The Current Discussion Regarding End-of-Life Care for Patients with Out-of-Hospital Cardiac Arrest with Initial Non-Shockable Rhythm: A Narrative Review

Despite recent advances in resuscitation science, outcomes in patients with out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythm remains poor. Those with initial non-shockable rhythm have some epidemiological features, including the proportion of patients with a witnessed arrest, bystander cardiopulmonary resuscitation (CPR), age, and presumed etiology of cardiac arrest have been reported, which differ from those with initial shockable rhythm. The discussion regarding better end-of-life care for patients with OHCA is a major concern among citizens. As one of the efforts to avoid unwanted resuscitation, advance directive is recognized as a key intervention, safeguarding patient autonomy. However, several difficulties remain in enhancing the effective use of advance directives for patients with OHCA, including local regulation of their use, insufficient utilization of advance directives by emergency medical services at the scene, and a lack of established tools for discussing futility of resuscitation in advance care planning. In addition, prehospital termination of resuscitation is a common practice in many emergency medical service systems to assist clinicians in deciding whether to discontinue resuscitation. However, there are also several unresolved problems, including the feasibility of implementing the rules for several regions and potential missed survivors among candidates for prehospital termination of resuscitation. Further investigation to address these difficulties is warranted for better end-of-life care of patients with OHCA

External validation of a risk classification at the emergency department of post-cardiac arrest syndrome patients undergoing targeted temperature management

[Introduction]There are no established risk classification for post-cardiac arrest syndrome (PCAS) patients at the Emergency Department (ED) undergoing targeted temperature management (TTM). The aim of this study was to externally validate a simplified version of our prognostic score, the “post-Cardiac Arrest Syndrome for Therapeutic hypothermia score” (revised CAST [rCAST]) and estimate the predictive accuracy of the risk classification based on it. [Methods]For the external validation, we used data from an out-of-hospital cardiac arrest (OHCA) registry of the Japanese Association for Acute Medicine (JAAM), which is a multicenter, prospective registry of OHCA patients across Japan. Eligible patients were PCAS patients treated with TTM at 33–36 °C between June 2014 and December 2015. We validated the accuracy of rCAST for predicting the neurological outcomes at 30 and 90 days. [Results]Among the 12, 024 OHCA patients, the data of 460 PCAS patients treated by TTM were eligible for the validation. The areas under the curve of rCAST for predicting the neurological outcomes at 30 and 90 days were 0.892 and 0.895, respectively. The estimated sensitivity and specificity of the risk categories for the outcomes were as follows: 0.95 (95% CI: 0.92–0.98) and 0.47 (0.40–0.55) for the low (rCAST: ≤5.5), 0.62 (0.56–0.68) and 0.48 (0.40–0.55) for the moderate (rCAST: 6.0–14.0), and 0.57 (0.51–0.63) and 0.95 (0.91–0.98) for the high severity category (rCAST: ≥14.5). [Conclusions]The rCAST was useful for predicting the neurological outcomes with high accuracy in PCAS patients, and the three grades was developed for a risk classification based on the rCAST

Differential Effectiveness of Hypothermic Targeted Temperature Management According to the Severity of Post-Cardiac Arrest Syndrome

International guidelines recommend targeted temperature management (TTM) to improve the neurological outcomes in adult patients with post-cardiac arrest syndrome (PCAS). However, it still remains unclear if the lower temperature setting (hypothermic TTM) or higher temperature setting (normothermic TTM) is superior for TTM. According to the most recent large randomized controlled trial (RCT), hypothermic TTM was not found to be associated with superior neurological outcomes than normothermic TTM in PCAS patients. Even though this represents high-quality evidence obtained from a well-designed large RCT, we believe that we still need to continue investigating the potential benefits of hypothermic TTM. In fact, several studies have indicated that the beneficial effect of hypothermic TTM differs according to the severity of PCAS, suggesting that there may be a subgroup of PCAS patients that is especially likely to benefit from hypothermic TTM. Herein, we summarize the results of major RCTs conducted to evaluate the beneficial effects of hypothermic TTM, review the recent literature suggesting the possibility that the therapeutic effect of hypothermic TTM differs according to the severity of PCAS, and discuss the potential of individualized TTM

Association between regional critical care capacity and the incidence of invasive mechanical ventilation for coronavirus disease 2019: a population-based cohort study

Abstract Background Coronavirus disease 2019 (COVID-19) has exposed critical care supply shortages worldwide. This study aimed to investigate the association between regional critical care capacity and the incidence of invasive mechanical ventilation following novel COVID-19 during the pandemic in Japan, a country with a limited intensive care unit (ICU) bed capacity of a median of 5.1 ICU beds per 100,000 individuals. Methods This population-based cohort study used data from the CRoss Icu Searchable Information System database and publicly available databases provided by the Japanese government and Japanese Society of Intensive Care Medicine. We identified patients recently diagnosed with COVID-19, those who received invasive mechanical ventilation, and those who received extracorporeal membrane oxygenation (ECMO) between February 2020 and March 2023. We analyzed the association between regional critical care capacity (ICU beds, high-dependency care unit (HDU) beds, resource-rich ICU beds, and intensivists) and the incidence of invasive mechanical ventilation, ECMO, and risk-adjusted mortality across 47 Japanese prefectures. Results Among the approximately 127 million individuals residing in Japan, 33,189,809 were recently diagnosed with COVID-19, with 12,203 and 1,426 COVID-19 patients on invasive mechanical ventilation and ECMO, respectively, during the study period. Prefecture-level linear regression analysis revealed that the addition of ICU beds, resource-rich ICU beds, and intensivists per 100,000 individuals increased the incidence of IMV by 5.37 (95% confidence interval, 1.99–8.76), 7.27 (1.61–12.9), and 13.12 (3.48–22.76), respectively. However, the number of HDU beds per 100,000 individuals was not statistically significantly associated with the incidence of invasive mechanical ventilation. None of the four indicators of regional critical care capacity was statistically significantly associated with the incidence of ECMO and risk-adjusted mortality. Conclusions The results of prefecture-level analyses demonstrate that increased numbers of ICU beds, resource-rich ICU beds, and intensivists are associated with the incidence of invasive mechanical ventilation among patients recently diagnosed with COVID-19 during the pandemic. These findings have important implications for healthcare policymakers, aiding in efficiently allocating critical care resources during crises, particularly in regions with limited ICU bed capacities. Registry and the registration no. of the study/trial The approval date of the registry was August 20, 2020, and the registration no. of the study was lUMIN000041450

Wolf Creek XVII part 9: Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award

The Wolf Creek Conferences on Cardiac Arrest Resuscitation began in 1975, and have served as an important forum for thought leaders and scientists from industry and academia to come together with the common goal of advancing the field of cardiac arrest resuscitation. The Wolf Creek XVII Conference was hosted by the Max Harry Weil Institute of Critical Care Research and Innovation in Ann Arbor, Michigan on June 14–17, 2023. A new component of the conference was the Wolf Creek Innovator in Cardiac Arrest and Resuscitation Science Award competition. The competition was designed to recognize early career investigators from around the world who’s science is challenging the current paradigms in the field. Finalists were selected by a panel of international experts and invited to present in-person at the conference. The winner was chosen by electronic vote of conference participants and awarded a $10,0000 cash prize. Finalists included Carolina Barbosa Maciel from the University of Florida, Adam Gottula from the University of Michigan, Rajat Kalra from the University of Minnesota, Ryan Morgan from the Children’s Hospital of Philadelphia, Mitsuaki Nishikimi form Hiroshima University, and Jacob Sunshine from the University of Washington. Ryan Morgan from the Children’s Hospital of Philadelphia was selected as the 2023 Wolf Creek Innovator Awardee. This manuscript provides a summary of the work presented by each of the finalists and provides a preview of the future of resuscitation science

Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer

Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obtained from three cohorts of patients: non-cancer controls, patients with benign ovarian tumors, and those with ovarian cancer. We did not find the LPA level to be higher in cancer samples. To understand this inconsistency, we observed that LPA content changed more significantly than other lysophospholipids as a function of plasma storage time while frozen. Additionally, only LPA was found to be adversely impacted by incubation time depending on the Ethylenediaminetetraacetic acid (EDTA) concentration used during blood drawing. We also show that the inhibition of autotaxin effectively prevented artificial LPA generation during incubation at room temperature. Our data suggests that the artificial changes in LPA content may contribute to the discrepancies reported in literature. Any future studies planning to measure plasma LPA should carefully design the study protocol to consider these confounding factors

Timing of administration of epinephrine predicts the responsiveness to epinephrine in norepinephrine-refractory septic shock: a retrospective study

Abstract Background Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock. Methods A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration. Results Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P < 0.001), and 28-day survival (83% vs. 18%; P < 0.001). In multivariable analysis, time of epinephrine administration after ICU admission (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.27–0.87; P = 0.011) and SOFA score (OR 0.19; 95% CI 0.04–0.88; P = 0.034) were associated with epinephrine response. Time of epinephrine administration was also significantly associated with survival from shock (OR 0.42; P = 0.005) and 28-day survival (OR 0.14; P = 0.006), while SOFA score did not. Using inverse probability of treatment weighing (IPTW) adjustment of propensity score, epinephrine administration later than 24 h after ICU admission was associated with poor response (OR 0.07; 95% CI 0.02–0.21; P < 0.001). Conclusions Early administration of epinephrine after ICU admission (i.e., within 24 h) is associated with better hemodynamic status in patients with refractory septic shock

Accuracy of the first interpretation of early brain CT images for predicting the prognosis of post-cardiac arrest syndrome patients at the emergency department

Abstract Background Early brain CT is one of the most useful tools for estimating the prognosis in patients with post-cardiac arrest syndrome (PCAS) at the emergency department (ED). The aim of this study was to evaluate the prognosis-prediction accuracy of the emergency physicians’ interpretation of the findings on early brain CT in PCAS patients treated by targeted temperature management (TTM). Methods This was a double-center, retrospective, observational study. Eligible subjects were cardiac arrest patients admitted to the intensive care unit (ICU) for TTM between April 2011 and March 2017. We performed the McNemar test to compare the predictive accuracies of the interpretation by emergency physicians and radiologists and calculated the kappa statistic for determining the concordance rate between the interpretations by these two groups. Results Of the 122 eligible patients, 106 met the inclusion criteria for this study. The predictive accuracies (sensitivity, specificity) of the interpretations by the emergency physicians and radiologists were (0.34, 1.00) and (0.41, 0.93), respectively, with no significant difference in either the sensitivity or specificity as assessed by the McNemar test. The kappa statistic calculated to determine the concordance between the two interpretations was 0.66 (0.48–0.83), which showed a good conformity. Conclusions The emergency physicians’ interpretation of the early brain CT findings in PCAS patients treated by TTM was as reliable as that of radiologists, in terms of prediction of the prognosis