differences in sedative medications when comparing subjects receiving APC-CMV versus VC-CMV majority modes.
CONCLUSIONS: APC-CMV was highly utilized in the medical ICU. Subjects on APC-CMV had more ventilator setting changes/d than those on VC-CMV. APC-CMV offered no advantage of reduced setting adjustments or less sedation compared to VC-CMV.

暂无摘要。

BACKGROUND: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes.
METHODS: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories.
RESULTS: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar-hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables.
CONCLUSIONS: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

BACKGROUND: Morbidly obese patients occasionally have respiratory problems owing to hypoventilation. Airway pressure release ventilation is one of the ventilation settings often used for respiratory management of acute respiratory distress syndrome. However, previous reports indicating that airway pressure release ventilation may become a therapeutic measure as ventilator management in morbid obesity with respiratory failure is limited. We report a case of markedly improved oxygenation in a morbidly obese patient after airway pressure release ventilation application.
METHODS: A 50s-year-old Asian man (body mass index 41 kg/m2) presented with breathing difficulties. The patient had respiratory failure with a PaO2/FIO2 ratio of approximately 100 and severe atelectasis in the left lung, and ventilator management was initiated. Although the patient was managed on a conventional ventilate mode, oxygenation did not improve. On day 11, we changed the ventilation setting to airway pressure release ventilation, which showed marked improvement in oxygenation with a PaO2/FIO2 ratio of approximately 300. We could reduce sedative medication and apply respiratory rehabilitation. The patient was weaned from the ventilator on day 29 and transferred to another hospital for further rehabilitation on day 31.
CONCLUSIONS: Airway pressure release ventilation ventilator management in morbidly obese patients may contribute to improving oxygenation and become one of the direct therapeutic measures in the early stage of critical care.

暂无摘要。

High-flow nasal therapy (HFNT) has an increasing role in the management of acute hypoxic respiratory failure. Due to its tolerable interface and ease of use, its role in chronic hypercapnic respiratory failure (CHRF) is emerging. This article examines the literature to date surrounding the short and long-term mechanisms of HFNT in sleep and wakefulness of CHRF patients. It is likely HFNT will have an increasing role in those patients intolerant of non-invasive ventilation.