Prognosticating the outcome of intensive care in older patients-a narrative review.

Prognosis determines major decisions regarding treatment for critically ill patients. Statistical models have been developed to predict the probability of survival and other outcomes of intensive care. Although they were trained on the characteristics of large patient cohorts, they often do not represent very old patients (age ≥ 80 years) appropriately. Moreover, the heterogeneity within this particular group impairs the utility of statistical predictions for informing decision-making in very old individuals. In addition to these methodological problems, the diversity of cultural attitudes, available resources as well as variations of legal and professional norms limit the generalisability of prediction models, especially in patients with complex multi-morbidity and pre-existing functional impairments. Thus, current approaches to prognosticating outcomes in very old patients are imperfect and can generate substantial uncertainty about optimal trajectories of critical care in the individual. This article presents the state of the art and new approaches to predicting outcomes of intensive care for these patients. Special emphasis has been given to the integration of predictions into the decision-making for individual patients. This requires quantification of prognostic uncertainty and a careful alignment of decisions with the preferences of patients, who might prioritise functional outcomes over survival. Since the performance of outcome predictions for the individual patient may improve over time, time-limited trials in intensive care may be an appropriate way to increase the confidence in decisions about life-sustaining treatment.

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.

30-Day Mortality among Very Old Patients Admitted to European Intensive Care Units for Major Trauma.

INTRODUCTION: Cases of major trauma in the very old (over 80 years) are increasingly common in the intensive care unit (ICU). Predicting outcome is challenging in this group of patients as chronological age is a poor marker of health and poor predictor of outcome. Increasingly, decisions are guided by the use of organ dysfunction scores of both acute conditions (e.g., sequential organ failure assessment [SOFA] score) and chronic health issues (e.g., clinical frailty scale [CFS]). Recent work suggests that increased CFS is associated with a worse outcome in elderly major trauma patients. We aimed to test whether this association held true in the very old (over 80) or whether SOFA had a stronger association with 30-day outcome. METHODS: Data from the very elderly intensive care patient (VIP)-1 and VIP-2 studies for patients over 80 years old with major trauma admissions were merged. These participants were recruited from 20 countries across Europe. Baseline characteristics, level of care provided, and outcome (ICU and 30-day mortality) were summarised. Uni- and multivariable regression analyses were undertaken to determine associations between CFS and SOFA score in the first 24 h, type of major trauma, and outcomes. RESULTS: Of the 8,062 acute patients recruited to the two VIP studies, 498 patients were admitted to intensive care because of major trauma. Median age was 84 years, median SOFA score was 6 (IQR 3, 9), and median CFS was 3 (IQR 2, 5). Survival for 30 days was 54%. Median and interquartile range of CFS were the same for survivors and non-survivors. In the logistic regression analysis, CFS was not associated with increased mortality. SOFA score (p < 0.001) and trauma with head injury (p < 0.01) were associated with increased mortality. CONCLUSIONS: Major trauma admissions in the very old are not uncommon, and 30-day mortality is high. We found that CFS was not a helpful predictor of mortality. SOFA and trauma with head injury were associated with worse outcomes in this patient group.

Frailty's influence on 30-day mortality in old critically ill ICU patients: a bayesian analysis evaluating the clinical frailty scale.

INTRODUCTION: Frailty is widely acknowledged as influencing health outcomes among critically ill old patients. Yet, the traditional understanding of its impact has predominantly been through frequentist statistics. We endeavored to explore this association using Bayesian statistics aiming to provide a more nuanced understanding of this multifaceted relationship. METHODS: Our analysis incorporated a cohort of 10,363 older (median age 82 years) patients from three international prospective studies, with 30-day all-cause mortality as the primary outcome. We defined frailty as Clinical Frailty Scale ≥ 5. A hierarchical Bayesian logistic regression model was employed, adjusting for covariables, using a range of priors. An international steering committee of registry members reached a consensus on a minimal clinically important difference (MCID). RESULTS: In our study, the 30-day mortality was 43%, with rates of 38% in non-frail and 51% in frail groups. Post-adjustment, the median odds ratio (OR) for frailty was 1.60 (95% CI 1.45-1.76). Frailty was invariably linked to adverse outcomes (OR > 1) with 100% probability and had a 90% chance of exceeding the minimal clinically important difference (MCID) (OR > 1.5). For the Clinical Frailty Scale (CFS) as a continuous variable, the median OR was 1.19 (1.16-1.22), with over 99% probability of the effect being more significant than 1.5 times the MCID. Frailty remained outside the region of practical equivalence (ROPE) in all analyses, underscoring its clinical importance regardless of how it is measured. CONCLUSIONS: This research demonstrates the significant impact of frailty on short-term mortality in critically ill elderly patients, particularly when the Clinical Frailty Scale (CFS) is used as a continuous measure. This approach, which views frailty as a spectrum, enables more effective, personalized care for this vulnerable group. Significantly, frailty was consistently outside the region of practical equivalence (ROPE) in our analysis, highlighting its clinical importance.

Validity of the total SOFA score in patients ≥ 80 years old acutely admitted to intensive care units: a post-hoc analysis of the VIP2 prospective, international cohort study.

BACKGROUND: Little is known about the performance of the Sequential Organ Failure Assessment (SOFA) score in older critically ill adults. We aimed to evaluate the prognostic impact of physiological disturbances in the six organ systems included in the SOFA score. METHODS: We analysed previously collected data from a prospective cohort study conducted between 2018 and 2019 in 22 countries. Consecutive patients ≥ 80 years old acutely admitted to intensive care units (ICUs) were eligible for inclusion. Patients were followed up for 30 days after admission to the ICU. We used logistic regression to study the association between increasing severity of organ dysfunction and mortality. RESULTS: The median SOFA score among 3882 analysed patients was equal to 6 (IQR: 4-9). Mortality was equal to 26.1% (95% CI 24.7-27.5%) in the ICU and 38.7% (95% CI 37.1-40.2%) at day 30. Organ failure defined as a SOFA score ≥ 3 was associated with variable adjusted odds ratios (aORs) for ICU mortality dependant on the organ system affected: respiratory, 1.53 (95% CI 1.29-1.81); cardiovascular 1.69 (95% CI 1.43-2.01); hepatic, 1.74 (95% CI 0.97-3.15); renal, 1.87 (95% CI 1.48-2.35); central nervous system, 2.79 (95% CI 2.34-3.33); coagulation, 2.72 (95% CI 1.66-4.48). Modelling consecutive levels of organ dysfunction resulted in aORs equal to 0.57 (95% CI 0.33-1.00) when patients scored 2 points in the cardiovascular system and 1.01 (0.79-1.30) when the cardiovascular SOFA equalled 3. CONCLUSIONS: Different components of the SOFA score have different prognostic implications for older critically ill adults. The cardiovascular component of the SOFA score requires revision.

Outcomes of patients aged ≥80 years with respiratory failure initially treated with non-invasive ventilation in European intensive care units before and during COVID-19 pandemic.

BACKGROUND: Non-invasive ventilation (NIV) has been commonly used to treat acute respiratory failure due to COVID-19. In this study we aimed to compare outcomes of older critically ill patients treated with NIV before and during the COVID-19 pandemic. METHODS: We analysed a merged cohort of older adults admitted to intensive care units (ICUs) due to respiratory failure. Patients were enrolled into one of two prospective observational studies: before COVID-19 (VIP2-2018 to 2019) and admitted due to COVID-19 (COVIP-March 2020 to January 2023). The outcomes included: 30-day mortality, intubation rate and NIV failure (death or intubation within 30 days). RESULTS: The final cohort included 1986 patients (1292 from VIP2, 694 from COVIP) with a median age of 83 years. NIV was used as a primary mode of respiratory support in 697 participants (35.1%). ICU admission due to COVID-19 was associated with an increased 30-day mortality (65.5% vs. 36.5%, HR 2.18, 95% CI 1.71 to 2.77), more frequent intubation (36.9% vs. 17.5%, OR 2.63, 95% CI 1.74 to 3.99) and NIV failure (76.2% vs. 45.3%, OR 4.21, 95% CI 2.84 to 6.34) compared to non-COVID causes of respiratory failure. Sensitivity analysis after exclusion of patients in whom life supporting treatment limitation was introduced during primary NIV confirmed higher 30-day mortality in patients with COVID-19 (52.5% vs. 23.4%, HR 2.64, 95% CI 1.83 to 3.80). CONCLUSION: The outcomes of patients aged ≥80 years treated with NIV during COVID-19 pandemic were worse compared then those treated with NIV in the pre-pandemic era.

Associations of anemia and blood transfusions with mortality in old, critically ill COVID-19 patients - Results from the prospective COVIP Study.

AIMS: Anemia is common in the old and often observed in critically ill patients. Increased age is associated with higher mortality following a COVID-19 infection, making old patients prone to poor outcomes. We investigated whether anemia at admission to the ICU or the need for blood transfusion was associated with 90-day mortality in older, critically ill COVID-19 patients. METHODS: In this prospective multicenter study, the 90-day mortality of COVID-19 patients≥70 years treated in 138 intensive care units (ICU) was analyzed. Associations between anemia (WHO definition) at admission and discharge from ICU and the use of red blood cell (RBC) transfusions with mortality were assessed. Hemoglobin thresholds of RBC transfusions in old, critically ill COVID-19 patients were recorded. RESULTS: In 493 patients (350 anemic, 143 non-anemic), anemia (WHO definition) at the time of ICU admission was not associated with impaired overall survival. Transfusion and severe anemia (hemoglobin≤10 g/dL) at ICU discharge were independently associated with a higher risk of 90-day mortality. CONCLUSION: The need for red blood cell transfusions and severe anemia at ICU discharge, but not at the timepoint of admission, were independently associated with 90-day mortality in critically-ill old COVID-19 patients.

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.

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Reporting SOFA in research: we should always present each of the SOFA subscores.

INTRODUCTION: The Sequential Organ Failure Assessment (SOFA) score is the sum of 6 components, each representing one organ system with dysfunction classified on a 4-point scale. In research, usually by default, the total SOFA score is taken into account, but it may not reflect the severity of the condition of the individual organs. Often, these values are expected to predict mortality. MATERIAL AND METHODS: In this study, we reanalysed 2 cohorts of critically ill elderly patients to explore the distribution of SOFA subscores and to assess the between-group differences. Both cohorts were adjusted to maintain similarity in terms of age and the primary cause of admission (respiratory cause). RESULTS: In total, 910 (non-COVID-19 cohort) and 551 patients (COVID-19 cohort) were included in the analysis. Both cohorts were similar in terms of the total SOFA score (median 5 vs. 5 points); however, the groups differed significantly in 4/6 SOFA subscores (respiratory, neurological, cardiovascular, and coagulation subscores). Moreover, the cohorts had different fractions of organ failures (defined as a SOFA subscore ≥ 3). CONCLUSIONS: This analysis revealed significant differences in SOFA subscores between the COVID-19 and non-COVID-19 respiratory cohorts, highlighting the importance of considering individual organ dysfunction rather than relying solely on the total SOFA score when reporting organ dysfunction in clinical research.

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.

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.