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Background Various methods have been used to control body temperature in targeted temperature management (TTM), but few studies have compared specific subtypes of surface cooling systems. The aim of this study was to compare the efficiencies and neurological outcomes between hydrogels pad and water-circulating blanket cooling methods. Methods We conducted a multicentre, prospective, registry-based study of out-of-hospital cardiac arrest patients treated with TTM between 2015 and 2018. We compared the neurological outcomes, efficacies for cooling, and adverse events between patients who received TTM using a hydrogel pad and water-circulating blanket cooling. Patients were one-to-one matched using propensity scores to adjust for differences in the baseline characteristics of each cooling method. The primary outcome was a favourable neurological outcome at 6 months. Results We included 1,132 patients in the analysis, 870 of whom underwent hydrogel pad cooling, and the remaining 262 underwent water-circulating blanket cooling. In the unmatched cohort, a greater number of adverse events occurred in the water-circulating blanket group. The favourable neurologic outcome rates at 6 months were similar between the hydrogel pad group and the water circulating blanket group (30.2% vs. 29.8%, p = 0.939). In the propensity-matched cohort, which included 184 pairs, the rates of adverse events between the two groups were similar. The similarity of favourable neurologic outcome rates at 6 months between the two groups persisted (28.8% vs. 29.9%, p = 0.819). Conclusion Neurological outcomes and adverse events between the hydrogel pad cooling and water-circulating blanket cooling groups were similar.

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.

Seismocardiography measures the vibrations produced by the beating heart using an accelerometer sensor placed on the chest. We evaluated the ability of smartphone seismocardiography to distinguish between the presence and absence of spontaneous circulation.Seismocardiography signals were obtained using a smartphone placed on the sternum in a convenience sample of 60 adult patients (30 comatose patients with spontaneous circulation and 30 deceased patients). The maximum, minimum, and standard deviation (SD) of acceleration values for head-to-foot, right-to-left, and dorsoventral axes and the three axis-root mean square (RMS) of the acceleration signals were calculated. Blinded observers (n = 156) were each asked to determine the presence or absence of spontaneous circulation based on seismocardiography video clips for each of the 60 patients.The seismocardiography revealed periodic large positive peaks in the patients with spontaneous circulation, which were absent in the patients without spontaneous circulation. For each of the four output measurements (three independent axes plus the three-axis RMS), the acceleration maxima and SD were significantly higher and the minima significantly lower in the patients with spontaneous circulation than in those without spontaneous circulation (all P 0.001 except the minimum of three axis-RMS results [P = 0.009]). The observers accurately identified the seismocardiography signals from patients without spontaneous circulation, with a sensitivity of 97.6% (95% confidence interval, 97.0%-98.2%) and a specificity of 98.4% (95% confidence interval, 97.8%-99.0%).In conclusion, blinded observers accurately distinguished between seismocardiography signals from patients with and without spontaneous circulation.

We aimed to verify whether slow heart rate (HR) is associated with neurologic outcome and the factors that can contribute to the development of bradycardia in out-of-hospital cardiac arrest (OHCA) survivors who underwent targeted temperature management (TTM). We extracted the data of comatose adult OHCA survivors who underwent TTM between October 2015 and December 2018 from the prospective multicenter registry. Data on HR recorded every 6 hours within 72 hours after return of spontaneous circulation and calculated minimal, mean, and maximal HR and time to the lowest HR were obtained. HR50 bpm was defined as bradycardia. The primary outcome was a 6-month neurologic outcome based on Pittsburgh-Glasgow Cerebral Performance Category Scale. Of the 814 included patients, 508 (62.4%) had poor neurologic outcome and 197 (24.2%) had bradycardia. Bradycardia (odds ratio [OR], 0.574; 95% confidence interval [CI], 0.362-0.192), minimal HR (OR, 1.023; 95% CI, 1.008-1.037), and mean HR (OR, 1.016; 95% CI, 1.002-1.030) were independently associated with poor neurologic outcome, but not maximal HR and time to the lowest HR. Preexisting arrhythmia (OR, 2.067; 95% CI, 1.037-4.118), renal disease (OR, 2.028; 95% CI, 1.153-3.567), cardiac etiology (OR, 1.526; 95% CI, 1.045-2.228), downtime (OR, 0.985; 95% CI, 0.974-0.996), and serum lactate levels (OR, 0.936; 95% CI, 0.900-0.974) were independently associated with bradycardia. Bradycardia and decreased mean and minimal HR were independently associated with good neurologic outcomes. Bradycardia was associated with preexisting arrhythmia, renal disease, cardiac etiology, shorter downtime, and lower serum lactate level.

This study aimed to investigate the efficacy of the combination of neuron-specific enolase (NSE) measurement and initial neurological examination in predicting the neurological outcomes of patients with cardiac arrest (CA) by retrospectively analyzing data from the Korean Hypothermia Network prospective registry. NSE levels were recorded at 48 and 72 h after CA. The initial Full Outline of UnResponsiveness (FOUR) and Glasgow Coma Scale (GCS) scores were recorded. These variables were categorized using the scorecard method. The primary endpoint was poor neurological outcomes at 6 months. Of the 475 patients, 171 (36%) had good neurological outcomes at 6 months. The areas under the curve (AUCs) of the categorized NSE levels at 72 h, GCS score, and FOUR score were 0.889, 0.722, and 0.779, respectively. The AUCs of the combinations of categorized NSE levels at 72 h with categorized GCS scores and FOUR score were 0.910 and 0.912, respectively. Each combination was significantly higher than the AUC value of the categorized NSE level at 72 h alone (with GCS: p = 0.015; with FOUR: p = 0.026). Combining NSE measurement and initial neurological examination improved the prediction of neurological outcomes.

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. 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. 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. 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.

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

Thrombocytopenia is common and associated with mortality in critically ill patients. However, the time course of platelet counts and its association with the neurologic outcome after out-of-hospital cardiac arrest (OHCA) are not well known. The purpose of this study is to describe the time course of platelet counts in relation to the neurologic outcome in patients undergoing targeted temperature management (TTM) after CA.Review of consecutive patients receiving TTM after out-of-hospital CA between 2009 and 2016. The blood sample was collected daily until 7 days. The primary outcome was poor neurologic outcome at 6 months after CA defined as Cerebral Performance Category of 3-5 and secondary outcome was mortality at 6 months.A total of 261 consecutive patients treated with TTM after OHCA between 2009 and 2016. One hundred seventy-five patients (67.0%) had poor neurologic outcomes 6 months after CA. The changes in the platelet counts over time between the good and poor outcome groups were statistically significant (p 0.001). The platelet counts declined during TTM in both groups. The platelet counts recovered to the normal range at the end of the first week in the good neurologic outcome group. However, the platelet counts remained low in the poor outcome group. Low platelet counts on the 7th day were associated with poor neurologic outcomes (aOR 0.975, 95% CI, 0.961-0.989) and mortality at 6 months (aOR 0.986, 95% CI, 0.975-0.997) after adjusting for covariates.The changes in platelet counts in OHCA patients have a biphasic pattern that is significantly different in patients with good neurologic outcomes and those with poor neurologic outcomes at 6 months. A low platelet count 7 days after CA was associated with a poor neurologic outcome and mortality at 6 months.

Several studies reported that disturbances in cellular ion homeostasis occur following ischaemia, the magnitude of which was proportional to illness severity. The changes in serum electrolyte levels following ischaemia were minor compared with the changes in ion concentrations in the extracellular fluid. To amplify the serum electrolyte changes, we devised a new index (ion shift index), which could be calculated using commonly measured serum electrolyte levels, and explored its prognostic value in adult cardiac arrest patients.This retrospective observational study included adult cardiac arrest survivors treated at a tertiary university hospital between January 2014 and December 2017. Using the first available serum electrolyte levels, the ion shift index was calculated as follows: ion shift index = (potassium + phosphate + magnesium) / calcium. The primary outcome was poor outcome at hospital discharge (cerebral performance categories 3-5).The area under the receiver operating characteristic curve (AUC) of ion shift index for predicting poor outcome was 0.878 (95% confidence interval [CI], 0.849-0.907). The AUC of ion shift index was greater than those of individual electrolytes (all p 0.001). In multivariate analysis, higher ion shift index levels were independently associated with poor outcome (odds ratio, 2.916; 95% CI, 1.798-4.730; p 0.001). The AUC of multivariate model including ion shift index was greater than that of multivariate model after excluding ion shift index (p = 0.007).Our results suggest that the ion shift index can be helpful in the early prognostication of adult cardiac arrest patients.

Comatose cardiac arrest patients frequently experience cardiogenic shock or recurrent arrest. Extracorporeal membrane oxygenation (ECMO) can be used to salvage patients with cardiogenic shock or cardiac arrest refractory to conventional therapies. However, in comatose cardiac arrest patients whose neurologic recovery is uncertain, the use of ECMO is restricted because it requires considerable financial and human resources. Amplitude-integrated electroencephalography is an easily applicable, real-time electroencephalography monitoring tool that has been increasingly used to monitor brain activity in comatose cardiac arrest patients. We describe our experience of using amplitude-integrated electroencephalography in decision-making to place ECMO for comatose cardiac arrest patients whose eventual neurologic recovery appeared uncertain at the time of ECMO placement.

Background From the viewpoint of cardiac pump theory, the area of the left ventricle (LV) subjected to compression increases as the LV lies closer to the sternum, possibly resulting in higher blood flow in patients with LV closer to the sternum. However, no study has evaluated LV position during cardiac arrest or its relationship with haemodynamic parameters during cardiopulmonary resuscitation (CPR). The objectives of this study were to determine whether the position of the LV relative to the anterior-posterior axis representing the direction of chest compression shifts during cardiac arrest and to examine the relationship between LV position and haemodynamic parameters during CPR. Methods Subcostal view echocardiograms were obtained from 15 pigs with the transducer parallel to the long axis of the sternum before inducing ventricular fibrillation (VF) and during cardiac arrest. Computed tomography was performed in three pigs to objectively observe LV position during cardiac arrest. LV position parameters including the shortest distance between the anterior-posterior axis and the mid-point of the LV chamber (D AP-MidLV ), the shortest distance between the anterior-posterior axis and the LV apex (D AP-Apex ), and the area fraction of the LV located on the right side of the anterior-posterior axis (LVA Right /LVA Total ) were measured. Results D AP-MidLV , D AP-Apex , and LVA Right /LVA Total decreased progressively during untreated VF and basic life support (BLS), and then increased during advanced cardiovascular life support (ACLS). A repeated measures analysis of variance revealed significant time effects for these parameters. During BLS, the end-tidal carbon dioxide and systolic right atrial pressure were significantly correlated with the LV position parameters. During ACLS, systolic arterial pressure and systolic right atrial pressure were significantly correlated with D AP-MidLV and D AP-Apex . Conclusions Left ventricular position changed significantly during cardiac arrest compared to the pre-arrest baseline. LV position during CPR had significant correlations with haemodynamic parameters.

Severe neurological impairment was more prevalent in cardiac arrest survivors who were administered epinephrine than in those administered placebo in a randomized clinical trial, short-term reduction of brain tissue O2 tension (PbtO2) after epinephrine administration in swine following a short duration of untreated cardiac arrest has also been reported. We investigated the effects of epinephrine administered during cardiopulmonary resuscitation (CPR) on cerebral oxygenation after restoration of spontaneous circulation (ROSC) in a swine model with a clinically relevant duration of untreated cardiac arrest. After 7 min of ventricular fibrillation, 24 pigs randomly received either epinephrine or saline placebo during CPR. Parietal cortex measurements during 60-min post-resuscitation period showed that the area under the curve (AUC) for PbtO2 was smaller in the epinephrine group than in the placebo group during the initial 10-min period and subsequent 50-min period (both p &lt, 0.05). The AUC for number of perfused cerebral capillaries was smaller in the epinephrine group during the initial 10-min period (p = 0.005), but not during the subsequent 50-min period. In conclusion, epinephrine administered during CPR reduced PbtO2 for longer than 10 min following ROSC in a swine model with a clinically relevant duration of untreated cardiac arrest.

Introduction This study aimed to investigate the ion shift index (ISI) as a prognostic factor of severe trauma. We hypothesized that the initial ISI measured in the emergency department (ED) is associated with discharge survival in severe non-isolated head injury (IHI) patients. Materials and methods This retrospective observational study included severe trauma patients with available medical records from January 2017 to December 2018 but excluded those with IHI. Logistic regression analysis was conducted to identify the risk factors for mortality in non-IHI patients, and adjustments were performed for relevant covariates. An area under the receiver operating characteristics curve (AUROC) analysis was performed to examine the primary outcome of our study, which was mortality at hospital discharge in severe non-IHI trauma patients. Results Of the 483 severe non-IHI trauma patients included in the study, 86 patients (17.8 %) died. The multiple logistic regression analysis demonstrated ISI (odds ratio [OR], 2.300; 95% CI, 1.183–4.470) was significantly associated with mortality in the non-IHI group. Additionally, trauma and injury severity score (TRISS; OR, 0.538; 95% CI, 0.447–0.649), lactate (OR, 1.410; 95% CI, 1.252–1.588), creatinine (OR, 1.554; 95% CI, 1.221–1.979), and activated partial thromboplastin time (aPTT; OR, 1.050; 95% CI, 1.021–1.080) were independently associated with mortality at hospital discharge. The AUROC values for TRISS, lactate, aPTT, creatinine, and ISI were as follows: 0.892 (95% CI, 0.861–0.918), 0.838 (95% CI, 0.803–0.870), 0.754 (95% CI, 0.712–0.792), 0.650 (95% CI, 0.606–0.693), and 0.848 (95% CI, 0.813–0.879), respectively. The AUROC for the multiple logistic regression model with ISI was 0.942 (95% CI, 0.917–0.962). In a model in which TRISS was omitted, the addition of ISI to other predictors significantly improved the AUROC to 0.900 (95% CI, 0.869-0.925) (p=0.039). Conclusion The initial ISI in the ED after trauma was associated with mortality in severe non-IHI trauma patients. In conjunction with other prognostic indicators, it could be used as an early prognostic marker, particularly if TRISS is unavailable.

Author's summary Few studies have focused on acute myocardial infarction (AMI) with cardiogenic shock after resuscitated out-of-hospital cardiac arrest (OHCA). Only a small number of studies have reported the timing of extracorporeal membrane oxygenation (ECMO) in patients with AMI with cardiogenic shock. The current study, which used the large nationwide OHCA registry, shows that ECMO treatment before revascularization can decrease 30-day mortality, compared to ECMO after revascularization, in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest. The current study emphasized the importance of early ECMO therapy before revascularization in circumstance which is difficult to determine optimal revascularization timing., Background and Objectives The study sought to investigate the impact of early extracorporeal membrane oxygenation (ECMO) support before revascularization in patients with acute myocardial infarction (AMI) complicated by profound cardiogenic shock after resuscitated cardiac arrest. It is difficult to determine optimal timing of ECMO in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest. Methods Among 116,374 patients experiencing out-of-hospital cardiac arrest in South Korea, a total of 184 resuscitated patients with AMI complicated by profound cardiogenic shock, and who were treated successfully with percutaneous coronary intervention (PCI) and ECMO, were enrolled. Patients were divided into 2 groups according to the timing of ECMO: pre-PCI ECMO (n=117) and post-PCI ECMO (n=67). We compared 30-day mortality between the 2 groups. Results In-hospital mortality was 78.8% in the entire study population and significantly lower in the pre-PCI ECMO group (73.5% vs. 88.1%, p=0.020). Thirty-day mortality was also lower in the pre-PCI ECMO group compared to the post-PCI ECMO group (74.4% vs. 91.0%; adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.017). Shockable rhythm at the emergency room (HR, 0.57; 95% CI, 0.36–0.91; p=0.019) and successful therapeutic hypothermia (HR, 0.40; 95% CI, 0.23–0.69; p=0.001) were also associated with improved 30-day survival. Conclusions ECMO support before revascularization was associated with an improved short-term survival rate compared to ECMO after revascularization in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest.

We investigated the association between post-rewarming fever (PRF) and 6-month neurologic outcomes in cardiac arrest survivors. This was a multicenter study based on a registry of comatose adult (&ge, 18 years) out-of-hospital cardiac arrest (OHCA) survivors who underwent targeted temperature management between October 2015 to December 2018. PRF was defined as peak temperature &ge, 38.0 &deg, C within 72 h after completion of rewarming, and PRF timing was categorized as within 24, 24&ndash, 48, and 48&ndash, 72 h epochs. The primary outcome was neurologic outcomes at six months after cardiac arrest. Unfavorable neurologic outcome was defined as cerebral performance categories three to five. A total of 1031 patients were included, and 642 (62.3%) had unfavorable neurologic outcomes. PRF developed in 389 (37.7%) patients in 72 h after rewarming: within 24 h in 150 (38.6%), in 24&ndash, 48 h in 155 (39.8%), and in 48&ndash, 72 h in 84 (21.6%). PRF was associated with improved neurologic outcomes (odds ratio (OR), 0.633, 95% confidence interval (CI), 0.416&ndash, 0.963). PRF within 24 h (OR, 0.355, 95% CI, 0.191&ndash, 0.659), but not in 24&ndash, 48 h or 48&ndash, 72 h, was associated with unfavorable neurologic outcomes. Early PRF within 24 h after rewarming was associated with favorable neurologic outcomes.

Although experimental extracorporeal membrane oxygenation (ECMO) animal models have been reported, there are few studies on the immune response to ECMO. We developed the venoarterial (VA) and venovenous (VV) model in rats and serially investigated the changes in the distribution of immune cells. Forty rats underwent both VA and VV modes of ECMO, and blood samples were collected at 1 day before ECMO (D-1), at the end of ECMO run (D+0), and 3 days after the ECMO (D+3). Flow cytometry was used to characterize surface marker expression (CD3, CD4, CD8, CD43, CD45, CD45R, CD161, and His48) on immune cells. Granulocytes were initially activated in both ECMO types and were further reduced but not normalized until 3 days of decannulation. Monocyte and natural killer cells were decreased initially in VA mode. B lymphocytes, helper T lymphocytes, and cytotoxic T lymphocytes also significantly decreased in VA modes after ECMO, but this phenomenon was not prominent in the VV modes. Overall immune cells proportion changed after ECMO run in both modes, and the immunologic balance altered significantly in the VA than in VV mode. Our ECMO model is feasible for the hemodynamic and immunologic research, and further long-term evaluation is needed.

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

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

Background We previously reported that pralidoxime facilitated restoration of spontaneous circulation by potentiating the pressor effect of epinephrine. We determined the optimal dose of pralidoxime during cardiopulmonary resuscitation and evaluated the involvement of α‐adrenoceptors in its pressor action. Methods and Results Forty‐four pigs randomly received 1 of 3 doses of pralidoxime (40, 80, or 120 mg/kg) or saline placebo during cardiopulmonary resuscitation, including epinephrine administration. Pralidoxime at 40 mg/kg produced the highest coronary perfusion pressure, whereas 120 mg/kg of pralidoxime produced the lowest coronary perfusion pressure. Restoration of spontaneous circulation was attained in 4 (36.4%), 11 (100%), 9 (81.8%), and 3 (27.3%) animals in the saline, 40, 80, and 120 mg/kg groups, respectively ( P Conclusions Pralidoxime at 40 mg/kg administered with epinephrine improved restoration of spontaneous circulation rate by increasing coronary perfusion pressure in a pig model of cardiac arrest, whereas 120 mg/kg did not improve coronary perfusion pressure or restoration of spontaneous circulation rate. The pressor effect of pralidoxime was unrelated to α‐adrenoceptors and buffered by its vasodepressor action mediated by sympathoinhibition.

ObjectiveThe 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.MethodsThis 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_B) and Glasgow Coma Scale motor (GCS_M) scores. The primary outcome was the neurologic outcome at hospital discharge.ResultsOf 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_B or GCS_M score to the OHCA score improved the prediction of poor neurologic outcome (with FOUR_B: AUROC = 0.899, p = 0.001; with GCS_M: AUROC = 0.880, p = 0.004). The results were similar with the C-GRApH and CAHP scores in predicting poor neurologic outcome.ConclusionsThis 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.

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

Early diagnosis of acute kidney injury (AKI) after cardiac arrest (CA) is challenging. We aimed to identify the diagnostic and prognostic performance of neutrophil gelatinase-associated lipocalin (NGAL) for AKI and its clinical outcomes. A retrospective observational study, involving adult comatose CA survivors treated with therapeutic hypothermia between May 2013 and December 2016, was conducted. AKI was classified according to the guidelines of Kidney Disease Improving Global Outcomes. NGAL levels were measured after return of spontaneous circulation (ROSC). The primary outcome was development of AKI within 7 days after CA, and the secondary outcome was inhospital mortality. The study included 279 patients, of which 111 (39.8%) developed AKI and 61 (21.9%) died. Thirty-seven (33.3%) of patients in the AKI group had stage 3 AKI, and 45 (40.5%) patients received renal replacement therapy. The area under the curve of NGAL levels for diagnosing AKI was 0.725 (95% confidence interval [CI] 0.668-0.776), and NGAL levels were independently associated with the development of AKI (odds ratio [OR] 1.004; 95% CI 1.002-1.006). Nonsurvivors had significantly higher NGAL levels (221.0 ng/mL [154.0-355.5] vs. 148.5 ng/mL [97.0-232.9]; p 0.001). The development of AKI was independently associated with mortality (OR 4.926; 95% CI 2.353-10.311); however, NGAL level was not associated with mortality (OR 1.000; 95% CI 0.999-1.001). Plasma NGAL level measured after ROSC can be an early predictor for the development of AKI after CA. The presence of AKI was associated with increased inhospital mortality.

The optimal timing for measurement of neutrophil gelatinase-associated lipocalin (NGAL) level to predict acute kidney injury (AKI) and prognosis in cardiac arrest (CA) survivors has not been elucidated. We aimed to compare the diagnostic and prognostic performance of NGAL levels after return of spontaneous circulation (ROSC) and at 48 h after CA.We included 231 adult cardiac arrest survivors who underwent targeted temperature management between May 2013 and December 2016. The primary outcome was stage 2 and 3 AKI (high stage AKI), and the secondary outcomes were in-hospital mortality and neurologic outcome. Sixty-one (26.4%) developed high stage AKI, 50 (21.6%) died, and 152 (65.8%) had a poor neurologic outcome.NGAL level at 48 h (0.876; 95% confidence interval [CI], 0.826-0.916) had a higher area under receiver operating characteristic curve than NGAL level after ROSC (0.694; 95% CI, 0.631-0.753). Both NGAL levels were independently associated with high stage AKI. NGAL level at 48 h (1.001; 95% CI, 1.000-1.002) remained a significant predictor for in-hospital mortality, while neither of the NGAL levels were independently associated with neurologic outcome.NGAL at 48 h after CA seems to be a robust predictor for high stage AKI and in-hospital mortality.

Purpose We examined the association between neuromuscular blockade (NMB) requirements and outcomes and lactate clearance in cardiac arrest survivors treated with targeted temperature management (TTM). Methods We included consecutive adult cardiac arrest survivors treated with TTM between 2012 and 2015. NMB use was categorized into 3 groups: no NMB, bolus NMB (intermittent bolus use), and continuous NMB (continuous infusion). Serum lactate levels were measured on admission and at 12 h, 24 h, and 48 h after admission. The primary outcome was neurologic outcome at discharge. The secondary outcomes were in-hospital mortality and lactate clearance. Results In total, 309 patients were included. Of these, 206 (66.7%) and 73 (23.6%) were discharged with poor neurologic outcome and death, respectively. Multivariate analysis revealed that continuous NMB, as opposed to no NMB use, was associated with decreased poor neurologic outcomes (odds ratio [OR], 0.317; 95% confidence interval [CI], 0.124–0.815) and decreased in-hospital mortality (OR, 0.414; 95% CI, 0.183–0.941). There were no differences in lactate clearance between the NMB groups. Conclusion Continuous NMB requirement was associated with improved neurologic outcome and decreased in-hospital mortality in cardiac arrest survivors treated with TTM. The NMB requirement was not associated with lactate clearance.

Newly updated guidelines suggest brain computed tomography for out-of-hospital cardiac arrest survivors to identify a neurologic cardiac arrest cause. We hypothesized that the "pseudo-subarachnoid hemorrhage" (p-SAH) sign in cardiac arrest survivors is associated with poor outcome.We retrospectively evaluated the registries of 2 tertiary hospitals, identifying 836 adult (≥18 years) patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest. Among them, 398 patients with brain computed tomography within 6 hours after return of spontaneous circulation and received targeted temperature management from 2009 to 2014 were included. Clinical characteristics and outcomes of patients with and without p-SAH were compared.The prevalence of p-SAH sign was 8.0%. The p-SAH group more frequently had asystole as first rhythm and nonwitnessed arrest, predominantly resulting from asphyxia (56.3%). Targeted temperature management characteristics were not different between groups, although the p-SAH cohort had worse neurologic outcomes at discharge (100% vs 67.2%; P.001). Pseudo-subarachnoid hemorrhage had 11.5% sensitivity, 100% specificity, 100% positive predictive value, and 32.8% negative predictive value for poor neurologic outcome.Pseudo-subarachnoid hemorrhage sign might be one of the simple methods to identify poor neurologic outcome early. However, further prospective studies will be needed to clarify the clinical implication of the p-SAH sign.

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

Introduction: We previously reported that pralidoxime potentiated the pressor effect of epinephrine and improved restoration of spontaneous circulation (ROSC) rate and short-term survival in pigs undergoing cardiopulmonary resuscitation (CPR). We sought to explore the optimal dose of pralidoxime to be used during CPR and to evaluate the involvement of α-adrenoceptors in its pressor action. Methods: In the first substudy, 44 pigs randomly received one of three doses of pralidoxime (40, 80, or 120 mg/kg) or saline placebo during CPR. All animals were given epinephrine every 3 minutes. In the second substudy, 49 rats were divided into 7 groups. In the first 4 groups, the effects of 40 mg/kg pralidoxime on arterial pressure were determined after pretreatment with saline, guanethidine, phenoxybenzamine, or phentolamine. In the other 3 groups, the effects of 200 mg/kg pralidoxime were determined after pretreatment with saline, propranolol, or phentolamine. Results: In the first substudy, 40 mg/kg pralidoxime resulted in the highest coronary perfusion pressure (CPP) among the groups, while 120 mg/kg pralidoxime resulted in the lowest CPP (group effect P P Conclusions: Forty mg/kg of pralidoxime administered with epinephrine led to a significantly higher ROSC rate by improving CPP in a pig model of cardiac arrest, whereas 120 mg/kg did not improve CPP or the ROSC rate. Our findings suggest that the pressor effect of pralidoxime is unrelated to α-adrenoceptors and that its pressor effect is buffered by its vasodepressor action mediated by the inhibition of the sympathetic nervous system.

Shockable rhythm in out-of-hospital cardiac arrest (OHCA) implies better outcome and underlying coronary stenosis. We investigated the neurologic outcome and coronary lesions between initial shockable rhythm and turn-to-shockable rhythm. This multicenter, retrospective observational study included adult nontraumatic OHCA survivors with any shockable rhythm during cardiopulmonary resuscitation (CPR) who underwent targeted temperature management between January 2010 and December 2016. Patients were divided into two groups according to the first monitored rhythm: initial shockable rhythm or turn-to-shockable rhythm. The primary outcome was good neurologic outcome at discharge based on cerebral performance categories, and the secondary outcomes were survival discharge, recurrent arrest, and coronary lesions. The two groups were matched in a 1:1 ratio using propensity score (PS). Of 426 patients, 137 and 289 patients were divided into the turn-to-shockable and initial shockable rhythm groups, respectively. Overall, 224 (52.6%) patients had good neurologic outcomes. The turn-to-shockable rhythm group had less patients with good neurologic outcome (57/137 vs. 167/289

We investigated whether achieving estimated average glucose (EAG) levels versus achieving standard glucose levels (180 mg/dL) was associated with neurologic outcome in cardiac arrest survivors. This single-center retrospective observational study included adult comatose cardiac arrest survivors undergoing therapeutic hypothermia (TH) from September 2011 to December 2017. EAG level was calculated using HbA1c obtained after the return of spontaneous circulation (ROSC), and the mean glucose level during TH was calculated. We designated patients to the EAG or standard glucose group according to whether the mean blood glucose level was closer to the EAG level or 180 mg/dL. Patients in the EAG and standard groups were propensity score- matched. The primary outcome was the 6-month neurologic outcome. The secondary outcomes were hypoglycemia (&le, 70 mg/dL) and serum neuron-specific enolase (NSE) at 48 h after ROSC. Of 384 included patients, 137 (35.7%) had a favorable neurologic outcome. The EAG group had a higher favorable neurologic outcome (104/248 versus 33/136), higher incidence of hypoglycemia (46/248 versus 11/136), and lower NSE level. After propensity score matching, both groups had similar favorable neurologic outcomes (24/93 versus 27/93) and NSE levels, the EAG group had a higher incidence of hypoglycemia (21/93 versus 6/93). Achieving EAG levels was associated with hypoglycemia but not neurologic outcome or serum NSE level.

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

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 2 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.

The association between long duration of resuscitation efforts in out-of-hospital cardiac arrest (OHCA) and neurologic outcome is unclear and understudied with advancements in post-cardiac arrest care and high-quality cardiopulmonary resuscitation. We investigated how downtime, defined as the interval from collapse-to-return of spontaneous circulation (ROSC), impacts on neurologic outcome in OHCA patients treated with targeted temperature management (TTM).A multicenter, registry-based, retrospective cohort study was conducted using cases from 24 hospitals across South Korea. Of the 930 adults (≥18 years) non-traumatic OHCA patients treated with TTM between January 2007 and December 2012 at these hospitals, we included 858 patients who had sufficient data for calculating downtime. Good neurologic outcome was defined as a cerebral performance category score of 1 or 2.Median downtime was 30.0 (22.0-41.0min) and 242 patients (28.2%) had good neurologic outcome. When downtime was divided by 10-min intervals (≤10min, 11-20min, 21-30min, 31-40min, 41-50min, 51-60min, and60min), their neurologically intact survival rate were 48.2%, 51.6%, 29.2%, 22.1%, 16.1%, 14.8%, and 7.1%, respectively (p=0.01). Although downtime was associated with poor neurologic outcome [odds ratio 1.06 (1.05-1.08), p0.01], the area under the receiver operating characteristic curve of downtime for outcome was only 0.67, 95% CI (0.63-0.71). Furthermore, even with downtime20min, 22.2% (150/526) patients still had a good neurologic outcome, and this percentage increased to 50.3% (93/185) in patients with an initial shockable rhythm, and 31.1% (134/431) with age65 years.We found that neurologically intact survival can occur at prolonged downtimes and were unable to identify a downtime for which survivability was clearly futile. These data suggest that downtime should not be considered as a factor in determining whether to provide aggressive post-arrest care, especially in patients with young patients or those with an initially shockable rhythm.

Ischemic contracture compromises the hemodynamic effectiveness of cardiopulmonary resuscitation (CPR) and resuscitability from cardiac arrest. In a pig model of cardiac arrest, 2,3-butanedione monoxime (BDM) attenuated ischemic contracture. We investigated the effects of different doses of BDM to determine whether increasing the dose of BDM could improve the hemodynamic effectiveness of CPR further, thus ultimately improving resuscitability.After 16minutes of untreated ventricular fibrillation and 8minutes of basic life support, 36 pigs were divided randomly into 3 groups that received 50mg/kg (low-dose group) of BDM, 100mg/kg (high-dose group) of BDM, or an equivalent volume of saline (control group) during advanced cardiovascular life support.During advanced cardiovascular life support, the control group showed an increase in left ventricular (LV) wall thickness and a decrease in LV chamber area. In contrast, the BDM-treated groups showed a decrease in the LV wall thickness and an increase in the LV chamber area in a dose-dependent fashion. Mixed-model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Central venous oxygen saturation at 3minutes after the drug administration was 21.6% (18.4-31.9), 39.2% (28.8-53.7), and 54.0% (47.5-69.4) in the control, low-dose, and high-dose groups, respectively (P.001). Sustained restoration of spontaneous circulation was attained in 7 (58.3%), 10 (83.3%), and 12 animals (100%) in the control, low-dose, and high-dose groups, respectively (P=.046).2,3-Butanedione monoxime administered during CPR attenuated ischemic contracture and improved the resuscitability in a dose-dependent fashion.

Background We sought to investigate the utility of arterial pressure, end-tidal carbon dioxide (ETCO2), and central venous oxygen saturation (SCVO2) to guide compression depth adjustment. Thus, in a pig model of cardiac arrest, we observed these parameters during cardiopulmonary resuscitation (CPR) with optimal and suboptimal compression depths. Methods Sixteen pigs underwent three experimental sessions after induction of ventricular fibrillation. First, the animals received two 4-min CPR trials with either optimal (20% of the anteroposterior diameter) or suboptimal (70% of the optimal depth) compression depth. Second, the animals received two 5-min CPR trials with optimal compression depth, in which adrenaline (0.02 mg/kg) or saline placebo was administered. Third, the animals randomly received compression with either optimal or suboptimal depth during advanced cardiovascular life support. Results The systolic arterial pressure reflected compression depth most accurately and immediately (area under the curve [AUC], 0.895–0.939 without adrenaline and 0.928–1.000 with adrenaline). Although the response of ETCO2 to the change in compression depth was 0.5 min slower than that of the systolic arterial pressure, the performance of ETCO2 was comparable with that of systolic arterial pressure. SCVO2 did not reflect compression depth. Adrenaline administration remarkably increased systolic arterial pressure, diastolic arterial pressure, and coronary perfusion pressure but did not affect the ETCO2 readings. Conclusion In a pig model of cardiac arrest, systolic arterial pressure reflected compression depth immediately and accurately. The performance of ETCO2 was comparable with that of systolic arterial pressure. SCVO2 did not reflect compression depth.

BackgroundPrognostication 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).MethodsA 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.ResultsA 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.ConclusionThe 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.

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.

The present study aimed to analyze and compare the prognostic performances of the Japanese Ministry of Health and Welfare (JMHW) score, the Korean Society on Thrombosis and Hemostasis (KSTH) score, the International Society on Thrombosis and Haemostasis (ISTH) score, the Japanese Association for Acute Medicine (JAAM) score, and the revised JAAM (rJAAM) score, for 28-day mortality in severe trauma. This retrospective observational study included patients admitted for severe trauma between 2012 and 2015. Receiver operating characteristics analysis was performed to examine the prognostic performance of the 5 different DIC score systems. The primary outcome was 28-day mortality following an injury. Of the 1266 patients included in the study, 28-day mortality rate was 19.7% (n = 249). The area under the curves (AUCs) of JMHW, KSTH, ISTH, JAAM, and rJAAM scores for 28-day mortality were 0.751 [95% confidence interval (95% CI), 0.726–0.775], 0.726 (95% CI, 0.701–0.750), 0.700 (95% CI, 0.674–0.725), 0.673 (95% CI, 0.646–0.699), and 0.676 (95% CI, 0.649–0.701), respectively. The AUC of JMHW score was significantly different from those of the other score systems. Fibrinogen levels ≤1.0 g/L [odds ratio (OR), 1.824; 95% CI, 1.029–3.232] and 1.0 to 1.5 g/L (OR, 1.697; 95% CI, 1.058–2.724) were independently associated with 28-day mortality compared with fibrinogen level above 1.5 g/L. JMHW score has the highest prognostic performance for 28-day mortality among DIC score systems in severe trauma. Fibrinogen level seemed to have a role in greater discrimination of JMHW scores than the other DIC score systems.

This study aimed to elucidate the association between the neutrophil-to-lymphocyte ratio (NLR) and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients treated with targeted temperature management (TTM).A retrospective study was performed on patients treated with TTM after OHCA. Patients were divided into two groups according to their calculated NLRs (NLR 6 and NLR ≥ 6). The primary outcome was poor neurological outcome at 6 months as defined by a Cerebral Performance Category between 3 and 5.A total of 216 were included and 131 subjects had poor neurological outcomes at 6 months. In the univariate model, NLRs ≥ 6 at 48 and 72 h after ROSC were associated with poor neurological outcomes (OR: 3.716, 95% CI: 1.243-11.114; OR: 7.429, 95% CI: 3.693-14.945, respectively). In the multivariate logistic regression analysis, an NLR ≥ 6 at 72 h was associated with poor neurological outcomes after adjusting for history of HTN, shockable rhythm, cardiac cause of arrest and time from collapse to ROSC and highest WBC, hs-CRP, lactate and pneumonia (OR = 3.299, 95% CI = 1.080-10.081).An NLR ≥ 6 at 72 h after the ROSC is associated with poor neurological outcomes at 6 months after CA.

Objective Hyperoxia could lead to a worse outcome after cardiac arrest. The aim of this study was to investigate the relationship between the cumulative partial pressure of arterial oxygen (PaO2) and neurological outcomes after cardiac arrest treated with targeted temperature management. Design Retrospective analysis of a prospective cohort. Setting An academic tertiary care hospital. Patients A total of 187 consecutive patients treated with targeted temperature management after cardiac arrest. Interventions None. Measurements and main results The area under the curve of PaO2 for different cutoff values of hyperoxia (≥ 100, ≥ 150, ≥ 200, ≥ 250, and ≥ 300 mm Hg) with different time intervals (0-24, 0-6, and 6-24 hr after return of spontaneous circulation) was calculated for each patient using the trapezoidal method. The primary outcome was the neurologic outcome, as defined by the cerebral performance category, at 6 months after cardiac arrest. Of 187 subjects, 77 (41%) had a good neurologic outcome at 6 months after cardiac arrest. The median age was 54 (43-69) years, and 128 (68%) were male. The area under the curve of PaO2 with cutoff values of greater than or equal to 200, greater than or equal to 250, and greater than or equal to 300 was higher in the poor outcome group at 0-6 and 0-24 hours. The adjusted odds ratios of area under the curve of PaO2 greater than or equal to 200 mm Hg were 1.659 (95% CI, 1.194-2.305) for 0-24 hours after return of spontaneous circulation and 1.548 (95% CI, 1.086-2.208) for 0-6 hours after return of spontaneous circulation. With a higher cumulative exposure to oxygen tension, we found significant increasing trends in the adjusted odds ratio for poor neurologic outcomes. Conclusion In a new method for PaO2 analysis, cumulative exposure to hyperoxia was associated with neurologic outcomes in a dose-dependent manner. Greater attention to oxygen supply during the first 6 hours appears to be important for outcome after cardiac arrest.

Aim of the study Ischaemic contracture compromises the haemodynamic effectiveness of cardiopulmonary resuscitation and resuscitability. 2,3-Butanedione monoxime (BDM) reduced ischaemic contracture by inhibiting actin-myosin crossbridge formation in an isolated heart model. We investigated the effects of BDM on ischaemic contracture and resuscitation outcomes in a pig model of out-of-hospital cardiac arrest (OHCA). Methods After 15min of untreated ventricular fibrillation, followed by 8min of basic life support, 16 pigs were randomised to receive either 2mlkg −1 of BDM solution (25gl −1 ) or 2mlkg −1 of saline during advanced cardiac life support (ACLS). Results During the ACLS, the control group showed an increase in left ventricular (LV) wall thickness from 10.0mm (10.0–10.8) to 13.0mm (13.0–13.0) and a decrease in LV chamber area from 8.13cm 2 (7.59–9.29) to 7.47cm 2 (5.84–8.43). In contrast, the BDM group showed a decrease in the LV wall thickness from 10mm (9.0–10.8) to 8.5mm (7.0–9.8) and an increase in the LV chamber area from 9.86cm 2 (7.22–12.39) to 12.15 cm 2 (8.02–14.40). Mixed model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Spontaneous circulation was restored in four (50%) animals in the control group and in eight (100%) animals in the BDM group ( p =0.077). All the resuscitated animals survived during an intensive care period of 4h. Conclusion BDM administered during cardiopulmonary resuscitation reversed ischaemic contracture in a pig model of OHCA.

Introduction Predicting neurologic outcomes after cardiac arrest (CA) is challenging. This study tested the hypothesis that a quantitative analysis of diffusion weighted imaging (DWI) using the FMRIB Software Library (FSL) can predict neurologic outcomes after CA and can clarify the optimal apparent diffusion coefficient (ADC) thresholds for predicting poor neurologic outcomes. Methods Out-of-hospital CA patients treated with targeted temperature management (TTM) who underwent DWI were included in this study. Voxel-based analysis was performed to calculate the mean ADC value. ADC thresholds (750, 700, 650, 600, 550, 500, 450 and 400) and brain volumes below each threshold were also analyzed for their correlation with outcomes. The patients were divided into early (within 48 h after return of spontaneous circulation (ROSC)) and late group (between 48 h and 7 days after ROSC) according to the DWI scan time. The primary outcome was a poor neurologic outcome at 6 months after CA, defined as a cerebral performance category (CPC) of 3–5. Results One hundred ten DWIs were analyzed. The mean ADC values were 789.0 (761.5–826.5) × 10−6 mm2/s for the good neurologic outcome group and 715.2 (663.1–778.4) × 10−6 mm2/s for the poor neurologic outcome group (p 2.5% ADC threshold of 400 × 10−6 mm2/s) in the early group and 79.2% (cutoff value; >1.66% ADC threshold of 400 × 10−6 mm2/s) in the late group. Conclusions Voxel-based analysis using FSL software can predict neurologic outcomes after CA. The ADC threshold of 400 × 10−6 mm2/s had the highest OR for predicting a poor neurologic outcome.

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.

Purpose We aimed to examine the serial changes in coagulofibrinolytic markers that occurred after the restoration of spontaneous circulation (ROSC) in cardiac arrest patients, who were treated with targeted temperature management (TTM). We also evaluated the association between the disseminated intravascular coagulation (DIC) score and clinical outcomes. Methods This was a single-centre, retrospective observational study that included cardiac arrest patients who were treated with TTM from May 2012 to December 2015. The prothrombin time (PT) and partial thromboplastin time (PTT), along with the levels of fibrinogen, fibrin degradation products (FDP), and D-dimer were obtained after ROSC and on day 1, 2, and 3. The DIC score was calculated after ROSC. The primary outcome was the neurologic outcome at discharge and the secondary outcome was the 6-month mortality. Results This study included 317 patients. Of these, 222 (70.0%) and 194 (61.2%) patients had a poor neurologic outcome at discharge and 6-month mortality, respectively. The PT, PTT, and fibrinogen level significantly increased over time, while the FDP and D-dimer levels decreased during first three days after ROSC. Multivariate logistic analyses revealed that the DIC score remained a significant predictor for poor neurologic outcome (odds ratio [OR], 1.800; 95% confidence interval [CI], 1.323–2.451) and 6-month mortality (OR, 1.773; 95% CI, 1.307–2.405). Conclusion The activity of coagulation and fibrinolysis decreased over time. An increased DIC score was an independent prognostic factor for poor neurologic outcome and 6-month mortality.

Purpose A step stool is an ordinary device to improve the quality of chest compression (CC) during in-hospital cardiopulmonary resuscitation (CPR). We investigated the effect of an inclined step stool on the quality of CC during CPR on a hospital bed. Methods We conducted a randomized crossover study of simulation using a manikin. Two different methods of CC were performed and compared: CC using a flat stool and CC using an inclined (20°) stool. Each session of CC was performed for 2 minutes using a metronome at a rate of 110 beats per minute. The primary outcome was the depth of CC. The adequate CC rate, duty cycle, rate of incomplete recoil, and the angle between the arm of the participants and the bed were also measured. Results The median value of the mean depth of CC was 50.5 mm (45.0-57.0 mm) in the flat stool group and 54.5 mm (47.0-58.3 mm) in the inclined stool group ( P = .014). The adequate CC rate was significantly higher in the inclined stool group (84.2% [37.6%-99.1%] vs 57.0% [15.2%-95.0%]; P = .016). The duty cycle and the rate of incomplete recoil were comparable between the 2 groups. The angles between the arm of the participants and the bed were more vertical in the inclined stool group (84.0° ± 5.2° vs 81.0° ± 4.8°; P = .014). Conclusion Using an inclined stool resulted in an improvement in the depth of CC and the adequate CC rate without increasing the rate of incomplete chest recoil.

Objectives Several studies in patients who underwent open heart surgery found that myocardial ischemic damage was reduced by potassium cardioplegia combined with lidocaine infusion. The authors evaluated the effects of potassium/lidocaine-induced cardiac standstill during conventional cardiopulmonary resuscitation (CPR) on myocardial injury and left ventricular dysfunction after resuscitation from prolonged ventricular fibrillation (VF) cardiac arrest in a pig model. Methods Ventricular fibrillation was induced in 16 pigs, and circulatory arrest was maintained for 14 minutes. Animals were then resuscitated by standard CPR. Animals were randomized at the start of CPR to receive 20 mL of saline (control group) or 0.9 mEq/kg potassium chloride and 1.2 mg/kg lidocaine diluted to 20 mL (K-lido group). Results Seven animals in each group achieved return of spontaneous circulation (ROSC; p = 1.000). Four of the K-lido group animals (50%) achieved ROSC without countershock. Resuscitated animals in the K-lido group required fewer countershocks (p = 0.004), smaller doses of epinephrine (p = 0.009), and shorter durations of CPR (p = 0.004) than did the control group. The uncorrected troponin-I at 4 hours after ROSC was lower in the K-lido group compared with the control group (2.82 ng/mL, 95% confidence interval [CI] = 1.07 to 3.38 ng/mL vs. 6.55 ng/mL, 95% CI = 4.84 to 13.30 ng/mL; p = 0.025), although the difference was not significant after Bonferroni correction. The magnitude of reduction in left ventricular ejection fraction (LVEF) between baseline and 1 hour after ROSC was significantly lower in the K-lido group (26.5%, SD ± 6.1% vs. 39.1%, SD ± 6.8%; p = 0.004). Conclusions In a pig model of untreated VF cardiac arrest for 14 minutes, resuscitation with potassium/lidocaine-induced cardiac standstill during conventional CPR tended to reduce myocardial injury and decreased the severity of postresuscitation myocardial dysfunction significantly. Resumen Objetivos Varios estudios en pacientes en los que se llevo a cabo una cirugia a corazon abierto documentaron que el dano isquemico del miocardio se redujo por la infusion cardioplejica de potasio combinada con lidocaina. Se evaluaron los efectos de la lidocaina y el potasio en la parada cardiaca inducida, durante la resucitacion cardiopulmonar (RCP) convencional (RCP), en la lesion miocardica y la disfuncion ventricular izquierda tras la RCP de la parada cardiaca por fibrilacion ventricular (FV) prolongada en un modelo de cerdo. Metodologia Se indujo fibrilacion ventricular en dieciseis cerdos, y se mantuvo la parada cardiorrespiratoria durante 14 minutos. Los animales fueron entonces resucitados mediante RCP convencional. Los animales se aleatorizaron a recibir 20 mL de salino (grupo control) o 0,9 mEq/kg de potasio clorhidrico y 1,2 mg/kg de lidocaina diluidos a 20 mL (grupo Lido-K), al inicio de la RCP. Resultados Siete animales en cada grupo consiguieron la recuperacion de la circulacion espontanea (RCE) (p = 1,000). Cuatro de los animales del grupo Lido-K (50%) alcanzaron la RCE sin choques electricos. Los animales resucitados del grupo Lido-K requirieron menor numero de choques electricos (p = 0,004), menor dosis de adrenalina (p = 0,009), y menor duracion de la RCP (p = 0,004) que el grupo control. La troponina-I a las 4 horas tras RCE fue menor en el grupo Lido-K en comparacion con el grupo control (2,82 ng/mL [IC 95% = 1,07 a 3,38 ng/mL] frente 6,55 ng/mL [IC 95% = 4,84 a 13,30 ng/mL] p = 0,025), aunque la diferencia no fue significativa tras la correccion de Bonferroni. La magnitud de la reduccion en la fraccion de eyeccion del ventriculo izquierdo entre el momento inicial y una hora tras la RCE fue significativamente menor en el grupo Lido-K (26,5% [DE ±6,1%] vs. 39,1% [DE ±6,8%]; p = 0,004). Conclusiones En un modelo cerdo de parada cardiaca por FV en cerdos no tratada durante 14 minutos, el uso de lidocaina y potasio durante la RCP convencional tendio a reducir la lesion miocardica y disminuyo la gravedad de la disfuncion miocardica tras la RCP de forma significativa.

We sought to assess the reliability of the method using the pressure measured at the intraosseous (IO) cannula while squeezing the involved limb (P(squeezing)) in determining the position of the IO needle and to compare its performance with that of the traditional confirmation method.Eighty limbs of twenty domestic swine were assigned to one of three conditions regarding the position of the IO needle; correct placement (n=40), incorrect placement in which the IO needle was placed into the subcutaneous space without entering the bone (incorrect-subcutaneous placement, n=20), or incorrect placement in which the IO needle passed entirely through the bone (incorrect-penetrating placement, n=20). A blinded investigator randomly identified the position of the needle by the traditional method or test method using P(squeezing). If P(squeezing) was 80 mmHg or higher, the IO cannula was regarded as incorrectly placed.P(squeezing) was higher in incorrect placements (176.0 mmHg (130.0-195.0)) compared with that in correct placements (27.0 mmHg (20.0-34.0)) (p0.001). The test method correctly identified all 40 placements, but the traditional method was incorrect for one (5%) of 20 correct placements (p=1.000) and 7 (35%) of 20 incorrect placements (p=0.008). In incorrect placements, false positive results occurred mainly in incorrect-penetrating placements.We suggest that the method using the pressure measured at the IO cannula can be used when there is uncertainty about the position of the IO cannula after determination using traditional methods.

Aim of the study We determined whether combining the grey-to-white matter ratio (GWR) on brain computed tomography (CT) and serum neuron specific enolase (NSE) improves the prognostic performance when compared to either alone in cardiac arrest patients treated with therapeutic hypothermia (TH). Methods We performed a retrospective study of a cohort of cardiac arrest patients treated with TH. The Hounsfield unit was measured in the caudate nucleus (CN), putamen (P), posterior limb of internal capsule (PIC) and corpus callosum (CC); GWR was calculated as CN/PIC and P/CC. The NSE value was obtained at 0, 24, and 48 h after restoration of spontaneous circulation (ROSC). We analysed the prognostic performance of GWR and NSE, singly and in combination, in predicting poor neurologic outcome (cerebral performance category 3–5). Results Of the 224 included patients, 82 showed good neurologic outcome at hospital discharge, while 142 showed poor neurologic outcome. The P/CC (area under receiver operating characteristics (AUROC) 0.864, sensitivity/specificity 52.9%/100%) showed better prognostic performance than did the CN/PIC (AUROC 0.721, sensitivity/specificity 19.8%/100%). The NSE value at 48 h after ROSC (AUROC 0.895, sensitivity/specificity 60.2%/100%) showed the highest prognostic value among the three NSE time points. Analysis of 119 patients undergoing both brain CT and NSE at 48 h indicated that combining P/CC and NSE improved the sensitivity (78.6%) compared to either alone (48.6%, 62.9%). Conclusion Combining brain CT and serum NSE improves the prognostic performance when compared to either alone in predicting poor neurologic outcome in cardiac arrest patients treated with TH.

Aim of the study Potassium-based cardioplegia has been the gold standard for cardioprotection during cardiac surgery. We sought to evaluate the feasibility and the effects of potassium-induced cardiac standstill during conventional cardiopulmonary resuscitation (CPR) in a pig model of prolonged ventricular fibrillation (VF). Methods VF was induced in 20 pigs, and circulatory arrest was maintained for 14 min. Animals were then resuscitated by standard CPR. Coincident with the start of CPR, 20 ml of saline (control group) or 0.9 mequiv. kg −1 of potassium chloride diluted to 20 ml (potassium group) was administered into right atrium. Results Administration of potassium resulted in asystole lasting for 1.0 min (0.2) in the potassium group animals. VF reappeared in all but one animal, in which wide QRS complex bradycardia followed. Restoration of spontaneous circulation (ROSC) was attained in two animals (20%) in the control group and in seven animals (70%) in the potassium group ( p = 0.070). Resuscitated animals in the potassium group required fewer countershocks (3, 4 vs. 2 (1–2)), smaller doses of adrenaline (1.84, 1.84 vs. 0.94 (0.90–1.00) mg), and shorter duration of CPR (8, 10 vs. 4.0 (4.0–4.0) min) than did the control group. Potassium concentrations normalised rapidly after ROSC in both groups, and the potassium concentrations at 5 min (5.5, 6.6 vs. 6.8 (6.5–7.8) mequiv. l −1 ) and 4 h (4.9, 5.4 vs. 5.9 (5.1–6.4) mequiv. l −1 ) after ROSC were similar in the both groups. Conclusion In a pig model of untreated VF cardiac arrest for 14 min, resuscitation with potassium-induced cardiac standstill during conventional CPR was found to be feasible.

Background This study aimed to present our 5-year experience of extracorporeal cardiopulmonary resuscitation (ECPR) performed by emergency physicians. Methods We retrospectively analyzed 58 patients who underwent ECPR between January 2010 and December 2014. The primary parameter analyzed was survival to hospital discharge. The secondary parameters analyzed were neurologic outcome at hospital discharge, cannulation time, and ECPR-related complications. Results Thirty-one patients (53.4%) were successfully weaned from extracorporeal membrane oxygenation, and 18 (31.0%) survived to hospital discharge. Twelve patients (20.7%) were discharged with good neurologic outcomes. The median cannulation time was 25.0 min (interquartile range 20.0-31.0 min). Nineteen patients (32.8%) had ECPR-related complications, the most frequent being distal limb ischemia. Regarding the initial presentation, 52 patients (83.9%) collapsed due to a cardiac etiology, and acute myocardial infarction (33/62, 53.2%) was the most common cause of cardiac arrest. Conclusions The survival to hospital discharge rate for cardiac arrest patients who underwent ECPR conducted by an emergency physician was within the acceptable limits. The cannulation time and complications following ECPR were comparable to those found in previous studies.