Lung- and diaphragm-protective strategies in acute respiratory failure: an in silico trial.

BACKGROUND: Lung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCO2R) to achieve LDP targets. METHODS: An in silico clinical trial was conducted using a previously published mathematical model of patient-ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics. Ventilation and sedation were titrated according to a pre-defined algorithm in pressure support ventilation (PSV) and proportional assist ventilation (PAV+) modes, with or without adjunctive ECCO2R, and using ECCO2R alone (without ventilation or sedation). Random forest modelling was employed to identify patient-level factors associated with achieving targets. RESULTS: After titration, the proportion of patients achieving targets was lower in PAV+ vs. PSV (37% vs. 43%, odds ratio 0.78, 95% CI 0.73-0.85). Adjunctive ECCO2R substantially increased the probability of achieving targets in both PSV and PAV+ (85% vs. 84%). ECCO2R alone without ventilation or sedation achieved LDP targets in 9%. The main determinants of success without ECCO2R were lung compliance, ventilatory ratio, and strong ion difference. In silico trial results corresponded closely with the results obtained in a clinical trial of the LDP titration algorithm (n = 30). CONCLUSIONS: In this in silico trial, many patients required ECCO2R in combination with mechanical ventilation and sedation to achieve LDP targets. ECCO2R increased the probability of achieving LDP targets in patients with intermediate degrees of derangement in elastance and ventilatory ratio.

Complex Lemierre syndrome with multisystemic abscesses.

We present here the challenging case of severe Lemierre syndrome in a healthy woman in her late twenties, whose clinical presentation was characterised by lung abscesses and disseminated systemic abscesses in the brain, the abdomen and the soft-tissues, as a likely consequence of a patent foramen ovale. Blood cultures were positive for Fusobacterium necrophorum and a right lingual vein thrombosis was detected at a late stage when the patient developed a septic shock. Initial antimicrobial therapy with metronidazole and ceftriaxone was modified to meropenem due to progressive worsening. The patient underwent laparoscopy and neurosurgical drainage of a cerebral abscess. She spent many days in the intensive care unit and recovered fully after 6 weeks on meropenem therapy. Although considered rare, the incidence of Lemierre syndrome, a potentially life-threatening condition, is increasing. The clinician should promptly recognise and treat it while being aware of its potential atypical presentations.

Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial.

BACKGROUND: Insufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing - 3 to - 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF. METHODS: In patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort. RESULTS: Of 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets. CONCLUSION: Respiratory effort is frequently absent  under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy. TRIAL REGISTRATION: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

2021 ELSO Adult and Pediatric Anticoagulation Guidelines.

DISCLAIMER: These guidelines for adult and pediatric anticoagulation for extracorporeal membrane oxygenation are intended for educational use to build the knowledge of physicians and other health professionals in assessing the conditions and managing the treatment of patients undergoing ECLS / ECMO and describe what are believed to be useful and safe practice for extracorporeal life support (ECLS, ECMO) but these are not necessarily consensus recommendations. The aim of clinical guidelines are to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise. These guidelines do not take the place of physicians' and other health professionals' judgment in diagnosing and treatment of particular patients. These guidelines are not intended to and should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. The ultimate judgment must be made by the physician and other health professionals and the patient in light of all the circumstances presented by the individual patient, and the known variability and biological behavior of the clinical condition. These guidelines reflect the data at the time the guidelines were prepared; the results of subsequent studies or other information may cause revisions to the recommendations in these guidelines to be prudent to reflect new data, but ELSO is under no obligation to provide updates. In no event will ELSO be liable for any decision made or action taken in reliance upon the information provided through these guidelines.

A physiology-based mathematical model for the selection of appropriate ventilator controls for lung and diaphragm protection.

Mechanical ventilation is used to sustain respiratory function in patients with acute respiratory failure. To aid clinicians in consistently selecting lung- and diaphragm-protective ventilation settings, a physiology-based decision support system is needed. To form the foundation of such a system, a comprehensive physiological model which captures the dynamics of ventilation has been developed. The Lung and Diaphragm Protective Ventilation (LDPV) model centers around respiratory drive and incorporates respiratory system mechanics, ventilator mechanics, and blood acid-base balance. The model uses patient-specific parameters as inputs and outputs predictions of a patient's transpulmonary and esophageal driving pressures (outputs most clinically relevant to lung and diaphragm safety), as well as their blood pH, under various ventilator and sedation conditions. Model simulations and global optimization techniques were used to evaluate and characterize the model. The LDPV model is demonstrated to describe a CO2 respiratory response that is comparable to what is found in literature. Sensitivity analysis of the model indicate that the ventilator and sedation settings incorporated in the model have a significant impact on the target output parameters. Finally, the model is seen to be able to provide robust predictions of esophageal pressure, transpulmonary pressure and blood pH for patient parameters with realistic variability. The LDPV model is a robust physiological model which produces outputs which directly target and reflect the risk of ventilator-induced lung and diaphragm injury. Ventilation and sedation parameters are seen to modulate the model outputs in accordance with what is currently known in literature.

Agreement between activated partial thromboplastin time and anti-Xa activity in critically ill patients receiving therapeutic unfractionated heparin.

BACKGROUND: No study supports the use of either aPTT or anti-Xa activity for heparin monitoring in critical care patients. There are no strong data on the agreement between aPTT and anti-Xa. The aims of this study were to: 1. Analyse the agreement between aPTT and anti-Xa in a large population of critically ill patients under unfractionated heparin therapy (UFH), 2. Identify clinical and biological factors associated to agreement or disagreement, and 3. Analyse the impact of anti-Xa availability on the use of aPTT and UFH therapy. METHODS: Retrospective study in a 35 beds mixed-ICU population between 2006 and 2016 in a University teaching hospital. INCLUSION CRITERIA: delivery of a UFH dose >15,000 U/24 h during at least one day with one anti-Xa determination. DATA: demographic variables, aPTT, anti-Xa, laboratory variables, presence of extracorporeal devices (ECD). Pairs of simultaneously dosed aPTT and anti-Xa [aPTT:anti-Xa] were analysed on the basis of their agreement within the sub-therapeutic, therapeutic (aPTT 50-80″, anti-Xa 0.3-0.7 U/ml) or supra-therapeutic ranges. RESULTS: 2283 patient admissions (2085 patients) were analysed. 35,595 [aPTT:anti-Xa] pairs were found. The overall [aPTT:anti-Xa] agreement was 59.6% and lowest (54.3%) in presence of ECD compared to non-ECD patients (61.6%; p < 0.001). Sixteen demographic and biological variables were analysed and were not predictive of [aPTT:anti-Xa] agreement. No significant difference in administered UFH dose was observed after anti-Xa introduction. CONCLUSION: In this large cohort, the [aPTT:anti-Xa] agreement is <60% and significantly lower in patients with ECD. None of the variables identified as potentially affecting the agreement were predictive. Availability of anti-Xa had neither effect on aPTT use nor on UFH-dose. These results call for a prospective study to determine the optimal UFH-therapy monitoring tool.

Impact of a Dedicated Noninvasive Ventilation Team on Intubation and Mortality Rates in Severe COPD Exacerbations.

BACKGROUND: Compared with usual care, noninvasive ventilation (NIV) lowers the risk of intubation and death for subjects with respiratory failure secondary to COPD exacerbations, but whether administration of NIV by a specialized, dedicated team improves its efficiency remains uncertain. Our aim was to test whether a dedicated team of respiratory therapists applying all acute NIV treatments would reduce the risk of intubation or death for subjects with COPD admitted for respiratory failure. METHODS: We carried out a retrospective study comparing subjects with COPD admitted to the ICU before (2001-2003) and after (2010-2012) the creation of a dedicated NIV team in a regional acute care hospital. The primary outcome was the risk of intubation or death. The secondary outcomes were the individual components of the primary outcome and ICU/hospital stay. RESULTS: A total of 126 subjects were included: 53 in the first cohort and 73 in the second. There was no significant difference in the demographic characteristics and severity of respiratory failure. Fifteen subjects (28.3%) died or had to undergo tracheal intubation in the first cohort, and only 10 subjects (13.7%) in the second cohort (odds ratio 0.40, 95% CI 0.16-0.99, P = .04). In-hospital mortality (15.1% vs 4.1%, P = .03) and median stay (ICU: 3.1 vs 1.9 d, P = .04; hospital: 11.5 vs 9.6 d, P = .04) were significantly lower in the second cohort, and a trend for a lower intubation risk was observed (20.8% vs 11% P = .13). CONCLUSIONS: The delivery of NIV by a dedicated team was associated with a lower risk of death or intubation in subjects with respiratory failure secondary to COPD exacerbations. Therefore, the implementation of a team administering all NIV treatments on a 24-h basis should be considered in institutions admitting subjects with COPD exacerbations.