Whether admission C-reactive protein (aCRP) concentrations are associated with neurological outcome after out-of-hospital cardiac arrest (OHCA) is controversial. Based on established kinetics of CRP, ...we hypothesized that aCRP may reflect the pre-arrest state of health and investigated associations with neurological outcome. Prospectively collected data from the Vienna Clinical Cardiac Arrest Registry of the Department of Emergency Medicine were analysed. Adults (≥ 18 years) who suffered a non-traumatic OHCA between January 2013 and December 2018, without return of spontaneous circulation or extracorporeal cardiopulmonary resuscitation therapy were eligible. The primary endpoint was a composite of unfavourable neurologic function or death (defined as Cerebral Performance Category 3-5) at 30 days. Associations of CRP levels drawn within 30 min of hospital admission were assessed using binary logistic regression. ACRP concentrations were overall low in our population (n = 832), but higher in the unfavourable outcome group median: 0.44 (quartiles 0.15-1.44) mg/dL vs. 0.26 (0.11-0.62) mg/dL, p < 0.001. The crude odds ratio for higher aCRP concentrations was 1.19 (95% CI 1.10-1.28, p < 0.001, per mg/dL) to have unfavourable neurological outcome. After multivariate adjustment for traditional prognostication markers the odds ratio of higher aCRP concentrations was 1.13 (95% CI 1.04-1.22, p = 0.002). Sensitivity of aCRP was low, but specificity for unfavourable neurological outcome was 90% for the cut-off at 1.5 mg/dL and 97.5% for 5 mg/dL CRP. In conclusion, high aCRP levels are associated with unfavourable neurological outcome at day 30 after OHCA.
Respiratory syncytial virus (RSV) is a well-known pathogen in paediatric patients. However, it also causes substantial morbidity and mortality in adults, posing a major healthcare problem. We present ...a patient with chronic pulmonary conditions and an acute RSV infection, thus leading to cardiac arrest (CA). We speculate that RSV as the causative agent for CA should be considered in post-resuscitation care. From a wider public health perspective, immuno-naivety for RSV caused by the coronavirus disease 2019 pandemic may induce a severe rise in cases, morbidity, and mortality in the future.
Background Once the return of spontaneous circulation after out-of-hospital cardiac arrest is achieved, a 12-lead ECG is strongly recommended to identify candidates for urgent coronary angiography. ...ECG has no apparent role in mortality risk stratification. We aimed to assess whether ECG features could be associated with 30-day survival in patients with out-of-hospital cardiac arrest. Methods and Results All the post-return of spontaneous circulation ECGs from January 2015 to December 2018 in 3 European centers (Pavia, Lugano, and Vienna) were collected. Prehospital data were collected according to the Utstein style. A total of 370 ECGs were collected: 287 men (77.6%) with a median age of 62 years (interquartile range, 53-70 years). After correction for the return of spontaneous circulation-to-ECG time, age >62 years (hazard ratio HR, 1.78 95% CI, 1.21-2.61;
=0.003), female sex (HR, 1.5 95% CI, 1.05-2.13;
=0.025), QRS wider than 120 ms (HR, 1.64 95% CI, 1.43-1.87;
<0.001), the presence of a Brugada pattern (HR, 1.49 95% CI, 1.39-1.59;
<0.001), and the presence of ST-segment elevation in >1 segment (HR, 1.75 95% CI, 1.59-1.93;
<0.001) were independently associated with 30-day mortality. A score ranging from 0 to 26 was created, and by dividing the population into 3 tertiles, 3 classes of risk were found with significantly different survival rate at 30 days (score 0-4, 73%; score 5-7, 66%; score 8-26, 45%). Conclusions The post-return of spontaneous circulation ECG can identify patients who are at high risk of mortality after out-of-hospital cardiac arrest earlier than other forms of prognostication. This provides important risk stratification possibilities in postcardiac arrest care that could help to direct treatments and improve outcomes in patients with out-of-hospital cardiac arrest.
Targeted temperature management (TTM) is part of standard post-resuscitation care. TTM may downregulate cytochrome enzyme activity and thus impact drug metabolism. This study compared the ...pharmacokinetics (PK) of pantoprazole, a probe drug of CYP2C19-dependent metabolism, at different stages of TTM following cardiac arrest.
This prospective controlled study was performed at the Medical University of Vienna and enrolled 16 patients following cardiac arrest. The patients completed up to three study periods (each lasting 24 h) in which plasma concentrations of pantoprazole were quantified: (P1) hypothermia (33 °C) after admission, (P2) normothermia after rewarming (36 °C, intensive care), and (P3) normothermia during recovery (normal ward, control group). PK was analysed using non-compartmental analysis and nonlinear mixed-effects modelling.
16 patients completed periods P1 and P2; ten completed P3. The median half-life of pantoprazole was 2.4 h (quartiles: 1.8–4.8 h) in P1, 2.8 h (2.1–6.8 h, p = 0.046 vs. P1, p = 0.005 vs. P3) in P2 and 1.2 h (0.9 – 2.3 h, p = 0.007 vs. P1) in P3. A two-compartment model described the PK data best. Typical values for clearance were estimated separately for each study period, indicating 40% and 29% reductions during P1 and P2, respectively, compared to P3. The central volume of distribution was estimated separately for P2, indicating a 64% increase compared to P1 and P3.
CYP2C19-dependent drug metabolism is downregulated during TTM following cardiac arrest. These results may influence drug choice and dosing of similarly metabolized drugs and may be helpful for designing studies in similar clinical situations.
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•We included cardiac arrest patients during therapeutic hypothermia at 33 °C, after rewarming (ICU) and after recovery.•The pharmacokinetics of pantoprazole, a CYP2C19 probe drug, during these treatment stages were compared.•During hypothermia and after rewarming (ICU), the metabolism of pantoprazole was reduced compared with normal ward stay.•The initial hypothermia and the systemic inflammatory response after cardiac arrest may impair CYP2C19 activity.
Background: The clinical value of a prognostic score depends on its out-of-sample validity because inaccurate outcome prediction can be not only useless but potentially fatal. We aimed to evaluate ...the out-of-sample validity of a recently developed and highly accurate Korean prognostic score for predicting neurologic outcome after cardiac arrest in an independent, plausibly related sample of European cardiac arrest survivors. Methods: Analysis of data from a European cardiac arrest center, certified in compliance with the specifications of the German Council for Resuscitation. The study sample included adults with nontraumatic out-of-hospital cardiac arrest admitted between 2013 and 2018. Exposure was the PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages (PROLOGUE) score, including 12 clinical variables readily available at hospital admission. The outcome was poor 30-day neurologic function, as assessed using the cerebral performance category scale. The risk of a poor outcome was calculated using the PROLOGUE score regression equation. Predicted risk deciles were compared to observed outcome estimates in a complete-case analysis, a best-case analysis, and a multiple-data-imputation analysis using the Markov chain Monte Carlo method. Results: A total of 1051 patients (median 61 years, IQR 50–71; 29% female) were analyzed. A total of 808 patients (77%) were included in the complete-case analysis. The PROLOGUE score overestimated the risk of poor neurologic outcomes in the range of 40% to 100% predicted risk, involving 63% of patients. The model fit did not improve after missing data imputation. Conclusions: In a plausibly related sample of European cardiac arrest survivors, risk prediction by the PROLOGUE score was largely too pessimistic and failed to replicate the high accuracy found in the original study. Using the PROLOGUE score as an example, this study highlights the compelling need for independent validation of a proposed prognostic score to prevent potentially fatal mispredictions.
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.
Background:
In cardiac arrest survivors, metabolic parameters pH value, lactate concentration, and base deficit (BD) are routinely added to peri-arrest factors (including age, sex, bystander ...cardiopulmonary resuscitation, shockable first rhythm, resuscitation duration, adrenaline dose) to enhance early outcome prediction. However, the additional value of this strategy remains unclear.
Methods:
We used our resuscitation database to screen all patients ≥18 years who had suffered in- or out-of-hospital cardiac arrest (IHCA, OHCA) between January 1st, 2005 and May 1st, 2019. Patients with incomplete data, without return of spontaneous circulation or treatment with sodium bicarbonate were excluded. To analyse the added value of metabolic parameters to prognosticate neurological function, we built three models using logistic regression. These models included: (1) Peri-arrest factors only, (2) peri-arrest factors plus metabolic parameters and (3) metabolic parameters only. Receiver operating characteristics curves regarding 30-day good neurological function (Cerebral Performance Category 1-2) were analysed.
Results:
A total of 2,317 patients (OHCA:
n
= 1842) were included. In patients with OHCA, model 1 and 2 had comparable predictive value. Model 3 was inferior compared to model 1. In IHCA patients, model 2 performed best, whereas both metabolic (model 3) and peri-arrest factors (model 1) demonstrated similar power. PH, lactate and BD had interchangeable areas under the curve in both IHCA and OHCA.
Conclusion:
Although metabolic parameters may play a role in IHCA, no additional value in the prediction of good neurological outcome could be found in patients with OHCA. This highlights the importance of accurate anamnesis especially in patients with OHCA.
Background:
The post-cardiac arrest (CA) phase is characterized by high fluid requirements, endothelial activation and increased vascular permeability. Erythrocytes are large cells and may not leave ...circulation despite massive capillary leak. We hypothesized that dynamic changes in hemoglobin concentrations may reflect the degree of vascular permeability and may be associated with neurologic function after CA.
Methods:
We included patients ≥18 years, who suffered a non-traumatic CA between 2013 and 2018 from the prospective Vienna Clinical Cardiac Arrest Registry. Patients without return of spontaneous circulation (ROSC), with extracorporeal life support, with any form of bleeding, undergoing surgery, receiving transfusions, without targeted temperature management or with incomplete datasets for multivariable analysis were excluded. The primary outcome was neurologic function at day 30 assessed by the Cerebral Performance Category scale. Differences of hemoglobin concentrations at admission and 12 h after ROSC were calculated and associations with neurologic function were investigated by uni- and multivariable logistic regression.
Results:
Two hundred and seventy-five patients were eligible for analysis of which 143 (52%) had poor neurologic function. For every g/dl increase in hemoglobin from admission to 12 h the odds of poor neurologic function increased by 26% (crude OR 1.26, 1.07–1.49,
p
= 0.006). The effect remained unchanged after adjustment for fluid balance and traditional prognostication markers (adjusted OR 1.27, 1.05–1.54,
p
= 0.014).
Conclusion:
Increasing hemoglobin levels in spite of a positive fluid balance may serve as a surrogate parameter of vascular permeability and are associated with poor neurologic function in the early post-cardiac arrest period.
Gastrointestinal ischemia with reperfusion tissue injury contributes to post-cardiac arrest syndrome. We hypothesized that diarrhea is a symptom of intestinal ischemia/reperfusion injury and ...investigated whether the occurrence of early diarrhea (≤12 hours) after successful cardiopulmonary resuscitation is associated with an unfavorable neurological outcome.We analyzed data from the Vienna Clinical Cardiac Arrest Registry. Inclusion criteria comprised ≥18 years of age, a witnessed, non-traumatic out-of-hospital cardiac arrest, return of spontaneous circulation (ROSC), initial shockable rhythm, and ST-segment elevation in electrocardiogram after ROSC with consecutive coronary angiography. Patients with diarrhea caused by other factors (e.g., infections, antibiotic treatment, or chronic diseases) were excluded. The primary endpoint was neurological function between patients with or without "early diarrhea" (≤12 hours after ROSC) according to cerebral performance categories.We included 156 patients between 2005 and 2012. The rate of unfavorable neurologic outcome was higher in patients with early diarrhea (67% vs 37%). In univariate analysis, the crude odds ratio for unfavorable neurologic outcome was 3.42 (95% confidence interval, 1.11-10.56, P = .03) for early diarrhea. After multivariate adjustment for traditional prognostication markers the odds ratio of early diarrhea was 5.90 (95% confidence interval, 1.28-27.06, P = .02).In conclusion, early diarrhea within 12 hours after successful cardiopulmonary resuscitation was associated with an unfavorable neurological outcome.
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