Association of lung recruitment and change in recruitment-to-inflation ratio from supine to prone position in acute respiratory distress syndrome.

Prone positioning is an evidence-based treatment for patients with moderate-to-severe acute respiratory distress syndrome. Lung recruitment has been proposed as one of the mechanisms by which prone positioning reduces mortality in this group of patients. Recruitment-to-inflation ratio (R/I) is a method to measure potential for lung recruitment induced by a change in positive end-expiratory pressure (PEEP) on the ventilator. The association between R/I and potential for lung recruitment in supine and prone position has not been studied with computed tomography (CT) scan imaging. In this secondary analysis, we sought to investigate the correlation between R/I measured in supine and prone position with CT and the potential for lung recruitment as measured by CT scan. Among 23 patients, the median R/I did not significantly change from supine (1.9 IQR 1.6-2.6) to prone position (1.7 IQR 1.3-2.8) (paired t test p = 0.051) but the individual changes correlated with the different response to PEEP. In supine and in prone position, R/I significantly correlated with the proportion of lung tissue recruitment induced by the change of PEEP. Lung tissue recruitment induced by a change of PEEP from 5 to 15 cmH2O was 16% (IQR 11-24%) in supine and 14.3% (IQR 8.4-22.6%) in prone position, as measured by CT scan analysis (paired t test p = 0.56). In this analysis, PEEP-induced recruitability as measured by R/I correlated with PEEP-induced lung recruitment as measured by CT scan, and could help to readjust PEEP in prone position.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Propofol and Fentanyl Pharmacokinetics and Pharmacodynamics in Extracorporeal Membrane Oxygenation.

RATIONALE: Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic/pharmacodynamic (PK/PD) data for propofol and fentanyl in patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). OBJECTIVE: Describe propofol and fentanyl PK/PD profiles in V-V ECMO patients. METHODS AND MEASUREMENTS: Prospective, single-center, open-label PK/PD study at the Toronto General Hospital ICU between July 2022 and January 2023. Using high-performance liquid chromatography-tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (PSI) for sedation, and expiratory occlusion pressure (Pocc), and airway occlusion pressure during the first 0.1 seconds (P0.1) for respiratory effort. MAIN RESULTS: Eleven patients underwent 106 evaluations over a median (IQR) follow-up of 146 (116-146) hours. Patient's average (±SD) age was 43 (±13) years, and 55% were female. Propofol and fentanyl PK were best described by a two-compartment model. Propofol-PSI PD was described using an effect compartment, with a coefficient of determination (ρ2) of 0.78. There was a significant increase in propofol (p=0.01) and fentanyl (p=0.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient over-sedation (PSI<40) occurred in 74% of the observations. Females exhibited higher sedative central volume of distribution and lower propofol clearance. CONCLUSION: ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK/PD parameters.

Key performance indicators in extracorporeal membrane oxygenation (ECMO): protocol for a systematic review.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is an intervention used in critically ill patients with severe cardiopulmonary failure that is expensive and resource intensive and requires specialised care. There remains a significant practice variation in its application. This systematic review will assess the evidence for key performance indicators (KPIs) in ECMO. METHODS AND ANALYSIS: We will search Ovid MEDLINE, Ovid EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library including the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and databases from the National Information Center of Health Services Research and Health Care Technology, for studies involving KPIs in ECMO. We will rate methodological quality using the Newcastle-Ottawa Quality Assessment Scale. Randomized controlled trials (RCTs) will be evaluated with the Cochrane Risk of Bias tool, and qualitative studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN checklist). Grey literature sources will be searched for technical reports, practice guidelines and conference proceedings. We will identify relevant organisations, industry leaders and non-profit organisations that represent key opinion leads in the use of ECMO. We will search the Agency of Healthcare Research and Quality National Quality Measures Clearinghouse for ECMO-related KPIs. Studies will be included if they contain quality measures that occur in critically ill patients and are associated with ECMO. The analysis will be primarily descriptive. Each KPI will be evaluated for importance, scientific acceptability, utility and feasibility using the four criteria proposed by the US Strategic Framework Board for a National Quality Measurement and Reporting System. Finally, KPIs will be evaluated for their potential operational characteristics, their potential to be integrated into electronic medical records and their affordability, if applicable. ETHICS AND DISSEMINATION: Ethical approval is not required as no primary data will be collected. Findings will be published in a peer-reviewed journal and presented at academic. PROSPERO REGISTRATION NUMBER: 9 August 2022. CRD42022349910.

Extracorporeal Membrane Oxygenation in COVID-19.

Extracorporeal membrane oxygenation (ECMO) is an intervention for severe acute respiratory distress syndrome (ARDS). Although COVID-19-related ARDS has some distinct features, its overall clinical presentation resembles ARDS from other etiologies. Thus, similar evidence-based practices for its management should be applied. These include lung-protective ventilation, prone positioning, and adjuvant strategies, such as ECMO, when appropriate. Current evidence suggests that ECMO in COVID-19-related ARDS has similar efficacy and safety profile as for non-COVID-19 ARDS. The high number of severe COVID-19 cases and demand for therapies, such as ECMO, poses a unique opportunity to increase the understanding on how to optimize this intervention.

Decline in Ventilatory Ratio as a Predictor of Mortality in Adults With ARDS Receiving Prone Positioning.

BACKGROUND: Prone positioning reduces mortality in patients with moderate/severe ARDS. It remains unclear which physiological parameters could guide clinicians to assess which patients are likely to benefit from prone position. This study aimed to determine the association between relative changes in physiological parameters at 24 h of prone positioning and ICU mortality in adult subjects with ARDS. METHODS: We conducted a cohort study using the VENTILA database, including adults with ARDS receiving prone positioning. We used multivariable logistic regression to assess the association between relative changes in physiological parameters (PaO2 /FIO2 , dynamic driving pressure, PaCO2 , and ventilatory ratio defined as [minute ventilation [mL/min] × PaCO2 [mm Hg]]/[predicted body weight × 100 [mL/min] × 37.5 [mm Hg] with ICU mortality) (primary outcome). We report adjusted odds ratios with 95% CI as measures of association. RESULTS: We included 156 subjects of which 82 (53%) died in the ICU. A relative decline in the ventilatory ratio at 24 h was associated with lower ICU mortality (odds ratio 0.80 [95% CI 0.66-0.97], every 10% decrease). Relative changes in PaO2 /FIO2 (odds ratio 0.89 [95% CI 0.77-1.03], every 25% increase), PaCO2 (odds ratio 0.97 [95% CI 0.82-1.16], every 10% decrease), and dynamic driving pressure (odds ratio 0.98 [95% CI 0.89-1.07], every 10% decrease) were not associated with ICU mortality. CONCLUSIONS: In subjects with ARDS receiving prone positioning, a relative decline in the ventilatory ratio at 24 h was associated with lower ICU mortality.

Association of different positive end-expiratory pressure selection strategies with all-cause mortality in adult patients with acute respiratory distress syndrome.

BACKGROUND: The acute respiratory distress syndrome (ARDS) has high morbidity and mortality. Positive end-expiratory pressure (PEEP) is commonly used in patients with ARDS but the best method to select the optimal PEEP level and reduce all-cause mortality is unclear. The primary objective of this network meta-analysis is to summarize the available evidence and to compare the effect of different PEEP selection strategies on all-cause mortality in adult patients with ARDS. METHODS: We will search MEDLINE, Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and LILACS from inception onwards for randomized controlled trials assessing the effect of PEEP selection strategies in adult patients with moderate to severe ARDS. We will exclude studies that did not use a lung-protective ventilation approach as part of the comparator or intervention strategy. The primary outcome will be all-cause mortality (at the longest available follow-up and up to 90 days). Secondary outcomes will include barotrauma, ventilator-free days, intensive care unit and hospital length of stay, and changes in oxygenation. Two reviewers will independently screen all citations, full-text articles, and extract study-data. We will assess the risk of bias for each of the outcomes using version 2 of the Cochrane risk of bias tool for randomized controlled trials. If feasible, Bayesian network meta-analyses will be conducted to obtain pooled estimates of all potential head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and risk differences, together with the associated 95% credible intervals. We will assess certainty in effect estimates using GRADE methodology. DISCUSSION: The present study will inform clinical decision-making for adult patients with ARDS and will improve our understanding of the limitations of the available literature assessing PEEP selection strategies. Finally, this information may also inform the design of future randomized trials, including the selection of interventions, comparators, and predictive enrichment strategies. TRIAL REGISTRATION: PROSPERO 2020 CRD42020193302 .

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

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 (VT), driving pressure (ΔP), or mechanical power. METHODS: The correlation between differences in VT, 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 (Powerelastic), excluding PEEP (Powerdynamic), and using ΔP (Powerdriving). 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 VT, ΔP, and Powerdynamic 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, Powerelastic 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, VT, ΔP, Powerelastic, Powerdynamic, and Powerdriving 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 VT or ΔP.

Cryoprobe biopsy for the diagnosis of acute hypoxemic respiratory failure of undetermined origin.

RATIONALE: Acute hypoxemic respiratory failure is a condition that comprises a wide array of entities. Obtaining a histological lung sample might help reach a diagnosis and direct an appropriate treatment in a select group of patients. OBJECTIVE: To describe our experience in the use of cryobiopsy for the diagnosis of acute hypoxemic respiratory failure of undetermined origin. METHODS: Retrospective analysis of case series of patients with acute hypoxemic respiratory failure who underwent lung cryobiopsy at the Intensive Care Unit of the Hospital Italiano de Buenos Aires, Argentina. RESULTS: Cryobiopsy yielded a histological diagnosis in all patients (n = 10, 100%). This led to either a change in therapy or continuation of a specific treatment in eight of these patients. Cryobiopsy was found to be contributive in all the patients who did not meet Berlin criteria for acute respiratory distress syndrome. No major complications were associated with the procedure. CONCLUSIONS: Cryobiopsy is a safe procedure with a high diagnostic yield in a selected group of patients.

[Use of Extracorporeal Membrane Oxygenation in idiopathic capillary leak syndrome: a case report]. / Utilización de membrana de circulación extracorpórea en síndrome de leak capilar idiopático: reporte de un caso.

Introduction: Idiopathic systemic capillary leak syndrome (ISCLS) or Clarkson's disease is unusual but potentially lethal, characterized by recurrent shock incidents and anasarca secondary to idiopathic increase of capillary permeability. In such a context, the use of venoarterial Extracorporeal Membrane Oxygenation (ECMO) as cardiorespiratory support is a rescue action that seeks hemodynamic stability generation until spontaneous disappearance of the capillary occurs with the objective of surpassing the complications of resorption phase. Case Report: A 42 year old patient presented ISCLS and required ECMO as hemodynamic support for 8 days. She remained 20 days in Intensive Care Unit and was given hospital release after 43 days. Conclusions: The use of ECMO in the reported case was a useful strategy in the ISCLS management as a bridge to recovery both in the leak stage and the fluid resorption phase. Notwithstanding its indication is limited to thoroughly selected patients and requires further debate between specialists about its risks and benefits.

Introducción: El Síndrome de Leak Capilar Idiopático (SLCI) o enfermedad de Clarkson es un entidad rara pero potencialmente letal, caracterizada por episodios recurrentes de shock y anasarca secundarios al aumento idiopático de la permeabilidad capilar. En este contexto, el uso de membrana de oxigenación extracorpórea (ECMO) venoarterial como soporte cardiorrespiratorio, es una medida de rescate que busca generar estabilidad hemodinámica a la espera de la desaparición espontánea del leak capilar con el fin de sortear las complicaciones de la fase de reabsorción. Caso Clínico: Se presenta el caso de un paciente un paciente de 42 años de edad que presentó SLCI y requirió ECMO durante 8 días como soporte hemodinámico. Cursó 20 días de internación en la unidad de terapia intensiva y se otorgó el alta hospitalaria luego de 43 días. Conclusiones: El uso de ECMO en el caso reportado significó una estrategia útil para el manejo del SLCI como puente a la recuperación, tanto en la etapa de leak como en la fase de reabsorción de fluidos. Sin embargo, su indicación se ve limitada a pacientes altamente seleccionados, y todavía requiere un mayor debate entre especialistas sobre los posibles riesgos y beneficios.