Quantitative analysis of apparent diffusion coefficients to predict neurological prognosis in cardiac arrest survivors: an observational derivation and internal-external validation study.

BACKGROUND: This study aimed to validate apparent diffusion coefficient (ADC) values and thresholds to predict poor neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors by quantitatively analysing the ADC values via brain magnetic resonance imaging (MRI). METHODS: This observational study used prospectively collected data from two tertiary academic hospitals. The derivation cohort comprised 70% of the patients randomly selected from one hospital, whereas the internal validation cohort comprised the remaining 30%. The external validation cohort used the data from another hospital, and the MRI data were restricted to scans conducted at 3 T within 72-96 h after an OHCA experience. We analysed the percentage of brain volume below a specific ADC value at 50-step intervals ranging from 200 to 1200 × 10-6 mm2/s, identifying thresholds that differentiate between good and poor outcomes. Poor neurological outcomes were defined as cerebral performance categories 3-5, 6 months after experiencing an OHCA. RESULTS: A total of 448 brain MRI scans were evaluated, including a derivation cohort (n = 224) and internal/external validation cohorts (n = 96/128, respectively). The proportion of brain volume with ADC values below 450, 500, 550, 600, and 650 × 10-6 mm2/s demonstrated good to excellent performance in predicting poor neurological outcomes in the derivation group (area under the curve [AUC] 0.89-0.91), and there were no statistically significant differences in performances among the derivation, internal validation, and external validation groups (all P > 0.5). Among these, the proportion of brain volume with an ADC below 600 × 10-6 mm2/s predicted a poor outcome with a 0% false-positive rate (FPR) and 76% (95% confidence interval [CI] 68-83) sensitivity at a threshold of > 13.2% in the derivation cohort. In both the internal and external validation cohorts, when using the same threshold, a specificity of 100% corresponded to sensitivities of 71% (95% CI 58-81) and 78% (95% CI 66-87), respectively. CONCLUSIONS: In this validation study, by consistently restricting the MRI types and timing during quantitative analysis of ADC values in brain MRI, we observed high reproducibility and sensitivity at a 0% FPR. Prospective multicentre studies are necessary to validate these findings.

Association between quantitative analysis of cerebral edema using CT imaging and neurological outcomes in cardiac arrest survivors.

BACKGROUND: To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72-96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3-5 at 6 months after OHCA. RESULTS: Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1-14, 23-35, and 39-56 (all P < 0.05). Only the ΔHUdp = 23-35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23-35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02-1.24; P = 0.02). CONCLUSION: In this cohort study, the increased displacement in ΔHUdp = 23-35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.

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.

Grey-to-White Matter Ratio Values in Early Head Computed Tomography (CT) as a Predictor of Neurologic Outcomes in Survivors of Out-of-Hospital Cardiac Arrest Based on Severity of Hypoxic-Ischemic Brain Injury.

BACKGROUND: Hypoxic-ischemic brain injury (HIBI) is a common complication of out-of-hospital cardiac arrest (OHCA). OBJECTIVES: We investigated whether grey-to-white matter ratio (GWR) values, measured using early head computed tomography (HCT), were associated with neurologic outcomes based on the severity of HIBI in survivors of OHCA. METHODS: This retrospective multicenter study included adult comatose OHCA survivors who underwent an HCT scan within 2 h after the return of spontaneous circulation. HIBI severity was assessed using the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) scale (low, moderate, and severe). Poor neurologic outcomes were defined as Cerebral Performance Categories 3 to 5 at 6 months after OHCA. RESULTS: Among 354 patients, 27% were women and 224 (63.3%) had poor neurologic outcomes. The distribution of severity was 19.5% low, 47.5% moderate, and 33.1% severe. The area under the receiver operating curves of the GWR values for predicting rCAST severity (low, moderate, and severe) were 0.52, 0.62, and 0.79, respectively. The severe group had significantly higher predictive performance than the moderate group (p = 0.02). Multivariate logistic regression analysis revealed a significant association between GWR values and poor neurologic outcomes in the moderate group (adjusted odds ratio = 0.012, 95% CI 0.0-0.54, p = 0.02). CONCLUSIONS: In this cohort study, GWR values measured using early HCT demonstrated variations in predicting neurologic outcomes based on HIBI severity. Furthermore, GWR in the moderate group was associated with poor neurologic outcomes.

Different neuroprognostication thresholds of neuron-specific enolase in shockable and non-shockable out-of-hospital cardiac arrest: a prospective multicenter observational study in Korea (the KORHN-PRO registry).

BACKGROUND: Serum neuron-specific enolase (NSE) is the only recommended biomarker for multimodal prognostication in postcardiac arrest patients, but low sensitivity of absolute NSE threshold limits its utility. This study aimed to evaluate the prognostic performance of serum NSE for poor neurologic outcome in out-of-hospital cardiac arrest (OHCA) survivors based on their initial rhythm and to determine the NSE cutoff values with false positive rate (FPR) < 1% for each group. METHODS: This study included OHCA survivors who received targeted temperature management (TTM) and had serum NSE levels measured at 48 h after return of spontaneous circulation in the Korean Hypothermia Network, a prospective multicenter registry from 22 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. The primary outcome was poor outcome at 6 month, defined as a cerebral performance category of 3-5. RESULTS: Of 623 patients who underwent TTM with NSE measured 48 h after the return of spontaneous circulation, 245 had an initial shockable rhythm. Median NSE level was significantly higher in the non-shockable group than in the shockable group (104.6 [40.6-228.4] vs. 25.9 [16.7-53.4] ng/mL, P < 0.001). Prognostic performance of NSE assessed by area under the receiver operating characteristic curve to predict poor outcome was significantly higher in the non-shockable group than in the shockable group (0.92 vs 0.86). NSE cutoff values with an FPR < 1% in the non-shockable and shockable groups were 69.3 (sensitivity of 42.1%) and 102.7 ng/mL (sensitivity of 76%), respectively. CONCLUSION: NSE prognostic performance and its cutoff values with FPR < 1% for predicting poor outcome in OHCA survivors who underwent TTM differed between shockable and non-shockable rhythms, suggesting postcardiac arrest survivor heterogeneity. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02827422.

Association of ultra-early diffusion-weighted magnetic resonance imaging with neurological outcomes after out-of-hospital cardiac arrest.

BACKGROUND: This study aimed to investigate the association between ultra-early (within 6 h after return of spontaneous circulation [ROSC]) brain diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological outcomes in comatose survivors after out-of-hospital cardiac arrest. METHODS: We conducted a registry-based observational study from May 2018 to February 2022 at a Chungnam national university hospital in Daejeon, Korea. Presence of high-signal intensity (HSI) (PHSI) was defined as a HSI on DW-MRI with corresponding hypoattenuation on the apparent diffusion coefficient map irrespective of volume after hypoxic ischemic brain injury; absence of HSI was defined as AHSI. The primary outcome was the dichotomized cerebral performance category (CPC) at 6 months, defined as good (CPC 1-2) or poor (CPC 3-5). RESULTS: Of the 110 patients (30 women [27.3%]; median (interquartile range [IQR]) age, 58 [38-69] years), 48 (43.6%) had a good neurological outcome, time from ROSC to MRI scan was 2.8 h (IQR 2.0-4.0 h), and the PHSI on DW-MRI was observed in 46 (41.8%) patients. No patients in the PHSI group had a good neurological outcome compared with 48 (75%) patients in the AHSI group. In the AHSI group, cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels were significantly lower in the group with good neurological outcome compared to the group with poor neurological outcome (20.1 [14.4-30.7] ng/mL vs. 84.3 [32.4-167.0] ng/mL, P < 0.001). The area under the curve for PHSI on DW-MRI was 0.87 (95% confidence interval [CI] 0.80-0.93), and the specificity and sensitivity for predicting a poor neurological outcome were 100% (95% CI 91.2%-100%) and 74.2% (95% CI 62.0-83.5%), respectively. A higher sensitivity was observed when CSF NSE levels were combined (88.7% [95% CI 77.1-95.1%]; 100% specificity). CONCLUSIONS: In this cohort study, PHSI findings on ultra-early DW-MRI were associated with poor neurological outcomes 6 months following the cardiac arrest. The combined CSF NSE levels showed higher sensitivity at 100% specificity than on DW-MRI alone. Prospective multicenter studies are required to confirm these results.

Quantitative analysis of early apparent diffusion coefficient values from MRIs for predicting neurological prognosis in survivors of out-of-hospital cardiac arrest: an observational study.

BACKGROUND: This study aimed to quantitatively analyse ultra-early brain diffusion-weighted magnetic resonance imaging (DW-MRI) findings to determine the apparent diffusion coefficient (ADC) threshold associated with neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective study included adult survivors of comatose OHCA who underwent DW-MRI imaging scans using a 3-T MRI scanner within 6 h of the return of spontaneous circulation (ROSC). We investigated the association between neurological outcomes and ADC values obtained through voxel-based analysis on DW-MRI. Additionally, we constructed multivariable logistic regression models with pupillary light reflex (PLR), serum neuron-specific enolase (NSE), and ADC values as independent variables to predict poor neurological outcomes. The primary outcome was poor neurological outcome 6 months after ROSC, determined by the Cerebral Performance Category 3-5. RESULTS: Overall, 131 patients (26% female) were analysed, of whom 74 (57%) showed poor neurological outcomes. The group with a poor neurological outcome had lower mean whole brain ADC values (739.1 vs. 787.1 × 10-6 mm/s) and higher percentages of voxels with ADC below threshold in all ranges (250-1150) (all P < 0.001). The mean whole brain ADC values (area under the receiver operating characteristic curve [AUC] 0.83) and the percentage of voxels with ADC below 600 (AUC 0.81) had the highest sensitivity of 51% (95% confidence interval [CI] 39.4-63.1; cut-off value ≤ 739.2 × 10-6 mm2/s and > 17.2%, respectively) when the false positive rate (FPR) was 0%. In the multivariable model, which also included PLR, NSE, and mean whole brain ADC values, poor neurological outcome was predicted with the highest accuracy (AUC 0.91; 51% sensitivity). This model showed more accurate prediction and sensitivity at an FPR of 0% than did the combination of PLR and NSE (AUC 0.86; 30% sensitivity; P = 0.03). CONCLUSIONS: In this cohort study, early voxel-based quantitative ADC analysis after ROSC was associated with poor neurological outcomes 6 months after cardiac arrest. The mean whole brain ADC value demonstrated the highest sensitivity when the FPR was 0%, and including it in the multivariable model improved the prediction of poor neurological outcomes.

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.

Role of electrocardiogram findings in predicting 48-h mortality in patients with traumatic brain injury.

OBJECTIVE: Electrocardiogram (ECG) patterns can change, especially in patients with central nervous system disorders such as spontaneous subarachnoid hemorrhage. However, the association between the prognosis of traumatic brain injury (TBI) and ECG findings is unknown. Therefore, this study aimed to compare and to analyze ECG findings to predict early mortality in patients with TBI. METHODS: This retrospective observational study included patients with severe trauma and TBI who were admitted to the emergency department (ED) between January 2018 and December 2020. TBI was defined as an abbreviated injury scale score of the head of ≥3. We examined ECG findings, including PR prolongation (≥ 200 ms), QRS complex widening (≥ 120 ms), corrected QT interval prolongation (QTP, ≥ 480 ms), ST-segment elevation, and ST-segment depression (STD) at ED arrival. The primary outcome was 48-h mortality. RESULTS: Of the total patients with TBI, 1024 patients were included in this study and 48-h mortality occurred in 89 patients (8.7%). In multivariate analysis, QTP (odds ratio [OR], 2.017; confidence interval [CI], 1.203-3.382) and STD (OR, 8.428; 95% CI, 5.019-14.152) were independently associated with 48-h mortality in patients with TBI. The areas under the curve (AUCs) of the revised trauma score (RTS), injury severity score (ISS), QTP, STD, and the combination of QTP and STD were 0.790 (95% CI, 0.764-0.815), 0.632 (95% CI, 0.602-0.662), 0.605 (95% CI, 0.574-0.635), 0.723 (95% CI, 0.695-0.750), and 0.786 (95% CI, 0.759-0.811), respectively. The AUC of the combination of QTP and STD significantly differed from that of ISS, QTP, and STD, but not RTS. CONCLUSION: Based on the ECG findings, QTP and STD were associated with 48-h mortality in patients with TBI.

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.

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.

Early identified risk factors and their predictive performance of brain death in out-of-hospital cardiac arrest survivors.

BACKGROUND: Early prediction of brain death (BD) after the return of spontaneous circulation (ROSC) in patients with cardiac arrest would be useful for the proper distribution of good quality transplantable organs and medical resources. We aimed to early identify independent risk factors of BD and their predictive performance in out-of-hospital cardiac arrest (OHCA) survivors. METHODS: This retrospective observational study included adult OHCA survivors from May 2018 to February 2021. Independent risk factors for progression to BD were identified by performing multivariate logistic regression analysis, including clinical, laboratory, biological parameters and prognostic factors, obtained within 6 h after ROSC. Neuron-specific enolase (NSE) level were categorized into quartile. The primary outcome was BD occurrence. RESULTS: Overall, 108 patients were included in this analysis, 31 (29%) of whom had BD. In multivariate logistic regression analysis, initial serum NSE levels in the fourth quartile compared to the first quartile (odds ratio [OR], 88.5; 95% confidence interval [CI]: 7.0-1113.6) and absence of pupil light reflex (PLR) (OR, 40.3; 95% CI: 3.8-430.3) were independently associated with BD. According to the receiver operating characteristic curve analysis, initial serum NSE levels and PLR showed good-to-excellent and fair-to-good prognostic performance, respectively (area under the curve [AUC], 0.90; 95% CI: 0.83-0.95 vs. 0.81; 95% CI: 0.72-0.88). Additionally, the combination of both the risk factors (AUC, 0.96; 95% CI: 0.90-0.99) showed significantly higher predictive performance for BD than when using them individually (P = 0.04 and P < 0.01, respectively). CONCLUSION: High levels of initial serum NSE and PLR obtained within 6 h after ROSC may help early predict progression to BD in OHCA survivors. A large prospective multicenter study should be conducted to confirm these results.

Diagnostic value of transthoracic echocardiography compared to electrocardiogram in predicting coronary artery stenosis among patients after cardiac arrest.

BACKGROUND: In the absence of ST-segment elevation (STE) in post-return of spontaneous circulation (ROSC) electrocardiogram (ECG), coronary angiography (CAG) is required in patients with suspected coronary artery disease (CAD). However, it is a challenge to identify patients with CAD after cardiac arrest (CA). Recent European Society of Cardiology guidelines recommends transthoracic echocardiography in patients presenting with cardiac arrest. We aimed to assess the diagnostic value of regional wall motion abnormalities (RWMAs) on transthoracic echocardiography (TTE) compared to ECG in diagnosing significant coronary artery stenosis in CA patients. METHODS: This is a retrospective, observational study of adult CA patients with presumed cardiac etiology who underwent CAG from a single tertiary care hospital. We compared the predictive value of RWMA on TTE and STE on ECG in significant stenosis of ≥70% of the coronary artery diameter. The primary outcome was significant stenosis on CAG. RESULTS: There were 145 patients included in this study and CAG revealed significant stenosis in 76 (52.4%) patients. Among the 76 patients with significant stenosis, 68 (89.5%) had RWMA on TTE and 41 (54.0%) had STE. RWMA on TTE (OR 3.67; 95% CI 1.52-8.85) was independently associated with significant stenosis. Combining both RWMA on TTE and STE on ECG improved performance in the receiver operating characteristic curve analysis (area under the curve 0.722) for predicting significant stenosis compared to using only ECG alone (p = 0.001). CONCLUSIONS: RWMAs on TTE was independently associated with significant stenosis. The RWMA and STE combination had better predictive performance than using only STE on ECG to predict significant stenosis.

Cerebrospinal Fluid Lactate Levels, Brain Lactate Metabolism and Neurologic Outcome in Patients with Out-of-Hospital Cardiac Arrest.

BACKGROUND/OBJECTIVE: Cerebrospinal fluid (CSF) and serum lactate levels were assessed to predict poor neurologic outcome 3 months after return of spontaneous circulation (ROSC). We compared arterio-CSF differences in the lactate (ACDL) levels between two neurologic outcome groups. METHODS: This retrospective observational study involved out-of-hospital cardiac arrest (OHCA) survivors who had undergone target temperature management. CSF and serum samples were obtained immediately (lactate0), and at 24 (lactate24), 48 (lactate48), and 72 (lactate72) h after ROSC, and ACDL was calculated at each time point. The primary outcome was poor 3-month neurologic outcome (cerebral performance categories 3-5). RESULTS: Of 45 patients, 27 (60.0%) showed poor neurologic outcome. At each time point, CSF lactate levels were significantly higher in the poor neurologic outcome group than in the good neurologic outcome group (6.97 vs. 3.37, 4.20 vs. 2.10, 3.50 vs. 2.00, and 2.79 vs. 2.06, respectively; all P < 0.05). CSF lactate's prognostic performance was higher than serum lactate at each time point, and lactate24 showed the highest AUC values (0.89, 95% confidence interval, 0.75-0.97). Over time, ACDL decreased from - 1.30 (- 2.70-0.77) to - 1.70 (- 3.2 to - 0.57) in the poor neurologic outcome group and increased from - 1.22 (- 2.42-0.32) to - 0.64 (- 2.31-0.15) in the good neurologic outcome group. CONCLUSIONS: At each time point, CSF lactate showed better prognostic performance than serum lactate. CSF lactate24 showed the highest prognostic performance for 3-month poor neurologic outcome. Over time, ACDL decreased in the poor neurologic outcome group and increased in the good neurologic outcome group.

The Association Between Neurological Prognosis and the Degree of Blood-Brain Barrier Disruption in Cardiac Arrest Survivors Who Underwent Target Temperature Management.

BACKGROUND: This study aimed to compare day-specific associations of blood-brain barrier (BBB) disruption with neurological outcome in survivors of out-of-hospital cardiac arrest (OHCA) treated with target temperature management (TTM) and lumbar drainage. METHODS: This retrospective single-center study included 68 survivors of OHCA who underwent TTM between April 2018 and December 2019. The albumin quotient (QA) was calculated as QA = albumincerebrospinal fluid/albuminserum immediately (day 1) and 24 (day 2), 48 (day 3), and 72 h (day 4) after the return of spontaneous circulation. The degree of BBB disruption was weighted using the following scoring system: QA value of 0.007 or less (normal), QA value greater than 0.007-0.01 (mild), QA value greater than 0.01-0.02 (moderate), and QA value greater than 0.02 (severe). Points were assigned as follows: 0 (normal), 1 (mild), 4 (moderate), and 9 (severe). Neurological outcome was determined at 6 months after the return of spontaneous circulation, as well as cerebral performance category (CPC), dichotomized as good (CPC score 1-2) and poor (CPC score 3-5) outcome. RESULTS: We enrolled 68 patients (48 men, 71%); 37 (54%) patients had a poor neurological outcome. The distributions of poor versus good outcomes at 6 months in patients with moderate and severe BBB disruption were 19 of 22 (80%) vs. 18 of 46 (50%) on day 1, 31 of 37 (79%) vs. 6 of 31 (32%) on day 2, 32 of 37 (81%) vs. 5 of 31 (30%) on day 3, and 32 of 39 (85%) vs. 5 of 29 (30%) on day 4 (P < 0.001), respectively. Using receiver operating characteristic analyses, optimal cutoff values (sensitivity, specificity) of QA levels for the prediction of neurological outcome were as follows: day 1, greater than 0.009 (56.8%, 87.1%); day 2, greater than 0.012 (81.1%, 87.1%); day 3, greater than 0.013 (83.8%, 87.1%); day 4, greater than 0.013 (86.5%, 87.1%); the sum of all time points, greater than 0.039 (89.5%, 79.4%); and scoring system, greater than 9 (91.9%, 87.1%). CONCLUSIONS: In this proof of concept study, QA was associated with poor neurological outcome in survivors of OHCA treated with TTM with no contraindication to lumbar drainage. A large multicenter prospective study is needed to validate the utility of BBB disruption as a prognosticator of neurological outcome.

Association of Participation in Health Check-ups with Risk Factors for Cardiovascular Diseases.

BACKGROUND: We compared the risk factors for cardiovascular diseases (CVDs) among Koreans who did and did not participate in national periodic health check-ups, after adjustment for demographic factors, socioeconomic status, and lifestyle factors. METHODS: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2018. Study subjects were classified as participants or non-participants in health check-ups, based on attendance at national periodic health check-ups during the previous two years. RESULTS: Comparison of participants and non-participants in health check-ups indicated statistically significant differences in age, gender, region, education level, monthly income, employment status, obesity, smoking, alcohol consumption, exercise, and marital status. After adjustment for demographic, socioeconomic factors, and health-related behaviors, woman non-participants were more likely to have metabolic syndrome, pre-hypertension, hypertension, prediabetes, and diabetes, and man non-participants were more likely to have pre-diabetes and diabetes. CONCLUSION: Subjects who participated in periodic health check-ups had fewer CVD-related risk factors than non-participants. Thus, health care providers should encourage non-participants to attend periodic health check-ups so that appropriate interventions can be implemented and decrease the risk for CVDs in these individuals.

The association between diastolic blood pressure and massive transfusion in severe trauma: a retrospective single-center study.

OBJECTIVE: To evaluate the association between diastolic blood pressure and massive transfusion in severe trauma. Method: The retrospective study was conducted at a tertiary emergency medical centre in Gwangju , Republic of Korea, and comprised data of severe trauma patients with injury severity score >15 presenting between January 2016 and December 2017. Multivariate logistic regression analysis was performed to evaluate the association between diastolic blood pressure and massive transfusion. Receiver operating characteristic curve analysis was performed to estimate the prognostic performance of diastolic blood pressure. Data was analysed using SPSS 18. RESULTS: Of the 827 patients, 64(7.7%) underwent massive transfusion. After adjusting the confounders, diastolic blood pressure was found to be an independent factor in predicting massive transfusion (odds ratio: 0.965; 95% confidence interval: 0.956-0.975). CONCLUSIONS: Initially low diastolic blood pressure was found to be an independent predictor for massive transfusion in severe trauma cases.

Pralidoxime-Induced Potentiation of the Pressor Effect of Adrenaline and Hastened Successful Resuscitation by Pralidoxime in a Porcine Cardiac Arrest Model.

PURPOSE: Pralidoxime potentiated the pressor effect of adrenaline and facilitated restoration of spontaneous circulation (ROSC) after prolonged cardiac arrest. In this study, we hypothesised that pralidoxime would hasten ROSC in a model with a short duration of untreated ventricular fibrillation (VF). We also hypothesised that potentiation of the pressor effect of adrenaline by pralidoxime would not be accompanied by worsening of the adverse effects of adrenaline. METHODS: After 5 min of VF, 20 pigs randomly received either pralidoxime (40 mg/kg) or saline, in combination with adrenaline, during cardiopulmonary resuscitation (CPR). Coronary perfusion pressure (CPP) during CPR, and ease of resuscitation were compared between the groups. Additionally, haemodynamic data, severity of ventricular arrhythmias, and cerebral microcirculation were measured during the 1-h post-resuscitation period. Cerebral microcirculatory blood flow and brain tissue oxygen tension (PbtO2) were measured on parietal cortices exposed through burr holes. RESULTS: All animals achieved ROSC. The pralidoxime group had higher CPP during CPR (P = 0.014) and required a shorter duration of CPR (P = 0.024) and smaller number of adrenaline doses (P = 0.024). During the post-resuscitation period, heart rate increased over time in the control group, and decreased steadily in the pralidoxime group. No inter-group differences were observed in the incidences of ventricular arrhythmias, cerebral microcirculatory blood flow, and PbtO2. CONCLUSION: Pralidoxime improved CPP and hastened ROSC in a model with a short duration of untreated VF. The potentiation of the pressor effect of adrenaline was not accompanied by the worsening of the adverse effects of adrenaline.

Pralidoxime administered during cardiopulmonary resuscitation facilitates successful resuscitation in a pig model of cardiac arrest.

Pralidoxime is a common antidote for organophosphate poisoning; however, studies have also reported pralidoxime's pressor effect, which may facilitate the restoration of spontaneous circulation (ROSC) after cardiac arrest by improving coronary perfusion pressure (CPP). We investigated the immediate cardiovascular effects of pralidoxime in anaesthetised normal rats and the effects of pralidoxime administration during cardiopulmonary resuscitation (CPR) in a pig model of cardiac arrest. To evaluate the immediate cardiovascular effects of pralidoxime, seven anaesthetised normal rats received saline or pralidoxime (20 mg/kg) in a randomised crossover design, and the responses were determined using the conductance catheter technique. To evaluate the effects of pralidoxime administration during CPR, 22 pigs randomly received either 80 mg/kg of pralidoxime or an equivalent volume of saline during CPR. In the rats, pralidoxime significantly increased arterial pressure than saline (P = .044). The peak effect on arterial pressure was observed in the first minute. In a pig model of cardiac arrest, CPP during CPR was higher in the pralidoxime group than in the control group (P = .002). ROSC was attained in three animals (27.3%) in the control group and nine animals (81.8%) in the pralidoxime group (P = .010). Three animals (27.3%) in the control group and eight animals (72.2%) in the pralidoxime group survived the 6-hour period (P = .033). In conclusion, pralidoxime had a rapid onset of pressor effect. Pralidoxime administered during CPR led to significantly higher rates of ROSC and 6-hour survival by improving CPP in a pig model.

Glycated Hemoglobin is Associated with Glycemic Control and 6-Month Neurologic Outcome in Cardiac Arrest Survivors Undergoing Therapeutic Hypothermia.

BACKGROUND: Glucose control status after cardiac arrest depending on chronic glycemic status and the association between chronic glycemic status and outcome in cardiac arrest survivors are not well known. We investigated the association between glycated hemoglobin (HbA1c) and 6-month neurologic outcome in cardiac arrest survivors undergoing therapeutic hypothermia (TH) and whether mean glucose, area under curve (AUC) of glucose during TH, and neuron-specific enolase (NSE) are different between normal and high HbA1c groups. METHODS: This retrospective single-center study included adult comatose cardiac arrest survivors who underwent TH from September 2011 to December 2017. HbA1c and glucose were measured after return of spontaneous circulation (ROSC), and normal or high HbA1c was defined using cutoff value of 6.4% of HbA1c. Blood glucose was measured at least every 4 h and treated with a written protocol to maintain the range of 80-200 mg/dL. Hypoglycemia and hyperglycemia were defined with glucose < 70 or > 180 mg/dL. Mean glucose during induction and rewarming phase and AUC of glucose during every 6 h of maintenance were calculated, and NSE at 48 h after cardiac arrest was recorded. The primary outcome was unfavorable neurologic outcome, defined as Glasgow Pittsburgh Cerebral Performance Category scale 3-5 at 6 months after cardiac arrest. RESULTS: Of 384 included patients, 81 (21.1%) had high HbA1c and 247 (64.3%) had an unfavorable neurologic outcome. Patients with high HbA1c were more common in the unfavorable group than in favorable group (27.5% vs 9.5%, p < 0.001), and the unfavorable group had significantly higher HbA1c level (5.8% [5.4-6.8%] vs 5.6% [5.3-6.0%], p = 0.007). HbA1c level was independently associated with worse neurologic outcome (odds ratio 1.414; 95% confidence interval 1.051-1.903). High HbA1c group had higher glucose after ROSC, glucose AUC during maintenance, and rewarming phase than normal HbA1c group. High HbA1c group had significantly higher incidence of hyperglycemia throughout the TH, while normal HbA1c group had significantly higher incidence of normoglycemia. However, no glucose parameter remained as an independent predictor of neurologic outcome after adjustment, irrespective of HbA1c level. NSE showed good prognostic performance (area under curve 0.892; cutoff value 26.3 ng/mL). Although NSE level was not different between HbA1c groups, high HbA1c group had higher proportion of patient having NSE over cutoff. CONCLUSIONS: Higher HbA1c was independently associated with unfavorable neurologic outcome. Glycemic status during TH was different between normal and high HbA1c groups.