Can't intubate, can't oxygenate? What is the preferred surgical strategy? A retrospective analysis.

INTRODUCTION: Cricothyrotomy (CTM) is currently recommended as the preferred method due to its ease, speed, and safety in life-threatening airway emergencies where standard tracheal intubation and mask ventilation fail. MATERIAL AND METHODS: This retrospective study analyzed 33 cases of "can't intubate, can't oxygenate or ventilate" (CICOV): 12 of percutaneous dilatational tracheostomy (PDT) and 21 of CTM. The CTM group was younger (median age 44) and mainly consisted of trauma patients. The PDT group was more diverse and procedures were performed by anesthesia and critical care consultants. RESULTS: Initial success rates were 100% for PDT (12/12) and 86% for CTM (18/21), with one conversion from CTM to PDT. No perioperative complications occurred in the PDT group, while the CTM group experienced two cases of false tracts requiring re-do and three cases of bleeding. Immediate mortality within 24 hours was reported in 5/19 CTM patients and none in the PDT group. Successful liberation from mechanical ventilation at hospital discharge was achieved in 6/12 PDT patients and 11/21 CTM patients. Among the 21 CTM cases, all 16 survivors underwent subsequent tracheostomy. Tracheal decannulation occurred in 4/12 PDT patients and 10/21 CTM patients. Favorable immediate neurological outcomes (GCS ≥ 11T) were observed in 8/12 PDT patients and 8/21 CTM patients, while 3 PDT patients remained anesthetized until death and 7 CTM patients died within the first 72 hours without recovery attempts. CONCLUSIONS: In experienced hands, PDT could be a legitimate clinical option for the surgical airway in cases of CICOV. CTM may be more suitable for practitioners who encounter CICOV infrequently.

Family centeredness of care: a cross-sectional study in intensive care units part of the European society of intensive care medicine.

PURPOSE: To identify key components and variations in family-centered care practices. METHODS: A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated family-centeredness, was assessed using a visual analog scale. Additionally, respondents completed the Maslach Burnout Inventory and the Ethical Decision Making Climate Questionnaire to capture burnout dimensions and assess the ethical decision-making climate. RESULTS: The response rate was 53% (respondents from 359/683 invited ICUs who actually open the email); participating healthcare professionals (HCPs) were from Europe (62%), Asia (9%), South America (6%), North America (5%), Middle East (4%), and Australia/New Zealand (4%). The importance of family-centeredness was ranked high, median 7 (IQR 6-8) of 10 on VAS. Significant differences were observed across quartiles of family centeredness, including in visitation policies availability of a waiting rooms, family rooms, family information leaflet, visiting hours, night visits, sleep in the ICU, and in team-family interactions, including daily information, routine day-3 conference, and willingness to empower nurses and relatives. Higher family centeredness correlated with family involvement in rounds, participation in patient care and end-of-life practices. Burnout symptoms (41% of respondents) were negatively associated with family-centeredness. Ethical climate and willingness to empower nurses were independent predictors of family centeredness. CONCLUSIONS: This study emphasizes the need to prioritize healthcare providers' mental health for enhanced family-centered care. Further research is warranted to assess the impact of improving the ethical climate on family-centeredness.

Limiting life-sustaining treatment for very old ICU patients: cultural challenges and diverse practices.

BACKGROUND: Decisions about life-sustaining therapy (LST) in the intensive care unit (ICU) depend on predictions of survival as well as the expected functional capacity and self-perceived quality of life after discharge, especially in very old patients. However, prognostication for individual patients in this cohort is hampered by substantial uncertainty which can lead to a large variability of opinions and, eventually, decisions about LST. Moreover, decision-making processes are often embedded in a framework of ethical and legal recommendations which may vary between countries resulting in divergent management strategies. METHODS: Based on a vignette scenario of a multi-morbid 87-year-old patient, this article illustrates the spectrum of opinions about LST among intensivsts with a special interest in very old patients, from ten countries/regions, representing diverse cultures and healthcare systems. RESULTS: This survey of expert opinions and national recommendations demonstrates shared principles in the management of very old ICU patients. Some guidelines also acknowledge cultural differences between population groups. Although consensus with families should be sought, shared decision-making is not formally required or practised in all countries. CONCLUSIONS: This article shows similarities and differences in the decision-making for LST in very old ICU patients and recommends strategies to deal with prognostic uncertainty. Conflicts should be anticipated in situations where stakeholders have different cultural beliefs. There is a need for more collaborative research and training in this field.

Apoptotic cells for treatment of acute respiratory distress syndrome associated with COVID-19.

Background: Hyper-inflammatory immune response, a hallmark of severe COVID-19, is associated with increased mortality. Acute respiratory distress syndrome (ARDS) is a common manifestation. We undertook two phase I/II studies in five and then 16 subjects with severe/critical COVID-19 to assess the safety and preliminary efficacy of apoptotic cells (Allocetra™-OTS, Enlivex Therapeutics), a cellular immunomodulatory therapy that reprograms macrophages to reduce hyper-inflammatory response severity. Methods: Eligible patients presenting to the Emergency Room with severe COVID-19 and respiratory dysfunction received one intravenous administration of Allocetra™-OTS and were monitored for adverse events (AEs) for 28 days. The primary aim was to determine the safety profile of treatment; secondary aims were recovery from ARDS, intensive care unit (ICU) and hospital length-of-stay, and mortality. Immune modulator markers were measured to elucidate the mechanism of action of Allocetra™-OTS. Results: 21 patients with severe-critical COVID-19 of Gamma, Alpha and Delta variants, were treated with a single dose of apoptotic cells. 19/21 patients had mild-to-severe ARDS at presentation. Median age was 53 years, 16/21 were males, 16/21 were overweight/obese. No serious related adverse events (SAEs) were reported. All 21 study subjects survived to day 28 (end of study); 19/21 recovered completely. Comparable mortality rates at the hospital were 3.8%-8.9% for age- and gender-matched patients, and 39%-55% for critical patients. Recovering patients exhibited rapid ARDS resolution and parallel resolution of inflammation markers and elevated cytokines/chemokines. Conclusion: In patients with severe/critical COVID-19 associated with ARDS, Allocetra™-OTS was safe, well-tolerated, and showed promising results for resolution of respiratory failure and inflammation. Trial registration: https://clinicaltrials.gov/ct2/show/study/NCT04513470, https://clinicaltrials.gov/ct2/show/study/NCT04590053, Identifiers NCT04513470, NCT04590053.

Prognostication in Very Old Intensive Care Patients with Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is a risk factor for morbidity and mortality during critical illness especially in very old patients admitted to intensive care units. OBJECTIVES: To identify prognostic markers for AKI patients. METHODS: This single-center retrospective study was based on a patient registry of a medical intensive care unit. Hospital records of patients aged 80 years or older admitted between 2005 and 2015 were examined. Patients who developed AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines within 4 days of admission were included in this study. RESULTS: The study comprised 96 patients with AKI and 81 age- and sex-matched controls without AKI. Mean acute physiology and chronic health evaluation (APACHE) II score was 30 with an ICU mortality of 27% in very old patients with AKI. The odds ratio of hospital mortality for these patients was 5.02 compared to controls (49% vs. 16%). APACHE II score and fluid balance in the first 2 days of ICU admission were the strongest predictors of ICU mortality with an area under the receiver operating characteristic of 0.76. Of the 47 patients with AKI who survived hospital admission, 30 were discharged home. CONCLUSIONS: Mortality was increased in very old ICU patients with AKI. Among survivors, two-thirds returned home.

The role of clinical phenotypes in decisions to limit life-sustaining treatment for very old patients in the ICU.

BACKGROUND: Limiting life-sustaining treatment (LST) in the intensive care unit (ICU) by withholding or withdrawing interventional therapies is considered appropriate if there is no expectation of beneficial outcome. Prognostication for very old patients is challenging due to the substantial biological and functional heterogeneity in that group. We have previously identified seven phenotypes in that cohort with distinct patterns of acute and geriatric characteristics. This study investigates the relationship between these phenotypes and decisions to limit LST in the ICU. METHODS: This study is a post hoc analysis of the prospective observational VIP2 study in patients aged 80 years or older admitted to ICUs in 22 countries. The VIP2 study documented demographic, acute and geriatric characteristics as well as organ support and decisions to limit LST in the ICU. Phenotypes were identified by clustering analysis of admission characteristics. Patients who were assigned to one of seven phenotypes (n = 1268) were analysed with regard to limitations of LST. RESULTS: The incidence of decisions to withhold or withdraw LST was 26.5% and 8.1%, respectively. The two phenotypes describing patients with prominent geriatric features and a phenotype representing the oldest old patients with low severity of the critical condition had the largest odds for withholding decisions. The discriminatory performance of logistic regression models in predicting limitations of LST after admission to the ICU was the best after combining phenotype, ventilatory support and country as independent variables. CONCLUSIONS: Clinical phenotypes on ICU admission predict limitations of LST in the context of cultural norms (country). These findings can guide further research into biases and preferences involved in the decision-making about LST. Trial registration Clinical Trials NCT03370692 registered on 12 December 2017.

Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study.

BACKGROUND: Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. METHODS: This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan-Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. RESULTS: This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06-1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. CONCLUSION: Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. STUDY REGISTRATION: NCT04321265, registered March 19th, 2020.

Improving awareness of kidney function through electronic urine output monitoring: a comparative study.

BACKGROUND: The current classification for acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria integrates both serum creatinine (SCr) and urine output (UO). Most reports on AKI claim to use KDIGO guidelines but fail to include the UO criterion. It has been shown that patients who had intensive UO monitoring, with or without AKI, had significantly less cumulative fluid volume and fluid overload, reduced vasopressor use, and improved 30-day mortality. We examined whether real-time monitoring of this simple, sensitive, and easy-to-use biomarker in the ICU led to more appropriate intervention by healthcare providers and better outcomes.  METHODS: RenalSense Clarity RMS Consoles were installed in the General ICU at the Hadassah Medical Center, Israel, from December 2019 to November 2020. The Clarity RMS system continuously and electronically monitors UO in real-time. 100 patients were randomly selected from this period as the study group (UOelec) and compared to a matched control group (UOmanual) from the same period two years earlier. To test whether there was an association between oliguric hours and fluid treatment in each group, the correlation was calculated and analyzed for each of the different UO monitoring methods. RESULTS: Therapeutic intervention: The correlation of the sum of all oliguric hours on Day 1 and 2 with the sum of any therapeutic intervention (fluid bolus or furosemide) showed a significant correlation for the study group UOelec (P = 0.017). The matched control group UOmanual showed no such correlation (P = 0.932). Length of Stay (LOS): Median LOS [IQR] in the ICU of UOelec versus UOmanual was 69.46 [44.7, 125.9] hours and 116.5 [62.46, 281.3] hours, respectively (P = 0.0002). CONCLUSIONS: The results of our study strongly suggest that ICU patients had more meaningful and better medical intervention, and improved outcomes, with electronic UO monitoring than with manual monitoring.

The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial.

BACKGROUND: In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients. METHODS: This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression. RESULTS: 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2-5 versus IQR 2-4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted analysis. CONCLUSION: Paracetamol intake prior to ICU admission was not associated with short-term and 3-month mortality in old, critically ill intensive care patients suffering from COVID-19. TRIAL REGISTRATION: This prospective international multicentre study was registered on ClinicalTrials.gov with the identifier "NCT04321265" on March 25, 2020.

A retrospective cohort study comparing differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in European tax-based healthcare systems (THS) versus social health insurance systems.

In Europe, tax-based healthcare systems (THS) and social health insurance systems (SHI) coexist. We examined differences in 30-day mortality among critically ill patients aged ≥ 70 years treated in intensive care units in a THS or SHI. Retrospective cohort study. 2406 (THS n = 886; SHI n = 1520) critically ill ≥ 70 years patients in 129 ICUs. Generalized estimation equations with robust standard errors were chosen to create population average adjusted odds ratios (aOR). Data were adjusted for patient-specific variables, organ support and health economic data. The primary outcome was 30-day-mortality. Numerical differences between SHI and THS in SOFA scores (6 ± 3 vs. 5 ± 3; p = 0.002) were observed, but clinical frailty scores were similar (> 4; 17% vs. 14%; p = 0.09). Higher rates of renal replacement therapy (18% vs. 11%; p < 0.001) were found in SHI (aOR 0.61 95%CI 0.40-0.92; p = 0.02). No differences regarding intubation rates (68% vs. 70%; p = 0.33), vasopressor use (67% vs. 67%; p = 0.90) and 30-day-mortality rates (47% vs. 50%; p = 0.16) were found. Mortality remained similar between both systems after multivariable adjustment and sensitivity analyses. The retrospective character of this study. Baseline risk and mortality rates were similar between SHI and THS. The type of health care system does not appear to have played a role in the intensive care treatment of critically ill patients ≥ 70 years with COVID-19 in Europe.

Clustering analysis of geriatric and acute characteristics in a cohort of very old patients on admission to ICU.

PURPOSE: The biological and functional heterogeneity in very old patients constitutes a major challenge to prognostication and patient management in intensive care units (ICUs). In addition to the characteristics of acute diseases, geriatric conditions such as frailty, multimorbidity, cognitive impairment and functional disabilities were shown to influence outcome in that population. The goal of this study was to identify new and robust phenotypes based on the combination of these features to facilitate early outcome prediction. METHODS: Patients aged 80 years old or older with and without limitations of life-sustaining treatment and with complete data were recruited from the VIP2 study for phenotyping and from the COVIP study for external validation. The sequential organ failure assessment (SOFA) score and its sub-scores taken on admission to ICU as well as demographic and geriatric patient characteristics were subjected to clustering analysis. Phenotypes were identified after repeated bootstrapping and clustering runs. RESULTS: In patients from the VIP2 study without limitations of life-sustaining treatment (n = 1977), ICU mortality was 12% and 30-day mortality 19%. Seven phenotypes with distinct profiles of acute and geriatric characteristics were identified in that cohort. Phenotype-specific mortality within 30 days ranged from 3 to 57%. Among the patients assigned to a phenotype with pronounced geriatric features and high SOFA scores, 50% died in ICU and 57% within 30 days. Mortality differences between phenotypes were confirmed in the COVIP study cohort (n = 280). CONCLUSIONS: Phenotyping of very old patients on admission to ICU revealed new phenotypes with different mortality and potential need for anticipatory intervention.

Sex-specific treatment characteristics and 30-day mortality outcomes of critically ill COVID-19 patients over 70 years of age-results from the prospective COVIP study.

PURPOSE: Older critically ill patients with COVID-19 have been the most vulnerable during the ongoing pandemic, with men being more prone to hospitalization and severe disease than women. We aimed to explore sex-specific differences in treatment and outcome after intensive care unit (ICU) admission in this cohort. METHODS: We performed a sex-specific analysis in critically ill patients ≥ 70 yr of age with COVID-19 who were included in the international prospective multicenter COVIP study. All patients were analyzed for ICU admission and treatment characteristics. We performed a multilevel adjusted regression analysis to elucidate associations of sex with 30-day mortality. RESULTS: A total of 3,159 patients (69.8% male, 30.2% female; median age, 75 yr) were included. Male patients were significantly fitter than female patients as determined by the Clinical Frailty Scale (fit, 67% vs 54%; vulnerable, 14% vs 19%; frail, 19% vs 27%; P < 0.001). Male patients more often underwent tracheostomy (20% vs 14%; odds ratio [OR], 1.57; P < 0.001), vasopressor therapy (69% vs 62%; OR, 1.25; P = 0.02), and renal replacement therapy (17% vs 11%; OR, 1.96; P < 0.001). There was no difference in mechanical ventilation, life-sustaining treatment limitations, and crude 30-day mortality (50% male vs 49% female; OR, 1.11; P = 0.19), which remained true after adjustment for disease severity, frailty, age and treatment limitations (OR, 1.17; 95% confidence interval, 0.94 to 1.45; P = 0.16). CONCLUSION: In this analysis of sex-specific treatment characteristics and 30-day mortality outcomes of critically ill patients with COVID-19 ≥ 70 yr of age, we found more tracheostomy and renal replacement therapy in male vs female patients, but no significant association of patient sex with 30-day mortality. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04321265); registered 25 March 2020).

RéSUMé: OBJECTIF: Les patients âgés gravement malades atteints de la COVID-19 ont été les plus vulnérables pendant la pandémie actuelle, les hommes étant plus sujets à l'hospitalisation et aux maladies graves que les femmes. Nous avons cherché à explorer les différences spécifiques au sexe dans le traitement et les devenirs après l'admission à l'unité de soins intensifs (USI) dans cette cohorte. MéTHODE: Nous avons effectué une analyse spécifique au sexe chez des patients gravement malades âgés de ≥ 70 ans atteints de COVID-19 qui ont été inclus dans l'étude prospective multicentrique internationale COVIP. Tous les patients ont été analysés pour connaître les détails de leur admission à l'USI et les caractéristiques de leur traitement. Nous avons réalisé une analyse de régression ajustée à plusieurs niveaux pour élucider les associations entre le sexe et la mortalité à 30 jours. RéSULTATS: Au total, 3159 patients (69,8 % d'hommes, 30,2 % de femmes; âge médian, 75 ans) ont été inclus. Les patients de sexe masculin étaient significativement plus en forme que les patientes, tel que déterminé par l'échelle de fragilité clinique (bonne santé, 67 % vs 54 %; vulnérables, 14 % vs 19 %; fragiles, 19 % vs 27 %; P < 0,001). Les patients de sexe masculin ont plus souvent bénéficié d'une trachéostomie (20 % vs 14 %; rapport de cotes [RC], 1,57; P < 0,001), d'un traitement vasopresseur (69 % vs 62 %; RC, 1,25; P = 0,02) et d'un traitement substitutif de l'insuffisance rénale (17 % vs 11 %; RC, 1,96; P < 0,001). Il n'y avait aucune différence en matière de ventilation mécanique, de limites des traitements de maintien en vie et de mortalité brute à 30 jours (50 % d'hommes vs 49 % de femmes; RC, 1,11; P = 0,19), ce qui est demeuré le cas après ajustement pour tenir compte de la gravité de la maladie, de la fragilité, de l'âge et des limites du traitement (RC, 1,17 ; intervalle de confiance à 95 %, 0,94 à 1,45; P = 0,16). CONCLUSION: Dans cette analyse des caractéristiques de traitement spécifiques au sexe et des résultats de mortalité à 30 jours des patients gravement malades atteints de COVID-19 de ≥ 70 ans, nous avons noté un nombre plus élevé de trachéotomies et de traitements substitutifs de l'insuffisance rénale chez les hommes vs les femmes, mais aucune association significative entre le sexe des patients et la mortalité à 30 jours. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04321265); enregistré le 25 mars 2020.

Who gets the ventilator? A multicentre survey of intensivists' opinions of triage during the first wave of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has caused a shortage of intensive care resources. Intensivists' opinion of triage and ventilator allocation during the COVID-19 pandemic is not well described. METHODS: This was a survey concerning patient numbers, bed capacity, triage guidelines, and three virtual cases involving ventilator allocations. Physicians from 400 ICUs in a research network were invited to participate. Preferences were assessed with a five-point Likert scale. Additionally, age, gender, work experience, geography, and religion were recorded. RESULTS: Of 437 responders 31% were female. The mean age was 44.4 (SD 11.1) with a mean ICU experience of 13.7 (SD 10.5) years. Respondents were mostly European (88%). Sixty-six percent had triage guidelines available. Younger patients and caretakers of children were favoured for ventilator allocation although this was less clear if this involved withdrawal of the ventilator from another patient. Decisions did not differ with ICU experience, gender, religion, or guideline availability. Consultation of colleagues or an ethical committee decreased with age and male gender. CONCLUSION: Intensivists appeared to prioritise younger patients for ventilator allocation. The tendency to consult colleagues about triage decreased with age and male gender. Many found such tasks to be not purely medical and that authorities should assume responsibility for triage during resource scarcity.

Time-dependent uncertainty of critical care transitions in very old patients - lessons for time-limited trials.

PURPOSE: Prognostication for patients with critical conditions remains challenging, especially for very old individuals. Time-limited trials (TLT) are used to decrease prognostic uncertainty in the individual patient by monitoring the response to treatment over a pre-determined period of time. However, there are substantial difficulties with determining the length of that period. This study presents a probabilistic method to estimate a suitable duration of a TLT based on temporal profiles of uncertainty about critical care and outcome. MATERIALS AND METHODS: The study included very old patients (age ≥ 80 years, n = 1209) from the VIP2 study cohort who were admitted to the ICU for between 2 and 14 days, with respiratory or circulatory support from day 1 and with either no limitations of life-sustaining treatment or a decision to withdraw that treatment, as well as with complete data. Multi-state modelling of critical care trajectories to obtain time-dependent probabilities for transitions between distinct levels of organ support and to outcome states. The extent of uncertainty is quantified by Shannon's entropy of probability distributions at discrete points in time. RESULTS: We detected periods of enhanced prognostic uncertainty of up to 7 days after admission. The duration of these periods depends on patient characteristics at baseline (frailty, severity of critical illness) and the extent of organ support. CONCLUSION: Time-dependent patterns of uncertainty concerning the response to critical care can inform decisions about the duration of TLTs which may last up to a week in very old patients.

Association of chronic heart failure with mortality in old intensive care patients suffering from Covid-19.

AIMS: Chronic heart failure (CHF) is a major risk factor for mortality in coronavirus disease 2019 (COVID-19). This prospective international multicentre study investigates the role of pre-existing CHF on clinical outcomes of critically ill old (≥70 years) intensive care patients with COVID-19. METHODS AND RESULTS: Patients with pre-existing CHF were subclassified as having ischaemic or non-ischaemic cardiac disease; patients with a documented ejection fraction (EF) were subclassified according to heart failure EF: reduced (HFrEF, n = 132), mild (HFmrEF, n = 91), or preserved (HFpEF, n = 103). Associations of heart failure characteristics with the 30 day mortality were analysed in univariate and multivariate logistic regression analyses. Pre-existing CHF was reported in 566 of 3917 patients (14%). Patients with CHF were older, frailer, and had significantly higher SOFA scores on admission. CHF patients showed significantly higher crude 30 day mortality [60% vs. 48%, P < 0.001; odds ratio 1.87, 95% confidence interval (CI) 1.5-2.3] and 3 month mortality (69% vs. 56%, P < 0.001). After multivariate adjustment for confounders (SOFA, age, sex, and frailty), no independent association of CHF with mortality remained [adjusted odds ratio (aOR) 1.2, 95% CI 0.5-1.5; P = 0.137]. More patients suffered from pre-existing ischaemic than from non-ischaemic disease [233 vs. 328 patients (n = 5 unknown aetiology)]. There were no differences in baseline characteristics between ischaemic and non-ischaemic disease or between HFrEF, HFmrEF, and HFpEF. Crude 30 day mortality was significantly higher in HFrEF compared with HFpEF (64% vs. 48%, P = 0.042). EF as a continuous variable was not independently associated with 30 day mortality (aOR 0.98, 95% CI 0.9-1.0; P = 0.128). CONCLUSIONS: In critically ill older COVID-19 patients, pre-existing CHF was not independently associated with 30 day mortality. TRIAL REGISTRATION NUMBER: NCT04321265.

The association of the Activities of Daily Living and the outcome of old intensive care patients suffering from COVID-19.

PURPOSE: Critically ill old intensive care unit (ICU) patients suffering from Sars-CoV-2 disease (COVID-19) are at increased risk for adverse outcomes. This post hoc analysis investigates the association of the Activities of Daily Living (ADL) with the outcome in this vulnerable patient group. METHODS: The COVIP study is a prospective international observational study that recruited ICU patients ≥ 70 years admitted with COVID-19 (NCT04321265). Several parameters including ADL (ADL; 0 = disability, 6 = no disability), Clinical Frailty Scale (CFS), SOFA score, intensive care treatment, ICU- and 3-month survival were recorded. A mixed-effects Weibull proportional hazard regression analyses for 3-month mortality adjusted for multiple confounders. RESULTS: This pre-specified analysis included 2359 patients with a documented ADL and CFS. Most patients evidenced independence in their daily living before hospital admission (80% with ADL = 6). Patients with no frailty and no disability showed the lowest, patients with frailty (CFS ≥ 5) and disability (ADL < 6) the highest 3-month mortality (52 vs. 78%, p < 0.001). ADL was independently associated with 3-month mortality (ADL as a continuous variable: aHR 0.88 (95% CI 0.82-0.94, p < 0.001). Being "disable" resulted in a significant increased risk for 3-month mortality (aHR 1.53 (95% CI 1.19-1.97, p 0.001) even after adjustment for multiple confounders. CONCLUSION: Baseline Activities of Daily Living (ADL) on admission provides additional information for outcome prediction, although most critically ill old intensive care patients suffering from COVID-19 had no restriction in their ADL prior to ICU admission. Combining frailty and disability identifies a subgroup with particularly high mortality. TRIAL REGISTRATION NUMBER: NCT04321265.