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OBJECTIVE:: In acute respiratory distress syndrome (ARDS), high-frequency oscillation (HFO) improves oxygenation relative to conventional mechanical ventilation (CMV). Alveolar ventilation is improved by adding tracheal gas insufflation (TGI) to CMV. We hypothesized that combined HFO and TGI (HFO-TGI) might result in improved gas exchange relative to both standard HFO and CMV according to the ARDS Network protocol. DESIGN:: Prospective, randomized, crossover study. SETTING:: A 30-bed university intensive care unit. PATIENTS:: A total of 14 patients with early (<72 hrs in duration), severe (Pao2/Fio2 of <150 mm Hg and prerecruitment oxygenation index of 22.8 +/- 1.9 [mean +/- sem]), primary ARDS. INTERVENTIONS:: Patients were ventilated with HFO without (60 mins) and combined with TGI (6.1 +/- 0.1 L/min, 60 mins) in random order. HFO sessions were repeated in inverse order within 24 hrs. HFO sessions were preceded and followed by ARDS Network CMV. Four recruitment maneuvers were performed during the study period. During HFO sessions, mean airway pressure was set at 1 cm H2O above the point of maximal curvature of the respiratory system expiratory pressure-volume curve. MEASUREMENTS AND MAIN RESULTS:: Gas exchange and hemodynamics were determined before, during, and after HFO sessions. HFO-TGI improved Pao2/Fio2 relative to HFO and CMV (174.5 +/- 10.4 vs. 136.0 +/- 10.0 and 105.0 +/- 3.7 mm Hg, respectively, p < .05 for both) and oxygenation index relative to HFO (17.1 +/- 1.3 vs. 22.3 +/- 1.7, respectively p < .05). Pao2/Fio2 returned to baseline within 3 hrs after HFO. During HFO-TGI, shunt fraction and mixed venous oxygen saturation improved relative to CMV (0.36 +/- 0.01 vs. 0.45 +/- 0.01 and 77.8% +/- 1.2% vs. 71.8% +/- 1.3%, respectively, p < .05 for both). Paco2 and hemodynamics were unaffected by HFO sessions. Respiratory mechanics remained unchanged throughout the study period. CONCLUSIONS:: In early onset, primary, severe ARDS, short-term HFO-TGI improves oxygenation relative to standard HFO and ARDS Network CMV. [ABSTRACT FROM AUTHOR]

Purpose: Limitations of life sustaining therapies (LLST) are frequent in intensive care units (ICUs), but no previous studies have examined end-of-life (EOL) care and LLST in South Africa (SA)., Materials and Methods: This study evaluated LLST in SA from the data of a prospective, international, multicentre, observational study (Ethicus-2) and compared practices with countries in the rest of the world., Results: LLST was relatively common in SA, and withholding was more frequent than withdrawing therapy. However, withdrawing and withholding therapy were less common, while failed CPR was more common, than in many other countries. No patients had an advance directive. Primary reasons for LLST in SA were poor quality of life, multisystem organ failure and patients' unresponsiveness to maximal therapy. Primary considerations for EOL decision-making were good medical practice and patients' best-interest, with the need for an ICU bed only rarely considered., Conclusions: Withholding was more common than withdrawing treatment both in SA and worldwide, although both were significantly less frequent in SA compared with the world average., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: A major barrier to performing cardiac arrest trials is the requirement for prospective informed consent, which is often infeasible during individual medical emergencies. In an effort to improve outcomes, some governments have adopted legislation permitting research without prior consent (RWPC) in these circumstances. We aimed to outline key differences between legislation in four Western locations and explore the effects of these differences on trial design and implementation in cardiac arrest research., Data Sources: We performed a narrative review of RWPC legislation in the United States (US), Canada, the European Union (EU) and the United Kingdom (UK)., Results: The primary criteria required to perform RWPC was similar across locations: the study must involve an individual medical emergency during which neither the prospective subject nor their authorized representative can provide informed consent. The US regulations were unique in their requirements for performing Community Consultation and Public Disclosure in the communities in which the research takes place. Another major difference was the requirement for consent for ongoing participation in Canada, the EU and the UK, while only notification of enrollment and the opportunity to discontinue participation are required in the US. Additionally, only Canada and the EU explicitly state that the subject or their representative may request withdrawal of their data., Conclusion: Regulations governing RWPC in the US, Canada, the EU and the UK have similar goals and protections for vulnerable populations during medical emergencies. Differences in the qualifying criteria and implementation procedures exist across locations and may affect study design., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Cardiac arrest affects millions of people per year worldwide. Although advances in cardiopulmonary resuscitation and intensive care have improved outcomes over time, neurologic impairment and multiple organ dysfunction continue to be associated with a high mortality rate. The pathophysiologic mechanisms underlying the post-resuscitation disease are complex, and a coordinated, evidence-based approach to post-resuscitation care has significant potential to improve survival. Critical care management of patients resuscitated from cardiac arrest focuses on the identification and treatment of the underlying cause(s), hemodynamic and respiratory support, organ protection, and active temperature control. This review provides a state-of-the-art appraisal of critical care management of the post-cardiac arrest patient.

Background: Prolonging life in the ICU increasingly is possible, so decisions to limit life-sustaining therapies frequently are made and communicated to patients and families or surrogates. Little is known about worldwide communication practices and influencing factors., Research Question: Are there regional differences in end-of-life communication practices in ICUs worldwide?, Study Design and Methods: This analysis of data from a prospective, international study specifically addressed end-of-life communications in consecutive patients who died or had limitation of life-sustaining therapy over 6 months in 199 ICUs in 36 countries, grouped regionally. End-of-life decisions were recorded for each patient and ethical practice was assessed retrospectively for each ICU using a 12-point questionnaire developed previously., Results: Of 87,951 patients admitted, 12,850 died or experienced a limitation of therapy (14.6%). Of these, 1,199 patients (9.3%) were known to have an advance directive, and wishes were elicited from 6,456 patients (50.2%). Limitations of life-sustaining therapy were implemented for 10,401 patients (80.9%), 1,970 (19.1%) of whom had mental capacity at the time, and were discussed with 1,507 patients (14.5%) and 8,461 families (81.3%). Where no discussions with patients occurred (n = 8,710), this primarily was because of a lack of mental capacity in 8,114 patients (93.2%), and where none occurred with families (n = 1,622), this primarily was because of unavailability (n = 720 [44.4%]). Regional variation was noted for all end points. In generalized estimating equation (GEE) analyses, the odds for discussions with the patient or family increased by 30% (OR, 1.30; 95% CI, 1.18-1.44; P < .001) for every one-point increase in the Ethical Practice Score and by 92% (OR, 1.92; 95% CI, 1.28-2.89; P = .002) in the presence of an advance directive., Interpretation: End-of-life communication with patients and families or surrogates varies markedly in different global regions. GEE analysis supports the hypothesis that communication may increase with ethical practice and an advance directive. Greater effort is needed to align treatment with patients' wishes., (Copyright © 2022 American College of Chest Physicians. All rights reserved.)

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis and fluid-filled alveoli. Coronavirus disease 19 (COVID-19)-associated ARDS (C-ARDS) is a novel etiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may present with distinct clinical features as a result of the viral pathobiology unique to SARS-CoV-2. In particular, severe injury to the pulmonary vascular endothelium, accompanied by the presence of diffuse microthrombi in the pulmonary microcirculation, can lead to a clinical presentation in which the severity of impaired gas exchange becomes uncoupled from lung capacity and respiratory mechanics. The purpose of this review is to highlight the key mechanistic features of C-ARDS and to discuss the implications these features have on its treatment. In some patients with C-ARDS, rigid adherence to guidelines derived from clinical trials in the pre-COVID era may not be appropriate.

Intracranial hypertension is a common finding in patients with severe traumatic brain injury. These patients need treatment in the intensive care unit, where intracranial pressure monitoring and, whenever possible, multimodal neuromonitoring can be applied. A three-tier approach is suggested in current recommendations, in which higher-tier therapies have more significant side effects. In this review, we explain the rationale for this approach, and analyze the benefits and risks of each therapeutic modality. Finally, we discuss, based on the most recent recommendations, how this approach can be adapted in low- and middle-income countries, where available resources are limited., Competing Interests: The authors declare no conflict of interest.

Background: In concordance with the results of large, observational studies, a 2015 European survey suggested variation in resuscitation/end-of-life practices and emergency care organization across 31 countries. The current survey-based study aimed to comparatively assess the evolution of practices from 2015 to 2019, especially in countries with "low" (i.e., average or lower) 2015 questionnaire domain scores., Methods: The 2015 questionnaire with additional consensus-based questions was used. The 2019 questionnaire covered practices/decisions related to end-of-life care (domain A); determinants of access to resuscitation/post-resuscitation care (domain B); diagnosis of death/organ donation (domain C); and emergency care organization (domain D). Responses from 25 countries were analyzed. Positive or negative responses were graded by 1 or 0, respectively. Domain scores were calculated by summation of practice-specific response grades., Results: Domain A and B scores for 2015 and 2019 were similar. Domain C score decreased by 1 point [95% confidence interval (CI): 1-3; p = 0.02]. Domain D score increased by 2.6 points (95% CI: 0.2-5.0; p = 0.035); this improvement was driven by countries with "low" 2015 domain D scores. In countries with "low" 2015 domain A scores, domain A score increased by 5.5 points (95% CI: 0.4-10.6; p = 0.047)., Conclusions: In 2019, improvements in emergency care organization and an increasing frequency of end-of-life practices were observed primarily in countries with previously "low" scores in the corresponding domains of the 2015 questionnaire.

Aim: Postresuscitation hemodynamics are associated with hospital mortality/functional outcome. We sought to determine whether low-dose steroids started during and continued after cardiopulmonary resuscitation (CPR) affect postresuscitation hemodynamics and other physiological variables in vasopressor-requiring, in-hospital cardiac arrest., Methods: We conducted a two-center, randomized, double-blind trial of patients with adrenaline (epinephrine)-requiring cardiac arrest. Patients were randomized to receive either methylprednisolone 40 mg (steroids group) or normal saline-placebo (control group) during the first CPR cycle post-enrollment. Postresuscitation shock was treated with hydrocortisone 240 mg daily for 7 days maximum and gradual taper (steroids group), or saline-placebo (control group). Primary outcomes were arterial pressure and central-venous oxygen saturation (ScvO 2 ) within 72 hours post - ROSC., Results: Eighty nine of 98 controls and 80 of 86 steroids group patients with ROSC were treated as randomized. Primary outcome data were collected from 100 patients with ROSC (control, n  = 54; steroids, n  = 46). In intention-to-treat mixed-model analyses, there was no significant effect of group on arterial pressure, marginal mean (95% confidence interval) for mean arterial pressure, steroids vs. control: 74 (68-80) vs. 72 (66-79) mmHg] and ScvO 2 [71 (68-75)% vs. 69 (65-73)%], cardiac index [2.8 (2.5-3.1) vs. 2.9 (2.5-3.2) L/min/m 2 ], and serum cytokine concentrations [e.g. interleukin-6, 89.1 (42.8-133.9) vs. 75.7 (52.1-152.3) pg/mL] determined within 72 hours post-ROSC ( P  = 0.12-0.86). There was no between-group difference in body temperature, echocardiographic variables, prefrontal blood flow index/cerebral autoregulation, organ failure-free days, and hazard for poor in-hospital/functional outcome, and adverse events ( P  = 0.08->0.99)., Conclusions: Our results do not support the use of low-dose corticosteroids in in-hospital cardiac arrest. Trial Registration: ClinicalTrials.gov number: NCT02790788 ( https://www.clinicaltrials.gov )., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Limitations of life-sustaining interventions in intensive care units (ICUs) exhibit substantial changes over time, and large, contemporary variation across world regions. We sought to determine whether a weighted end-of-life practice score can explain a large, contemporary, worldwide variation in limitation decisions., Methods: The 2015-2016 (Ethicus-2) vs. 1999-2000 (Ethicus-1) comparison study was a two-period, prospective observational study assessing the frequency of limitation decisions in 4952 patients from 22 European ICUs. The worldwide Ethicus-2 study was a single-period prospective observational study assessing the frequency of limitation decisions in 12,200 patients from 199 ICUs situated in 8 world regions. Binary end-of-life practice variable data (1 = presence; 0 = absence) were collected post hoc (comparison study, 22/22 ICUs, n = 4592; worldwide study, 186/199 ICUs, n = 11,574) for family meetings, daily deliberation for appropriate level of care, end-of-life discussions during weekly meetings, written triggers for limitations, written ICU end-of-life guidelines and protocols, palliative care and ethics consultations, ICU-staff taking communication or bioethics courses, and national end-of-life guidelines and legislation. Regarding the comparison study, generalized estimating equations (GEE) analysis was used to determine associations between the 12 end-of-life practice variables and treatment limitations. The weighted end-of-life practice score was then calculated using GEE-derived coefficients of the end-of-life practice variables. Subsequently, the weighted end-of-life practice score was validated in GEE analysis using the worldwide study dataset., Results: In comparison study GEE analyses, end-of-life discussions during weekly meetings [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.30-0.99], end-of-life guidelines [OR 0.52, (0.31-0.87)] and protocols [OR 15.08, (3.88-58.59)], palliative care consultations [OR 2.63, (1.23-5.60)] and end-of-life legislation [OR 3.24, 1.60-6.55)] were significantly associated with limitation decisions (all P < 0.05). In worldwide GEE analyses, the weighted end-of-life practice score was significantly associated with limitation decisions [OR 1.12 (1.03-1.22); P = 0.008]., Conclusions: Comparison study-derived, weighted end-of-life practice score partly explained the worldwide study's variation in treatment limitations. The most important components of the weighted end-of-life practice score were ICU end-of-life protocols, palliative care consultations, and country end-of-life legislation., (© 2022. The Author(s).)

Aim: To perform a systematic review and individual participant data meta-analysis of vasopressin and glucocorticoids for the treatment of cardiac arrest., Methods: The PRISMA-IPD guidelines were followed. We searched Medline, Embase, and the Cochrane Library for randomized trials comparing vasopressin and glucocorticoids to placebo during cardiac arrest. The population included adults with cardiac arrest in any setting. Pairs of investigators reviewed studies for relevance, extracted data, and assessed risk of bias. Meta-analyses were conducted using individual participant data. A Bayesian framework was used to estimate posterior treatment effects assuming various prior beliefs. The certainty of evidence was evaluated using GRADE., Results: Three trials were identified including adult in-hospital cardiac arrests only. Individual participant data were obtained from all trials yielding a total of 869 patients. There was some heterogeneity in post-cardiac arrest interventions between the trials. The results favored vasopressin and glucocorticoids for return of spontaneous circulation (odds ratio: 2.09, 95%CI: 1.54 to 2.84, moderate certainty). Estimates for survival at discharge (odds ratio: 1.39, 95%CI: 0.90 to 2.14, low certainty) and favorable neurological outcome (odds ratio: 1.64, 95%CI, 0.99 to 2.72, low certainty) were more uncertain. The Bayesian estimates for return of spontaneous circulation were consistent with the primary analyses, whereas the estimates for survival at discharge and favorable neurological outcome were more dependent on the prior belief., Conclusions: Among adults with in-hospital cardiac arrest, vasopressin and glucocorticoids compared to placebo, improved return of spontaneous circulation. Larger trials are needed to determine whether there is an effect on longer-term outcomes., Competing Interests: Declaration of Competing Interest All authors have been involved in previous trials comparing the use of vasopressin and glucocorticoids to placebo in cardiac arrest (ClinicalTrials.Gov: NCT00411879, NCT00729794, and NCT03640949). Dr Andersen reported nonfinancial support from Amomed Pharma GmbH, which provided the trial drug during the conduct of the VAM-IHCA trial. Dr Granfeldt reported receiving personal fees from Noorik Biopharmaceuticals outside the conduct of the VAM-IHCA trial. The Scientific Council of Evaggelismos General Hospital granted permission to Dr. Mentzelopoulos for sharing of the data from NCT00411879 and NCT00729794 (Decision No. 195/10/6/2021)., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: End-of-life practices vary among intensive care units (ICUs) worldwide. Differences can result in variable use of disproportionate or non-beneficial life-sustaining interventions across diverse world regions. This study investigated global disparities in end-of-life practices., Methods: In this prospective, multinational, observational study, consecutive adult ICU patients who died or had a limitation of life-sustaining treatment (withholding or withdrawing life-sustaining therapy and active shortening of the dying process) during a 6-month period between Sept 1, 2015, and Sept 30, 2016, were recruited from 199 ICUs in 36 countries. The primary outcome was the end-of-life practice as defined by the end-of-life categories: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, or failed cardiopulmonary resuscitation (CPR). Patients with brain death were included in a separate predefined end-of-life category. Data collection included patient characteristics, diagnoses, end-of-life decisions and their timing related to admission and discharge, or death, with comparisons across different regions. Patients were studied until death or 2 months from the first limitation decision., Findings: Of 87 951 patients admitted to ICU, 12 850 (14·6%) were included in the study population. The number of patients categorised into each of the different end-of-life categories were significantly different for each region (p<0·001). Limitation of life-sustaining treatment occurred in 10 401 patients (11·8% of 87 951 ICU admissions and 80·9% of 12 850 in the study population). The most common limitation was withholding life-sustaining treatment (5661 [44·1%]), followed by withdrawing life-sustaining treatment (4680 [36·4%]). More treatment withdrawing was observed in Northern Europe (1217 [52·8%] of 2305) and Australia/New Zealand (247 [45·7%] of 541) than in Latin America (33 [5·8%] of 571) and Africa (21 [13·0%] of 162). Shortening of the dying process was uncommon across all regions (60 [0·5%]). One in five patients with treatment limitations survived hospitalisation. Death due to failed CPR occurred in 1799 (14%) of the study population, and brain death occurred in 650 (5·1%). Failure of CPR occurred less frequently in Northern Europe (85 [3·7%] of 2305), Australia/New Zealand (23 [4·3%] of 541), and North America (78 [8·5%] of 918) than in Africa (106 [65·4%] of 162), Latin America (160 [28·0%] of 571), and Southern Europe (590 [22·5%] of 2622). Factors associated with treatment limitations were region, age, and diagnoses (acute and chronic), and country end-of-life legislation., Interpretation: Limitation of life-sustaining therapies is common worldwide with regional variability. Withholding treatment is more common than withdrawing treatment. Variations in type, frequency, and timing of end-of-life decisions were observed. Recognising regional differences and the reasons behind these differences might help improve end-of-life care worldwide., Funding: None., Competing Interests: Declaration of interests AD reports grants, personal fees, and non-financial support from Philips, and Respinor; personal fees from Baxter, Getinge, Lowenstein, and Gilead; personal fees and non-financial support from Fisher & Paykel and Lungpacer; and grants from the French Ministry of Health, outside of the submitted work. JCS reports grants from Orion Pharma, Abbott Nutrition International, B Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, and Phagenesis, outside of the submitted work. Monies went into departmental funds directly. AG and and MP report grants from the Austrian Center for Documentation and Quality Assurance in Intensive Care during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Patients in intensive care units (ICUs) have treatment limited or withdrawn if further treatment is considered futile. This multicentre prospective observational study was part of a European study of patterns of limitations., Methods: In the first six months of 2016, all patients admitted to three Danish ICUs were screened and those with treatment limitations or death in the ICU were included. End-of-life outcomes were classified into five mutually exclusive categories: withholding, withdrawing, shortening of dying process, failed cardio-pulmonary resuscitation and brain death. This sub-study compared interdepartmental variation in limitation patterns among Danish ICUs., Results: A total of 1,132 ICU patients were admitted, and 264 (23.3%) had limitations to their treatment and/or died and were therefore included. Mortality among these patients was 71.5%, with interdepartmental differences of 52-85% in mortality, but no difference in overall mortality. Specifically, eight different limitations were described with distinct differences amongst departments, most likely due to case mix differences. A total of 96% of patients with limitations suffered from one or more chronic conditions, and 15-48% of the patients with limitations survived to ICU discharge., Conclusion: Many Danish ICU patients have limitations imposed on therapy during their ICU stay, but large interdepartmental differences are primarily based on case mix differences. Although a large proportion of patients with limitations ultimately die, limitations do not portend imminent death., Funding: None., Trial Registration: Not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

In cardiac surgery patients with pre-extubation PaO 2 /inspired oxygen fraction (FiO 2 ) < 200 mmHg, the possible benefits and optimal level of high-flow nasal cannula (HFNC) support are still unclear; therefore, we compared HFNC support with an initial gas flow of 60 or 40 L/min and conventional oxygen therapy. Ninety nine patients were randomly allocated (respective ratio: 1:1:1) to I = intervention group 1 (HFNC initial flow = 60 L/min, FiO 2 = 0.6), intervention group 2 (HFNC initial flow = 40 L/min, FiO 2 = 0.6), or control group (Venturi mask, FiO 2 = 0.6). The primary outcome was occurrence of treatment failure. The baseline characteristics were similar. The hazard for treatment failure was lower in intervention group 1 vs. control (hazard ratio (HR): 0.11, 95% CI: 0.03-0.34) and intervention group 2 vs. control (HR: 0.30, 95% CI: 0.12-0.77). During follow-up, the probability of peripheral oxygen saturation (SpO 2 ) > 92% and respiratory rate within 12-20 breaths/min was 2.4-3.9 times higher in intervention group 1 vs. the other 2 groups. There was no difference in PaO 2 /FiO 2 , patient comfort, intensive care unit or hospital stay, or clinical course complications or adverse events. In hypoxemic cardiac surgery patients, postextubation HFNC with an initial gas flow of 60 or 40 L/min resulted in less frequent treatment failure vs. conventional therapy. The results in terms of SpO 2 /respiratory rate targets favored an initial HFNC flow of 60 L/min.

These European Resuscitation Council Ethics guidelines provide evidence-based recommendations for the ethical, routine practice of resuscitation and end-of-life care of adults and children. The guideline primarily focus on major ethical practice interventions (i.e. advance directives, advance care planning, and shared decision making), decision making regarding resuscitation, education, and research. These areas are tightly related to the application of the principles of bioethics in the practice of resuscitation and end-of-life care., (Copyright © 2021. Published by Elsevier B.V.)

These European Resuscitation Council Ethics guidelines provide evidence-based recommendations for the ethical, routine practice of resuscitation and end-of-life care of adults and children. The guideline primarily focus on major ethical practice interventions (i.e. advance directives, advance care planning, and shared decision making), decision making regarding resuscitation, education, and research. These areas are tightly related to the application of the principles of bioethics in the practice of resuscitation and end-of-life care., Competing Interests: InteressenkonfliktM. Blom declares her role of co-coordinator EU project ESCAPE-NET. G.D. Perkins reports funding from Elsevier for his role as an editor of the journal Resuscitation. He reports research funding from the National Institute for Health Research (NIHR) in relation to the PARAMEDIC2 trial and the RESPECT project. [Stand 17.5. aus Originalartikel in Resuscitation]. S.D. Mentzelopoulos, K. Couper, P. Van de Voorde, P. Druwé, I. Lulic, J. Djakow, V. Raffay, G. Lilja und L. Bossaert declare that they have no competing interests., (© European Resuscitation Council (ERC), German Resuscitation Council (GRC), Austrian Resuscitation Council (ARC) 2021.)

Importance: End-of-life decisions occur daily in intensive care units (ICUs) around the world, and these practices could change over time., Objective: To determine the changes in end-of-life practices in European ICUs after 16 years., Design, Setting, and Participants: Ethicus-2 was a prospective observational study of 22 European ICUs previously included in the Ethicus-1 study (1999-2000). During a self-selected continuous 6-month period at each ICU, consecutive patients who died or had any limitation of life-sustaining therapy from September 2015 until October 2016 were included. Patients were followed up until death or until 2 months after the first treatment limitation decision., Exposures: Comparison between the 1999-2000 cohort vs 2015-2016 cohort., Main Outcomes and Measures: End-of-life outcomes were classified into 5 mutually exclusive categories (withholding of life-prolonging therapy, withdrawing of life-prolonging therapy, active shortening of the dying process, failed cardiopulmonary resuscitation [CPR], brain death). The primary outcome was whether patients received any treatment limitations (withholding or withdrawing of life-prolonging therapy or shortening of the dying process). Outcomes were determined by senior intensivists., Results: Of 13 625 patients admitted to participating ICUs during the 2015-2016 study period, 1785 (13.1%) died or had limitations of life-prolonging therapies and were included in the study. Compared with the patients included in the 1999-2000 cohort (n = 2807), the patients in 2015-2016 cohort were significantly older (median age, 70 years [interquartile range {IQR}, 59-79] vs 67 years [IQR, 54-75]; P < .001) and the proportion of female patients was similar (39.6% vs 38.7%; P = .58). Significantly more treatment limitations occurred in the 2015-2016 cohort compared with the 1999-2000 cohort (1601 [89.7%] vs 1918 [68.3%]; difference, 21.4% [95% CI, 19.2% to 23.6%]; P < .001), with more withholding of life-prolonging therapy (892 [50.0%] vs 1143 [40.7%]; difference, 9.3% [95% CI, 6.4% to 12.3%]; P < .001), more withdrawing of life-prolonging therapy (692 [38.8%] vs 695 [24.8%]; difference, 14.0% [95% CI, 11.2% to 16.8%]; P < .001), less failed CPR (110 [6.2%] vs 628 [22.4%]; difference, -16.2% [95% CI, -18.1% to -14.3%]; P < .001), less brain death (74 [4.1%] vs 261 [9.3%]; difference, -5.2% [95% CI, -6.6% to -3.8%]; P < .001) and less active shortening of the dying process (17 [1.0%] vs 80 [2.9%]; difference, -1.9% [95% CI, -2.7% to -1.1%]; P < .001)., Conclusions and Relevance: Among patients who had treatment limitations or died in 22 European ICUs in 2015-2016, compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in life-prolonging therapies occurred significantly less frequently. These findings suggest a shift in end-of-life practices in European ICUs, but the study is limited in that it excluded patients who survived ICU hospitalization without treatment limitations.

The original version of this article unfortunately contained a mistake. In Table 2, the frequency of Septic Shock reported just below the frequency of "At least 1 Episode of VAP" actually corresponds to the First (and not the Second) Episode of VAP during the postresuscitation period.

Background: Recent, large trials of high-frequency oscillation (HFO) versus conventional ventilation (CV) in acute respiratory distress syndrome (ARDS) reported negative results. This could be explained by an HFO-induced right ventricular (RV) dysfunction/failure due to high intrathoracic pressures and hypercapnia. We hypothesized that HFO strategies aimed at averting/attenuating hypercapnia, such as "low-frequency" (i.e., 4 Hz) HFO and 4-Hz HFO with tracheal-gas insufflation (HFO-TGI), may result in an improved RV function relative to "high-frequency" (i.e., 7 Hz) HFO (which may promote hypercapnia) and similar RV function relative to lung protective CV., Methods: We studied 17 patients with moderate-to-severe ARDS [PaO 2 -to-inspiratory O 2 fraction ratio (PaO 2 /FiO 2 ) < 150]. RV function was assessed by transesophageal echocardiography (TEE). Patients received 60 min of CV for TEE-guided, positive end-expiratory pressure (PEEP) "optimization" and subsequent stabilization; 60 min of 4-Hz HFO for "study mean airway pressure (mPaw)" titration to peripheral oxygen saturation ≥ 95%, without worsening RV function as assessed by TEE; 60 min of each tested HFO strategy in random order; and another 60 min of CV using the pre-HFO, TEE-guided PEEP setting. Study measurements (i.e., gas exchange, hemodynamics, and TEE data) were obtained over the last 10 min of pre-HFO CV, of each one of the three tested HFO strategies, and of post-HFO CV., Results: The mean "study HFO mPaw" was 8-10 cmH 2 O higher relative to pre-HFO CV. Seven-Hz HFO versus 4-Hz HFO and 4-Hz HFO-TGI resulted in higher mean ± SD right-to-left ventricular end-diastolic area ratio (RVEDA/LVEDA) (0.64 ± 0.15 versus 0.56 ± 0.14 and 0.52 ± 0.10, respectively, both p  < 0.05). Higher diastolic/systolic eccentricity indexes (1.33 ± 0.19/1.42 ± 0.17 versus 1.21 ± 0.10/1.26 ± 0.10 and 1.17 ± 0.11/1.17 ± 0.13, respectively, all p  < 0.05). Seven-Hz HFO resulted in 18-28% higher PaCO 2 relative to all other ventilatory strategies (all p  < 0.05). Four-Hz HFO-TGI versus pre-HFO CV resulted in 15% lower RVEDA/LVEDA, and 7%/10% lower diastolic/systolic eccentricity indexes (all p  < 0.05). Mean PaO 2 /FiO 2 improved by 77-80% during HFO strategies versus CV (all p  < 0.05). Mean cardiac index varied by ≤ 10% among strategies. Percent changes in PaCO 2 among strategies were predictive of concurrent percent changes in measures of RV function ( R 2  = 0.21-0.43)., Conclusions: In moderate-to-severe ARDS, "short-term" 4-Hz HFO strategies resulted in better RV function versus 7-Hz HFO, partly attributable to improved PaCO 2 control, and similar or improved RV function versus CV., Trial Registration: This study was registered 40 days prior to the enrollment of the first patient at ClinicalTrials.gov, ID no. NCT02027129, Principal Investigator Spyros D. Mentzelopoulos, date of registration January 3, 2014., Competing Interests: This study was approved by the Evaggelismos Hospital Scientific Committee (approval no. 271-30-10-2013; Chairman, Athanassios Skoutelis, MD, PHD, Professor of Internal Medicine), and written informed consent was obtained from the next-of-kin of all participating patients.Surrogates who provided informed consent for study participation also granted permission to the sharing of de-identified study data with persons authorized by the principal investigator and first author.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose: Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock., Methods: We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressor-requiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an "as-treated" principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88)., Results: Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as "hypotension and/or myocardial ischemia" did not appreciably affect the aforementioned CSHRs., Conclusions: In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Purpose: A rapidly evolving resuscitation science provides more effective treatments to an aging population with multiple comorbidites. Concurrently, emergency care has become patient-centered. This review aims to describe challenges associated with the application of key principles of bioethics in resuscitation and post-resuscitation care; propose actions to address these challenges; and highlight the need for evidence-based ethics and consensus on ethical principles interpretation., Methods: Following agreement on the article's outline, subgroups of 2-3 authors provided narrative reviews of ethical issues concerning autonomy and honesty, beneficence/nonmaleficence and dignity, justice, specific practices/circumstances such as family presence during resuscitation, and emergency research. Proposals for addressing ethical challenges were also offered., Results: Respect for patient autonomy can be realized through honest provision of information, shared decision-making, and advance directives/care planning. Essential prerequisites comprise public and specific healthcare professionals' education, appropriate regulatory provisions, and allocation of adequate resources. Regarding beneficence/nonmaleficence, resuscitation should benefit patients, while avoiding harm from futile interventions; pertinent practice should be based on neurological prognostication and patient/family-reported outcomes. Regarding dignity, aggressive life-sustaining treatments against patients preferences should be avoided. Contrary to the principle of justice, resuscitation quality may be affected by race/income status, age, ethnicity, comorbidity, and location (urban versus rural or country-specific/region-specific). Current evidence supports family presence during resuscitation. Regarding emergency research, autonomy should be respected without hindering scientific progress; furthermore, transparency of research conduct should be promoted and funding increased., Conclusions: Major ethical challenges in resuscitation science need to be addressed through complex/resource-demanding interventions. Such actions require support by ongoing/future research.

Rationale: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality., Objectives: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV., Methods: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects., Measurements and Main Results: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline Pa O 2 /Fi O 2 of 114 ± 39 mm Hg; 40% had severe ARDS (Pa O 2 /Fi O 2 <100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with Pa O 2 /Fi O 2 among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04)., Conclusions: HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.