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Introduction: Post-resuscitation care of cardiac arrest patients may be complicated by systemic inflammation elicited in response to whole-body ischaemia–reperfusion injury. We assessed the association between early WBC with one-year mortality in a large, unselected population of cardiac arrest patients. Methods: We collected a retrospective multicentre cohort of ICU-treated CA patients from the Finnish national ICU registry. We used locally estimated scatterplot smoothing (LOESS) curve to assess the association between the most abnormal WBC of the first 24 h in the ICU with the likelihood of death within a year. Multivariable logistic regression analyses were performed to assess the independent association between WBC and one-year mortality. In nested cohort analysis, we tested the association of delay from collapse to return of spontaneous circulation (ROSC) with WBC in linear regression models. Results: The LOESS curve was U-shaped, with the lowest predicted mortality at 7.5 109/L WBC. Based on this cut-off value, patients were divided into high (≥ 7.5 109/L) and low (< 7.5 109/L) WBC groups. In 4229 patients with high WBC, higher WBC was independently associated with increased one-year mortality (adjusted odds ratio (OR) 1.03 per 109/L, 95 % confidence interval (CI) 1.02–1.04, p

Abstract Background Severity of illness scoring systems are used in intensive care units to enable the calculation of adjusted outcomes for audit and benchmarking purposes. Similar tools are lacking for pre-hospital emergency medicine. Therefore, using a national helicopter emergency medical services database, we developed and internally validated a mortality prediction algorithm. Methods We conducted a multicentre retrospective observational register-based cohort study based on the patients treated by five physician-staffed Finnish helicopter emergency medical service units between 2012 and 2019. Only patients aged 16 and over treated by physician-staffed units were included. We analysed the relationship between 30-day mortality and physiological, patient-related and circumstantial variables. The data were imputed using multiple imputations employing chained equations. We used multivariate logistic regression to estimate the variable effects and performed derivation of multiple multivariable models with different combinations of variables. The models were combined into an algorithm to allow a risk estimation tool that accounts for missing variables. Internal validation was assessed by calculating the optimism of each performance estimate using the von Hippel method with four imputed sets. Results After exclusions, 30 186 patients were included in the analysis. 8611 (29%) patients died within the first 30 days after the incident. Eleven predictor variables (systolic blood pressure, heart rate, oxygen saturation, Glasgow Coma Scale, sex, age, emergency medical services vehicle type [helicopter vs ground unit], whether the mission was located in a medical facility or nursing home, cardiac rhythm [asystole, pulseless electrical activity, ventricular fibrillation, ventricular tachycardia vs others], time from emergency call to physician arrival and patient category) were included. Adjusted for optimism after internal validation, the algorithm had an area under the receiver operating characteristic curve of 0.921 (95% CI 0.918 to 0.924), Brier score of 0.097, calibration intercept of 0.000 (95% CI -0.040 to 0.040) and slope of 1.000 (95% CI 0.977 to 1.023). Conclusions Based on 11 demographic, mission-specific, and physiologic variables, we developed and internally validated a novel severity of illness algorithm for use with patients encountered by physician-staffed helicopter emergency medical services, which may help in future quality improvement.

Abstract Background In refractory out-of-hospital cardiac arrest, the patient is commonly transported to hospital with mechanical continuous chest compressions (CCC). Limited data are available on the optimal ventilation strategy. Accordingly, we compared arterial oxygenation and haemodynamics during manual asynchronous continuous ventilation and compressions with a 30:2 compression-to-ventilation ratio together with the use of 10 cmH2O positive end-expiratory pressure (PEEP). Methods Intubated and anaesthetized landrace pigs with electrically induced ventricular fibrillation were left untreated for 5 min (n = 31, weight ca. 55 kg), after which they were randomized to either the CCC group or the 30:2 group with the the LUCAS® 2 piston device and bag-valve ventilation with 100% oxygen targeting a tidal volume of 8 ml/kg with a PEEP of 10 cmH2O for 35 min. Arterial blood samples were analysed every 5 min, vital signs, near-infrared spectroscopy and electrical impedance tomography (EIT) were measured continuously, and post-mortem CT scans of the lungs were obtained. Results The arterial blood values (median + interquartile range) at the 30-min time point were as follows: PaO2: 180 (86–302) mmHg for the 30:2 group; 70 (49–358) mmHg for the CCC group; PaCO2: 41 (29–53) mmHg for the 30:2 group; 44 (21–67) mmHg for the CCC group; and lactate: 12.8 (10.4–15.5) mmol/l for the 30:2 group; 14.7 (11.8–16.1) mmol/l for the CCC group. The differences were not statistically significant. In linear mixed models, there were no significant differences between the groups. The mean arterial pressures from the femoral artery, end-tidal CO2, distributions of ventilation from EIT and mean aeration of lung tissue in post-mortem CTs were similar between the groups. Eight pneumothoraces occurred in the CCC group and 2 in the 30:2 group, a statistically significant difference (p = 0.04). Conclusions The 30:2 and CCC protocols with a PEEP of 10 cmH2O resulted in similar gas exchange and vital sign outcomes in an experimental model of prolonged cardiac arrest with mechanical compressions, but the CCC protocol resulted in more post-mortem pneumothoraces.

Abstract Acute brain injuries, such as traumatic brain injury and ischemic and hemorragic stroke, are a leading cause of death and disability worldwide. While characterized by clearly distict primary events—vascular damage in strokes and biomechanical damage in traumatic brain injuries—they share common secondary injury mechanisms influencing long-term outcomes. Growing evidence suggests that a more personalized approach to optimize energy substrate delivery to the injured brain and prognosticate towards families could be beneficial. In this context, continuous invasive and/or non-invasive neuromonitoring, together with clinical evaluation and neuroimaging to support strategies that optimize cerebral blood flow and metabolic delivery, as well as approaches to neuroprognostication are gaining interest. Recently, the European Society of Intensive Care Medicine organized a 2-day course focused on a practical case-based clinical approach of acute brain-injured patients in different scenarios and on future perspectives to advance the management of this population. The aim of this manuscript is to update clinicians dealing with acute brain injured patients in the intensive care unit, describing current knowledge and clinical practice based on the insights presented during this course.

Summary: 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.

Abstract 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

Abstract Background In refractory out-of-hospital cardiac arrest, transportation to hospital with continuous chest compressions (CCC) from a chest compression device and ventilation with 100% oxygen through an advanced airway is common practice. Despite this, many patients are hypoxic and hypercapnic on arrival, possibly related to suboptimal ventilation due to the counterpressure caused by the CCC. We hypothesized that a compression/ventilation ratio of 30:2 would provide better ventilation and gas exchange compared to asynchronous CCC during prolonged experimental cardiopulmonary resuscitation (CPR). Methods We randomized 30 anaesthetized domestic swine (weight approximately 50 kg) with electrically induced ventricular fibrillation to the CCC or 30:2 group and bag-valve ventilation with a fraction of inspired oxygen (FiO2) of 100%. We started CPR after a 5-min no-flow period and continued until 40 min from the induction of ventricular fibrillation. Chest compressions were performed with a Stryker Medical LUCAS® 2 mechanical chest compression device. We collected arterial blood gas samples every 5 min during the CPR, measured ventilation distribution during the CPR using electrical impedance tomography (EIT) and analysed post-mortem computed tomography (CT) scans for differences in lung aeration status. Results The median (interquartile range [IQR]) partial pressure of oxygen (PaO2) at 30 min was 110 (52–117) mmHg for the 30:2 group and 70 (40–171) mmHg for the CCC group. The median (IQR) partial pressure of carbon dioxide (PaCO2) at 30 min was 70 (45–85) mmHg for the 30:2 group and 68 (42–84) mmHg for the CCC group. No statistically significant differences between the groups in PaO2 (p = 0.40), PaCO2 (p = 0.79), lactate (p = 0.37), mean arterial pressure (MAP) (p = 0.47) or EtCO2 (p = 0.19) analysed with a linear mixed model were found. We found a deteriorating trend in PaO2, EtCO2 and MAP and rising PaCO2 and lactate levels through the intervention. There were no differences between the groups in the distribution of ventilation in the EIT data or the post-mortem CT findings. Conclusions The 30:2 and CCC protocols resulted in similar gas exchange and lung pathology in an experimental prolonged mechanical CPR model.

Abstract Background Hypotension following out-of-hospital cardiac arrest (OHCA) may cause secondary brain injury and increase mortality rates. Current guidelines recommend avoiding hypotension. However, the optimal blood pressure following OHCA is unknown. We hypothesised that exposure to hypotension and hypertension in the first 24 h in ICU would be associated with mortality following OHCA. Methods We conducted a retrospective analysis of OHCA patients included in the Intensive Care National Audit and Research Centre Case Mix Programme from 1 January 2010 to 31 December 2019. Restricted cubic splines were created following adjustment for important prognostic variables. We report the adjusted odds ratio for associations between lowest and highest mean arterial pressure (MAP) and systolic blood pressure (SBP) in the first 24 h of ICU care and hospital mortality. Results A total of 32,349 patients were included in the analysis. Hospital mortality was 56.2%. The median lowest and highest MAP and SBP were similar in survivors and non-survivors. Both hypotension and hypertension were associated with increased mortality. Patients who had a lowest recorded MAP in the range 60–63 mmHg had the lowest associated mortality. Patients who had a highest recorded MAP in the range 95–104 mmHg had the lowest associated mortality. The association between SBP and mortality followed a similar pattern to MAP. Conclusions We found an association between hypotension and hypertension in the first 24 h in ICU and mortality following OHCA. The inability to distinguish between the median blood pressure of survivors and non-survivors indicates the need for research into individualised blood pressure targets for survivors following OHCA. Graphical Abstract

Abstract Background Randomised clinical trials with a factorial design may assess the effects of multiple interventions in the same population. Factorial trials are carried out under the assumption that the trial interventions have no interactions on outcomes. Here, we present a protocol for a simulation study investigating the consequences of different levels of interactions between the trial interventions on outcomes for the future 2×2×2 factorial designed randomised clinical Sedation, TEmperature, and Pressure after Cardiac Arrest and REsuscitation (STEPCARE) trial in comatose patients after out-of-hospital cardiac arrest. Methods By simulating a multisite trial with 50 sites and 3278 participants, and a presumed six-month all-cause mortality of 60% in the control population, we will investigate the validity of the trial results with different levels of interaction effects on the outcome. The primary simulation outcome of the study is the risks of type-1 and type-2 errors in the simulated scenarios, i.e. at what level of interaction is the desired alpha and beta level exceeded. When keeping the overall risk of type-1 errors ≤ 5% and the risk of type-2 errors ≤ 10%, we will quantify the maximum interaction effect we can accept if the planned sample size is increased by 5% to take into account possible interaction between the trial interventions. Secondly, we will assess how interaction effects influence the minimal detectable difference we may confirm or reject to take into account 5% (small interaction effect), 10% (moderate), or 15% (large) positive interactions in simulations with no ‘true’ intervention effect (type-1 errors) and small (5%), moderate (10%), or large negative interactions (15%) in simulations with ‘true’ intervention effects (type-2 errors). Moreover, we will investigate how much the sample size must be increased to account for a small, moderate, or large interaction effects. Discussion This protocol for a simulation study will inform the design of a 2×2×2 factorial randomised clinical trial of how potential interactions between the assessed interventions might affect conclusions. Protocolising this simulation study is important to ensure valid and unbiased results. Trial registration Not relevant

Summary: Background: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. Methods: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. Findings: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18–4.90]). No adverse events were reported. Interpretation: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. Trial registration: NCT03237910. Funding: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Abstract Background Temperature control with target temperature management (TTM) after cardiac arrest has been endorsed by expert societies and adopted in international clinical practice guidelines but recent evidence challenges the use of hypothermic TTM. Methods Systematic review and Bayesian meta-analysis of clinical trials on adult survivors from cardiac arrest undergoing TTM for at least 12 h comparing TTM versus no TTM or with a separation > 2 °C between intervention and control groups using the PubMed/MEDLINE, EMBASE, CENTRAL databases from inception to 1 September 2021 (PROSPERO CRD42021248140). All randomised and quasi-randomised controlled trials were considered. The risk ratio and 95% confidence interval for death (primary outcome) and unfavourable neurological recovery (secondary outcome) were captured using the original study definitions censored up to 180 days after cardiac arrest. Bias was assessed using the updated Cochrane risk-of-bias for randomised trials tool and certainty of evidence assessed using the Grading of Recommendation Assessment, Development and Evaluation methodology. A hierarchical robust Bayesian model-averaged meta-analysis was performed using both minimally informative and data-driven priors and reported by mean risk ratio (RR) and its 95% credible interval (95% CrI). Results In seven studies (three low bias, three intermediate bias, one high bias, very low to low certainty) recruiting 3792 patients the RR by TTM 32–34 °C was 0.95 [95% CrI 0.78—1.09] for death and RR 0.93 [95% CrI 0.84—1.02] for unfavourable neurological outcome. The posterior probability for no benefit (RR ≥ 1) by TTM 32–34 °C was 24% for death and 12% for unfavourable neurological outcome. The posterior probabilities for favourable treatment effects of TTM 32–34 °C were the highest for an absolute risk reduction of 2–4% for death (28–53% chance) and unfavourable neurological outcome (63–78% chance). Excluding four studies without active avoidance of fever in the control arm reduced the probability to achieve an absolute risk reduction > 2% for death or unfavourable neurological outcome to ≤ 50%. Conclusions The posterior probability distributions did not support the use of TTM at 32–34 °C compared to 36 °C also including active control of fever to reduce the risk of death and unfavourable neurological outcome at 90–180 days. Any likely benefit of hypothermic TTM is smaller than targeted in RCTs to date.

Abstract Oxygen (O2) toxicity remains a concern, particularly to the lung. This is mainly related to excessive production of reactive oxygen species (ROS). Supplemental O 2 , i.e. inspiratory O2 concentrations (FIO2) > 0.21 may cause hyperoxaemia (i.e. arterial (a) PO2 > 100 mmHg) and, subsequently, hyperoxia (increased tissue O2 concentration), thereby enhancing ROS formation. Here, we review the pathophysiology of O2 toxicity and the potential harms of supplemental O2 in various ICU conditions. The current evidence base suggests that PaO2 > 300 mmHg (40 kPa) should be avoided, but it remains uncertain whether there is an “optimal level” which may vary for given clinical conditions. Since even moderately supra-physiological PaO2 may be associated with deleterious side effects, it seems advisable at present to titrate O2 to maintain PaO2 within the normal range, avoiding both hypoxaemia and excess hyperoxaemia.

Abstract Background Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. Methods A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. Results In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p

Abstract Background Cardiac arrest (CA) is a leading cause of death worldwide. As population ages, the need for research focusing on CA in elderly increases. This study investigated treatment intensity, 12-month neurological outcome, mortality and healthcare-associated costs for patients aged over 75 years treated for CA in an intensive care unit (ICU) of a tertiary hospital. Methods This single-centre retrospective study included adult CA patients treated in a Finnish tertiary hospital’s ICU between 2005 and 2013. We stratified the study population into two age groups:

Abstract Fibroblast growth factor (FGF) 21 is a marker associated with mitochondrial and cellular stress. Cardiac arrest causes mitochondrial stress, and we tested if FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest. We measured serum concentrations of FGF 21 in 112 patients on ICU admission and 24, 48 and 72 h after out-of-hospital cardiac arrest with shockable initial rhythm included in the COMACARE study (NCT02698917). All patients received targeted temperature management for 24 h. We defined 6-month cerebral performance category 1–2 as good and 3–5 as poor neurological outcome. We used samples from 40 non-critically ill emergency room patients as controls. We assessed group differences with the Mann Whitney U test and temporal differences with linear modeling with restricted maximum likelihood estimation. We used multivariate logistic regression to assess the independent predictive value of FGF 21 concentration for neurologic outcome. The median (inter-quartile range, IQR) FGF 21 concentration was 0.25 (0.094–0.91) ng/ml in controls, 0.79 (0.37–1.6) ng/ml in patients at ICU admission (P

OBJECTIVES:. To investigate rebound hyperthermia following targeted temperature management after cardiac arrest and its impact on functional outcome. DESIGN:. Post hoc analysis. SETTING:. Ten European ICUs. PATIENTS:. Patients included in the time-differentiated therapeutic hypothermia in out-of-hospital cardiac arrest survivors trial treated with targeted temperature management at 33°C for 48 or 24 hours. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 6 months. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 338 included patients, 103 (30%) experienced rebound hyperthermia defined as a maximum temperature after targeted temperature management and rewarming exceeding 38.5°C. Using multivariate logistic regression analysis, increasing age (odds ratio, 0.97; 95% CI, 0.95–0.99; p = 0.02) and severe acute kidney injury within 72 hours of ICU admission (odds ratio, 0.35; 95% CI, 0.13–0.91; p = 0.03) were associated with less rebound hyperthermia, whereas male gender (odds ratio, 3.94; 95% CI, 1.34–11.57; p = 0.01), highest C-reactive protein value (odds ratio, 1.04; 95% CI, 1.01–1.07; p = 0.02), and use of mechanical chest compression during cardiopulmonary resuscitation (odds ratio, 2.00; 95% CI, 1.10–3.67; p = 0.02) were associated with more rebound hyperthermia. Patients with favorable functional outcome spent less time after rewarming over 38.5°C (2.5% vs 6.3%; p = 0.03), 39°C (0.14% vs 2.7%; p < 0.01), and 39.5°C (0.03% vs 0.71%; p < 0.01) when compared with others. Median time to rebound hyperthermia was longer in the unfavorable functional outcome group (33.2 hr; interquartile range, 14.3–53.0 hr vs 6.5 hr; interquartile range, 2.2–34.1; p < 0.01). In a predefined multivariate binary logistic regression model, rebound hyperthermia was associated with decreased odds of favorable functional outcome (odds ratio, 0.42; 95% CI, 0.22–0.79). CONCLUSIONS:. One-third of targeted temperature management patients experience rebound hyperthermia, and it is more common in younger male patients with an aggravated inflammatory response and those treated with a mechanical chest compression device. Later onset of rebound hyperthermia and temperatures exceeding 38.5°C associate with unfavorable outcome.

Abstract Background The national early warning score (NEWS) enables early detection of in-hospital patient deterioration and timely activation of hospital’s rapid response team (RRT). NEWS was updated in 2017 to include a separate SpO2 scale for those patients with type II respiratory failure (T2RF). In this study we investigated whether NEWS with and without the new SpO2 scale for the T2RF patients is associated with immediate and in-hospital patient outcomes among the patients actually attended by the RRT. Methods We conducted a two-year prospective observational study including all adult RRT patients without limitations of medical treatment (LOMT) in a large Finnish university associated tertiary level hospital. According to the first vital signs measured by the RRT, we calculated NEWSs for the RRT patients and further utilized the new SpO2 scale for the patients with confirmed T2RF. We used multivariate logistic regression and area under the receiver operating characteristic analyses to test NEWS’s accuracy to predict two distinct outcomes: RRT patient’s I) immediate need for intensive care and/or new LOMT and 2) in-hospital death or discharge with cerebral performance category >2 and/or LOMT. Results The final cohort consisted of 886 RRT patients attended for the first time during their hospitalization. Most common reasons for RRT activation were respiratory (343, 39%) and circulatory (226, 26%) problems. Cohort’s median (Q1, Q3) NEWS at RRT arrival was 8 (5, 10) and remained unchanged if the new SpO2 scale was applied for the 104 patients with confirmed T2RF. Higher NEWS was independently associated with both immediate (OR 1.28; 95% CI 1.22–1.35) and in-hospital (1.15; 1.10–1.21) adverse outcomes. Further, NEWS had fair discrimination for both the immediate (AUROC 0.73; 0.69–0.77) and in-hospital (0.68; 0.64–0.72) outcomes. Utilizing the new SpO2 scale for the patients with confirmed T2RF did not improve the discrimination capability (0.73; 0.69–0.76 and 0.68; 0.64–0.71) for these outcomes, respectively. Conclusions We found that in patients attended by a RRT, the NEWS predicts patient’s hospital outcome with moderate accuracy. We did not find any improvement using the new SpO2 scale in T2RF patients.

Abstract Background Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. Methods We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1–2) and poor (CPC 3–5) neurological outcome. Results The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4–25.0) μg/l in patients with good neurological outcome and 35.2 (22.6–95.8) μg/l in those with poor outcome, p

Abstract Background The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest. Methods A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status. Results A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h (p = 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1–4.0] vs. 4.2 [2.7–6.0] h, p

Abstract Background Organ dysfunction is common after cardiac arrest and associated with worse short-term outcome, but its impact on long-term outcome and treatment costs is unknown. Methods We used nationwide registry data from the intensive care units (ICU) of the five Finnish university hospitals to evaluate the association of 24-h extracerebral Sequential Organ Failure Assessment (24h-EC-SOFA) score with 1-year survival and healthcare-associated costs after cardiac arrest. We included adult cardiac arrest patients treated in the participating ICUs between January 1, 2003, and December 31, 2013. We acquired the confirmed date of death from the Finnish Population Register Centre database and gross 1-year healthcare-associated costs from the hospital billing records and the database of the Finnish Social Insurance Institution. Results A total of 5814 patients were included in the study, and 2401 were alive 1 year after cardiac arrest. Median (interquartile range (IQR)) 24h-EC-SOFA score was 6 (5–8) in 1-year survivors and 7 (5–10) in non-survivors. In multivariate regression analysis, adjusting for age and prior independency in self-care, the 24h-EC-SOFA score had an odds ratio (OR) of 1.16 (95% confidence interval (CI) 1.14–1.18) per point for 1-year mortality. Median (IQR) healthcare-associated costs in the year after cardiac arrest were €47,000 (€28,000–75,000) in 1-year survivors and €12,000 (€6600–25,000) in non-survivors. In a multivariate linear regression model adjusting for age and prior independency in self-care, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €170 (95% CI €150–190) in the cost per day alive in the year after cardiac arrest. In the same model, an increase of one point in the 24h-EC-SOFA score was associated with an increase of €4400 (95% CI €3300–5500) in the total healthcare-associated costs in 1-year survivors. Conclusions Extracerebral organ dysfunction is associated with long-term outcome and gross healthcare-associated costs of ICU-treated cardiac arrest patients. It should be considered when assessing interventions to improve outcomes and optimize the use of resources in these patients.

Abstract Background Arterial carbon dioxide tension (PaCO2), oxygen tension (PaO2), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists. Methods The Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low- or high-normal PaCO2, PaO2, and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 23 factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO2, PaO2, and MAP target levels for 36 h after admission. The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest. Discussion The trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low- or high-normal PaCO2, PaO2, and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified. Trial registration ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.

Abstract Background Intensive care scoring systems are widely used in intensive care units (ICU) around the world for case-mix adjustment in research and benchmarking. The aim of our study was to investigate the usefulness of common intensive care scoring systems in predicting mid-term mortality in patients with spontaneous intracerebral hemorrhage (ICH) treated in intensive care units (ICU). Methods We performed a retrospective observational study including adult patients with spontaneous ICH treated in Finnish ICUs during 2003–2012. We used six-month mortality as the primary outcome of interest. We used logistic regression to customize Acute Physiology and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA) for six-month mortality prediction. To assess the usefulness of the scoring systems, we compared their discrimination and calibration with two simpler models consisting of age, Glasgow Coma Scale (GCS) score, and premorbid functional status. Results Totally 3218 patients were included. Overall six-month mortality was 48%. APACHE II and SAPS II outperformed SOFA (area under the receiver operator curve [AUC] 0.83 and 0.84, respectively, vs. 0.73) but did not show any benefit over the simpler models in terms of discrimination (AUC 0.84, p > 0.05 for all models). SAPS II showed satisfactory calibration (p = 0.058 in the Hosmer-Lemeshow test), whereas all other models showed poor calibration (p

Introduction It is standard of care to provide sedation to critically ill patients to reduce anxiety, discomfort and promote tolerance of mechanical ventilation. Given that sedatives can have differing effects based on a variety of patient and pharmacological characteristics, treatment approaches are largely based on targeting the level of sedation. The benefits of differing levels of sedation must be balanced against potential adverse effects including haemodynamic instability, causing delirium, delaying awakening and prolonging the time of mechanical ventilation and intensive care stay. This systematic review with meta-analysis aims to investigate the current evidence and compare the effects of differing sedation levels in adult critically ill patients.Methods and analyses We will conduct a systematic review based on searches of preidentified major medical databases (eg, MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify trials meeting inclusion criteria. We will include randomised clinical trials comparing any degree of sedation with no sedation and lighter sedation with deeper sedation for critically ill patients admitted to the intensive care unit. We will include aggregate data meta-analyses and trial sequential analyses. Risk of bias will be assessed with domains based on the Cochrane risk of bias tool. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed using Grades of Recommendations, Assessment, Development and Evaluation.Ethics and dissemination No formal approval or review of ethics is required as individual patient data will not be included. This systematic review has the potential to highlight (1) whether one should believe sedation to be beneficial, harmful or neither in critically ill adults; (2) the existing knowledge gaps and (3) whether the recommendations from guidelines and daily clinical practice are supported by current evidence. These results will be disseminated through publication in a peer-reviewed journal.

Background Mechanical chest compression (CC) is currently suggested to deliver sustained high‐quality CC in a moving ambulance. This study compared the hemodynamic support provided by a mechanical piston device or manual CC during ambulance transport in a porcine model of cardiopulmonary resuscitation. Methods and Results In a simulated urban ambulance transport, 16 pigs in cardiac arrest were randomized to 18 minutes of mechanical CC with the LUCAS (n=8) or manual CC (n=8). ECG, arterial and right atrial pressure, together with end‐tidal CO2 and transthoracic impedance curve were continuously recorded. Arterial lactate was assessed during cardiopulmonary resuscitation and after resuscitation. During the initial 3 minutes of cardiopulmonary resuscitation, the ambulance was stationary, while then proceeded along a predefined itinerary. When the ambulance was stationary, CC‐generated hemodynamics were equivalent in the 2 groups. However, during ambulance transport, arterial and coronary perfusion pressure, and end‐tidal CO2 were significantly higher with mechanical CC compared with manual CC (coronary perfusion pressure: 43±4 versus 18±4 mmHg; end‐tidal CO2: 31±2 versus 19±2 mmHg, P