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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.)

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., Competing Interests: The authors have declared that no competing interests exist.

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.

Several studies have suggested that sympathetic overstimulation causes deleterious effects in septic shock. A previous study suggested that pralidoxime exerted a pressor effect through a mechanism unrelated to the sympathetic nervous system; this effect was buffered by the vasodepressor action of pralidoxime mediated through sympathoinhibition. In this study, we explored the effects of pralidoxime on hemodynamics and survival in rats with peritonitis-induced sepsis. This study consisted of two sub-studies: survival and hemodynamic studies. In the survival study, 66 rats, which survived for 10 hours after cecal ligation and puncture (CLP), randomly received saline placebo, pralidoxime, or norepinephrine treatment and were monitored for up to 24 hours. In the hemodynamic study, 44 rats were randomly assigned to sham, CLP-saline placebo, CLP-pralidoxime, or CLP-norepinephrine groups, and hemodynamic measurements were performed using a conductance catheter placed in the left ventricle. In the survival study, 6 (27.2%), 15 (68.1%), and 5 (22.7%) animals survived the entire 24-hour monitoring period in the saline, pralidoxime, and norepinephrine groups, respectively (log-rank test P = 0.006). In the hemodynamic study, pralidoxime but not norepinephrine increased end-diastolic volume (P <0.001), stroke volume (P = 0.002), cardiac output (P = 0.003), mean arterial pressure (P = 0.041), and stroke work (P <0.001). The pressor effect of norepinephrine was short-lived, such that by 60 minutes after the initiation of norepinephrine infusion, it no longer had any significant effect on mean arterial pressure. In addition, norepinephrine significantly increased heart rate (P <0.001) and the ratio of arterial elastance to ventricular end-systolic elastance (P = 0.010), but pralidoxime did not. In conclusion, pralidoxime improved the hemodynamics and 24-hour survival rate in rats with peritonitis-induced sepsis, but norepinephrine did not., Competing Interests: The authors have declared that no competing interests exist.

Brain tissue oxygen tension (PbtO2)-guided care, a therapeutic strategy to treat or prevent cerebral hypoxia through modifying determinants of cerebral oxygen delivery, including arterial oxygen tension (PaO2), end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP), has recently been introduced. Studies have reported that cerebral hypoxia occurs after cardiac arrest in the absence of hypoxemia or hypotension. To obtain preliminary information on the degree to which PbtO2 is responsive to changes in the common target variables for PbtO2-guided care in conditions without hypoxemia or hypotension, we investigated the relationships between the common target variables for PbtO2-guided care and PbtO2 using data from an experimental study in which the animals did not experience hypoxemia or hypotension after resuscitation. We retrospectively analyzed 170 sets of MAP, ETCO2, PaO2, PbtO2, and cerebral microcirculation parameters obtained during the 60-min post-resuscitation period in 10 pigs resuscitated from ventricular fibrillation cardiac arrest. PbtO2 and cerebral microcirculation parameters were measured on parietal cortices exposed through burr holes. Multiple linear mixed effect models were used to test the independent effects of each variable on PbtO2. Despite the absence of arterial hypoxemia or hypotension, seven (70%) animals experienced cerebral hypoxia (defined as PbtO2 <20 mmHg). Linear mixed effect models revealed that neither MAP nor ETCO2 were related to PbtO2. PaO2 had a significant linear relationship with PbtO2 after adjusting for significant covariates (P = 0.030), but it could explain only 17.5% of the total PbtO2 variance (semi-partial R2 = 0.175; 95% confidence interval, 0.086-0.282). In conclusion, MAP and ETCO2 were not significantly related to PbtO2 in animals without hypoxemia or hypotension during the early post-resuscitation period. PaO2 had a significant linear association with PbtO2, but its ability to explain PbtO2 variance was small., Competing Interests: The authors have declared that no competing interests exist.

Background: Prognostication after cardiac arrest (CA) needs a multimodal approach, but the optimal method is not known. We tested the hypothesis that the combination of neuron-specific enolase (NSE) and neuroimaging could improve outcome prediction after CA treated with targeted temperature management (TTM)., Methods: A retrospective observational cohort study was performed on patients who underwent at least one NSE measurement between 48 and 72 hr; received both a brain computed tomography (CT) scan within 24 hr and diffusion-weighted magnetic resonance imaging (DW-MRI) within 7 days after return of spontaneous circulation (ROSC); and were treated with TTM after out-of-hospital CA between 2009 and 2017 at the Seoul St. Mary's Hospital in Korea. The primary outcome was a poor neurological outcome at 6 months after CA, defined as a cerebral performance category of 3-5., Results: A total of 109 subjects underwent all three tests and were ultimately included in this study. Thirty-four subjects (31.2%) experienced good neurological outcomes at 6 months after CA. The gray matter to white matter attenuation ratio (GWR) was weakly correlated with the mean apparent diffusion coefficient (ADC), PV400 and NSE (Spearman's rho: 0.359, -0.362 and -0.263, respectively). NSE was strongly correlated with the mean ADC and PV400 (Spearman's rho: -0.623 and 0.666, respectively). Serum NSE had the highest predictive value among the single parameters (area under the curve (AUC) 0.912, sensitivity 70.7% for maintaining 100% specificity). The combination of a DWI parameter (mean ADC or PV400) and NSE had better prognostic performance than the combination of the CT parameter (GWR) and NSE. The addition of the GWR to a DWI parameter and NSE did not improve the prediction of neurological outcomes., Conclusion: The GWR (≤ 24 hr) is weakly correlated with the mean ADC (≤ 7 days) and NSE (highest between 48 and 72 hr). The combination of a DWI parameter and NSE has better prognostic performance than the combination of the GWR and NSE. The addition of the GWR to a DWI parameter and NSE does not improve the prediction of neurological outcomes after CA treatment with TTM., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM) was to evaluate the prognostic value of OHCA, C-GRApH, and CAHP scores with initial neurologic examinations for predicting neurologic outcomes., Methods: This retrospective study included OHCA patients treated with TTM from 2009 to 2017. We calculated three cardiac arrest (CA)-specific risk scores (OHCA, C-GRApH, and CAHP) at the time of admission. The initial neurologic examination included an evaluation of the Full Outline of UnResponsiveness brainstem reflexes (FOUR&#95;B) and Glasgow Coma Scale motor (GCS&#95;M) scores. The primary outcome was the neurologic outcome at hospital discharge., Results: Of 311 subjects, 99 (31.8%) had a good neurologic outcome at hospital discharge. The OHCA score had an area under the receiver operating characteristic curve (AUROC) of 0.844 (95% confidence interval (CI): 0.798-0.884), the C-GRApH score had an AUROC of 0.779 (95% CI: 0.728-0.824), and the CAHP score had an AUROC of 0.872 (95% CI: 0.830-0.907). The addition of the FOUR&#95;B or GCS&#95;M score to the OHCA score improved the prediction of poor neurologic outcome (with FOUR&#95;B: AUROC = 0.899, p = 0.001; with GCS&#95;M: AUROC = 0.880, p = 0.004). The results were similar with the C-GRApH and CAHP scores in predicting poor neurologic outcome., Conclusions: This study confirms the good prognostic performance of CA-specific scores to predict neurologic outcomes in OHCA patients treated with TTM. By adding new variables associated with the initial neurologic examinations, the prognoses of neurologic outcomes improved compared to the existing scoring models., Competing Interests: The authors have declared that no competing interests exist.

Ischemia-induced left ventricular (LV) wall thickening compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR). However, accurate assessment of the severity of ischemia-induced LV wall thickening during CPR is challenging. We investigated, in a swine model, whether hemodynamic parameters, including end-tidal carbon dioxide (ETCO2) level, are linearly associated with the severity of ischemia-induced LV wall thickening during CPR of consistent quality. We retrospectively analyzed 96 datasets for ETCO2 level, arterial pressure, LV wall thickness, and the percent of measured end-diastolic volume (%EDV) relative to EDV at the onset of ventricular fibrillation from eight pigs. Animals underwent advanced cardiovascular life support based on resuscitation guidelines. During CPR, LV wall thickness progressively increased while %EDV progressively decreased. Systolic and diastolic arterial pressure and ETCO2 level were significantly correlated with LV wall thickness and %EDV. Linear mixed effect models revealed that, after adjustment for significant covariates, systolic and diastolic arterial pressure were not associated with LV wall thickness or %EDV. ETCO2 level had a significant linear relationship with %EDV (P = 0.004). However, it could explain only 28.2% of the total variance of %EDV in our model. In conclusion, none of the hemodynamic parameters examined in this study appeared to provide sufficient information on the severity of ischemia-induced LV wall thickening., Competing Interests: The authors have declared that no competing interests exist.

Unrecognized endobronchial intubation frequently occurs after emergency intubation. However, no study has evaluated the effect of one-lung ventilation on end-tidal carbon dioxide (ETCO2) during cardiopulmonary resuscitation (CPR). We compared the hemodynamic parameters, blood gases, and ETCO2 during one-lung ventilation with those during conventional two-lung ventilation in a pig model of CPR, to determine the effect of the former on ETCO2. A randomized crossover study was conducted in 12 pigs intubated with double-lumen endobronchial tube to achieve lung separation. During CPR, the animals underwent three 5-min ventilation trials based on a randomized crossover design: left-lung, right-lung, or two-lung ventilation. Arterial blood gases were measured at the end of each ventilation trial. Ventilation was provided using the same tidal volume throughout the ventilation trials. Comparison using generalized linear mixed model revealed no significant group effects with respect to aortic pressure, coronary perfusion pressure, and carotid blood flow; however, significant group effect in terms of ETCO2 was found (P < 0.001). In the post hoc analyses, ETCO2 was lower during the right-lung ventilation than during the two-lung (P = 0.006) or left-lung ventilation (P < 0.001). However, no difference in ETCO2 was detected between the left-lung and two-lung ventilations. The partial pressure of arterial carbon dioxide (PaCO2), partial pressure of arterial oxygen (PaO2), and oxygen saturation (SaO2) differed among the three types of ventilation (P = 0.003, P = 0.001, and P = 0.001, respectively). The post hoc analyses revealed a higher PaCO2, lower PaO2, and lower SaO2 during right-lung ventilation than during two-lung or left-lung ventilation. However, the levels of these blood gases did not differ between the left-lung and two-lung ventilations. In a pig model of CPR, ETCO2 was significantly lower during right-lung ventilation than during two-lung ventilation. However, interestingly, ETCO2 during left-lung ventilation was comparable to that during two-lung ventilation.