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The optimal anticoagulation strategy for venovenous extracorporeal membrane oxygenation (VV-ECMO) is not known.To evaluate the safety of anticoagulation strategies and monitoring during VV-ECMO for respiratory failure.We conducted a systematic review to evaluate the association between anticoagulation strategies during VV-ECMO and prespecified outcomes, including major bleeding episodes, thrombotic events, and in-hospital mortality. We included articles published between 1977 and January 30, 2015. Study quality was assessed using the Newcastle-Ottawa scoring system. A separate meta-analysis was not planned.Data were independently extracted by two authors and collected on a standardized report form.A total of 18 studies (n = 646) were included; 17 studies enrolled patients with acute respiratory distress syndrome. Across all studies, the duration of VV-ECMO support ranged from 4 to 20 days. Patients received an average of 2.3 (±3.9) units of transfused red blood cells per day. The bleeding rate across all studies was 16%, and the rate of thrombosis was 53%. Among seven studies (199 patients) targeting a specified activated partial thromboplastin time (aPTT), there were 37 (19%) major bleeding episodes and 53 (27%) major thromboses. Among five studies (43 patients) with aPTT targets of 60 seconds or greater, there were 24 (56%) bleeding episodes and 3 (7%) clotting events. Three studies (156 patients) with an aPTT target under 60 seconds reported 13 (8%) and 50 (32%) significant bleeding and thrombotic events, respectively. The most commonly reported thrombotic events were circuit-related clotting and deep-vein thrombosis. Mortality during VV-ECMO varied across the studies, ranging from 0 to at least 50% at heterogeneous time points. The total number of deaths for all studies combined was 186 (29%).The role and optimal therapeutic targets for anticoagulation during VV-ECMO are unclear. Previously published studies are limited by retrospective, observational design, small cohorts, and patient heterogeneity. The clinical significance of reported thrombotic complications is largely unknown. This systematic review underscores the need for randomized controlled trials of anticoagulation strategies for patients undergoing VV-ECMO for respiratory failure.

Background: Veno-arterial extracorporeal life support (VA-ECLS) is widely used to treat refractory cardiogenic shock. However, increased left ventricular (LV) afterload in VA-ECLS can worsen pulmonary congestion and compromise myocardial recovery. Our objectives were to explore the efficacy, safety, and optimal timing of adjunctive LV venting strategies. Methods: A systematic search was performed on Medline, EMBASE, PubMed, CDSR, CCRCT, CINAHL, ClinicalTrials.Gov, and WHO ICTRP from inception until January 2019 for all relevant studies, including LV venting. Data were analyzed for mortality and weaning from VA-ECLS on the basis of timing of LV venting, along with adverse complications. Results: A total of 7995 patients were included from 62 observational studies, wherein 3458 patients had LV venting during VA-ECLS. LV venting significantly improved weaning from VA-ECLS (odds ratio, 0.62 [95% CI, 0.47–0.83]; P =0.001) and reduced short-term (30 day; risk ratio [RR], 0.86 [95% CI, 0.77–0.96]; P =0.008) but not in-hospital (RR, 0.92 [95% CI, 0.83–1.01] P =0.09) or long-term (6 months; RR, 0.96 [95% CI, 0.90–1.03]; P =0.27) mortality. Early (P =0.03) but not late (≥12 hours; RR, 0.99 [95% CI, 0.71–1.38]; P =0.93) LV venting significantly reduced short-term mortality. Patients with LV venting spent more time on VA-ECLS (3.6 versus 2.8 days, P P =0.013). With the exception of hemolysis (RR, 2.18 [95% CI, 1.58–3.01]; P Conclusions: LV venting, especially if done early (

Background Routine application of chlorhexidine oral rinse is recommended to reduce risk of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Recent reappraisal of the evidence from two meta-analyses suggests chlorhexidine may cause excess mortality in non-cardiac surgery patients and does not reduce VAP. Mechanisms for possible excess mortality are unclear. The CHORAL study will evaluate the impact of de-adopting chlorhexidine and implementing an oral care bundle (excluding chlorhexidine) on mortality, infection-related ventilator-associated complications (IVACs), and oral health status. Methods The CHORAL study is a stepped wedge, cluster randomized controlled trial in six academic intensive care units (ICUs) in Toronto, Canada. Clusters (ICU) will be randomly allocated to six sequential steps over a 14-month period to de-adopt oral chlorhexidine and implement a standardized oral care bundle (oral assessment, tooth brushing, moisturization, and secretion removal). On study commencement, all clusters begin with a control period in which the standard of care is oral chlorhexidine. Clusters then begin crossover from control to intervention every 2 months according to the randomization schedule. Participants include all mechanically ventilated adults eligible to receive the standardized oral care bundle. The primary outcome is ICU mortality; secondary outcomes are IVACs and oral health status. We will determine demographics, antibiotic usage, mortality, and IVAC rates from a validated local ICU clinical registry. With six clusters and 50 ventilated patients on average each month per cluster, we estimate that 4200 patients provide 80% power after accounting for intracluster correlation to detect an absolute reduction in mortality of 5.5%. We will analyze our primary outcome of mortality using a generalized linear mixed model adjusting for time to account for secular trends. We will conduct a process evaluation to determine intervention fidelity and to inform interpretation of the trial results. Discussion The CHORAL study will inform understanding of the effectiveness of de-adoption of oral chlorhexidine and implementation of a standardized oral care bundle for decreasing ICU mortality and IVAC rates while improving oral health status. Our process evaluation will inform clinicians and decision makers about intervention delivery to support future de-adoption if justified by trial results. Trial registration ClinicalTrials.gov, NCT03382730. Registered on December 26, 2017.

Rationale: Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting ...

Collection and analysis of health data are crucial to achieving high-quality clinical care, research, and quality improvement. This review explores existing hospital, regional, provincial and national data platforms in Canada to identify gaps and barriers, and recommend improvements for data science. The Canadian Critical Care Trials Group and the Canadian Critical Care Translational Biology Group undertook an environmental survey using list-identified names and keywords in PubMed and the grey literature, from the Canadian context. Findings were grouped into sections, corresponding to geography, purpose, and patient sub-group initiatives, using a narrative qualitative approach. Emerging themes, impressions, and recommendations towards improving data initiatives were generated. In Canada, the Canadian Institute for Health Information Discharge Abstract Database contains high-level clinical data on every adult and child discharged from acute care facilities; however, it does not contain data from Quebec, critical care-specific severity of illness risk-adjustment scores, physiologic data, or data pertaining to medication use. Provincially mandated critical care platforms in four provinces contain more granular data, and can be used to risk adjust and link to within-province data sets; however, no inter-provincial collaborative mechanism exists. There is very limited infrastructure to collect and link biological samples from critically ill patients nationally. Comprehensive international clinical data sets may inform future Canadian initiatives. Clinical and biological data collection among critically ill patients in Canada is not sufficiently coordinated, and lags behind other jurisdictions. An integrated and inclusive critical care data platform is a key clinical and scientific priority in Canada.

Research evaluating outcomes in critically ill patients with acute respiratory and cardiac failure supported with extracorporeal membrane oxygenation has increased significantly. The objective was to identify a core set of outcomes that are essential to include in all clinical research evaluating the use of either venoarterial or venovenous extracorporeal membrane oxygenation in critically ill patients, particularly regarding safety and adverse events.A three-round modified Delphi process.Patients, caregivers, multidisciplinary clinicians, researchers, industry partners, and research funders were included.Participants represented key extracorporeal membrane oxygenation organizations, including the Extracorporeal Life Support Organization, the International Extracorporeal Membrane Oxygenation Network, clinicians from high volume extracorporeal membrane oxygenation centers, and extracorporeal membrane oxygenation researchers or former extracorporeal membrane oxygenation patients from five continents.We used recommended standards for the development of a core outcome set. Outcome measures identified from systematic reviews of the literature and from qualitative studies of survivors were mapped to the domains identified by the Core Outcome Measures in Effectiveness Trials initiative separately for venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation.Participant response rates were 40 of 47 (85%), 35 of 37 (95%), and 64 of 69 (93%) for survey rounds 1, 2, and 3, respectively, with participants representing 10 different countries on five continents. After the third round survey, 8 outcome measures met consensus for both venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation.This study identified core outcomes to assess in all research evaluating the use of extracorporeal membrane oxygenation, including adverse events specific to this intervention, permitting standardization of outcome reporting for the first time. Identifying appropriate measurement instruments to evaluate these outcomes is an important next step to enable synthesis of extracorporeal membrane oxygenation research.

Mechanical ventilation has long been the cornerstone of treatment for acute respiratory failure to facilitate gas exchange while allowing time for the underlying lung injury to heal. However, ventilator-induced lung injury (VILI) may contribute to the morbidity and mortality associated with acute

There is limited data available to guide management of patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). An international cross-sectional survey of medical directors/program coordinators from Extracorporeal Life Support Organization centers was conducted. A hierarchical clustering on principle components was used. A total of 243 (55%) centers responded and were divided into three clusters: Cluster 1 (n = 102) had few high volumes and low specialized heart failure (HF) involvement; Cluster 2 (n = 75) had few high volumes and moderate HF involvement; Cluster 3 (n = 66) contained the majority of centers with >50 annual cases and high HF involvement. The most divergent responses were observed between Clusters 1 and 3 wherein Cluster 1 centers were less likely to change management based on pulse pressure (77% vs. 100%; p < 0.001) and would rather avoid inotropes to "rest the heart" (28%). Cluster 3 centers were more likely to perform daily echocardiograms (50% vs. 24%, p < 0.001), which were less likely to be exclusively performed by cardiologist (36% vs. 58%, p < 0.046) and base weaning on echocardiographic findings, when compared to Cluster 1 (3.97/5 vs. 3.56, p < 0.001). Responses were variable in management reflecting the lack of evidence for hemodynamic care for those supported with VA-ECMO.

Patient-ventilator asynchrony is common among critically ill patients undergoing mechanical ventilation and has been associated with adverse outcomes. Neurally adjusted ventilatory assist is a ventilatory mode that may lead to improved patient-ventilator synchrony. We conducted a systematic review to determine the impact of neurally adjusted ventilatory assist on patient-ventilator asynchrony, other physiologic variables, and clinical outcomes in adult patients undergoing invasive mechanical ventilation in comparison with conventional pneumatically triggered ventilatory modes.We searched Medline, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central, CINAHL, Scopus, Web of Science, conference abstracts, and ClinicalTrials.gov until July 2018.Two authors independently screened titles and abstracts for randomized and nonrandomized controlled trials (including crossover design) comparing the occurrence of patient-ventilator asynchrony between neurally adjusted ventilatory assist and pressure support ventilation during mechanical ventilation in critically ill adults. The asynchrony index and severe asynchrony (i.e., asynchrony index10%) were the primary outcomes.Two authors independently extracted study characteristics and outcomes and assessed risk of bias of included studies.Of 11,139 unique citations, 26 studies (522 patients) met the inclusion criteria. Sixteen trials were included in the meta-analysis using random effects models through the generic inverse variance method. In several different clinical scenarios, the use of neurally adjusted ventilatory assist was associated with significantly reduced asynchrony index (mean difference, -8.12; 95% CI, -11.61 to -4.63; very low quality of evidence) and severe asynchrony (odds ratio, 0.42; 95% CI, 0.23-0.76; moderate quality of evidence) as compared with pressure support ventilation. Furthermore, other measurements of asynchrony were consistently improved during neurally adjusted ventilatory assist.Neurally adjusted ventilatory assist improves patient-ventilator synchrony; however, its effects on clinical outcomes remain uncertain. Randomized controlled trials are needed to determine whether the physiologic efficiency of neurally adjusted ventilatory assist affects patient-important outcomes in critically ill adults.

Background: The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. Methods: We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. Results: The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. Conclusions: A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Prediction scoring systems for coronary artery bypass grafting (CABG) patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) have not yet been reported. This study was designed to develop a predictive score for in-hospital mortality for cardiogenic shock patients who received VA-ECMO after isolated CABG. Methods Retrospective cohort study of consecutive CABG patients supported with VA-ECMO (n = 166) at the Beijing Anzhen Hospital between February 2004 and March 2017. Results One hundred and six patients (64%) could be weaned from VA-ECMO, and 74 patients (45%) survived to hospital discharge. On the basis of multivariable logistic regression analyses, the pRedicting mortality in patients undergoing veno-arterial Extracorporeal MEMBrane oxygenation after coronary artEry bypass gRafting (REMEMBER) score was created with six pre-ECMO parameters: older age, left main coronary artery disease, inotropic score > 75, CK-MB > 130 IU/L, serum creatinine > 150 umol/L, and platelet count 25) with their corresponding mortality (13%, 55%, 70%, and 94%, respectively), were identified. The area under the receiver operating characteristic curve 0.85(95% CI 0.79–0.91) for the REMEMBER score was better than those for the SOFA, SAVE, EuroSCORE, and ENCOURAGE scores in this population. Conclusions The REMEMBER score might help clinicians at bedside to predict in-hospital mortality for patients receiving VA-ECMO after isolated CABG for refractory cardiogenic shock. Prospective studies are needed to externally validate this scoring system. Electronic supplementary material The online version of this article (10.1186/s13054-019-2307-y) contains supplementary material, which is available to authorized users.

International audience; Importance:Bayesian analysis of clinical trial data may provide useful information to aid in study interpretation, especially when trial evidence suggests that the benefits of an intervention are uncertain, such as in a trial that evaluated early extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS).Objective:To demonstrate the potential utility of Bayesian analyses by estimating the posterior probability, under various assumptions, that early ECMO was associated with reduced mortality in patients with very severe ARDS in a randomized clinical trial (RCT).Design and Evidence:A post hoc Bayesian analysis of data from an RCT (ECMO to Rescue Lung Injury in Severe ARDS [EOLIA]) that included 249 patients with very severe ARDS who had been randomized to receive early ECMO (n = 124; mortality at 60 days, 35%) vs initial conventional lung-protective ventilation with the option for rescue ECMO (n = 125, mortality at 60 days, 46%). The trial was designed to detect an absolute risk reduction (ARR) of 20%, relative risk (RR) of 0.67. Statistical prior distributions were specified to represent varying levels of preexisting enthusiasm or skepticism for ECMO and by Bayesian meta-analysis of previously published studies (with downweighting to account for differences and quality between studies). The RR, credible interval (CrI), ARR, and probability of clinically important mortality benefit (varying from RR less than 1 to RR less than 0.67 and ARR from 2% or more to 20% or more) were estimated with Bayesian modeling.Findings:Combining a minimally informative prior distribution with the findings of the EOLIA trial, the posterior probability of RR less than 1 for mortality at 60 days after randomization was 96% (RR, 0.78 [95% CrI, 0.56-1.04]); the posterior probability of RR less than 0.67 was 18%, the probability of ARR of 2% or more was 92%, and the probability of ARR of 20% or more was 2%. With a moderately enthusiastic prior, equivalent to information from a trial of 264 patients with an RR of 0.78, the estimated RR was 0.78 (95% CrI, 0.63-0.96), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 8%, the probability of ARR of 2% or more was 97%, and the probability of ARR of 20% or more was 0%. With a strongly skeptical prior, equivalent to information from a trial of 264 patients with an RR of 1.0, the estimated RR was 0.88 (95% CrI, 0.71-1.09), the probability of RR less than 1 was 88%, the probability of RR less than 0.67 was 0%, the probability of ARR of 2% or more was 78%, and the probability of ARR of 20% or more was 0%. If the prior was informed by previous studies, the estimated RR was 0.71 (95% CrI, 0.55-0.94), the probability of RR less than 1 was 99%, the probability of RR less than 0.67 was 48%, the probability of ARR of 2% or more was 98%, and the probability of ARR of 20% or more was 4%.Conclusions and Relevance:Post hoc Bayesian analysis of data from a randomized clinical trial of early extracorporeal membrane oxygenation compared with conventional lung-protective ventilation with the option for rescue extracorporeal membrane oxygenation among patients with very severe acute respiratory distress syndrome provides information about the posterior probability of mortality benefit under a broad set of assumptions that may help inform interpretation of the study findings.

Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population.This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: "worsening" if moderate or severe acute respiratory distress syndrome criteria were met, "persisting" if mild acute respiratory distress syndrome criteria were the most severe category, and "improving" if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2.Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening.Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population.

Key Points Question What are the characteristics of intensive care unit admissions identified by 2 proposed pandemic ventilator allocation triage guidelines using Sequential Organ Failure Assessment scores when applied retrospectively to critically ill US patients who received mechanical ventilation? Findings In this cohort study of 40 439 admissions to intensive care units that received mechanical ventilation, the New York State guideline identified 9% who would likely meet criteria for the lowest priority for ventilator allocation compared with 4% from the original White and Lo guideline. Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with 39% survival to hospital discharge for admissions identified as lowest priority using the New York State guideline compared with 56% for admissions identified using White and Lo. Meaning Two distinct approaches to triage for mechanical ventilation showed little agreement, suggesting that further clinical assessment of different potential criteria for triage decisions is important to ensure equitable allocation of resources., Importance In the current setting of the coronavirus disease 2019 pandemic, there is concern for the possible need for triage criteria for ventilator allocation; to our knowledge, the implications of using specific criteria have never been assessed. Objective To determine which and how many admissions to intensive care units are identified as having the lowest priority for ventilator allocation using 2 distinct sets of proposed triage criteria. Design, Setting, and Participants This retrospective cohort study conducted in spring 2020 used data collected from US hospitals and reported in the Philips eICU Collaborative Research Database. Adult admissions (N = 40 439) to 291 intensive care units from 2014 to 2015 who received mechanical ventilation and were not elective surgery patients were included. Exposures New York State triage criteria and original triage criteria proposed by White and Lo. Main Outcomes and Measures Sequential Organ Failure Assessment (SOFA) scores were calculated for admissions. The proportion of patients who met initial criteria for the lowest level of priority for mechanical ventilation using each set of criteria and their characteristics and outcomes were assessed. Agreement was compared between the 2 sets of triage criteria, recognizing differences in stated criteria aims. Results Among 40 439 intensive care unit admissions of patients who received mechanical ventilation, the mean (SD) age was 62.6 (16.6) years, 54.9% were male, and the mean (SD) SOFA score was 4.5 (3.7). Using the New York State triage criteria, 8.9% (95% CI, 8.7%-9.2%) were in the lowest priority category; these lowest priority admissions had a mean (SD) age of 62.9 (16.6) years, used a median (interquartile range) of 57.3 (20.1-133.5) ventilator hours each, and had a hospital survival rate of 38.6% (95% CI, 37.0%-40.2%). Using the White and Lo triage criteria, 4.3% (95% CI, 4.1%-4.5%) were in the lowest priority category; these admissions had a mean (SD) age of 68.6 (13.2) years, used a median (interquartile range) of 61.7 (24.3-142.8) ventilator hours each, and had a hospital survival rate of 56.2% (95% CI, 53.8%-58.7%). Only 655 admissions (1.6%) were in the lowest priority category for both guidelines, with the κ statistic for agreement equal to 0.20 (95% CI, 0.18-0.21). Conclusions and Relevance Use of 2 initially proposed ventilator triage guidelines identified approximately 1 in every 10 to 25 admissions as having the lowest priority for ventilator allocation, with little agreement. Clinical assessment of different potential criteria for triage decisions in critically ill populations is important to ensure valid and equitable allocation of resources., This cohort study compares the New York State Ventilator Allocation Guideline with the original triage criteria proposed by White and Lo to determine which and how many admissions to US intensive care units are identified as having the lowest priority for ventilator allocation.

Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design.To stratify patients for post-ICU disability and recovery to 1 year after critical illness.We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling.The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year.ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

Background: Intensive care unit-acquired paresis (ICUAP) is associated with poor outcomes. Our objective was to evaluate predictors for ICUAP and the short-term outcomes associated with this condition. Methods: A secondary analysis of a prospective study including 4157 mechanically ventilated adults in 494 intensive care units from 39 countries. After sedative interruption, patients were screened for ICUAP daily, which was defined as the presence of symmetric and flaccid quadriparesis associated with decreased or absent deep tendon reflexes. A multinomial logistic regression was used to create a predictive model for ICUAP. Propensity score matching was used to estimate the relationship between ICUAP and short-term outcomes (ie, weaning failure and intensive care unit [ICU] mortality). Results: Overall, 114 (3%) patients had ICUAP. Variables associated with ICUAP were duration of mechanical ventilation (relative risk ratio [RRR] per day, 1.10; 95% confidence interval [CI] 1.08-1.12), steroid therapy (RRR 1.8; 95% CI, 1.2-2.8), insulin therapy (RRR 1.8; 95% CI 1.2-2.7), sepsis (RRR 1.9; 95% CI: 1.2 to 2.9), acute renal failure (RRR 2.2; 95% CI 1.5-3.3), and hematological failure (RRR 1.9; 95% CI: 1.2-2.9). Coefficients were used to generate a weighted scoring system to predict ICUAP. ICUAP was significantly associated with both weaning failure (paired rate difference of 22.1%; 95% CI 9.8-31.6%) and ICU mortality (paired rate difference 10.5%; 95% CI 0.1-24.0%). Conclusions: Intensive care unit-acquired paresis is relatively uncommon but is significantly associated with weaning failure and ICU mortality. We constructed a weighted scoring system, with good discrimination, to predict ICUAP in mechanically ventilated patients at the time of awakening.

Purpose Fulminant myocarditis (FM) is a rare disease that may progress rapidly to refractory cardiogenic shock requiring temporary mechanical circulatory support. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been used to provide biventricular support in these patients, however, studies have demonstrated conflicting results, likely due to small sample size. We conducted a systematic review and meta-analysis to evaluate short-term mortality after VA-ECMO in patients with FM. Methods Seven relevant databases were systematically searched on June 1st, 2019 to identify studies evaluating death at 30 days and/or hospital discharge (short-term mortality) after VA-ECMO support for FM. We included studies with n≥5, published after 2009. Mortality risk was meta-analyzed using random effect models. We performed a meta-regression analysis to explore heterogeneity based on a priori defined factors. We assessed the quality of the evidence using the GRADE approach. Results We included 12 retrospective studies (Figure) with 859 patients, mean age 38 ± 12 years to 59 ± 17 years, proportion of female patients ranged from 40% to 60%. In 5 studies (n=144), FM was verified by biopsy. In 4 studies (n=67), the reported use of steroids ranged from 13% to 41%, and in 4 studies (n=207), co-therapy with IABP ranged from 65% to 96%. The pooled short-term mortality was 41% (95% CI 34-47%; I2=64%). The exploration of heterogeneity showed that age and sex significantly impacted short-term mortality after VA-ECMO with lowest mortality in studies with younger populations and higher proportion of female patients. Conclusion In patients with rapidly progressive FM, short-term mortality was 41%. Mortality might be even lower in younger and in female patients. Cardiopulmonary support with VA-ECMO provides an invaluable tool in the treatment of fatal FM, where appropriate patient selection can further improve their outcomes.

Importance Low diaphragm muscle mass at the outset of mechanical ventilation may predispose critically ill patients to poor clinical outcomes. Objective To determine whether lower baseline diaphragm thickness (Tdi) is associated with delayed liberation from mechanical ventilation and complications of acute respiratory failure (reintubation, tracheostomy, prolonged ventilation >14 days, or death in the hospital). Design, Setting, and Participants Secondary analysis (July 2018 to June 2019) of a prospective cohort study (data collected May 2013 to January 2016). Participants were 193 critically ill adult patients receiving invasive mechanical ventilation at 3 intensive care units in Toronto, Ontario, Canada. Exposures Diaphragm thickness was measured by ultrasonography within 36 hours of intubation and then daily. Patients were classified as having low or high diaphragm muscle mass according to the median baseline Tdi. Main Outcomes and Measures The primary outcome was time to liberation from ventilation accounting for the competing risk of death and adjusting for age, body mass index, severity of illness, sepsis, change in Tdi during ventilation, baseline comorbidity, and study center. Secondary outcomes included in-hospital death and complications of acute respiratory failure. Results A total of 193 patients were available for analysis; the mean (SD) age was 60 (15) years, 73 (38%) were female, and the median (interquartile range) Sequential Organ Failure Assessment score was 10 (8-13). Median (interquartile range) baseline Tdi was 2.3 (2.0-2.7) mm. In the primary prespecified analysis, baseline Tdi of 2.3 mm or less was associated with delayed liberation from mechanical ventilation (adjusted hazard ratio for liberation, 0.51; 95% CI, 0.36-0.74). Lower baseline Tdi was associated a higher risk of complications of acute respiratory failure (adjusted odds ratio, 1.77; 95% CI, 1.20-2.61 per 0.5-mm decrement) and prolonged weaning (adjusted odds ratio, 2.30; 95% CI, 1.42-3.74). Lower baseline Tdi was also associated with a higher risk of in-hospital death (adjusted odds ratio, 1.47; 95% CI, 1.00-2.16 per 0.5-mm decrement), particularly after discharge from the intensive care unit (adjusted odds ratio, 2.68; 95% CI, 1.35-5.32 per 0.5-mm decrement). Conclusions and Relevance In this study, low baseline diaphragm muscle mass in critically ill patients was associated with prolonged mechanical ventilation, complications of acute respiratory failure, and an increased risk of death in the hospital.

Objectives Venovenous extracorporeal membrane oxygenation is increasingly being used to support patients with severe acute respiratory distress syndrome, but its cost-effectiveness is unknown. We assessed the cost-utility of venovenous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome in adults compared with standard lung protective ventilation from the perspective of the healthcare system. Design We conducted a cost-utility analysis with a cohort state transition decision model using a lifetime time horizon, 1.5% discount rate, and outcomes reported as cost per quality-adjusted life year. Literature reviews were conducted to inform the model variables. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty in the model. Setting Canadian publicly funded healthcare system. Patients Hypothetical cohort of adults with severe acute respiratory distress syndrome. Interventions Venovenous extracorporeal membrane oxygenation or standard lung protective ventilation. Measurements and main results In our model, the use of venovenous extracorporeal membrane oxygenation compared with lung protective ventilation resulted in a gain of 5.2 life years and 4.05 quality-adjusted life years, at an additional lifetime cost of $145,697 Canadian dollars. The incremental cost-effectiveness ratio was $36,001/quality-adjusted life year. Sensitivity analyses show that the incremental cost-effectiveness ratio is sensitive to the efficacy of extracorporeal membrane oxygenation therapy and costs. Conclusions Based on current data, venovenous extracorporeal membrane oxygenation is cost-effective for patients with severe acute respiratory distress syndrome. Additional evidence on the efficacy of venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome and in different subgroups of patients will allow for greater certainty in its cost-effectiveness.

Background Management of patients with acute respiratory distress syndrome (ARDS) remains supportive with lung protective mechanical ventilation. In this article, we discuss the physiological concept of driving pressure, current data, ongoing trials, and future directions needed to clarify the role of driving pressure in patients with ARDS. Body Driving pressure is the plateau airway pressure minus PEEP. It can also be expressed as the ratio of tidal volume to respiratory system compliance, indicating the decreased functional size of the lung observed in patients with ARDS (i.e., baby lung). Driving pressure as a strong predictor of mortality in patients with ARDS is supported by a post hoc analysis of previous randomized controlled trials and a subsequent meta-analysis. Importantly, the meta-analysis suggested targeting driving pressure below 13–15 cmH2O. Ongoing clinical trials of driving pressure in patients with ARDS focus mainly on physiological rather than clinical outcome but will provide important insights for the design of future clinical trials. Conclusion Currently, no definite clinical recommendations on the routine use of driving pressure in patients with ARDS can be made, as the available data are hypothesis-generating. Randomized controlled trials are needed to evaluate the efficacy of a driving pressure-based ventilation strategy.

To characterize current practice in fluid administration and deresuscitation (removal of fluid using diuretics or renal replacement therapy), the relationship between fluid balance, deresuscitative measures, and outcomes and to identify risk factors for positive fluid balance in critical illness.Retrospective cohort study.Ten ICUs in the United Kingdom and Canada.Adults receiving invasive mechanical ventilation for a minimum of 24 hours.None.Four-hundred patients were included. Positive cumulative fluid balance (fluid input greater than output) occurred in 87.3%: the largest contributions to fluid input were from medications and maintenance fluids rather than resuscitative IV fluids. In a multivariate logistic regression model, fluid balance on day 3 was an independent risk factor for 30-day mortality (odds ratio 1.26/L [95% CI, 1.07-1.46]), whereas negative fluid balance achieved in the context of deresuscitative measures was associated with lower mortality. Independent predictors of greater fluid balance included treatment in a Canadian site.Fluid balance is a practice-dependent and potentially modifiable risk factor for adverse outcomes in critical illness. Negative fluid balance achieved with deresuscitation on day 3 of ICU stay is associated with improved patient outcomes. Minimization of day 3 fluid balance by limiting maintenance fluid intake and drug diluents, and using deresuscitative measures, represents a potentially beneficial therapeutic strategy which merits investigation in randomized trials.

Commentary on: Alobaidi R, Morgan C, Basu RK, et al . Association between fluid balance and outcomes in critically ill children: a systematic review and meta-analysis. JAMA Pediatr. 2018;172(3):257–268. Early goal-directed fluid resuscitation is the foundation of paediatric clinical practice parameters for septic shock and hypovolaemic shock management.1 Moderating fluid resuscitation is the observation that fluid overloaded children have higher mortality rates and longer lengths of stay.2 The Fluid Expansion as Supportive Therapy randomised controlled trial found African children with febrile illness and impaired perfusion who received fluid bolus therapy had a higher mortality rate than those who received no bolus therapy. However, it was conducted in hospitals without intensive care units and therefore does not generalise to high resource states.3 This systematic review and meta-analysis examines the measure and definition of fluid overload and its association with …

BACKGROUND: Stress index provides a noninvasive approach to detect injurious ventilation patterns and to personalize ventilator settings. Obtaining the stress index (SI), however, requires quantitatively analyzing the shape of pressure-time curve with dedicated instruments or a specific ventilator, which may encumber its clinical implementation. We hypothesized that the SI could be qualitatively determined through a visual inspection of ventilator waveforms. METHODS: Thirty-six adult subjects undergoing volume controlled ventilation without spontaneous breathing were enrolled. For each subject, 2 trained clinicians visually inspected the pressure-time curve directly from the ventilator screen. They then qualitatively categorized the shape of pressure-time curve as linear, a downward concavity, or an upward concavity at the bedside. We simultaneously recorded airway pressure and flow signals using a dedicated instrument. A quantitative off-line analysis was performed to calculate the SI using specific research software. This quantitative analysis of the SI served as the reference method for classifying the shape of the pressure-time curve (ie, linear, a downward concavity, or an upward concavity). We compared the SI categorized by visual inspection with that by the reference. RESULTS: We obtained 200 SI assessments of pressure-time curves, among which 125 (63%) were linear, 55 (27%) were a downward concavity, and 20 (10%) were an upward concavity as determined by the reference method. The overall accuracy of visual inspection and weighted kappa statistic (95% CI) was 93% (88–96%) and 0.88 (0.82–0.94), respectively. The sensitivity and specificity to distinguish a downward concavity from a linear shape were 91% and 98%, respectively. The respective sensitivity and specificity to distinguish an upward concavity from a linear shape were 95% and 95%. CONCLUSIONS: Visual inspection of the pressure-time curve on the ventilator screen is a simple and reliable approach to assess SI at the bedside. This simplification may facilitate the implementation of SI in clinical practice to personalize mechanical ventilation. (ClinicalTrials.gov registration NCT03096106.)

Summary Several mechanisms of diaphragm muscle injury (myotrauma) can result in ventilator-induced diaphragm dysfunction, including ventilator over-assistance, under-assistance, eccentric contractions, and end-expiratory shortening. In this Personal View, we summarise the evidence for the clinical relevance of these mechanisms, and present new data based on mediation analysis supporting the hypothesis that myotrauma due to ventilator over-assistance and under-assistance contribute, in part, to the effect of mechanical ventilation on clinical outcomes. The concept of diaphragmatic myotrauma has important implications for research and clinical practice.

Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory cardiogenic shock, refractory ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest, and acute or decompensated right heart failure. Evidence is emerging to guide the use of this therapy for some of these indications, but there remains a need for additional evidence to guide best practices. As a result, the use of ECMO may vary widely across centers. The purpose of this document is to highlight key aspects of care delivery, with the goal of codifying the current use of this rapidly growing technology. A major challenge in this field is the need to emergently deploy ECMO for cardiac failure, often with limited time to assess the appropriateness of patients for the intervention. For this reason, we advocate for a multidisciplinary team of experts to guide institutional use of this therapy and the care of patients receiving it. Rigorous patient selection and careful attention to potential complications are key factors in optimizing patient outcomes. Seamless patient transport and clearly defined pathways for transition of care to centers capable of providing heart replacement therapies (e.g., durable ventricular assist device or heart transplantation) are essential to providing the highest level of care for those patients stabilized by ECMO but unable to be weaned from the device. Ultimately, concentration of the most complex care at high-volume centers with advanced cardiac capabilities may be a way to significantly improve the care of this patient population.

Importance Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure that affects approximately 200 000 patients each year in the United States, resulting in nearly 75 000 deaths annually. Globally, ARDS accounts for 10% of intensive care unit admissions, representing more than 3 million patients with ARDS annually. Objective To review advances in diagnosis and treatment of ARDS over the last 5 years. Evidence Review We searched MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 2012 to 2017 focusing on randomized clinical trials, meta-analyses, systematic reviews, and clinical practice guidelines. Articles were identified for full text review with manual review of bibliographies generating additional references. Findings After screening 1662 citations, 31 articles detailing major advances in the diagnosis or treatment of ARDS were selected. The Berlin definition proposed 3 categories of ARDS based on the severity of hypoxemia: mild (200 mm Hg 2 /Fio 2 ≤300 mm Hg), moderate (100 mm Hg 2 /Fio 2 ≤200 mm Hg), and severe (Pao 2 /Fio 2 ≤100 mm Hg), along with explicit criteria related to timing of the syndrome’s onset, origin of edema, and the chest radiograph findings. The Berlin definition has significantly greater predictive validity for mortality than the prior American-European Consensus Conference definition. Clinician interpretation of the origin of edema and chest radiograph criteria may be less reliable in making a diagnosis of ARDS. The cornerstone of management remains mechanical ventilation, with a goal to minimize ventilator-induced lung injury (VILI). Aspirin was not effective in preventing ARDS in patients at high-risk for the syndrome. Adjunctive interventions to further minimize VILI, such as prone positioning in patients with a Pao 2 /Fio 2 ratio less than 150 mm Hg, were associated with a significant mortality benefit whereas others (eg, extracorporeal carbon dioxide removal) remain experimental. Pharmacologic therapies such as β 2 agonists, statins, and keratinocyte growth factor, which targeted pathophysiologic alterations in ARDS, were not beneficial and demonstrated possible harm. Recent guidelines on mechanical ventilation in ARDS provide evidence-based recommendations related to 6 interventions, including low tidal volume and inspiratory pressure ventilation, prone positioning, high-frequency oscillatory ventilation, higher vs lower positive end-expiratory pressure, lung recruitment maneuvers, and extracorporeal membrane oxygenation. Conclusions and Relevance The Berlin definition of acute respiratory distress syndrome addressed limitations of the American-European Consensus Conference definition, but poor reliability of some criteria may contribute to underrecognition by clinicians. No pharmacologic treatments aimed at the underlying pathology have been shown to be effective, and management remains supportive with lung-protective mechanical ventilation. Guidelines on mechanical ventilation in patients with acute respiratory distress syndrome can assist clinicians in delivering evidence-based interventions that may lead to improved outcomes.

Objectives: Radiographic criteria for acute respiratory distress syndrome have been criticized for poor reliability. Our objective was to test an educational intervention to improve the radiographic identification of acute respiratory distress syndrome by participants in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure study. Design: Randomized controlled trial. Settings: Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure study centers. Subjects: Study coordinators in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure study. Interventions: Participants were randomized to either an online training module followed by a test module (intervention) or test module followed by training module (control). Measurements and Main Results: The primary outcome was the number of radiographs correctly identified as meeting criteria for acute respiratory distress syndrome on an online test module (out of 11). Prespecified secondary analyses included a comparison of agreement between the groups and subgroup analyses by profession, age, years of experience, and stated familiarity with diagnostic criteria for acute respiratory distress syndrome. Four-hundred sixty-three study participants consented to participate. There was no effect of the intervention on correct answers by participants (proportion correct 58% [intervention] vs 56% [control]; p = 0.15), or in any subgroup analyses. Overall agreement between raters was 0.296 for the intervention and 0.272 for the control (p < 0.001). Conclusions: Participant recognition of radiographic criteria for acute respiratory distress syndrome was low, with poor agreement. This was not impacted by an educational intervention designed to improve accuracy of identification of radiographic criteria for acute respiratory distress syndrome

Airway pressure release ventilation (APRV) is a pressure-limited and time-cycled mode of mechanical ventilation that is without the need for patient-ventilator interaction. The original concept, first described by Downs and Stock in 1987, was to keep the patient at an elevated continuous positive airway pressure (CPAP) pressure most of the time, with periodic releases to facilitate CO 2 clearance (1).

Mechanical circulatory and respiratory support is a rapidly expanding field. Available devices can potentially completely accomplish the primary function of the heart and lung, i.e., the transport of oxygen and nutrients to cells and the maintenance of perfusion pressure. If oxygenation and tissue perfusion are compromised, multiorgan dysfunction ensues and is potentially irreversible in established cases. Depending on the acuity and severity of the pathological state encountered and despite the timely introduction of pharmacological and ventilatory support, selected cases of cardiorespiratory failure require such measures. This may take the form of short-term support such as intra-aortic balloon pumps, short-term ventricular assist devices, extracorporeal membrane oxygenation, or long-term ventricular assist devices. The effective design and use of such advanced therapies require a thorough understanding of normal cardiorespiratory anatomy, physiology, and pathophysiology and is, therefore, reviewed in this chapter.

Extracorporeal carbon dioxide removal (ECCO2R) has been proposed as an adjunctive intervention to avoid worsening respiratory acidosis, thereby preventing or shortening the duration of invasive mechanical ventilation (IMV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD). This review will present a comprehensive summary of the pathophysiological rationale and clinical evidence of ECCO2R in patients suffering from severe COPD exacerbations.

Background Despite a supportive evidence base and a push to implement, the uptake of early rehabilitation in critical care has been inconsistent. The objective of this study was to explore barriers and facilitators to early rehabilitation for critically ill patients receiving invasive mechanical ventilation. Methods Using the Theoretical Domains Framework (TDF) of behavior change, we conducted semi-structured interviews exploring barriers and facilitators to early rehabilitation among four purposively sampled ICU clinician groups (nurses, rehabilitation professionals, respiratory therapists, and physicians). The TDF is a comprehensive framework of 14 “construct domains,” synthesized from 33 theories of behavior that was developed to study determinants of behavior and to design interventions to improve evidence-based healthcare practice. A topic guide was developed and piloted based on the TDF and expert knowledge. Interviews were audio-recorded and transcribed verbatim. Transcripts were content analyzed by coding items into domains and then synthesized into more specific, over-arching themes or “beliefs.” An expert consensus group used structured decision rules to classify beliefs as high, moderate, or low in importance. Results We interviewed 40 stakeholders from the four clinician groups and identified 135 separate beliefs. Of these, 19 were classified as high, 40 as moderate, and 76 of low importance as barriers or facilitators. All beliefs classified as highly important fell within one of seven TDF domains: skills, social/professional role and identity, beliefs about capabilities, beliefs about consequences, environmental context/resources, social influences, and behavioral regulation. Beliefs of lower importance fell under the following seven domains: knowledge; optimism; reinforcement; intention; goals; memory, attention, and decision processes; and emotion. Quantitative differences in stated beliefs about early rehabilitation between professional groups were not common. Conclusions This study identified important barriers and facilitators to early rehabilitation in critical care patients. Domains identified as important should be considered when designing interventions to increase uptake of early rehabilitation. Electronic supplementary material The online version of this article (10.1186/s40560-018-0273-0) contains supplementary material, which is available to authorized users.

Adopted from: Fan E., Del Sorbo L., Goligher E.C., Hodgson C.L., Munshi L., Walkey A.J., Adhikari N.K.J., Amato M.B.P., Branson R., Brower R.G., Ferguson N.D., Gajic O., Gattinoni L., Hess D., Mancebo J., Meade M.O., McAuley D.F., Pesenti A., Ranieri V.M., Rubenfeld G.D., Rubin E., Seckel M., Slutsky A.S., Talmor D., Thompson B. T., Wunsch H., Uleryk E., Brozek J., Brochard L.J. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med. 2017; 195 (9): 1253–1263. DOI: 10.1164/rccm.201703-0548STThe aim of this guideline is to provide clinical recommendation on the use of mechanical ventilation in adult patients with acute respiratory distress syndrome (ARDS).Methods. This guideline is based on systematic review and metaanalysis of available literature on the use of mechanical ventilation in adult patients with ARDS.Results. All patients with ARDS should be mechanically ventilated with the use of lower tidal volumes (4–8 ml/kg predicted bodyweight) and lower inspiratory pressures (plateau pressure, 30 cm H2O). In severe ARDS, the prone positioning for more than 12 h/d is strongly recommended. In patients with moderate to severe ARDS, routine use of high-frequency oscillatory ventilation is not recommended; a conditional recommendation has been developed for the use of higher positive end-expiratory pressure and recruitment maneuvers. CuОР – ently, there is not enough evidence for the use of extracorporeal membrane oxygenation in patients with severe ARDS.Conclusions. Practical recommendations on selected methods to coОР – ect ventilation disturbances in adult patients with ARDS have been developed. Clinicians involved in the management of patients with ARDS should use personalized approach to the treatment of these patients.

Extracorporeal life support (ECLS) was developed more than 50 years ago, initially with venoarterial and subsequently with venovenous configurations. As the technique of ECLS significantly improved and newer skills developed, complexity in terminology and advances in cannula design led to some misunderstanding of and inconsistency in definitions, both in clinical practice and in scientific research. This document is a consensus of multispecialty international representatives of the Extracorporeal Life Support Organization, including the North America, Latin America, EuroELSO, South West Asia and Africa, and Asia-Pacific chapters, imparting a global perspective on ECLS. The goal is to provide a consistent and unambiguous nomenclature for ECLS and to overcome the inconsistent use of abbreviations for ECLS cannulation. Secondary benefits are ease of multicenter collaboration in research, improved registry data quality, and clear communication among practitioners and researchers in the field.