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Enhancing global health security responses through greater inclusion of the global south in infectious disease modelling.

ERS International Congress, Madrid, 2019: highlights from the Respiratory Intensive Care Assembly.

The Respiratory Intensive Care Assembly of the European Respiratory Society is delighted to present the highlights from the 2019 International Congress in Madrid, Spain. We have selected four sessions that discussed recent advances in a wide range of topics: from acute respiratory failure to cough augmentation in neuromuscular disorders and from extra-corporeal life support to difficult ventilator weaning. The subjects are summarised by early career members in close collaboration with the Assembly leadership. We aim to give the reader an update on the most important developments discussed at the conference. Each session is further summarised into a short list of take-home messages.

Impact of Country Income Level on Outcomes in Patients with Acute Brain Injury Requiring Invasive Mechanical Ventilation: A Secondary Analysis of the ENIO Study.

BackgroundInvasive mechanical ventilation can present complex challenges for patients with acute brain injury (ABI) in middle-income countries (MICs). We characterized the impact of country income level on weaning strategies and outcomes in patients with ABI.MethodsA secondary analysis was performed on a registry of critically ill patients with ABI admitted to 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Patients were classified as high-income country (HIC) or MIC. The primary outcome was ICU mortality. Secondary outcomes were days to first extubation, tracheostomy, extubation failure, ICU length of stay, and hospital mortality. Multivariable analyses were adjusted for clinically preselected covariates such as age, sex, body mass index, neurological severity, comorbidities, and ICU management. Extubation and tracheostomy outcomes were also adjusted for arterial blood gas values and ventilatory settings.ResultsOf 1512 patients (median age = 54 years, 66% male), 1170 (77%) were from HICs, and 342 (23%) were from MICs. Median age was significantly lower in MICs [35 (range 26-52) vs. 58 (range 45-68) years in HICs]. Neurosurgical procedures (47.7% vs. 38.2%) and decompressive craniectomy (30.7% vs. 15.9%) were more common in MICs, whereas intracranial pressure monitoring (12.0% vs. 51.5%) and external ventricular drain (7.6% vs. 35.6%) were less common. Compared with HICs, patients from MICs had 2.27 times the odds of ICU mortality [p = 0.009, 95% confidence interval (CI) 1.22-4.21]. Frequency of extubation failure was lower in MICs but not significant after adjustment. Patients from MICs had 3.38 times the odds of tracheostomy (p ≤ 0.001, 95% CI 2.28-5.01), 5.59 days shorter mean ICU stay (p ConclusionsIn an international registry of patients with ABI requiring invasive mechanical ventilation, MICs had higher odds of ICU mortality, tracheostomy placement, and hospital mortality compared with HICs, which may be due to difference in neurocritical care resources and management.

Individual and combined effects of chemical and mechanical power on postoperative pulmonary complications: a secondary analysis of the REPEAT study.

IntroductionIntra-operative supplemental oxygen and mechanical ventilation expose the lungs to potentially injurious energy. This can be quantified as 'chemical power' and 'mechanical power', respectively. In this study, we sought to determine if intra-operative chemical and mechanical power, individually and/or in combination, are associated with postoperative pulmonary complications.MethodsUsing an individual patient data analysis of three randomised clinical trials of intra-operative ventilation, we summarised intra-operative chemical and mechanical power using time-weighted averages. We evaluated the association between intra-operative chemical and mechanical power and a collapsed composite of postoperative pulmonary complications using multivariable logistic regression to estimate the odds ratios related to the effect of 1 J.min-1 increase in chemical or mechanical power with adjustment for demographic and intra-operative characteristics. We also included an interaction term to assess for potential synergistic effects of chemical and mechanical power on postoperative pulmonary complications.ResultsOf 3837 patients recruited to three individual trials, 2492 with full datasets were included in the analysis. Intra-operative time-weighted average (SD) chemical power was 10.2 (3.9) J.min-1 and mechanical power was 10.5 (4.4) J.min-1. An increase of 1 J.min-1 in chemical power was associated with 8% higher odds of postoperative pulmonary complications (OR 1.08, 95%CI 1.05-1.10, p DiscussionBoth chemical and mechanical power are independently associated with postoperative pulmonary complications. Further work is required to determine causality.

Right Ventricular Injury Definition and Management in Veno-Venous Extracorporeal Membrane Oxygenation.

Right ventricular injury (RVI) in respiratory failure receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is associated with significant mortality. A scoping review is necessary to map the current literature and guide future research regarding the definition and management of RVI in patients receiving VV ECMO. We searched for relevant publications on RVI in patients receiving VV ECMO in Medline, EMBASE, and Web of Science. Of 1,868 citations screened, 30 studies reported on RVI (inclusive of right ventricular dilation, right ventricular dysfunction, and right ventricular failure) during VV ECMO. Twenty-three studies reported on the definition of RVI including echocardiographic indices of RV function and dimensions, whereas 13 studies reported on the management of RVI, including veno-pulmonary (VP) ECMO, veno-arterial (VA) ECMO, positive inotropic agents, pulmonary vasodilators, ultra-lung-protective ventilation (Ultra-LPV), and optimization of positive end-expiratory pressure (PEEP). The definitions of RVI in patients receiving VV ECMO used in the literature are heterogeneous. Despite the high incidence of RVI during VV ECMO support and its strong association with mortality, studies investigating therapeutic strategies for RVI are also lacking. To fill the existing knowledge gaps, a consensus on the definition of RVI and research investigating RV-targeted therapies during VV ECMO is urgently warranted.

Medical Triage: Ethical Implications and Management Strategies.

Natural or man-made medical disasters have repeatedly affected human communities. The impact on health care resources may vary depending on the magnitude of each crisis, catastrophe or pandemic, and the resources available. Medical triage protocols serve as invaluable tools to address clinical needs, particularly when resources, including supplies, equipment, and personnel, are limited. Although resources should be allocated to maximize the benefit, resource allocations need to be ethically sound. Existing triage protocols have inherent limitations.

Respiratory mechanics and mechanical power during low vs. high positive end-expiratory pressure in obese surgical patients - A sub-study of the PROBESE randomized controlled trial.

Study objectiveWe aimed to characterize intra-operative mechanical ventilation with low or high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) regarding intra-tidal recruitment/derecruitment and overdistension using non-linear respiratory mechanics, and mechanical power in obese surgical patients enrolled in the PROBESE trial.DesignProspective, two-centre substudy of the international, multicentre, two-arm, randomized-controlled PROBESE trial.SettingOperating rooms of two European University Hospitals.PatientsForty-eight adult obese patients undergoing abdominal surgery.InterventionsIntra-operative protective ventilation with either PEEP of 12 cmH2O and repeated RM (HighPEEP+RM) or 4 cmH2O without RM (LowPEEP).MeasurementsThe index of intra-tidal recruitment/de-recruitment and overdistension (%E2) as well as airway pressure, tidal volume (VT), respiratory rate (RR), resistance, elastance, and mechanical power (MP) were calculated from respiratory signals recorded after anesthesia induction, 1 h thereafter, and end of surgery (EOS).Main resultsTwenty-four patients were analyzed in each group. PEEP was higher (mean ± SD, 11.7 ± 0.4 vs. 3.7 ± 0.6 cmH2O, P 2O, P T and RR did not differ significantly (7.3 ± 0.6 vs. 7.4 ± 0.8 ml∙kg-1, P = 0.835; and 14.6 ± 2.5 vs. 15.7 ± 2.0 min-1, P = 0.150, respectively). %E2 was higher in HighPEEP+RM than in LowPEEP following induction (-3.1 ± 7.2 vs. -12.4 ± 10.2%; P 2O∙l∙s-2, P = 0.009; and 15.7 ± 5.5 vs. 28.5 ± 8.4 cmH2O∙l, P -1, P ConclusionsIn this sub-cohort of PROBESE, intra-operative ventilation with high PEEP and RM reduced intra-tidal recruitment/de-recruitment as well as driving pressure, elastance, resistance, and mechanical power, as compared with low PEEP.Trial registrationThe PROBESE study was registered at www.Clinicaltrialsgov, identifier: NCT02148692 (submission for registration on May 23, 2014).

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PurposeLower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes.MethodsA prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups.Results1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates.ConclusionVHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

The diagnostic accuracy of lung ultrasound to determine PiCCO-derived extravascular lung water in invasively ventilated patients with COVID-19 ARDS.

BackgroundLung ultrasound (LUS) can detect pulmonary edema and it is under consideration to be added to updated acute respiratory distress syndrome (ARDS) criteria. However, it remains uncertain whether different LUS scores can be used to quantify pulmonary edema in patient with ARDS.ObjectivesThis study examined the diagnostic accuracy of four LUS scores with the extravascular lung water index (EVLWi) assessed by transpulmonary thermodilution in patients with moderate-to-severe COVID-19 ARDS.MethodsIn this predefined secondary analysis of a multicenter randomized-controlled trial (InventCOVID), patients were enrolled within 48 hours after intubation and underwent LUS and EVLWi measurement on the first and fourth day after enrolment. EVLWi and ∆EVLWi were used as reference standards. Two 12-region scores (global LUS and LUS-ARDS), an 8-region anterior-lateral score and a 4-region B-line score were used as index tests. Pearson correlation was performed and the area under the receiver operating characteristics curve (AUROCC) for severe pulmonary edema (EVLWi > 15 mL/kg) was calculated.Results26 out of 30 patients (87%) had complete LUS and EVLWi measurements at time point 1 and 24 out of 29 patients (83%) at time point 2. The global LUS (r = 0.54), LUS-ARDS (r = 0.58) and anterior-lateral score (r = 0.54) correlated significantly with EVLWi, while the B-line score did not (r = 0.32). ∆global LUS (r = 0.49) and ∆anterior-lateral LUS (r = 0.52) correlated significantly with ∆EVLWi. AUROCC for EVLWi > 15 ml/kg was 0.73 for the global LUS, 0.79 for the anterior-lateral and 0.85 for the LUS-ARDS score.ConclusionsOverall, LUS demonstrated an acceptable diagnostic accuracy for detection of pulmonary edema in moderate-to-severe COVID-19 ARDS when compared with PICCO. For identifying patients at risk of severe pulmonary edema, an extended score considering pleural morphology may be of added value.Trial registrationClinicalTrials.gov identifier NCT04794088, registered on 11 March 2021. European Clinical Trials Database number 2020-005447-23.

Comparison of Mechanical Power During Adaptive Support Ventilation Versus Nonautomated Pressure-Controlled Ventilation-A Pilot Study.

ObjectivesThe aim of this pilot study was to compare the amount of "mechanical power of ventilation" under adaptive support ventilation with nonautomated pressure-controlled ventilation.DesignSingle-center, observational prospective pilot study adjoining unitwide implementation of adaptive support ventilation in our department.SettingThe ICU of a nonacademic teaching hospital in the Netherlands.PatientsTwenty-four passive invasively ventilated critically ill patients expected to need of invasive ventilation beyond the following calendar day.Measurements and main resultsIn patients under adaptive support ventilation, only positive end-expiratory pressure and Fio2 were set by the caregivers-all other ventilator settings were under control of the ventilator; in patients under pressure-controlled ventilation, maximum airway pressure (Pmax), positive end-expiratory pressure, Fio2, and respiratory rate were set by the caregivers. Mechanical power of ventilation was calculated three times per day. Compared with pressure-controlled ventilation, mechanical power of ventilation with adaptive support ventilation was lower (15.1 [10.5-25.7] vs 22.9 [18.7-28.8] J/min; p = 0.04). Tidal volume was not different, but Pmax (p = 0.012) and respiratory rate (p = 0.012) were lower with adaptive support ventilation.ConclusionsThis study suggests adaptive support ventilation may have benefits compared with pressure-controlled ventilation with respect to the mechanical power of ventilation transferred from the ventilator to the respiratory system in passive invasively ventilated critically ill patients. The difference in mechanical power of ventilation is not a result of a difference in tidal volume, but the reduction in applied pressures and respiratory rate. The findings of this observational pilot study need to be confirmed in a larger, preferably randomized clinical trial.

Systematic review of diagnostic methods for acute respiratory distress syndrome.

RationaleAcute respiratory distress syndrome (ARDS) is currently diagnosed by the Berlin definition, which does not include a direct measure of pulmonary oedema, endothelial permeability or pulmonary inflammation. We hypothesised that biomarkers of these processes have good diagnostic accuracy for ARDS.MethodsMedline and Scopus were searched for original diagnostic studies using minimally invasive testing. Primary outcome was the diagnostic accuracy per test and was categorised by control group. The methodological quality was assessed with QUADAS-2 tool. Biomarkers that had an area under the receiver operating characteristic curve (AUROCC) of >0.75 and were studied with minimal bias against an unselected control group were considered to be promising.ResultsForty-four articles were included. The median AUROCC for all evaluated tests was 0.80 (25th to 75th percentile: 0.72-0.88). The type of control group influenced the diagnostic accuracy (p=0.0095). Higher risk of bias was associated with higher diagnostic accuracy (AUROCC 0.75 for low-bias, 0.77 for intermediate-bias and 0.84 for high-bias studies; p=0.0023). Club cell protein 16 and soluble receptor for advanced glycation end-products in plasma and two panels with biomarkers of oxidative stress in breath showed good diagnostic accuracy in low-bias studies that compared ARDS patients to an unselected intensive care unit (ICU) population.ConclusionThis systematic review revealed only four diagnostic tests fulfilling stringent criteria for a promising biomarker in a low-bias setting. For implementation into the clinical setting, prospective studies in a general unselected ICU population with good methodological quality are needed.

Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial.

BackgroundAccumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the 'Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial' (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients.ResultsIn this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33).ConclusionIn adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube. Trial registration Clinicaltrials.gov Identifier: NCT02159196.

Effects of higher PEEP and recruitment manoeuvres on mortality in patients with ARDS: a systematic review, meta-analysis, meta-regression and trial sequential analysis of randomized controlled trials.

PurposeIn patients with acute respiratory distress syndrome (ARDS), lung recruitment could be maximised with the use of recruitment manoeuvres (RM) or applying a positive end-expiratory pressure (PEEP) higher than what is necessary to maintain minimal adequate oxygenation. We aimed to determine whether ventilation strategies using higher PEEP and/or RMs could decrease mortality in patients with ARDS.MethodsWe searched MEDLINE, EMBASE and CENTRAL from 1996 to December 2019, included randomized controlled trials comparing ventilation with higher PEEP and/or RMs to strategies with lower PEEP and no RMs in patients with ARDS. We computed pooled estimates with a DerSimonian-Laird mixed-effects model, assessing mortality and incidence of barotrauma, population characteristics, physiologic variables and ventilator settings. We performed a trial sequential analysis (TSA) and a meta-regression.ResultsExcluding two studies that used tidal volume (VT) reduction as co-intervention, we included 3870 patients from 10 trials using higher PEEP alone (n = 3), combined with RMs (n = 6) or RMs alone (n = 1). We did not observe differences in mortality (relative risk, RR 0.96, 95% confidence interval, CI [0.84-1.09], p = 0.50) nor in incidence of barotrauma (RR 1.22, 95% CI [0.93-1.61], p = 0.16). In the meta-regression, the PEEP difference between intervention and control group at day 1 and the use of RMs were not associated with increased risk of barotrauma. The TSA reached the required information size for mortality (n = 2928), and the z-line surpassed the futility boundary.ConclusionsAt low VT, the routine use of higher PEEP and/or RMs did not reduce mortality in unselected patients with ARDS.Trial registrationPROSPERO CRD42017082035 .

Fluids in ARDS: more pros than cons.

In acute respiratory distress syndrome (ARDS), increased pulmonary vascular permeability makes the lung vulnerable to edema. The use of conservative as compared to liberal fluid strategies may increase the number of ventilator-free days and survival, as well as reduce organ dysfunction. Monitoring the effects of fluid administration is of the utmost importance; dynamic indexes, such as stroke volume and pulse pressure variations, outperform static ones, such as the central venous pressure. The passive leg raise and end-expiratory occlusion tests are recommended for guiding fluid management decisions. The type of intravenous fluids should also be taken into consideration: crystalloids, colloids, and human albumin have all been used for fluid resuscitation. Recent studies have also shown differences in outcome between balanced and non-balanced intravenous solutions. In preclinical studies, infusion of albumin promotes maintenance of the glycocalyx layer, reduces inflammation, and improves alveolar-capillary membrane permeability. Fluids in ARDS must be administered cautiously, considering hemodynamic and perfusion status, oncotic and hydrostatic pressures, ARDS severity, fluid type, volume and infusion rate, and cardiac and renal function. Of note, no guideline to date has recommended a specific fluid composition for use in ARDS; most physicians currently follow recommendations for sepsis.

PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic is rapidly expanding across the world, with more than 100,000 new cases each day as of end-June 2020. Healthcare workers are struggling to provide the best care for COVID-19 patients. Approaches for invasive ventilation vary widely between and within countries and new insights are acquired rapidly. We aim to investigate invasive ventilation practices and outcome in COVID-19 patients in the Netherlands.MethodsPRoVENT-COVID ('study of PRactice of VENTilation in COVID-19') is an investigator-initiated national, multicenter observational study to be undertaken in intensive care units (ICUs) in The Netherlands. Consecutive COVID-19 patients aged 18 years or older, who are receiving invasive ventilation in the participating ICUs, are to be enrolled during a 10-week period, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cmH2O) during the first 3 days of ventilation. Secondary outcomes include other ventilatory variables, use of rescue therapies for refractory hypoxemia such as prone positioning and extracorporeal membrane oxygenation, use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; acute kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality.DiscussionPRoVENT-COVID will be the largest observational study to date, with high density ventilatory data and major outcomes. There is urgent need for a better understanding of ventilation practices, and the effects of ventilator settings on outcomes in COVID-19 patients. The results of PRoVENT-COVID will be rapidly disseminated through electronic presentations, such as webinars and electronic conferences, and publications in international peer-reviewed journals. Access to source data will be made available through local, regional and national anonymized datasets on request, and after agreement of the PRoVENT-COVID steering committee.Trial registrationPRoVENT-COVID is registered at clinicaltrials.gov (identifier NCT04346342).

Extubation strategies in neuro-intensive care unit patients and associations with outcomes: the ENIO multicentre international observational study.

BackgroundProlonged invasive ventilation is common in patients with severe brain injury. Information on optimal management of extubation and on the use of tracheostomy in these patients is scarce. International guidelines regarding the ventilator liberation and tracheostomy are currently lacking.MethodsThe aim of 'Extubation strategies in Neuro-Intensive care unit patients and associations with Outcomes' (ENIO) study is to describe current management of weaning from invasive ventilation, focusing on decisions on timing of tracheal extubation and tracheostomy in intensive care unit (ICU) patients with brain injury. We conducted a prospective, international, multi-centre observational study enrolling patients with various types of brain injury, including trauma, stroke, and subarachnoid haemorrhage, with an initial Glasgow Coma Score equal or less than 12, and a duration of invasive ventilation longer than 24 hours from ICU admission. ENIO is expected to include at least 1,500 patients worldwide. The primary endpoint of the ENIO study is extubation success in the 48 hours following endotracheal tube removal. The primary objective is to validate a score predictive of extubation success. To accomplish this, the study population will be randomly divided to a development cohort (2/3 of the included patients) and a validation cohort (the remaining 1/3). Secondary objectives are: to determine the incidence of extubation success rate according to various time-frames (within 96 hours, >96 hours after extubation); to validate (existing) prediction scores for successful extubation according to various time-frames and definitions (i.e., tracheostomy as extubation failure); and to describe the current practices of extubation and tracheostomy, and their associations.DiscussionENIO will be the largest prospective observational study of ventilator liberation and tracheostomy practices in patients with severe brain injury undergoing invasive mechanical ventilation, providing a validated predictive score of successful extubation.Trial registrationThe ENIO study is registered in the Clinical Trials database: NCT03400904.

Pulmonary complement depositions in autopsy of critically ill patients have no relation with ARDS.

BackgroundThe complement system has frequently been suggested to play a role in the pathophysiology of acute respiratory distress syndrome (ARDS). The current study explored the association between pulmonary depositions of a complement activation product and the clinical diagnosis of ARDS.MethodsLung tissue material from autopsied critically ill patients who died whilst on invasively mechanical ventilation was collected and stained for complement C3d. The diagnosis of ARDS was by the Berlin Definition. Lung injury scores (LIS) and driving pressures were calculated, 48 and 24 h prior to death. A pathologist who remained blinded for the clinical data scored the extent of C3d depositions, using a C3d deposition score (a minimum and maximum score of 0 and 24), and of diffuse alveolar damage (DAD). The primary analysis focused on the association between the C3d deposition score and the clinical diagnosis of ARDS. Secondary analyses focused on associations between the C3d deposition score and the presence of diffuse alveolar damage (DAD) in histopathology, and LIS and driving pressures in the last 2 days before death.ResultsOf 36 patients of whom autopsy material was available, 12 were diagnosed as having had ARDS. In all patients, C3d depositions were found in various parts of the lungs, and to a different extent. Notably, C3d deposition scores were similar for patients with ARDS and those without ARDS (4.5 [3.3-6.8] vs. 5.0 [4.0-6.0]; not significant). C3d deposition scores were also independent from the presence or absence of DAD, and correlations between C3d scores and LIS and driving pressures prior to death were poor.ConclusionPulmonary C3d depositions are found in the lungs of all deceased ICU patients, independent of the diagnosis of ARDS. The presence of complement C3d was not associated with the presence of DAD on histopathology and had a poor correlation with ventilation characteristics prior to death.

The role of hypercapnia in acute respiratory failure.

The biological effects and physiological consequences of hypercapnia are increasingly understood. The literature on hypercapnia is confusing, and at times contradictory. On the one hand, it may have protective effects through attenuation of pulmonary inflammation and oxidative stress. On the other hand, it may also have deleterious effects through inhibition of alveolar wound repair, reabsorption of alveolar fluid, and alveolar cell proliferation. Besides, hypercapnia has meaningful effects on lung physiology such as airway resistance, lung oxygenation, diaphragm function, and pulmonary vascular tree.In acute respiratory distress syndrome, lung-protective ventilation strategies using low tidal volume and low airway pressure are strongly advocated as these have strong potential to improve outcome. These strategies may come at a price of hypercapnia and hypercapnic acidosis. One approach is to accept it (permissive hypercapnia); another approach is to treat it through extracorporeal means. At present, it remains uncertain what the best approach is.

Antithrombin plus alpha-1 protease inhibitor does not affect coagulation and inflammation in two murine models of acute lung injury.

BackgroundIn acute respiratory distress syndrome (ARDS), uncontrolled production of activators of coagulation and proinflammatory mediators results in a shift from an adequate local innate immune response to hypercoagulability and inflammation. This study aimed to investigate whether the protease inhibitors antithrombin (AT) and alpha-1 protease inhibitor (A1PI) may attenuate an exaggerated pulmonary immune response.MethodsLung injury was induced either by single intranasal administration of lipopolysaccharide (LPS) (5 mg/kg) in BALB/c mice or by combination of an intravenous injection of LPS (10 mg/kg) with subsequent injurious ventilation using high tidal volumes (12-15 ml/kg) for 4 h in RccHan Wistar rats. Animals received either a single bolus of AT (250 IU/kg) or A1PI (60 mg/kg) alone or in combination, with or without intravenous low-dose heparin (100 U/kg). Control animals received saline. Additional controls received neither LPS, nor ventilation, nor treatment. Endpoints were local and systemic markers of coagulation, e.g., thrombin-antithrombin complexes (TATc), and inflammation, e.g., interleukin-6.ResultsBoth lung injury models resulted in a pronounced immune response within the pulmonary compartment shown by elevated levels of markers of coagulation and inflammation. The two-hit lung injury model also induced profound systemic coagulopathy and inflammation. Monotherapy with AT or A1PI did not reduce pulmonary coagulopathy or inflammation in any lung injury model. Nor did combination therapy with AT and A1PI result in a decrease of coagulation or inflammatory parameters. AT markedly reduced systemic levels of TATc in the two-hit lung injury model. Systemic inflammation was not affected by the different interventions. Additional administration of heparin did not lead to macroscopic bleeding incidences.ConclusionsIn two different murine models of acute lung injury, neither single therapy with AT or A1PI nor combination of both agents attenuates the pronounced pulmonary coagulation or inflammatory response.

European Respiratory Society International Congress 2018: highlights from Assembly 2 on respiratory intensive care.

The respiratory intensive care Assembly of the European Respiratory Society is proud to present a summary of several important sessions held at the International Congress in Paris in 2018. For the highly esteemed reader who may have missed the Congress, a concise review was written on three topics: the state-of-the-art session on respiratory critical care, hot topics in weaning and the best abstracts in noninvasive ventilation.