Variations in reporting of nurse involvement in end-of-life practices in intensive care units worldwide (ETHICUS-2): A prospective observational study.

BACKGROUND: ICU nurses are most frequently at the patient's bedside, providing care for both patients and family members. They perform an essential role and are involved in decision-making. Despite this, research suggests that nurses have a limited role in the end-of-life decision-making process and are occasionally not involved. OBJECTIVE: Explore global ICU nurse involvement in end of life decisions based on the physician's perceptions and sub-analyses from the ETHICUS-2 study. DESIGN: This is a secondary analysis of a prospective multinational, observational study of the ETHICUS-2 study. SETTING: End of life decision-making processes in ICU patients were studied during a 6-month period between Sept 1, 2015, and Sept 30, 2016, in 199 ICUs in 36 countries. INTERVENTION: None. METHODS: The ETHICUS II study instrument contained 20 questions. This sub-analysis addressed the four questions related to nurse involvement in end-of-life decision-making: Who initiated the end-of-life discussion? Was withholding or withdrawing treatment discussed with nurses? Was a nurse involved in making the end-of-life decision? Was there agreement between physicians and nurses? These 4 questions are the basis for our analysis. Global regions were compared. RESULTS: Physicians completed 91.8 % of the data entry. A statistically significant difference was found between regions (p < 0.001) with Northern Europe and Australia/New Zealand having the most discussion with nurses and Latin America, Africa, Asia and North America the least. The percentages of end-of-life decisions in which nurses were involved ranged between 3 and 44 %. These differences were statistically significant. Agreement between physicians and nurses related to decisions resulted in a wide range of responses (27-86 %) (p < 0.001). There was a wide range of those who replied "not applicable" to the question of agreement between physicians and nurses on EOL decisions (0-41 %). CONCLUSION: There is large variability in nurse involvement in end-of-life decision-making in the ICU. The most concerning findings were that in some regions, according to physicians, nurses were not involved in EOL decisions and did not initiate the decision-making process. There is a need to develop the collaboration between nurses and physicians. Nurses have valuable contributions for best possible patient-centered decisions and should be respected as important parts of the interdisciplinary team. TWEETABLE ABSTRACT: Wide global differences were found in nurse end of life decision involvement, with low involvement in North and South America and Africa and higher involvement in Europe and Australia/New Zealand.

Limitations of life-sustaining therapies in South Africa.

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.

The impact of religion on changes in end-of-life practices in European intensive care units: a comparative analysis over 16 years.

PURPOSE: Religious beliefs affect end-of-life practices in intensive care units (ICUs). Changes over time in end-of-life practices were not investigated regarding religions. METHODS: Twenty-two European ICUs (3 regions: Northern, Central, and Southern Europe) participated in both Ethicus-1 (years 1999-2000) and Ethicus-2 studies (years 2015-2016). Data of ICU patients who died or had limitations of life-sustaining therapy were analysed regarding changes in end-of-life practices and patient/physician religious affiliations. Frequencies, timing of decision-making, and religious affiliations of physicians/patients were compared using the same definitions. RESULTS: In total, 4592 adult ICU patients (n = 2807 Ethicus-1, n = 1785 Ethicus-2) were analysed. In both studies, patient and physician religious affiliations were mostly Catholic, Greek Orthodox, Jewish, Protestant, or unknown. Treating physicians (but not patients) commonly reported no religious affiliation (18%). Distribution of end-of-life practices with respect to religion and geographical regions were comparable between the two studies. Withholding [n = 1143 (40.7%) Ethicus-1 and n = 892 (50%) Ethicus-2] and withdrawing [n = 695 (24.8%) Ethicus-1 and n = 692 (38.8%) Ethicus-2] were most commonly decided. No significant changes in end-of-life practices were observed for any religion over 16 years. The number of end-of-life discussions with patients/ families/ physicians increased, while mortality and time until first decision decreased. CONCLUSIONS: Changes in end-of-life practices observed over 16 years appear unrelated to religious affiliations of ICU patients or their treating physicians, but the effects of religiosity and/or culture could not be assessed. Shorter time until decision in the ICU and increased numbers of patient and family discussions may indicate increased awareness of the importance of end-of-life decision-making in the ICU.

Critical Care Staffing in Pandemics and Disasters: A Consensus Report From a Subcommittee of the Task Force for Mass Critical Care - Systems Strategies to Sustain the Health Care Workforce.

BACKGROUND: The COVID-19 pandemic has led to unprecedented mental health disturbances, burnout, and moral distress among health care workers, affecting their ability to care for themselves and their patients. RESEARCH QUESTION: In health care workers, what are key systemic factors and interventions impacting mental health and burnout? STUDY DESIGN AND METHODS: The Workforce Sustainment subcommittee of the Task Force for Mass Critical Care (TFMCC) utilized a consensus development process, incorporating evidence from literature review with expert opinion through a modified Delphi approach to determine factors affecting mental health, burnout, and moral distress in health care workers, to propose necessary actions to help prevent these issues and enhance workforce resilience, sustainment, and retention. RESULTS: Consolidation of evidence gathered from literature review and expert opinion resulted in 197 total statements that were synthesized into 14 major suggestions. These suggestions were organized into three categories: (1) mental health and well-being for staff in medical settings; (2) system-level support and leadership; and (3) research priorities and gaps. Suggestions include both general and specific occupational interventions to support health care worker basic physical needs, lower psychological distress, reduce moral distress and burnout, and foster mental health and resilience. INTERPRETATION: The Workforce Sustainment subcommittee of the TFMCC offers evidence-informed operational strategies to assist health care workers and hospitals plan, prevent, and treat the factors affecting health care worker mental health, burnout, and moral distress to improve resilience and retention following the COVID-19 pandemic.

Outcome predictors and patient progress following delivery in pregnant and postpartum patients with severe COVID-19 pneumonitis in intensive care units in Israel (OB-COVICU): a nationwide cohort study.

BACKGROUND: A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery. METHODS: In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery). FINDINGS: From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO2), SpO2 to fraction of inspired oxygen (FiO2) ratio (S/F ratio), partial pressure of arterial oxygen to FiO2 ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores. INTERPRETATION: In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation. FUNDING: None.

The Impact of the Society of Critical Care Medicine's Flagship Journal: Critical Care Medicine: Reflections of Critical Care Pioneers.

On the 50th anniversary of the Society of Critical Care Medicine's journal Critical Care Medicine, critical care pioneers reflect on the importance of the journal to their careers and to the development of the field of adult and pediatric critical care.

Patient-Level Meta-Analysis of Low-Dose Hydrocortisone in Adults with Septic Shock.

BACKGROUND: Trials and study-level meta-analyses have failed to resolve the role of corticosteroids in the management of patients with septic shock. Patient-level meta-analyses may provide more precise estimates of treatment effects, particularly subgroup effects. METHODS: We pooled individual patient data from septic shock trials investigating the adjunctive use of intravenous hydrocortisone. The primary outcome was 90-day all-cause mortality, and it was also analyzed across predefined subgroups. Secondary outcomes included mortality at intensive care unit and hospital discharge, at 28 and 180 days, and vasopressor-, ventilator-, and organ failure­free days. Adverse events included superinfection, muscle weakness, hyperglycemia, hypernatremia, and gastroduodenal bleeding. RESULTS: Of 24 eligible trials (n=8528), 17 (n=7882) provided individual patient data, and 7 (n=5929) provided 90-day mortality. The marginal relative risk (RR) for 90-day mortality of hydrocortisone versus placebo was 0.93 (95% confidence interval [CI], 0.82 to 1.04; P=0.22; moderate certainty). It was 0.86 (95% CI, 0.79 to 0.92) for hydrocortisone with fludrocortisone and 0.96 (95% CI, 0.82 to 1.12) without fludrocortisone. There was no significant differential treatment effect across subgroups. Hydrocortisone was associated with little to no difference in any of the secondary outcomes except vasopressor-free days (mean difference, 1.24 days; 95% CI, 0.74 to 1.73; high certainty). Hydrocortisone may not be associated with an increase in the risk of superinfection (RR, 1.04; 95% CI, 0.95 to 1.15; low certainty), hyperglycemia (RR, 1.05; 95% CI, 0.98 to 1.12; low certainty), or gastroduodenal bleeding (RR, 1.11; 95% CI, 0.83 to 1.48; low certainty). Hydrocortisone may be associated with an increase in the risk of hypernatremia (RR, 2.01; 95% CI, 1.56 to 2.60; low certainty) and muscle weakness (n=2647; RR, 1.73; 95% CI, 1.49 to 1.99; low certainty). CONCLUSIONS: In this patient-level meta-analysis, hydrocortisone compared with placebo was not associated with reduced mortality for patients with septic shock. (Funded by "Programme d'Investissements d'Avenir," a research Professorship from the National Institute of Health and Care Research, Leadership Fellowships from the National Health and Medical Research Council of Australia, and Emerging Leaders Fellowship from the National Health and Medical Research Council of Australia; PROSPERO registration number, CRD42017062198.)

Outcomes and Predictors of 28-Day Mortality in Patients With Solid Tumors and Septic Shock Defined by Third International Consensus Definitions for Sepsis and Septic Shock Criteria.

BACKGROUND: Data assessing outcomes of patients with solid tumors demonstrating septic shock using the Third International Consensus Definitions for Sepsis and Septic Shock are scarce. RESEARCH QUESTION: What are the independent predictors of 28-day mortality in critically ill adults with solid tumors and septic shock? STUDY DESIGN AND METHODS: Cohort of solid tumor patients admitted to the ICU with septic shock. Demographic and clinical characteristics were gathered from the electronic health records. We developed a reduced multivariate logistics regression model to identify independent predictors of 28-day mortality and used Kaplan-Meier plots to assess survival. RESULTS: A total of 271 patients were included. The median age was 62 years (range, 19-94 years); 57.2% were men and 53.5% were White. The most common underlying malignancies were lung (19.2%), breast (7.7%), pancreatic (7.7%), and colorectal (7.4%) cancers. Most patients (84.5%) harbored metastatic disease. Twenty-eight days after ICU admission, 188 patients (69.4%) had died. Nonsurvivors showed a higher rate of advanced cancer, longer hospital stays before ICU admission, and higher Sequential Organ Failure Assessment scores at admission and throughout the ICU stay (P < .001 for all). The multivariate analysis identified metastatic disease (OR, 3.17; 95% CI, 1.43-7.03), respiratory failure (OR, 2.34; 95% CI, 1.15-4.74), elevated lactate levels (OR, 3.19; 95% CI, 1.90-5.36), and Eastern Cooperative Oncology Group performance scores of 3 or 4 (OR, 2.72; 95% CI, 1.33-5.57) as independent predictors of 28-day mortality. Only 38 patients (14%) were discharged home without medical assistance. INTERPRETATION: The 28-day mortality rate of patients with solid tumors and septic shock was considerably high. Factors associated with worse survival included advanced oncologic disease, poor performance status, high lactate level, and concomitant acute respiratory failure. Early goals-of-care discussions should be considered for frail patients with septic shock and advanced metastatic disease without denying access to the appropriate level of care.

Global Comparison of Communication of End-of-Life Decisions in the ICU.

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.

Derivation and performance of an end-of-life practice score aimed at interpreting worldwide treatment-limiting decisions in the critically ill.

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.

Outcomes and Predictors of 28-Day Mortality in Patients With Hematologic Malignancies and Septic Shock Defined by Sepsis-3 Criteria.

BACKGROUND: To describe short-term outcomes and independent predictors of 28-dayx mortality in adult patients with hematologic malignancies and septic shock defined by the new Third International Consensus Definitions (Sepsis-3) criteria. METHODS: We performed a retrospective cohort study of patients admitted to the medical ICU with septic shock from April 2016 to March 2019. Demographic and clinical features and short-term outcomes were collected. We used descriptive statistics to summarize patient characteristics, logistic regression to identify predictors of 28-day mortality, and Kaplan-Meier plots to assess survival. RESULTS: Among the 459 hematologic patients with septic shock admitted to the ICU, 109 (23.7%) had received hematopoietic stem cell transplant. The median age was 63 years (range, 18-89 years), and 179 (39%) were women. Nonsurvivors had a higher Charlson comorbidity index (P=.007), longer length of stay before ICU admission (P=.01), and greater illness severity at diagnosis and throughout the hospital course (P<.001). The mortality rate at 28 days was 67.8% and increased with increasing sequential organ failure assessment score on admission (odds ratio [OR], 1.11; 95% CI, 1.03-1.20), respiratory failure (OR, 3.12; 95% CI, 1.49-6.51), and maximum lactate level (OR, 1.16; 95% CI, 1.10-1.22). Aminoglycosides administration (OR, 0.42; 95% CI, 0.26-0.69), serum albumin (OR, 0.51; 95% CI, 0.31-0.86), and granulocyte colony-stimulating factor (G-CSF) (OR, 0.40; 95% CI, 0.24-0.65) were associated with lower 28-day mortality. Life support limitations were present in 81.6% of patients at death. At 90 days, 19.4% of the patients were alive. CONCLUSIONS: Despite efforts to enhance survival, septic shock in patients with hematologic malignancies is still associated with high mortality rates and poor 90-day survival. These results demonstrate the need for an urgent call to action with higher awareness, including the further evaluation of interventions such as earlier ICU admission, aminoglycosides administration, and G-CSF treatment.

Mass Critical Care Surge Response During COVID-19: Implementation of Contingency Strategies - A Preliminary Report of Findings From the Task Force for Mass Critical Care.

BACKGROUND: After the publication of a 2014 consensus statement regarding mass critical care during public health emergencies, much has been learned about surge responses and the care of overwhelming numbers of patients during the COVID-19 pandemic. Gaps in prior pandemic planning were identified and require modification in the midst of severe ongoing surges throughout the world. RESEARCH QUESTION: A subcommittee from The Task Force for Mass Critical Care (TFMCC) investigated the most recent COVID-19 publications coupled with TFMCC members anecdotal experience in order to formulate operational strategies to optimize contingency level care, and prevent crisis care circumstances associated with increased mortality. STUDY DESIGN AND METHODS: TFMCC adopted a modified version of established rapid guideline methodologies from the World Health Organization and the Guidelines International Network-McMaster Guideline Development Checklist. With a consensus development process incorporating expert opinion to define important questions and extract evidence, the TFMCC developed relevant pandemic surge suggestions in a structured manner, incorporating peer-reviewed literature, "gray" evidence from lay media sources, and anecdotal experiential evidence. RESULTS: Ten suggestions were identified regarding staffing, load-balancing, communication, and technology. Staffing models are suggested with resilience strategies to support critical care staff. ICU surge strategies and strain indicators are suggested to enhance ICU prioritization tactics to maintain contingency level care and to avoid crisis triage, with early transfer strategies to further load-balance care. We suggest that intensivists and hospitalists be engaged with the incident command structure to ensure two-way communication, situational awareness, and the use of technology to support critical care delivery and families of patients in ICUs. INTERPRETATION: A subcommittee from the TFMCC offers interim evidence-informed operational strategies to assist hospitals and communities to plan for and respond to surge capacity demands resulting from COVID-19.

Changes in intensive care unit nurse involvement in end of life decision making between 1999 and 2016: Descriptive comparative study.

OBJECTIVE: Comparison of nurse involvement in end of life decision making in European countries participating in ETHICUS I- 1999 and ETHICUS II- 2015. METHODOLOGY: This was a prospective observational study of 22 European ICUs included in the ETHICUS-II and I. Data were collected as per the ETHICUS-I and ETHICUS-II protocols. Four questions within the ETHICUS protocols related to nurse involvement in end of life decision making were analyzed. This is a comparison of changes in nurse involvement in end of life decisions from 1999 to 2015. SETTING: International e-based questionnaire completed by an intensive care clinician when an end of life decision was performed on any patient. SUBJECTS: Intensive care physicians and nurses, no interventions were performed. MEASUREMENTS: A 20 question survey was used to describe the decision making process, on what basis was the decision made, who was involved in the decision making process, and what precise decisions were made. RESULTS: A total of 4592 cases from 22 centres are included. While there was more agreement between nurses and physicians in ETHICUS-I compared to ETHICUS-I, fewer discussions with nurses occurred in ETHICUS-II. The frequency of end of life decisions that were discussed with nurses decreased in all three regions between ETHICUS-I and ETHICUS-II. CONCLUSION: Based on the results of the current study, nurses should be further encouraged to increase their involvement in end of life decision-making, especially those in southern Europe.

Changes in communication of end-of-life decisions in European ICUs from 1999 to 2016 (Ethicus-2) - a prospective observational study.

PURPOSE: We investigated changes in communication practice about end-of-life decisions in European ICUs over 16 years. MATERIALS AND METHODS: This prospectively planned secondary analysis of two observational studies in 22 European ICUs in 1999-2000 (Ethicus-1) and 2015-16 (Ethicus-2) included consecutive patients who died or with limitation of life-sustaining therapy. ICUs were grouped into North, Central and South European regions. RESULTS: A total 4592 patients were included in 1999-2000 (n = 2807) and 2015-16 (n = 1785). Information about patient wishes increased overall (from 25.4% [570] to 51.1% [840]) and in all regions (42% to 61% [North], 22% to 56% [Central] and 20% to 32% [South], all p < 0.001). Discussions of treatment limitations with patients or families increased overall (66.0% to 76.1%) and in Northern and Central Europe (87% to 94% and 75% to 82.2%, respectively, all p < 0.001) but not in the South. Strongest predictor for discussions was the region (North>Central>South) followed by patient decision-making capacity. CONCLUSION: End-of-life decisions are increasingly discussed but communication practices vary by region and follow a North-South gradient. Despite increased availability of information, patient preferences still remain unknown in every second patient. This calls for increased efforts to assess patient preference in advance and make them known to ICU clinicians.

Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study.

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.

The Influence of Geography, Religion, Religiosity and Institutional Factors on Worldwide End-of-Life Care for the Critically Ill: The WELPICUS Study.

PURPOSE: To evaluate the association between provider religion and religiosity and consensus about end-of-life care and explore if geographical and institutional factors contribute to variability in practice. MATERIALS AND METHODS: Using a modified Delphi method 22 end-of-life issues consisting of 35 definitions and 46 statements were evaluated in 32 countries in North America, South America, Eastern Europe, Western Europe, Asia, Australia and South Africa. A multidisciplinary, expert group from specialties treating patients at the end-of-life within each participating institution assessed the association between 7 key statements and geography, religion, religiosity and institutional factors likely influencing the development of consensus. RESULTS: Of 3049 participants, 1366 (45%) responded. Mean age of respondents was 45 ± 9 years and 55% were females. Following 2 Delphi rounds, consensus was obtained for 77 (95%) of 81 definitions and statements. There was a significant difference in responses across geographical regions. South African and North American respondents were more likely to encourage patients to write advance directives. Fewer Eastern European and Asian respondents agreed with withdrawing life-sustaining treatments without consent of patients or surrogates. While respondent's religion, years in practice or institution did not affect their agreement, religiosity, physician specialty and responsibility for end-of-life decisions did. CONCLUSIONS: Variability in agreement with key consensus statements about end-of-life care is related primarily to differences among providers, with provider-level variations related to differences in religiosity and specialty. Geography also plays a role in influencing some end-of-life practices. This information may help understanding ethical dilemmas and developing culturally sensitive end-of-life care strategies.

Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock.

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the database from the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The identified theranostic marker was validated against data from a cohort of the Hellenic Sepsis Study Group (HSSG) (n = 246), patients enrolled in the clinical trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, n = 118), and another, smaller clinical trial (Crossover study, n = 20). In addition, in vitro blood culture experiments and in vivo experiments in mouse models were performed to assess biological plausibility. A low serum IFNγ/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this marker for a decision rule, we applied it to three validation sets and observed the same trend. Experimental studies in vitro revealed that IFNγ/IL10 was negatively associated with the load of (heat inactivated) pathogens in spiked human blood and in septic mouse models. Accordingly, an in silico analysis of published IFNγ and IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory Response Syndrome supported this association between the ratio and pathogen burden. We propose IFNγ/IL10 as a molecular marker supporting the decision to administer hydrocortisone to patients in septic shock. Prospective clinical studies are necessary and standard operating procedures need to be implemented, particularly to define a generic threshold. If confirmed, IFNγ/IL10 may become a suitable theranostic marker for an urging clinical need.