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OBJECTIVES: This study aimed to describe the burden of illness and impact on health and working situation among former intensive care patients treated for COVID-19. METHODS: A prospective cohort study was performed at one intensive care unit of a university hospital in Sweden during the first wave of COVID-19 in spring 2020. The burden of illness in health status, cognitive, physical, and psychological outcomes, and working situation were assessed at four and 12 months after discharge from intensive care, using nine validated instruments. RESULTS: Forty-six participants treated for COVID-19 participated in both follow-ups and were included in this study. General fatigue was reported by 37 of 46 participants (82%) at both follow-ups (p = 1.000). For overall health status 28 (61%) participants at the first follow-up and 26 (57%) (p = 0.414) at the second reported lower values than the general population. Cognitive impairment was seen in 22 (52%) participants at four months and in 13 (31%) at 12 months (p = 0.029). The proportion of participants on sick-leave decreased between the first and second follow-up (24% vs 13%, p = 0.025), but the proportion of participants working full-time was almost the same at both follow-ups (35% vs 37%, p = 0.317). CONCLUSIONS: The burden of illness of patients treated in intensive care due to COVID-19 included cognitive, physical, and psychological impacts. Cognitive functions were improved after 12 months, but no clear improvements could be distinguished in the physical or psychological outcome. Higher burden of illness was associated with inability to return to work.

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 aim of this study was to investigate potential markers of coagulopathy and the effects of thromboprophylaxis with low-molecular-weight heparin (LMWH) on thromboelastography (TEG) and anti-factor Xa in critically ill COVID-19 patients. Material and Methods We conducted a prospective study in 31 consecutive adult intensive care unit (ICU) patients. TEG with and without heparinase and anti-factor Xa analysis were performed. Standard thromboprophylaxis was given with dalteparin (75–100 IU/kg subcutaneously). Results Five patients (16%) had symptomatic thromboembolic events. All patients had a maximum amplitude (MA) > 65 mm and 13 (42%) had MA > 72 mm at some point during ICU stay. Anti-factor Xa activity were below the target range in 23% of the patients and above target range in 46% of patients. There was no significant correlation between dalteparin dose and anti-factor Xa activity. Conclusions Patients with COVID-19 have hypercoagulability with high MA on TEG. The effect of LMWH on thromboembolic disease, anti-factor Xa activity and TEG was variable and could not be reliably predicted. This indicates that standard prophylactic doses of LMWH may be insufficient. Monitoring coagulation and the LMWH effect is important in patients with COVID-19 but interpreting the results in relation to risk of thromboembolic disease poses difficulties., Highlights • COVID-19 is associated with increased maximum amplitude on thromboelastography. • The association between dalteparin dose and anti-factor Xa activity is weak. • Standard prophylactic low molecular weight heparin dose may be insufficient. • Monitoring coagulation and LMWH effects in COVID-19 patients is important.

ImportanceWhile much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.ObjectiveTo estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recoveryDesignWe jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.ResultsAnalyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8–312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38–7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9–92.4), 60.4% (18.9–89.1), and 35.4% (9.4–75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84–4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10–9.78]). At twelve months, 15.1% (10.3–21.1) continued to experience long COVID symptoms.Conclusions and relevanceThe occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key PointsQuestionWhat are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?FindingsGlobally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.MeaningThe substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

Introduction Low socioeconomic status has been associated with worse outcome after cardiac arrest. This study aims to investigate if patients´ income influences the probability to receive early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients. Methods In this nationwide retrospective observational study, 3906 OHCA patients admitted alive and registered in the Swedish Registry for Cardiopulmonary Resuscitation were included. Individual data on income and educational level, prehospital parameters, coronary angiography results and comorbidity were linked from SWEDEHEART and other national registers. Results Patients were divided into quarters depending on their income level. In the unadjusted model there was a strong correlation between income level and rate of early coronary angiography where 35.5% of patients in the highest income quarters received early angiography compared to 15.4% in the lowest income quarters. When adjusting for educational level, sex, age, comorbidity and hospital type, there were still higher chance of receiving early coronary angiography with increasing income, OR 1.31 (CI 1.01–1.68) and 1.67 (CI 1.29–2.16) for the two highest income quarters respectively compared to the lowest income quarter. When adding potential mediators to the model (first recorded ECG rhythm by the EMS, location, response time, bystander cardiopulmonary resuscitation and if the arrest was witnessed) no difference in early angiography related to income level where found. The main mediator was first recorded ECG rhythm. Conclusion Income level is associated with the probability to undergo early coronary angiography in OHCA patients. This association seems to be mediated by the initial ECG rhythm.

This is a non-final version of an article published in final form in Lipcsey, Tenhunen, Pischke, Kuitunen, Flaatten, De Geer, Sjölin, Frithiof, Chew, Bendel, Kawati, Larsson, Mollnes, Tønnessen, Rubertsson. Endotoxin removal in septic shock with the Alteco LPS Adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial - the Asset Study. Shock. 2020;54(2):224-231. Purpose: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed. Methods: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients. Results: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups. Conclusions: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care.

Background The remaining symptoms in patients with coronavirus disease 2019 (COVID‐19) treated in intensive care unit are limited described. Therefore, we assessed patient's perception of their COVID‐19 disease, stay in intensive care, and remaining symptoms three to six months after intensive care. Methods Prospective cohort study was performed in one intensive care unit of a university hospital in Sweden during the first wave. A questionnaire with open‐ended questions and closed‐ended questions was used. Data were analyzed using qualitative and quantitative content analysis and descriptive statistics. Results Out of 123 patients treated for COVID‐19, 64 answered the questionnaire 3–6 months after discharge from intensive care. Memories from illness and hospital stay revealed in three categories; awareness of the illness, losing anchor to reality and being cared for in a dynamic environment. Information was perceived as spare by 48% and they wanted the information to be more personal. The diary was perceived as personal and was received by 33% patients. The relationship with family was affected among 39% and 13% of the patients indicated that they had not resumed their daily life. A large amount, 84%, indicated that they had remaining symptoms from COVID‐19. The dominated symptoms were impaired strength and energy both physically and mentally. Conclusion Patients reported a variety of physical and mental symptoms, and revealed memories from the ICU, and specific awareness of other patients’ health. It illustrates the need for screening patients for remaining symptoms after COVID‐19 disease and ICU care and may affect resuming patients’ daily life.

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. Supplementary Information The online version contains supplementary material available at 10.1007/s00439-021-02397-7.

Introduction We investigated the impact of gender in performance and findings of early coronary angiography (CAG) and percutaneous coronary intervention (PCI), comorbidity and outcome in a large population of out-of-hospital cardiac arrest (OHCA) patients with an initially shockable rhythm. Methods Retrospective cohort study. Data retrieved 2008–2013 from the Swedish Register for Cardio-Pulmonary Resuscitation, Swedeheart Registry and National Patient Register. Results We identified 1498 patients of whom 78% were men. Men and women had the same pathology on the first registered electrocardiogram (ECG): 30% vs. 29% had ST-elevation and 10% vs. 9% had left bundle branch block (LBBB) (P = 0.97). Proportions of performed CAG did not differ between genders. Among patients without ST-elevation/LBBB men more often had at least one significant stenosis, 78% vs. 54% (P = 0.001), more multi-vessel disease (P = 0.01), had normal coronary angiography less often, 22% vs. 46% and PCI more often, 59% vs. 42% (P = 0.03). Among patients without ST-elevation/LBBB on the initial ECG, more men had previously known ischaemic heart disease, 27% vs. 19% (P = 0.02) and a presumed cardiac origin of the cardiac arrest, 86% vs. 72% (P Conclusion Despite no gender differences in ECG findings indicating an early CAG, men had more severe coronary artery disease while women more frequently had normal coronary angiography. However, this did not influence 1-year survival.

Background: In out-of-hospital cardiac arrest, chest compression–only cardiopulmonary resuscitation (CO-CPR) has emerged as an alternative to standard CPR (S-CPR), using both chest compressions and rescue breaths. Since 2010, CPR guidelines recommend CO-CPR for both untrained bystanders and trained bystanders unwilling to perform rescue breaths. The aim of this study was to describe changes in the rate and type of CPR performed before the arrival of emergency medical services (EMS) during 3 consecutive guideline periods in correlation to 30-day survival. Methods: All bystander-witnessed out-of-hospital cardiac arrests reported to the Swedish register for cardiopulmonary resuscitation in 2000 to 2017 were included. Nonwitnessed, EMS-witnessed, and rescue breath–only CPR cases were excluded. Patients were categorized as receivers of no CPR (NO-CPR), S-CPR, or CO-CPR before EMS arrival. Guideline periods 2000 to 2005, 2006 to 2010, and 2011 to 2017 were used for comparisons over time. The primary outcome was 30-day survival. Results: A total of 30 445 patients were included. The proportions of patients receiving CPR before EMS arrival changed from 40.8% in the first time period to 58.8% in the second period, and to 68.2% in the last period. S-CPR changed from 35.4% to 44.8% to 38.1%, and CO-CPR changed from 5.4% to 14.0% to 30.1%, respectively. Thirty-day survival changed from 3.9% to 6.0% to 7.1% in the NO-CPR group, from 9.4% to 12.5% to 16.2% in the S-CPR group, and from 8.0% to 11.5% to 14.3% in the CO-CPR group. For all time periods combined, the adjusted odds ratio for 30-day survival was 2.6 (95% CI, 2.4–2.9) for S-CPR and 2.0 (95% CI, 1.8–2.3) for CO-CPR, in comparison with NO-CPR. S-CPR was superior to CO-CPR (adjusted odds ratio, 1.2; 95% CI, 1.1–1.4). Conclusions: In this nationwide study of out-of-hospital cardiac arrest during 3 periods of different CPR guidelines, there was an almost a 2-fold higher rate of CPR before EMS arrival and a concomitant 6-fold higher rate of CO-CPR over time. Any type of CPR was associated with doubled survival rates in comparison with NO-CPR. These findings support continuous endorsement of CO-CPR as an option in future CPR guidelines because it is associated with higher CPR rates and overall survival in out-of-hospital cardiac arrest.

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.

Background Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. Methods Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury. Results There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine. Conclusions Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.

BACKGROUND: Acute kidney Injury (AKI) is a syndrome of reduced glomerular filtration rate and/or reduced urine flow associated with mortality in corona virus disease 2019 (COVID-19). AKI is often associated with renal tissue damage, which may lead to chronic kidney disease. Biomarkers of tissue damage may identify patients of particular risk. METHODS: In a prospective observational study of 57 patients admitted to intensive care, AKI incidence and characteristics was evaluated according to KDIGO criteria and related to days after admission. Urinary albumin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM-1) and Plasma Tissue Inhibitor of MetalloProteinase 2 (TIMP-2) were analysed in 52 patients at admission. RESULTS: The majority (n=51, 89%) of patients developed AKI, and 27 (47%) patients had predominantly oliguric AKI where oliguria was more severe than plasma Creatinine increase. Severe oliguria within first 2 days after admission was common (n=37, 65%) while stage 2 and 3 AKI due to Creatinine occurred later than day 2 in 67% (12/18) of cases. Renal replacement therapy was started in 9 (16%) patients, and 30-day mortality was 28%. Urinary biomarkers were increased in a majority of patients, but did not robustly predict KDIGO stage. Most patients had microalbuminuria, and severe albuminuria (albumin Creatinine ratio > 30 mg/mmol) was found in n=9 (17%) patients. CONCLUSIONS: A majority of patients with COVID-19 admitted to the ICU develop AKI. The functional deficit is often low urinary volume, and initial levels of biomarkers are generally increased without clear relation to final AKI stage.

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.

Aim Strategies to increase provision of bystander CPR include mass education of laypersons. Additionally, programs directed at emergency dispatchers to provide CPR instructions during emergency calls to untrained bystanders have emerged. The aim of this study was to evaluate the association between dispatcher-assisted CPR (DA- CPR) and 30-day survival compared with no CPR or spontaneously initiated CPR by lay bystanders prior to emergency medical services in out of hospital cardiac arrest (OHCA). Methods Nationwide observational cohort study including all consecutive lay bystander witnessed OHCAs reported to the Swedish Register for Cardiopulmonary Resuscitation in 2010–2017. Exposure was categorized as: no CPR (NO-CPR), DA-CPR and spontaneously initiated CPR (SP-CPR) prior to EMS arrival. Propensity-score matched cohorts were used for comparison between groups. Main Outcome was 30-day survival. Results A total of 15 471 patients were included and distributed as follows: NO-CPR 6440 (41.6%), DA-CPR 4793 (31.0%) and SP-CPR 4238 (27.4%). Survival rates to 30 days were 7.1%, 13.0% and 18.3%, respectively. In propensity-score matched analysis (DA-CPR as reference), NO-CPR was associated with lower survival (conditional OR 0.61, 95% CI 0.52–0.72) and SP-CPR was associated with higher survival (conditional OR 1.21 (95% CI 1.05–1.39). Conclusions DA-CPR was associated with a higher survival compared with NO-CPR. However, DA-CPR was associated with a lower survival compared with SP-CPR. These results reinforce the vital role of DA-CPR, although continuous efforts to disseminate CPR training must be considered a top priority if survival after out of hospital cardiac arrest is to continue to increase.

The potential benefit of early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients without ST elevation on ECG is unclear. The aim of this study was to evaluate the association between early coronary angiography and survival in these patients.Nationwide observational study between 2008 and 2013. Included were patients admitted to hospital after witnessed OHCA, with shockable rhythm, age 18 to 80 years and unconscious. Patients with ST-elevation on ECG were excluded. Patients that underwent early CAG (within 24 hours) were compared with no early CAG (later during the hospital stay or not at all). Outcomes were survival at 30 days, 1 year, and 3 years. Multivariate analysis included pre-hospital factors, comorbidity and ECG-findings.In total, 799 OHCA patients fulfilled the inclusion criteria, of which 275 (34%) received early CAG versus 524 (66%) with no early CAG. In the early CAG group, the proportion of patients with an occluded coronary artery was 27% and 70% had at least one significant coronary stenosis (defined as narrowing of coronary lumen diameter of ≥50%). The 30-day survival rate was 65% in early CAG group versus 52% with no early CAG (P.001). The adjusted OR was 1.42 (95% CI 1.00-2.02). The one-year survival rate was 62% in the early CAG group versus 48% in the no early CAG group with the adjusted hazard ratio of 1.35 (95% CI 1.04-1.77).In this population of bystander-witnessed cases of out-of-hospital cardiac arrest with shockable rhythm and ECG without ST elevation, early coronary angiography may be associated with improved short and long term survival.

Background Using cerebral oxygen venous saturation post-cardiac arrest (CA) is limited because of a small sample size and prior to establishment of target temperature management (TTM). We aimed to describe variations in jugular bulb oxygen saturation during intensive care in relation to neurological outcome at 6 months post- CA in cases where TTM 33°C was applied. Method Prospective observational study in patients over 18 years, comatose immediately after resuscitation from CA. Patients were treated with TTM 33°C M and received a jugular bulb catheter within the first 26 hours post-CA. Neurological outcome was assessed at 6 months using the Cerebral Performance Categories (CPC) and dichotomized into good (CPC 1-2) and poor outcome (CPC 3-5). Results Seventy-five patients were included and 37 (49%) patients survived with a good outcome at 6 months post-CA. No differences were found between patients with good outcome and poor outcome in jugular bulb oxygen saturation. Higher values were seen in differences in oxygen content between central venous oxygen saturation and jugular bulb oxygen saturation in patients with good outcome compared to patients with poor outcome at 6 hours (12 [8-21] vs 5 [-0.3 to 11]% P = .001) post-CA. Oxygen extraction fraction from the brain illustrated lower values in patients with poor outcome compared to patients with good outcome at 96 hours (14 [9-23] vs 31 [25-34]% P = .008). Conclusions Oxygen delivery and extraction differed in patients with a good outcome compared to those with a poor outcome at single time points. Based on the present findings, the usefulness of jugular bulb oxygen saturation for prognostic purposes is uncertain in patients treated with TTM 33°C post-CA.

Background: No practical tool quantitates the risk of circulatory-etiology death (CED) immediately after successful cardiopulmonary resuscitation in patients without ST-segment–elevation myocardial infarction. We developed and validated a prediction model to rapidly determine that risk and facilitate triage to individualized treatment pathways. Methods: With the use of INTCAR (International Cardiac Arrest Registry), an 87-question data set representing 44 centers in the United States and Europe, patients were classified as having had CED or a combined end point of neurological-etiology death or survival. Demographics and clinical factors were modeled in a derivation cohort, and backward stepwise logistic regression was used to identify factors independently associated with CED. We demonstrated model performance using area under the curve and the Hosmer-Lemeshow test in the derivation and validation cohorts, and assigned a simplified point-scoring system. Results: Among 638 patients in the derivation cohort, 121 (18.9%) had CED. The final model included preexisting coronary artery disease (odds ratio [OR], 2.86; confidence interval [CI], 1.83–4.49; P ≤0.001), nonshockable rhythm (OR, 1.75; CI, 1.10–2.77; P=0.017), initial ejection fractionP =0.002), shock at presentation (OR, 2.27; CI, 1.42–3.62; P25 minutes (OR, 1.42; CI, 0.90–2.23; P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow test P=0.47. Outcomes were similar in the 318-patient validation cohort (area under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for each associated factor in the derivation model, the average predicted versus observed probability of CED with a CREST score (coronary artery disease, initial heart rhythm, low ejection fraction, shock at the time of admission, and ischemic time >25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus 19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%. Conclusions: The CREST model stratified patients immediately after resuscitation according to risk of a circulatory-etiology death. The tool may allow for estimation of circulatory risk and improve the triage of survivors of cardiac arrest without ST-segment–elevation myocardial infarction at the point of care.

There is limited knowledge about the long-term effects on pulmonary function of COVID-19 in patients that required intensive care treatment. Spirometry and diffusing capacity for carbon monoxide (DLCO) were measured in 60 subjects at 3-6 months post discharge. Impaired lung function was found in 52% of the subjects, with reduced DLCO as the main finding. The risk increased with age above 60 years, need for mechanical ventilation and longer ICU stay as well as lower levels of C-reactive protein at admission. This suggests the need of follow-up with pulmonary function testing in intensive-care treated patients.

3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016.The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse.3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry.In the clinical case, the concentration of 3-MeO-PCP was 0.14μg/g at admission, 0.08μg/g 2.5h after admission, 0.06μg/g 5h after admission and 0.04μg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05μg/g to 0.38μg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well.Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.

Introduction The relations between specific ECG patterns and coronary angiographic findings in cardiac arrest patients with different comorbidities are not properly assessed. More evidence is needed to identify patients with the highest risk for acute coronary artery disease as a cause of the cardiac arrest. This study aims to describe the coronary artery findings after cardiac arrest in relation to ECG and comorbidity. Method A retrospective study of out-of-hospital cardiac arrest patients, with coronary angiography performed within 28 days. ECG on admission, comorbidity, PCI attempts and angiographic findings are described. Data were retrieved from national registries in Sweden. Results Among 1133 patients with available ECG and angiography information the mean age was 64 years. The rate of shockable rhythm was 79%. The total incidence of any significant stenosis in cardiac arrest patients without ST-elevation who underwent coronary angiography within 28 days was 71%. The incidence of any stenosis in patients with normal ECG was 62.1% and in patients with LBBB, 59.3%. In patients with ST-depression or RBBB, PCI attempts were made in 47.1% and 42.4% respectively, compared with 33.3% in patients with normal ECG. Among patients without ST-elevation, those with diabetes mellitus and those with initial shockable rhythm respectively, 84.8% and 71.5 had at least one significant stenosis. Conclusion Our study suggests, that evaluation of ECG patterns and comorbidities in out-of-hospital cardiac arrest patients without ST-segment elevation may be important to identify those with a high risk of coronary artery lesions that could benefit from early revascularization.

Highlights • Fifteen cytokines were increased at ICU admission in Covid-19 patients. • A relatively moderate increase in cytokine concentrations was observed. • IL-1ra, IL-6 and IP-10 correlated with respiratory failure and acute kidney injury. • IL-8 may be a future biomarker due to its correlation with 30-day mortality., Background The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients. Method 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality. Results A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality. Conclusion The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.

The aim of this review is to update and discuss the use of mechanical chest compression devices in treatment of cardiac arrest.Three recently published large multicenter randomized trials have not been able to show any improved outcome in adult out-of-hospital cardiac arrest patients when compared with manual chest compressions.Mechanical chest compression devices have been developed to better deliver uninterrupted chest compressions of good quality. Prospective large randomized studies have not been able to prove a better outcome compared to manual chest compressions; however, latest guidelines support their use when high-quality manual chest compressions cannot be delivered. Mechanical chest compressions can also be preferred during transportation, in the cath-lab and as a bridge to more invasive support like extracorporeal membrane oxygenation.

We studied resuscitation process metrics in patients with out-of-hospital cardiac arrest enrolled in a randomized trial comparing one protocol designed to best use a mechanical CPR device, with another based on the 2005 European Resuscitation Council guidelines for manual CPR.We analyzed clinical data, ECG signals, and transthoracic impedance signals for a subset of the patients in the LUCAS in Cardiac Arrest (LINC) trial, including 124 patients randomized to mechanical and 82 to manual CPR. Chest compression fraction (CCF) was defined as the fraction of time during cardiac arrest that chest compressions were administered.Patients in the mechanical CPR group had a higher CCF than those in the manual CPR group [0.84 (0.78, 0.91) vs. 0.79 (0.70, 0.86), p0.001]. The median duration of their pauses for defibrillation was also shorter [0 s (0, 6.0) vs. 10.0 s (7.0, 14.3), p0.001]. Compressions were interrupted for a median of 36.0 s to apply the compression device. There was no difference between groups in duration of the longest pause in compressions [32.5s vs. 26.0 s, p = 0.24], number of compressions received per minute [86.5 vs. 88.3, p = 0.47], defibrillation success rate [73.2% vs. 81.0%, p = 0.15], or refibrillation rate [74% vs. 77%, p = 0.79].A protocol using mechanical chest compression devices reduced interruptions in chest compressions, and enabled defibrillation during ongoing compressions, without adversely affecting other resuscitation process metrics. Future emphasis on optimizing device deployment may be beneficial.

To evaluate the outcomes of cardiac arrest survivors with myoclonus receiving modern postresuscitation care.

Aim of the study To investigate serum levels of glial fibrillary acidic protein (GFAP) for evaluation of neurological outcome in cardiac arrest (CA) patients and compare GFAP sensitivity and specificity to that of more studied biomarkers neuron-specific enolas (NSE) and S100B. Method A prospective observational study was performed in three hospitals in Sweden during 2008-2012. The participants were 125 CA patients treated with therapeutic hypothermia (TH) to 32-34 °C for 24 hours. Samples were collected from peripheral blood (n = 125) and the jugular bulb (n = 47) up to 108 hours post-CA. GFAP serum levels were quantified using a novel, fully automated immunochemical method. Other biomarkers investigated were NSE and S100B. Neurological outcome was assessed using the Cerebral Performance Categories scale (CPC) and dichotomized into good and poor outcome. Results GFAP predicted poor neurological outcome with 100% specificity and 14-23% sensitivity at 24, 48 and 72 hours post-CA. The corresponding values for NSE were 27-50% sensitivity and for S100B 21-30% sensitivity when specificity was set to 100%. A logistic regression with stepwise combination of the investigated biomarkers, GFAP, did not increase the ability to predict neurological outcome. No differences were found in GFAP, NSE and S100B levels when peripheral and jugular bulb blood samples were compared. Conclusion Serum GFAP increase in patients with poor outcome but did not show sufficient sensitivity to predict neurological outcome after CA. Both NSE and S100B were shown to be better predictors. The ability to predict neurological outcome did not increased when combining the three biomarkers.

Despite a lack of randomized trials, practice guidelines recommend that mild induced hypothermia be considered for comatose survivors of in-hospital cardiac arrest. This study describes the safety, feasibility, and outcomes of mild induced hypothermia treatment following in-hospital cardiac arrest.Prospective, observational, registry-based study.Forty-six critical care facilities in eight countries in Europe and the United States reporting in the Hypothermia Network Registry and the International Cardiac Arrest Registry.A total of 663 patients with in-hospital cardiac arrest and treated with mild induced hypothermia were included between January 2004 and February 2012.None.A cerebral performance category of 1 or 2 was considered a good outcome. At hospital discharge 41% of patients had a good outcome. At median 6-month follow-up, 34% had a good outcome. Among in-hospital deaths, 52% were of cardiac causes and 44% of cerebral cause. A higher initial body temperature was associated with reduced odds of a good outcome (odds ratio, 0.79; 95% CI, 0.68-0.92). Adverse events were common; bleeding requiring transfusion (odds ratio, 0.56; 95% CI, 0.31-1.00) and sepsis (odds ratio, 0.52; 95% CI, 0.30-0.91) were associated with reduced odds for a good outcome.In this registry study of an in-hospital cardiac arrest population treated with mild induced hypothermia, we found a 41% good outcome at hospital discharge and 34% at follow-up. Infectious complications occurred in 43% of cases, and 11% of patients required a transfusion for bleeding. The majority of deaths were of cardiac origin.

Magnetic resonance imaging (MRI) of the brain including diffusion-weighted imaging (DWI) is reported to have high prognostic accuracy in unconscious post-cardiac arrest (CA) patients. We documented acute MRI findings in the brain in both conscious and unconscious post-CA patients treated with target temperature management (TTM) at 32-34°C for 24 h as well as the relation to patients' neurological outcome after 6 months.A prospective observational study with MRI was performed regardless of the level of consciousness in post-CA patients treated with TTM. Neurological outcome was assessed using the Cerebral Performance Categories scale and dichotomized into good and poor outcome.Forty-six patients underwent MRI at 3-5 days post-CA. Patients with good outcome had minor, mainly frontal and parietal, lesions. Acute hypoxic/ischemic lesions on MRI including DWI were more common in patients with poor outcome (P = 0.007). These lesions affected mostly gray matter (deep or cortical), with or without involvement of the underlying white matter. Lesions in the occipital and temporal lobes, deep gray matter and cerebellum showed strongest associations with poor outcome. Decreased apparent diffusion coefficient, was more common in patients with poor outcome.Extensive acute hypoxic/ischemic MRI lesions in the cortical regions, deep gray matter and cerebellum detected by visual analysis as well as low apparent diffusion coefficient values from quantitative measurements were associated with poor outcome. Patients with good outcome had minor hypoxic/ischemic changes, mainly in the frontal and parietal lobes.

Assessment of neurologic prognosis after cardiac arrest. Updated recommendations from the Swedish CPR Council Expert Group European Resuscitation Council (ERC) issued updated guidelines for postresuscitation care in 2015. This paper provides updated Swedish recommendations for neurological prognostication of patients remaining unconscious after cardiac arrest (CA). The prognostication should be based on independent methods; clinical and neurophysiological examinations, imaging and biomarkers. It should not be performed earlier than three days after CA and any influence from sedatives must be negligible. Bilateral absence of both corneal and pupillary reflexes and bilaterally absent Somatosensory Evoked N20 Potentials (SSEP) at 72 hours are reliable predictors of poor outcome but the ocular reflexes have limited sensitivity and SSEP has limited availability. Hence, further delay of at least 24 hours and combinations of findings from multiple methods are often needed for reliable prognostication. If firm evidence of a poor prognosis is lacking four days after CA, further expectation with repeated examinations is recommended.

Acute coronary syndrome is a common cause of out-of-hospital cardiac arrest (OHCA). In patients with OHCA presenting with ST elevation, immediate coronary angiography and potential percutaneous coronary intervention (PCI) after return of spontaneous circulation are recommended. However, the evidence for this invasive strategy in patients without ST elevation is limited. Observational studies have shown a culprit coronary artery occlusion in about 30% of these patients, indicating the electrocardiogram's (ECG's) limited sensitivity. The aim of this study is to determine whether immediate coronary angiography and subsequent PCI will provide outcome benefits in OHCA patients without ST elevation.We describe the design of the DIrect or Subacute Coronary angiography in Out-of-hospital cardiac arrest study (DISCO)-a pragmatic national, multicenter, randomized, clinical study. OHCA patients presenting with no ST elevation on their first recorded ECG will be randomized to a strategy of immediate coronary angiography or to standard of care with admission to intensive care and angiography after 3days at the earliest unless the patient shows signs of acute ischemia or hemodynamic instability. Primary end point is 30-day survival. An estimated 1,006 patients give 80% power (α = .05) to detect a 20% improved 30-day survival rate from 45% to 54%. Secondary outcomes include good neurologic recovery at 30days and 6months, and cognitive function and cardiac function at 6months.This randomized clinical study will evaluate the effect of immediate coronary angiography after OHCA on 30-day survival in patients without ST elevation on their first recorded ECG.

Aim To describe changes in rate of CPR, Compression Only CPR (CO-CPR), and 30–day survival over 3 different time-periods of CPR guidelines in Sweden. We hypothesised that increased use of CO-CPR would be associated with increased CPR-rates and similar survival compared to standard CPR. Methods Registry based cohort study including all bystander witnessed cases of out-of-hospital cardiac arrests reported to the Swedish register for cardio-pulmonary resuscitation in 2000–2014. Exposure was categorised as bystander CPR or No-CPR. Bystander CPR was further categorised into Standard CPR with rescue breathing and ventilation (S-CPR) or CO-CPR. Primary outcome was 30 day survival. Results 23620 patients were included. Total rates of bystander CPR increased from 36% in 2000 to 68% in 2014. S-CPR increased from 31% in 2000 to 38% in 2014. CO-CPR increased from 5% in 2000 to 30% 2014. Overall, there was no significant difference in survival among patients receiving CO-CPR or S-CPR (13.6% vs. 12.9% p=0.3). Conclusion Increase in bystander CPR during the last 15 years in Sweden was associated with an increase in CO-CPR. Overall 30 day survival was not different when comparing CO-CPR to S-CPR. Conflict of interest None declared. Funding None declared.

Cardiopulmonary resuscitation is started in 5000 victims of out-of-hospital cardiac arrest in Sweden each year and the survival rate is approximately 10%. The subsequent development of a global ischaemic brain injury is the major determinant of the neurological prognosis for those patients who reach the hospital alive. Induced hypothermia is a recommended treatment after cardiac arrest and has been implemented in most Swedish hospitals. Recent studies indicate that induced hypothermia may affect neurological prognostication and previous international recommendations are therefore no longer valid when hypothermia is applied. An expert group from the Swedish Resuscitation Council has reviewed the literature and made recommendations taking into account the effects of induced hypothermia and concomitant sedation. A delayed neurological evaluation at 72 h after rewarming is recommended for hypothermia treated patients. This evaluation should be based on several independent methods and the possibility of lingering pharmacological effects should be considered.

Decrease of the human brain temperature was induced by intranasal cooling. The main purpose of this study was to compare the two magnetic resonance methods for monitoring brain temperature changes during cooling: phase-difference and magnetic resonance spectroscopic imaging (MRSI) with high spatial resolution. Ten healthy volunteers were measured. Selective brain cooling was performed through nasal cavities using saline-cooled balloon catheters. MRSI was based on a radiofrequency spoiled gradient echo sequence. The spectral information was encoded by incrementing the echo time of the subsequent eight image records. Reconstructed voxel size was 1×1×5 mm(3). Relative brain temperature was computed from the positions of water spectral lines. Phase maps were obtained from the first image record of the MRSI sequence. Mild hypothermia was achieved in 15-20 min. Mean brain temperature reduction varied in the interval-3.0; -0.6°C and-2.7; -0.7°C as measured by the MRSI and phase-difference methods, respectively. Very good correlation was found in all locations between the temperatures measured by both techniques except in the frontal lobe. Measurements in the transversal slices were more robust to the movement artifacts than those in the sagittal planes. Good agreement was found between the MRSI and phase-difference techniques.

The LINC trial evaluated two ALS-CPR algorithms for OHCA patients, consisting of 3min' mechanical chest compression (LUCAS) cycles with defibrillation attempt through compressions vs. 2min' manual compressions with compression pause for defibrillation. The PARAMEDIC trial, using 2min' algorithm found worse outcome for patients with initial VF/VT in the LUCAS group and they received more adrenalin compared to the manual group. We wanted to evaluate if these algorithms had any outcome effect for patients still in VF/VT after the initial defibrillation and how adrenalin timing impacted it.Both groups received manual chest compressions first. Based on non-electronic CPR process documentation, outcome, neurologic status and its relation to CPR duration prior to the first detected return of spontaneous circulation (ROSC), time to defibrillation and adrenalin given were analysed in the subgroup of VF/VT patients.Seven hundred and fifty-seven patients had still VF/VT after initial chest compressions combined with a defibrillation attempt (374 received mechanical CPR) or not (383 received manual CPR). No differences were found for ROSC (mechanical CPR 58.3% vs. manual CPR 58.6%, p=0.94), or 6-month survival with good neurologic outcome (mechanical CPR 25.1% vs. manual CPR 23.0%, p=0.50). A significant difference was found regarding the time from start of manual chest compression to the first defibrillation (mechanical CPR: 4 (2-5) min vs manual CPR 3 (2-4) min, P0.001). The time from the start of manual chest compressions to ROSC was longer in the mechanical CPR group.No difference in short- or long-term outcomes was found between the 2 algorithms for patients still in VF/VT after the initial defibrillation. The time to the 1st defibrillation and the interval between defibrillations were longer in the mechanical CPR group without impacting the overall outcome. The number of defibrillations required to achieve ROSC or adrenalin doses did not differ between the groups.

To describe relatives' experiences during the next of kin's hospital stay after surviving a cardiac arrest (CA) treated with hypothermia at an intensive care unit (ICU).Twenty relatives were interviewed when the person having suffered the CA was discharged from hospital, 1.5 to 6 weeks post-CA. Data were analysed using qualitative content analysis.Three themes are described: The first period of chaos, Feeling secure in a difficult situation, and Living in a changed existence. Relatives found it difficult to assimilate the medical information and wanted it in written form. They wanted honest and clear information about their next of kin's condition and prognosis. They lacked rehabilitation plans after discharge from the medical ward. Relatives felt a need to maintain telephone contact with family members and friends, which was time-consuming. They felt guilty and had a conscience about these feelings. Relatives felt uncertain about the future, but still hopeful.Relatives asked for more information and individual rehabilitation plans. Booklets describing CA, the ICU stay and continuing care and rehabilitation directed at both the patients and their relatives are needed. Follow-up visits to the ICU staff, for both patients and relatives, need to be arranged. Hospitals should consider having a rehabilitation plan for this group of patients, which is presented by a team of healthcare professionals and that focuses on the individual's situation, including the consequences of their heart disease and brain damage.

Aim of the study We recently reported that female sex protects against cerebral and cardiac injury after hypovolemic cardiac arrest (CA), independent of sex hormone effects. As female sex was also associated with a smaller increase in inducible and neuronal nitric oxide synthase (NOS), we hypothesised that nitric oxide inhibition with methylene blue (MB) improves the outcome, primarily in male animals. Methods Twenty sexually immature piglets (10 males and 10 females) were bled to mean arterial blood pressure of 35mmHg, and were subjected to 2min of untreated CA followed by 8min of open chest cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3mlkg −1 hypertonic saline-dextran. Methylene blue was then administered as bolus of 2.5mgkg −1 over 20min, followed by 1.5mgkg −1 infusion over 40min. Historical data from 21 animals were used as control (no MB). Hemodynamic parameters, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. Histopathological evaluation of heart specimens was performed. Results There were no differences between male and female animals in survival or resuscitation rate. After CA female piglets had significantly greater systolic and mean arterial pressures, and had lower troponin I plasma concentrations compared to male piglets, with or without MB. No difference was observed in histopathological analysis of heart specimens between sexes. Conclusions After resuscitation from hypovolemic CA, female sex protects against cardiac injury, independent of sex hormones. Modulation of NO expression with MB does not improve survival or myocardial histological injury in either sex.

Background Neurological outcome after cardiac arrest (CA) is difficult to predict in the acute phase. In this pilot study, we assessed blood levels of tau protein as a prognostic marker for the neurological outcome after 6 months in patients treated with hypothermia after resuscitation from CA. Methods 22 unconscious patients resuscitated after CA were treated with mild hypothermia (32–34°C) for 26 h. Blood samples were collected at 2, 6, 12, 24, 48, and 96 h after CA, and the concentration of tau protein was analyzed. Neurological outcome was assessed with the Glasgow-Pittsburgh cerebral performance category (CPC) scale at intensive care unit (ICU) discharge and after 6 months. The higher of the two CPC scores was used. Results At ICU discharge, 21/22 patients were alive, of whom 10 had a good (CPC 1–2) outcome. After 6 months, 15/22 patients were alive, of whom 14 had a good outcome. Tau protein levels were higher among those with a poor outcome at 48 h and 96 h. At 96 h sampling, tau concentration predicted a poor outcome (CPC 3–5) with a sensitivity of 71% and a specificity of 93%. Conclusions Although in a pilot study, a late increase in plasma tau protein seems to be associated with a worse outcome after hypothermia treatment after CA, although more studies are needed.

The LUCAS™ device has been shown to improve organ perfusion during cardiac arrest in experimental studies. In this pilot study the aim was to compare short-term survival between cardiopulmonary resuscitation (CPR) performed with mechanical chest compressions using the LUCAS™ device and CPR performed with manual chest compressions. The intention was to use the results for power calculation in a larger randomised multicentre trial.In a prospective pilot study, from February 1, 2005, to April 1, 2007, 149 patients with out-of hospital cardiac arrest in two Swedish cities were randomised to mechanical chest compressions or standard CPR with manual chest compressions.After exclusion, the LUCAS and the manual groups contained 75 and 73 patients, respectively. In the LUCAS and manual groups, spontaneous circulation with a palpable pulse returned in 30 and 23 patients (p = 0.30), spontaneous circulation with blood pressure above 80/50 mm Hg remained for at least 5 min in 23 and 19 patients (p = 0.59), the number of patients hospitalised alive4h were 18 and 15 (p = 0.69), and the number discharged, alive 6 and 7 (p = 0.78), respectively.In this pilot study of out-of-hospital cardiac arrest patients we found no difference in early survival between CPR performed with mechanical chest compression with the LUCAS™ device and CPR with manual chest compressions. Data have been used for power calculation in a forthcoming multicentre trial.

Objective Representatives of five international critical care societies convened topic specialists and a nonexpert jury to review, assess, and report on studies of targeted temperature management and to provide clinical recommendations. Data sources Questions were allocated to experts who reviewed their areas, made formal presentations, and responded to questions. Jurors also performed independent searches. Sources used for consensus derived exclusively from peer-reviewed reports of human and animal studies. Study selection Question-specific studies were selected from literature searches; jurors independently determined the relevance of each study included in the synthesis. Conclusions and recommendations 1) The jury opines that the term "targeted temperature management" replace "therapeutic hypothermia." 2) The jury opines that descriptors (e.g., "mild") be replaced with explicit targeted temperature management profiles. 3) The jury opines that each report of a targeted temperature management trial enumerate the physiologic effects anticipated by the investigators and actually observed and/or measured in subjects in each arm of the trial as a strategy for increasing knowledge of the dose/duration/response characteristics of temperature management. This enumeration should be kept separate from the body of the report, be organized by body systems, and be made without assertions about the impact of any specific effect on the clinical outcome. 4) The jury STRONGLY RECOMMENDS targeted temperature management to a target of 32°C-34°C as the preferred treatment (vs. unstructured temperature management) of out-of-hospital adult cardiac arrest victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation, moderate quality of evidence). 5) The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33°C-35.5°C (vs. less structured management) in the treatment of term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy (weak recommendation, moderate quality of evidence).

OBJECTIVE: To conduct a pilot study to evaluate the blood levels of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100B as prognostic markers for neurological outcome 6 months after hypothermia treatment following resuscitation from cardiac arrest. DESIGN: Prospective observational study. SETTING: One intensive care unit at Uppsala University Hospital. PATIENTS: Thirty-one unconscious patients resuscitated after cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Unconscious patients after cardiac arrest with restoration of spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34°C for 26h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108h after ROSC. Neurological outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC) scale at discharge from intensive care and again 6 months later, when 15/31 patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the predictive biomarkers, S-100B at 24h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96h after ROSC predicted poor outcome, with sensitivity of 57% and specificity of 93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest to target temperature was shorter for those with poor outcome. CONCLUSIONS: The blood concentration of S-100B at 24h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest.