Neuroprotection with hypothermic reperfusion and extracorporeal cardiopulmonary resuscitation - A randomized controlled animal trial of prolonged ventricular fibrillation cardiac arrest in rats.

Extracorporeal cardiopulmonary resuscitation (ECPR) facilitates resuscitation with immediate and precise temperature control. This study aimed to determine the optimal reperfusion temperature to minimize neurological damage after ventricular fibrillation cardiac arrest (VFCA). Twenty-four rats were randomized (n = 8 per group) to normothermia (NT = 37°C), mild hypothermia (MH = 33°C) or moderate hypothermia (MOD = 27°C). The rats were subjected to 10 minutes of VFCA, before 15 minutes of ECPR at their respective target temperature. After ECPR weaning, rats in the MOD group were rapidly rewarmed to 33°C, and temperature maintained at 33°C (MH/MOD) or 37°C (NT) for 12 hours before slow rewarming to normothermia (MH/MOD). The primary outcome was 30-day survival with overall performance category (OPC) 1 or 2 (1 = normal, 2 = slight disability, 3 = severe disability, 4 = comatose, 5 = dead). Secondary outcomes included awakening rate (OPC ≤ 3) and neurological deficit score (NDS, from 0 = normal to 100 = brain dead). The survival rate did not differ between reperfusion temperatures (NT = 25%, MH = 63%, MOD = 38%, p = 0.301). MH had the lowest NDS (NT = 4[IQR 3-4], MH = 2[1-2], MOD = 5[3-5], p = 0.044) and highest awakening rate (NT = 25%, MH = 88%, MOD = 75%, p = 0.024). In conclusion, ECPR with 33°C reperfusion did not statistically significantly improve survival after VFCA when compared with 37°C or 27°C reperfusion but was neuroprotective as measured by awakening rate and neurological function.

Feasibility of resuscitative transesophageal echocardiography at out-of-hospital emergency scenes of cardiac arrest.

Guidelines recommend the use of ultrasound in cardiac arrest. Transthoracic echocardiography, has issues with image quality and by increasing hands-off times during resuscitation. We assessed the feasibility of transesophageal echocardiography (TEE), which does not have both problems, at out-of-hospital cardiac arrest (OHCA) emergency scenes. Included were 10 adults with non-traumatic OHCA in Vienna, Austria. An expert in emergency ultrasound was dispatched to the scenes in addition to the resuscitation team. Feasibility was defined as the ability to collect specific items of information by TEE within 10 min. Descriptive statistics were compiled and hands-off times were compared to a historical control group. TEE examinations were feasible in 9 of 10 cases and prompted changes in clinical management in 2 cases (cardiac tamponade: n = 1; right ventricular dilatation: n = 1). Their mean time requirement was 5.1 ± 1.7 (2.8-8.0) min, and image quality was invariably rated as excellent or good during both compressions and pauses. No TEE-related complications, or interferences with activities of advanced life support were observed. The hands-off times during resuscitation were comparable to a historical control group not involving ultrasound (P = 0.24). Given these feasibility results, we expect that TEE can be used routinely at OHCA emergency scenes.

Resuscitative transoesophageal echocardiography performed by emergency physicians in the emergency department: insights from a 1-year period.

AIMS: Transoesophageal echocardiography (TOE) has increasingly been described as a possible complementary and point-of-care approach for patients with cardiac arrest (CA). It provides information about potentially reversible causes and prognosis and allows monitoring of resuscitation efforts without affecting ongoing chest compressions. The aim of this study was to assess the feasibility of TOE performed by emergency physicians (EPs) during CA in an emergency department (ED). METHODS AND RESULTS: This prospective study was performed at the Department of Emergency Medicine at the Medical University of Vienna from February 2020 to February 2021. All patients of ≥18 years old presenting with ongoing resuscitation efforts were screened. After exclusion of potential contraindications, a TOE examination was performed and documented by EPs according to a standardized four-view imaging protocol. The primary endpoint represents feasibility defined as successful probe insertion and acquisition of interpretable images. Of 99 patients with ongoing non-traumatic CA treated in the ED, a total of 62 patients were considered to be examined by TOE. The examination was feasible in 57 patients (92%) [females, 14 (25%), mean age 53 ± 13, and witnessed collapse 48 (84%)]. Within these, the examiners observed 51 major findings in 32 different patients (66%). In 21 patients (37%), these findings led to a direct change of therapy. In 18 patients (32%), the examiner found ventricular contractions without detectable pulse. No TOE-related complications were found. CONCLUSION: Our findings suggest that EPs may be able to acquire and interpret TOE images in the majority of patients during CA using a standardized four-view imaging protocol.

The difference between arterial pCO2 and etCO2 after cardiac arrest - Outcome predictor or marker of unfavorable resuscitation circumstances?

INTRODUCTION: In former studies, the arterio-alveolar carbon dioxide gradient (ΔCO2) predicted in-hospital mortality after initially survived cardiac arrest. As early outcome predictors are urgently needed, we evaluated ΔCO2 as predictor for good neurological outcome in our cohort. METHODS: We retrospectively analyzed all patients ≥18 years of age after non-traumatic in- and out of hospital cardiac arrest in the year 2018 from our resuscitation database. Patients without advanced airway management, incomplete datasets or without return of spontaneous circulation were excluded. The first arterial pCO2 after admission and the etCO2 in mmHg at the time of blood sampling were recorded from patient's charts. We then calculated ΔCO2 (pCO2 - etCO2). For baseline analyses, ΔCO2 was dichotomized into a low and high group with separation at the median. Good neurological outcome on day 30, expressed as Cerebral Performance Category 1-2, defined our primary endpoint. Survival to 30 days was used as secondary endpoint. RESULTS: Out of 302 screened patients, 128 remained eligible for analyses. ΔCO2 was lower in 30-day survivors with good neurological outcome (12.2 mmHg vs. 18.8 mmHg, p = 0.009) and in 30-day survivors (12.5 mmHg vs. 20.0 mmHg, p = 0.001). In patients with high ΔCO2, a cardiac etiology of arrest was found less often. They had a higher body mass index, longer duration of resuscitation, higher amounts of epinephrine, lower pO2 levels but both higher pCO2 and blood lactate levels, resulting in lower blood pH and HCO3- levels at admission. In a crude binary logistic regression analysis, ΔCO2 was associated with 30-day neurological outcome (OR = 1.041 per mmHg of ΔCO2, 95% CI 1.008-1.074, p = 0.014). This association persisted after the adjustment for age, sex, witnessed arrest and shockable first rhythm. However, after addition of the duration of resuscitation or the cumulative epinephrine dosage to the model, ΔCO2 lost its association. CONCLUSION: ΔCO2 at admission after a successfully resuscitated cardiac arrest is associated with 30 days survival with good neurological outcome. However, a higher ΔCO2 may rather be a surrogate for unfavorable resuscitation circumstances than an independent outcome predictor.

Out-of-Sample Validity of the PROLOGUE Score to Predict Neurologic Function after Cardiac Arrest.

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.

[Extracorporeal resuscitation-criteria, prerequisites, outcome : A reality check]. / Extrakorporale Reanimation ­ Kriterien, Bedingungen, Outcome : Ein Reality-Check.

In select patients, in whom conventional cardiopulmonary resuscitation (cCPR) fails to re-establish circulation, the 2021 European Resuscitation Council guidelines suggest considering extracorporeal resuscitation (eCPR) as a rescue therapy in settings in which it can be implemented. eCPR is becoming established during refractory cardiac arrest as a bridge-to-therapy for diagnosis and treatment of reversible causes of cardiac arrest, such as myocardial infarction, pulmonary embolism, accidental hypothermia, overdose with cardiotoxic substances, and acute hypoxia. Patient selection criteria comprise prognostic characteristics of cardiac arrest such as witnessed status, resuscitation efforts within 5 min, shockable initial rhythm, and characteristics of effective cCPR such as signs of life during resuscitation, persistent ventricular fibrillation, intermittent episodes of spontaneous circulation or end-tidal CO2 levels constantly > 10 mm Hg, patient age and health status. The timeframe from cardiac arrest to eCPR is a major contributor for neurologically favourable survival and should not exceed 60 min according to current guidelines. This may be achieved with an efficient "load & go" strategy, including early patient selection and rapid transport with ongoing mechanical cCPR to the eCPR centre, or with a prehospital eCPR strategy. Two randomized controlled eCPR trials demonstrated survival rates of 43% and 31.5% in patients with refractory ventricular fibrillation and cardiac-origin cardiac arrest, respectively. Whether these results are generalizable outside such highly specialized centres, and which prehospital and in-hospital strategy is best for which patients, remains to be determined in future studies.

Targeted temperature management after cardiac arrest is associated with reduced metabolism of pantoprazole - A probe drug of CYP2C19 metabolism.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The association of early diarrhea after successful resuscitation following out-of-hospital cardiac arrest with neurological outcome: A retrospective observational study.

ABSTRACT: 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.

Copeptin Levels Are Independent from Mild Therapeutic Hypothermia but Do Not Predict Infarct Size in Patients Presenting with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Mild therapeutic hypothermia (MTH) is a treatment adjunct in ST-segment elevation myocardial infarction (STEMI) that deserves investigation. Copeptin-a surrogate marker for vasopressin-is an early biomarker in STEMI. Data from cardiac arrest patients suggest a reduction of copeptin levels through MTH; however, copeptin levels have not been investigated in MTH during STEMI. METHODS: We analyzed patients treated with MTH during STEMI in a sub-study of the STATIM trial (Testori, Heart 2019). Patients were randomized to normothermia or MTH with out-of-hospital initiation. Seven copeptin samples were collected from each patient. Primary endpoint was the difference in copeptin levels between the groups. As secondary endpoints, we defined differences in the kinetics between the sampling timepoints and the correlation between copeptin and the infarct size in relation to left ventricular myocardium. RESULTS: We included 99 patients (MTH n = 47, control n = 52) in our intention to treat analysis. No differences in copeptin values at first medical contact between the MTH and normothermia groups were found. MTH showed no effect on copeptin levels, neither during cooling phase nor through the course. Copeptin peaked at first medical contact and hospital admission in both groups. No differences in kinetics between the timepoints were found. Copeptin showed no correlation with infarct size, neither at first medical contact nor hospital admission. CONCLUSIONS: Copeptin levels were not influenced by MTH in STEMI, suggesting the use of this biomarker also during temperature management. Furthermore, copeptin levels were not usable as a surrogate marker for infarct size at any timepoint.

Initial Blood pH, Lactate and Base Deficit Add No Value to Peri-Arrest Factors in Prognostication of Neurological Outcome After Out-of-Hospital Cardiac Arrest.

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.

Coronary angiography in patients after cardiac arrest without ST-elevation myocardial infarction : A retrospective cohort analysis.

BACKGROUND: Coronary artery disease (CAD) is the most common cause of sudden cardiac arrest (SCA). Although coronary angiography (CAG) should be performed also in the absence of ST-elevation (STE) after sustained return of spontaneous circulation (ROSC), this recommendation is not well implemented in daily routine. METHODS: A retrospective database analysis was conducted in a tertiary care center between January 2005 and December 2014. We included all SCA patients aged ≥ 18 years with presumed cardiac cause and sustained ROSC in the absence of STE at hospital admission. The rate and timing of CAG were defined as the primary endpoints. As secondary endpoints, the reasons pro and contra CAG were analyzed. Furthermore, we observed if the signs and symptoms used for decision making occurred more often in patients with treatable CAD. RESULTS: We included 645 (53.6%) of the 1203 screened patients, CAG was performed in 343 (53.2%) patients with a diagnosis of occlusive CAD in 214 (62.4%) patients. Of these, 151 (71.0%) patients had occlusive CAD treated with coronary intervention, thrombus aspiration, or coronary artery bypass grafting. In an adjusted binomial logistic regression analysis, age ≥ 70 years, female sex, non-shockable rhythms, and cardiomyopathy were associated with withholding of CAG. In patients diagnosed and treated with occlusive CAD, initially shockable rhythms, previously diagnosed CAD, hypertension, and smoking were found more often. CONCLUSION: Although selection bias is unavoidable due to the retrospective design of this study, a high proportion of the examined patients had occlusive CAD. The criteria used for patient selection may be suboptimal.

Change of Hemoglobin Levels in the Early Post-cardiac Arrest Phase Is Associated With Outcome.

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.

Admission C-reactive protein concentrations are associated with unfavourable neurological outcome after out-of-hospital cardiac arrest.

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.

Thrombolysis of a massive intracardiac thrombus during resuscitation: documentation by transoesophageal echocardiography.

Acute pulmonary embolism is a frequent potentially reversible cause of sudden cardiac arrest. The early diagnosis is challenging but essential for further treatment. New therapeutic options in resuscitation, such as extracorporeal resuscitation, are leading to frequent transports of patients to emergency rooms with ongoing resuscitation. A transoesophageal echo performed during resuscitation can give hints for reversible causes for the cardiac arrest. We present a case of a 40-year-old female patient who was transferred to our department with ongoing resuscitation and received a transoesophageal echo immediately on arrival. The examination showed a massive intracardiac thrombus. The subsequent thrombolysis and following resuscitation were observed and documented via transoesophageal echo.

Prolonged Activated Partial Thromboplastin Time after Successful Resuscitation from Cardiac Arrest is Associated with Unfavorable Neurologic Outcome.

Coagulation abnormalities after successful resuscitation from cardiac arrest may be associated with unfavorable neurologic outcome. We investigated a potential association of activated partial thromboplastin time (aPTT) with neurologic outcome in adult cardiac arrest survivors. Therefore, we included all adults ≥18 years of age who suffered a nontraumatic cardiac arrest and had achieved return of spontaneous circulation between January 2013 and December 2018. Patients receiving anticoagulants or thrombolytic therapy and those subjected to extracorporeal membrane oxygenation support were excluded. Routine blood sampling was performed on admission as soon as a vascular access was available. The primary outcome was 30-day neurologic function, assessed by the Cerebral Performance Category scale (3-5 = unfavorable neurologic function). Multivariable regression was used to assess associations between normal (≤41 seconds) and prolonged (>41 seconds) aPTT on admission (exposure) and the primary outcome. Results are given as odds ratio (OR) with 95% confidence intervals (95% CIs). Out of 1,591 cardiac arrest patients treated between 2013 and 2018, 360 patients (32% female; median age: 60 years [interquartile range: 48-70]) were eligible for analysis. A total of 263 patients (73%) had unfavorable neurologic function at day 30. aPTT prolongation >41 seconds was associated with a 190% increase in crude OR of unfavorable neurologic function (crude OR: 2.89; 95% CI: 1.78-4.68, p < 0.001) and with more than double the odds after adjustment for traditional risk factors (adjusted OR: 2.01; 95% CI: 1.13-3.60, p = 0.018). In conclusion, aPTT prolongation on admission is associated with unfavorable neurologic outcome after successful resuscitation from cardiac arrest.

A Case Report of Nebulized Tranexamic Acid for Post-tonsillectomy Hemorrhage in an Adult.

INTRODUCTION: Post-tonsillectomy hemorrhage is a potentially life-threatening, postoperative complication that is commonly encountered in the emergency department (ED). CASE REPORT: Herein, we describe the case of a 22-year-old male who presented to the ED with an active post-tonsillectomy hemorrhage. He rapidly became hypotensive and experienced an episode of syncope. Immediate interventions included intravenous fluids, emergency release blood and nebulized tranexamic acid (TXA). After completion of the nebulized TXA, the patient's bleeding was controlled. CONCLUSION: To our knowledge, this is the first case in the emergency medicine literature that describes the use of nebulized TXA in an adult to achieve hemostasis in post-tonsillectomy hemorrhage.

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 165ng/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.