Early Identification of Resuscitated Patients with a Significant Coronary Disease in Out-of-Hospital Cardiac Arrest Survivors without ST-Segment Elevation

This study aimed to develop a machine learning (ML)-based model for identifying patients who had a significant coronary artery disease among out-of-hospital cardiac arrest (OHCA) survivors without ST-segment elevation (STE). This multicenter observational study used data from the Korean Hypothermia Network prospective registry (KORHN-PRO) gathered between October 2015 and December 2018. We used information available before targeted temperature management (TTM) as predictor variables, and the primary outcome was a significant coronary artery lesion in coronary angiography (CAG). Among 1373 OHCA patients treated with TTM, 331 patients without STE who underwent CAG were enrolled. Among them, 127 patients (38.4%) had a significant coronary artery lesion. Four ML algorithms, namely regularized logistic regression (RLR), random forest classifier (RF), CatBoost classifier (CBC), and voting classifier (VC), were used with data collected before CAG. The VC model showed the highest accuracy for predicting significant lesions (area under the curve of 0.751). Eight variables (older age, male, initial shockable rhythm, shorter total collapse duration, higher glucose and creatinine, and lower pH and lactate) were significant to ML models. These results showed that ML models may be useful in developing early predictive tools for identifying high-risk patients with a significant stenosis in CAG.

Cardiac Arrest Survival Postresuscitation In-Hospital (CASPRI) Score Predicts Neurological Favorable Survival in Emergency Department Cardiac Arrest

Background: This study was conducted to identify the predictive factors for survival and favorable neurological outcome in patients with emergency department cardiac arrest (EDCA). Methods: ED patients who suffered from in-hospital cardiac arrest (IHCA) from July 2014 to June 2019 were enrolled. The electronic medical records were retrieved and data were extracted according to the IHCA Utstein-style guidelines. Results: The cardiac arrest survival post-resuscitation in-hospital (CASPRI) score was associated with survival, and the CASPRI scores were lower in the survival group. Three components of the CASPRI score were associated with favorable neurological survival, and the CASPRI scores were lower in the favorable neurological survival group of patients who were successfully resuscitated. The independent predictors of survival were presence of hypotension/shock, metabolic illnesses, short resuscitation time, receiving coronary angiography, and TTM. Receiving coronary angiography and low CASPRI score independently predicted favorable neurological survival in resuscitated patients. The performance of a low CASPRI score for predicting favorable neurological survival was fair, with an AUROCC of 0.77. Conclusions: The CASPRI score can be used to predict survival and neurological status of patients with EDCA. Post-cardiac arrest care may be beneficial for IHCA, especially in patients with EDCA.

Impact of Center Volume on Outcomes in Myocardial Infarction Complicated by Cardiogenic Shock: A CULPRIT‐SHOCK Substudy

Background Little is known about the impact of center volume on outcomes in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to investigate the association between center volume, treatment strategies, and subsequent outcome in patients with acute myocardial infarction complicated by cardiogenic shock. Methods and Results In this subanalysis of the randomized CULPRIT‐SHOCK (Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock) trial, study sites were categorized based on the annual volume of acute myocardial infarction complicated by cardiogenic shock into low‐/intermediate‐/high‐volume centers (<50; 50–100; and >100 cases/y). Subjects from the study/compulsory registry with available volume data were included. Baseline/procedural characteristics, overall treatment, and 1‐year all‐cause mortality were compared across categories. n=1032 patients were included in this study (537 treated at low‐volume, 240 at intermediate‐volume, and 255 at high‐volume centers). Baseline risk profile of patients across the volume categories was similar, although high‐volume centers included a larger number of older patients. Low‐/intermediate‐volume centers had more resuscitated patients (57.5%/58.8% versus 42.2%; P <0.01), and more patients on mechanical ventilation in comparison to high‐volume centers. There were no differences in reperfusion success despite considerable differences in adjunctive pharmacological/device therapies. There was no difference in 1‐year all‐cause mortality across volume categories (51.1% versus 56.5% versus 54.4%; P =0.34). Conclusions In this study of patients with acute myocardial infarction complicated by cardiogenic shock, considerable differences in adjunctive medical and mechanical support therapies were observed. However, we could not detect an impact of center volume on reperfusion success or mortality.

Beyond return of spontaneous circulation: update on post-cardiac arrest management in the intensive care unit

A well-functioning chain of survival is critical for good outcomes following out-of-hospital cardiac arrest, a major public health concern in Singapore. While the percentage of survivors to hospital admission has increased over the years, the percentage of survivors to hospital discharge and the number of patients with good neurological recovery can be greatly improved. This underscores the urgent need to focus on ‘post-cardiac arrest care’, the fifth link in the chain of survival, to improve the outcomes of patients who are admitted to the intensive care unit (ICU) after return of spontaneous circulation. This review builds on earlier recommendations of the Singapore National Targeted Temperature Management Workgroup in 2017 to provide a focused update on post-cardiac arrest management and a practical guide for physicians managing resuscitated patients with cardiac arrest in the ICU.

Predictive Model of Good Clinical Outcomes in Patients Undergoing Coronary Angiography after Out-of-Hospital Cardiac Arrest: A Prospective, Multicenter Observational Study Conducted by the Korean Cardiac Arrest Research Consortium

This observational study aimed to develop novel nomograms that predict the benefits of coronary angiography (CAG) after resuscitating patients with out-of-hospital cardiac arrest (OHCA) regardless of the electrocardiography findings and to perform an external validation of these models. Data were extracted from a prospective, multicenter registry of resuscitated patients with OHCA (October 2015–June 2018). New nomograms were developed based on variables associated with survival discharge and neurologic outcomes; their analysis included 723 and 709 patients, respectively. Patient age (p < 0.001), prehospital defibrillation by emergency medical technicians (EMTs) (p = 0.003), prehospital return of spontaneous circulation (ROSC) (p = 0.02), and time from collapse to ROSC (p < 0.001) were associated with survival discharge. Patient age (p < 0.001), prehospital defibrillation by EMTs (p < 0.001), and time from collapse to ROSC (p < 0.001) were associated with neurologic outcomes. The new nomogram had a good predictive performance, with an area under the curve (AUC) of 0.8832 (95% confidence interval (CI): 0.8358–0.9305) for survival discharge and an AUC of 0.9048 (95% CI: 0.8627–0.9469) for neurologic outcomes. Novel nomograms that predict survival discharge and good neurological outcomes after CAG in patients with OHCA were developed and validated; they can be quickly and easily applied to identify patients who will benefit from CAG.

Brain Protection after Anoxic Brain Injury: Is Lactate Supplementation Helpful?

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest.

A description of the clinical course of severe benzonatate poisonings reported in the literature and to NPDS: A systematic review supplemented with NPDS cases

Background: Benzonatate is a commonly prescribed medication that can be lethal in acute overdose of a small number of capsules. Objective: This was a systematic review to describe the course of severe poisoning and deaths from benzonatate supplemented with the National Poison Data System (NPDS) fatalities module. Methods: The NPDS was queried from 2000 to 2018 for benzonatate fatalities. Pubmed, Cochrane, Embase, and Google Scholar were searched for combinations of benzonatate and “poisoning,” “overdose,” and “toxicity.” References of relevant articles were searched for additional publications. Articles were included if they described the clinical course of at least one patient suffering from benzonatate poisoning and available in English. Dual independent review and extraction were performed. Results: Seventeen cases from NPDS and 19 published reports met the inclusion criteria resulting in 36 cases, mostly (28/36) self-harm ingestions. Most patients were young [17 (11–29), median (IQR)] and female (22). Onset of toxicity was rapid at <5 min (9). Most common symptoms included cardiac arrest (29), seizures (24), and dysrhythmias (24). Treatments included intubation (26), cardiopulmonary resuscitation (28), vasopressors (20) and others. Return of spontaneous circulation was achieved in 23/28 patients, but most had significant neurologic deficits or other end organ damage and 5 survived with a good neurologic outcome. Conclusion and relevance: Overdose ingestions of benzonatate can cause significant toxicity with a rapid onset. Interventions performed were generally supportive in nature. Duration of directly toxic effects is short, but dramatic with neurologic devastation and resuscitated patients often still have a poor outcome.

Antiplatelet effects and pharmacokinetics of crushed ticagrelor in resuscitated patients after cardiac arrest

Funding Acknowledgements Type of funding sources: None. Introduction Based on the PLATO-trial and its sub-studies, ticagrelor can be used for patients with an acute coronary syndrome (ACS). Some of these patients are not awake or not able to swallow tablets. Alternatively the tablets can be crushed and given through a nasogastric tube. An extra obstacle for adequate intake is medication-induced gastroparesis caused by sedatives. Purpose The first aim of the study was to evaluate the platelet function analyser closure time (CT) in patients treated with crushed ticagrelor, after successful being resuscitated after cardiac arrest of acute ischaemic origin. Either they underwent PCI or urgent CABG, either they were treated conservatively. The second aim of the study was to determine plasma concentrations of ticagrelor and its main active metabolite AR-C124910XX. Methods We included 20 patients after successful resuscitation for cardiac arrest of acute ischaemic origin (16 STEMI + 4 NSTEMI). Only 1 patient was treated conservatively, 2 patients underwent an urgent CABG, the remainder were treated with PCI. All patients received a loading dose of ticagrelor before starting daily therapy. As patients were not able to swallow, tablets were crushed and given through a nasogastric tube. Measurements for Platelet Function Analysis were done at 0h, 2h, 4h, 8h, 12h, 24h and at day 4 + 4h. Platelet inhibition was tested with Platelet Function Analyser (PFA) activated by Adenosine Di Phosphate (ADP). A closure time (CT) longer than 113 seconds indicates full platelet inhibition by ticagrelor. Plasma concentration were determined at 30min, 1h, 2h, 4h, 8h, 24h and day 4 + 4h. Plasma concentrations were measured after protein precipitation, by using liquid chromatography with mass spectrometry detection. Results Out of 20 resuscitated patients enlisted in this study, 13 were still alive at day 4. At 24h, more than 80% of the survivors showed platelet inhibition as proven by a CT &gt;113s. In 92% of the survivors, the PFA showed platelet inhibition at day 4 with a median CT of &gt; 300s. For ticagrelor, the median time to peak plasma concentration (Tmax) was 100h [8; 100] for a median Cmax of 615.5 ng/ml [217.5; 1385.0]. The geometric mean was 467 ng/ml (248.5; 877.4). For the metabolite of ticagrelor, AR-C124910XX, median Tmax was 100h [8; 100] for a Cmax of 131.0 ng/ml [52.1; 177.7]. The geometric mean for the metabolite was 69.5 ng/ml (32.4; 149.0). Conclusions At day 4 of therapy, 92% of the survivors showed a CT longer than 113s, meaning full platelet inhibition by ticagrelor. In more than 80%, this was even the case at 24h. The median time to reach peak concentrations was 4 days, which is comparable to pharmacokinetic studies with ticagrelor in healthy volunteers. It should be noted that the dispersion in achieving Cmax is wide and can be reached earlier than at 4 days.