Use of drugs for hypertension or heart failure and the risk of death in COVID-19: association with loop-diuretics.

PURPOSE: To study the association between the use of drugs for hypertension or heart failure, particularly diuretics, and risk of death in COVID-19. METHODS: We conducted a cohort study, based on record linked individual-based data from national registers, of all Swedish inhabitants 50 years and older (n = 3,909,321) at the start of the first SARS-CoV-2 wave in Sweden. The association between use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), thiazides, loop diuretics, aldosterone antagonists, beta blocking agents and calcium channel blockers at the index date 6 March 2020, and death in COVID-19 during 7 March to 31 July 2020, was analysed using Cox-proportional hazards regression, adjusted for a wide range of possible confounders. RESULTS: Use of loop diuretics was associated with higher risk [adjusted hazard ratio (HR) 1.26; 95% confidence interval (95% CI) 1.17-1.35] and thiazides with reduced risk (0.78; 0.69-0.88) of death in COVID-19. In addition, lower risk was observed for ACEI and higher risk for beta-blocking agents, although both associations were weak. For ARB, aldosterone antagonists and calcium channel blockers no significant associations were found. CONCLUSION: In this nationwide cohort of nearly 4 million persons 50 years and older, the use of loop diuretics was associated with increased risk of death in COVID-19 during the first SARS-CoV-2 wave in Sweden. This contrasted to the decreased risk observed for thiazides. As treatment with loop diuretics is common, particularly in the elderly, the group most affected by severe COVID-19, this finding merit further investigation.

The association of premorbid conditions with 6-month mortality in acutely admitted ICU patients over 80 years.

BACKGROUND: Premorbid conditions influence the outcome of acutely ill adult patients aged 80 years and over who are admitted to the ICU. The aim of this study was to determine the influence of such premorbid conditions on 6 month survival. METHODS: Prospective cohort study in 242 ICUs from 22 countries including patients 80 years or above, admitted over a 6 months period to an ICU between May 2018 and May 2019. Only emergency (acute) ICU admissions in adult patients ≥ 80 years of age were eligible. Patients who were admitted after planned/elective surgery were excluded. We measured the Clinical Frailty Scale (CFS), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), disability with the Katz activities of daily living (ADL) score, comorbidities and a Polypharmacy Score (CPS). RESULTS: Overall, the VIP2 study included 3920 patients. During ICU stay 1191 patients died (30.9%), and another 436 patients (11.1%) died after ICU discharge but within the first 30 days of admission, and an additional 895 patients died hereafter but within the first 6 months after admission (22.8%). The 6 months mortality was 64%. The median CFS was 4 (IQR 3-6). Frailty (CFS ≥ 5) was present in 26.6%. Cognitive decline (IQCODE above 3.5) was found in 30.2%. The median IQCODE was 3.19. A Katz ADL of 4 or less was present in 27.7%. Patients who surviving > 6 months were slightly younger (median age survivors 84 with IQR 81-86) than patients dying within the first 6 months (median age 84, IQR 82-87, p = 0.013), were less frequently frail (CFS > 5 in 19% versus 34%, p < 0.01) and were less dependent based on their Katz activities of daily living measurement (median Katz score 6, IQR 5-6 versus 6 points, IQR 3-6, p < 0.01). CONCLUSIONS: We found that Clinical Frailty Scale, age, and SOFA at admission were independent prognostic factors for 6 month mortality after ICU admission in patients age 80 and above. Adding other geriatric syndromes and scores did not improve the model. This information can be used in shared-decision making. CLINICALTRIALS: gov: NCT03370692.

Effects of education, income and employment on ICU and post-ICU survival - A nationwide Swedish cohort study of individual-level data with 1-year follow up.

PURPOSE: The aim of this study was to examine relationships between education, income, and employment (socioeconomic status, SES) and intensive care unit (ICU) survival and survival 1 year after discharge from ICU (Post-ICU survival). METHODS: Individual data from ICU patients were linked to register data of education level, disposable income, employment status, civil status, foreign background, comorbidities, and vital status. Associations between SES, ICU survival and 1-year post-ICU survival was analysed using Cox's regression. RESULTS: We included 58,279 adults (59% men, median length of stay in ICU 4.0 days, median SAPS3 score 61). Survival rates at discharge from ICU and one year after discharge were 88% and 63%, respectively. Risk of ICU death (Hazard ratios, HR) was significantly higher in unemployed and retired compared to patients who worked prior to admission (1.20; 95% CI: 1.10-1.30 and 1.15; (1.07-1.24), respectively. There was no consistent association between education, income and ICU death. Risk of post-ICU death decreased with greater income and was roughly 16% lower in the highest compared to lowest income quintile (HR 0.84; 0.79-0.88). Higher education levels appeared to be associated with reduced risk of death during the first year after ICU discharge. CONCLUSIONS: Significant relationships between low SES in the critically ill and increased risk of death indicate that it is important to identify and support patients with low SES to improve survival after intensive care. Studies of survival after critical illness need to account for participants SES.

Prognosis after Intensive Care for COPD Exacerbation in Relation to Long-Term Oxygen Therapy: A Nationwide Cohort Study.

Decisions to admit or refuse admission to intensive care for acute exacerbations of COPD (AECOPD) can be difficult, due to an uncertainty about prognosis. Few studies have evaluated outcomes after intensive care for AECOPD in patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT). In this nationwide observational cohort study, we investigated survival after first-time admission for AECOPD in all patients aged ≥40 years admitted to Swedish intensive care units between January 2008 and December 2015, comparing patients with and without LTOT. Among the 4,648 patients enrolled in the study, 450 were on LTOT prior to inclusion. Respiratory support data was available for 2,631 patients; 73% of these were treated with noninvasive ventilation (NIV) only, 17% were treated with immediate invasive ventilation, and 10% were intubated after failed attempt with NIV. Compared to patients without LTOT, patients with LTOT had higher 30-day mortality (38% vs. 25%; p < 0.001) and one-year mortality (70% vs. 43%; p < 0.001). Multivariable logistic and Cox regression models adjusted for age, sex and SAPS3 score confirmed higher mortality in LTOT, odds ratio for 30-day mortality was 1.8 ([95% confidence interval] 1.5-2.3) and hazard ratio for one-year mortality was 1.8 (1.6-2.0). In summary, although need for LTOT is a negative prognostic marker for survival after AECOPD requiring intensive care, a majority of patients with LTOT survived the AECOPD and 30% were alive after one year.

Consent is a confounding factor in a prospective observational study of critically ill elderly patients.

During analysis of a prospective multinational observation study of critically ill patients ≥80 years of age, the VIP2 study, we also studied the effects of differences in country consent for study inclusion. This is a post hoc analysis where the ICUs were analyzed according to requirement for study consent. Group A: ICUs in countries with no requirement for consent at admission but with deferred consent in survivors. Group B: ICUs where some form of active consent at admission was necessary either from the patient or surrogates. Patients' characteristics, the severity of disease and outcome variables were compared. Totally 3098 patients were included from 21 countries. The median age was 84 years (IQR 81-87). England was not included because of changing criteria for consent during the study period. Group A (7 countries, 1200 patients), and group B (15 countries, 1898 patients) were comparable with age and gender distribution. Cognition was better preserved prior to admission in group B. Group A suffered from more organ dysfunction at admission compared to group B with Sequential Organ Failure Assessment score median 8 and 6 respectively. ICU survival was lower in group A, 66.2% compared to 78.4% in group B (p<0.001). We hence found profound effects on outcomes according to differences in obtaining consent for this study. It seems that the most severely ill elderly patients were less often recruited to the study in group B. Hence the outcome measured as survival was higher in this group. We therefore conclude that consent likely is an important confounding factor for outcome evaluation in international studies focusing on old patients.

A nationwide evaluation of antibiotics consumption in Swedish intensive care units.

BACKGROUND: Around 70% of all ICU patients are treated with antibiotics whereas up to 30% are suggested as unnecessary. Measuring antibiotic consumption is a prerequisite to improving its use and the purpose of the present investigation was to explore the use of antibiotics in Swedish ICUs. MATERIAL AND METHODS: Daily Defined Doses (DDDs) of antimicrobials delivered to Swedish ICUs, 2016-2018, were retrieved from Swedish pharmacies. From the Swedish Intensive Care Registry, we extracted data on a number of patient admissions, occupied bed days and Simplified Acute Physiology Score (SAPS)3. RESULTS: There was a similar annual rate of total DDDs per admission of 3.7, 3.5, 3.8 and total DDDs per 100 occupied bed days of 111, 111, and 115 but with an approximately 6-fold difference of DDDs per occupied bed days (61-366) between the ICUs. The most frequently used antibiotics were isoxazolyl penicillins (J01CF), penicillins with betalactamase-inhibitors, mainly piperacillin/tazobactam (J01CR), 3rd and 4th generation cephalosporins (J01DD + DE) and carbapenems (J01DH). Together these four classes accounted for a median of 52% of all antibiotic use. The use of carbapenems had a moderate positive correlation with the mean SAPS3 score (r = 0.6, p = .01). The use of other broad-spectrum antibiotics showed no such correlation. CONCLUSION: Overall antibiotic use remained similar in Swedish ICUs during the years 2016-2018. Broad-spectrum antibiotics accounted for 50% of all DDDs but with a large inter-ICU variation which only partly can be explained by differences in patient case mix and microbial resistance. Presumably, it also reflects varying local prescribing practices.

Short-term mortality of patients ≥80 years old admitted to European intensive care units: an international observational study.

BACKGROUND: Limited evidence suggests variation in mortality of older critically ill adults across Europe. We aimed to investigate regional differences in mortality among very old ICU patients. METHODS: Multilevel analysis of two international prospective cohort studies. We included patients ≥80 yr old from 322 ICUs located in 16 European countries. The primary outcome was mortality within 30 days from admission to the ICU. Results are presented as n (%) with 95% confidence intervals and odds ratios (ORs). RESULTS: Of 8457 patients, 2944 (36.9% [35.9-38.0%]) died within 30 days. Crude mortality rates varied widely between participating countries (from 10.1% [6.4-15.6%] to 45.1% [41.1-49.2%] in the ICU and from 21.3% [16.3-28.9%] to 55.3% [51.1-59.5%] within 30 days). After adjustment for confounding variables, the variation in 30-day mortality between countries was substantially smaller than between ICUs (median OR 1.14 vs 1.58). Healthcare expenditure per capita (OR=0.84 per $1000 [0.75-0.94]) and social health insurance framework (OR=1.43 [1.01-2.01]) were associated with ICU mortality, but the direction and magnitude of these relationships was uncertain in 30-day follow-up. Volume of admissions was associated with lower mortality both in the ICU (OR=0.81 per 1000 annual ICU admissions [0.71-0.94]) and in 30-day follow-up (OR=0.86 [0.76-0.97]). CONCLUSION: The apparent variation in short-term mortality rates of older adults hospitalised in ICUs across Europe can be largely attributed to differences in the clinical profile of patients admitted. The volume-outcome relationship identified in this population requires further investigation.

Intensive care unit to unit capacity transfers are associated with increased mortality: an observational cohort study on patient transfers in the Swedish Intensive Care Register.

BACKGROUND: Transfers from one intensive care unit (ICU) to another ICU are associated with increased length of intensive care and hospital stay. Inter-hospital ICU transfers are carried out for three main reasons: clinical transfers, capacity transfers and repatriations. The aim of the study was to show that different ICU transfers differ in risk-adjusted mortality rate with repatriations having the least risk. RESULTS: Observational cohort study of adult patients transferred between Swedish ICUs during 3 years (2016-2018) with follow-up ending September 2019. Primary and secondary end-points were survival to 30 days and 180 days after discharge from the first ICU. Data from 75 ICUs in the Swedish Intensive Care Register, a nationwide intensive care register, were used for analysis (89% of all Swedish ICUs), covering local community hospitals, district general hospitals and tertiary care hospitals. We included adult patients (16 years or older) admitted to ICU and subsequently discharged by transfer to another ICU. Only the first admission was used. Exposure was discharge to any other ICU (ICU-to-ICU transfer), whether in the same or in another hospital. Transfers were grouped into three predefined categories: clinical transfer, capacity transfer, and repatriation. We identified 15,588 transfers among 112,860 admissions (14.8%) and analysed 11,176 after excluding 4112 repeat transfer of the same individual and 300 with missing risk adjustment. The majority were clinical transfers (62.7%), followed by repatriations (21.5%) and capacity transfers (15.8%). Unadjusted 30-day mortality was 25.0% among capacity transfers compared to 14.5% and 16.2% for clinical transfers and repatriations, respectively. Adjusted odds ratio (OR) for 30-day mortality were 1.25 (95% CI 1.06-1.49 p = 0.01) for capacity transfers and 1.17 (95% CI 1.02-1.36 p = 0.03) for clinical transfers using repatriation as reference. The differences remained 180 days post-discharge. CONCLUSIONS: There was a large proportion of ICU-to-ICU transfers and an increased odds of dying for those transferred due to other reasons than repatriation.

A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries.

BACKGROUND: We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. METHODS: Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. RESULTS: Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%. CONCLUSION: There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

Mortality in hospitalized COVID-19 patients was associated with the COVID-19 admission rate during the first year of the pandemic in Sweden.

INTRODUCTION: Studies from the first pandemic wave found associations between COVID-19 hospital load and mortality. Here, we aimed to study if mortality of hospitalized COVID-19 patients was associated with the COVID-19 admission rate during a full year of the pandemic in Sweden. METHOD: Observational review of all patients admitted to hospital with COVID-19 in Sweden between March 2020 and February 2021 (n = 42,017). Primary outcome was 60-day all-cause mortality related to number of COVID-19 hospital admissions per month/100,000 inhabitants. Poisson regression was used to estimate the relative risk for death by month of admission, adjusting for pre-existing factors. RESULTS: The overall mortality was 17.4%. Excluding March 2020, mortality was clearly correlated to the number of COVID-19 admissions per month (coefficient of correlation ρ=.96; p<.0001). After adjustment for pre-existing factors, the correlation remained significant (ρ=.75, p=.02). Patients admitted in December (high admission rate and high mortality) had more comorbidities and longer hospital stays, and patients treated in intensive care units (ICU) had longer pre-ICU hospital stays and worse respiratory status on ICU admission than those admitted in July to September (low admission rate and low mortality). CONCLUSION: Mortality in hospitalized COVID-19 patients was clearly associated with the COVID-19 admission rate. Admission of healthier patients between pandemic waves and delayed ICU care during wave peaks could contribute to this pattern. The study supports measures to flatten-the-curve to reduce the number of COVID-19 patients admitted to hospital.

Management and outcomes in critically ill nonagenarian versus octogenarian patients.

BACKGROUND: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. METHODS: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. RESULTS: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). CONCLUSION: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions. TRIAL REGISTRATION: NCT03134807 and NCT03370692 .

Relationship between the Clinical Frailty Scale and short-term mortality in patients ≥ 80 years old acutely admitted to the ICU: a prospective cohort study.

BACKGROUND: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. METHODS: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient's age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. RESULTS: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81-87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). CONCLUSION: Knowledge about a patient's frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2).

Provision of critical care for the elderly in Europe: a retrospective comparison of national healthcare frameworks in intensive care units.

OBJECTIVES: In Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI. SETTING: ICUs in 16 European countries. PARTICIPANTS: In total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems. PRIMARY AND SECONDARY OUTCOMES MEASURES: We chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies. RESULTS: In SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p<0.001), longer length of ICU stays (90±162 vs 72±134 hours; p<0.001) and increased levels of organ support. The ICU mortality (aOR 1.50, 95% CI 1.09 to 2.06; p=0.01) was consistently higher in the SHI; however, the 30-day mortality (aOR 0.89, 95% CI 0.66 to 1.21; p=0.47) was similar between THS and SHI. In a sensitivity analysis stratifying for the health economic data, the 30-day mortality was higher in SHI, in low GDP per capita (aOR 2.17, 95% CI 1.42 to 3.58) and low HDI (aOR 1.22, 95% CI 1.64 to 2.20) settings. CONCLUSIONS: The 30-day mortality was similar in both systems. Patients in SHI were older, sicker and frailer at baseline, which could be interpreted as a sign for a more liberal admission policy in SHI. We believe that the observed trend towards ICU excess mortality in SHI results mainly from a more liberal admission policy and an increase in treatment limitations. TRIAL REGISTRATION NUMBERS: NCT03134807 and NCT03370692.

Mortality trends among hospitalised COVID-19 patients in Sweden: A nationwide observational cohort study.

BACKGROUND: It is important to know if mortality among hospitalised COVID-19 patients has changed as the pandemic has progressed. The aim of this study was to describe the dynamics over time of mortality among patients hospitalised for COVID-19 in Sweden, using nationwide data compiled by the Swedish National Board of Health and Welfare. METHODS: Observational cohort study where all patients hospitalised in Sweden between March 1 and September 30, 2020, with SARS-CoV-2 RNA positivity 14 days before to 5 days after admission and a discharge code for COVID-19 were included. Outcome was 60-day all-cause mortality. Patients were categorised according to month of hospital admission. Poisson regression was used to estimate the relative risk of death by month of admission, adjusting for, age, sex, comorbidities, care dependency, country of birth, healthcare region, and Simplified Acute Physiology, version 3 (patients in intensive care units; ICU). FINDINGS: A total of 17,140 patients were included, of which 2943 died within 60 days of admission. The overall 60-day mortality was thus 17·2% (95% CI, 16·6%-17·7%), and it decreased from 24·7% (95% CI, 23·0%-26·5%) in March to 10·4% (95% CI, 8·9%-12·1%) post-wave (July-September). Adjusted relative risk (RR) of death was 0·46 (95% CI, 0·39-0·54) post-wave, using March as reference. Corresponding RR for patients not admitted to ICU and those admitted to ICU were 0·49 (95% CI, 0·42-0·59) and 0·49 (95% CI, 0·33-0·72), respectively. The proportion of patients admitted to ICU decreased from 19·4% (95% CI, 17·9%-21·1%) in the March cohort to 8·9% (95% CI, 7·5%-10·6%) post-wave. INTERPRETATION: There was a gradual decline in mortality during the spring of 2020 in Swedish hospitalised COVID-19 patients, independent of baseline patient characteristics. Future research is needed to explain the reasons for this decline. The changing COVID-19 mortality should be taken into account when management and results of studies from the first pandemic wave are evaluated. FUNDING: This study was funded by Sweden's National Board of Health and Welfare.

The relationship between life-sustaining treatment limitation and organ donation in Swedish intensive care: A nationwide register study.

BACKGROUND: Life-sustaining treatment limitation (LSTL) on the intensive care unit (ICU) may affect the rate of organ donation after brain death (DBD). The primary aim of this study was to examine whether there is a relationship between LSTL and DBD. Furthermore, we aimed to determine the rate of LSTL involved in ICU deaths and to describe technical and procedural characteristics of LSTL on Swedish ICUs. METHODS: This was an observational cohort study on all ICU deaths (n = 13 156) in Sweden between 2014 and 2017. We analysed differences in DBD rates between deaths in ICU with and those without LSTL, using descriptive statistics and logistic regression. RESULTS: After excluding 1084 deaths on specialised ICUs and units not registering goals of treatment, the study population comprised 12 072 deaths including 615 DBDs, of which 7865 had LSTL, 1706 had no LSTL and 2501 had no stated goals of treatment. The final cohort on which the relationship between DBD and LSTL was analysed comprised 9571 deaths including 419 DBDs. When no LSTL was documented, the rate of organ donation was 9.5% compared to 3.3% when LSTL was documented (P < .001). LSTL was associated with a lower DBD rate after adjusting for patient- and ICU-related factors (OR 0.41, 95% CI 0.31-0.53, P < .001). CONCLUSION: There was an inverse relationship between LSTL and DBD amongst patients who died on the ICU. This relationship remained after adjusting for factors known to influence organ donation. The reason remains to be determined.

Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs.

BACKGROUND: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. OBJECTIVE: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. DESIGN: Prospective cohort study. SETTING: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. SUBJECTS: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. METHODS: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. RESULTS: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001). CONCLUSIONS: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.