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To determine the association between the induction rate and 6-month neurologic outcomes in out-of-hospital cardiac arrest (OHCA) survivors who underwent targeted temperature management (TTM). This retrospective observational study analyzed data prospectively collected from adult comatose OHCA survivors treated with TTM at the Chonnam National University Hospital in Gwangju, Korea, between October 2015 and December 2020. We measured the core body temperature (BT) through an esophageal probe and recorded it every 5 minutes throughout TTM. Induction time was defined as the elapsed time between the initiation of TTM and the achievement of target BT of 33°C. We calculated the induction rate as the change of BT divided by induction time. The primary outcome was a poor 6-month neurologic outcome, defined as cerebral performance category 3-5. Of the OHCA survivors, 218 patients were included, and 137 (62.8%) patients had a poor neurologic outcome. Patients with a poor neurologic outcome had lower BT at the initiation of TTM, shorter induction time, and higher induction rate than those with good neurologic outcomes. After adjusting for confounders, induction time (odds ratio [OR] 0.995; 95% confidence interval [CI], 0.992-0.999) and induction rate (OR 2.362; 95% CI, 1.178-4.734) were independently associated with poor neurologic outcome. BT at TTM initiation was not associated with a poor neurologic outcome. Induction rate was independently associated with a poor neurologic outcome in OHCA survivors who underwent TTM at 33°C.

We investigated the association of insulin administration method with the achievement of mean glucose ≤ 180 mg/dL and neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors who had hyperglycemia after the return of spontaneous circulation. From a multicenter prospective registry, we extracted the data of adult OHCA survivors who underwent targeted temperature management (TTM) between 2015 and 2018. Blood glucose levels every 4 h after initiating TTM were obtained for 72 h. We divided insulin administration methods into three categories: subcutaneous (SQI), intravenous bolus (IBI), and continuous intravenous (CII). We calculated the mean glucose and standard deviation (SD) of glucose. The primary outcome was the achievement of mean glucose ≤ 180 mg/dL. The secondary outcomes were the 6-month neurological outcome based on the Cerebral Performance Category (CPC) scale (good, CPC 1-2; poor, CPC 3-5), mean glucose, and SD of glucose. Of the 549 patients, 296 (53.9%) achieved mean glucose ≤ 180 mg/dL, and 438 (79.8%) had poor neurological outcomes, 134 (24.4%), 132 (24.0), and 283 (51.5%) were in the SQI, IBI, and CII groups, respectively. The SQI (adjusted odds ratio [aOR], 0.848; 95% confidence intervals [CIs], 0.493-1.461) and IBI (aOR, 0.673; 95% CIs, 0.415-1.091) groups were not associated with mean glucose ≤ 180 mg/dL and the SQI (aOR, 0.660; 95% CIs, 0.335-1.301) and IBI (aOR, 1.757; 95% CIs, 0.867-3.560) groups were not associated with poor neurological outcomes compared to the CII group. The CII (168 mg/dL [147-202]) group had the lowest mean glucose than the SQI (181 mg/dL [156-218]) and IBI (184 mg/dL [162-216]) groups. The CII (45.0[33.9-63.5]) group had a lower SD of glucose than the IBI (50.8 [39.1-72.0]) group. The insulin administration method was not associated with achieving mean glucose ≤ 180 mg/dL and 6-month neurological outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We examined the association between variability in body temperature (BT) and water temperature (WT) during the maintenance period of targeted temperature management (TTM) and neurologic outcomes in out-of-hospital cardiac arrest (OHCA) survivors. Adult (≥18 years), comatose OHCA survivors who underwent TTM at 33°C between October 2015 and December 2019 were included. We collected data on BT and WT recorded every minute during the TTM maintenance period. Temperature variability was measured as the standard deviation of BT and WT during the 33°C maintenance period. The primary outcome was a poor neurologic outcome, defined as a cerebral performance category scale 3-5 at 6 months. Of the 154 included patients, 96 (62.3%) had poor outcomes. The BT variability in the poor outcome group was lower than that in the good outcome group (0.16°C [0.13-0.27°C] vs. 0.13°C [0.11-0.18°C]). In addition, the WT variability during the maintenance period in the poor outcome group was lower than that in the good outcome group (2.24°C [1.80-3.96°C] vs. 1.77°C [1.26-2.32°C]). In the multivariate analysis, WT variability (odds ratio 0.508; 95% confidence interval, 0.295-0.874; p  = 0.014) was independently associated with poor neurologic outcome. BT variability and cooling beyond 33.0°C ± 1.0°C were not associated with poor neurologic outcomes. WT variability during the maintenance period was independently associated with neurologic outcomes in OHCA survivors who underwent TTM at 33°C. In addition, overcooling or undercooling during the maintenance period was not associated with neurologic outcomes.

We evaluated the performance of cardiac arrest-specific prognostication scores developed for outcome prediction in the early hours after out-of-hospital cardiac arrest (OHCA) in predicting long-term outcomes using independent data. The following scores were calculated for 1,163 OHCA patients who were treated with targeted temperature management (TTM) at 21 hospitals in South Korea: OHCA, cardiac arrest hospital prognosis (CAHP), C-GRApH (named on the basis of its variables), TTM risk, 5-R, NULL-PLEASE (named on the basis of its variables), Serbian quality of life long-term (SR-QOLl), cardiac arrest survival, revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST), Polish hypothermia registry (PHR) risk, and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages (PROLOGUE) scores and prediction score by Aschauer et al. Their accuracies in predicting poor outcome at 6 months after OHCA were determined using the area under the receiver operating characteristic curve (AUC) and calibration belt. In the complete-case analyses, the PROLOGUE score showed the highest AUC (0.923; 95% confidence interval [CI], 0.904-0.941), whereas the SR-QOLl score had the lowest AUC (0.749; 95% CI, 0.711-0.786). The discrimination performances were similar in the analyses after multiple imputation. The PROLOGUE, TTM risk, CAHP, NULL-PLEASE, 5-R, and cardiac arrest survival scores were well calibrated. The rCAST and PHR risk scores showed acceptable overall calibration, although they showed miscalibration under the 80% CI level at extreme prediction values. The OHCA score, C-GRApH score, prediction score by Aschauer et al., and SR-QOLl score showed significant miscalibration in both complete-case (P = 0.026, 0.013, 0.005, and < 0.001, respectively) and multiple-imputation analyses (P = 0.007, 0.018, < 0.001, and < 0.001, respectively). In conclusion, the discrimination performances of the prognostication scores were all acceptable, but some showed significant miscalibration., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings., Design: Retrospective analysis of the Korean Hypothermia Network Pro registry., Setting: Multicenter ICU., Patients: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018., Interventions: None., Measurements and Main Results: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes., Conclusions: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Rearrest occurs commonly after initial resuscitation following out-of-hospital cardiac arrest (OHCA). We determined (1) the predictors of rearrest during hospitalisation that can be identified in the hours immediately after OHCA, (2) the association between rearrest and favourable long-term outcomes, and (3) the predictors of favourable long-term outcomes in rearrest patients., Methods: Conditional multivariable logistic regression analyses were performed using the Korean Hypothermia Network prospective registry data, which included details of adult OHCA patients treated with targeted temperature management at 22 teaching hospitals in South Korea., Results: Among the 1,233 patients, 260 (21.1%) experienced rearrest. Of the 192 patients resuscitated from first rearrest, 33 (17.2%) achieved 6-month favourable outcomes. Arrhythmia, heart failure, ST-segment elevation, lower initial Glasgow coma scale (GCS) motor score, higher initial lactate level, and antiarrhythmic drug use within 1 h were independently associated with rearrest. Higher lactate level and antiarrhythmic drug use were associated with shockable first rearrest, while arrhythmia, heart failure, ST-segment elevation, and lower GCS motor score were associated with non-shockable first rearrest. Rearrest was independently associated with a lower likelihood of 6-month favourable outcomes (P = 0.003). Initial shockable rhythm after OHCA, absence of diabetes, shorter cumulative time to restoration of spontaneous circulation, coronary angiography, and hypophosphataemia within 7 d were independently associated with 6-month favourable outcomes in the patients resuscitated from first rearrest., Conclusions: Rearrest during hospitalisation after OHCA was inversely associated with 6-month favourable outcomes. We identified several risk factors for rearrest and prognostic factors for patients resuscitated from first rearrest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We aimed to verify whether slow heart rate (HR) is associated with neurologic outcome and the factors that can contribute to the development of bradycardia in out-of-hospital cardiac arrest (OHCA) survivors who underwent targeted temperature management (TTM). We extracted the data of comatose adult OHCA survivors who underwent TTM between October 2015 and December 2018 from the prospective multicenter registry. Data on HR recorded every 6 hours within 72 hours after return of spontaneous circulation and calculated minimal, mean, and maximal HR and time to the lowest HR were obtained. HR <50 bpm was defined as bradycardia. The primary outcome was a 6-month neurologic outcome based on Pittsburgh-Glasgow Cerebral Performance Category Scale. Of the 814 included patients, 508 (62.4%) had poor neurologic outcome and 197 (24.2%) had bradycardia. Bradycardia (odds ratio [OR], 0.574; 95% confidence interval [CI], 0.362-0.192), minimal HR (OR, 1.023; 95% CI, 1.008-1.037), and mean HR (OR, 1.016; 95% CI, 1.002-1.030) were independently associated with poor neurologic outcome, but not maximal HR and time to the lowest HR. Preexisting arrhythmia (OR, 2.067; 95% CI, 1.037-4.118), renal disease (OR, 2.028; 95% CI, 1.153-3.567), cardiac etiology (OR, 1.526; 95% CI, 1.045-2.228), downtime (OR, 0.985; 95% CI, 0.974-0.996), and serum lactate levels (OR, 0.936; 95% CI, 0.900-0.974) were independently associated with bradycardia. Bradycardia and decreased mean and minimal HR were independently associated with good neurologic outcomes. Bradycardia was associated with preexisting arrhythmia, renal disease, cardiac etiology, shorter downtime, and lower serum lactate level.

Background: Early prognostication after cardiac arrest would be useful. We aimed to develop a scoring model for early prognostication in unselected adult cardiac arrest patients., Methods: We retrospectively analysed data of adult non-traumatic cardiac arrest patients treated at a tertiary hospital between 2014 and 2018. The primary outcome was poor outcome at hospital discharge (cerebral performance category, 3-5). Using multivariable logistic regression analysis, independent predictors were identified among known outcome predictors, that were available at intensive care unit admission, in patients admitted in the first 3 years (derivation set, N = 671), and a scoring system was developed with the variables that were retained in the final model. The scoring model was validated in patients admitted in the last 2 years (validation set, N = 311)., Results: The poor outcome rates at hospital discharge were similar between the derivation (66.0%) and validation sets (64.3%). Age <59 years, witnessed collapse, shockable rhythm, adrenaline dose <2 mg, low-flow duration <18 min, reactive pupillary light reflex, Glasgow Coma Scale motor score ≥2, and levels of creatinine <1.21 mg dl -1 , potassium <4.4 mEq l -1 , phosphate <5.8 mg dl -1 , haemoglobin ≥13.2 g dl -1 , and lactate <8 mmol l -1 were retained in the final multivariable model and used to develop the scoring system. Our model demonstrated excellent discrimination in the validation set (area under the curve of 0.942, 95% confidence interval 0.917-0.968)., Conclusions: We developed a scoring model for early prognostication in unselected adult cardiac arrest patients. Further validations in various cohorts are needed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: To examine the association between heat index (HI) during the induction, maintenance, and rewarming periods of targeted temperature management (TTM) and neurologic outcome in out-of-hospital cardiac arrest (OHCA) survivors., Methods: Adult (≥18 years) comatose OHCA survivors who underwent TTM at 33 °C between 2016 and 2018 were included. We collected data on water temperature (WT) recorded every minute during TTM. We calculated HI during induction as the inverse of the average WT × induction time (h) × 100 and HI of maintenance and rewarming as the inverse of the average WT × 100. The primary outcome was a poor neurologic outcome, based on Cerebral Performance Category 3-5 after 6 months., Results: Of the 118 included patients, 78 (66.1%) had poor outcome. Poor outcome group had lower HI during each of three periods than good outcome group. The areas under the curves for poor outcome of HI during the induction, maintenance, and rewarming periods were 0.819 (95% confidence interval [CI], 0.737-0.883), 0.781 (95% CI, 0.696-0.852), and 0.844 (95% CI, 0.765-0.904), respectively. Induction time (odds ratio [OR], 0.991; 95% CI, 0.983-0.999) and HI during induction (OR, 0.916; 95% CI, 0.854-0.983), maintenance (OR, 0.082; 95% CI, 0.011-0.589), and rewarming (OR, 0.009; 95% CI, 0.000-0.285) were associated with poor outcome., Conclusions: Heat generation was independently associated with neurologic outcome in OHCA survivors who underwent TTM at 33 °C. The performance of HI was higher in the rewarming period than in the induction or maintenance period in association with poor neurologic outcomes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Lipid profiles are known to be a risk factor for development of cardiovascular disease. However, the relationship between lipid profiles and outcome in out-of-hospital cardiac arrest (OHCA) survivors remains unclear. We aimed to examine the association between lipid profiles and neurologic outcome in OHCA survivors., Methods: This retrospective observational study included adult (≥18 years) OHCA survivors between January 2016 and December 2018. We measured patients' lipid profiles after return of spontaneous circulation (ROSC) including total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride. The primary outcome was neurologic outcome at hospital discharge. Good neurologic outcome was defined cerebral performance categories 1 and 2., Results: A total of 182 patients were included. Of them, 57 (31.3%) were discharged with good neurologic outcomes. Median serum levels of total cholesterol (178.0 vs. 123.0 mg/dL), HDL (44.0 vs. 31.0 mg/dL), and LDL (104.0 vs. 75.0 mg/dL) were significantly higher in patients with good neurologic outcome. The area under the curves of total cholesterol, HDL, LDL, and triglyceride were 0.742 (95% confidence interval [CI], 0.672-0.803), 0.729 (95% CI, 0.658-0.792), 0.683 (95% CI, 0.610-0.750), and 0.572 (95% CI, 0.497-0.645), respectively. Total cholesterol (odds ratio [OR], 1.013; 95% CI, 1.000-1.025; p = 0.043) and HDL (OR, 1.071; 95% CI, 1.021-1.123; p = 0.005) levels were associated with good neurologic outcomes., Conclusions: The levels of total cholesterol and HDL after ROSC were associated with good neurologic outcomes in patients with OHCA, without considering the effect of other lipid profiles simultaneously., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim of the Study: Brain swelling after cardiac arrest may affect the ventricles. We aimed to investigate the prognostic performance of ventricular characteristics on brain computed tomography (CT) in cardiac arrest survivors who underwent targeted temperature management (TTM)., Methods: This retrospective cohort study included adult comatose cardiac arrest survivors who underwent brain CT scan within 24 h after resuscitation and underwent TTM from 2014 to 2016. The ventricular areas (lateral, third, and fourth ventricle), distances between the anterior horns of the lateral ventricle (LV) and the posterior horns of the LV, and maximal internal diameter of the skull were measured. Grey-to-white matter ratio (GWR), Evans' index, and relative LV area were calculated. The primary outcome was a 6-month neurologic outcome., Results: Of 258 patients, 176 (68.2%) had an unfavourable neurologic outcome. GWR, LV area, third ventricle area, distance between the anterior horns of the LV, distance between the posterior horns of the LV, Evans' index, and relative LV area were different between neurologic outcome groups. Evans' index (0.683; 95% confidence interval [CI], 0.623-0.739) and relative LV area (0.670; 95% CI, 0.609-0.727) had higher value of area under the curve than the other ventricular characteristics and showed prognostic performance comparable with GWR (0.600; 95% CI, 0.538-0.661). All ventricular characteristics and GWR were not independently associated with neurologic outcome after adjusting for covariates., Conclusion: Ventricular characteristics on brain CT were associated with 6 months neurologic outcome in cardiac arrest survivors. Ventricular characteristics were objective measures that had comparable prognostic performance with GWR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim of the Study: Previous studies on the relationship between age and outcomes after cardiac arrest were performed in settings where the majority of patients died after the withdrawal of life support (WLS). We examined the association between age and outcomes of comatose cardiac arrest survivors in a setting where WLS was not performed., Methods: This single-centre retrospective observational study included adult comatose cardiac arrest survivors treated with targeted temperature management. In Korea, WLS is not permitted unless the patient is pronounced brain-dead. The primary outcome was poor neurologic outcome at hospital discharge, defined as Cerebral Performance Categories scores of 3-5. The secondary outcomes were in-hospital and six-month mortalities., Results: A total of 534 patients were analysed. In multivariate analysis, age was not associated with in-hospital mortality (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.99-1.02), but it was independently associated with neurologic outcome at hospital discharge (OR, 1.03; 95% CI, 1.02-1.05) and six-month mortality (OR, 1.05; 95% CI, 1.03-1.07). When age was categorised into 10-year intervals, age groups less than 61-70 years had significantly lower OR for poor neurologic outcome compared with the reference group (61-70 years), while the OR for poor neurologic outcome in age groups greater than 70 years did not differ from that in the reference group., Conclusion: In a setting where WLS is not performed, we found that age was not associated with in-hospital mortality but was independently associated with neurologic outcome at hospital discharge and six-month mortality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim of the Study: Studies examining associations between time to target temperature and outcomes in cardiac arrest patients who underwent targeted temperature management (TTM) have shown inconsistent results. We examined these associations separately for time from restoration of spontaneous circulation to TTM initiation (pre-induction time) and time from TTM initiation to target temperature (induction time). Furthermore, we examined whether critical time thresholds exist if there is an association., Methods: This was a single-centre retrospective observational study including adult cardiac arrest patients treated with TTM from 2008 to 2015. We tested the associations of pre-induction time and induction time with outcomes at hospital discharge using multivariate logistic regression analysis. We then performed additional multivariate analyses, each with the significant timing variable at different binary cutoffs., Results: A total of 515 patients were analysed. At hospital discharge, 357 patients (69.3%) were alive, of whom 161 (31.3%) had a favourable neurologic outcome. In multivariate analysis, a shorter pre-induction time was independently associated with a favourable neurologic outcome (odds ratio [OR], 1.110; 95% confidence interval [CI], 1.025-1.202), whereas the induction time was not (OR, 0.954; 95% CI, 0.852-1.067). We found two pre-induction time thresholds (120 and 360min) that were associated with neurologic outcome., Conclusion: We found that a shorter pre-induction time was independently associated with a favorable neurologic outcome at hospital discharge, whereas induction time was not. We also found two time thresholds at 120 and 360min, after which initiation of cooling was associated with a worse neurologic outcome., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim of the Study: Previous studies found that the gray matter to white matter ratio (GWR) on brain computed tomography (CT) could be used to predict poor outcomes in cardiac arrest survivors. However, these studies have included cardiac arrests of both cardiac and non-cardiac etiologies. We sought to evaluate if the GWR on brain CT can help to predict poor outcomes after out-of-hospital cardiac arrest (OHCA) of cardiac etiology., Methods: Using a multicenter retrospective registry of adult cardiac arrest survivors treated with therapeutic hypothermia, we identified survivors of OHCA of cardiac etiology who underwent brain CT within 24h after successful resuscitation. Gray and white matter attenuations were measured, and the GWRs were calculated as in previous studies. The prognostic values of the GWRs were analyzed, and a logistic regression analysis was performed to determine the contribution of the GWR in predicting poor outcomes (Cerebral Performance Category 3-5)., Results: of 283 included patients, 140 had good outcomes and 143 had poor outcomes. Although the GWRs could predict poor outcomes with statistical significance, the sensitivities were remarkably low (3.5% to 5.6%) at cutoff values with 100% specificity. No significant difference in predictive performance was found between the primary predictive model, containing independent poor outcome predictors, and the primary predictive model combined with the GWR., Conclusion: In a cohort of comatose adults after OHCA of cardiac etiology, the GWR demonstrated poor predictive performance and was not helpful in predicting poor outcomes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)