Circulating glycocalyx shedding products as biomarkers for evaluating prognosis of patients with out-of-hospital cardiac arrest after return of spontaneous circulation.

The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan-Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes.

Temperature management in acute brain injury: A narrative review.

Temperature management has been used in patients with acute brain injury resulting from different conditions, such as post-cardiac arrest hypoxic-ischaemic insult, acute ischaemic stroke, and severe traumatic brain injury. However, current evidence offers inconsistent and often contradictory results regarding the clinical benefit of this therapeutic strategy on mortality and functional outcomes. Current guidelines have focused mainly on active prevention and treatment of fever, while therapeutic hypothermia (TH) has fallen into disuse, although doubts persist as to its effectiveness according to the method of application and appropriate patient selection. This narrative review presents the most relevant clinical evidence on the effects of TH in patients with acute neurological damage, and the pathophysiological concepts supporting its use.

Soluble Urokinase-Type Plasminogen Activator Receptor in Comatose Survivors After Out-of-Hospital Cardiac Arrest Treated with Targeted Temperature Management.

Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. This study investigated serial levels of suPAR in differentiated target temperature management and the associations with mortality and 6-month neurological outcome. This is a single-center substudy of the randomized Targeted Temperature Management (TTM) for 24-hour versus 48-hour trial. In this analysis, we included 82 patients and measured serial levels of suPAR at 24, 48, and 72 hours after achievement of target temperature (32-34°C). We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories (CPC) at 6 months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method and serial measurements of suPAR (log2 transformed) were investigated by Cox proportional-hazards models. Good neurological outcome at 6 months was assessed by logistic regression analyses. Levels of suPAR were significantly different between TTH groups (pinteraction = 0.04) with the highest difference at 48 hours, 4.7 ng/mL (95% CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95% CI: 2.2-3.5 ng/mL) in the TTH48 group, p < 0.0001. Levels of suPAR above the median value were significantly associated with increased all-cause mortality at any time point (plog-rank<0.05). The interaction of suPAR levels and TTH group was not significant (pinteraction = NS). A twofold increase in levels of suPAR was significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (pinteraction = NS). Prolonged TTM of 48 hours versus 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at 6 months with no significant interaction of TTH group.

Efficacy and safety of the Arctic Sun device for hypoxic-ischemic encephalopathy in adult patients following cardiopulmonary resuscitation: A systematic review and meta-analysis.

AIM: The principal objective of this study was to carry out a comprehensive and thorough analysis to compare the safety and effectiveness of the Arctic Sun, a servo-controlled surface cooling device, with conventional cooling techniques for providing therapeutic hypothermia in adult patients who had experienced hypoxic-ischemic brain injury following cardiopulmonary resuscitation. METHODS: In order to achieve our goal, we conducted an extensive search of multiple databases including PubMed, Embase, Cochrane, and ClinicalTrials.gov up to the date of July 30, 2021. We only included studies that compared the safety and efficacy of the Arctic Sun surface cooling equipment with standard cooling approaches such as cooling blankets, ice packs, and intravenous cold saline for treating comatose adult patients who had recovered after experiencing cardiac arrest. We evaluated various outcomes, including all-cause mortality, good neurological outcome at 1 month, and the occurrence of adverse effects such as infections, shock, and bleeding. We employed a random-effects meta-analysis to estimate the odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes. RESULTS: One hundred and fourteen records were identified through our search; however, only three studies met our eligibility criteria, resulting in overall 187 patients incorporated in the meta-analysis. The findings indicated no significant difference in mortality rates among the Arctic Sun device and conventional cooling techniques (OR: 0.64; 95% CI: 0.34-1.19; P = 0.16; I2 = 0%). In addition, we found no significant difference in occurrence of good neurological outcomes (OR: 1.74; 95% CI: 0.94-3.25; P = 0.08; I2 = 0%) between the two cooling methods. However, the application of the Arctic Sun device was associated with increased incidence of infections compared to standard cooling methods (OR: 2.46; 95% CI: 1.18-5.11; P = 0.02; I2 = 0%). While no significant difference occurred in the incidence of shock (OR: 0.29; 95% CI: 0.07-1.18; P = 0.08; I2 = 40%), the use of the Arctic Sun device was linked to significantly fewer bleeding complications compared to standard cooling methods (OR: 0.11; 95% CI: 0.02-0.79; P = 0.03; I2 = 0%). CONCLUSIONS: After analyzing the results of our meta-analysis, we concluded that the use of the Arctic Sun device for targeted temperature management following cardiopulmonary resuscitation did not result in significant differences in mortality rates or improve neurological outcomes when compared to standard cooling techniques.

Optimal Timing of Targeted Temperature Management for Post-Cardiac Arrest Syndrome: Is Sooner Better?

Targeted temperature management (TTM) is often considered to improve post-cardiac arrest patients' outcomes. However, the optimal timing to initiate cooling remained uncertain. This retrospective analysis enrolled all non-traumatic post-cardiac arrest adult patients with either out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA) who received TTM from July 2015 to July 2021 at our hospital. The values of time delay before TTM and time to target temperature were divided into three periods according to optimal cut-off values identified using receiver operating characteristic curve analysis. A total of 177 patients were enrolled. A shorter time delay before TTM (pre-induction time) was associated with a lower survival chance at 28 days (32.00% vs. 54.00%, p = 0.0279). Patients with a longer cooling induction time (>440 minis) had better neurological outcomes (1.58% vs. 1.05%; p = 0.001) and survival at 28 days (58.06% vs. 29.25%; p = 0.006). After COX regression analysis, the influence of pre-induction time on survival became insignificant, but patients who cooled slowest still had a better chance of survival at 28 days. In conclusion, a shorter delay before TTM was not associated with better clinical outcomes. However, patients who took longer to reach the target temperature had better hospital survival and neurological outcomes than those who were cooled more rapidly. A further prospective study was warranted to evaluate the appropriate time window of TTM.

Feasibility of electroacupuncture at Baihui (GV20) and Zusanli (ST36) on survival with a favorable neurological outcome in patients with postcardiac arrest syndrome after in-hospital cardiac arrest: study protocol for a pilot randomized controlled trial.

BACKGROUND: At present, even the first-line medication epinephrine still shows no evidence of a favourable neurological outcome in patients with sudden cardiac arrest (SCA). The high mortality of patients with postcardiac arrest syndrome (PCAS) can be attributed to brain injury, myocardial dysfunction, systemic ischaemia/reperfusion response, and persistent precipitating pathology. Targeted temperature management, the only clinically proven method in the treatment of PCAS, is still associated with a series of problems that have not been completely resolved. Acupuncture is a crucial therapy in traditional Chinese medicine. On the basis of the results of previous studies, we hypothesize that electroacupuncture (EA) might provide therapeutic benefits in the treatment of PCAS. This study will explore the feasibility of EA on SCA patients. METHODS: This is a prospective pilot, randomized controlled clinical trial. Eligible patients with PCAS after in-hospital cardiac arrest (IHCA) admitted to our department will be randomly allocated to the control group or the EA group. Both groups will receive standard therapy according to American Heart Association guidelines for cardiopulmonary resuscitation. However, the EA group will also receive acupuncture at the Baihui acupoint (GV20) and Zusanli acupoint (ST36) with EA stimulation for 30 min using a dense-dispersed wave at frequencies of 20 and 100 Hz, a current intensity of less than 10 mA, and a pulse width of 0.5 ms. EA treatment will be administered for up to 14 days (until either discharge or death). The primary endpoint is survival with a favourable neurological outcome. The secondary endpoints are neurological scores, cardiac function parameters, and other clinical parameters, including Sequential Organ Failure Assessment (SOFA) scores and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, on days 0 to 28. DISCUSSION: This study will provide crucial clinical evidence on the efficacy of EA in PCAS when used as an adjunctive treatment with AHA standard therapy. TRIAL REGISTRATION: chictr.org.cn : ChiCTR2000040040. Registered on 19 November 2020. Retrospectively registered. http://www.chictr.org.cn/ .

Fibrinolysis in Cardiac Arrest Patients Treated with Hypothermia.

Hypothermia affects coagulation, but the effect of hypothermia on fibrinolysis is not clarified. Imbalance in the fibrinolytic system may lead to increased risk of bleeding or thrombosis. Our aim was to investigate if resuscitated cardiac arrest patients treated with hypothermia had an unbalanced fibrinolysis. A prospective cohort study, including 82 patients were treated with hypothermia at 33°C ± 1°C after out-of-hospital cardiac arrest. Blood samples were collected at 24 hours (hypothermia) and at 72 hours (normothermia). Samples were analyzed for fibrin D-dimer, tissue plasminogen activator (tPA), plasminogen, plasminogen activator Inhibitor-1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and an in-house dynamic fibrin clot formation and lysis assay.Compared with normothermia, hypothermia significantly increased plasminogen activity (mean difference = 10.4%, 95% confidence interval [CI] 7.9-12.9), p < 0.001), PAI-1 levels (mean difference = 275 ng/mL, 95% CI 203-348, p < 0.001), and tPA levels (mean difference = 1.0 ng/mL, 95% CI 0.2-1.7, p = 0.01). No differences between hypothermia and normothermia were found in TAFI activity (p = 0.59) or in the fibrin D-dimer levels (p = 0.08). The fibrin clot lysis curves showed three different patterns: normal-, flat-, or resistant clot lysis curve. At hypothermia 45 (55%) patients had a resistant clot lysis curve and 33 (44%) patients had a resistant clot lysis curve at normothermia (p = 0.047). Comatose, resuscitated, cardiac arrest patients treated with hypothermia express an inhibited fibrinolysis even after rewarming. This could potentially increase the thromboembolic risk. ClinicalTrials.gov ID: NCT02258360.

Markers of neutrophil mediated inflammation associate with disturbed continuous electroencephalogram after out of hospital cardiac arrest.

BACKGROUND: Achieving an acceptable neurological outcome in cardiac arrest survivors remains challenging. Ischemia-reperfusion injury induces inflammation, which may cause secondary neurological damage. We studied the association of ICU admission levels of inflammatory biomarkers with disturbed 48-hour continuous electroencephalogram (cEEG), and the association of the daily levels of these markers up to 72 h with poor 6-month neurological outcome. METHODS: This is an observational, post hoc sub-study of the COMACARE trial. We measured serum concentrations of procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), osteopontin (OPN), myeloperoxidase (MPO), resistin, and proprotein convertase subtilisin/kexin type 9 (PCSK9) in 112 unconscious, mechanically ventilated ICU-treated adult OHCA survivors with initial shockable rhythm. We used grading of 48-hour cEEG monitoring as a measure for the severity of the early neurological disturbance. We defined 6-month cerebral performance category (CPC) 1-2 as good and CPC 3-5 as poor long-term neurological outcome. We compared the prognostic value of biomarkers for 6-month neurological outcome to neurofilament light (NFL) measured at 48 h. RESULTS: Higher OPN (p = .03), MPO (p < .01), and resistin (p = .01) concentrations at ICU admission were associated with poor grade 48-hour cEEG. Higher levels of ICU admission OPN (OR 3.18; 95% CI 1.25-8.11 per ln[ng/ml]) and MPO (OR 2.34; 95% CI 1.30-4.21) were independently associated with poor 48-hour cEEG in a multivariable logistic regression model. Poor 6-month neurological outcome was more common in the poor cEEG group (63% vs. 19% p < .001, respectively). We found a significant fixed effect of poor 6-month neurological outcome on concentrations of PCT (F = 7.7, p < .01), hsCRP (F = 4.0, p < .05), and OPN (F = 5.6, p < .05) measured daily from ICU admission to 72 h. However, the biomarkers did not have independent predictive value for poor 6-month outcome in a multivariable logistic regression model with 48-hour NFL. CONCLUSION: Elevated ICU admission levels of OPN and MPO predicted disturbances in cEEG during the subsequent 48 h after cardiac arrest. Thus, they may provide early information about the risk of secondary neurological damage. However, the studied inflammatory markers had little value for long-term prognostication compared to 48-hour NFL.

Development, implementation, and refinement of a comprehensive postcardiac arrest care training course in Japan.

Aim: In Japan, no training course is dedicated to postcardiac arrest care (PCAC), including venoarterial extracorporeal membrane oxygenation (VA-ECMO); thus, faculty members of the Japanese Circulation Society developed an original, comprehensive PCAC training course. This report reviews the development, implementation, and refinement of this PCAC training course. Methods: We examined the preserved data from the Japanese Circulation Society PCAC training courses between 2014 and 2020. Data related to the learning content and number of the attendees and instructors were collected and summarized. Results: Sixteen courses were held between August 2014 and February 2020, before the coronavirus disease 2019 (COVID-19) pandemic. A total of 677 health care providers participated: 351 doctors, 225 nurses, 62 perfusionists, five emergency medical professionals, and two pharmacists. Thirty-two attendees' data were missing. The core learning contents of all the courses included a standardized postcardiac arrest algorithm, targeted temperature management, VA-ECMO cannulation skills, and postcannulation management. Concerning curriculum evolution, extracorporeal cardiopulmonary resuscitation simulation, postarrest neurological examination and monitoring, and ultrasound-guided Seldinger technique training were added in the 4th, 5th, and 13th courses, respectively. Conclusion: The Japanese Circulation Society PCAC training course has been developed and refined to provide an organized, comprehensive opportunity for health care providers to acquire specific knowledge and skills in PCAC and VA-ECMO.

Comparing Doppler Echocardiography and Thermodilution for Cardiac Output Measurements in a Contemporary Cohort of Comatose Cardiac Arrest Patients Undergoing Targeted Temperature Management.

Measuring cardiac output is used to guide treatment during postresuscitation care. The aim of this study was to compare Doppler echocardiography (Doppler-CO) with thermodilution using pulmonary artery catheters (PAC-CO) for cardiac output estimation in a large cohort of comatose out-of-hospital cardiac arrest (OHCA) patients undergoing targeted temperature management (TTM). Single-center substudy of 141 patients included in the TTM trial randomly assigned to 33 or 36°C for 24 hours after OHCA. Per protocol, PAC-CO and Doppler-CO were measured simultaneously shortly after admission and again at 24 and 48 hours. Linear correlation was assessed between methods and positive predictive value (PPV) and negative predictive value (NPV) of Doppler to estimate low cardiac output (<3.5 L/min) was calculated. A total of 301 paired cardiac output measurements were available. Average cardiac output was 5.28 ± 1.94 L/min measured by thermodilution and 4.06 ± 1.49 L/min measured by Doppler with a mean bias of 1.22 L/min (limits of agreements -1.92 to 4.36 L/min). Correlation between methods was moderate (R2 = 0.36). Using PAC-CO as the gold standard, PPV of a low cardiac output measurement (<3.5 L/min) by Doppler was 33%. However, the NPV was 92%. Hypothermia at 33°C did not negatively affect the correlations of CO methods. In the lowest quartile of Doppler, 13% had elevated lactate (>2 mmol/L). In the lowest quartile of thermodilution, 36% had elevated lactate (>2 mmol/L). In ventilated OHCA patients, the two methods for estimating cardiac output correlated moderately and there was a consistent underestimation of Doppler-CO. Absolute cardiac output values from Doppler-CO should be interpreted with caution. However, Doppler can be used to exclude low cardiac output with high accuracy. TTM at 33°C did not negatively affect the correlation or bias of cardiac output measurements. ClinicalTrials.gov ID: NCT01020916.

Target Temperature Management and Survival with Favorable Neurological Outcome After Out-of-Hospital Cardiac Arrest in Children: A Nationwide Multicenter Prospective Study in Japan.

To assess whether target temperature management (TTM) is effective for 1-month survival with favorable neurological outcome among pediatric patients who achieved return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). The Japanese Association for Acute Medicine-out-of-hospital cardiac arrest (JAAM-OHCA) Registry, a multicenter prospective observational registry in Japan, included OHCA patients aged ≤17 years who achieved ROSC between June 2014 and December 2017. The primary outcome was 1-month survival with favorable neurological outcomes, defined as pediatric cerebral performance category 1 or 2. We conducted a propensity score analysis with inverse-probability-of-treatment weighting (IPTW) and evaluated the effect of TTM using logistic regression models with IPTW. A total of 167 patients [120 in the non-TTM group (71.9%) and 47 in the TTM group (28.1%)] were eligible for our analysis. The proportion of patients demonstrating 1-month survival with favorable neurological outcomes was 25.5% (12/47) in the TTM group and 16.7% (20/120) in the non-TTM group; there were no significant differences in favorable neurological outcomes (odds ratio, 1.36; 95% confidence interval, 0.55-3.35) between the non-TTM and TTM groups after performing adjustments with IPTW. In our study population composed of pediatric patients who achieved ROSC after OHCA, we did not find a positive association between TTM implementation and 1-month survival with favorable neurological outcomes.

Postcardiac Arrest Neuroprognostication Practices: A Survey of Brazilian Physicians.

End-of-life care and decisions on withdrawal of life-sustaining therapies vary across countries, which may affect the feasibility of future multicenter cardiac arrest trials. In Brazil, withdrawal of life-sustaining therapy is reportedly uncommon, allowing the natural history of postcardiac arrest hypoxic-ischemic brain injury to present itself. We aimed to characterize approaches to neuroprognostication of cardiac arrest survivors among physicians in Brazil. DESIGN: Cross-sectional study. SETTING: Between August 2, 2019, and July 31, 2020, we distributed a web-based survey to physicians practicing in Brazil. SUBJECTS: Physicians practicing in Brazil and members of the Brazilian Association of Neurointensive Care, who care for patients resuscitated following cardiac arrest. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Responses from 185 physicians were obtained. Pupillary reflexes, corneal reflexes, and motor responses were considered critical to prognostication, whereas neuroimaging and electroencephalography were also regarded as important. For patients without targeted temperature management, absent pupillary and corneal reflexes at 24 hours postarrest were considered strongly predictive of poor neurologic outcome by 31.8% and 33.0%, respectively. For targeted temperature management-treated patients, absent pupillary and corneal reflexes at 24-hour postrewarming were considered prognostic by 22.9% and 20.0%, respectively. Physicians felt comfortable making definitive prognostic recommendations at day 6 postarrest or later (34.2%) for nontargeted temperature management-treated patients, and at day 6 postrewarming (20.4%) for targeted temperature management-treated patients. Over 90% believed that improving neuroprognostic accuracy would affect end-of-life decision-making. CONCLUSIONS: There is significant variability in neuroprognostic approaches to postcardiac arrest patients and timing of prognostic studies among Brazilian physicians, with practices frequently deviating from current guidelines, underscoring a need for greater neuroprognostic accuracy. Nearly all physicians believed that improving neuroprognostication will impact end-of-life decision-making. Given the tendency to delay prognostic recommendations while using similar neuroprognostic tools, Brazil offers a unique cohort in which to examine the natural history of hypoxic-ischemic brain injury in future studies.

Impact of Hypothermia on Oxygenation Variables and Metabolism in Survivors of Out-of-Hospital Cardiac Arrest Undergoing Targeted Temperature Management at 33°C Versus 36°C.

Targeted temperature management (TTM) exerts substantial impact on hemodynamic function in out-of-hospital cardiac arrest (OHCA) patients. Whole-body oxygen consumption (VO2) and delivery (DO2) have not previously been investigated in a clinical setting during TTM at different levels of temperature after OHCA. A substudy of 151 patients randomized at a single center in the TTM-trial, where patients were randomly assigned TTM at 33°C (TTM33) or 36°C (TTM36) for 24 hours. We calculated VO2 according to the principle of Fick (VO2 = cardiac output*arteriovenous oxygen content difference). DO2 was calculated as cardiac output*arterial oxygen content. Cardiac output was measured by pulmonary artery catheter with thermodilution. Arteriovenous oxygen content difference was calculated from arterial and mixed venous oxygen saturation and hemoglobin. Oxygen extraction ratio = VO2/DO2. At 24 hours, the VO2 was 169 ± 59 mL O2 per minute in TTM33 and 217 ± 53 mL O2 per minute in TTM36 (p < 0.0001). During 24 hours of TTM, the overall difference was 53 mL O2 minute (95% confidence interval [CI]: 31-74, pgroup < 0.0001). After rewarming at 36 and 48 hours, there was no difference in VO2 between the groups. DO2 was overall 277 mL O2 per minute (95% CI: 175-379, pgroup < 0.0001) higher in the TTM36-group during TTM. Oxygen extraction ratio during TTM was not significantly different between the two groups (2% [95% CI: -0.1 to 5, pgroup = 0.09]). VO2 during the first 36 hours after OHCA correlated significantly with temperature, and VO2 was 19 mL O2 per minute lower per degree reduction in temperature (95% CI: 15-22), p < 0.0001. TTM at 33°C compared to 36°C after OHCA is associated with significantly lower VO2 and DO2, however, oxygen extraction ratio was not significantly different. For each degree lower body temperature, the VO2 fell by 19 mL O2 per minute.

Prognostic value of repeated thromboelastography measurement for favorable neurologic outcome during targeted temperature management in out-of-hospital cardiac arrest survivors.

BACKGROUND: Cardiac arrest can activate blood coagulation, which clinically manifests as obstruction of the microcirculation and multiple organ dysfunction. Thromboelastography (TEG) provides a rapid and comprehensive assessment of hemostatic processes, but there are limited data on the use of sequential TEG values during targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA) survivors. The aim of this study was to investigate the prognostic value of coagulopathy assessed by repeated TEG to predict neurologically intact survival. METHODS: A prospective cohort of consecutive non-trauma OHCA patients who were successfully resuscitated and treated with TTM. Patients with a target temperature of 36 ℃, no TEG data, and who declined appropriate treatment were excluded. TEG was measured at three time points of TTM (initial phase, target phase, and rewarming phase). The primary outcome was 28 day favorable neurologic function, defined as a Cerebral Performance Category of 1 or 2. RESULTS: A total of 125 patients (mean age, 61 years; 63.2% male) were analyzed. A favorable neurologic outcome at 28 days was seen in 40 patients (32.0%). TEG values of R and LY30 in the initial phase were significantly lower in the favorable neurologic outcome group than in the unfavorable group (5.8 vs. 8.1 and 0.1 vs. 0.7, respectively; p < 0.01). TEG values of R < 5 or LY30 < 7.5 in the initial phase were more frequently seen in the favorable outcomes group than in the unfavorable group (37.5% vs. 12.9%, p = 0.002 and 95.0% vs. 72.9%, p = 0.004, respectively). However, no significant differences were seen between the two groups in other TEG values (R, K, alpha, and MA) in the target and rewarming phases (p > 0.05 for all). Univariate analysis showed higher D-dimer levels, prothrombin time, and activated partial thromboplastin time in the unfavorable outcome group. In the multivariable analysis, TEG values of combination of R < 5 and LY30 < 7.5 in the initial phase were the only coagulation profiles seen to be independently associated with favorable neurologic outcome (OR, 4.508, 95% CI, 1.254-16.210). CONCLUSION: TEG results are available within minutes, and shorted R values or the absence of prolonged LY30 values in the initial phase are an early predictor of neurologically intact survival in successfully resuscitated OHCA patients.

Precision and Safety of an Intravascular Temperature Management System for Postcardiac Arrest Syndrome Patients: A Multicenter Clinical Trial (COOL-ARREST JP).

Rapid induction and maintaining a target temperature of 32.0-36.0°C within a narrow range for <24 hours are essential, but those are very hard to perform in postcardiac arrest syndrome (PCAS) patients. We investigated the usability of an intravascular temperature management (IVTM) system with neurolept-anesthesia (NLA; droperidol and fentanyl). Single-arm, prospective multicenter trial was carried out in the seven university and the three affiliated hospitals. In the 24 comatose PCAS patients, the target temperature (33.0°C) was rapidly induced and maintained for 24 hours using an IVTM system with NLA. The rewarming speed was 0.1°C/h until 36.5°C and was maintained for 24 hours. The primary end point was the ability to achieve ≤34.0°C for <3 hours after starting cooling, and the secondary end points were the cooling rate, deviation from the target temperature, and adverse events. Cerebral Performance Category (CPC) score at 14 days was also evaluated. Statistical analyses were performed by SPSS software, using the intention-to-treat data sets. The target temperature of ≤34.0°C was reached by 45 minutes (35-73 minutes) and was within 3 hours in all patients. The cooling rate from 36.4°C to 33.0°C was 2.7°C/h (2.4-3.6°C/h). The temperature of 33.1°C (33.1-33.1°C) and 36.7°C (36.6-36.9°C) for 24 hours each was held during the maintenance and the after rewarming phases, respectively. Temperature deviations >0.2°C from 33.0°C in the maintenance phase occurred once each in two patients. The favorable neurological outcomes (CPC1, 2) were relatively good (50%). Five patients experienced serious adverse events; none was device related. We rapidly achieved therapeutic hypothermia within a narrow temperature range without major complications using the IVTM system with NLA in PCAS patients.

Optimal Hemodynamic Parameter to Predict the Neurological Outcome in Out-of-Hospital Cardiac Arrest Survivors Treated with Target Temperature Management.

Current guidelines suggest the maintenance of systolic blood pressure (SBP) at >90 mmHg and mean arterial pressure (MAP) at >65 mmHg in postcardiac arrest patients. There remains a lack of clarity regarding optimal values and timing of blood pressure parameters associated with the improvement of neurologic outcome. We investigated the association of time-weighted average (TWA) blood pressure parameters with favorable neurological outcome (FO) in postcardiac arrest patients. This was a registry-based observational study with consecutive adult out-of-hospital cardiac arrest (OHCA) survivors who were treated using targeted temperature management (TTM). During 72 hours of TTM period, we abstracted hemodynamic parameters such as SBP, diastolic blood pressure, pulse rate (PR), and MAP. Shock index (SI; PR/SBP) and modified shock index (MSI; PR/MAP) were calculated from each measured hemodynamics. Logistic regression was performed to assess the associations between TWA blood pressure parameters and FO, defined as cerebral performance category 1 or 2 at hospital discharge. Among the 173 patients (median age: 58 years; 64% male), 51 (29.3%) had FO in this study. MAP, SI, and MSI at 6 hours after return of spontaneous circulation (ROSC) showed considerable differences in patients with FO (MAP: 89.1 ± 14.7 vs. 83.6 ± 15.8 mmHg, p = 0.033, SI: 0.7 ± 0.2 vs. 0.9 ± 0.9, p = 0.002, MSI: 1.0 ± 0.3 vs. 1.2 ± 0.3, p ≤ 0.001). Among them, MSI, especially at 6 hours, had the highest area under the curve for prediction of FO (0.685; 95% confidence interval: 0.597-0.772, p < 0.001). Also, MSI <1.0 had a sensitivity of 64.7%, a specificity of 64.2% to predict FO. In comatose survivors of OHCA with TTM, MSI at 6 hours after ROSC had the highest prognostic value for neurologic outcome among blood pressure parameters.

Independent Risk Factors for the Shivering Occurrence During Induction Period in Out-of-Hospital Cardiac Arrest Survivors Treated with Targeted Temperature Management.

The occurrence of shivering during the induction period of targeted temperature management (TTM) remains a therapeutic obstacle, which delays the achievement of target temperature. The aim of this study was to identify risk factors leading to shivering during the induction period. We analyzed a prospective cohort of adult out-of-hospital cardiac arrest (OHCA) survivors treated with TTM from January 2015 to June 2017. Patients who developed shivering during the induction period were compared to those who did not. Multivariable analysis was performed to determine risk factors of shivering. Among 80 patients treated with TTM, shivering occurred in 22 patients (27.5%). In the shivering group, the time to achieve target temperature was significantly delayed (245 minutes vs. 151 minutes, p = 0.005). Multivariable analysis showed that being underweight (OR, 18.40; 95% CI, 1.89-179.19) or overweight (OR, 8.65; 95% CI, 1.60-46.80), age <65 years (OR, 5.54; 95% CI, 1.25-16.12), and duration of cardiac arrest <20 minutes (OR, 4.50; 95% CI, 1.25-16.12) were predictors for the occurrence of shivering. OHCA patients with abnormal body weight, age <65 years, and duration of cardiac arrest <20 minutes should be monitored thoroughly for early recognition of shivering.

Prognostic Impact of Serum Albumin Concentration for Neurologically Favorable Outcome in Patients Treated with Targeted Temperature Management After Out-of-Hospital Cardiac Arrest: A Multicenter Prospective Study.

To assess whether serum albumin concentration measured upon hospital arrival was useful as an early prognostic biomarker for neurologically favorable outcome in out-of-hospital cardiac arrest (OHCA) patients treated with target temperature management (TTM). This prospective, multicenter observational study (The CRITICAL Study) carried out between July 1, 2012 and December 31, 2014 in Osaka Prefecture, Japan involving 13 critical care medical centers (CCMCs) and one non-CCMC with an emergency department. This study included patients ≥18 years of age who underwent an OHCA, for whom resuscitation was attempted by Emergency Medical Services personnel and were then transported to participating institutions, and who were then treated with TTM. Based on the serum albumin concentration upon hospital arrival, involved patients were divided into four quartiles (Q1-Q4) defined as Q1 (<3.0 g/dL), Q2 (≥3.0, <3.4 g/dL), Q3 (≥3.4, <3.8 g/dL), and Q4 (≥3.8 g/dL). The primary outcome of this study was 1-month survival with neurologically favorable outcome defined by cerebral performance category 1 or 2. During the study period, a total of 327 were eligible for our analysis. The overall proportion of neurologically favorable outcome was 33.0% (108/327). The Q4 group had the highest proportion of neurologically favorable outcome (52.5% [48/91]), followed by Q3 (34.5% [30/87]), Q2 (27.3% [21/77]), and Q1 (12.5% [9/72]). The multivariable logistic regression analysis demonstrated that the proportion of neurologically favorable outcome was significantly higher in the Q4 group than that in the Q1 group (adjusted odds ratio 10.39; 95% confidence interval 3.36-32.17). The adjusted proportion of neurologically favorable outcome increased in a stepwise fashion across increasing quartiles (p < 0.001). In this study, higher serum albumin concentration upon hospital arrival had a positive association with neurologically favorable outcome after OHCA in a dose-dependent manner.

Decreased a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 activity and neurologic outcome in patients with successful resuscitation of out-of-hospital cardiac arrest: A prospective observational study.

PURPOSE: The purpose of this study is to investigate the association between a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and neurologic outcome in patients with resuscitation of out-of-hospital cardiac arrest (R-OHCA). MATERIALS AND METHODS: A prospective observational study of adult patients with R-OHCA was conducted. Plasma activity of ADAMTS13 and inflammatory markers, an immunologic marker, and a marker of endothelial damage were measured on admission and day 2. Neurologic outcome was evaluated using the Cerebral Performance Categories on day 90. RESULTS: Plasma activity of ADAMTS13 on day 2 was lower in patients with poor neurologic outcome (n = 18) than that in those with good neurologic outcome (n = 16; P = .008). It was also lower in 28-day nonsurvivors (n = 12) than in survivors (n = 21; P = .019). Soluble thrombomodulin showed a strong correlation with ADAMTS13 (P = .021). Furthermore, ADAMTS13 activity was negatively correlated with the Sequential Organ Failure Assessment score (P < .001), levels of high-mobility group box 1 (P = .028), and levels of interleukin 6 (P = .047) but positively correlated with the monocyte expression of human leukocyte antigen DR (P = .023). CONCLUSION: Decreased ADAMTS13 activity was associated with poor neurologic outcome, high mortality, and worsened immune-inflammatory status in patients with R-OHCA. These results suggest that ADAMTS13 may have pathophysiologic relevance in postcardiac arrest syndrome.

The association between hemoglobin concentration and neurologic outcome after cardiac arrest.

PURPOSE: The purpose of the study is to determine the association between hemoglobin concentration (Hgb) and neurologic outcome in postarrest patients. METHODS: We conducted a retrospective cohort study using the Penn Alliance for Therapeutic Hypothermia (PATH) cardiac arrest registry. Inclusion criteria were resuscitated cardiac arrest (inhospital or out of hospital) and an Hgb value recorded within 24 hours of return of spontaneous circulation. The primary outcome was favorable neurologic status at hospital discharge. Survival to hospital discharge was a secondary outcome. RESULTS: There were 598 eligible patients from 21 hospitals. Patients with favorable neurologic outcome had significantly higher median Hgb in the first 2 hours (12.7 vs 10.5 g/dL; P<.001) and 6 hours (12.6 vs 10.6 g/dL; P<.001) postarrest. Controlling for age, pulseless rhythm, etiology, location of arrest, receipt of targeted temperature management, hematologic or metastatic malignancy, or preexisting renal insufficiency, there was a significant relationship between Hgb and neurologic outcome within the first 6 hours after arrest (odds ratio, 1.23; 95% confidence interval, 1.09-1.38) and survival to hospital discharge (odds ratio, 1.20; 95% confidence interval, 1.08-1.34). CONCLUSION: Higher Hgb after cardiac arrest is associated with favorable neurologic outcome, particularly within the first 6 hours. It is unclear if this effect is due to impaired oxygen delivery or if Hgb is a marker for more severe illness.