Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness

Background: Individualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness. Methods: A systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards. Results: Out of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively. Conclusion: CPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential. Trial registration number PROSPERO— CRD42022301715 . Registered 05 February, 2022

Analysis and applications of respiratory surface EMG:report of a round table meeting

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited—in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.</p

Analysis and applications of respiratory surface EMG:report of a round table meeting

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited—in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure.</p

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial

Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged >= 18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0.95 [95% CI 0.76-1.20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0.51 [0.27-0.95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0.52 (95% CI 0.26-1.05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1.07 (0.63-1.80; p=0.81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0.0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. Copyright (C) 2021 Elsevier Ltd. All rights reserved.Pathogenesis and treatment of chronic pulmonary disease

New type of wasted effort during neurally adjusted ventilatory assist: A case report

In patients with dynamic hyperinflation, such as patients with chronic obstructive pulmonary disease (COPD), development of intrinsic positive end-expiratory pressure (PEEPi) complicates ventilator triggering in conventional assisted ventilation modes, such as pressure support, and causes wasted efforts. The use of extrinsic PEEP (PEEPe) can counterbalance PEEPi and as such facilitate triggering. With neurally adjusted ventilatory assist (NAVA) the ventilator is triggered by an increase in diaphragm electrical activity and does not depend on generation of inspiratory flow. Numerous studies report the absence of ‘classical’ wasted efforts with NAVA. Therefore, the widespread assumption among physicians is that wasted efforts cannot occur with NAVA. We present a 58-year-old male with an acute exacerbation of COPD in which we identify a new type of wasted effort unique to NAVA. We show that during NAVA in the presence of PEEPi it is as important to perform titration of PEEPe as with conventional modes, in order to prevent wasted efforts

Zuurstoftoediening met hoge nasale flow bij covid-19

High flow nasal oxygen (HFNO) is proven to be effective in non-COVID-19 hypoxemic respiratory failure. In the beginning of the COVID-19 pandemic, HFNO was quickly introduced into daily clinical practice, although the evidence of its effectiveness in COVID-19 was limited. Randomized controlled trials suggest that HFNO has no effect on survival. However, HFNO may lead to less intubations in comparison with conventional oxygen therapy. The evidence of HFNO use in patients with do-not-intubate orders remains very limited. However, in these patients, improvement in comfort could be an important argument to start treatment with HFNO. Additional research is needed to make an evidence based consideration about the clinical use of HFNO in COVID-19 care

High flow nasal oxygen in patients with COVID-19

Zuurstoftoediening met hoge nasale flow (‘high flow nasal oxygen’; HFNO) verbetert de uitkomsten bij hypoxemisch respiratoirfalen.Of deze therapie ook effectief is bij patiënten met covid-19 is niet bekend; desondanks werd HFNO in veel ziekenhuizen ingezetgedurende de covid-19-pandemie.Gerandomiseerde onderzoeken suggereren dat HFNO geen effect heeft op overleving van patiënten met covid-19; mogelijk leidt hetwel tot minder intubaties vergeleken met conventionele zuurstoftherapie.Er is nauwelijks onderzoek verricht naar de effectiviteit van HFNO bij patiënten met een behandelbeperking; juist bij deze categoriepatiënten is het mogelijk betere comfort een belangrijk argument om toch met een proefbehandeling te beginnen.Duidelijk is dat er meer studies nodig zijn om een onderbouwde afweging te kunnen maken over wanneer en bij wie HFNO in tezetten.High flow nasal oxygen (HFNO) is proven to be effective in non-COVID-19 hypoxemic respiratory failure. In the beginning of the COVID-19 pandemic, HFNO was quickly introduced into daily clinical practice, although the evidence of its effectiveness in COVID-19 was limited. Randomized controlled trials suggest that HFNO has no effect on survival. However, HFNO may lead to less intubations in comparison with conventional oxygen therapy. The evidence of HFNO use in patients with do-not-intubate orders remains very limited. However, in these patients, improvement in comfort could be an important argument to start treatment with HFNO. Additional research is needed to make an evidence based consideration about the clinical use of HFNO in COVID-19 care.</p