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Traditional models to predict intensive care outcomes do not perform well in COVID-19. We undertook a comprehensive study of factors affecting mortality and functional outcome after severe COVID-19.In this prospective multicentre cohort study, we enrolled laboratory-confirmed, critically ill COVID-19 patients at six ICUs in the Skåne Region, Sweden, between May 11, 2020, and May 10, 2021. Demographics and clinical data were collected. ICU burden was defined as the total number of ICU-treated COVID-19 patients in the region on admission. Surviving patients had a follow-up at 90 days for assessment of functional outcome using the Glasgow Outcome Scale-Extended (GOSE), an ordinal scale (1-8) with GOSE ≥5 representing a favourable outcome. The primary outcome was 90-day mortality; the secondary outcome was functional outcome at 90 days.Among 498 included patients, 74% were male with a median age of 66 years and a median body mass index (BMI) of 30 kg/mIn critically ill COVID-19 patients, the 90-day mortality was 39% and increased considerably at age 60 or older. The ICU burden was associated with mortality, whereas a high BMI was not. A longer stay in the ICU was associated with unfavourable functional outcomes at 90 days.

Background Bioactive adrenomedullin (bio-ADM) is a vasoactive peptide with a key role in reducing vascular hyperpermeability and improving endothelial stability during infection, but it also has vasodilatory properties. Bioactive ADM has not been studied in conjunction with acute respiratory distress syndrome (ARDS), but it has recently been shown to correlate with outcomes after severe COVID-19. Therefore, this study investigated the association between circulating bio-ADM on intensive care unit (ICU) admission and ARDS. The secondary aim was the association between bio-ADM and ARDS mortality. Methods We analysed bio-ADM levels and assessed the presence of ARDS in adult patients admitted to two general intensive care units in southern Sweden. Medical records were manually screened for the ARDS Berlin criteria. The association between bio-ADM levels and ARDS and mortality in ARDS patients was analysed using logistic regression and receiver-operating characteristics analysis. The primary outcome was an ARDS diagnosis within 72 h of ICU admission, and the secondary outcome was 30-day mortality. Results Out of 1224 admissions, 11% (n = 132) developed ARDS within 72 h. We found that elevated admission bio-ADM level was associated with ARDS independently of sepsis status and of organ dysfunction as measured by the Sequential organ failure assessment (SOFA) score. Both lower levels (< 38 pg/L) and high (> 90 pg/L) levels of bio-ADM were independently (of the Simplified acute physiology score, SAPS-3) predictive of mortality. Patients with indirect mechanisms of lung injury had higher bio-ADM levels than those with a direct mechanism of injury, and bio-ADM increased with increasing ARDS severity. Conclusions High levels of bio-ADM on admission are associated with ARDS, and bio-ADM levels significantly differ depending on the injury mechanism. In contrast, both high and low levels of bio-ADM are associated with mortality, possibly due to the dual action of bio-ADM in stabilising the endothelial barrier and causing vasodilation. These findings could lead to improved diagnostic accuracy of ARDS and potentially lead to new therapeutic strategies.

We studied the association between cardiorenal function and survival, neurological outcome and trends in survival after in-hospital cardiac arrest (IHCA).We included cases aged ≥ 18 years in the Swedish Cardiopulmonary Resuscitation Registry during 2008 to 2020. The CKD-EPI equation was used to calculate estimated glomerular filtration rate (eGFR). A history of heart failure was defined according to contemporary guideline criteria. Logistic regression was used to study survival. Neurological outcome was assessed using cerebral performance category (CPC).We studied 22,819 patients with IHCA. The 30-day survival was 19.3%, 16.6%, 22.5%, 28.8%, 39.3%, 44.8% and 38.4% in cases with eGFR 15, 15-29, 30-44, 45-59, 60-89, 90-130 and 130-150 ml/min/1.73 mAll eGFR levels below and above normal range are associated with increased mortality and this association is modified by the presence of heart failure. Neurological outcome is good in the majority of cases, across kidney function levels and survival is increasing.

Aim Previous studies evaluating the relationship between sex and post-resuscitation care and outcomes following out-of-hospital cardiac arrest (OHCA) are conflicting. We investigated the association between sex and outcomes as well as neurodiagnostic testing in a prospective multicenter international registry of patients admitted to intensive care units following OHCA. Methods OHCA survivors enrolled in the International Cardiac Arrest Registry (INTCAR) from 2012 to 2017 were included. We assessed the independent association between sex and survival to hospital discharge, good neurologic outcome (Cerebral Performance Category 1 or 2), neurodiagnostic testing, and withdrawal of life-sustaining therapy (WLST). Results Of 2407 eligible patients, 809 (33.6%) were women. Baseline characteristics differed by sex, with less bystander CPR and initial shockable rhythms among women. Women were less likely to survive to hospital discharge, however significance abated following adjusted analysis (30.1% vs 42.7%, adjusted OR 0.85, 95% CI 0.67–1.08). Women were less likely to have good neurologic outcome at discharge (21.4% vs 34.0%, adjusted OR 0.74, 95% CI 0.57–0.96) and at six months post-arrest (16.7% vs 29.4%, adjusted OR 0.73, 95% CI 0.54–0.98) that persisted after adjustment. Neuroimaging (75.5% vs 74.3%, p = 0.54) and other neurophysiologic testing (78.8% vs 78.6%, p = 0.91) was similar across sex. Women were more likely to undergo WLST (55.6% vs 42.8%, adjusted OR 1.35, 95% CI 1.09–1.66). Conclusions Women with cardiac arrest have lower odds of good neurologic outcomes and higher odds of WLST, despite comparable rates of neurodiagnostic testing and after controlling for baseline differences in clinical characteristics and cardiac arrest features.

Background Out of Hospital Cardiac arrest (OHCA) survivors with ST elevation (STE) with or without shockable rhythms often benefit from coronary angiography (CAG) and, if indicated, percutaneous coronary intervention (PCI). However, the benefits of CAG and PCI in OHCA survivors with nonshockable rhythms (PEA/asystole) and no STE are debated. Methods Using the International Cardiac Arrest Registry (INTCAR 2.0), representing 44 centers in the US and Europe, comatose OHCA survivors with known presenting rhythms and post resuscitation ECGs were identified. Survival to hospital discharge, neurological recovery on discharge, and impact of CAG with or without PCI on such outcome were assessed and compared with other groups (shockable rhythms with or without STE). Results Total of 2113 OHCA survivors were identified and described as; nonshockable/no STE (Nsh-NST) (n = 940, 44.5%), shockable/no STE (Sh-NST) (n = 716, 33.9%), nonshockable/STE (Nsh-ST) (n = 110, 5.2%), and shockable/STE (Sh-ST) (n = 347, 16.4%). Of Nsh-NST, 13.7% (129) were previously healthy before CA and only 17.3% (161) underwent CAG; of those, 30.4% (52) underwent PCI. A total of 18.6% (174) Nsh-NST patients survived to hospital discharge, with 57.5% (100) of such survivors having good neurological recovery (cerebral performance category 1 or 2) on discharge. Coronary angiography was associated with improved odds for survival and neurological recovery among all groups, including those with NSh-NST. Conclusions Nonshockable initial rhythms with no ST elevation post resuscitation was the most common presentation after OHCA. Although most of these patients did not undergo coronary angiography, among those who did, 1 in 4 patients had a culprit lesion and underwent revascularization. Invasive CAG should be at least considered for all OHCA survivors, including those with nonshockable rhythms and no ST elevation post resuscitation. Brief abstract Out of hospital cardiac arrest (OHCA) survivors with ST elevation and/or shockable rhythms benefit from coronary angiography and revascularization. Nonshockable cardiac arrest survivors with no ST elevation have the worst prognosis and rarely undergo coronary angiography. Nonshockable rhythms with no ST elevation was the most common presentation after OHCA and among a small subgroup underwent coronary angiography, 1 in 4 patients with had culprit lesion and underwent revascularization. Coronary angiography was associated with high prevalence of acute culprit coronary lesions and should be considered for those with a probably cardiac cause for their arres.

Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06481-4.

Background Cardiac arrest (CA) represents the third leading cause of death worldwide. Among patients resuscitated and admitted to hospital, death and severe neurological sequelae are frequent but difficult to predict. Blood biomarkers offer clinicians the potential to improve prognostication. Previous studies suggest that circulating non-coding RNAs constitute a reservoir of novel biomarkers. Therefore, this study aims to identify circulating circular RNAs (circRNAs) associated with clinical outcome after CA. Results Whole blood samples obtained 48 h after return of spontaneous circulation in 588 survivors from CA enrolled in the Target Temperature Management trial (TTM) were used in this study. Whole transcriptome RNA sequencing in 2 groups of 23 sex-matched patients identified 28 circRNAs associated with neurological outcome and survival. The circRNA circNFAT5 was selected for further analysis using quantitative PCR. In the TTM-trial (n = 542), circNFAT5 was upregulated in patients with poor outcome as compared to patients with good neurological outcome (p Conclusion We identified circulating circRNAs associated with clinical outcome after CA, among which circNFAT5 may have potential to aid in predicting neurological outcome and survival when used in combination with established biomarkers of CA.

Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.

Background Our aim was to investigate the prognostic potential of circulating dipeptidyl peptidase 3 (cDPP3) to predict mortality and development of organ dysfunction in a mixed intensive care unit (ICU) population, and for this reason, we analysed prospectively collected admission blood samples from adult ICU patients at four Swedish hospitals. Blood samples were stored in a biobank for later batch analysis. The association of cDPP3 levels with 30-day mortality and Sequential Organ Failure Assessment (SOFA) scores on day two was investigated before and after adjustment for the simplified acute physiology score III (SAPS-3), using multivariable (ordinal) logistic regression. The predictive power of cDPP3 was assessed using the area under the receiver operating characteristic curve (AUROC). Results Of 1978 included consecutive patients in 1 year (2016), 632 fulfilled the sepsis 3-criteria, 190 were admitted after cardiac arrest, and 157 because of trauma. Admission cDPP3 was independently (of SAPS-3) associated with 30-day mortality with odds ratios of 1.45 (95% confidence interval (CI) 1.28–1.64) in the entire ICU population, 1.30 (95% CI 1.08–1.57) in the sepsis subgroup and 2.28 (95% CI 1.50–3.62) in cardiac arrest. For trauma, there was no clear association. Circulating DPP3 alone was a moderate predictor of 30-day mortality with AUROCs of 0.68, 0.62, and 0.72 in the entire group, the sepsis subgroup, and the cardiac arrest subgroup, respectively. By adding cDPP3 to SAPS-3, AUROC improved for the entire group, the sepsis subgroup, and the cardiac arrest subgroup (p = 0.023). Conclusion Circulating DPP3 on admission is a SAPS-3 independent prognostic factor of day-two organ dysfunction and 30-day mortality in a mixed ICU population and needs further evaluation. Supplementary Information The online version contains supplementary material available at (10.1186/s40560-021-00561-9).

BACKGROUND: A large proportion of adult survivors of cardiac arrest have a poor neurological outcome. Guidelines recommend multimodal neuro-prognostication no earlier than 72-96 hours after cardiac arrest. There is great interest in earlier prognostic markers, including very early markers at admission. The novel blood biomarkers proenkephalin A 119-159 (penKid), bioactive adrenomedullin (bio-ADM) and circulating dipeptidyl peptidase 3 (cDPP3) have not been previously investigated for the early prognosis of cardiac arrest survivors.METHODS: This multicentre observational study included adult survivors of cardiac arrest admitted to intensive care at four Swedish intensive care units (ICUs) during 2016. Blood samples were collected at ICU admission and batch analysed. The association between admission plasma penKid, bio-ADM and cDPP3 and poor long-term neurological outcome, according to the Cerebral Performance Category (CPC) scale, was assessed by binary logistic regression. Their prognostic performance was assessed using the area under the receiver operating characteristic curve (AUC).RESULTS: A total of 190 patients were included, of which 136 patients had suffered out-of-hospital and 54 patients in-hospital cardiac arrest. Poor long-term neurological outcome was associated with elevated admission plasma concentrations of penKid and cDPP3, but not with bio-ADM. The association for penKid, but not for cDPP3, remained after adjusting for clinical cardiac arrest variables with prognostic value (time to return of spontaneous circulation (ROSC), initial rhythm, admission Glasgow Coma Scale (GCS) motor score and absence of pupillary reflexes). The prognostic performance of above mentioned clinical cardiac arrest variables alone was very good with an AUC of 0.90 (95% confidence interval, CI, 0.86-0.95), but improved further with the addition of penKid resulting in an AUC of 0.93 (95% CI 0.89-0.97, p < 0.026). Plasma penKid and cDPP3 alone provided moderate long-term prognostic information with AUCs of 0.70 and 0.71, respectively.CONCLUSION: After cardiac arrest, admission plasma levels of penKid and cDPP3, but not bio-ADM, predicted long-term neurological outcome. When added to clinical cardiac arrest variables, penKid further improved prognostic performance. (Less)

Purpose The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (V-T) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH(2)0, plateau pressure was 20 cmH(2)0 (IQR = 17-23), driving pressure was 12 cmH(2)0 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36-45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003-1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001-1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes. Funding Agencies|Universita degli Studi di Genova; Swedish Research Council [Vetenskapsradet]; Swedish Heart-Lung Foundation; Stig and Ragna Gorthon Foundation; Knutsson Foundation; Laerdal Foundation; Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research; Region Skane; Swedish National Health Service

ImportanceBlood phosphorylated tau (p-tau) and amyloid-β peptides (Aβ) are promising peripheral biomarkers of Alzheimer disease (AD) pathology. However, their potential alterations due to alternative mechanisms, such as hypoxia in patients resuscitated from cardiac arrest, are not known.ObjectiveTo evaluate whether the levels and trajectories of blood p-tau, Aβ42, and Aβ40 following cardiac arrest, in comparison with neural injury markers neurofilament light (NfL) and total tau (t-tau), can be used for neurological prognostication following cardiac arrest.Design, Setting, and ParticipantsThis prospective clinical biobank study used data from the randomized Target Temperature Management After Out-of-Hospital Cardiac Arrest (TTM) trial. Unconscious patients with cardiac arrest of presumed cardiac origin were included between November 11, 2010, and January 10, 2013, from 29 international sites. Serum analysis for serum NfL and t-tau were performed between August 1 and August 23, 2017. Serum p-tau, Aβ42, and Aβ40 were analyzed between July 1 and July 15, 2021, and between May 13 and May 25, 2022. A total of 717 participants from the TTM cohort were examined: an initial discovery subset (n = 80) and a validation subset. Both subsets were evenly distributed for good and poor neurological outcome after cardiac arrest.ExposuresSerum p-tau, Aβ42, and Aβ40 concentrations using single molecule array technology. Serum levels of NfL and t-tau were included as comparators.Main Outcomes and MeasuresBlood biomarker levels at 24 hours, 48 hours, and 72 hours after cardiac arrest. Poor neurologic outcome at 6-month follow-up, defined according to the cerebral performance category scale as category 3 (severe cerebral disability), 4 (coma), or 5 (brain death).ResultsThis study included 717 participants (137 [19.1%] female and 580 male [80.9%]; mean [SD] age, 63.9 [13.5] years) who experienced out-of-hospital cardiac arrest. Significantly elevated serum p-tau levels were observed at 24 hours, 48 hours, and 72 hours in cardiac arrest patients with poor neurological outcome. The magnitude and prognostication of the change was greater at 24 hours (area under the receiver operating characteristic curve [AUC], 0.96; 95% CI, 0.95-0.97), which was similar to NfL (AUC, 0.94; 95% CI, 0.92-0.96). However, at later time points, p-tau levels decreased and were weakly associated with neurological outcome. In contrast, NfL and t-tau maintained high diagnostic accuracies, even 72 hours after cardiac arrest. Serum Aβ42 and Aβ40 concentrations increased over time in most patients but were only weakly associated with neurological outcome.Conclusions and RelevanceIn this case-control study, blood biomarkers indicative of AD pathology demonstrated different dynamics of change after cardiac arrest. The increase of p-tau at 24 hours after cardiac arrest suggests a rapid secretion from the interstitial fluid following hypoxic-ischemic brain injury rather than ongoing neuronal injury like NfL or t-tau. In contrast, delayed increases of Aβ peptides after cardiac arrest indicate activation of amyloidogenic processing in response to ischemia.

To explore if electrographic status epilepticus (ESE) after cardiac arrest causes additional secondary brain injury reflected by serum levels of two novel biomarkers of brain injury: neurofilament light chain (NfL) originating from neurons and glial fibrillary acidic protein (GFAP) from glial cells.Simplified continuous EEG (cEEG) and serum levels of NfL and GFAP, sampled at 24, 48 and 72 h after cardiac arrest, were collected during the Target Temperature Management (TTM)-trial. Two statistical methods were used: multivariable regresssion analysis; and a matched control group of patients without ESE matched for early predictors of poor neurological outcome.128 patients had available biomarkers and cEEG. Twenty-six (20%) patients developed ESE, the majority (69%) within 24 h. ESE was an independent predictor of elevated serum NfL (p 0.001) but not of serum GFAP (p = 0.16) at 72 h after cardiac arrest. Compared to a control group matched for early predictors of poor neurological outcome, patients who developed ESE had higher levels of serum NfL (p = 0.03) and GFAP (p = 0.04) at 72 h after cardiac arrest.ESE after cardiac arrest is associated with higher levels of serum NfL which may suggest increased secondary neuronal injury compared to matched patients without ESE but similar initial brain injury. Associations with GFAP reflecting glial injury are less clear. The study design cannot exclude imperfect matching or other mechanisms of secondary brain injury contributing to the higher levels of biomarkers of brain injury seen in the patients with ESE.

Hypotension after cardiac arrest could aggravate prolonged hypoxic ischemic encephalopathy. The association of circulatory shock at hospital admission with outcome after cardiac arrest has not been well studied. The objective of this study was to investigate the independent association of circulatory shock at hospital admission with neurologic outcome, and to evaluate whether cardiovascular comorbidities interact with circulatory shock. 4004 adult patients with out-of-hospital cardiac arrest enrolled in the International Cardiac Arrest Registry 2006–2017 were included in analysis. Circulatory shock was defined as a systolic blood pressure below 90 mmHg and/or medical or mechanical supportive measures to maintain adequate perfusion during hospital admission. Primary outcome was cerebral performance category (CPC) dichotomized as good, (CPC 1–2) versus poor (CPC 3–5) outcome at hospital discharge. 38% of included patients were in circulatory shock at hospital admission, 32% had good neurologic outcome at hospital discharge. The adjusted odds ratio for good neurologic outcome in patients without preexisting cardiovascular disease with circulatory shock at hospital admission was 0.60 [0.46–0.79]. No significant interaction was detected with preexisting comorbidities in the main analysis. We conclude that circulatory shock at hospital admission after out-of-hospital cardiac arrest is independently associated with poor neurologic outcome.

Title: Self-reported limitations in physical function are common 6 months after out-of-hospital cardiac arrest. Background: Out-of-hospital cardiac arrest (OHCA) survivors generally report good health-related quality of life, but physical aspects of health seem more affected than other domains. Limitations in physical function after surviving OHCA have received little attention. Aims: To describe physical function 6 months after OHCA and compare it with a group of ST elevation myocardial infarction (STEMI) controls, matched for country, age, sex and time of the cardiac event. A second aim was to explore variables potentially associated with self-reported limitations in physical function in OHCA survivors. Methods: A cross-sectional sub-study of the Targeted Temperature Management at 33 °C versus 36 °C (TTM) trial with a follow-up 6 months post-event. Physical function was the main outcome assessed with the self-reported Physical Functioning-10 items scale (PF-10). PF-10 is presented as T-scores (0–100), where 50 represents the norm mean. Scores

To analyze the impact of a time-gain selective, first-responder dispatch system on the presence of a shockable initial rhythm (SIR), return of spontaneous circulation (ROSC) and 30-day survival after out-of-hospital cardiac arrest (OHCA).A retrospective observational study comprising OHCA registry data and dispatch data in the Skåne Region, Sweden (2010-2018). Data were categorized according to dispatch procedures, two ambulances (AMB-only) versus two ambulances and firefighter first-responders (DUAL-dispatch), based on the dispatcher's estimation of a time-gain. Dual dispatch was sub-categorized by arrival of first vehicle (first-responder or ambulance). Logistic regressions were used, additionally with groups matched (1:1) for age, sex, location, witnessed event, bystander cardiopulmonary resuscitation and ambulance response time. Adjusted and conditional odds-ratios (aOR, cOR) with 95% confidence intervals (CI) are presented.Of 3,245 eligible cases, 43% were DUAL-dispatches with first-responders first on scene (FR-first) in 72%. Despite a five-minute median reduction in response time in the FR-first group, no association with SIR was found (aOR 0.83, 95%CI 0.64-1.07) nor improved 30-day survival (aOR 1.03, 95%CI 0.72-1.47). A positive association between ROSC and the FR-first group (aOR 1.25, 95%CI 1.02-1.54) disappeared in the matched analysis (cOR 1.12, 95%CI 0.87-1.43). Time to first monitored rhythm was 7:06 minutes in the FR-first group versus 3:01 in the combined AMB-only/AMB-first groups.In this time-gain selective first-responder dispatch system, a shorter response time was not associated with increased SIR, improved ROSC rate or survival. Process measures differed between the study groups which could account for the observed findings and requires further investigation.

Post-covid syndrome is an emerging condition involving a wide range of symptoms, including high rates of poor mental health. The diagnostic relevance and clinical severity of these symptoms are largely unknown, and evidence for treatment of post-covid mental health symptoms is lacking. This protocol describes a pilot randomized clinical trial, primarily aiming to assess feasibility, participant adherence and satisfaction in a novel phycho-therapeutic intervention on post-covid anxiety and depression symptoms ≥1 year after critically ill COVID-19. Whether the intervention may generate improvements in post-covid depression, anxiety, post-traumatic stress and health-related quality of life (HRQoL) will be addressed in a following larger trial.A multicenter, investigator-initiated randomized controlled trial (Clinical Trial Identifier number NCT05119608) including Intensive Care Unit (ICU)-treated COVID-19 survivors, who display symptoms of anxiety and/or depression at follow-up 12 months after hospitalization (Hospital Anxiety and Depression Scale ≥8 for depression or anxiety). Eligible individuals are referred to a psychiatrist for structured diagnostic assessment and inclusion in the trial. Participants will be randomized to either a 10-week cognitive behavioral therapy intervention with added acceptance and commitment therapy (CBT-ACT) or standard care (primary care referral). Primary study outcome measure is feasibility and patient adherence, defined as the proportion of participants who consent to randomization and remain in the study including follow-up. Secondary outcome measures include reduced symptoms in the HADS depression/anxiety subscales, post-traumatic symptoms, HRQoL and user satisfaction at 3 months after the intervention.This protocol describes a pilot trial to assess feasibility and preliminary effects of a structured psycho-therapeutic intervention to ameliorate mental health in a population severely affected by COVID-19, where evidence for structured psycho-therapy is lacking.

Cardiac arrest is characterized depending on location as in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA). Strategies for Post Cardiac Arrest Care were developed based on evidence from OHCA. The aim of this study was to compare characteristics and outcomes in patients admitted to intensive care after IHCA and OHCA.A retrospective multicenter observational study of adult survivors of cardiac arrest admitted to intensive care in southern Sweden between 2014-2018. Data was collected from registries and medical notes. The primary outcome was neurological outcome according to the Cerebral Performance Category (CPC) scale at 2-6 months.799 patients were included, 245 IHCA and 554 OHCA. IHCA patients were older, less frequently male and less frequently without comorbidity. In IHCA the first recorded rhythm was more often non-shockable, all delay-times (ROSC, no-flow, low-flow, time to advanced life support) were shorter and a cardiac cause of the arrest was less common. Good long-term neurological outcome was more common after IHCA than OHCA. In multivariable analysis, witnessed arrest, age, shorter arrest duration (no-flow and low-flow times), low lactate, shockable rhythm, and a cardiac cause were all independent predictors of good long-term neurological outcome whereas location of arrest (IHCA vs OHCA) was not.In patients admitted to intensive care after cardiac arrest, patients who suffered IHCA vs OHCA differed in demographics, co-morbidities, cardiac arrest characteristics and outcomes. In multivariable analyses, cardiac arrest characteristics were independent predictors of outcome, whereas location of arrest (IHCA vs OHCA) was not.

Objective To explore associations between four methods assessing long-term neurocognitive outcome after out-of-hospital cardiac arrest and early hypoxic-ischemic neuronal brain injury assessed by the biomarker serum neurofilament light (NFL), and to compare the agreement for the outcome methods. Methods An explorative post-hoc study was conducted on survivor data from the international Target Temperature Management after Out-of-hospital Cardiac Arrest trial, investigating serum NFL sampled 48/72-hours post-arrest and neurocognitive outcome 6 months post-arrest. Results Among the long-term surviving participants (N = 457), serum NFL (n = 384) was associated to all outcome instruments, also when controlling for demographic and cardiovascular risk factors. Associations between NFL and the patient-reported Two Simple Questions (TSQ) were however attenuated when adjusting for vitality and mental health. NFL predicted results on the outcome instruments to varying degrees, with an excellent area under the curve for the clinician-report Cerebral Performance Category (CPC 1-2: 0.90). Most participants were classified as CPC 1 (79%). Outcome instrument correlations ranged from small (Mini-Mental State Examination [MMSE]-TSQ) to strong (CPC-MMSE). Conclusions The clinician-reported CPC was mostly related to hypoxic-ischemic brain injury, but with a ceiling effect. These results may be useful when selecting methods and instruments for clinical follow-up models.

Background Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting. Methods Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO2 or PaCO2 values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO2 and PaCO2 values, defined as hyperoxemia (PaO2 > 40 kPa), hypoxemia (PaO2 2 > 6.7 kPa) and hypocapnemia (PaCO2 2 > 40 kPa with PaCO2 2 8.0–40 kPa with PaCO2 > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO2 levels and decreasing PaCO2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1–2) and poor (CPC 3–5) was used as outcome measure. Results Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO2 or PaCO2 values and neurological outcome (P = 0.13–0.49). Our secondary analyses showed no significant associations between combinations of PaO2 and PaCO2 and neurological outcome (P = 0.11–0.86). There was no PaO2 or PaCO2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates. Conclusions Exposure to extreme PaO2 or PaCO2 values in the first 24 h after OHCA was common, but not independently associated with neurological outcome at discharge.

Background Sepsis is a common indication for admission to the intensive care unit (ICU). Since definitions vary across studies, comparisons of prevalence and outcomes have been challenging. We aimed to compare sepsis according to ICU discharge codes with sepsis according to Sepsis-3 criteria and to investigate the epidemiology of sepsis in the ICU. We hypothesized that sepsis using discharge codes is underreported. Methods Adult ICU admissions to four ICUs in Sweden between 2015 and 2017 were screened for sepsis according to the Sepsis-3 criteria. Medical records were reviewed and data extracted from the Swedish Intensive Care Registry. Results Of 5990 adult ICU patients, 28% fulfilled the Sepsis-3 criteria on admission, but only 31% of them had sepsis as the registered main diagnosis at ICU discharge. Of the 1654 Sepsis-3 patients, 38% met the septic shock criteria. The Sepsis-3 in-hospital mortality was 26% compared to 33% in patients with septic shock. The incidence rate for ICU-treated sepsis was 81 cases per 100 000 person-years. One in four had a positive blood culture, and 44% were culture negative. Conclusion This large Swedish multicentre study showed that 28% of adult ICU patients fulfilled the Sepsis-3 criteria, but only one third of them had sepsis according to ICU discharge codes. We could confirm our hypothesis, that sepsis is severely underreported in Swedish ICUs, and we conclude that discharge codes should not be used for quality control or research purposes.

Introduction Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been recommended in international guidelines since 2005. The TTM-trial published in 2013 showed no difference in survival or neurological outcome for patients randomised to 33 °C or 36 °C, and many hospitals have changed practice. The optimal utilization of TTM is still debated. This study aimed to analyse if a difference in temperature goal was associated with outcome in an unselected international registry population. Methods This is a retrospective observational study based on a prospective registry — the International Cardiac Arrest Registry 2. Patients were categorized as receiving TTM in the lower range at 32–34 °C (TTM-low) or at 35–37 °C (TTM-high). Primary outcome was good functional status defined as cerebral performance category (CPC) of 1–2 at hospital discharge and secondary outcome was adverse events related to TTM. A logistic regression model was created to evaluate the independent effect of temperature by correcting for clinical and demographic factors associated with outcome. Results Of 1710 patients included, 1242 (72,6%) received TTM-low and 468 (27,4%) TTM-high. In patients receiving TTM-low, 31.3% survived with good outcome compared to 28.8% in the TTM-high group. There was no significant association between temperature and outcome (p = 0.352). In analyses adjusted for baseline differences the OR for a good outcome with TTM-low was 1.27, 95% CI (0.94–1.73). Haemodynamic instability leading to discontinuation of TTM was more common in TTM-low. Conclusions No significant difference in functional outcome at hospital discharge was found in patients receiving lower- versus higher targeted temperature management.

Aims Trends in characteristics, management, and survival in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) were studied in the Swedish Cardiopulmonary Resuscitation Registry (SCRR). Methods and results The SCRR was used to study 106 296 cases of OHCA (1990–2020) and 30 032 cases of IHCA (2004–20) in whom resuscitation was attempted. In OHCA, survival increased from 5.7% in 1990 to 10.1% in 2011 and remained unchanged thereafter. Odds ratios [ORs, 95% confidence interval (CI)] for survival in 2017–20 vs. 1990–93 were 2.17 (1.93–2.43) overall, 2.36 (2.07–2.71) for men, and 1.67 (1.34–2.10) for women. Survival increased for all aetiologies, except trauma, suffocation, and drowning. OR for cardiac aetiology in 2017–20 vs. 1990–93 was 0.45 (0.42–0.48). Bystander cardiopulmonary resuscitation increased from 30.9% to 82.2%. Shockable rhythm decreased from 39.5% in 1990 to 17.4% in 2020. Use of targeted temperature management decreased from 42.1% (2010) to 18.2% (2020). In IHCA, OR for survival in 2017–20 vs. 2004–07 was 1.18 (1.06–1.31), showing a non-linear trend with probability of survival increasing by 46.6% during 2011–20. Myocardial ischaemia or infarction as aetiology decreased during 2004–20 from 67.4% to 28.3% [OR 0.30 (0.27–0.34)]. Shockable rhythm decreased from 37.4% to 23.0% [OR 0.57 (0.51–0.64)]. Approximately 90% of survivors (IHCA and OHCA) had no or mild neurological sequelae. Conclusion Survival increased 2.2-fold in OHCA during 1990–2020 but without any improvement in the final decade, and 1.2-fold in IHCA during 2004–20, with rapid improvement the last decade. Cardiac aetiology and shockable rhythms were halved. Neurological outcome has not improved.

The aim of these guidelines is to provide evidence based guidance for temperature control in adults who are comatose after resuscitation from either in-hospital or out-of-hospital cardiac arrest, regardless of the underlying cardiac rhythm. These guidelines replace the recommendations on temperature management after cardiac arrest included in the 2021 post-resuscitation care guidelines co-issued by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). The guideline panel included thirteen international clinical experts who authored the 2021 ERC-ESICM guidelines and two methodologists who participated in the evidence review completed on behalf of the International Liaison Committee on Resuscitation (ILCOR) of whom ERC is a member society. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations. The panel provided suggestions on guideline implementation and identified priorities for future research. The certainty of evidence ranged from moderate to low. In patients who remain comatose after cardiac arrest, we recommend continuous monitoring of core temperature and actively preventing fever (defined as a temperature > 37.7 degrees C) for at least 72 hours. There was insufficient evidence to recommend for or against temperature control at 32-36 degrees C or early cooling after cardiac arrest. We recommend not actively rewarming comatose patients with mild hypothermia after return of spontaneous circulation (ROSC) to achieve normothermia. We recommend not using prehospital cooling with rapid infusion of large volumes of cold intravenous fluids immediately after ROSC.

Adrenomedullin is a vasoactive hormone with potentially prognostic and therapeutic value, which mainly has been investigated in intensive care unit (ICU) settings. The triaging in the emergency department (ED) of patients to the right level of care is crucial for patient outcome.The primary aim of this study was to investigate the association of bioactive adrenomedullin (bio-ADM) with mortality among sepsis patients in the ED. Secondary aims were to investigate the association of bio-ADM with multiple organ failure (MOF), ICU admission and ED discharge.In this prospective observational cohort study, adult sepsis patients in the ED (2013-2015) had blood samples collected for later batch analysis of bio-ADM. Odds ratios (OR) with 95% confidence interval (CI) for bio-ADM were calculated.Bio-ADM in 594 sepsis patients was analyzed of whom 51 died within 28 days (8.6%), 34 developed severe MOF, 27 were ICU admitted and 67 were discharged from the ED. The median (interquartile range) bio-ADM was 36 (26-56) and 63 (42-132) pg/mL among survivors and non-survivors, respectively, 81 (56-156) pg/mL for patients with severe MOF and 77 (42-133) pg/mL for ICU admitted patients. Each log-2 increment of bio-ADM conferred an OR of 2.30 (95% CI 1.74-3.04) for mortality, the adjusted OR was 2.39 (95% CI 1.69-3.39). The area under the receiver operating characteristic curve of a prognostic mortality model based on demographics and biomarkers increased from 0.80 to 0.86 (p = 0.02) when bio-ADM was added. Increasing bio-ADM was associated with severe MOF, ICU admission and ED discharge with adjusted ORs of 3.30 (95% CI 2.13-5.11), 1.75 (95% CI 1.11-2.77) and 0.46 (95% CI 0.32-0.68), respectively.Bio-ADM in sepsis patients in the ED is associated with mortality, severe MOF, ICU admission and ED discharge, and may be of clinical importance for triage of sepsis patients in the ED.

Background Sedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians. We evaluated differences in patient-level sedation and analgesia dosing in an international multicenter TTM trial to better characterize current practice and clinically important outcomes. Methods A total 950 patients in the international TTM trial were randomly assigned to a TTM of 33 °C or 36 °C after resuscitation from cardiac arrest in 36 intensive care units. We recorded cumulative doses of sedative and analgesic drugs at 12, 24, and 48 h and normalized to midazolam and fentanyl equivalents. We compared number of medications used, dosing, and titration among centers by using multivariable models, including common severity of illness factors. We also compared dosing with time to awakening, incidence of clinical seizures, and survival. Results A total of 614 patients at 18 centers were analyzed. Propofol (70%) and fentanyl (51%) were most frequently used. The average dosages of midazolam and fentanyl equivalents were 0.13 (0.07, 0.22) mg/kg/h and 1.16 (0.49, 1.81) µg/kg/h, respectively. There were significant differences in number of medications (p p p p = 0.40). There were associations between higher dosing at 48 h (p = 0.003, odds ratio [OR] 1.75) and increased titration of analgesics between 24 and 48 h (p = 0.005, OR 4.89) with awakening after 5 days, increased titration of sedatives between 24 and 48 h with awakening after 5 days (p 100), and increased titration of sedatives between 24 and 48 h with a higher incidence of clinical seizures in the multivariate analysis (p = 0.04, OR 240). There were also significant associations between decreased titration of analgesics and survival at 6 months in the multivariate analysis (p = 0.048). Conclusions There is significant variation in choice of drug, dosing, and titration when providing sedation and analgesics between centers. Sedation and analgesia dosing and titration were associated with delayed awakening, incidence of clinical seizures, and survival, but the causal relation of these findings cannot be proven.

BackgroundProenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC).ResultsOf 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75–2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68–0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61–0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction.ConclusionPlasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.

EEG is widely used for prediction of neurologic outcome after cardiac arrest. To better understand the relationship between EEG and neuronal injury, we explored the association between EEG and neurofilament light (NfL) as a marker of neuroaxonal injury, evaluated whether highly malignant EEG patterns are reflected by high NfL levels, and explored the association of EEG backgrounds and EEG discharges with NfL.We performed a post hoc analysis of the Target Temperature Management After Out-of-Hospital Cardiac Arrest trial. Routine EEGs were prospectively performed after the temperature intervention ≥36 hours postarrest. Patients who awoke or died prior to 36 hours postarrest were excluded. EEG experts blinded to clinical information classified EEG background, amount of discharges, and highly malignant EEG patterns according to the standardized American Clinical Neurophysiology Society terminology. Prospectively collected serum samples were analyzed for NfL after trial completion. The highest available concentration at 48 or 72 hours postarrest was used.A total of 262/939 patients with EEG and NfL data were included. Patients with highly malignant EEG patterns had 2.9 times higher NfL levels than patients with malignant patterns and NfL levels were 13 times higher in patients with malignant patterns than those with benign patterns (95% CI 1.4-6.1 and 6.5-26.2, respectively; effect size 0.47;Benign, malignant, and highly malignant EEG patterns reflect the extent of brain injury as measured by NfL in serum. The extent of brain injury is more strongly related to the EEG background than superimposed discharges. Combining EEG and NfL may be useful to better identify patients misclassified by single methods.ClinicalTrials.gov NCT01020916.

Background The clinical importance of immediate coronary angiography, with potentially subsequent percutaneous coronary intervention (PCI), in out-of-hospital cardiac arrest (OHCA) patients without ST-elevation on the ECG is unclear. In this study, we assessed feasibility and safety aspects of performing immediate coronary angiography in a pre-specified pilot phase of the ‘DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest’ (DISCO) randomized controlled trial (ClinicalTrials.gov ID: NCT02309151). Methods Resuscitated bystander witnessed OHCA patients >18 years without ST-elevation on the ECG were randomized to immediate coronary angiography versus standard of care. Event times, procedure related adverse events and safety variables within 7 days were recorded. Results In total, 79 patients were randomized to immediate angiography (n = 39) or standard of care (n = 40). No major differences in baseline characteristics between the groups were found. There were no differences in the proportion of bleedings and renal failure. Three patients randomized to immediate angiography and six patients randomized to standard care died within 24 h. The median time from EMS arrival to coronary angiography was 135 min in the immediate angiography group. In patients randomized to immediate angiography a culprit lesion was found in 14/38 (36.8%) and PCI was performed in all these patients. In 6/40 (15%) patients randomized to standard of care, coronary angiography was performed before the stipulated 3 days. Conclusion In this out-of-hospital cardiac arrest population without ST-elevation, randomization to a strategy to perform immediate coronary angiography was feasible although the time window of 120 min from EMS arrival at the scene of the arrest to start of coronary angiography was not achieved. No significant safety issues were reported.

Aim To describe the detailed health-related quality of life (HRQoL) in survivors from the TTM-trial and to investigate potential differences related to sex and age. Methods This is a cross-sectional study originating from a large prospective international, multicentre trial, including 442 respondents who answered the Short Form-36 item Questionnaire Health Survey version 2® (SF-36v2®) at a structured follow-up 6 months after out-of-hospital cardiac arrest (OHCA). Statistical analysis between independent groups were performed with Mann-Whitney U or Chi-square. Age was analysed primarily as a dichotomised variable. Results Although overall physical and mental health were within the normal range, a substantial proportion of respondents had impaired function at domain-specific levels, particularly in Role-Physical (50%) and Role-Emotional (35%). Females scored significantly lower than males in; Physical Functioning (41.7 vs. 47.9, p 65 years scored significantly better in Vitality (50.8 vs. 53.7, p = 0.006) and Mental Health (50.3 vs. 52.6, p = 0.04). Conclusions Many OHCA survivors demonstrated impaired function in HRQoL at a domain level, despite most patients reporting an acceptable general HRQoL. Females reported worse HRQoL than males. Older age was associated with a worse Physical Functioning but better Vitality and Mental Health. Role-Physical and Role-Emotional aspects of health were especially affected, even when effects of age and sex where accounted for.

Background Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. Methods Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument. Results Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0–3 vs. 4–6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95–100% specificities. Conclusions This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.

Introduction The main objective was to present characteristics and outcome of patients without sustained field return of spontaneous circulation (ROSC) transported to hospital with ongoing cardiopulmonary resuscitation (CPR). Our secondary objectives were to investigate hospital-based interventions and the performance of the universal Termination of Resuscitation-rule (uTOR). Methods In this retrospective observational cohort study, out-of-hospital cardiac arrest (OHCA) patients arriving to the emergency department of a university hospital in Sweden during a six-year period (2010–2015) were identified using a prospectively recorded hospital-based registry. Additional data were retrieved from medical records and from the Swedish cardiopulmonary resuscitation registry. Results Among 409 patients transported with ongoing CPR, 7 survived to hospital discharge (1.7%). Hospital-based interventions against a suspected cause of arrest were attempted during ongoing resuscitation in 34 patients (8.3%), of whom 3 survived to hospital discharge. The remaining 4 survivors had spontaneous in-hospital ROSC. Survivors presented with either a shockable rhythm (n = 4) or pulseless electrical activity (n = 3). The uTOR identified non-survivors with a positive predictive value (PPV) of 98.4% and a specificity of 71.4% for termination. Conclusion Survival after OHCA where sustained prehospital ROSC is not achieved is rare and available in-hospital interventions are rarely utilised. No patient with asystole as the first recorded rhythm survived. The uTOR identified non-survivors with a PPV of 98.4% but showed poor specificity.

The European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) have collaborated to produce these post-resuscitation care guidelines for adults, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include the post-cardiac arrest syndrome, diagnosis of cause of cardiac arrest, control of oxygenation and ventilation, coronary reperfusion, haemodynamic monitoring and management, control of seizures, temperature control, general intensive care management, prognostication, long-term outcome, rehabilitation and organ donation. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06368-4.

Highlights • The results of this study will provide novel information about physical activity among OHCA-survivors. • Physical activity after a cardiac arrest is currently an important knowledge-gap. • The results of this study have a potential to improve support and rehabilitation for OHCA-survivors., Aims The primary aim of this study is to investigate whether out-of-hospital cardiac arrest (OHCA) survivors have lower levels of self-reported physical activity compared to a non-cardiac arrest (CA) control group who had acute myocardial infarction (MI). Additional aims are to explore potential predictors of physical inactivity (older age, female gender, problems with general physical function, global cognition, mental processing speed/attention, anxiety symptoms, depression symptoms, kinesiophobia, fatigue), and to investigate the relationship between self-reported and objectively measured physical activity among OHCA-survivors. Methods The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial) collects information regarding age, gender, self-reported physical activity, general physical function, global cognition and mental processing speed/attention at 6 months after OHCA. In this TTM2-trial cross-sectional prospective sub-study, participants at selected sites are invited to an additional follow-up meeting within 4 weeks from the main study follow-up. At this meeting, information regarding anxiety symptoms, depression symptoms, kinesiophobia and fatigue is collected. The OHCA-survivors are then provided with an objective measure of physical activity, a hip-placed accelerometer, to wear for one week, together with a training diary. At the end of the week, participants are asked to once again answer two self-reported questions regarding physical activity for that specific week. MI-controls attend a single follow-up meeting and perform the same assessments as the OHCA-survivors, except from wearing the accelerometer. We aim to include 110 OHCA-survivors and 110 MI-controls in Sweden, Denmark and the United Kingdom. Conclusion The results from this sub-study will provide novel information about physical activity among OHCA-survivors. Trial registration Registered at ClinicalTrials.gov: NCT03543332, date of registration June 1, 2018

Aim To study the characteristics and outcome among cardiac arrest cases with COVID-19 and differences between the pre-pandemic and the pandemic period in out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). Method and results We included all patients reported to the Swedish Registry for Cardiopulmonary Resuscitation from 1 January to 20 July 2020. We defined 16 March 2020 as the start of the pandemic. We assessed overall and 30-day mortality using Cox regression and logistic regression, respectively. We studied 1946 cases of OHCA and 1080 cases of IHCA during the entire period. During the pandemic, 88 (10.0%) of OHCAs and 72 (16.1%) of IHCAs had ongoing COVID-19. With regards to OHCA during the pandemic, the odds ratio for 30-day mortality in COVID-19-positive cases, compared with COVID-19-negative cases, was 3.40 [95% confidence interval (CI) 1.31–11.64]; the corresponding hazard ratio was 1.45 (95% CI 1.13–1.85). Adjusted 30-day survival was 4.7% for patients with COVID-19, 9.8% for patients without COVID-19, and 7.6% in the pre-pandemic period. With regards to IHCA during the pandemic, the odds ratio for COVID-19-positive cases, compared with COVID-19-negative cases, was 2.27 (95% CI 1.27–4.24); the corresponding hazard ratio was 1.48 (95% CI 1.09–2.01). Adjusted 30-day survival was 23.1% in COVID-19-positive cases, 39.5% in patients without COVID-19, and 36.4% in the pre-pandemic period. Conclusion During the pandemic phase, COVID-19 was involved in at least 10% of all OHCAs and 16% of IHCAs, and, among COVID-19 cases, 30-day mortality was increased 3.4-fold in OHCA and 2.3-fold in IHCA., Graphical Abstract Graphical Abstract

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Background Prognostication of neurological outcome in patients who remain comatose after cardiac arrest resuscitation is complex. Clinical variables, as well as biomarkers of brain injury, cardiac injury, and systemic inflammation, all yield some prognostic value. We hypothesised that cumulative information obtained during the first three days of intensive care could produce a reliable model for predicting neurological outcome following out-of-hospital cardiac arrest (OHCA) using artificial neural network (ANN) with and without biomarkers. Methods We performed a post hoc analysis of 932 patients from the Target Temperature Management trial. We focused on comatose patients at 24, 48, and 72 h post-cardiac arrest and excluded patients who were awake or deceased at these time points. 80% of the patients were allocated for model development (training set) and 20% for internal validation (test set). To investigate the prognostic potential of different levels of biomarkers (clinically available and research-grade), patients’ background information, and intensive care observation and treatment, we created three models for each time point: (1) clinical variables, (2) adding clinically accessible biomarkers, e.g., neuron-specific enolase (NSE) and (3) adding research-grade biomarkers, e.g., neurofilament light (NFL). Patient outcome was the dichotomised Cerebral Performance Category (CPC) at six months; a good outcome was defined as CPC 1–2 whilst a poor outcome was defined as CPC 3–5. The area under the receiver operating characteristic curve (AUROC) was calculated for all test sets. Results AUROC remained below 90% when using only clinical variables throughout the first three days in the ICU. Adding clinically accessible biomarkers such as NSE, AUROC increased from 82 to 94% (p Conclusions In this exploratory study, ANNs provided good to excellent prognostic accuracy in predicting neurological outcome in comatose patients post OHCA. The models which included NSE after 72 h and NFL on all days showed promising prognostic performance.

Background Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis. Methods In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis. Results Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better. Conclusions Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.

The American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.This study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.Using the INTCAR (International Cardiac Arrest Registry), the impact of each proposed "unfavorable feature" on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.Seven unfavorable features (of 10 total) were captured in 2,508 patients successfully resuscitated after cardiac arrest (ongoing cardiopulmonary resuscitation and noncardiac etiology were exclusion criteria in our registry). Chronic kidney disease was used in lieu of end-stage renal disease. In total, 39% survived to hospital discharge. The odds ratio (OR) of survival to hospital discharge for each unfavorable feature was as follows: age85 years OR: 0.30 (95% CI: 0.15 to 0.61), time-to-ROSC30 min OR: 0.30 (95% CI: 0.23 to 0.39), nonshockable rhythm OR: 0.39 (95% CI: 0.29 to 0.54), no bystander cardiopulmonary resuscitation OR: 0.49 (95% CI: 0.38 to 0.64), lactate7 mmol/l OR: 0.50 (95% CI: 0.40 to 0.63), unwitnessed arrest OR: 0.58 (95% CI: 0.44 to 0.78), pH 7.2 OR: 0.78 (95% CI: 0.63 to 0.98), and chronic kidney disease OR: 0.96 (95% CI: 0.70 to 1.33). The presence of any 3 or more unfavorable features predicted 40% survival. Presence of the 3 strongest risk factors (age85 years, time-to-ROSC30 min, and non-ventricular tachycardia/ventricular fibrillation) together or ≥6 unfavorable features predicted a ≤10% chance of survival to discharge.Patients successfully resuscitated from cardiac arrest with 6 or more unfavorable features have a poor long-term prognosis. Delaying or even forgoing invasive procedures in such patients is reasonable.

Purpose To assess the performance of a 4-step algorithm for neurological prognostication after cardiac arrest recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). Methods Retrospective descriptive analysis with data from the Target Temperature Management (TTM) Trial. Associations between predicted and actual neurological outcome were investigated for each step of the algorithm with results from clinical neurological examinations, neuroradiology (CT or MRI), neurophysiology (EEG and SSEP) and serum neuron-specific enolase. Patients examined with Glasgow Coma Scale Motor Score (GCS-M) on day 4 (72–96 h) post-arrest and available 6-month outcome were included. Poor outcome was defined as Cerebral Performance Category 3–5. Variations of the ERC/ESICM algorithm were explored within the same cohort. Results The ERC/ESICM algorithm identified poor outcome patients with 38.7% sensitivity (95% CI 33.1–44.7) and 100% specificity (95% CI 98.8–100) in a cohort of 585 patients. An alternative cut-off for serum neuron-specific enolase, an alternative EEG-classification and variations of the GCS-M had minor effects on the sensitivity without causing false positive predictions. The highest overall sensitivity, 42.5% (95% CI 36.7–48.5), was achieved when prognosticating patients irrespective of GCS-M score, with 100% specificity (95% CI 98.8–100) remaining. Conclusion The ERC/ESICM algorithm and all exploratory multimodal variations thereof investigated in this study predicted poor outcome without false positive predictions and with sensitivities 34.6–42.5%. Our results should be validated prospectively, preferably in patients where withdrawal of life-sustaining therapy is uncommon to exclude any confounding from self-fulfilling prophecies. Electronic supplementary material The online version of this article (10.1007/s00134-020-06080-9) contains supplementary material, which is available to authorized users.

Background This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA. Methods This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite z-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses. Discussion In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA. Trial registration ClinicalTrials.gov, NCT03543371. Registered 1 June 2018