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.

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.

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.

Early evaluation of organ failure using MELD-XI in critically ill elderly COVID-19 patients.

PURPOSECritically ill elderly patients who suffer from Sars-CoV-2 disease are at high risk for organ failure. The modified MELD-XI score has not been evaluated for outcome prediction in these most vulnerable patients.METHODSThe Corona Virus disease (COVID19) in Very Elderly Intensive Care Patients study (COVIP, NCT04321265) prospectively recruited patients on intensive care units (ICU), who were = 70 years. Data were collected from March 2020 to February 2021. The MELD-XI score was calculated using the highest serum bilirubin and creatinine on ICU admission. Univariate and multivariable logistic regression analyses were performed to assess associations between the MELD-XI score and mortality. The primary outcome was 30-day-mortality, the secondary outcomes were ICU- and 3-month-mortality.RESULTSIn total, data from 2,993 patients were analyzed. Most patients had a MELD-XI <12 on admission (76%). The patients with MELD-XI = 12 had a significantly higher 30-day-, ICU- and 3-month-mortality (44%vs 64%, and 42%vs. 59%, and 57%vs. 76%, p < 0.001). After adjustment for multiple confounders, MELD-XI = 12 remained significantly associated with 30-day- (aOR 1.572, CI 1.268-1.949, p < 0.001), ICU-, and 3-month-mortality.CONCLUSIONIn critically ill elderly intensive care patients with COVID-19, the MELD-XI score constitutes a valuable tool for an early outcome prediction.

Lactate is associated with mortality in very old intensive care patients suffering from COVID-19: results from an international observational study of 2860 patients.

PURPOSE: Lactate is an established prognosticator in critical care. However, there still is insufficient evidence about its role in predicting outcome in COVID-19. This is of particular concern in older patients who have been mostly affected during the initial surge in 2020. METHODS: This prospective international observation study (The COVIP study) recruited patients aged 70 years or older (ClinicalTrials.gov ID: NCT04321265) admitted to an intensive care unit (ICU) with COVID-19 disease from March 2020 to February 2021. In addition to serial lactate values (arterial blood gas analysis), we recorded several parameters, including SOFA score, ICU procedures, limitation of care, ICU- and 3-month mortality. A lactate concentration ≥ 2.0 mmol/L on the day of ICU admission (baseline) was defined as abnormal. The primary outcome was ICU-mortality. The secondary outcomes 30-day and 3-month mortality. RESULTS: In total, data from 2860 patients were analyzed. In most patients (68%), serum lactate was lower than 2 mmol/L. Elevated baseline serum lactate was associated with significantly higher ICU- and 3-month mortality (53% vs. 43%, and 71% vs. 57%, respectively, p < 0.001). In the multivariable analysis, the maximum lactate concentration on day 1 was independently associated with ICU mortality (aOR 1.06 95% CI 1.02-1.11; p = 0.007), 30-day mortality (aOR 1.07 95% CI 1.02-1.13; p = 0.005) and 3-month mortality (aOR 1.15 95% CI 1.08-1.24; p < 0.001) after adjustment for age, gender, SOFA score, and frailty. In 826 patients with baseline lactate ≥ 2 mmol/L sufficient data to calculate the difference between maximal levels on days 1 and 2 (∆ serum lactate) were available. A decreasing lactate concentration over time was inversely associated with ICU mortality after multivariate adjustment for SOFA score, age, Clinical Frailty Scale, and gender (aOR 0.60 95% CI 0.42-0.85; p = 0.004). CONCLUSION: In critically ill old intensive care patients suffering from COVID-19, lactate and its kinetics are valuable tools for outcome prediction. TRIAL REGISTRATION NUMBER: NCT04321265.