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

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

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

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

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

We investigated the association of insulin administration method with the achievement of mean glucose ≤ 180 mg/dL and neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors who had hyperglycemia after the return of spontaneous circulation. From a multicenter prospective registry, we extracted the data of adult OHCA survivors who underwent targeted temperature management (TTM) between 2015 and 2018. Blood glucose levels every 4 h after initiating TTM were obtained for 72 h. We divided insulin administration methods into three categories: subcutaneous (SQI), intravenous bolus (IBI), and continuous intravenous (CII). We calculated the mean glucose and standard deviation (SD) of glucose. The primary outcome was the achievement of mean glucose ≤ 180 mg/dL. The secondary outcomes were the 6-month neurological outcome based on the Cerebral Performance Category (CPC) scale (good, CPC 1-2; poor, CPC 3-5), mean glucose, and SD of glucose. Of the 549 patients, 296 (53.9%) achieved mean glucose ≤ 180 mg/dL, and 438 (79.8%) had poor neurological outcomes, 134 (24.4%), 132 (24.0), and 283 (51.5%) were in the SQI, IBI, and CII groups, respectively. The SQI (adjusted odds ratio [aOR], 0.848; 95% confidence intervals [CIs], 0.493-1.461) and IBI (aOR, 0.673; 95% CIs, 0.415-1.091) groups were not associated with mean glucose ≤ 180 mg/dL and the SQI (aOR, 0.660; 95% CIs, 0.335-1.301) and IBI (aOR, 1.757; 95% CIs, 0.867-3.560) groups were not associated with poor neurological outcomes compared to the CII group. The CII (168 mg/dL [147-202]) group had the lowest mean glucose than the SQI (181 mg/dL [156-218]) and IBI (184 mg/dL [162-216]) groups. The CII (45.0[33.9-63.5]) group had a lower SD of glucose than the IBI (50.8 [39.1-72.0]) group. The insulin administration method was not associated with achieving mean glucose ≤ 180 mg/dL and 6-month neurological outcomes.

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

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

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

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

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

We evaluated the performance of cardiac arrest-specific prognostication scores developed for outcome prediction in the early hours after out-of-hospital cardiac arrest (OHCA) in predicting long-term outcomes using independent data. The following scores were calculated for 1,163 OHCA patients who were treated with targeted temperature management (TTM) at 21 hospitals in South Korea: OHCA, cardiac arrest hospital prognosis (CAHP), C-GRApH (named on the basis of its variables), TTM risk, 5-R, NULL-PLEASE (named on the basis of its variables), Serbian quality of life long-term (SR-QOLl), cardiac arrest survival, revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST), Polish hypothermia registry (PHR) risk, and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages (PROLOGUE) scores and prediction score by Aschauer et al. Their accuracies in predicting poor outcome at 6 months after OHCA were determined using the area under the receiver operating characteristic curve (AUC) and calibration belt. In the complete-case analyses, the PROLOGUE score showed the highest AUC (0.923; 95% confidence interval [CI], 0.904-0.941), whereas the SR-QOLl score had the lowest AUC (0.749; 95% CI, 0.711-0.786). The discrimination performances were similar in the analyses after multiple imputation. The PROLOGUE, TTM risk, CAHP, NULL-PLEASE, 5-R, and cardiac arrest survival scores were well calibrated. The rCAST and PHR risk scores showed acceptable overall calibration, although they showed miscalibration under the 80% CI level at extreme prediction values. The OHCA score, C-GRApH score, prediction score by Aschauer et al., and SR-QOLl score showed significant miscalibration in both complete-case (P = 0.026, 0.013, 0.005, and < 0.001, respectively) and multiple-imputation analyses (P = 0.007, 0.018, < 0.001, and < 0.001, respectively). In conclusion, the discrimination performances of the prognostication scores were all acceptable, but some showed significant miscalibration.

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

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings. DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry. SETTING: Multicenter ICU. PATIENTS: Adult (≥ 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36°C between October 2015 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes. CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

Rearrest during hospitalisation in adult comatose out-of-hospital cardiac arrest patients: Risk factors and prognostic impact, and predictors of favourable long-term outcomes.

BACKGROUND: Rearrest occurs commonly after initial resuscitation following out-of-hospital cardiac arrest (OHCA). We determined (1) the predictors of rearrest during hospitalisation that can be identified in the hours immediately after OHCA, (2) the association between rearrest and favourable long-term outcomes, and (3) the predictors of favourable long-term outcomes in rearrest patients. METHODS: Conditional multivariable logistic regression analyses were performed using the Korean Hypothermia Network prospective registry data, which included details of adult OHCA patients treated with targeted temperature management at 22 teaching hospitals in South Korea. RESULTS: Among the 1,233 patients, 260 (21.1%) experienced rearrest. Of the 192 patients resuscitated from first rearrest, 33 (17.2%) achieved 6-month favourable outcomes. Arrhythmia, heart failure, ST-segment elevation, lower initial Glasgow coma scale (GCS) motor score, higher initial lactate level, and antiarrhythmic drug use within 1 h were independently associated with rearrest. Higher lactate level and antiarrhythmic drug use were associated with shockable first rearrest, while arrhythmia, heart failure, ST-segment elevation, and lower GCS motor score were associated with non-shockable first rearrest. Rearrest was independently associated with a lower likelihood of 6-month favourable outcomes (P = 0.003). Initial shockable rhythm after OHCA, absence of diabetes, shorter cumulative time to restoration of spontaneous circulation, coronary angiography, and hypophosphataemia within 7 d were independently associated with 6-month favourable outcomes in the patients resuscitated from first rearrest. CONCLUSIONS: Rearrest during hospitalisation after OHCA was inversely associated with 6-month favourable outcomes. We identified several risk factors for rearrest and prognostic factors for patients resuscitated from first rearrest.

Discrimination between the presence and absence of spontaneous circulation using smartphone seismocardiography: A preliminary investigation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: In conclusion, blinded observers accurately distinguished between seismocardiography signals from patients with and without spontaneous circulation.

Effect of Epinephrine Administered during Cardiopulmonary Resuscitation on Cerebral Oxygenation after Restoration of Spontaneous Circulation in a Swine Model with a Clinically Relevant Duration of Untreated Cardiac Arrest.

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 < 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.

Pralidoxime improves the hemodynamics and survival of rats with peritonitis-induced sepsis.

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.

Association between ion shift index and prognosis in severe trauma patients without isolated head injury.

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.

Relationship of common hemodynamic and respiratory target parameters with brain tissue oxygen tension in the absence of hypoxemia or hypotension after cardiac arrest: A post-hoc analysis of an experimental study using a pig model.

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.

PROLOGUE (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages): Development and validation of a scoring system for early prognostication in unselected adult cardiac arrest patients.

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

Slow Heart Rate Within 72 Hours After Cardiac Arrest Is Associated with Good Neurologic Outcome in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management with 33°C.

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

Early Post-Rewarming Fever Is Associated with Favorable 6-Month Neurologic Outcomes in Patients with Out-Of-Hospital Cardiac Arrest: A Multicenter Registry Study.

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 (≥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 ≥ 38.0 °C within 72 h after completion of rewarming, and PRF timing was categorized as within 24, 24-48, and 48-72 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 24-48 h in 155 (39.8%), and in 48-72 h in 84 (21.6%). PRF was associated with improved neurologic outcomes (odds ratio (OR), 0.633; 95% confidence interval (CI), 0.416-0.963). PRF within 24 h (OR, 0.355; 95% CI, 0.191-0.659), but not in 24-48 h or 48-72 h, was associated with unfavorable neurologic outcomes. Early PRF within 24 h after rewarming was associated with favorable neurologic outcomes.

High heat generation is associated with good neurologic outcome in out-of-hospital cardiac arrest survivors underwent targeted temperature management at 33 °C.

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.

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

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

Effects of Different Doses of Pralidoxime Administered During Cardiopulmonary Resuscitation and the Role of α-Adrenergic Receptors in Its Pressor Action.

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<0.001). In 49 rats, arterial pressure response to 40 mg/kg of pralidoxime was determined after saline, guanethidine, phenoxybenzamine, or phentolamine pretreatment, and the response to 200 mg/kg pf pralidoxime was determined after saline, propranolol, or phentolamine pretreatment. Pralidoxime at 40 mg/kg elicited a pressor response. Phenoxybenzamine completely inhibited the pressor response, but guanethidine and phentolamine did not. The pressor response of pralidoxime was even greater after guanethidine or phentolamine pretreatment. Pralidoxime at 200 mg/kg produced an initial vasodepressor response followed by a delayed pressor response. Unlike propranolol, phentolamine eliminated the initial vasodepressor response. 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.

Turn-to-Shockable Rhythm Has Comparable Neurologic Outcomes to Initial Shockable Rhythm in Out-of-Hospital Cardiac Arrest Patients Who Underwent Targeted Temperature Management.

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; p = 0.002) and less culprit lesions in the left anterior descending and left circumflex arteries. However, survival discharge and recurrent arrest were not different between the two groups, and the turn-to-shockable rhythm had no independent association with neurologic outcome (odds ratio, 1.874; 95% confidence interval, 0.909-3.863). In the PS-matched cohort, the turn-to-shockable rhythm group had similar good neurologic outcome (47/100 vs. 35/100, p = 0.083). Survival discharge, recurrent arrest, and coronary culprit lesions were not different between the two groups. In this PS-matched study, OHCA with any shockable rhythm during CPR had similar neurologic outcome and coronary culprit lesions, irrespective of the first monitored rhythm.