Optimal Time of Collapse to Return of Spontaneous Circulation to Apply Targeted Temperature Management for Cardiac Arrest: A Bayesian Network Meta-Analysis

Background: Both the American Heart Association (AHA) and European Resuscitation Council (ERC) have strongly recommended targeted temperature management (TTM) for patients who remain in coma after return of spontaneous circulation (ROSC). However, the role of TTM, especially hypothermia, in cardiac arrest patients after TTM2 trials has become much uncertain.Methods: We searched four online databases (PubMed, Embase, CENTRAL, and Web of Science) and conducted a Bayesian network meta-analysis. Based on the time of collapse to ROSC and whether the patient received TTM or not, we divided this analysis into eight groups (<20 min + TTM, <20 min, 20–39 min + TTM, 20–39 min, 40–59 min + TTM, 40–59 min, ≥60 min + TTM and ≥60 min) to compare their 30-day and at-discharge survival and neurologic outcomes.Results: From an initial search of 3,023 articles, a total of 9,005 patients from 42 trials were eligible and were included in this network meta-analysis. Compared with other groups, patients in the <20 min + TTM group were more likely to have better survival and good neurologic outcomes (probability = 46.1 and 52.5%, respectively). In comparing the same time groups with and without TTM, only the survival and neurologic outcome of the 20–39 min + TTM group was significantly better than that of the 20–39 min group [odds ratio = 1.41, 95% confidence interval (1.04–1.91); OR = 1.46, 95% CI (1.07–2.00) respectively]. Applying TTM with <20 min or more than 40 min of collapse to ROSC did not improve survival or neurologic outcome [ <20 min vs. <20 min + TTM: OR = 1.02, 95% CI (0.61–1.71)/OR = 1.03, 95% CI (0.61–1.75); 40–59 min vs. 40–59 min + TTM: OR = 1.50, 95% CI (0.97–2.32)/OR = 1.40, 95% CI (0.81–2.44); ≧60 min vs. ≧60 min + TTM: OR = 2.09, 95% CI (0.70–6.24)/OR = 4.14, 95% CI (0.91–18.74), respectively]. Both survival and good neurologic outcome were closely related to the time from collapse to ROSC.Conclusion: Survival and good neurologic outcome are closely associated with the time of collapse to ROSC. These findings supported that 20–40 min of collapse to ROSC should be a more suitable indication for TTM for cardiac arrest patients. Moreover, the future trials should pay more attention to these patients who suffer from moderate injury.Systematic Review Registration: [https://inplasy.com/?s=202180027], identifier [INPLASY202180027]

Clinical Significance of Gray to White Matter Ratio after Cardiopulmonary Resuscitation in Children

Cardiopulmonary resuscitation (CPR) successfully restores systemic circulation approximately 50% of the time; however, many successfully restored patients have severe neurologic damage. In adults, the gray matter to white matter attenuation ratio (GWR) in brain computed tomography (CT) correlates with the neurologic outcome. However, in children, the clinical significance of GWR still remains unclear. The aim of this study was to evaluate the clinical characteristics of children who underwent CPR for cardiac arrest according to the survival and to demonstrate the differentiation of grey/white matter by Hounsfield units of brain CT and to characterize the attenuations of grey and white matters. Methods: This is a retrospective single-center study. We enrolled those who underwent brain CT within 24 h after return of spontaneous circulation (ROSC) from January 2005 to June 2018. Brain CTs were taken within 24 h of ROSC. We measured the attenuation of grey and white matter in Hounsfield units and calculated GWR. They were compared with healthy controls. Patients were analyzed as follows: survivors vs. non-survivors and better neurologic outcome vs. worse neurologic outcome. Results: Among 100 pediatric patients who had CPR, 56 met inclusion criteria. There were 24 patients who survived and 32 non-survivors. Our study revealed that the incidence of seizure, duration of CPR, and instances of hypothermia were significantly different between survivors and non-survivors. In both survivors and non-survivors, the attenuation of the caudate nucleus, putamen, GWR-basal ganglia, and average GWR were significantly different from controls. In regression analyses, the medial cortex and average GWR were the significant variables to predict survival, and the receiver operating curves revealed areas under curve of 0.733 and 0.666, respectively. Also, the medial cortex 1 was the only variable that predicted the neurologic outcome. Conclusions: There was some predictive survival value of GWR and medial cortex at the centrum semiovale level in early brain CT within 24 h after cardiac arrest. Although we could not find the predictive value of GWR in the neurologic outcome of pediatric patients, we found that the absolute attenuation of the medial cortex was low in patients with worse neurologic outcomes. Further prospective, multicenter studies are needed to determine the predictive value of GWR and the medial cortex.

Review of novel therapeutics in cardiac arrest (ReNTICA): systematic review protocol

IntroductionCardiac arrest remains a common and devastating cause of death and disability worldwide. While targeted temperature management has become standard of care to improve functional neurologic outcome, few pharmacologic interventions have shown similar promise.Methods/analysisThis systematic review will focus on prospective human studies from 2015 to 2020 available in PubMed, Web of Science and EMBASE with a primary focus on impact on functional neurologic outcome. Prospective studies that include pharmacologic agents given during or after cardiac arrest will be included. Study selection will be in keeping with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. If sufficient data involving a given agent are available, a meta-analysis will be conducted and compared with current evidence for therapies recommended in international practice guidelines.Ethics and disseminationFormal ethical approval will not be required as primary data will not be collected. The results will be disseminated through peer-reviewed publication, conference presentation and lay press.PROSPERO registration numberInternational Prospective Register for Systematic Reviews (CRD42021230216).

High Dose Steroids as First-Line Treatment Increased the Risk of In-Hospital Infections in Patients With Anti-NMDAR Encephalitis

ObjectiveTo address the effects of high dose steroids on in-hospital infection and neurologic outcome in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients.MethodsWe retrospectively reviewed the clinical data of anti-NMDAR encephalitis patients in West China Hospital, the Third Hospital of Mianyang and Mianyang Central Hospital between October 2011 and August 2020. The development of infections, inflammatory factors, neurologic outcome at discharge and risk factors for in-hospital infection were assessed in patients with and without high dose steroid therapy before and after immunotherapy. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression models were established to assess risk factors for in-hospital infection.ResultsA total of 278 patients with anti-NMDAR encephalitis were included in the study. Thirty-four patients received high dose methylprednisolone (IVMP) therapy only, 84 patients received intravenous immunoglobulin (IVIG) therapy, and 160 patients received IVIG and IVMP therapy. Compared with the IVIG group, IVIG + IVMP group had a higher infection rate (64.38% vs 39.29%, P < 0.001), a higher incidence of noninfectious complications (76.25% vs 61.90%, P = 0.018) and a higher modified Rankin Scale (mRS) score at discharge from the hospital (3 vs 2, P < 0.001). Inflammatory indicators, including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), were higher (9.93 vs 5.65, 6.94 vs 3.47 and 1.47 vs 0.70, respectively, P < 0.001) in the IVIG + IVMP group than in the IVIG group. Moreover, lymphocyte-to-monocyte ratio (LMR) was lower (2.20 vs 2.54, P = 0.047) in the IVIG + IVMP group. The LASSO model showed that mRS score on admission, seizure, body temperature, uric acid (URIC), cerebrospinal fluid immunoglobulin G (CSF IgG), NLR and LMR were risk factors for in-hospital infection. The prediction model exhibited an area under the curve (AUC) of 0.885.ConclusionsHigh dose steroids therapy was significantly associated with higher in-hospital infectious complication rates and a poor short-term prognosis in relatively severe anti-NMDAR encephalitis patients. The established prediction model might be helpful to reduce the risk of in-hospital infection.

ICU delirium burden predicts functional neurologic outcomes

Background We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness. Methods Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016. Altogether, patients were assessed daily for delirium 2941days using the Confusion Assessment Method for the ICU (CAM-ICU). Hospitalization delirium burden (DB) was quantified as number of hospital days with delirium divided by total days at risk. Survival status up to 2.5 years and neurologic outcomes using the Glasgow Outcome Scale were recorded at discharge 3, 6, and 12 months post-discharge. Results Of 178 patients, 19 (10.7%) were excluded from outcome analyses due to persistent coma. Among the remaining 159, 123 (77.4%) experienced delirium. DB was independently associated with >4-fold increased mortality at 2.5 years following ICU admission (adjusted hazard ratio [aHR], 4.77; 95% CI, 2.10–10.83; P < .001), and worse neurologic outcome at discharge (adjusted odds ratio [aOR], 0.02; 0.01–0.09; P < .001), 3 (aOR, 0.11; 0.04–0.31; P < .001), 6 (aOR, 0.10; 0.04–0.29; P < .001), and 12 months (aOR, 0.19; 0.07–0.52; P = .001). DB in the ICU alone was not associated with mortality (HR, 1.79; 0.93–3.44; P = .082) and predicted neurologic outcome less strongly than entire hospital stay DB. Similarly, the number of delirium days in the ICU and for whole hospitalization were not associated with mortality (HR, 1.00; 0.93–1.08; P = .917 and HR, 0.98; 0.94–1.03, P = .535) nor with neurological outcomes, except for the association between ICU delirium days and neurological outcome at discharge (OR, 0.90; 0.81–0.99, P = .038). Conclusions Delirium burden throughout hospitalization independently predicts long term neurologic outcomes and death up to 2.5 years after critical illness, and is more predictive than delirium burden in the ICU alone and number of delirium days.

Fetal Central Nervous System Derived Extracellular Vesicles: Potential for Non-invasive Tracking of Viral Mediated Fetal Brain Injury

Introduction: Extracellular vesicles derived from the fetal central nervous system (FCNSEs) can be purified from maternal serum or plasma using the protein Contactin-2/TAG1that is expressed almost exclusively by developing neurons in the hippocampus, cerebral cortex and cerebellum. We hypothesized that fetal CNSEs could be used to non-invasively detect and quantify viral mediated in-utero brain injury in the first trimester.Materials and Methods: First trimester maternal samples were collected from a human clinical population infected with primary cytomegalovirus (CMV) and a non-human primate model of Zika (ZIKV) infection. In the CMV cohort, a nested case control study was performed comparing pregnancies with and without fetal infection. Cases of fetal infection were further subdivided into those with and without adverse neurologic outcome. ZIKV samples were collected serially following maternal inoculation or saline. All ZIKV cases had histopathologic findings on necropsy. Serum was precipitated with ExoQuick solution and FCEs were isolated with biotinylated anti-Contactin-2/TAG1 antibody-streptavidin matrix immunoabsorption. FCE Synaptopodin (SYNPO) and Neurogranin (NG) protein levels were measured using standard ELISA kits and normalized to the exosome marker CD81.Results: Fetal CNSE SYNPO and NG were significantly reduced in cases of first trimester fetal CMV infection compared to those with infection limited to the mother but could not discriminate between fetal infection with and without adverse neurologic outcome. Following ZIKV inoculation, fetal CNSE SYNPO was reduced by 48 h and significantly reduced by day 4.Discussion: These data are the first to suggest that first trimester non-invasive diagnosis of fetal viral infection is possible. Fetal CNSEs have the potential to augment clinical and pre-clinical studies of perinatal viral infection. Serial sampling may be needed to discriminate between fetuses that are responding to treatment and/or recovering due to innate defenses and those that have ongoing neuronal injury. If confirmed, this technology may advance the paradigm of first trimester prenatal diagnosis and change the calculus for the cost benefit of CMV surveillance programs in pregnancy.

Alpha-power in Electroencephalography as Good Outcome Predictor for Out-of-Hospital Cardiac Arrest Survivors

Background This study aimed to identify the quantitative EEG biomarkers for predicting good neurologic outcomes in OHCA survivors treated with targeted temperature management (TTM) using power spectral density (PSD), event-related spectral perturbation (ERSP), and spectral entropy (SE). Methods This observational registry-based study was conducted at a tertiary care hospital in Korea using data of adult nontraumatic comatose OHCA survivors who underwent standard EEG and treated with TTM between 2010 and 2018. Good neurological outcome at 1 month (Cerebral Performance Category scores 1 and 2) was the primary outcome. The linear mixed model analysis was performed for PSD, ESRP, and SE values of all and each frequency band. Results Thirteen of the 54 comatose OHCA survivors with TTM and EEG, 13 were excluded due to poor EEG quality or periodic/rhythmic pattern, leaving 41 patients for analysis. The median time to EEG was 21 h, and the rate of the good neurologic outcome at 1 month was 52.5%. The good neurologic outcome group was significantly younger and showed higher PSD and ERSP and lower SE features for each frequency than the poor outcome group. After age adjustment, only the alpha-PSD was significantly higher in the good neurologic outcome group (1.13 ± 1.11 vs. 0.09 ± 0.09, p = 0.031) and had best performance with 0.903 of the area under the curve for predicting good neurologic outcome. Conclusions Alpha-PSD best predicts good neurologic outcome in OHCA survivors and is an early biomarker for prognostication. Larger studies are needed to conclusively confirm these findings.

Background frequency can enhance the prognostication power of EEG patterns categories in comatose cardiac arrest survivors: a prospective, multicenter, observational cohort study

Background We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns (“highly malignant,” “malignant,” and “benign”) according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest. Methods This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3–5) at 1 month. Results Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the “highly malignant” pattern (40.7%) was most prevalent, followed by the “benign” (33.9%) and “malignant” (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with “malignant” patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of “highly malignant” or “malignant” EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%. Conclusions The “highly malignant” patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016—Retrospectively registered.

Abstract 13945: Central Cannulation During Pediatric Extracorporeal Cardiopulmonary Resuscitation is Faster Than Peripheral Approaches

Introduction: Favorable survivorship after pediatric extracorporeal cardiopulmonary resuscitation (ECPR) may be limited by prolonged resuscitations. Surgical cannulation metrics for pediatric ECPR have not been widely reported by centers that use time interval benchmarks with a cardiovascular service responding to different hospital locations. Hypothesis: We hypothesize that survival is associated with resuscitation duration, and cannulation duration differs between peripheral and central approaches. Methods: This was a single-center retrospective study of patients 0-18 years with in-hospital ECPR between January 2015 and December 2020. Primary outcome was survival to hospital discharge. Secondary outcomes were odds of favorable neurologic outcome (dichotomized pediatric cerebral performance category), total resuscitation duration defined as cardiac arrest start to ECMO flow start (CA-ECMO), and cannulation duration. Non-parametric and regression methods were used. Results: Of the 92 events that met ECPR criteria, median weight and age were 4 months (IQR 1 month, 16 years) and 4.4 kg (range 1.9-133 kg). Cannulation occurred in the cardiac intensive care unit (ICU) (66%, 61 of 92), followed by operating room (13%, 12 of 92), pediatric ICU (12%, 11 of 92), and catheterization lab (9%, 8 of 92). Central cannulation was performed in 43% (40 of 92), and 21% (19 of 92) had open chests at the time of the event. Median duration of CA-ECMO was 35 min (IQR 26, 45 min); cannulation duration was 11 min (IQR 5, 16.5 min) for central compared to 18.5 min (IQR 12, 23 min) for peripheral approaches (P=0.01). Survival was 40% (37 of 92), and favorable neurologic outcome occurred in 38% (35 of 92). Survival (adjusted OR, 0.94; 95% CI 0.91-0.99, P=0.018) and favorable neurologic outcome (adjusted OR, 0.95; 95% CI 0.917-1.000, P=0.053) were associated with CA-ECMO duration after adjusting for cannulation approach, location, difficulty, shockable rhythm, and weight. Conclusion: In pediatric in-hospital ECPR, total CA-ECMO duration remains a key metric associated with patient outcomes. Central cannulation is faster than peripheral approaches. Since cannulation strategy alters CPR maneuvers, CPR effectiveness with each approach needs further study.