Abstract 10029: Near-Infrared Spectroscopy Assessments for the Prediction of Neurological Outcome in the Rat Model of Cardiac Arrest

Introduction: Clinical studies have demonstrated that the initial rapid decrement in regional cerebral oxygen saturation (rSO 2 ) level by near-infrared spectroscopy shortly after ROSC was associated with good neurological outcomes. Aim: To evaluate whether the timing of rSO 2 decline shortly after ROSC reflects the severity of brain injury in a well-established rat model of CA/CPR. Methods: We used a total of 85 Wister SD rats (male, 435.2±3.1 g).To produce variable severities of brain injury, CA was induced by different asphyxial times and resuscitated by finger chest compressions and mechanical ventilation. Survival time was recorded for 72 hours after ROSC. Daily neurofunctional scores (NFS) were evaluated by an investigator blinded to the experiments. Electroencephalography (EEG), immunohistochemistry, plasma IL-6, and the gene expressions of cytokines (IL-1, IL-6, TNF-α, HMGB-1) and mitochondrial fission-related proteins (Dnm1L, Fis1, Mief1) in the brain were also evaluated. Result: Animals in the 12-min CA group exhibited a longer time to EEG recovery after CA/CPR compared with the 6-min group (P<.0001), suggesting the longer CA duration induces a delayed brain electrical recovery. Time from ROSC to achieving the initial minimum rSO 2 value (defined as T nadir ) was significantly prolonged as CA time increased; 15.3 ± 2.3, 32.1 ± 22.1, and 44.0 ± 2.8 min in 6, 9, and 12min CA, respectively (ANOVA: P<.0001). T nadir cut-off of 24-min provided the optimal sensitivity and specificity for predicting good neurologic outcomes (NFS≥60%) at 72 hours after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; P<.01). T nadir showed a better predictive power for the good neurological outcome compared with plasma IL-6. Immunohistochemistry at 24 hours post-CA revealed that FJB-positive degenerating neurons in cortex, caudoputamen, and hippocampus were conspicuous in animals with T nadir >24-min, but not in animals with T nadir ≤24-min. Animals with T nadir >24 tended to have a higher gene expression level of IL-6 in the brain at 2 hours post-ROSC compared to those with T nadir ≤24. T nadir did not show associations with other inflammatory or mitochondrial fission markers. Conclusion: T nadir can be a novel predictor for a good neurological outcome after CA/CPR.

Reliability of prognostic biomarkers after prehospital extracorporeal cardiopulmonary resuscitation with target temperature management

Background Extracorporeal cardiopulmonary resuscitation (ECPR) performed at the emergency scene in out-of-hospital cardiac arrest (OHCA) can minimize low-flow time. Target temperature management (TTM) after cardiac arrest can improve neurological outcome. A combination of ECPR and TTM, both implemented as soon as possible on scene, appears to have promising results in OHCA. To date, it is still unknown whether the implementation of TTM and ECPR on scene affects the time course and value of neurological biomarkers. Methods 69 ECPR patients were examined in this study. Blood samples were collected between 1 and 72 h after ECPR and analyzed for S100, neuron-specific enolase (NSE), lactate, D-dimers and interleukin 6 (IL6). Cerebral performance category (CPC) scores were used to assess neurological outcome after ECPR upon hospital discharge. Resuscitation data were extracted from the Regensburg extracorporeal membrane oxygenation database and all data were analyzed by a statistician. The data were analyzed using non-parametric methods. Diagnostic accuracy of biomarkers was determined by area under the curve (AUC) analysis. Results were compared to the relevant literature. Results Non-hypoxic origin of cardiac arrest, manual chest compression until ECPR, a short low-flow time until ECPR initiation, low body mass index (BMI) and only a minimal need of extra-corporeal membrane oxygenation support were associated with a good neurological outcome after ECPR. Survivors with good neurological outcome had significantly lower lactate, IL6, D-dimer, and NSE values and demonstrated a rapid decrease in the initial S100 value compared to non-survivors. Conclusions A short low-flow time until ECPR initiation is important for a good neurological outcome. Hypoxia-induced cardiac arrest has a high mortality rate even when ECPR and TTM are performed at the emergency scene. ECPR patients with a higher BMI had a worse neurological outcome than patients with a normal BMI. The prognostic biomarkers S100, NSE, lactate, D-dimers and IL6 were reliable indicators of neurological outcome when ECPR and TTM were performed at the emergency scene.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a nationwide multicentre study

Background Extracorporeal cardiopulmonary resuscitation (ECPR) has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). Despite growing interest in and a growing body of literature on ECPR for refractory OHCA, robust evidence on patient eligibility is still lacking. Purpose To describe the survival, neurological outcome, and adherence to the national consensus with respect to use of ECPR for OHCA, and to identify factors associated with outcome. Methods Retrospective, observational cohort study of patients who underwent ECPR for OHCA at four cardiac arrest centres. Binary logistic regression and Kaplan-Meier survival curves were performed to assess association with 30-day mortality. Results A total of 259 patients receiving ECPR for OHCA between July 2011 and December 2020 were included in the study. Thirty-day survival was 26% and a good neurological outcome Cerebral Performance Category (CPC) 1–2 was observed in 94% of patients at discharge. Strict adherence to the national consensus showed a 30-day survival rate of 30%. Adding one or more of the following criteria to the national consensus: signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow &lt;100 minutes, pH &gt;6.8 and lactate &lt;15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified initial presenting rhythm with asystole (RR 1.36, 95% CI 1.18–1.57), pulseless electrical activity (PEA) (RR 1.20, 95% CI 1.03–1.41), initial pH &lt;6.8 (RR 1.28, 95% CI 1.12–1.46) and lactate levels &gt;15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had threefold higher survival rate than patients without signs of life (45% versus 13%, p&lt;0.001) Conclusion A high survival rate with a good neurological outcome was observed in this population of patients treated with ECPR for OHCA. Signs of life during CPR may aid the decision-making in the selection of appropriate candidates. Stringent patient selection for ECPR may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors, why optimization of the selection criteria is still necessary. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported by the Danish Heart Foundation [20-R142-A9498-22178]; and Health Research Foundation of Central Denmark Region [R64-A3178-B1349] Survival and adherence to consensus Signs of life during CPR

Per-pass analysis of recanalization and good neurological outcome in thrombectomy for stroke: Systematic review and meta-analysis

Background and aim First pass effect (FPE) is defined as achieving a complete recanalization with a single thrombectomy device pass. Although clinically desired, FPE is reached in less than 30% of thrombectomy procedures. Multiple device passes are often necessary to achieve successful or complete recanalization. We performed a systematic review and meta-analysis to determine the recanalization rate after each pass of mechanical thrombectomy and its association with good neurological outcome. Methods A literature search was performed for studies reporting the number of device passes required for either successful (mTICI 2b or higher) or complete (mTICI 2c or higher) recanalization. Using random-effect meta-analysis, we evaluated the likelihood of recanalization and good neurological outcome (measured with the modified Rankin Score <2 at 90 days) after each device pass. Results Thirteen studies comprising 4197 patients were included. Among cases with failed first pass, 24% of them achieved final complete recanalization and 45% of them achieved final successful recanalization. Independently to the total number of previously failed attempts, the likelihood of achieving successful recanalization was 30% per pass, and the likelihood to achieve complete recanalization was about 20% per pass. The likelihood of good neurological outcome in patients with final successful recanalization decreased after each device pass: 55% after the first pass, 48% after the second pass, 42% after the third pass, 36% after the fourth pass, and 26% for 5 passes or more. Conclusion Each pass is associated with a stable likelihood of recanalization but a decreased likelihood of good neurological outcome.

Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

Purpose: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. Methods: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. Results: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR ( P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) ( P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. Conclusions: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study

Background Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. Methods This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. Results A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18–1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03–1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12–1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76). Conclusions A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Prehospital Advanced Cardiac Life Support with a Smartphone-Based Direct Medical Oversight in a Metropolitan City, Korea

Out-of-hospital cardiac arrest is considered an important health care problem because it causes family breakdown and enormous social loss due to sudden death. Despite the efforts of many medical policymakers, paramedics, and doctors, the survival rate after cardiac arrest is only marginally increasing. Objective: This study aimed to determine whether advanced life support (ALS) under physician’s direct medical oversight during an emergency through video call on smartphones was associated with improved out-of-hospital cardiac arrest (OHCA) outcomes on the "Smart Advanced Life Support (SALS)" pilot project. Methods: This study was conducted using a "Before-After" controlled trial. The OHCA patients were divided into two periods in a metropolitan city. The basic life support (BLS group) and ALS using video calls on smartphones (SALS group) were performed in the 'Before' and 'After' phases in 2014 and 2015, respectively. The OHCA patients over 18 years of age were included in this study. On the other hand, the patients with trauma, poisoning, and family’s unwillingness, as well as those who received no resuscitation were excluded from the study. The primary and secondary outcomes were survival to discharge and a good neurological outcome (cerebral performance category [CPC] 1-2), respectively. A propensity score matching was conducted to equalize potential prognostic factors in both groups. The adjusted odds ratio (OR) and 95% confidence interval (95% CI) were calculated for survival to discharge and good neurological outcome. Results: In total, 235 and 198 OHCA patients were enrolled in the BLS and the SALS groups, respectively. The outcomes were better in the SALS group, compared to the BLS group regarding the survival to discharge (9.8% vs. 6.8%, P<0.001) and good neurological outcome (6.6% vs. 4.0%, P<0.001), respectively. Regarding propensity score matching, 304 cases were randomly assigned to the SALS and BLS groups. The survivals to discharge rates after matching were 9.2% and 7.2% in the SALS and the BLS groups, respectively (P=0.06). Furthermore, the good neurological outcome rate was 5.9% in the SALS group versus 3.9% in the BLS group (p=0.008). The adjusted ORs of the SALS group were estimated at 1.33 (95% CI: 1.00-1.77) for survival to discharge and 1.73 (95% CI: 1.19-2.53) for the good neurologic outcome, compared to those in the BLS group. Conclusion: An emergency medical system intervention using the SALS protocol was associated with a significant increase in prehospital ROSC and improved survival and neurologic outcome after OHCA.