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The prognosis after out-of-hospital cardiac arrest (OHCA) has improved in the past few decades because of advances in interventions used outside and in hospital. About half of patients who have OHCA with initial ventricular tachycardia or ventricular fibrillation and who are admitted to hospital in coma after return of spontaneous circulation will survive to discharge with a reasonable neurological status. In this Series paper we discuss in-hospital management of patients with post-cardiac-arrest syndrome. In most patients, the most important in-hospital interventions other than routine intensive care are continuous active treatment (in non-comatose and comatose patients and including circulatory support in selected patients), cooling of core temperature to 32–36°C by targeted temperature management for at least 24 h, immediate coronary angiography with or without percutaneous coronary intervention, and delay of final prognosis until at least 72 h after OHCA. Prognosis should be based on clinical observations and multimodal testing, with focus on no residual sedation.

The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far. The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies. As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%). The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.

Quantitative pupillometry is part of multimodal neuroprognostication of comatose patients after out-of-hospital cardiac arrest (OHCA). However, the reproducibility, repeatability, and reliability of quantitative pupillometry in this setting have not been investigated. In a prospective blinded validation study, we compared manual and quantitative measurements of pupil size. Observer and device variability for all available parameters are expressed as mean difference (bias), limits of agreement (LoA), and reliability expressed as intraclass correlation coefficients (ICC) with a 95% confidence interval. Fifty-six unique quadrupled sets of measurement derived from 14 sedated and comatose patients (mean age 70±12 years) were included. Automated quantitative pupillometry has excellent reliability and twice the reproducibility and repeatability than manual pupillometry. This study further presents novel estimates of variability for all quantitative pupillary response parameters with excellent reliability.

Background Pre-hospital circumstances, cardiac arrest characteristics, comorbidities and clinical status on admission are strongly associated with outcome after out-of-hospital cardiac arrest (OHCA). Early prediction of outcome may inform prognosis, tailor therapy and help in interpreting the intervention effect in heterogenous clinical trials. This study aimed to create a model for early prediction of outcome by artificial neural networks (ANN) and use this model to investigate intervention effects on classes of illness severity in cardiac arrest patients treated with targeted temperature management (TTM). Methods Using the cohort of the TTM trial, we performed a post hoc analysis of 932 unconscious patients from 36 centres with OHCA of a presumed cardiac cause. The patient outcome was the functional outcome, including survival at 180 days follow-up using a dichotomised Cerebral Performance Category (CPC) scale with good functional outcome defined as CPC 1–2 and poor functional outcome defined as CPC 3–5. Outcome prediction and severity class assignment were performed using a supervised machine learning model based on ANN. Results The outcome was predicted with an area under the receiver operating characteristic curve (AUC) of 0.891 using 54 clinical variables available on admission to hospital, categorised as background, pre-hospital and admission data. Corresponding models using background, pre-hospital or admission variables separately had inferior prediction performance. When comparing the ANN model with a logistic regression-based model on the same cohort, the ANN model performed significantly better ( p  = 0.029). A simplified ANN model showed promising performance with an AUC above 0.852 when using three variables only: age, time to ROSC and first monitored rhythm. The ANN-stratified analyses showed similar intervention effect of TTM to 33 °C or 36 °C in predefined classes with different risk of a poor outcome. Conclusion A supervised machine learning model using ANN predicted neurological recovery, including survival excellently, and outperformed a conventional model based on logistic regression. Among the data available at the time of hospitalisation, factors related to the pre-hospital setting carried most information. ANN may be used to stratify a heterogenous trial population in risk classes and help determine intervention effects across subgroups.

PurposeNew-onset atrial fibrillation (NOAF) is common and associated with increased morbidity and mortality. However, its clinical importance and management in critically ill patients are not well described. The aim of this scoping review is to assess the epidemiology and management strategies of NOAF during critical illness.MethodThe review was conducted in accordance with the PRISMA extension for scoping reviews. We searched PubMed, EMBASE and the Cochrane Library for studies assessing the incidence, outcome and management strategies of NOAF in adult critically ill patients. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.ResultsA total of 99 studies were included, of which 79 were observational and 20 were interventional. The incidence of NOAF varied from 1.7% to 43.9% with considerable inter-population variation (very low quality of evidence). Commonly identified risk factors for NOAF included higher age, cardiovascular comorbidities and sepsis. The occurrence of NOAF was associated with adverse outcomes, including stroke, prolonged length of stay and mortality (very low quality of evidence). We found limited data on the optimal management strategy with no evidence for firm benefit or harm for any intervention (very low/low quality of evidence).ConclusionsThe definition and incidence of NOAF in critically ill patients varied considerably and many risk factors were identified. NOAF seemed to be associated with adverse outcomes, but data were very limited and current management strategies are not evidence-based.

Most studies in acute myocardial infarction complicated by cardiogenic shock (AMICS) include patients presenting with and without out-of-hospital cardiac arrest (OHCA). The aim was to compare OHCA and non-OHCA AMICS patients in terms of hemodynamics, management in the intensive care unit (ICU) and outcome. From a cohort corresponding to two thirds of the Danish population, all patients with AMICS admitted from 2010-2017 were individually identified through patient records. A total of 1716 AMICS patients were identified of which 723 (42%) presented with OHCA. A total of 1532 patients survived to ICU admission. At the time of ICU arrival, there were no differences between OHCA and non-OHCA AMICS patients in variables commonly used in the AMICS definition (mean arterial pressure (MAP) (72mmHg vs 70mmHg, p = 0.12), lactate (4.3mmol/L vs 4.0mmol/L, p = 0.09) and cardiac output (CO) (4.6L/min vs 4.4L/min, p = 0.30)) were observed. However, during the initial days of ICU treatment OHCA patients had a higher MAP despite a lower need for vasoactive drugs, higher CO, SVO2 and lactate clearance compared to non-OHCA patients (p<0.05 for all). In multivariable analysis outcome was similar but cause of death differed significantly with hypoxic brain injury being leading cause in OHCA and cardiac failure in non-OHCA AMICS patients. OHCA and non-OHCA AMICS patients initially have comparable metabolic and hemodynamic profiles, but marked differences develop between the groups during the first days of ICU treatment. Thus, pooling of OHCA and non-OHCA patients as one clinical entity in studies should be done with caution.

Cardiogenic shock remains the leading cause of in-hospital death in acute myocardial infarction (AMI). Because of temporary changes in management of cardiogenic shock with widespread implementation of early revascularization along with increasing attention to the use of mechanical circulatory devices, complete and longitudinal data are important in this subject. The objective of this study was to examine temporal trends of first-time hospitalization, management, and short-term mortality for patients with AMI-related cardiogenic shock (AMICS). Using nationwide medical registries, we identified patients hospitalized with first-time AMI and cardiogenic shock from January 1, 2005, through December 31, 2017. We calculated annual incidence proportions of AMICS. Thirty-day mortality was estimated with use of Kaplan-Meier estimator comparing AMICS and AMI-only patients. Multivariable Cox regression models were used to assess mortality rate ratios. We included 101,834 AMI patients of whom 7,040 (7%) had AMICS. The median age was 72 (interquartile range: 62-80) for AMICS and 69 (interquartile range: 58-79) for AMI-only patients. The gender composition was similar between AMICS and AMI-only patients (male: 64% vs 63%). The annual incidence proportion of AMICS decreased slightly over time (2005: 7.0% vs 2017: 6.1%, P for trend < .0001). In AMICS, use of coronary angiography increased between 2005 and 2017 from 48% to 71%, as did use of left ventricular assist device (1% vs 10%) and norepinephrine (30% to 70%). In contrast, use of intra-aortic balloon pump (14% vs 1%) and dopamine (34% vs 20%) decreased. Thirty-day mortality for AMICS patients was 60% (95% CI: 59-61) and substantially higher than the 8% (95% CI: 7.8-8.2) for AMI-only patients (mortality rate ratio: 11.4, 95% CI: 10.9-11.8). Over time, the mortality decreased after AMICS (2005: 68% to 2017: 57%, P for temporal change in adjusted analysis < .0001). We observed a slight decrease in AMICS hospitalization over time with changing practice patterns. Thirty-day mortality was markedly higher for patients with AMICS compared with AMI only, yet our results suggest improved 30-day survival over time after AMICS.

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  < 0.01). The prognostic accuracy remained excellent from day 1 to day 3 with an AUROC at approximately 95% when adding research-grade biomarkers. The models which included NSE after 72 h and NFL on any of the three days had a low risk of false-positive predictions while retaining a low number of false-negative predictions. 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 Comatose patients admitted after resuscitation from cardiac arrest have a significant risk of poor outcome due to hypoxic brain injury. While numerous studies have investigated and challenged the target temperature as the efficacious part of the guideline endorsed Targeted Temperature Management (TTM) protocols, our knowledge and how the remaining parts of the TTM are optimized remain sparse. The present randomized trial investigated two aspects of the TTM protocol: target blood pressure during the ICU stay and oxygenation during mechanical ventilation. Furthermore, the efficacy of device-based post-TTM fever management is addressed. Methods Investigator-initiated, dual-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Patients are eligible for inclusion if unconscious, older than 18 years of age, and have return of spontaneous circulation for more than 20 min. Intervention: allocation 1:1:1:1 into a group defined by (a) blood pressure targets in double-blind intervention targeting a mean arterial blood pressure of 63 or 77 mmHg and (b) restrictive (9–10 kPa) or liberal (13–14 kPa) of arterial oxygen concentration during mechanical ventilation. As a subordinate intervention, device-based active fever management is discontinued after 36 h or 72. Patients will otherwise receive protocolized standard of care according to international guidelines, including targeted temperature management at 36 °C for 24 h, sedation with fentanyl and propofol, and multimodal neuro-prognostication. Primary endpoint: Discharge from hospital in poor neurological status (Cerebral Performance category 3 or 4) or death, whichever comes first. Secondary outcomes: Time to initiation of renal replacement therapy or death, neuron-specific enolase (NSE) level at 48 h, MOCA score at day 90, Modified Ranking Scale (mRS) and CPC at 3 months, NT-pro-BNP at 90 days, eGFR and LVEF at 90 days, daily cumulated vasopressor requirement during ICU stay, and need for a combination of vasopressors and inotropic agents or mechanical circulatory support. Discussion We hypothesize that low or high target blood pressure and restrictive and liberal oxygen administration will have an impact on mortality by reducing the risk and degree of hypoxic brain injury. This will be assessment neurological outcome and biochemical and neuropsychological testing after 90 days. Trial registration ClinicalTrials.gov NCT03141099. Registered on May 2017 (retrospectively registered)

Background Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. Methods This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. Results A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients . Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18–1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03–1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12–1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76). Conclusions A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.