Importance Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined. Objective To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome. Design, Setting, and Participants This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025. Interventions Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days. Main Outcome and Measures The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles. Results Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P = .047; fragility index = 1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P = .34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P = .34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P = .72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P = .03). Conclusions and Relevance In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate. Trial Registration ClinicalTrials.gov Identifier: NCT02968654

BACKGROUND:The Glasgow Coma Scale-based score (GCS) is used to describe the level of consciousness in critically ill patients. In risk-prediction models, an abnormal GCS carries a heavy weight, without considering the cause of impaired consciousness. We assessed the association between low GCS and mortality across individual diagnoses. METHODS:In this retrospective register-based study, we examined 58,982 admissions to 20 ICUs in Finland, Estonia, and Switzerland between 2015 and 2017. We divided the patients into two categories using Acute Physiology And Chronic Health Evaluation (APACHE) III diagnoses: Neurologic and Other diagnoses. We used the lowest GCS recorded during the first 24 h after intensive care unit (ICU) admission. We defined GCS below 9 as low. We analysed the association between low GCS and the risk of death in each APACHE III diagnosis and in the Neurologic and Other diagnoses categories using hierarchical logistic regression. RESULTS:There were 17,275 (29%) patients in the Neurologic category and 41,707 (71%) in the Other diagnoses category. Low GCS was recorded in 4266 (25%) patients in the Neurologic category and 6078 (15%) in the Other diagnoses category. Low GCS was associated with increased risk of death in the Neurologic category [odds ratio (OR) 11.3, 95% confidence interval (CI) 8.0-15.9] and in the Other diagnoses category (OR 4.8, 95% CI 3.9-5.8). The impact of low GCS varied widely between individual diagnoses within both categories. CONCLUSION:Low GCS was a strong predictor of death, but its relative weight was highly dependent on the diagnosis.

INTRODUCTION:Hyperglycaemia is common in intensive care unit (ICU) patients and blood glucose management practices likely vary, but there are limited contemporary data on ICU doctors' and nurses' preferences. METHODS:We conducted an international online survey of ICU doctors and nurses. The 16-question survey covered respondent characteristics, glucose management practices, perceived challenges with intermittent point of care (iPOC) glucose monitoring and continuous glucose monitoring (CGM), and preferences for a future trial on CGM versus usual care. Data were reported descriptively for all respondents and stratified by profession. RESULTS:We received 1424 responses from 12 countries, of which 63% were from nurses. The overall response rate was 36% and the highest proportion of missing data for any question was 9%. Most respondents (92%) reported that their ICU had a glucose management protocol. The median reported insulin initiation threshold was blood glucose of 10 mmol/L. Long-acting insulin was reported to be used occasionally by 68% of respondents. As needed pro re nata insulin was reported as most often given subcutaneously (43%) or intravenously (25%). Overall, 61% of ICU nurses reported concerns related to iPOC use versus 53% among ICU doctors (concerns among nurses versus doctors included risk of hypoglycaemia in 41% vs. 28%; risk of hyperglycaemia in 28% vs. 16%; patient discomfort in 26% vs. 27%). Overall, 75% of respondents never used CGM and 18% of ICU nurses reported concerns related to CGM use versus 22% of ICU doctors (accuracy and reliability in 14% vs. 18%; calibration and maintenance in 9% versus 16%; patient discomfort in 5% vs. 6%, respectively). Most respondents (89%) supported a randomised trial on CGM versus usual care in ICU and 68% preferred an intervention arm with a specific CGM-treatment protocol. CONCLUSIONS:Glucose management preferences varied among ICU staff, particularly in the administration of as needed doses and long-acting insulin. ICU nurses appeared more concerned about iPOC use than ICU doctors. The concerns about use of CGM appeared less common than concerns about iPOC. Most nurses and doctors would support a randomised trial on CGM versus usual care for glucose management in ICU and reported a preference for CGM to be used with a specific treatment protocol. EDITORIAL COMMENT:This international survey highlights substantial professional differences and heterogeneity in ICU glucose management practices, particularly regarding as-needed and long-acting insulin use. Nurses expressed greater concern than doctors about intermittentpoint point-of-care glucose monitoring, especially the risks of hypoglycaemia and hyperglycaemia. Although continuous glucose monitoring was rarely used, it was viewed favourably overall, with broad support for a future protocolised randomised CGM trial.

BACKGROUND:Pain is common in intensive care unit (ICU) patients with up to one-third experiencing pain at rest and even more during mobilization and clinical procedures. This survey aimed to explore physicians' attitudes and preferences regarding pain management in adult ICU patients in the Nordic countries. METHODS:We conducted an electronic survey targeting physicians working regularly in an ICU in the Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. The survey focused on pain assessment, pharmacological treatments, and post-discharge follow-up of adult ICU patients. RESULTS:The survey was distributed to 606 physicians, and 360 responses were received (overall response rate 59%). Respondents were primarily from Denmark, with only a few respondents from the remaining Nordic countries. Most respondents were specialists in anesthesiology working in mixed ICUs in public specialist hospitals. Standardized pain assessment tools were widely used in non-sedated patients, while only half of respondents employed standardized pain assessment tools in sedated patients. Respondents reported that pain was assessed multiple times daily in both non-sedated and sedated patients. Daily wake-up calls in sedated patients were considered important by almost all respondents. Morphine was the preferred opioid for oral- and intravenous bolus administration, while remifentanil was preferred for intravenous continuous administration. However, preferences varied across countries with regard to both opioid- and non-opioid analgesics. Nearly half of respondents expressed concerns regarding the development of opioid-induced hyperalgesia. Methadone was the most frequently preferred drug for opioid weaning, although preferences varied between countries. Most respondents acknowledged the importance of ICU-follow up programs, but only about half of respondents reported that their ICU currently offered a follow-up service. CONCLUSION:This Nordic survey explored ICU physicians' attitudes and preferences regarding pain management in adult ICU patients. Respondents reported assessing pain frequently, employing standardized pain assessment tools primarily in non-sedated patients. Daily wake-up calls in sedated patients were generally perceived as important. Interestingly, preferences regarding opioid- and non-opioid analgesics varied between Nordic countries. ICU-follow up programs were recognized as important but were not consistently implemented. Despite a high overall response rate, the generalizability of our findings is impaired by limited participation in most Nordic countries except Denmark. EDITORIAL COMMENT:This survey describes the physician perspective on predominantly pharmacological pain management in selected ICUs within the Nordic countries.

INTRODUCTION:Staffing at hospital wards is at its lowest during nighttime, which may endanger prompt recognition of the need for intensive care. High severity of illness of patients admitted to the intensive care unit (ICU) in the morning may reflect delayed referral for intensive care during the night. We investigated whether severity of illness at ICU admission is dependent on admission time. METHODS:We analysed data from 25 Finnish ICUs between 2005 and 2022, utilising the national ICU registry. We excluded readmissions, children, non-emergency admissions, cardiac surgery patients and patients admitted for the purpose of organ donation. We explored the severity of illness, as quantified with the Simplified Acute Physiology Score (SAPS) II score, and in-hospital mortality according to admission hours. We also conducted linear and logistic regression analyses adjusting for age, sex, admission type, source of admission, diagnosis category and severity of illness. RESULTS:The study population comprised 131,175 ICU patients. The mean (± SD) SAPS II score at admission was 37.9 ± 17.4, and overall in-hospital mortality was 14.7%. The mean SAPS II score was 39.0 ± 17.9 for morning admissions (6-12 a.m.) and 37.6 ± 17.2 during other times (p < 0.001). The corresponding in-hospital mortalities were 17.5% and 13.9%, respectively (p < 0.001). After adjusting for differences in patient characteristics, morning admissions remained independently associated with higher SAPS II score (mean difference 0.87 points, 95% CI, 0.65-1.09) and in-hospital mortality (OR 1.17, 95% CI, 1.13-1.21). CONCLUSIONS:Patients admitted to intensive care during morning hours experienced higher severity of illness and higher in-hospital mortality. EDITORIAL COMMENT:This analysis, from the national ICU database in Finland, shows that cases with morning admission to the ICU appear to have more severe illness compared to those admitted at other times of day. The authors consider if there might be some nighttime delay for recognition of ICU need which could contribute to this observation.

BACKGROUND:Guidelines discourage prediction of neurological outcome in comatose patients within the first 72 h after cardiac arrest. Increasing evidence suggests that patients with the most severe brain injury and those with no or minimal brain injury may be identified before 72 h using novel methods. We present a protocol for the EARLY-NEURO study, which aims to evaluate whether good and poor outcomes can be reliably predicted already from 24 h after cardiac arrest using the most commonly available methods. METHODS:Protocol for a prospective international multicenter substudy within the Sedation, TEmperature and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial where adults post-arrest are randomized to minimal or deep sedation, fever treatment with or without a temperature management device and to two different targets of mean arterial blood pressure. Patients sedated or still unconscious at 24 h are examined with head computed tomography (CT) and electroencephalogram (EEG). Blood samples are collected at 24 h after randomization, and stored for analysis of the brain injury marker neurofilament light. CT and EEG examinations will be centrally evaluated for signs of a likely poor or good outcome applying standardized criteria by raters blinded to treatment allocations and patient outcomes. Intensive care treatment, neurological prognostication, and criteria for withdrawal of care will be according to the STEPCARE protocol. Timepoint and reasons for withdrawal of life-sustaining therapy (WLST) will be recorded. WLST prior to 72 h after randomization based on a presumed futile neurological prognosis is strongly discouraged. Primary outcome will be good or poor functional outcome, assessed by the modified Rankin Scale (dichotomized as 0-3 versus 4-6) at 6 months. Results will be reported in accordance with the Standards for Reporting Diagnostic Accuracy (STARD). CONCLUSIONS:Earlier prognostication aims to balance the avoidance of premature treatment withdrawal in patients with favorable potential against the prevention of unnecessary intervention in patients with a definitely poor prognosis.

Introduction Extracorporeal cardiopulmonary resuscitation (ECPR) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a treatment option for refractory cardiac arrest patients, but it has mostly been restricted to hospitals with on-site cardiothoracic surgery support. We report the implementation of the ECPR protocol in a rural hospital without on-site cardiothoracic surgery. Methods The ECPR protocol was initiated in June 2020 in North Karelia Central Hospital in Eastern Finland, in collaboration with the tertiary center, Kuopio University Hospital, where patients were transferred for further treatment. After successful initiation of the ECPR protocol, the emergency ECMO treatment was extended to patients with refractory cardiogenic shock or respiratory failure. We retrospectively analyzed patient outcomes. Results Between June 2020 and June 2024, 15 patients suffering from refractory cardiac arrest were treated with ECPR. The median age of the patients was 56 years [interquartile range (IQR) 46-63]. Ten (67%) patients were treated because of out-of-hospital cardiac arrest and five (33%) patients because of in-hospital cardiac arrest. The median time from cardiac arrest to VA-ECMO was 58 (IQR 37-65) min. At six months, three (20%) ECPR patients were alive with a favorable neurological outcome. In addition, one patient with cardiogenic shock was treated successfully with VA-ECMO and one respiratory failure patient with VV-ECMO. Conclusion The ECPR protocol involving the initiation of emergency VA-ECMO in a hospital without on-site cardiac surgery and transfer to a tertiary center for further treatment is feasible and led to the survival of 20% of the ECPR-treated patients and 25% of all VA-ECMO-treated patients.

BACKGROUND: The optimal hemoglobin (Hb) threshold to trigger red blood cell transfusions (RBCT) in subarachnoid hemorrhage (SAH) patients is unclear. This study evaluated the impact of liberal versus restrictive transfusion strategies on neurological outcome in patients with SAH. METHODS: This is a pre-planned secondary analysis of the "TRansfusion Strategies in Acute brain INjured Patients" (TRAIN) study. We included all SAH patients from the original study that were randomized to receive RBCT when Hb levels dropped below 9 g/dL (liberal group) or 7 g/dL (restrictive group). The primary outcome was an unfavorable neurological outcome at 180 days, defined by a Glasgow Outcome Scale Extended score of 1-5. RESULTS: Of the 190 SAH patients in the trial, 188 (98.9%) had data available for the primary outcome, with 86 (45.3%) in the liberal group and 102 (53.6%) in the restrictive group. Patients in the liberal group were older than in the restrictive group, but otherwise had similar baseline characteristics. Patients in the liberal group received more RBCT and showed higher Hb levels over time. At 180 days, 57 (66.3%) patients in the liberal group and 78 (76.4%) in the restrictive group had unfavorable outcomes (risk ratio, RR 0.87; 95% confidence intervals, 95% CI 0.71-1.04). Patients in the liberal group had a significantly lower risk of cerebral ischemia (RR 0.63; 95% CI 0.41-0.97). In a multivariate analysis, randomization to the liberal group was associated with a lower risk of unfavorable outcome (RR 0.83, 95% CI 0.70-0.99). CONCLUSIONS: A liberal transfusion strategy was not associated with a lower incidence of unfavorable outcome after SAH when compared to a restrictive strategy. However, in a multivariable analysis adjusted for confounders randomization to the liberal group was associated with lower risk of unfavorable outcome. The occurrence of cerebral ischemia was significantly lower in the liberal transfusion strategy group. TRIAL REGISTRATION: ClinicalTrials.gov number-NCT02968654 registered on November 16th, 2016.

OBJECTIVES:The standardized mortality ratio (SMR) is a common metric to benchmark ICUs. However, SMR may be artificially distorted by the admission of potential organ donors (POD), who have nearly 100% mortality, although risk prediction models may not identify them as high-risk patients. We aimed to evaluate the impact of PODs on SMR. DESIGN:Retrospective registry-based multicenter study. SETTING:Twenty ICUs in Finland, Estonia, and Switzerland in 2015-2017. PATIENTS:Sixty thousand forty-seven ICU patients. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:We used a previously validated mortality risk model to calculate the SMRs. We investigated the impact of PODs on the overall SMR, individual ICU SMR and ICU benchmarking. Of the 60,047 patients admitted to the ICUs, 514 (0.9%) were PODs, and 477 (93%) of them died. POD deaths accounted for 7% of the total 6738 in-hospital deaths. POD admission rates varied from 0.5 to 18.3 per 1000 admissions across ICUs. The risk prediction model predicted a 39% in-hospital mortality for PODs, but the observed mortality was 93%. The ratio of the SMR of the cohort without PODs to the SMR of the cohort with PODs was 0.96 (95% CI, 0.93-0.99). Benchmarking results changed in 70% of ICUs after excluding PODs. CONCLUSIONS:Despite their relatively small overall number, PODs make up a large proportion of ICU patients who die. PODs cause bias in SMRs and in ICU benchmarking. We suggest excluding PODs when benchmarking ICUs with SMR.

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.

Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co-administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP-ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP-ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time-varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p-values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding.

Background The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. Methods We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. Findings Among 1642632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95%CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95%CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. Interpretation Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

OBJECTIVE Posttraumatic hydrocephalus (PTH) is a recognized long-term complication of traumatic brain injury (TBI). The authors assessed the incidence and risk factors of PTH and its association with outcome in patients with TBI who were treated in the intensive care unit (ICU). METHODS The authors used the Finnish Intensive Care Consortium (FICC) database to retrospectively identify all adult patients with TBI treated in 4 Finnish tertiary ICUs during 2003-2013. All patients were followed up from hospital discharge to a diagnosis of PTH, death, or the end of 2016. PTH was defined as a need for a postdischarge ventriculoperitoneal or ventriculoatrial shunt. The authors collected data on shunt-insertion procedures, mortality, and disability status from nationwide registries cross-linked to the FICC database. The authors calculated the occurrence and incidence rates of PTH and used multivariable logistic regression modeling to determine risk factors for PTH and its association with outcome. RESULTS Sixty-one of 2882 patients (2.1%) developed PTH during a median follow-up time of 4.6 years, with a median of 102 days (interquartile range 54-220 days) between hospital discharge and PTH. Risk factors for PTH were increasing age (OR 1.02 per year, 95% CI 1.01-1.04); a midline shift of > 5 mm (OR 1.88, 95% CI 1.01-3.48); traumatic subarachnoid hemorrhage (OR 3.59, 95% CI 1.79-7.21); external ventricular drainage (OR 3.54, 95% CI 1.68-7.46); and decompressive craniectomy (OR 3.68, 95% CI 1.37-9.88). PTH was independently associated with permanent disability after case-mix adjustment (OR 3.62, 95% CI 2.11-6.22). CONCLUSIONS PTH is an uncommon long-term complication of TBI, with several risk factors that are identifiable early during neurointensive care. The development of PTH is independently associated with poor functional outcome. Whether earlier detection and treatment of PTH leads to improved outcomes remains unknown, highlighting the importance of adequate follow-up and prompt detection and treatment of the condition.

BACKGROUND:We studied the prognostic ability of serum ubiquitin C-terminal hydrolase L1 (UCH-L1) after out-of-hospital cardiac arrest (OHCA), compared to that of neuron-specific enolase (NSE).METHODS:In this post-hoc analysis of the FINNRESUSCI study, we measured serum concentrations of UCH-L1 in 249 OHCA patients treated in 21 Finnish intensive care units in 2010-2011. We evaluated the ability of UCH-L1 to predict unfavourable outcome at 12 months (defined as cerebral performance category 3-5) by assessing the area under the receiver operating characteristic curve (AUROC), in comparison with NSE.RESULTS:The concentrations of UCH-L1 were higher in patients with unfavourable outcome than for those with favourable outcome: median concentration 10.8 ng/mL (interquartile range, 7.5-18.5 ng/mL) versus 7.8 ng/mL (5.9-11.8 ng/mL) at 24 h (p < .001), and 16.2 ng/mL (12.2-27.7 ng/mL) versus 11.5 ng/mL (9.0-17.2 ng/mL) (p < .001) at 48 h after OHCA. For UCH-L1 as a 12-month outcome predictor, the AUROC was 0.66 (95% confidence interval, 0.60-0.73) at 24 h and 0.66 (0.59-0.74) at 48 h. For NSE, the AUROC was 0.66 (0.59-0.73) at 24 h and 0.72 (0.65-0.80) at 48 h. The prognostic ability of UCH-L1 was not different from that of NSE at 24 h (p = .82) and at 48 h (p = .23).CONCLUSION:Concentrations of UCH-L1 in serum were higher in patients with unfavourable outcome than in those with favourable outcome. However, the ability of UCH-L1 to predict unfavourable outcome after OHCA was only moderate and not superior to that of NSE.

Objectives: Recombinant erythropoietin (EPO) administered during intensive care is one possible treatment method for patients with traumatic brain injury that may increase short-term survival. Its effect on long-term outcome including functional outcome is unknown. Methods: We conducted a long-term follow up of patients included in the multi-center erythropoietin in traumatic brain injury (TBI) trial (Clinical Trials.gov NCT00987454) conducted between 2010 and 2014. We invited patients treated in all countries except France to participate in a follow-up and evaluated survival and functional outcome with the Glasgow outcome scale extended (GOSE) with categories 5 to 8 defined as good outcome. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT-TBI) model and calculated adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Of 603 patients included in the original trial, 371 were included in the follow-up at a median of six years from injury (interquartile range 3-8 years). Out of 185 patients treated with EPO, 140 (76%) were alive and 110 (60%) had good outcome. The corresponding numbers for the 180 placebo patients were 136 (73%) and 100 (53%) (p=0.57, p=0.27). A multivariable model adjusting for the IMPACT severity provided comparable results the effect of EPO for survival (OR 1.3 95% CI 0.8-2.2, p=0.31)) and good outcome (OR 1.5 95% 0.9-2.4, p=0.09). Conclusions: EPO did not decrease mortality or improve outcome but the limited sample size does not rule out clinically meaningful effects suggesting the need for a larger study.

BACKGROUND:Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. METHODS:The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. DISCUSSION:Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. TRIAL REGISTRATION:ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

Background Antiplatelet and anticoagulant medication are increasingly common and can increase the risks of morbidity and mortality in traumatic brain injury (TBI) patients. Our study aimed to quantify the association of antiplatelet or anticoagulant use in intensive care unit (ICU)–treated TBI patients with 1-year mortality and head CT findings. Method We conducted a retrospective, multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted to four university hospital ICUs during 2003–2013. The patients were followed up until the end of 2016. The national drug reimbursement database provided information on prescribed medication for our study. We used multivariable logistic regression models to assess the association between TBI severity, prescribed antiplatelet and anticoagulant medication, and their association with 1-year mortality. Results Of 3031 patients, 128 (4%) had antiplatelet and 342 (11%) anticoagulant medication before their TBI. Clopidogrel (2%) and warfarin (9%) were the most common antiplatelets and anticoagulants. Three patients had direct oral anticoagulant (DOAC) medication. The median age was higher among antiplatelet/anticoagulant users than in non-users (70 years vs. 52 years, p < 0.001), and their head CT findings were more severe (median Helsinki CT score 3 vs. 2, p < 0.05). In multivariable analysis, antiplatelets (OR 1.62, 95% CI 1.02–2.58) and anticoagulants (OR 1.43, 95% CI 1.06–1.94) were independently associated with higher odds of 1-year mortality. In a sensitivity analysis including only patients over 70, antiplatelets (OR 2.28, 95% CI 1.16–4.22) and anticoagulants (1.50, 95% CI 0.97–2.32) were associated with an increased risk of 1-year mortality. Conclusions Both antiplatelet and anticoagulant use before TBI were risk factors in our study for 1-year mortality. Antiplatelet and anticoagulation medication users had a higher radiological intracranial injury burden than non-users defined by the Helsinki CT score. Further investigation on the effect of DOACs on mortality should be done in ICU–treated TBI patients.

Admission computed tomography (CT) scoring systems can be used to objectively quantify the severity of traumatic brain injury (TBI) and aid in outcome prediction. We aimed to externally validate the NeuroImaging Radiological Interpretation System (NIRIS) and the Helsinki CT score. In addition, we compared the prognostic performance of the NIRIS and the Helsinki CT score to the Marshall CT classification and to a clinical model. We conducted a retrospective multicenter observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted in four university hospital ICUs during 2003–2013. We analyzed the CT scans using the NIRIS and the Helsinki CT score and compared the results to 6-month mortality as the primary outcome. In addition, we created a clinical model (age, Glasgow Coma Scale score, Simplified Acute Physiology Score II, presence of severe comorbidity) and combined clinical and CT models to see the added predictive impact of radiological data to conventional clinical information. We measured model performance using area under curve (AUC), Nagelkerke’s R2 statistics, and the integrated discrimination improvement (IDI). A total of 3031 patients were included in the analysis. The 6-month mortality was 710 patients (23.4%). Of the CT models, the Helsinki CT displayed best discrimination (AUC 0.73 vs. 0.70 for NIRIS) and explanatory variation (Nagelkerke’s R2 0.20 vs. 0.15). The clinical model displayed an AUC of 0.86 (95% CI 0.84–0.87). All CT models increased the AUC of the clinical model by + 0.01 to 0.87 (95% CI 0.85–0.88) and the IDI by 0.01–0.03. In patients with TBI treated in the ICU, the Helsinki CT score outperformed the NIRIS for 6-month mortality prediction. In isolation, CT models offered only moderate accuracy for outcome prediction and clinical variables outweighing the CT-based predictors in terms of predictive performance.