Validation of neuron-specific enolase in cardiac arrest patients with limited withdrawal of life-sustaining therapy.

Aim: We validated the prognostic performance of neuron-specific enolase (NSE) according to the recommended values in cardiac arrest (CA) survivors. Methods: We analyzed the data of adult CA survivors who underwent targeted temperature management between January 2014 and December 2020. We measured the NSE level 48 h and 72 h after CA. We performed receiver operating characteristics (ROC) and used the reference value (17 µg/L) and the guidelines-suggested value (60 µg/L) as thresholds. The primary outcome was 6-month neurological outcomes with Cerebral Performance Category (CPC), dichotomized into good (CPC 1 or 2) or poor (CPC 3-5). Results: Of the 513 included patients, 346 (67.4 %) patients had poor neurological outcomes. The area under ROC (AUC) of NSE at 48 h was 0.887 (95 % confidence intervals [CIs], 0.851-0.909) with the Youden index of 35.6 µg/L. A false positive rate (FPR) of <2 % was observed (54.1 µg/L). The thresholds values (17, 60) had a sensitivity of 86.1% and 56.7 % and a specificity of 66.7%and 98.8 %, respectively. The AUC of NSE at 72 h was 0.892 (95 % CIs, 0.849-0.920) with the Youden index of 30.4 µg/L. The threshold values (17, 60) had a sensitivity of 86.0%and 59.4 % with a specificity of 72.2%and 98.3 %, respectively. An FPR of <2 % was observed (53.6 µg/L). Among the 156 patients and 113 patients with NSE at 48 h and at 72 h ≤ 17 µg/L, respectively, 109 and 83 patients had good neurological outcomes. Conclusions: The cut-off value of NSE (60 µg/L) was acceptable to predict poor neurological outcomes with an FPR <2 % in cardiac arrest survivors, irrespective of at 48 or 72 h. NSE (17 µg/L) can function as mitigating factor to deter early WLST.

Relationships of Jugular Bulb Parameters with Cerebral Perfusion and Metabolism After Resuscitation from Cardiac Arrest: A Post-Hoc Analysis of Experimental Studies Using a Minipig Model.

BACKGROUND: Cerebral blood flow (CBF) decreases in the first few hours or days following resuscitation from cardiac arrest, increasing the risk of secondary cerebral injury. Using data from experimental studies performed in minipigs, we investigated the relationships of parameters derived from arterial and jugular bulb blood gas analyses and lactate levels (jugular bulb parameters), which have been used as indicators of cerebral perfusion and metabolism, with CBF and the cerebral lactate to creatine ratio measured with dynamic susceptibility contrast magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. METHODS: We retrospectively analyzed 36 sets of the following data obtained during the initial hours following resuscitation from cardiac arrest: percent of measured CBF relative to that at the prearrest baseline (%CBF), cerebral lactate to creatine ratio, and jugular bulb parameters, including jugular bulb oxygen saturation, jugular bulb lactate, arterial-jugular bulb oxygen content difference, cerebral extraction of oxygen, jugular bulb-arterial lactate content difference, lactate oxygen index, estimated respiratory quotient, and arterial-jugular bulb hydrogen ion content difference. Linear mixed-effects models were constructed to examine the effects of each jugular bulb parameter on the %CBF and cerebral lactate to creatine ratio. RESULTS: The arterial-jugular bulb oxygen content difference (P = 0.047) and cerebral extraction of oxygen (P = 0.030) had a significant linear relationship with %CBF, but they explained only 12.0% (95% confidence interval [CI] 0.002-0.371) and 14.2% (95% CI 0.005-0.396) of the total %CBF variance, respectively. The arterial-jugular bulb hydrogen ion content difference had a significant linear relationship with cerebral lactate to creatine ratio (P = 0.037) but explained only 13.8% (95% CI 0.003-0.412) of the total variance in the cerebral lactate to creatine ratio. None of the other jugular bulb parameters were related to the %CBF or cerebral lactate to creatine ratio. CONCLUSIONS: In conclusion, none of the jugular bulb parameters appeared to provide sufficient information on cerebral perfusion and metabolism in this setting.

Acute kidney injury as a prognostic predictor of in-hospital mortality and neurological outcomes in patients after extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly being applied to patients with refractory cardiac arrest, but the survival rate to hospital discharge is only approximately 29%. Because ECPR requires intensive resources, it is important to predict outcomes. We therefore investigated the prognostic association between acute kidney injury (AKI) and ECPR to confirm the performance of AKI as a prognostic predictor of in-hospital mortality and neurological outcomes in ECPR. METHODS: We conducted a retrospective observational study on patients undergoing ECPR for cardiac etiology at Chonnam National University Hospital from 2015 to 2021. The group diagnosed with AKI in any KDIGO category within the first 48 h after ECPR was compared to that without AKI, and the primary outcome of the study was in-hospital mortality. RESULTS: Of 138 enrolled patients, 83 were studied. Hospital mortality occurred in 49 patients (59%), and 55 (66.3%) showed poor neurological outcomes. The AKI group displayed significantly elevated in-hospital mortality (77.8% vs 24.1%) and poor neurological outcomes (81.5% vs 37.9%) compared to the non-AKI group (p < 0.001). Regression analysis showed that AKI was associated with significantly higher rates of both in-hospital mortality (odds ratio (OR) range 10.75-12.88) and neurologic outcomes (OR range 5.9-6.22). CONCLUSIONS: There was a significant association of AKI with both in-hospital mortality and poor neurologic outcome in patients after ECPR, and AKI can be used as an early prognostic predictor in these patients.

Early single session of hyperbaric oxygen therapy mitigates renal apoptosis in lipopolysaccharides-induced endotoxemia in rats.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a prominent sepsis complication, often resulting in adverse clinical outcomes. Hyperbaric oxygen therapy (HBOT), known for its anti-inflammatory characteristics, antioxidant effects, and ability to deliver high oxygen tension to hypo-perfused tissues, offers potential benefits for SA-AKI. This study investigated whether HBOT improved renal injury in sepsis and elucidated its underlying mechanisms. Methods: A lipopolysaccharide (LPS)-induced endotoxemia model was established using 8-week-old C57BL/6 mice. Thirty minutes post-LPS administration, a group of mice underwent HBOT at a 2.5 atmospheric pressure absolute with 100% oxygen for 60 minutes. After 24 hours, all mice were euthanized for measurements. Results: Our results demonstrated that HBOT effectively mitigated renal tubular cell apoptosis. Additionally, HBOT significantly reduced phosphorylated p53 proteins and cytochrome C levels, suggesting that HBOT may attenuate renal apoptosis by impeding p53 activation and cytochrome C release. Notably, HBOT preserved manganese-dependent levels of superoxide dismutase, an antioxidant enzyme, compared to the LPS group. Furthermore, transforming growth factor beta (TGF-ß)/Smad4 and alpha smooth muscle actin expressions were significantly reduced in the LPS + HBOT group. Conclusion: An early single session of HBOT exhibited renoprotective effects in LPS-induced endotoxemia mice models by suppressing p53 activation and cytochrome C levels to mitigate apoptosis. The observed TGF-ß decrease, downstream Smad expression reduction, and antioxidant capacity preservation following HBOT may contribute to these effects.

Feasibility of Magnetic Resonance-Based Conductivity Imaging as a Tool to Estimate the Severity of Hypoxic-Ischemic Brain Injury in the First Hours After Cardiac Arrest.

BACKGROUND: Early identification of the severity of hypoxic-ischemic brain injury (HIBI) after cardiac arrest can be used to help plan appropriate subsequent therapy. We evaluated whether conductivity of cerebral tissue measured using magnetic resonance-based conductivity imaging (MRCI), which provides contrast derived from the concentration and mobility of ions within the imaged tissue, can reflect the severity of HIBI in the early hours after cardiac arrest. METHODS: Fourteen minipigs were resuscitated after 5 min or 12 min of untreated cardiac arrest. MRCI was performed at baseline and at 1 h and 3.5 h after return of spontaneous circulation (ROSC). RESULTS: In both groups, the conductivity of cerebral tissue significantly increased at 1 h after ROSC compared with that at baseline (P = 0.031 and 0.016 in the 5-min and 12-min groups, respectively). The increase was greater in the 12-min group, resulting in significantly higher conductivity values in the 12-min group (P = 0.030). At 3.5 h after ROSC, the conductivity of cerebral tissue in the 12-min group remained increased (P = 0.022), whereas that in the 5-min group returned to its baseline level. CONCLUSIONS: The conductivity of cerebral tissue was increased in the first hours after ROSC, and the increase was more prominent and lasted longer in the 12-min group than in the 5-min group. Our findings suggest the promising potential of MRCI as a tool to estimate the severity of HIBI in the early hours after cardiac arrest.

High incidence of acute kidney injury in extracorporeal resuscitation, Leading to poor prognosis.

Background: Extracorporeal membrane oxygenation (ECMO) patients have a high incidence of acute kidney injury (AKI). Extracorporeal cardiopulmonary resuscitation (ECPR) patients are more likely to develop AKI than ECMO patients because of serious injury during cardiac arrest (CA). Objectives: This study aims to assess the occurrence and outcomes of AKI in ECPR and ECMO, and to identify specific risk factors and clinical implications of AKI in ECPR. Methods: This is a retrospective observational study from a single tertiary care hospital in Gwangju, Korea. Adults (≥18 years) who received ECMO with cardiac etiology in the emergency and inpatient departments from January 2015 to December 2021 were included. The patients (n = 169) were divided into two groups, ECPR and ECMO without CA, and the occurrence of AKI was investigated. The primary outcome of the study was in-hospital mortality, and the secondary outcomes were six-month cerebral performance category (CPC) and AKI during hospitalization. Results: The incidence of AKI was significantly higher with ECPR (67.5 %) than with ECMO without CA (38.4 %). ECPR was statistically significant for Expire (adjusted OR (aOR) 2.45, 95 % CI 1.28-4.66) and Poor CPC (2.59, 1.32-5.09). AKI was also statistically significant for Expire (6.69, 3.37-13.29) and Poor CPC (5.45, 2.73-10.88). AKI was the determining factor for the outcomes of ECPR (p = 0.01). Conclusions: ECPR patients are more likely to develop AKI than ECMO without CA patients. In ECPR patients, AKI leads to poor outcomes. Therefore, clinicians should be careful not to develop AKI in ECPR patients.

Assessment of the Effects of Sodium Nitroprusside Administered Via Intracranial Subdural Catheters on the Cerebral Blood Flow and Lactate Using Dynamic Susceptibility Contrast Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy in a Pig Cardiac Arrest Model.

Background Cerebral blood flow (CBF) is impaired in the early phase after return of spontaneous circulation. Sodium nitroprusside (SNP) administration via intracranial subdural catheters improves cerebral cortical microcirculation. We determined whether the SNP treatment improves CBF in the subcortical tissue and evaluated the effects of this treatment on cerebral lactate. Methods and Results Sixty minutes after return of spontaneous circulation following 14 minutes of untreated cardiac arrest, 14 minipigs randomly received 4 mg SNP or saline via intracranial subdural catheters. CBF was measured in regions of interest within the cerebrum and thalamus using dynamic susceptibility contrast-magnetic resonance imaging. After return of spontaneous circulation, CBF was expressed as a percentage of the baseline value. In the saline group, the %CBF in the regions of interest within the cerebrum remained at approximately 50% until 3.5 hours after return of spontaneous circulation, whereas %CBF in the thalamic regions of interest recovered to approximately 73% at this time point. The percentages of the baseline values in the cortical gray matter and subcortical white matter were higher in the SNP group (group effect P=0.026 and 0.025, respectively) but not in the thalamus. The cerebral lactate/creatine ratio measured using magnetic resonance spectroscopy increased over time in the saline group but not in the SNP group (group-time interaction P=0.035). The thalamic lactate/creatine ratio was similar in the 2 groups. Conclusions SNP administered via intracranial subdural catheters improved CBF not only in the cortical gray matter but also in the subcortical white matter. The CBF improvement by SNP was accompanied by a decrease in cerebral lactate.

Benefits, key protocol components, and considerations for successful implementation of extracorporeal cardiopulmonary resuscitation: a review of the recent literature.

The application of venoarterial extracorporeal membrane oxygenation (ECMO) in patients unresponsive to conventional cardiopulmonary resuscitation (CPR) has significantly increased in recent years. To date, three published randomized trials have investigated the use of extracorporeal CPR (ECPR) in adults with refractory out-of-hospital cardiac arrest. Although these trials reported inconsistent results, they suggest that ECPR may have a significant survival benefit over conventional CPR in selected patients only when performed with strict protocol adherence in experienced emergency medical services-hospital systems. Several studies suggest that identifying suitable ECPR candidates and reducing the time from cardiac arrest to ECMO initiation are key to successful outcomes. Prehospital ECPR or the rendezvous approach may allow more patients to receive ECPR within acceptable timeframes than ECPR initiation on arrival at a capable hospital. ECPR is only one part of the system of care for resuscitation of cardiac arrest victims. Optimizing the chain of survival is critical to improving outcomes of patients receiving ECPR. Further studies are needed to find the optimal strategy for the use of ECPR.

THE INITIAL ION SHIFT INDEX AS A PROGNOSTIC INDICATOR TO PREDICT PATIENT SURVIVAL IN TRAUMATIC DAMAGE CONTROL LAPAROTOMY PATIENTS.

ABSTRACT: Objective: The ion shift index (ISI), which considers extracellular fluid ions such as phosphate, calcium, and magnesium, represents the ion shift following ischemia; concentrations of these ions are maintained within narrow normal ranges by adenosine triphosphate-dependent homeostasis. The ISI is defined as follows: {potassium (mmol/L-1) + phosphate (mmol/L-1) + Mg (mmol/L-1)}/calcium (mmol/L-1). This study investigated the possibility of predicting the 30-day survival rate of patients who underwent traumatic damage control laparotomy by comparing ISI and other laboratory findings, as well as the initial Trauma and Injury Severity Score (TRISS) and shock indices. Methods: Among the 134 patients who underwent damage control surgery between November 2012 and December 2021, 115 patients were enrolled in this study. Data regarding injury mechanism, age, sex, laboratory findings, vital signs, Glasgow Coma Scale score, Injury Severity Score, Abbreviated Injury Scale score, blood component transfusion, type of surgery, postoperative laboratory outcomes, morbidity, mortality rates, fluids administered, and volume of transfusions were collected and analyzed. Results: In univariate analysis, the odds ratio of the initial ISI was 2.875 (95% confidence interval, 1.52-5.43; P = 0.04), which showed a higher correlation with mortality compared with other indices. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were derived from different multivariable logistic regression models. The initial ISI had high sensitivity and specificity in predicting patient mortality (AUC, 0.7378). In addition, in the model combining the initial ISI, crystalloids, and TRISS, the AUC showed a high value (AUC, 0.8227). Conclusion: The ISI evaluated using electrolytes immediately after admission in patients undergoing traumatic damage control surgery may be a predictor of patient mortality.

The Association Between Induction Rate and Neurologic Outcome in Patients Undergoing Targeted Temperature Management at 33°C.

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.

Association between insulin administration method and six-month neurological outcome in survivors of out-of-hospital cardiac arrest who underwent targeted temperature management.

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.

Supranormal arterial oxygen tension only during the first six hours after cardiac arrest is associated with unfavourable outcomes.

BACKGROUND: Multiple studies have investigated the association between hyperoxaemia following cardiac arrest (CA) and unfavourable outcomes; however, they have yielded inconsistent results. Most previous studies quantified oxygen exposure without considering its timing or duration. We investigated the relationship between unfavourable outcomes and supranormal arterial oxygen tension (PaO2 ), commonly defined as PaO2 > 100 mmHg, at specific time intervals within 24 h following CA. METHODS: This retrospective observational study included 838 adult non-traumatic patients with CA. The first 24 h following CA were divided into four 6-h time intervals, and the first 6-h period was further divided into three 2-h segments. Multivariable logistic regression analyses were conducted to assess associations of the highest PaO2 and time-weighted average PaO2 (TWA-PaO2 ) values at each time interval with unfavourable outcomes at hospital discharge (cerebral performance categories 3-5). RESULTS: The highest PaO2 (p = .028) and TWA-PaO2 (p = .022) values during the 0-6-h time interval were significantly associated with unfavourable outcomes, whereas those at time intervals beyond 6 h were not. The association was the strongest at supranormal PaO2 values within the 0-2-h time interval, becoming significant at PaO2 values ≥ 150 mmHg. During the first 6 h, longer time spent at ≥150 mmHg of PaO2 was associated with an increased risk of unfavourable outcomes (p = .038). The results were consistent across several sensitivity analyses. CONCLUSION: Supranormal PaO2 during but not after the first 6 h following cardiac arrest was independently associated with unfavourable outcomes.

The association of different target temperatures in targeted temperature management with neurological outcome after out-of-hospital cardiac arrest based on a prospective multicenter observational study in Korea (the KORHN-PRO registry): IPTW analysis.

BACKGROUND: Among comatose survivors of out-of-hospital cardiac arrest (OHCA), targeted temperature management (TTM) has improved neurological outcomes. However, although the target temperature shifted from 33°C to 33°C~36°C, the optimal target temperature is still unclear. The goal of this study was to evaluate neurological outcomes at 6 months at target temperatures of 33°C and 36°C. MATERIALS AND METHODS: We analyzed OHCA survivors who underwent TTM and were recorded in the Korean Hypothermia Network, a prospective multicenter registry, from October 2015 to December 2018. The primary outcome was good neurological outcome at six months, defined as a cerebral performance category of 1-2, and the secondary outcome was survival at 6 months. RESULTS: A total of 1339 patients were treated with TTM in twenty-two emergency departments. Of those, 1054 were treated at 33°C, and 285 were treated at 36°C. There was no significant difference in good neurological outcomes at 6 months (30.6% vs. 31.2%, p = 0.850, adjusted OR 0.97, 95% CI = 0.73-1.29]) and survival at six months (41.4% vs. 38.7%, p = 0.401, adjusted HR 1.08, 95% CI = 0.91-1.28]) between TTM 33°C and TTM 36°C. After propensity score matching, good neurological outcomes at 6 months (OR 0.93, 95% CI = 0.74-1.18) and survival at 6 months (HR 1.05, 95% CI = 0.92-1.21) were still not associated with TTM 33°C and TTM 36°C. CONCLUSION: In this study, patients treated with a target temperature of 33°C had similar good neurological outcomes and survival at six months compared with those treated with a target temperature of 36°C.

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model.

Background Postischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest. Methods and Results Twenty-nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT-SNP group) or saline placebo (IT-saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT-saline group, the IT-SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P<0.05) monitored on the cerebral cortex during the 5-hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude-integrated electroencephalography. Repeated-measures analysis of variance revealed significant group-time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters. Conclusions Sodium nitroprusside administered via a subdural intracranial catheter increased post-restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long-term neurologic outcomes.

External validation of the 2020 ERC/ESICM prognostication strategy algorithm after cardiac arrest.

PURPOSE: To assess the performance of the post-cardiac arrest (CA) prognostication strategy algorithm recommended by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) in 2020. METHODS: This was a retrospective analysis of the Korean Hypothermia Network Prospective Registry 1.0. Unconscious patients without confounders at day 4 (72-96 h) after return of spontaneous circulation (ROSC) were included. The association between the prognostic factors included in the prognostication strategy algorithm, except status myoclonus and the neurological outcome, was investigated, and finally, the prognostic performance of the prognostication strategy algorithm was evaluated. Poor outcome was defined as cerebral performance categories 3-5 at 6 months after ROSC. RESULTS: A total of 660 patients were included in the final analysis. Of those, 108 (16.4%) patients had a good neurological outcome at 6 months after CA. The 2020 ERC/ESICM prognostication strategy algorithm identified patients with poor neurological outcome with 60.2% sensitivity (95% CI 55.9-64.4) and 100% specificity (95% CI 93.9-100) among patients who were unconscious or had a GCS_M score ≤ 3 and with 58.2% sensitivity (95% CI 53.9-62.3) and 100% specificity (95% CI 96.6-100) among unconscious patients. When two prognostic factors were combined, any combination of prognostic factors had a false positive rate (FPR) of 0 (95% CI 0-5.6 for combination of no PR/CR and poor CT, 0-30.8 for combination of No SSEP N20 and NSE 60). CONCLUSION: The 2020 ERC/ESICM prognostication strategy algorithm predicted poor outcome without an FPR and with sensitivities of 58.2-60.2%. Any combinations of two predictors recommended by ERC/ESICM showed 0% of FPR.

Heat loss augmented by extracorporeal circulation is associated with overcooling in cardiac arrest survivors who underwent targeted temperature management.

We investigated the association of extracorporeal circuit-based devices with temperature management and neurological outcome in out-of-hospital cardiac arrest survivors who underwent targeted temperature management. Patients with extracorporeal membrane oxygenation and/or continuous renal replacement therapy were classified as the extracorporeal group. We calculated the cooling rate during the induction period and time-weighted core temperatures (TWCT) during the maintenance period. We defined the sum of TWCT above or below 33 °C as positive and negative TWCT, respectively, and the sum of TWCT above 33.5 °C or below 32.5 °C as undercooling or overcooling, respectively. The primary outcome was the negative TWCT. The secondary outcomes were positive TWCT, cooling rate, undercooling, overcooling, and poor neurological outcomes, defined as Cerebral Performance Category 3-5. Among 235 patients, 150 (63.8%) had poor neurological outcomes and 52 (22.1%) were assigned to the extracorporeal group. The extracorporeal group (ß, 0.307; p < 0.001) had increased negative TWCT, rapid cooling rate (1.77 °C/h [1.22-4.20] vs. 1.24 °C/h [0.77-1.79]; p = 0.005), lower positive TWCT (33.4 °C∙min [24.9-46.2] vs. 54.6 °C∙min [29.9-87.0]), and higher overcooling (5.01 °C min [0.00-10.08] vs. 0.33 °C min [0.00-3.78]). However, the neurological outcome was not associated with the use of extracorporeal devices (odds ratio, 1.675; 95% confidence interval, 0.685-4.094).

External validation of cardiac arrest-specific prognostication scores developed for early prognosis estimation after out-of-hospital cardiac arrest in a Korean multicenter cohort.

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.

Prediction of 6-Month Mortality Using Pre-Extracorporeal Membrane Oxygenation Lactate in Patients with Acute Coronary Syndrome Undergoing Veno-Arterial-Extracorporeal Membrane Oxygenation.

BACKGROUND: The effectiveness of extracorporeal membrane oxygenation (ECMO) for patients with refractory cardiogenic shock or cardiac arrest is being established, and serum lactate is well known as a biomarker of end-organ perfusion. We evaluated the efficacy of pre-ECMO lactate for predicting 6-month survival in patients with acute coronary syndrome (ACS) undergoing ECMO. METHODS: We reviewed the medical records of 148 patients who underwent veno-arterial (VA) ECMO for ACS between January 2015 and June 2020. These patients were divided into survivors and non-survivors based on 6-month survival. All clinical data before and during ECMO were compared between the 2 groups. RESULTS: Patients' mean age was 66.0±10.5 years, and 116 (78.4%) were men. The total survival rate was 45.9% (n=68). Cox regression analysis showed that the pre-ECMO lactate level was an independent predictor of 6-month mortality (hazard ratio, 1.210; 95% confidence interval [CI], 1.064-1.376; p=0.004). The area under the receiver operating characteristic curve of pre-ECMO lactate was 0.64 (95% CI, 0.56-0.72; p=0.002; cut-off value=9.8 mmol/L). Kaplan-Meier survival analysis showed that the cumulative survival rate at 6 months was significantly higher among patients with a pre-ECMO lactate level of 9.8 mmol/L or less than among those with a level exceeding 9.8 mmol/L (57.3% vs. 31.8%, p=0.0008). CONCLUSION: A pre-ECMO lactate of 9.8 mmol/L or less may predict a favorable outcome at 6 months in ACS patients undergoing VA-ECMO. Further research aiming to improve the accuracy of predictions of reversibility in patients with high pre-ECMO lactate levels is essential.

Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

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.

Water Temperature Variability Is Associated with Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Survivors Who Underwent Targeted Temperature Management at 33°C.

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.