Publications by authors named "Lorenzo Del Sorbo"

93 Publications

Propensity-Adjusted Comparison of Mortality of Elderly Versus Very Elderly Ventilated Patients.

Respir Care 2021 Mar 2. Epub 2021 Mar 2.

Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.

Background: The growing proportion of elderly intensive care patients constitutes a public health challenge. The benefit of critical care in these patients remains unclear. We compared outcomes in elderly versus very elderly subjects receiving mechanical ventilation.

Methods: In total, 5,557 mechanically ventilated subjects were included in our post hoc retrospective analysis, a subgroup of the VENTILA study. We divided the cohort into 2 subgroups on the basis of age: very elderly subjects (age ≥ 80 y; = 1,430), and elderly subjects (age 65-79 y; = 4,127). A propensity score on being very elderly was calculated. Evaluation of associations with 28-d mortality was done with logistic regression analysis.

Results: Very elderly subjects were clinically sicker as expressed by higher SAPS II scores (53 ± 18 vs 50 ± 18, < .001), and their rates of plateau pressure < 30 cm HO were higher, whereas other parameters did not differ. The 28-d mortality was higher in very elderly subjects (42% vs 34%, < .001) and remained unchanged after propensity score adjustment (adjusted odds ratio 1.31 [95% CI 1.16-1.49], < .001).

Conclusions: Age was an independent and unchangeable risk factor for death in mechanically ventilated subjects. However, survival rates of very elderly subjects were > 50%. Denial of critical care based solely on age is not justified. (ClinicalTrials.gov registration NCT02731898.).
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http://dx.doi.org/10.4187/respcare.08547DOI Listing
March 2021

Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.

N Engl J Med 2021 Feb 25. Epub 2021 Feb 25.

From Baylor College of Medicine, Houston (I.O.R.); James J. Peters Veterans Affairs Medical Center, Bronx, and Icahn School of Medicine at Mount Sinai, New York - both in New York (N.B.); eStudy Site, Chula Vista (M.W.), Genentech, South San Francisco (M.B., L.T.), and the University of California, San Diego, La Jolla (A.M.) - all in California; Hackensack Meridian School of Medicine and Hacksensack University Medical Center, Hackensack, NJ (R.C.G.); Intermountain Healthcare, Salt Lake City (B.D.H.); Royal Free Hospital (S.B.) and Imperial College London (N.C., T.Y.), London, Leeds Teaching Hospitals NHS Trust and National Institute for Health Research-Leeds Biomedical Research Centre, Leeds (S.S.), North Manchester General Hospital, Manchester (A.U.), and Roche Products, Welwyn Garden City (S.D., E.G., B.M., H.S.) - all in the United Kingdom; the University of Massachusetts Medical School-Baystate, Springfield (D.S.); Rush University Medical Center, Chicago (M.S.A.); Denver Health Medical Center, Denver (I.S.D.), and the University of Colorado, Anschutz School of Medicine, Aurora (I.S.D.); University Health Network, Toronto (L.D.S.); Hospital Universitario HM Sanchinarro, Centro Integral, Oncológico Clara Campal and Departamento de Ciencias Médicas Clínicas, Facultad de Medicina, Universidad CEU San Pablo, Madrid (A.C.G.); and the University of Miami Miller School of Medicine, Miami (D.J.D.L.Z.).

Background: Coronavirus disease 2019 (Covid-19) is associated with immune dysregulation and hyperinflammation, including elevated interleukin-6 levels. The use of tocilizumab, a monoclonal antibody against the interleukin-6 receptor, has resulted in better outcomes in patients with severe Covid-19 pneumonia in case reports and retrospective observational cohort studies. Data are needed from randomized, placebo-controlled trials.

Methods: In this phase 3 trial, we randomly assigned patients who were hospitalized with severe Covid-19 pneumonia in a 2:1 ratio receive a single intravenous infusion of tocilizumab (at a dose of 8 mg per kilogram of body weight) or placebo. Approximately one quarter of the participants received a second dose of tocilizumab or placebo 8 to 24 hours after the first dose. The primary outcome was clinical status at day 28 on an ordinal scale ranging from 1 (discharged or ready for discharge) to 7 (death) in the modified intention-to-treat population, which included all the patients who had received at least one dose of tocilizumab or placebo.

Results: Of the 452 patients who underwent randomization, 438 (294 in the tocilizumab group and 144 in the placebo group) were included in the primary and secondary analyses. The median value for clinical status on the ordinal scale at day 28 was 1.0 (95% confidence interval [CI], 1.0 to 1.0) in the tocilizumab group and 2.0 (non-ICU hospitalization without supplemental oxygen) (95% CI, 1.0 to 4.0) in the placebo group (between-group difference, -1.0; 95% CI, -2.5 to 0; P = 0.31 by the van Elteren test). In the safety population, serious adverse events occurred in 103 of 295 patients (34.9%) in the tocilizumab group and in 55 of 143 patients (38.5%) in the placebo group. Mortality at day 28 was 19.7% in the tocilizumab group and 19.4% in the placebo group (weighted difference, 0.3 percentage points (95% CI, -7.6 to 8.2; nominal P = 0.94).

Conclusions: In this randomized trial involving hospitalized patients with severe Covid-19 pneumonia, the use of tocilizumab did not result in significantly better clinical status or lower mortality than placebo at 28 days. (Funded by F. Hoffmann-La Roche and the Department of Health and Human Services; COVACTA ClinicalTrials.gov number, NCT04320615.).
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http://dx.doi.org/10.1056/NEJMoa2028700DOI Listing
February 2021

Donor ventilation parameters as predictors for length of mechanical ventilation after lung transplantation: Results of a prospective multicenter study.

J Heart Lung Transplant 2021 Jan 28;40(1):33-41. Epub 2020 Oct 28.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: The evaluation of donor lungs heavily depends on the subjective judgment of the retrieval surgeon. As a consequence, acceptance rates vary significantly among transplant centers. We aimed to determine donor ventilation parameters in a prospective study and test if they could be used as objective quality criteria during organ retrieval.

Methods: A prospective evaluation of lung donors was performed in 3 transplant centers. Ventilation parameters were collected at the time of retrieval using a standardized ventilation protocol. Recipient length of mechanical ventilation (LMV) was defined as the primary end point, and collected data was used to build linear models predicting LMV.

Results: In total, 166 donors were included in this study. Median LMV after transplantation was 32 hours (interquartile range: 20-63 hours). Peak inspiratory pressure and dynamic compliance (C) at the time of retrieval, but not the partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio, correlated with recipient LMV in Spearman correlations (r = 0.280, p = 0.002; r = -0.245, p = 0.003; and r = 0.064, p = 0.432, respectively). Linear models were built to further evaluate the impact of donor ventilation parameters on LMV. The first model was based on donor P/F ratio, donor age, donor intubation time, donor smoking history, donor partial pressure of carbon dioxide, aspiration, chest trauma, and pathologic chest X-ray. This model performed poorly (multiple R-squared = 0.063). In a second model, donor ventilation parameters were included, and C was identified as the strongest predictor for LMV. The third model was extended by recipient factors, which significantly improved the robustness of the model (multiple R-squared = 0.293).

Conclusion: In this prospective evaluation of donor lung parameters, currently used donor quality criteria poorly predicted recipient LMV. Our data suggest that C is a strong donor-bound parameter to predict short-term graft performance; however, recipient factors are similarly relevant.
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http://dx.doi.org/10.1016/j.healun.2020.10.008DOI Listing
January 2021

Impact of therapeutic hypothermia on bleeding events in adult patients treated with extracorporeal life support peri-cardiac arrest.

J Crit Care 2020 Nov 16;62:12-18. Epub 2020 Nov 16.

Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

Purpose: Whether therapeutic hypothermia (TH) adds to the risk of bleeding in patients on extracorporeal life support (ECLS) peri-cardiac arrest remains unknown.

Material And Methods: Single center retrospective study on patients receiving veno-arterial ECLS peri-cardiac arrest ± TH at 32-34 °C (January 2009-December 2015).

Primary Outcome: major bleeding (including intracerebral hemorrhage, ICH) < 72 h of cardiac arrest. Logistic regression and marginal structural models were used to analyze associations with major bleeding.

Results: Of 66 patients receiving ECLS, 36 were treated with TH. Major bleeding occurred in 14 patients (39%) treated with ECLS+TH and in 17 patients (57%) with ECLS alone. ICH was reported in 3 (8%) and one patient (3%), respectively. There was no difference in mortality, but lung injury occurred more often in ECLS+TH. A platelet count <60 × 10/L but not TH was associated with major bleeding (including ICH). The estimated causal risk ratio of TH on the occurrence of major bleeding (including ICH) at 72 h post cardiac arrest was 0.95 (95%CI 0.62-1.45).

Conclusions: Bleeding complications were common in our study. However, TH (32-34 °C) was not associated with an increased risk of major bleeding in patients on ECLS peri-cardiac arrest.
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http://dx.doi.org/10.1016/j.jcrc.2020.11.008DOI Listing
November 2020

Ventilation parameters and early graft function in double lung transplantation.

J Heart Lung Transplant 2021 Jan 13;40(1):4-11. Epub 2020 Oct 13.

Division of Thoracic Surgery, Medical University of Vienna, Vienna, Austria. Electronic address:

Background: Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU).

Methods: A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (P), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest.

Results: In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (P, cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679.

Conclusions: The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter.
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http://dx.doi.org/10.1016/j.healun.2020.10.003DOI Listing
January 2021

Veno-venous ECMO as a platform to evaluate lung lavage and surfactant replacement therapy in an animal model of severe ARDS.

Intensive Care Med Exp 2020 Oct 27;8(1):63. Epub 2020 Oct 27.

Latner Thoracic Surgery Research Laboratories, Toronto, Canada.

Background: There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT.

Methods: Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized post-injury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n = 5) or recruitment maneuvers alone (control, n = 5) during ECMO.

Results: PaO/FiO after aspiration injury was 62.6 ± 8 mmHg and 60.9 ± 9.6 mmHg in the control and treatment group, respectively (p = 0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls.

Conclusions: A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.
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http://dx.doi.org/10.1186/s40635-020-00352-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591687PMC
October 2020

Effect of Driving Pressure Change During Extracorporeal Membrane Oxygenation in Adults With Acute Respiratory Distress Syndrome: A Randomized Crossover Physiologic Study.

Crit Care Med 2020 Dec;48(12):1771-1778

1Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada. 2Latner Thoracic Surgery Research Laboratories, University Health Network, University of Toronto, Toronto, ON, Canada. 3Extracorporeal Life Support Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. 4Department of Medicine, Division of Respirology, University Health Network and Sinai Health System, Toronto, ON, Canada. 5Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada. 6Department of Medicine, University Health Network and Sinai Health System, Toronto, ON, Canada. 7Division of Thoracic Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. 8Keenan Research Center at the Li-Ka-Shing Knowledge Institute of St. Michael´s Hospital, Toronto, ON, Canada. 9Toronto General Hospital Research Institute, Toronto, ON, Canada.

Objectives: Venovenous extracorporeal membrane oxygenation is an effective intervention to improve gas exchange in patients with severe acute respiratory distress syndrome. However, the mortality of patients with severe acute respiratory distress syndrome supported with venovenous extracorporeal membrane oxygenation remains high, and this may be due in part to a lack of standardized mechanical ventilation strategies aimed at further minimizing ventilator-induced lung injury. We tested whether a continuous positive airway pressure ventilation strategy mitigates ventilator-induced lung injury in patients with severe acute respiratory distress syndrome on venovenous extracorporeal membrane oxygenation, compared with current ventilation practice that employs tidal ventilation with limited driving pressure. We used plasma biomarkers as a surrogate outcome for ventilator-induced lung injury.

Design: Randomized crossover physiologic study.

Setting: Single-center ICU.

Patients: Ten patients with severe acute respiratory distress syndrome supported on venovenous extracorporeal membrane oxygenation.

Interventions: The study included four phases. After receiving pressure-controlled ventilation with driving pressure of 10 cm H2O for 1 hour (phase 1), patients were randomly assigned to receive first either pressure-controlled ventilation 20 cm H2O for 2 hours (phase 2) or continuous positive airway pressure for 2 hours (phase 3), and then crossover to the other phase for 2 hours; during phase 4 ventilation settings returned to baseline (pressure-controlled ventilation 10 cm H2O) for 4 hours.

Measurements And Main Results: There was a linear relationship between the change in driving pressure and the plasma concentration of interleukin-6, soluble receptor for advanced glycation end products, interleukin-1ra, tumor necrosis factor alpha, surfactant protein D, and interleukin-10.

Conclusions: Ventilator-induced lung injury may occur in acute respiratory distress syndrome patients on venovenous extracorporeal membrane oxygenation despite the delivery of volume- and pressure-limited mechanical ventilation. Reducing driving pressure to zero may provide more protective mechanical ventilation in acute respiratory distress syndrome patients supported with venovenous extracorporeal membrane oxygenation. However, the risks versus benefits of such an approach need to be confirmed in studies that are designed to test patient centered outcomes.
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http://dx.doi.org/10.1097/CCM.0000000000004637DOI Listing
December 2020

Comparing the Effects of Tidal Volume, Driving Pressure, and Mechanical Power on Mortality in Trials of Lung-Protective Mechanical Ventilation.

Respir Care 2021 Feb 25;66(2):221-227. Epub 2020 Aug 25.

Interdepartmenal Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.

Background: The unifying goal of lung-protective ventilation strategies in ARDS is to minimize the strain and stress applied by mechanical ventilation to the lung to reduce ventilator-induced lung injury (VILI). The relative contributions of the magnitude and frequency of mechanical stress and the end-expiratory pressure to the development of VILI is unknown. Consequently, it is uncertain whether the risk of VILI is best quantified in terms of tidal volume (V), driving pressure (ΔP), or mechanical power.

Methods: The correlation between differences in V, ΔP, and mechanical power and the magnitude of mortality benefit in trials of lung-protective ventilation strategies in adult subjects with ARDS was assessed by meta-regression. Modified mechanical power was computed including PEEP (Power), excluding PEEP (Power), and using ΔP (Power). The primary analysis incorporated all included trials. A secondary subgroup analysis was restricted to trials of lower versus higher PEEP strategies.

Results: We included 9 trials involving 4,731 subjects in the analysis. Odds ratios for moderation derived from meta-regression showed that variations in V, ΔP, and Power were associated with increased mortality with odds ratios of 1.24 (95% CI 1.03-1.49), 1.31 (95% CI 1.03-1.66), and 1.37 (95% CI 1.05-1.78), respectively. In trials comparing higher versus lower PEEP strategies, Power was increased in the higher PEEP arm (24 ± 1.7 vs 20 ± 1.5 J/min, respectively), whereas the other parameters were not affected on average by a higher PEEP ventilation strategy.

Conclusions: In trials of lung-protective ventilation strategies, V, ΔP, Power, Power, and Power exhibited similar moderation of treatment effect on mortality. In this study, modified mechanical power did not add important information on the risk of death from VILI in comparison to V or ΔP.
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http://dx.doi.org/10.4187/respcare.07876DOI Listing
February 2021

Intracranial hemorrhage on extracorporeal membrane oxygenation: an international survey.

Perfusion 2020 Jun 24:267659120932705. Epub 2020 Jun 24.

Interdepartmental Division of Critical Care Medicine, Toronto General Hospital, Toronto, ON, Canada.

Introduction: Intracranial hemorrhage is one of the most dreaded complications associated with extracorporeal membrane oxygenation. However, robust data to guide clinical practice are lacking. We aimed to describe the current perceptions and practices surrounding the risk, prevention, diagnosis, management, and prognosis of intracranial hemorrhage in patients on extracorporeal membrane oxygenation.

Methods: We conducted an international, cross-sectional survey of adult extracorporeal membrane oxygenation centers using a self-administered electronic questionnaire sent to medical directors and program coordinators of all 290 adult centers member of the Extracorporeal Life Support Organization.

Results: There were 143 respondents (49%). The median proportion of patients having neuroimaging performed was only 1-25% in venovenous-extracorporeal membrane oxygenation patients and 26-50% in venoarterial-extracorporeal membrane oxygenation and extracorporeal cardiopulmonary resuscitation. The majority of participants (58%) tolerated a PaO < 60 mm Hg on venovenous-extracorporeal membrane oxygenation. Lower PaO targets were inversely correlated with the reported incidence of intracranial hemorrhage (r =-0.247; p = 0.024). In patients with intracranial hemorrhage, most participants reported stopping anticoagulation, and median targets for blood product administration were 70,000-99,000 platelets/µL, 1.5-1.9 of international normalized ratio, and 1.6-2.0 g/L of fibrinogen.

Conclusion: We found significant heterogeneity in the perceptions and practices. This underlines the need for more research to appropriately guide patient management. Importantly, neuroimaging was performed only in a minority of patients. Considering the important management implications reported by most centers when intracranial hemorrhage is diagnosed, perhaps clinicians should consider widening their indications for early neuroimaging.
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http://dx.doi.org/10.1177/0267659120932705DOI Listing
June 2020

Association of Noninvasive Oxygenation Strategies With All-Cause Mortality in Adults With Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-analysis.

JAMA 2020 07;324(1):57-67

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.

Importance: Treatment with noninvasive oxygenation strategies such as noninvasive ventilation and high-flow nasal oxygen may be more effective than standard oxygen therapy alone in patients with acute hypoxemic respiratory failure.

Objective: To compare the association of noninvasive oxygenation strategies with mortality and endotracheal intubation in adults with acute hypoxemic respiratory failure.

Data Sources: The following bibliographic databases were searched from inception until April 2020: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and LILACS. No limits were applied to language, publication year, sex, or race.

Study Selection: Randomized clinical trials enrolling adult participants with acute hypoxemic respiratory failure comparing high-flow nasal oxygen, face mask noninvasive ventilation, helmet noninvasive ventilation, or standard oxygen therapy.

Data Extraction And Synthesis: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a bayesian framework to derive risk ratios (RRs) and risk differences along with 95% credible intervals (CrIs) were conducted. GRADE methodology was used to rate the certainty in findings.

Main Outcomes And Measures: The primary outcome was all-cause mortality up to 90 days. A secondary outcome was endotracheal intubation up to 30 days.

Results: Twenty-five randomized clinical trials (3804 participants) were included. Compared with standard oxygen, treatment with helmet noninvasive ventilation (RR, 0.40 [95% CrI, 0.24-0.63]; absolute risk difference, -0.19 [95% CrI, -0.37 to -0.09]; low certainty) and face mask noninvasive ventilation (RR, 0.83 [95% CrI, 0.68-0.99]; absolute risk difference, -0.06 [95% CrI, -0.15 to -0.01]; moderate certainty) were associated with a lower risk of mortality (21 studies [3370 patients]). Helmet noninvasive ventilation (RR, 0.26 [95% CrI, 0.14-0.46]; absolute risk difference, -0.32 [95% CrI, -0.60 to -0.16]; low certainty), face mask noninvasive ventilation (RR, 0.76 [95% CrI, 0.62-0.90]; absolute risk difference, -0.12 [95% CrI, -0.25 to -0.05]; moderate certainty) and high-flow nasal oxygen (RR, 0.76 [95% CrI, 0.55-0.99]; absolute risk difference, -0.11 [95% CrI, -0.27 to -0.01]; moderate certainty) were associated with lower risk of endotracheal intubation (25 studies [3804 patients]). The risk of bias due to lack of blinding for intubation was deemed high.

Conclusions And Relevance: In this network meta-analysis of trials of adult patients with acute hypoxemic respiratory failure, treatment with noninvasive oxygenation strategies compared with standard oxygen therapy was associated with lower risk of death. Further research is needed to better understand the relative benefits of each strategy.
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http://dx.doi.org/10.1001/jama.2020.9524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273316PMC
July 2020

Protective Mechanical Ventilation in Organ Donors: A Lifesaving Maneuver.

Am J Respir Crit Care Med 2020 07;202(2):167-169

Interdepartmental Division of Critical Care MedicineUniversity of TorontoToronto, Ontario, Canadaand.

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http://dx.doi.org/10.1164/rccm.202005-1559EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365355PMC
July 2020

Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Supported with Extracorporeal Membrane Oxygenation. Lost in Translational Research?

Am J Respir Crit Care Med 2020 08;202(3):314-315

Interdepartmental Division of Critical Care MedicineUniversity of TorontoToronto, Ontario, Canadaand.

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http://dx.doi.org/10.1164/rccm.202004-1139EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397807PMC
August 2020

Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis.

Syst Rev 2020 04 26;9(1):95. Epub 2020 Apr 26.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

Background: Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure.

Methods: We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology.

Discussion: This study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure.

Systematic Review Registration: PROSPERO CRD42019121755.
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http://dx.doi.org/10.1186/s13643-020-01363-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184712PMC
April 2020

The Early Change in Pa after Extracorporeal Membrane Oxygenation Initiation Is Associated with Neurological Complications.

Am J Respir Crit Care Med 2020 06;201(12):1525-1535

Interdepartmental Division of Critical Care Medicine, Toronto General Hospital, and.

: Large decreases in Pa that occur when initiating extracorporeal membrane oxygenation (ECMO) in patients with respiratory failure may cause cerebral vasoconstriction and compromise brain tissue perfusion.: To determine if the magnitude of Pa correction upon ECMO initiation is associated with an increased incidence of neurological complications in patients with respiratory failure.: We conducted a multicenter, international, retrospective cohort study using the Extracorporeal Life Support Organization Registry, including adults with respiratory failure receiving ECMO via any mode between 2012 and 2017. The relative change in Pa in the first 24 hours was calculated as (24-h post-ECMO Pa - pre-ECMO Pa)/pre-ECMO Pa. The primary outcome was the occurrence of neurological complications, defined as seizures, ischemic stroke, intracranial hemorrhage, or brain death.: We included 11,972 patients, 88% of whom were supported with venovenous ECMO. The median relative change in Pa was -31% (interquartile range, -46% to -12%). Neurological complications were uncommon overall (6.9%), with a low incidence of seizures (1.1%), ischemic stroke (1.9%), intracranial hemorrhage (3.5%), and brain death (1.6%). Patients with a large relative decrease in Pa (>50%) had an increased incidence of neurological complications compared with those with a smaller decrease (9.8% vs. 6.4%;  < 0.001). A large relative decrease in Pa was independently associated with neurological complications after controlling for previously described risk factors (odds ratio, 1.7; 95% confidence interval, 1.3 to 2.3;  < 0.001).: In patients receiving ECMO for respiratory failure, a large relative decrease in Pa in the first 24 hours after ECMO initiation is independently associated with an increased incidence of neurological complications.
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http://dx.doi.org/10.1164/rccm.202001-0023OCDOI Listing
June 2020

Impact of imipenem concentration in lung perfusate and tissue biopsy during clinical ex-vivo lung perfusion of high-risk lung donors.

Minerva Anestesiol 2020 Jun 27;86(6):617-626. Epub 2020 Jan 27.

Department of Medical and Surgical Sciences, Anesthesia, and Intensive Care Medicine, Sant'Orsola Polyclinic Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy.

Background: Normothermic ex-vivo lung perfusion (EVLP) limits organ donor shortage by potentially using high-risk donor lungs. Microbial burden reduction has been demonstrated after EVLP using antibiotic prophylaxis with imipenem. However, no data have been published on the clinical consequences of the potential residual bacterial burden.

Methods: Imipenem concentration was measured every hour (T0 to T6) in the lung perfusate and at the end of EVLP (Tf) in biopsies. The antimicrobial activity of perfusate at T1 and Tf against E. coli and K. pneumoniae was evaluated. Lungs were distinguished: no bacterial species in recipients and donors (donor-/recipient-); bacterial species isolated from donors and not from recipients (donor+/recipient-); same bacterial species in both recipients and donors (donor+/recipient+). Interleukin 6 (IL-6) and IL-8 concentrations in lung perfusate, clinical pulmonary infection score (CPIS) and primary graft dysfunction (PGD) were evaluated.

Results: Imipenem concentration in perfusate decreased over time. T1 and Tf perfusates exhibited bactericidal activity against E. coli and K. pneumoniae. Overall, T1 perfusates yielded higher bactericidal titers (BTs) than Tf. The donor+/recipient+ group (26% of cases) had higher IL-6 and IL-8 in perfusate and higher CPIS.

Conclusions: Recipients with the same bacterial species isolated in their donors had higher risk of pulmonary inflammation and early post-transplant pneumonia. Improvements in antimicrobial strategies during EVLP are warranted to minimize the consequences of donor associated respiratory infection.
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http://dx.doi.org/10.23736/S0375-9393.20.13840-9DOI Listing
June 2020

Inter-country variability over time in the mortality of mechanically ventilated patients.

Intensive Care Med 2020 03 7;46(3):444-453. Epub 2020 Jan 7.

Hospital Universitario de Getafe, Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Carretera de Toledo km 12, 500 28905, Madrid, Spain.

Purpose: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management.

Methods: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed.

Results: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72-0.93); 2010: 0.63 (95% CI 0.53-0.75); 2016: 0.49 (95% CI 0.39-0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57-2.48); in 2004: 1.76 (95% CI 1.47-2.06); in 2010: 1.55 (95% CI 1.37-1.74), and in 2016: 1.39 (95% CI 1.25-1.54).

Conclusions: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898).
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http://dx.doi.org/10.1007/s00134-019-05867-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222132PMC
March 2020

A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation.

Crit Care 2019 11 6;23(1):346. Epub 2019 Nov 6.

Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.

Background: Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔP) could be used as a highly feasible non-invasive technique to screen for these conditions.

Methods: Respiratory muscle pressure (P), dynamic transpulmonary driving pressure (ΔP, the difference between peak and end-expiratory transpulmonary pressure), and ΔP were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔP and P from ΔP was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China).

Results: Fifty-two daily recordings were collected in 16 patients. In this sample, P and ΔP were frequently excessively high: P exceeded 10 cm HO on 84% of study days and ΔP exceeded 15 cm HO on 53% of study days. ΔP measurements accurately detected P > 10 cm HO (AUROC 0.92, 95% CI 0.83-0.97) and ΔP > 15 cm HO (AUROC 0.93, 95% CI 0.86-0.99). In the external validation cohort (n = 12), estimating P and ΔP from ΔP measurements detected excessively high P and ΔP with similar accuracy (AUROC ≥ 0.94).

Conclusions: Measuring ΔP enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients.
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http://dx.doi.org/10.1186/s13054-019-2617-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836358PMC
November 2019

Easy prognostic assessment of concomitant organ failure in critically ill patients undergoing mechanical ventilation.

Eur J Intern Med 2019 Dec 9;70:18-23. Epub 2019 Oct 9.

Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf 40225, Germany. Electronic address:

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening disease. We evaluated the prognostic utility of Model for End-stage Liver Disease excluding INR (MELD-XI) score for predicting mortality in a cohort of critically ill patients on mechanical ventilation.

Methods: In total, 11,091 mechanically ventilated patients were included in our post-hoc retrospective analysis, a subgroup of the VENTILA study (NCT02731898). Evaluation of associations with mortality was done by logistic and Cox regression analysis, an optimal cut-off was calculated using the Youden Index. We divided the cohort in two sub-groups based on their MELD-XI score at the optimal cut-off (12 score points).

Results: Peak-, plateau- and positive end-expiratory pressure were higher in patients with MELD-XI>12. Patients with MELD-XI>12 had higher driving pressures (14 ± 6 cmH2O versus 13 ± 6; p < 0.001). MELD-XI was associated with 28-day mortality after correction for relevant cofounders including SAPS II and ventilation pressures (HR 1.04 95%CI 1.03-1.05; p < 0.001. Patients with MELD-XI>12 evidenced both increased hospital (46% versus 27%; p < 0.001) and 28-day mortality (39% versus 22%).

Conclusions: MELD-XI is independently associated with mortality and constitutes a useful and easily applicable tool for risk stratification in critically ill patients receiving mechanical ventilation.

Trial Registration: NCT02731898, registered 4 April 2016.
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http://dx.doi.org/10.1016/j.ejim.2019.09.002DOI Listing
December 2019

When kidneys are too bright…a rare cause of shock.

Intensive Care Med 2020 04 8;46(4):804-805. Epub 2019 Oct 8.

Interdepartmental Division of Critical Care Medicine, Medical Surgical Intensive Care, University of Toronto, Toronto General Hospital, PMB 11-122, Toronto, ON, M5G 2N2, Canada.

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http://dx.doi.org/10.1007/s00134-019-05798-5DOI Listing
April 2020

Potential for Lung Recruitment Estimated by the Recruitment-to-Inflation Ratio in Acute Respiratory Distress Syndrome. A Clinical Trial.

Am J Respir Crit Care Med 2020 01;201(2):178-187

Keenan Research Centre and Li Ka Shing Institute, Department of Critical Care, St. Michael's Hospital, Toronto, Ontario, Canada.

Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the presence of complete airway closure. To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP. Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm HO of PEEP. Multiple pressure-volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm HO) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio. Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated ( = 0.798;  < 0.0001) with small bias (-21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0-2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation ( = 0.004), whereas low recruiters experienced lower systolic arterial pressure ( = 0.008). A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.Clinical trial registered with www.clinicaltrials.gov (NCT02457741).
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http://dx.doi.org/10.1164/rccm.201902-0334OCDOI Listing
January 2020

Alveolar recruitment in acute respiratory distress syndrome: should we open the lung (no matter what) or may accept (part of) the lung closed?

Intensive Care Med 2019 10 16;45(10):1436-1439. Epub 2019 Aug 16.

Anesthesia and Intensive Care Medicine, Alma Mater Studiorum University of Bologna, Policlinico di Sant'Orsola, Via Massarenti 9, 40138, Bologna, Italy.

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http://dx.doi.org/10.1007/s00134-019-05734-7DOI Listing
October 2019

Principlism and Personalism. Comparing Two Ethical Models Applied Clinically in Neonates Undergoing Extracorporeal Membrane Oxygenation Support.

Front Pediatr 2019 30;7:312. Epub 2019 Jul 30.

Department of Critical Care, The Hospital for Sick Children, Toronto, ON, Canada.

Extracorporeal membrane oxygenation (ECMO) is a technology used to temporarily assist critically ill patients with acute and reversible life-threatening cardiac and/or respiratory failure. This technology can often be lifesaving but is also associated with several complications that may contribute to reduced survival. Currently, neonates supported with ECMO are complex and bear an increased risk of mortality. This means that clinicians must be particularly prepared not only to deal with complex clinical scenarios, but also ethical issues associated with ECMO. In particular, clinicians should be trained to handle unsuccessful ECMO runs with attention to high quality end of life care. Within this manuscript we will compare and contrast the application of two ethical frameworks, used in the authors' institutions (Toronto and Rome). This is intended to enhance a broader understanding of cultural differences in applied ethics which is useful to the clinician in an increasingly multicultural and diverse patient mix.
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http://dx.doi.org/10.3389/fped.2019.00312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682695PMC
July 2019

Extracorporeal life support and systemic inflammation.

Intensive Care Med Exp 2019 Jul 25;7(Suppl 1):46. Epub 2019 Jul 25.

Interdepartmental Division of Critical Care Medicine, Toronto General Hospital, University of Toronto, Toronto, Canada.

Extracorporeal life support (ECLS) encompasses a wide range of extracorporeal modalities that offer short- and intermediate-term mechanical support to the failing heart or lung. Apart from the daily use of cardiopulmonary bypass (CPB) in the operating room, there has been a resurgence of interest and utilization of veno-arterial and veno-venous extracorporeal membrane oxygenation (VA- and VV-ECMO, respectively) and extracorporeal carbon dioxide removal (ECCOR) in recent years. This might be attributed to the advancement in technology, nonetheless the morbidity and mortality associated with the clinical application of this technology is still significant. The initiation of ECLS triggers a systemic inflammatory response, which involves the activation of the coagulation cascade, complement systems, endothelial cells, leukocytes, and platelets, thus potentially contributing to morbidity and mortality. This is due to the release of cytokines and other biomarkers of inflammation, which have been associated with multiorgan dysfunction. On the other hand, ECLS can be utilized as a therapy to halt the inflammatory response associated with critical illness and ICU therapeutic intervention, such as facilitating ultra-protective mechanical ventilation. In addition to addressing the impact on outcome of the relationship between inflammation and ECLS, two different but complementary pathophysiological perspectives will be developed in this review: ECLS as the cause of inflammation and ECLS as the treatment of inflammation. This framework may be useful in guiding the development of novel therapeutic strategies to improve the outcome of critical illness.
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http://dx.doi.org/10.1186/s40635-019-0249-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658641PMC
July 2019

Extracorporeal carbon dioxide removal for acute hypercapnic respiratory failure.

Ann Intensive Care 2019 Jul 2;9(1):79. Epub 2019 Jul 2.

Intensive Care Unit, Hospital Universitario Sagrado Corazón, Barcelona, Spain.

In the past, the only treatment of acute exacerbations of obstructive diseases with hypercapnic respiratory failure refractory to medical treatment was invasive mechanical ventilation (IMV). Considerable technical improvements transformed extracorporeal techniques for carbon dioxide removal in an attractive option to avoid worsening respiratory failure and respiratory acidosis, and to potentially prevent or shorten the duration of IMV in patients with exacerbation of COPD and asthma. In this review, we will present a summary of the pathophysiological rationale and evidence of ECCOR in patients with severe exacerbations of these pathologies.
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http://dx.doi.org/10.1186/s13613-019-0551-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606679PMC
July 2019

Veno-venous extracorporeal life support for blastomycosis-associated acute respiratory distress syndrome.

Perfusion 2019 11 26;34(8):660-670. Epub 2019 Apr 26.

Interdepartmental Division of Critical Care Medicine, Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.

Background: Blastomyces is a dimorphic fungus endemic to regions of North America, which can lead to pneumonia and fatal severe acute respiratory diseases syndrome in up to 89% of patients. Extracorporeal life support can provide adequate oxygenation while allowing the lungs to rest and heal, which might be an ideal therapy in this patient group, although long-term clinical and radiological outcomes are not known.

Clinical Features: We report on five consecutive patients admitted to Toronto General Hospital intensive care unit between January 2012 and September 2016, with progressive respiratory failure requiring veno-venous extracorporeal life support within 24-96 hours following mechanical ventilation. Ultra-lung protective mechanical ventilation was achieved within 24 hours. Recovery was the initial goal in all patients. Extracorporeal life support was provided for a prolonged period (up to 49 days), and four patients were successfully discharged from the intensive care unit. Long-term radiological assessment in three patients showed major improvement within 2 years of follow-up with some persistent disease-related changes (bronchiectasis, fibrosis, and cystic changes). In two patients, long-term functional and neuropsychological outcomes showed similar limitations to what is seen in acute respiratory distress syndrome patients who are not supported with extracorporeal life support and in acute respiratory distress syndrome patients without blastomycosis, but worse pulmonary function outcomes in the form of obstructive and restrictive changes that correlated with the radiological imaging.

Conclusion: Veno-venous extracorporeal life support can effectively provide prolonged support for patients with blastomycosis-associated acute respiratory distress syndrome that is safe and associated with favorable long-term outcomes.
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http://dx.doi.org/10.1177/0267659119844391DOI Listing
November 2019

Donor prone positioning protects lungs from injury during warm ischemia.

Am J Transplant 2019 10 25;19(10):2746-2755. Epub 2019 Apr 25.

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, ON, Canada.

A large proportion of controlled donation after circulatory death (cDCD) donor lungs are declined because cardiac arrest does not occur within a suitable time after the withdrawal of life-sustaining therapy. Improved strategies to preserve lungs after asystole may allow the recovery team to arrive after death actually occurs and enable the recovery of lungs from more cDCD donors. The aim of this study was to determine the effect of donor positioning on the quality of lung preservation after cardiac arrest in a cDCD model. Cardiac arrest was induced by withdrawal of ventilation under anesthesia in pigs. After asystole, animals were divided into 2 groups based on body positioning (supine or prone). All animals were subjected to 3 hours of warm ischemia. After the observation period, donor lungs were explanted and preserved at 4°C for 6 hours, followed by 6 hours of physiologic and biological lung assessment under normothermic ex vivo lung perfusion. Donor lungs from the prone group displayed significantly greater quality as reflected by better function during ex vivo lung perfusion, less edema formation, less cell death, and decreased inflammation compared with the supine group. A simple maneuver of donor prone positioning after cardiac arrest significantly improves lung graft preservation and function.
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http://dx.doi.org/10.1111/ajt.15363DOI Listing
October 2019

Mechanical Ventilation in Acute Respiratory Distress Syndrome: Time Heals All Wounds, or Does It?

Anesthesiology 2019 May;130(5):680-682

From the Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada (L.D.S., A.S.S.) University Health Network, Toronto General Hospital, Toronto, Ontario, Canada (L.D.S.) Department of Medicine and Physiology, Mayo Clinic, Rochester, Minnesota (R.H.) Department of Medicine, University of Minnesota, Minneapolis, Minnesota (R.H.) Keenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada (A.S.S.).

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http://dx.doi.org/10.1097/ALN.0000000000002671DOI Listing
May 2019

lung perfusion as a platform for organ repair in acute respiratory distress syndrome.

J Thorac Dis 2019 Jan;11(1):30-34

Latner Thoracic Surgery Laboratories, Toronto General Hospital Research Institute, Department of Surgery and Department of Critical Care, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.21037/jtd.2018.11.58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384357PMC
January 2019

The Impact of High-Flow Nasal Oxygen in the Immunocompromised Critically Ill: A Systematic Review and Meta-Analysis.

Respir Care 2018 Dec;63(12):1555-1566

Interdepartmental Division of Critical Care Medicine, Sinai Health System/University Health Network, University of Toronto, Ontario, Canada.

Background: High-flow nasal-cannula (HFNC) may be an oxygen modality useful for preventing invasive mechanical ventilation and mortality; however, its role in acute hypoxemic respiratory failure is not clearly defined. We sought to evaluate the impact of HFNC on mortality across immunocompromised subjects compared to alternative noninvasive oxygen therapies, namely conventional oxygen therapy and noninvasive ventilation (NIV).

Methods: We systematically searched the major databases to identify randomized, controlled trials (RCTs) or observational studies (until May 2018). We included studies reporting the use of HFNC in immunocompromised subjects and evaluated its impact on mortality and invasive mechanical ventilation.

Results: Upon review of 6,506 titles, 13 studies (1,956 subjects) fulfilled our inclusion criteria (4 RCTs, 9 observational studies). The predominant cause of immunocompromised status was cancer. Bacterial pneumonia was the most common cause of acute hypoxemic respiratory failure with a median P/F of 145 mm Hg (interquartile range 115-175). HFNC was used as the first oxygen strategy in 474 subjects compared to NIV (242 subjects) and conventional O therapy (703 subjects). There was a 46% rate of invasive mechanical ventilation and 36% mortality. Mortality at the longest available follow-up was lower with HFNC compared to the oxygen therapy controls (NIV or conventional O therapy) in 7 studies (1,429 subjects; relative risk 0.72, 95% CI 0.56-0.93, = .01). There was a lower rate of invasive mechanical ventilation with HFNC compared to the oxygen therapy controls across 8 studies (1,529 subjects, relative risk 0.81, 95% CI 0.67-0.96, = .02). These results were robust across a series of sensitivity analyses.

Conclusions: There exists a need to develop a greater evidence base evaluating the utility of HFNC in immunocompromised subjects. In our exploratory analysis, HFNC was found to decrease mortality and use of invasive mechanical ventilation compared to alternative noninvasive oxygen controls. These results are meant to be exploratory. Higher-quality studies evaluating a more homogeneous population are needed to further elucidate its benefit.
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http://dx.doi.org/10.4187/respcare.05962DOI Listing
December 2018

Effects of liver ischemia-reperfusion injury on respiratory mechanics and driving pressure during orthotopic liver transplantation.

Minerva Anestesiol 2019 05 30;85(5):494-504. Epub 2018 Oct 30.

Department of Anesthesia and Intensive Care Medicine, Umberto I Polyclinic Hospital, Sapienza University, Rome, Italy.

Background: During orthotopic liver transplantation (OLT), liver graft ischemia-reperfusion injury (IRI) triggers a cytokine-mediated systemic inflammatory response, which impairs graft function and disrupts distal organ homeostasis. The objective of this prospective, observational trial was to assess the effects of IRI on lung and chest wall mechanics in the intraoperative period of patients undergoing OLT.

Methods: In 26 patients undergoing OLT, we measured elastance of the respiratory system (ERS), partitioned into lung (EL) and chest wall (ECW), hemodynamics, and fluid and blood product intake before laparotomy (T1), after portal/caval surgical clamp (T2), and immediately (T3) and, at 90 and 180 minutes post-reperfusion (T4 and T5, respectively). Interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β and tumor necrosis factor-α plasma concentrations were assessed at T1, T4 and T5.

Results: EL significantly decreased from T1 to T2 (13.5±4.4 vs 9.7±4.8 cmH2O/L, P<0.05), remained stable at T3, while at T4 (12.3±4.4 cmH2O/L, P<0.05) was well above levels recorded at T2, reaching its highest value at T5 (15±3.9 cmH2O/L, P<0.05). Variations in ERS, EL, driving pressure (∆P) and trans-pulmonary pressure (∆PL) significantly correlated with changes in IL-6 and MCP-1 plasma concentrations, but not with changes in wedge pressure, fluid amounts, and red blood cells and platelets administered. No correlation was found between changes in cytokine concentrations and ECW.

Conclusions: We found that EL, ECW, ∆P and ∆PL underwent significant variations during the OLT procedure. Further, we documented a significant association between the respiratory mechanics changes and the inflammatory response following liver graft reperfusion.
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http://dx.doi.org/10.23736/S0375-9393.18.12890-2DOI Listing
May 2019