Complete blood count, coagulation biomarkers, and lung function 6 months after critical COVID-19.

BACKGROUND: Understanding the recovery of post-COVID-19 organ dysfunction is essential. We evaluated coagulation 6 months post-COVID-19, examining its recovery and association with lung function. METHODS: Patients treated for COVID-19 at intensive care units between 3/2020 and 1/2021 were analyzed for complete blood count (CBC) and coagulation biomarkers (prothrombin time activity (%) (PT%), activated partial thromboplastin time (APTT), fibrinogen, coagulation factor VIII (FVIII), antithrombin (AT), and D-dimer) during the 6 months post-hospitalization. Results were compared with acute phase values and correlated with pulmonary function tests (PFT), including forced vital capacity (FVC) and hemoglobin-corrected diffusing capacity percentage of predicted (DLCOc%), recorded 6 months post-hospitalization. We examined the association between coagulation biomarkers and DLCOc% using linear regression with age, sex, and invasive mechanical ventilation (IMV) duration, and FVIII (correlated with DLCOc%) as covariates. RESULTS: Most CBCs and coagulation biomarkers had median values within the normal range. However, only 21% (15/70) of patients achieved full normalization of all biomarkers. Compared to acute COVID-19, hemoglobin, PT%, and AT increased, while leukocytes, fibrinogen, FVIII, and D-dimer decreased. Despite decreased levels, FVIII remained elevated in 46% (31/68), leukocytes in 26% (18/70), and D-dimer in 27% (18/67) at 6 months. A weak negative correlation (r = -0.37, p = .036) was found between DLCOc% and FVIII. Multivariable analysis revealed a weak, independent association between DLCOc% and FVIII. Excluding patients with anticoagulation therapy, FVIII no longer correlated with DLCOc%, while AT showed a moderate correlation with DLCOc%. CONCLUSION: Only a few patients had normal CBC and coagulation biomarker values 6 months after critical COVID-19. A weak negative correlation between DLCOc% and FVIII suggests that deranged coagulation activity may be associated with reduced diffusing capacity.

Syndecan-1 Levels and Early Positive Fluid Balance Are Associated with Disease Severity in Acute Pancreatitis.

OBJECTIVES: To study fluid balance and endothelial glycocalyx degradation, reflected by syndedan-1 and heparan sulfate (HS) levels, in early stages of acute pancreatitis (AP). METHODS: This study comprised of 210 AP patients (104 mild, 53 moderately severe, 17 severe). Blood was sampled within 72 h from the onset of symptoms, and plasma syndecan-1 and HS levels were determined using ELISA. Fluid balance up to sampling and up to 4 days was determined retrospectively from medical records. RESULTS: Syndecan-1 levels predicted severe AP (SAP) in receiver operating characteristic analysis [area under curve 0.699, 95% confidence interval (CI) 0.546 to 0.851, p = 0.021]. Increasing AP severity was associated with higher intravenous fluid intake and lower urine output. In multivariate binary logistic regression analysis, positive fluid balance up to sampling [odds ratio (OR) 1.05 per 100 ml, 95% CI 1.02 to 1.11, p = 0.010] and higher APACHE-II score at sampling (OR 1.48, 95% CI 1.20 to 1.83, p < 0.001) were independently associated with severe AP, while syndecan-1 level was not. CONCLUSIONS: SAP is associated with high positive fluid balance in the early stages of treatment. Although increased in SAP, syndecan-1 was not independently associated with SAP when controlling for fluid balance and APACHE-II score.

Effect of level of sedation on outcomes in critically ill adult patients: a systematic review of clinical trials with meta-analysis and trial sequential analysis.

Background: Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults. Methods: Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960. Findings: Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected. Interpretation: The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor. Funding: None.

The effectiveness of a brief intervention for intensive care unit patients with hazardous alcohol use: a randomized controlled trial.

BACKGROUND: Screening for hazardous alcohol use and performing brief interventions (BIs) are recommended to reduce alcohol-related negative health consequences. We aimed to compare the effectiveness (defined as an at least 10% absolute difference) of BI with usual care in reducing alcohol intake in intensive care unit survivors with history of hazardous alcohol use. METHODS: We used Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score to assess history of alcohol use. PATIENTS: Emergency admitted adult ICU patients in three Finnish university hospitals, with an AUDIT-C score > 5 (women), or > 6 (men). We randomized consenting eligible patients to receive a BI or treatment as usual (TAU). INTERVENTION: BI was delivered by the time of ICU discharge or shortly thereafter in the hospital ward. CONTROLS: Control patients received TAU. OUTCOME: The primary outcome was self-reported alcohol consumption during the preceding week 6 and 12 months after randomization. Secondary outcomes were the change in AUDIT-C scores from baseline to 6 and 12 months, health-related quality of life, and mortality. The trial was terminated early due to slow recruitment during the pandemic. RESULTS: We randomized 234 patients to receive BI (N = 117) or TAU (N = 117). At 6 months, the median alcohol intake in the BI and TAU groups were 6.5 g (interquartile range [IQR] 0-141) and 0 g (0-72), respectively (p = 0.544). At 12 months, it was 24 g (0-146) and 0 g (0-96) in the BI and TAU groups, respectively (p = 0.157). Median change in AUDIT-C from baseline to 6 months was - 1 (- 4 to 0) and 2 (- 6 to 0), (p = 0.144) in the BI and TAU groups, and to 12 months - 3 (- 5 to - 1) and - 4 (- 7 to - 1), respectively (p = 0.187). In total, 4% (n = 5) of patients in the BI group and 11% (n = 13) of patients in the TAU group were abstinent at 6 months, and 10% (n = 12) and 15% (n = 17), respectively, at 12 months. No between-groups difference in mortality emerged. CONCLUSION: As underpowered, our study cannot reject or confirm the hypothesis that a single BI early after critical illness is effective in reducing the amount of alcohol consumed compared to TAU. However, a considerable number in both groups reduced their alcohol consumption. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03047577).

Physicians' perceptions of intensive care patients' 1-year prognoses compared to realistic prognoses.

BACKGROUND: It is unknown whether physicians treating critically ill patients have realistic perceptions of their patients' prognoses. METHODS: We sent a survey by email to Finnish anesthesiologists to investigate their ability to estimate the probability of 1-year survival of intensive care unit (ICU) patients based on data available at the beginning of intensive care. We presented 12 fictional but real-life-based patient cases and asked the respondent to estimate the probability of 1-year survival in each case by choosing one of the alternatives 5%, 10%-90% in 10% intervals and 95%. We compared the physicians' estimates to registry data-based realistic prognoses of comparable patients treated in the ICU. Based on the difference between the estimate and the realistic prognosis, we categorized the estimates into three groups: (1) difference less than 10 percentage points, (2) difference between 10 and 20 percentage points, and (3) difference over 20 percentage points. RESULTS: We received 210 responses (totally 2520 estimates). Of the respondents, 43 (20.5%) were specialists working mainly in the ICU, 81 (38.6%) were specialists working occasionally in the ICU, 47 (22.4%) were specialists not working in the ICU, and 39 (18.6%) were doctors in training. The difference between the estimate and the realistic prognosis was less than 10 percentage points for 1083 (43.0%) estimates, between 10 and 20 percentage points for 645 (25.6%) estimates, and over 20 percentage points for 792 (31.4%) estimates, out of which 612 (24.3% of all estimates) underestimated and 180 (7.1%) overestimated the likelihood of survival. The median error (the median of the differences between the estimate and the realistic prognosis) for all estimates was -8.8 [interquartile range (IQR), -20.0 to -0.2], which means that the most typical response underestimated the likelihood of survival by 9 percentage points. Based on the 12 estimates, we calculated the median error for each respondent. The median (IQR) of these median errors was -8.6 (-12.6 to -5.0) for specialists working mainly in the ICU, -8.1 (-13.0 to -5.2) for specialists working occasionally in the ICU, -9.7 (-17.7 to -6.3) for specialists not working in the ICU, and -9.1 (-14.5 to -5.1) for doctors in training (p = .29). CONCLUSION: Finnish anesthesiologists commonly misestimate the long-term prognoses of ICU patients, more often underestimating than overestimating the likelihood of 1-year survival. More education about critically ill patients' prognoses and better prediction tools are needed.

PeptiVAX: A new adaptable peptides-delivery platform for development of CTL-based, SARS-CoV-2 vaccines.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a threat to public health and the global economy, necessitating the development of various vaccination strategies. Mutations in the SPIKE protein gene, a crucial component of mRNA and adenovirus-based vaccines, raised concerns about vaccine efficacy, prompting the need for rapid vaccine updates. To address this, we leveraged PeptiCRAd, an oncolytic vaccine based on tumor antigen decorated oncolytic adenoviruses, creating a vaccine platform called PeptiVAX. First, we identified multiple CD8 T-cell epitopes from highly conserved regions across coronaviruses, expanding the range of T-cell responses to non-SPIKE proteins. We designed short segments containing the predicted epitopes presented by common HLA-Is in the global population. Testing the immunogenicity, we characterized T-cell responses to candidate peptides in peripheral blood mononuclear cells (PBMCs) from pre-pandemic healthy donors and ICU patients. As a proof of concept in mice, we selected a peptide with epitopes predicted to bind to murine MHC-I haplotypes. Our technology successfully elicited peptide-specific T-cell responses, unaffected by the use of unarmed adenoviral vectors or adeno-based vaccines encoding SPIKE. In conclusion, PeptiVAX represents a fast and adaptable SARS-CoV-2 vaccine delivery system that broadens T-cell responses beyond the SPIKE protein, offering potential benefits for vaccine effectiveness.

Factors associated with fever after cardiac arrest: A post-hoc analysis of the FINNRESUSCI study.

BACKGROUND: Fever after cardiac arrest may impact outcome. We aimed to assess the incidence of fever in post-cardiac arrest patients, factors predicting fever and its association with functional outcome in patients treated without targeted temperature management (TTM). METHODS: The FINNRESUSCI observational cohort study in 2010-2011 included intensive care unit (ICU)-treated out-of-hospital cardiac arrest (OHCA) patients from all five Finnish university hospitals and 14 of 15 central hospitals. This post hoc analysis included those FINNRESUSCI study patients who were not treated with TH. We defined fever as at least one temperature measurement of ≥37.8°C within 72 h of ICU admission. The primary outcome was favourable functional outcome at 12 months, defined as cerebral performance category (CPC) of 1 or 2. Binary logistic regression models including witnessed arrest, bystander cardiopulmonary resuscitation (CPR), initial rhythm and delay of return of spontaneous circulation were used to compare the functional outcomes of the groups. RESULTS: There were 67,428 temperature measurements from 192 patients, of whom 89 (46%) experienced fever. Twelve-month CPC was missing in 7 patients, and 51 (28%) patients had favourable functional outcome at 12 months. The patients with shockable initial rhythms had a lower incidence of fever within 72 h of ICU admission (28% vs. 72%, p < .01), and the patients who experienced fever had a longer median return of spontaneous circulation (ROSC) delay (20 [IQR 10-30] vs. 14 [IQR 9-22] min, p < .01). Only initial non-shockable rhythm (OR 2.99, 95% CI 1.51-5.94) was associated with increased risk of fever within the first 72 h of ICU admission. Neither time in minutes nor area (minutes × degree celsius over threshold) over 37°C, 37.5°C, 38°C, 38.5°C, 39°C, 39.5°C or 40°C were significantly different in those with favourable functional outcome compared to those with unfavourable functional outcome within the first 24, 48 or 72 h from ICU admission. Fever was not associated with favourable functional outcome at 12 months (OR 0.90, 95% CI 0.44-1.84). CONCLUSIONS: Half of OHCA patients not treated with TTM developed fever. We found no association between fever and outcome.

Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium.

PURPOSE: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. METHODS: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. RESULTS: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of - 6.4%-points (95% confidence interval [CI] - 12.8%-points to - 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI - 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI - 9.3 to 17.5; P = 0.142) for EQ VAS. CONCLUSIONS: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.

A novel score for predicting 1-year mortality of intensive care patients.

BACKGROUND: We aimed to develop a simple scoring table for predicting probability of death within 1-year after admission to an intensive care unit. We analysed data on emergency admissions from the nationwide Finnish intensive care quality registry. METHODS: We included first admissions of adult patients with data available on 1-year vital status (dead or alive) and all five variables included in a premorbid functional status score, which is the number of activities the person can manage independently of the following five: get out of bed, move indoors, dress, climb stairs and walk 400 m. We analysed data on patient characteristics and admission-associated factors from 2012 to 2014 to find predictors of 1-year mortality and to develop a score for predicting probability of death. We tested the performance of this score in data from 2015. We assessed the 1-year functional status score of survivors with data available. RESULTS: Out of 25,261 patients, 20,628 (81.7%) patients were able to perform all five functional activities independently prior to the intensive care unit admission. At 1-year post admission, 19,625 (77.7%) patients were alive. 1-year functional status score was known for 11,011 patients and 8970 (81.5%) patients achieved functional status score 5, managing all five activities independently. The score based on age, sex, preceding functional status, type of intensive care unit admission, severity of acute illness and the most significant diagnoses predicted 1-year mortality with an area under the receiver operating characteristic curve 0.78 (95% CI, 0.76-0.79). The calibration of our prediction model was good, with calibration intercept -0.01 (-0.07 to 0.05) and calibration slope 0.96 (0.90 to 1.02). CONCLUSION: Our score based on data available at intensive care unit admission predicted 1-year mortality with fairly good discrimination. Most survivors achieved good functional recovery.

Hazardous alcohol consumption and perioperative complications in a cardiac surgery patient. A retrospective study.

BACKGROUND: We investigated the prevalence and effects of hazardous alcohol consumption on perioperative complications in cardiac surgery patients. Preoperative hazardous alcohol consumption has been associated with an increased risk of postoperative complications in noncardiac patient populations. METHODS: We retrospectively collected data from the Finnish Intensive Care Consortium database and electronic patient records on all cardiac surgery patients treated in the intensive care units (ICUs) of Helsinki University Hospital (n = 919) during 2017. Data on preoperative alcohol consumption were routinely collected using the alcohol use disorder identification test consumption (AUDIT-C) questionnaire. We analyzed perioperative data and outcomes for any associations with hazardous alcohol consumption. Outcome measures were length of stay in the ICU, re-admissions to ICU, bleeding and infectious complications, and incidence of postoperative arrhythmias. RESULTS: AUDIT-C scores were available for 758 (82.5%) patients, of whom 107 (14.1%) fulfilled the criteria for hazardous alcohol consumption (AUDIT-C score of 5/12 or higher for women and 6/12 or higher for men). Patients with hazardous alcohol consumption were younger, median age 59 (IQR 52.0-67.0) vs. 69.0 (IQR 63.0-74.0), p < .001, and more often men 93.5% vs. 71.9%, p < .001 than other patients and had an increased risk for ICU re-admissions [adjusted OR (aOR) 4.37 (95% CI, 1.60-11.95)] and severe postoperative infections aOR 3.26 (95% CI, 1.42-7.54). CONCLUSION: Cardiac surgery patients with a history of hazardous alcohol consumption are younger than other patients and are predominantly men. Hazardous alcohol consumption is associated with an increased risk of severe postoperative infections and ICU re-admissions.

Brain magnetic resonance imaging findings six months after critical COVID-19: A prospective cohort study.

BACKGROUND: COVID-19 patients suffered from neurological symptoms in the acute phase. Whether this led to long-term consequences was unknown. We studied long-term brain MRI findings in ICU-treated COVID-19 patients and compared them with findings in groups with less severe acute disease. MATERIALS AND METHODS: In this prospective cohort study, 69 ICU-treated, 46 ward-treated, and 46 home-isolated patients, as well as 53 non-COVID-19 controls, underwent brain MRI six months after acute COVID-19. Plasma neurofilament light chain (NfL), a biomarker of neuroaxonal injury, was measured simultaneously. RESULTS: Ischaemic infarctions existed in 5.8% of ICU-treated patients. Cerebral microbleeds (CMBs) existed in 27 (39.1%) ICU-treated, 13 (28.3%) ward-treated, 8 (17.4%) home-isolated COVID-19 patients, and 12 (22.6%) non-COVID controls. Patients with CMBs were older (p < 0.001), had a higher level of plasma NfL (p = 0.003), and higher supplementary oxygen days (p < 0.001). In multivariable analysis, age (OR 1.06, 95% CI 1.02-1.09) and supplementary oxygen days (OR 1.07, 95% CI 1.02-1.13) were associated with CMBs. The ICU group showed prevalent distribution of CMBs in deep regions. CONCLUSION: Age and supplementary oxygen days were independently associated with CMBs; COVID-19 status showed no association. Accumulation of risk factors in the ICU group may explain the higher prevalence of CMBs. TRIAL REGISTRATION: ClinicalTrials.govNCT04864938, registered February 9, 2021.

The effect of higher or lower mean arterial pressure on kidney function after cardiac arrest: a post hoc analysis of the COMACARE and NEUROPROTECT trials.

BACKGROUND: We aimed to study the incidence of acute kidney injury (AKI) in out-of-hospital cardiac arrest (OHCA) patients treated according to low-normal or high-normal mean arterial pressure (MAP) targets. METHODS: A post hoc analysis of the COMACARE (NCT02698917) and Neuroprotect (NCT02541591) trials that randomized patients to lower or higher targets for the first 36 h of intensive care. Kidney function was defined using the Kidney Disease Improving Global Outcome (KDIGO) classification. We used Cox regression analysis to identify factors associated with AKI after OHCA. RESULTS: A total of 227 patients were included: 115 in the high-normal MAP group and 112 in the low-normal MAP group. Eighty-six (38%) patients developed AKI during the first five days; 40 in the high-normal MAP group and 46 in the low-normal MAP group (p = 0.51). The median creatinine and daily urine output were 85 µmol/l and 1730 mL/day in the high-normal MAP group and 87 µmol/l and 1560 mL/day in the low-normal MAP group. In a Cox regression model, independent AKI predictors were no bystander cardiopulmonary resuscitation (p < 0.01), non-shockable rhythm (p < 0.01), chronic hypertension (p = 0.03), and time to the return of spontaneous circulation (p < 0.01), whereas MAP target was not an independent predictor (p = 0.29). CONCLUSION: Any AKI occurred in four out of ten OHCA patients. We found no difference in the incidence of AKI between the patients treated with lower and those treated with higher MAP after CA. Higher age, non-shockable initial rhythm, and longer time to ROSC were associated with shorter time to AKI. CLINICAL TRIAL REGISTRATION: COMACARE (NCT02698917), NEUROPROTECT (NCT02541591).

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Health-related quality of life after surviving intensive care for COVID-19: a prospective multicenter cohort study.

In survivors of severe coronavirus disease 2019 (COVID-19) incomplete mental and physical recovery may considerably impact daily activities and health-related quality of life (HRQoL). HRQoL can be evaluated with the RAND-36 questionnaire, a multidimensional instrument that assesses physical and mental aspects of health in eight dimensions. The objective was to investigate HRQoL in intensive care patients previously treated for COVID-19 at three Nordic university hospitals, in a prospective multi-center cohort study. HRQoL was measured using RAND-36, 3-9 months after discharge from intensive care units (ICU). One hospital performed a second follow-up 12 months after discharge. A score under the lower limit of the 95% confidence interval in the reference cohorts was considered as significantly reduced HRQoL. We screened 542 and included 252 patients. There was more than twice as many male (174) as female (78) patients and the median age was 61 (interquartile range, IQR 52-69) years. Hypertension was the most common comorbidity observed in 132 (52%) patients and 121 (48%) patients were mechanically ventilated for a median of 8 (IQR 4-14) days. In RAND-36 physical functioning, physical role functioning, general health (p < 0.001 for all) and social functioning (p < 0.05) were below reference, whereas bodily pain, emotional role functioning and mental health were not. In a time-to-event analysis female sex was associated with a decreased chance of reaching the reference HRQoL in the physical function, bodily pain and mental health dimensions. Higher body mass index was found in the physical functioning dimension and hypertension in the physical functioning, vitality and social functioning dimensions. Similar results were seen for diabetes mellitus in general health, vitality and mental health dimensions, as well as pulmonary illness in the physical role functioning dimension and psychiatric diagnosis in the social functioning dimension. Mechanical ventilation was associated with a decreased likelihood of achieving reference HRQoL in the bodily pain and physical functioning dimensions. Patients treated in an ICU because of COVID-19 had lower HRQoL 3-9 months after ICU discharge than 95% of the general population. Physical dimensions were more severely affected than mental dimensions. Female sex and several comorbidities were associated with a slower rate of recovery.Study registration: clinicaltrials.gov: NCT04316884 registered on the 13th of March 2020, NCT04474249 registered on the 29th of June 2020 and NCT04864938 registered on the 4th of April 2021.

Risk of malignant disease in 1-year sepsis survivors, a registry-based nationwide follow-up study.

BACKGROUND: Cancer and sepsis share risk factors, and sepsis patients may have impaired immune response and increased morbidity long after intensive care. This study aimed to assess whether sepsis survivors are at increased risk for cancer. Our objective was to assess the incidence of new cancer in 1-year sepsis survivors and test the hypothesis that it is higher than that of the general population. METHODS: We obtained data on ICU admissions of adult patients from Swedish Intensive care registry (SICR) from 2005 to 2017. We included patients with an explicit ICD-10 code for sepsis for the primary ICU admission. We obtained data on cancer diagnoses (2001-2018), death (2005-2018) and emigration (2005-2018) from Cancer and Cause of death and National Patient Registry databases of the National Board of Health and Welfare; age and sex-specific cancer incidence rates in Sweden from NORDCAN registry from 2006 to 2018. One-year survivors formed the final cohort, that was followed for new cancer diagnoses until death, emigration, or end of 2018, whichever came first. The main outcome measure was standardized incidence rate ratio (SIR) to compare the incidence of cancer in 1-year sepsis survivors to that in the general population (NORDCAN). We also performed several sensitivity analyses. RESULTS: In a cohort of 18,550 1-year survivors, 75,427 person years accumulated during a median follow-up (FU) of 3.36 years (IQR 1.72-5.86), 6366 (34.3%) patients died, and 1625 (8.8%) patients were diagnosed with a new cancer after a median FU of 2.51 (IQR 1.09-4.48) years. The incidence ratio of any new cancer over the whole FU was 1.31 (95% CI 1.23-1.40) for men and 1.74 (95% CI 1.61-1.88) for women. The difference in incidence rates persisted in several sensitivity analyses. The SIRs were highest in cancers of gastrointestinal tract, genital organs, and skin. CONCLUSION AND RELEVANCE: Compared to general population, incidence of cancer is increased in 1-year sepsis survivors. Variation in the findings depending on follow-up time suggests that factors other than sepsis alone are involved. Surveillance for malignant disease may be warranted in sepsis survivors.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Higher versus lower blood pressure targets after cardiac arrest: Systematic review with individual patient data meta-analysis.

PURPOSE: Guidelines recommend targeting mean arterial pressure (MAP) > 65 mmHg in patients after cardiac arrest (CA). Recent trials have studied the effects of targeting a higher MAP as compared to a lower MAP after CA. We performed a systematic review and individual patient data meta-analysis to investigate the effects of higher versus lower MAP targets on patient outcome. METHOD: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, BIOSIS, CINAHL, Scopus, the Web of Science Core Collection, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, Google Scholar and the Turning Research into Practice database to identify trials randomizing patients to higher (≥71 mmHg) or lower (≤70 mmHg) MAP targets after CA and resuscitation. We used the Cochrane Risk of Bias tool, version 2 (RoB 2) to assess for risk of bias. The primary outcomes were 180-day all-cause mortality and poor neurologic recovery defined by a modified Rankin score of 4-6 or a cerebral performance category score of 3-5. RESULTS: Four eligible clinical trials were identified, randomizing a total of 1,087 patients. All the included trials were assessed as having a low risk for bias. The risk ratio (RR) with 95% confidence interval for 180-day all-cause mortality for a higher versus a lower MAP target was 1.08 (0.92-1.26) and for poor neurologic recovery 1.01 (0.86-1.19). Trial sequential analysis showed that a 25% or higher treatment effect, i.e., RR < 0.75, can be excluded. No difference in serious adverse events was found between the higher and lower MAP groups. CONCLUSIONS: Targeting a higher MAP compared to a lower MAP is unlikely to reduce mortality or improve neurologic recovery after CA. Only a large treatment effect above 25% (RR < 0.75) could be excluded, and future studies are needed to investigate if relevant but lower treatment effect exists. Targeting a higher MAP was not associated with any increase in adverse effects.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.