Low PCSK-9 levels Are Associated with Favorable Neurologic Function after Resuscitation from out of Hospital Cardiac Arrest

Endotoxemia after cardiopulmonary resuscitation (CPR) is associated with unfavorable outcome. Proprotein convertase subtilisin/kexin type-9 (PCSK–9) regulates low-density lipoprotein receptors, which mediate the hepatic uptake of endotoxins. We hypothesized that PCSK–9 concentrations are associated with neurological outcome in patients after CPR. Successfully resuscitated out-of-hospital cardiac arrest patients were included prospectively (n = 79). PCSK–9 levels were measured on admission, 12 h and 24 h thereafter, and after rewarming. The primary outcome was favorable neurologic function at day 30, defined by cerebral performance categories (CPC 1–2 = favorable vs. CPC 3–5 = unfavorable). Receiver operating characteristic curve analysis was used to identify the PCSK–9 level cut-off for optimal discrimination between favorable and unfavorable 30-day neurologic function. Logistic regression models were calculated to estimate the effect of PCSK–9 levels on the primary outcome, given as odds ratio (OR) and 95% confidence interval (95%CI). PCSK–9 levels on admission were significantly lower in patients with favorable 30-day neurologic function (median 158 ng/mL, (quartiles: 124–225) vs. 207 ng/mL (174–259); p = 0.019). The optimally discriminating PCSK–9 level cut-off was 165 ng/mL. In patients with PCSK–9 levels ≥ 165 ng/mL, the odds of unfavorable neurological outcome were 4.7-fold higher compared to those with PCSK–9 levels < 165 ng/mL. In conclusion, low PCSK–9 levels were associated with favorable neurologic function.

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A Practical Risk-Score for Early Prediction of Neurological Outcome after Out-of-Hospital Cardiac Arrest –MIRA2CLE2

10.1101/2020.04.12.20045146 ◽

2020 ◽

Author(s):

Nilesh Pareek ◽

Peter Kordis ◽

Nicholas Beckley-Hoelscher ◽

Dominic Pimenta ◽

Spela Tadel Kocjancic ◽

...

Keyword(s):

Cardiac Arrest ◽

Risk Score ◽

Neurological Outcome ◽

Heart Attack ◽

Primary Outcome ◽

Cerebral Performance Category ◽

Epinephrine Administration ◽

Poor Outcome ◽

Poor Neurological Outcome ◽

Hospital Cardiac Arrest

AimsThe purpose of this study was to develop a practical risk−score to predict poor neurological outcome after out−of−hospital cardiac arrest (OOHCA) for use on arrival to a Heart Attack Centre.Methods and ResultsBetween May 2012 and December 2017, 1055 patients had OOHCA in our region, of whom 373 patients were included in the King's Out of Hospital Cardiac Arrest Registry (KOCAR). We performed prediction modelling with multi-variable logistic regression to identify factors independently predictive of the primary outcome in order to derive a risk score. This was externally validated in two independent cohorts comprising 474 patients. The primary outcome was poor neurological function at 6−month follow−up (Cerebral Performance Category 3-−). Seven independent variables for prediction of outcome were identified: Missed (Unwitnessed) arrest, Initial non-shockable rhythm, non-Reactivity of pupils, Age, Changing intra-arrest rhythms, Low pH<;7.20 and Epinephrine administration. From these variables, the MIRA2CLE2 score was developed which had an AUC of 0.90 in the development and 0.85 and 0.89 in the validation cohorts. 3 risk groups of the MIRA2CLE2 were defined − Low risk (≤2−5.6% risk of poor outcome; Intermediate risk (3−4−55.4% of poor outcome) and high risk (≥5−92.3% risk of poor outcome). The risk-score performance was equivalent in a sub-group of patients referred for early angiography and revascularisation where appropriate.ConclusionsThe MIRA2CLE2 score is a practical risk score for early accurate prediction of poor neurological outcome after OOHCA, which has been developed for simplicity of use on admission to a Heart Attack Centre.

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Abstract 44: Time to Epinephrine Impacts Mortality Following Pediatric In-Hospital Nonshockable Cardiac Arrest

Circulation ◽

10.1161/circ.130.suppl_2.44 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Lars W Andersen ◽

Katherine Berg ◽

Brian Z Saindon ◽

Joseph M Massaro ◽

Tia T Raymond ◽

...

Keyword(s):

Cardiac Arrest ◽

Hospital Discharge ◽

Neurological Outcome ◽

Spontaneous Circulation ◽

National Registry ◽

Epinephrine Administration ◽

Negatively Associated ◽

Logistic Regression Models ◽

Shockable Rhythm ◽

Hospital Cardiac Arrest

Background: Delay in administration of the first epinephrine dose has been shown to be associated with a lower chance of good outcome in adult, in-hospital, non-shockable cardiac arrest. Whether this association is true in pediatric in-hospital non-shockable cardiac arrest remains unknown. Methods: We utilized the Get With the Guidelines - Resuscitation national registry to identify pediatric patients (age < 18 years) with an in-hospital cardiac arrest between 2000 and 2010. We included patients with an initial non-shockable rhythm who received at least one dose of epinephrine. To assess the association between time to epinephrine administration and survival to discharge we used multivariate logistic regression models with adjustment for multiple predetermined variables including age, gender, illness category, pre-existing mechanical ventilation, monitored, witnessed, location, time of the day/week, year of arrest, insertion of an airway, initial rhythm, time to initiation of cardiopulmonary resuscitation, hospital type and hospital teaching status. Secondary outcomes included return of spontaneous circulation (ROSC) and neurological outcome. Results: 1,131 patients were included. Median age was 9 months (quartiles: 21 days - 6 years) and 46% were female. Overall survival to hospital discharge was 29%. Longer time to epinephrine was negatively associated with survival to discharge in multivariate analysis (OR: 0.94 [95%CI: 0.90 - 0.98], per minute delay). Longer time to epinephrine was negatively associated with ROSC (OR: 0.93 [95%CI: 0.90 - 0.97], per minute delay) but was not statistically significantly associated with survival with good neurological outcome (OR: 0.95 [95%CI: 0.89 - 1.03], per minute delay). Conclusions: Delay in administration of epinephrine during pediatric in-hospital cardiac arrest with a non-shockable rhythm is associated with a lower chance of ROSC and lower survival to hospital discharge.

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Factors Associated with the Prescribing of High-Intensity Statins

Journal of Clinical Medicine ◽

10.3390/jcm9123850 ◽

2020 ◽

Vol 9 (12) ◽

pp. 3850

Author(s):

Armando Chaure-Pardos ◽

Sara Malo ◽

María José Rabanaque ◽

Federico Arribas ◽

Belén Moreno-Franco ◽

...

Keyword(s):

Statin Therapy ◽

High Intensity ◽

Management Practices ◽

Characteristic Curve ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Statin Treatment ◽

Moderate Intensity ◽

Physically Active ◽

Logistic Regression Models

In this study, we investigated the relationship between sociodemographic, clinical, anthropometric, and lifestyle characteristics and the type of statin prescribed for primary prevention of cardiovascular disease (CVD). We conducted an observational study in workers who began statin treatment. Statin therapy was categorized as “high-intensity” or “low–moderate-intensity”. Workers were classified according to the alignment of their statin therapy with the recommended management practices. Logistic regression models were used to evaluate the association between the different variables studied and the probability of being prescribed high-intensity statins. The only variables associated with a higher probability of being treated with high-intensity statins were increased physical activity (>40 versus <20 METs (metabolic equivalent of task) h/wk; odds ratio (OR), 1.65; 95%CI, 1.08–2.50) and, in diabetics, higher low-density lipoprotein cholesterol (LDL-C) levels (≥155 mg/dL versus <155 mg/dL; OR, 4.96; 95%CI, 1.29–19.10). The model that best predicted treatment intensity included LDL-C, diabetes, hypertension, smoking, and age (area under the Receiver Operating Characteristic curve (AUC), 0.620; 95%CI, 0.574–0.666). The prescribing and type of statin used in primary CVD prevention did not correspond with the indications in current guidelines. The probability of receiving high-intensity statins was higher in diabetics with high LDL-C levels and in more physically active individuals. These findings underscore the great variability and uncertainty in the prescribing of statins.

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Serum S100 Protein Is a Reliable Predictor of Brain Injury After Out-of-Hospital Cardiac Arrest: A Cohort Study

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.624825 ◽

2021 ◽

Vol 8 ◽

Author(s):

Martin Kleissner ◽

Marek Sramko ◽

Jan Kohoutek ◽

Josef Kautzner ◽

Jiri Kettner

Keyword(s):

Cardiac Arrest ◽

Neurological Outcome ◽

Characteristic Curve ◽

S100 Protein ◽

Cerebral Performance Category ◽

False Positive Prediction ◽

Multivariable Regression ◽

Favorable Neurological Outcome ◽

Hospital Cardiac Arrest

Purpose: To evaluate serum S100 protein at hospital admission and after 48 h in early neuroprognostication of comatose survivors of out-of-hospital cardiac arrest (OHCA).Methods: The study included 48 consecutive patients after OHCA, who survived for at least 72 h after the event. The patients were divided based on their best cerebral performance category (CPC) achieved over a 30 day follow-up period: favorable neurological outcome (CPC 1–2) vs. unfavorable neurological outcome (CPC 3–4). Predictors of an unfavorable neurological outcome were identified by multivariable regression analysis. Analysis of the receiver operating characteristic curve (ROC) was used to determine the cut-off value for S100, having a 0% false-positive prediction rate.Results: Of the 48 patients, 30 (63%) had a favorable and 18 (38%) had an unfavorable neurological outcome. Eleven patients (23%) died over the 30 day follow-up. Increased S100 levels at 48 h after OHCA, but not the baseline S100 levels, were independently associated with unfavorable neurological outcome, with an area under the ROC curve of 0.85 (confidence interval 0.74–0.96). A 48 h S100 value ≥0.37 μg/L had a specificity of 100% and sensitivity of 39% in predicting an unfavorable 30 day neurological outcome.Conclusion: This study showed that S100 values assessed 48 h after an OHCA could independently predict an unfavorable neurological outcome at 30 days.

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Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study

Critical Care ◽

10.1186/s13054-021-03606-5 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Sivagowry Rasalingam Mørk ◽

Carsten Stengaard ◽

Louise Linde ◽

Jacob Eifer Møller ◽

Lisette Okkels Jensen ◽

...

Keyword(s):

Logistic Regression ◽

Cardiac Arrest ◽

Survival Rate ◽

Neurological Outcome ◽

Mechanical Circulatory Support ◽

Circulatory Support ◽

Good Neurological Outcome ◽

Factors Associated ◽

National Consensus ◽

Hospital Cardiac Arrest

Abstract 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.

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Echocardiographic parameters during prolonged targeted temperature Management in out-of-hospital Cardiac Arrest Survivors to predict neurological outcome – a post-hoc analysis of the TTH48 trial

Scandinavian Journal of Trauma Resuscitation and Emergency Medicine ◽

10.1186/s13049-021-00849-7 ◽

2021 ◽

Vol 29 (1) ◽

Author(s):

Thomas Hvid Jensen ◽

Peter Juhl-Olsen ◽

Bent Roni Ranghøj Nielsen ◽

Johan Heiberg ◽

Christophe Henri Valdemar Duez ◽

...

Keyword(s):

Cardiac Arrest ◽

Neurological Outcome ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Targeted Temperature Management ◽

Temperature Management ◽

Left Ventricular Ejection ◽

Secondary Outcome ◽

Ventricular Ejection Fraction ◽

Hospital Cardiac Arrest

Abstract Background Transthoracic echocardiographic (TTE) indices of myocardial function among survivors of out-of-hospital cardiac arrest (OHCA) have been related to neurological outcome; however, results are inconsistent. We hypothesized that changes in average peak systolic mitral annular velocity (s’) from 24 h (h) to 72 h following start of targeted temperature management (TTM) predict six-month neurological outcome in comatose OHCA survivors. Methods We investigated the association between peak systolic velocity of the mitral plane (s’) and six-month neurological outcome in a population of 99 patients from a randomised controlled trial comparing TTM at 33 ± 1 °C for 24 h (h) (n = 47) vs. 48 h (n = 52) following OHCA (TTH48-trial). TTE was conducted at 24 h, 48 h, and 72 h after reaching target temperature. The primary outcome was 180 days neurological outcome assessed by Cerebral Performance Category score (CPC180) and the primary TTE outcome measure was s’. Secondary outcome measures were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), e’, E/e’ and tricuspid annular plane systolic excursion (TAPSE). Results Across all three scan time points s’ was not associated with neurological outcome (ORs: 24 h: 1.0 (95%CI: 0.7–1.4, p = 0.98), 48 h: 1.13 (95%CI: 0.9–1.4, p = 0.34), 72 h: 1.04 (95%CI: 0.8–1.4, p = 0.76)). LVEF, GLS, E/e’, and TAPSE recorded on serial TTEs following OHCA were neither associated with nor did they predict CPC180. Estimated median e’ at 48 h following TTM was 5.74 cm/s (95%CI: 5.27–6.22) in patients with good outcome (CPC180 1–2) vs. 4.95 cm/s (95%CI: 4.37–5.54) in patients with poor outcome (CPC180 3–5) (p = 0.04). Conclusions s’ assessed on serial TTEs in comatose survivors of OHCA treated with TTM was not associated with CPC180. Our findings suggest that serial TTEs in the early post-resuscitation phase during TTM do not aid the prognostication of neurological outcome following OHCA. Trial registration NCT02066753. Registered 14 February 2014 – Retrospectively registered,

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The Effect of Implementing Mechanical Cardiopulmonary Resuscitation Devices on Out-of-Hospital Cardiac Arrest Patients in an Urban City of Taiwan

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073636 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3636

Author(s):

Yi-Rong Chen ◽

Chi-Jiang Liao ◽

Han-Chun Huang ◽

Cheng-Han Tsai ◽

Yao-Sing Su ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Primary Outcome ◽

Medical Service ◽

Spontaneous Circulation ◽

High Quality ◽

Urban City ◽

Service Response Time ◽

Mechanical Cpr ◽

Hospital Cardiac Arrest

High-quality cardiopulmonary resuscitation (CPR) is a key element in out-of-hospital cardiac arrest (OHCA) resuscitation. Mechanical CPR devices have been developed to provide uninterrupted and high-quality CPR. Although human studies have shown controversial results in favor of mechanical CPR devices, their application in pre-hospital settings continues to increase. There remains scant data on the pre-hospital use of mechanical CPR devices in Asia. Therefore, we conducted a retrospective cohort study between September 2018 and August 2020 in an urban city of Taiwan to analyze the effects of mechanical CPR devices on the outcomes of OHCA; the primary outcome was attainment of return of spontaneous circulation (ROSC). Of 552 patients with OHCA, 279 received mechanical CPR and 273 received manual CPR, before being transferred to the hospital. After multivariate adjustment for the influencing factors, mechanical CPR was independently associated with achievement of any ROSC (OR = 1.871; 95%CI:1.195–2.930) and sustained (≥24 h) ROSC (OR = 2.353; 95%CI:1.427–3.879). Subgroup analyses demonstrated that mechanical CPR is beneficial in shorter emergency medical service response time (≤4 min), witnessed cardiac arrest, and non-shockable cardiac rhythm. These findings support the importance of early EMS activation and high-quality CPR in OHCA resuscitation.

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Intraosseous versus intravenous vascular access during cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a systematic review and meta-analysis of observational studies

Scandinavian Journal of Trauma Resuscitation and Emergency Medicine ◽

10.1186/s13049-021-00858-6 ◽

2021 ◽

Vol 29 (1) ◽

Author(s):

Yu-Lin Hsieh ◽

Meng-Che Wu ◽

Jon Wolfshohl ◽

James d’Etienne ◽

Chien-Hua Huang ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Hospital Discharge ◽

Vascular Access ◽

Subgroup Analysis ◽

Observational Studies ◽

Primary Outcome ◽

Meta Analysis ◽

Cochrane Library ◽

Hospital Cardiac Arrest

Abstract Introduction This study is aimed to investigate the association of intraosseous (IO) versus intravenous (IV) route during cardiopulmonary resuscitation (CPR) with outcomes after out-of-hospital cardiac arrest (OHCA). Methods We systematically searched PubMed, Embase, Cochrane Library and Web of Science from the database inception through April 2020. Our search strings included designed keywords for two concepts, i.e. vascular access and cardiac arrest. There were no limitations implemented in the search strategy. We selected studies comparing IO versus IV access in neurological or survival outcomes after OHCA. Favourable neurological outcome at hospital discharge was pre-specified as the primary outcome. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the I2 statistics. Time to intervention, defined as time interval from call for emergency medical services to establishing vascular access or administering medications, was hypothesized to be a potential outcome moderator and examined in subgroup analysis with meta-regression. Results Nine retrospective observational studies involving 111,746 adult OHCA patients were included. Most studies were rated as high quality according to Newcastle-Ottawa Scale. The pooled results demonstrated no significant association between types of vascular access and the primary outcome (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27–1.33; I2, 95%). In subgroup analysis, time to intervention was noted to be positively associated with the pooled OR of achieving the primary outcome (OR: 3.95, 95% CI, 1.42–11.02, p: 0.02). That is, when the studies not accounting for the variable of “time to intervention” in the statistical analysis were pooled together, the meta-analytic results between IO access and favourable outcomes would be biased toward inverse association. No obvious publication bias was detected by the funnel plot. Conclusions The meta-analysis revealed no significant association between types of vascular access and neurological outcomes at hospital discharge among OHCA patients. Time to intervention was identified to be an important outcome moderator in this meta-analysis of observation studies. These results call for the need for future clinical trials to investigate the unbiased effect of IO use on OHCA CPR.

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Predictive Value of Estimated Lean Body Mass for Neurological Outcomes after Out-of-Hospital Cardiac Arrest

Journal of Clinical Medicine ◽

10.3390/jcm10010071 ◽

2020 ◽

Vol 10 (1) ◽

pp. 71

Author(s):

Sung Eun Lee ◽

Hyuk Hoon Kim ◽

Minjung Kathy Chae ◽

Eun Jung Park ◽

Sangchun Choi

Keyword(s):

Cardiac Arrest ◽

Critically Ill ◽

Lean Body Mass ◽

Body Mass ◽

Multivariate Regression ◽

Characteristic Curve ◽

Cerebral Performance Category ◽

High Body Mass Index ◽

Neurological Outcomes ◽

Hospital Cardiac Arrest

Background: Postcardiac arrest patients with a return of spontaneous circulation (ROSC) are critically ill, and high body mass index (BMI) is ascertained to be associated with good prognosis in patients with a critically ill condition. However, the exact mechanism has been unknown. To assess the effectiveness of skeletal muscles in reducing neuronal injury after the initial damage owing to cardiac arrest, we investigated the relationship between estimated lean body mass (LBM) and the prognosis of postcardiac arrest patients. Methods: This retrospective cohort study included adult patients with ROSC after out-of-hospital cardiac arrest from January 2015 to March 2020. The enrolled patients were allocated into good- and poor-outcome groups (cerebral performance category (CPC) scores 1–2 and 3–5, respectively). Estimated LBM was categorized into quartiles. Multivariate regression models were used to evaluate the association between LBM and a good CPC score. The area under the receiver operating characteristic curve (AUROC) was assessed. Results: In total, 155 patients were analyzed (CPC score 1–2 vs. 3–5, n = 70 vs. n = 85). Patients’ age, first monitored rhythm, no-flow time, presumed cause of arrest, BMI, and LBM were different (p < 0.05). Fourth-quartile LBM (≥48.98 kg) was associated with good neurological outcome of postcardiac arrest patients (odds ratio = 4.81, 95% confidence interval (CI), 1.10–25.55, p = 0.04). Initial high LBM was also a predictor of good neurological outcomes (AUROC of multivariate regression model including LBM: 0.918). Conclusions: Initial LBM above 48.98kg is a feasible prognostic factor for good neurological outcomes in postcardiac arrest patients.

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