Targeted Temperature Management Group Research Articles

Impact of immediate postrecanalization cooling on outcome in acute ischemic stroke patients with a large ischemic core: prospective cohort study.

Patients with large acute ischemic strokes (AIS) often have a poor prognosis despite successful recanalization due to multiple factors including reperfusion injury. The authors aim to describe our preliminary experience of endovascular cooling in patients with a large AIS after recanalization. From January 2021 to July 2022, AIS patients presenting with large infarcts (defined as ASPECTS ≤5 on noncontrast CT or ischemic core ≥50ml on CT perfusion) who achieved successful recanalization after endovascular treatment were analyzed in a prospective registry. Patients were divided into targeted temperature management (TTM) and non-TTM group. Patients in the TTM group received systemic cooling with a targeted core temperature of 33° for at least 48h. The primary outcome is 90-day favorable outcome [modified Rankin Scale (mRS) 0-2]. The secondary outcomes are 90-day good outcome (mRS 0-3), mortality, intracranial hemorrhage and malignant cerebral edema within 7 days or at discharge. Forty-four AIS patients were recruited (15 cases in the TTM group and 29 cases in the non-TTM group). The median Alberta Stroke Program Early CT Score (ASPECTS) was 3 (2-5). The median time for hypothermia duration was 84 (71.5-147.6) h. The TTM group had a numerically higher proportion of 90-day favorable outcomes than the non-TTM group (46.7 vs. 27.6%, P=0.210), and no significant difference were found regarding secondary outcomes (all P>0.05). The TTM group had a numerically higher rates of pneumonia (66.7 vs. 58.6%, P=0.604) and deep vein thrombosis (33.3 vs. 13.8%, P=0.138). Shivering occurred in 4/15 (26.7%) of the TTM patients and in none of the non-TTM patients (P=0.009). Postrecanalization cooling is feasible in patients with a large ischemic core. Future randomized clinical trials are warranted to validate its efficacy.

Decreased human leukocyte antigen-D–related expression on CD14+ monocytes in patients with out-of-hospital cardiac arrest provided target temperature management therapy: a prospective observational study

Decreased human leukocyte antigen-D–related expression on CD14+ monocytes in patients with out-of-hospital cardiac arrest provided target temperature management therapy: a prospective observational study

Comparative before-after study of fever prevention versus targeted temperature management following out-of-hospital cardiac arrest

BackgroundInternational guidelines for neuroprotection following out-of-hospital cardiac arrest (OHCA) recommend fever prevention ahead of routine temperature management. This study aimed to identify any effect of changing from targeted temperature management to fever prevention on neurological outcome following OHCA. MethodsA retrospective observational cohort study was conducted of consecutive admissions to an ICU at a tertiary OHCA centre. Comparison was made between a period of protocolised targeted temperature management (TTM) to 36 °C and a period of fever prevention. ResultsData were available for 183 patients. Active temperature management was administered in 86/118 (72%) of the TTM cohort and 20/65 (31%) of the fever prevention group. The median highest temperature prior to the start of temperature management was significantly lower in the TTM group at 35.6 (IQR 34.9–36.2) compared to 37.9 °C (IQR 37.7–38.2) in the fever prevention group (adjusted p < 0.001).There was no difference in the proportion of patients discharged with Cerebral Performance Category 1 or 2 between the groups (42% vs. 40%, p = 0.88). Patients in the fever prevention group required a reduced duration of noradrenaline (36 vs. 46 h, p = 0.03) and a trend towards a reduced duration of propofol (37 vs. 56 h, p = 0.06).In unadjusted analysis, use of active temperature management (irrespective of group) appeared to be associated with decreased risk of poor outcome (OR = 0.43, 95% CI 0.23–0.78) but after adjustment for patient age, presenting rhythm, witnessed arrest and duration of CPR, this was no longer significant (OR = 0.93, 95% CI 0.37–2.31, p = 0.88). ConclusionSwitching from TTM to fever prevention following OHCA was associated with similar rates of neurological outcomes, with a possible decrease in sedation and vasopressor requirements.

Abstract 148: Differential Neuroprotective Effects of Targeted Temperature Management in Adult and Aged Rats Post-Cardiac Arrest

Background: Targeted temperature management (TTM) has been recognized as a crucial brain protective method post-cardiac arrest (CA). However, its efficacy has recently been questioned due to several clinical trials. Hypothesis: TTM may not offer significant neuroprotective benefits in older individuals post-CA. Aims: This study aims to evaluate the therapeutic efficacy of TTM on neurological dysfunction in aged rats post-CA. Methods: Fifty-six male Sprague-Dawley (SD) rats were divided into two age groups: adult group (3-4 months, n=28) and aged group (19-22 months, n=28). Each group was then randomized into four subgroups: 1) sham, 2) sham + TTM, 3) control, 4) control + TTM. Control and control + TTM groups underwent 6 minutes of asphyxiation followed by cardiopulmonary resuscitation. TTM was applied at 32-34°C for 2 hour post-return of spontaneous circulation (ROSC). Neurological outcomes were assessed five days post-CA using the Y-maze and the Open field test. Serum IL-17 and IL-6 levels were measured four hours post-CA. Results: TTM significantly enhanced the spontaneous alternation in the Y-maze (p &lt;0.05), increased moter active in Open field test (p&lt;0.05), and reduced serum IL-17 and IL-6 levels in the adult group (p &lt;0.05). Conversely, in the aged group, TTM did not exhibit any significant benefits in Y maze performance, Open field test, IL-17 or IL-6 serum levels reduction (p &gt;0.05). Conclusion(s): TTM demonstrated improvement in post-CA neurological deficits in adult rats, yet it failed to deliver similar benefits in aged rats. IL-6 and IL-17 might play a role in the differential neuroprotective effects of TTM.

Abstract 212: The Effect Of 33 °C Vs. 36 °C Targeted Temperature Management To The Metabolism Following Out-of-hospital Cardiac Arrest.

Targeted Temperature Management (TTM) following shockable out-of-hospital cardiac arrest (OHCA) has been recommended. The effect of different targeted temperatures on the human metabolome has not been compared. Elevated levels of metabolites from the Krebs cycle have recently been associated with a poor outcome in OHCA patients. Similarly, decreased levels of the amino acids valine and leucine have been linked with a poor outcome in septic shock patients. Method: From a single center in the randomized clinical TTM trial, we analyzed blood samples from resuscitated unconscious OHCA patients at two timepoints (hospital arrival and 48 hours later) using ultra-performance liquid mass-spectrometry. Patients were randomized to either 33°C or 36°C hypothermia for the first 28 hours. Sixty-one metabolites of the ~3000 compounds detected were prespecified for quantification and analyzed in the current study. Differences (95% CI) in metabolite concentrations from a constrained linear mixed model are reported, and p-values from the interaction term timepoint x TTM arm. Results: Of the 146 patients, 70 (48 %) were randomized to TTM 33°C. The baseline characteristics (age, gender, shockable rhythm, time to return of spontaneous circulation) and outcome (180 days mortality) were similar in the TTM groups. After 48 hours, approx. 24 hours from the cessation of TTM, fourteen metabolites differed significantly between the two groups. Among these, lactate acid (190 μM (74-305 μM), p&lt;0.001 ), pyruvic acid (26 μM (8-44 μM), p&lt;0. 0 1 ), 2-oxoglutaric acid (2.7 μM (1.0-4.4 μM), p&lt;0.01 ) and prostaglandin E2 (0.60 nM (0.24-1.0 nM), p&lt;0.01 ) were increased in the TTM 33 °C arm whereas valine (25 μM (15-35 μM), p&lt;0.001 ) and leucine (14 μM (8.3 - 20 μM), p&lt;0.001 ) were decreased. Conclusion: TTM at 33°C for 24 hours after OHCA results in a prognostically poorer metabolome even 24 hours later compared with TTM at 36°C.

Comparison Between Complications of Pentothal Coma Therapy and Targeted Temperature Management in Traumatic Brain Injury Patients

BackgroundPentothal coma therapy (PCT) and targeted temperature management (TTM) are considered the most aggressive medical care for patients with severe traumatic brain injury (TBI). However, there is very little comparison between these two options. We compared the survival rates and complications between the two treatments.MethodsNineteen patients who received treatment for PCT or TTM after severe TBI between March 2018 and April 2022 were retrospectively enrolled. Medical records were reviewed, including general information, neurologic status, treatment courses, survival rate, and complications. Patients were divided into two groups according to the treatment modalities (PCT vs. TTM), and comparison analyses were conducted.ResultsThe survival rate in the TTM group was 33.3% (3/9), which was higher than that in the PCT group (1/10, 10%). However, this difference was not significant (p = 0.213). In terms of complications, there were no statistically significant differences in hemodynamic instability, cardiovascular disability, hepatic dysfunction, renal dysfunction, pneumonia, urinary tract infection, hyperkalemia, hypokalemia, coagulopathy, or hyperglycemia. Commonly observed complications included hypokalemia in the TTM group (100% in the TTM group vs 70% in the PCT group; p = 0.073) and hyperkalemia in the PCT group (50% in the PCT group vs 11.1% in the TTM group; p = 0.069).ConclusionSevere TBI patients treated with TTM has non-significantly lower mortality than them with PCT (66.7% vs. 90%); however, complications of hypokalemia can be frequently observed (100%). Further study was necessary to evaluate the efficacy and safety of TTM.

Should targeted temperature management be used in cardiogenic shock patients? Systematic review and meta-analysis.

Therapeutic hypothermia, or targeted temperature management (TTM), is a strategy of reducing the core body temperature of survivors of sudden cardiac arrest, cardiogenic shock (CS) or stroke. Therefore, a systematic literature review and meta-analysis were performed to tackle the question about whether the implementation of TTM is actually beneficial for patients with CS. Study was designed as a systematic review and meta-analysis. PubMed, Cochrane Library, Web of Science and Scopus were searched from these databases inception to July 17, 2022. Eligible studies were those comparing TTM and non-TTM treatment in CS patients. Data were pooled with the Mantel-Haenszel method. Thirty-day mortality was reported in 3 studies. Polled analysis of 30-day mortality was 44.2% for TTM group and 48.9% for non-TTM group (risk ratio: 0.90; 95% confidence interval: 0.75 to 1.08; p = 0.27). Other mortality follow-up periods showed also no statistically significant differences (p > 0.05). The occurrence of adverse events in the studied groups also did not show statistically significant differences between TTM and non-TTM groups (p > 0.05 for myocardial infarction, stent thrombosis, sepsis, pneumonia, stroke or bleeding events). The present analysis shows no significant benefit of TTM in patients with CS. Moreover, no statistically significant increase of the incidence of adverse effects was found. However, further randomized studies with higher sample size and greater validity are needed to determine if TTM is worth implementing in CS patients.

Kinetics of 2 different high-sensitive troponins during targeted temperature management in out-of-hospital cardiac arrest patients with acute myocardial infarction: a post hoc sub-study of a randomised clinical trial

IntroductionShort term hypothermia has been suggested to have cardio protective properties in acute myocardial infarction (AMI) by reducing infarct size as assessed by troponins. There are limited data on the kinetics of these biomarkers in comatose out-of-hospital cardiac arrest (OHCA) patients, with and without AMI, undergoing targeted temperature management (TTM) in the ICU.PurposeThe aim of this post hoc analyses was to evaluate and compare the kinetics of two high-sensitivity cardiac troponins in OHCA survivors, with and without acute myocardial infarction (AMI), during TTM of different durations [24 h (standard) vs. 48 h (prolonged)].MethodsIn a sub-cohort (n = 114) of the international, multicentre, randomized controlled study “TTH48” we measured high-sensitive troponin T (hs-cTnT), high-sensitive troponin I (hs-cTnI) and CK-MB at the following time points: Arrival, 24 h, 48 h and 72 h from reaching the target temperature range of 33 ± 1 °C. All patients diagnosed with an AMI at the immediate coronary angiogram (CAG)—18 in the 24-h group and 25 in the 48-h group—underwent PCI with stent implantation. There were no stent thromboses.ResultsBoth the hs-cTnT and hs-cTnI changes over time were highly influenced by the cause of OHCA (AMI vs. non-AMI). In contrast to non-AMI patients, both troponins remained elevated at 72 h in AMI patients. There was no difference between the two time-differentiated TTM groups in the kinetics for the two troponins.ConclusionIn comatose OHCA survivors with an aetiology of AMI levels of both hs-cTnI and hs-cTnT remained elevated for 72 h, which is in contrast to the well-described kinetic profile of troponins in normotherm AMI patients. There was no difference in kinetic profile between the two high sensitive assays. Different duration of TTM did not influence the kinetics of the troponins.Trial registration: Clinicaltrials.gov Identifier: NCT01689077, 20/09/2012.

Quantitative pupillometry in comatose out-of-hospital cardiac arrest patients: A post-hoc analysis of the TTH48 trial.

BackgroundQuantitative pupillometry is an objective method to examine pupil reaction and subsequently grade the response on a neurological pupil index (NPi) scale from 0 to 5. The aim of the present sub‐study was to explore the long‐term prognostic value of NPi in comatose out‐of‐hospital cardiac arrest patients undergoing targeted temperature management (TTM).MethodsThis planned sub‐study of the “Targeted temperature management for 48 versus 24 h and neurological outcome after out‐of‐hospital cardiac arrest: A randomized clinical trial.” NPi was assessed from admission and throughout day 3 and linked to the Cerebral Performance Categories score at 6 months. We compared the prognostic performance of NPi in 65 patients randomized to a target temperature of 33 ± 1°C for 24 or 48 h.ResultsThe NPi values were not different between TTM groups (p > .05). When data were pooled, NPi was strongly associated with neurological outcome at day 1 with a mean NPi of 3.6 (95% CI 3.4–3.8) versus NPi 3.9 (3.6–4.1) in the poor versus good outcome group, respectively (p < .01). At day 2, NPi values were 3.6 (3.1–4.0) and 4.1 (3.9–4.2) (p = .01) and at day 3, the values were 3.3 (2.6–4.0) and 4.3 (4.1–4.6), respectively (p < .01). The prognostic ability of NPi, defined by area under the receiver operating characteristic curve was best at day three.ConclusionQuantitative pupillometry measured by NPi was not different in the two TTM groups, but overall, significantly associated with good and poor neurological outcomes at 6 months. NPI has a promising diagnostic accuracy, but larger studies are warranted.

Prognostic value of targeted temperature management on outcomes of hanging-induced out-of-hospital cardiac arrest: A nationwide observational study.

This study aimed to evaluate the prognostic significance of targeted temperature management (TTM) on hanging-induced out-of-hospital cardiac arrest (OHCA) patients using nationwide data of South Korea.Adult hanging-induced OHCA patients from 2008 to 2018 were included in this nationwide observational study. Patients who assigned into 2 groups based on whether they did (TTM group) or did not (non-TTM group) receive TTM. Outcome measures included survival to hospital discharge and a good neurological outcome at hospital discharge.Among the 293,852 OHCA patients, 3545 patients (non-TTM, n = 2762; TTM, n = 783) were investigated. After propensity score matching for all patients, 783 matched pairs were available for analysis. We observed no significant inter-group differences in the survival to hospital discharge (non-TTM, n = 27 [3.4%] vs TTM, n = 23 [2.9%], P = .666) or good neurological outcomes (non-TTM, n = 23 [2.9%] vs TTM, n = 14 [1.8%], P = .183). In the multivariate analysis, prehospital return of spontaneous circulation (odds ratio [OR], 22.849; 95% confidence interval [CI], 11.479–45.481, P < .001) was associated with an increase in survival to hospital discharge, and age (OR, 0.971; 95% CI, 0.944–0.998, P = .035), heart disease (OR, 16.875; 95% CI, 3.028–94.036, P = .001), and prehospital return of spontaneous circulation (OR, 133.251; 95% CI, 30.512–581.930, P < .001) were significant prognostic factors of good neurological outcome. However, TTM showed no significant association with either outcome.There were no significant differences in the survival to hospital discharge and good neurological outcomes between non-TTM and TTM groups of hanging-induced OHCA patients.

Survival to hospital discharge and neurological outcomes with targeted temperature management after in-hospital cardiac arrest: a systematic review and meta-analysis.

Multiple randomized controlled trials have shown that targeted temperature management (TTM) has favorable effects in out-of-hospital cardiac arrest. However, the benefit of TTM in patients with in-hospital cardiac arrest (IHCA) remains to be verified. The PubMed, Cochrane Library, and EMBASE databases were searched for clinical studies with the primary outcomes of survival to hospital discharge and neurological outcomes. Neurological outcomes were evaluated by the categorical scale of cerebral function (CPC); a score of 1-2 points was considered neurologically good, and a score of 3-5 points was considered a poor outcome. Revman 5.3 and Stata 14 software with the random effects model were used for analysis. P<0.05 was considered statistically significant. Six retrospective controlled studies with a total of 14,607 patients (TTM group: 1,845, control group: 12,762) were included and analyzed. There were no statistically significant differences between the two groups in survival to hospital discharge [odds ratio (OR) =1.02, 95% CI: 0.77-1.35, P=0.89, I2=47%] or favorable neurological outcomes (OR =1.06, 95% CI: 0.56-2.02, P=0.85, I2=79%). After excluding patients with non-shockable initial rhythms, TTM did not show any significant improvement in survival to hospital discharge. Subgroup analysis was performed according to the sample size. No significant improvement was observed between the two groups in terms of survival to hospital discharge or neurological outcome. In this meta-analysis, the effects of TTM on discharge survival and neurological prognosis were evaluated by studying the results of IHCA in 14,607 patients. We found that the TTM did not improve survival and neurological function in discharged patients. Our results showed that the sample size discrepancy had a large effect on the heterogeneity; to address this, subgroup analyses were performed according to the different sample sizes. However, TTM treatment in different sample size subgroups showed no significant effect on survival to hospital discharge. Moreover, in the large sample size subgroup, therapeutic hypothermia was associated with increased unfavorable neurological outcome compared with no hypothermia.

Interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest

PurposePrevious clinical studies have suggested an effect of gender on outcome after out-of-hospital cardiac arrest, but the results are conflicting and there is no uniform agreement regarding gender differences in survival and prognosis. The present study was aimed to investigate the interaction between gender and post resuscitation interventions on neurological outcome in an asphyxial rat model of cardiac arrest.MethodsAsphyxia was induced by blocking the endotracheal tube in 120 adult Sprague–Dawley rats (60 males and 60 females) at the same age. Cardiopulmonary resuscitation (CPR) was started after 5 min of untreated cardiac arrest. Animals were randomized into one of the three post resuscitation care intervention groups (n = 40, 20 males) immediately after resuscitation: (1) normothermic control (NC): ventilated with 2% N2/98% O2 for 1 h under normothermia; (2) targeted temperature management (TTM): ventilated with 2% N2/98% O2 for 1 h under hypothermia; (3) hydrogen inhalation (HI): ventilated with 2% H2/98% O2 for 1 h under normothermia. Physiological variables were recorded during the 5 h post resuscitation monitoring period. Neurological deficit score (NDS) and accumulative survival were used to assess 96 h outcomes. Mutual independence analysis and Mantel–Haenszel stratified analysis were used to explore the associations among gender, intervention and survival.ResultsThe body weights of female rats were significantly lighter than males, but CPR characteristics did not differ between genders. Compared with male rats, females had significantly lower mean arterial pressure, longer onset time of the electroencephalogram (EEG) burst and time to normal EEG trace (TTNT) in the NC group; relatively longer TTNT in the TTM group; and substantially longer TTNT, lower NDSs, and higher survival in the HI group. Mutual independence analysis revealed that both gender and intervention were associated with neurological outcome. Mantel–Haenszel stratified analysis demonstrated that female rats had significantly higher survival rate than males when adjusted for the confounder intervention.ConclusionIn this rat model cardiac arrest and CPR, gender did not affect resuscitation but associated with neurological outcome. The superiority of female rats in neurological recovery was affected by post resuscitation interventions and female rats were more likely to benefit from hydrogen therapy.

Quality of targeted temperature management and outcome of out-of-hospital cardiac arrest patients: A post hoc analysis of the TTH48 study

BackgroundNo data are available on the quality of targeted temperature management (TTM) provided to out-of-hospital cardiac arrest (OHCA) patients and its association with outcome. MethodsPost hoc analysis of the TTH48 study (NCT01689077), which compared the effects of prolonged TTM at 33 °C for 48 h to standard 24-h TTM on neurologic outcome. Admission temperature, speed of cooling, rewarming rates, precision (i.e. temperature variability), overcooling and overshooting as post-cooling fever (i.e. >38.0 °C) were collected. A specific score, ranging from 1 to 9, was computed to define the “quality of TTM”. ResultsOn a total of 352 patients, most had a moderate quality of TTM (n = 217; 62% — score 4–6), while 80 (23%) patients had a low quality of TTM (score 1–3) and only 52 (16%) a high quality of TTM (score 7–9). The proportion of patients with unfavorable neurological outcome (UO; Cerebral Performance Category of 3–5 at 6 months) was similar between the different quality of TTM groups (p = 0.90). Although a shorter time from arrest to target temperature and a lower proportion of time outside the target ranges in the TTM 48-h than in the TTM 24-h group, quality of TTM was similar between groups. Also, the proportion of patients with UO was similar between the different quality of TTM groups when TTM 48-h and TTM 24-h were compared. ConclusionsIn this study, high quality of TTM was provided to a small proportion of patients. However, quality of TTM was not associated with patients’ outcome.

Neurological Outcomes of Normothermia versus Targeted Temperature Management in Post-cardiac Arrest Syndrome.

To determine the neurological outcome of targeted temperature management (TTM)for patients scoring lower than 8 on the Glasgow coma scale (GCS) upon return of spontaneous circulation (ROSC) after cardiac arrest. Retrospective cohort study. Department of Anaesthesiology and Reanimation, Sakarya University Education And Research Hospital, Sakarya, Turkey from January 2018 to October 2019. Data of patients hospitalised in the AnaesthesiaIntensive Care unit for cardiac arrest receiving TTM and standard supportive therapy were analysed. Neurological outcome was evaluated with cerebral performance category (CPC) scores. Hospital stay and 30-day mortality was also noted. Data from 58 patients were analysed; 31 had received standard supportive therapy (non-TTM group) and 27 were treated with TTM (TTM group). There was no significant difference in hospital stay and patients' 30-day mortality between the two groups. The number of patients in the TTM group with CPC scores of 1 and 2, rated as a good neurological result, was significantly higher (n=11,40.7%) than in the non-TTM group (n=2, 6.5%;p=0.002). The number of patients with CPC scores of 3 and 4, rated as having a neurological disability,was higher in the non-TTM group (n = 9, 29%) than in the TTM group (n=1, 3.7%). Neurological results were better in the TTM group of patients with ROSC. However, there was no significant difference in mortality between the TTMand non-TTM groups. Key Words:Targeted temperature management, Cardiac arrest, Neurological outcome, Cerebral performance category.

Efficacy of Targeted Temperature Management after Pediatric Cardiac Arrest: A Meta-Analysis of 2002 Patients.

Cardiac arrest (CA) is associated with high mortality and poor life quality. Targeted temperature management (TTM) or therapeutic hypothermia is a therapy increasing the survival of adult patients after CA. The study aim was to assess the feasibility of therapeutic hypothermia after pediatric CA. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the use of TTM after pediatric CA. The primary outcome was survival to hospital discharge or 30-day survival. Secondary outcomes included a one-year survival rate, survival with a Vineland adaptive behavior scale (VABS-II) score ≥ 70, and occurrence of adverse events. Ten articles (n = 2002 patients) were included, comparing TTM patients (n = 638) with controls (n = 1364). In a fixed-effects meta-analysis, survival to hospital discharge in the TTM group was 49.7%, which was higher than in the non-TTM group (43.5%; odds ratio, OR = 1.22; 95% confidence interval, CI: 1.00, 1.50; p = 0.06). There were no differences in the one-year survival rate or the occurrence of adverse events between the TTM and non-TTM groups. Altogether, the use of TTM was associated with a higher survival to hospital discharge; however, it did not significantly increase the annual survival. Additional high-quality prospective studies are necessary to confer additional TTM benefits.

Repetitive anodal transcranial direct current stimulation improves neurological recovery by preserving the neuroplasticity in an asphyxial rat model of cardiac arrest

BackgroundNon-shockable rhythms present an increasing proportion of out-of-hospital cardiac arrest (CA) patients, but are associated with poor prognosis and received limited therapeutic effect of targeted temperature management (TTM). Previous study showed repetitive anodal transcranial direct current stimulation (tDCS) improved neurological outcomes in animals with ventricular fibrillation. Here, we examine the effectiveness of tDCS on neurological recovery and the potential mechanisms in a rat model of asphyxial CA. MethodCardiopulmonary resuscitation was initiated after 5 min of untreated asphyxial CA. Animals were randomized to three experimental groups immediately after successful resuscitation (n = 12/group, 6 males): no-treatment control (NTC) group, TTM group, and tDCS group. Post resuscitation hemodynamics, quantitative electroencephalogram (EEG), neurological deficit score, and 96-h survival were evaluated. Brain tissues of additional animals undergoing same experimental procedure was harvested for enzyme-linked immunoassay-based quantification assays of neuroplasticity-related biomarkers and compared with the sham-operated rats (n = 6/group). ResultsWe observed that after resuscitation tDCS-treated animals exhibited significantly higher mean arterial pressure and left ventricular ejection fraction than NTC group and showed greatly improved EEG characteristics including weighted-permutation entropy and gamma band power, and neurologic deficit scores and 96-h survival rates compared to NTC and TTM groups. Furthermore, neuroplastic biomarkers including microtubule-associated protein 2, growth-associated protein 43, postsynaptic density protein 95 and synaptophysin, were significantly higher in tDCS group when compared with NTC and TTM groups. ConclusionIn this rat model of asphyxial CA, repetitive anodal tDCS commenced after resuscitation improved neurological recovery, and it may exert a neuroprotective effect by preserving the neuroplasticity.

Targeted temperature management at 33°C or 36℃ induces equivalent myocardial protection by inhibiting HMGB1 release in myocardial ischemia/reperfusion injury.

Acute myocardial infarction (AMI) is lethal and causes myocardial necrosis via time-dependent ischemia due to prolonged occlusion of the infarct-related artery. No effective therapy or potential therapeutic targets can prevent myocardial ischemia/reperfusion (I/R) injury. Targeted temperature management (TTM) may reduce peri-infarct regions by inhibiting the extracellular release of high mobility group box-1 (HMGB1) as a primary mediator of the innate immune response. We used a rat left anterior descending (LAD) coronary artery ligation model to determine if TTM at 33°C and 36°C had similar myocardial protective effects. Rats were divided into sham, LAD I/R+37°C normothermia, LAD I/R+33°C TTM, and LAD I/R+36°C TTM groups (n = 5 per group). To verify the cardioprotective effect of TTM by specifically inhibiting HMGB1, rats were assigned to sham, LAD I/R, and LAD I/R after pre-treatment with glycyrrhizin (known as a pharmacological inhibitor of HMGB1) groups (n = 5 per group). Different target temperatures of 33°C and 36°C caused equivalent reductions in infarct volume after myocardial I/R, inhibited the extracellular release of HMGB1 from infarct tissue, and suppressed the expression of inflammatory cytokines from peri-infarct regions. TTM at 33°C and 36°C significantly attenuated the elevation of cardiac troponin, a sensitive and specific marker of heart muscle damage, after injury. Similarly, glycyrrhizin alleviated myocardial damage by suppressing the extracellular release of HMGB1. TTM at 33°C and 36°C had equivalent myocardial protective effects by similar inhibiting HMGB1 release against myocardial I/R injury. This is the first study to suggest that a target core temperature of 36°C is applicable for cardioprotection.

Abstract 347: The Effect of Targeted Temperature Management at 34 °C and 36 °C on Day-30 Neurological Outcomes in Out-of-hospital Cardiac Arrest Patients

Introduction: Targeted temperature management (TTM) has established evidence for improving neurological outcomes in cardiac arrest patients who sustained coma after return of spontaneous circulation (ROSC). The target temperature has been recommended to be between 32 and 36 °C. However optimal temperature remains unestablished. This study aimed to assess the relationship between target temperature and neurological outcome by using the Japanese nationwide registry. Methods: This retrospective observational cohort study was based on the Japanese association for acute medicine - out-of-hospital cardiac arrest (JAAM-OHCA) registry during 2014 to 2017. Our study included all initial rhythms and any cause of OHCA patients and excluded age &lt; 18 and Glasgow Coma Scale score &gt; 8. The primary outcome was 30 day favorable neurological outcome, defined as cerebral performance category (CPC) scale 1 and 2. First, to clarify the efficacy of TTM, the neurological outcome was compared whether patients received TTM or not. Next, to evaluate the relationship between neurological outcome and target temperature on TTM, the neurological outcome was compared hypothermia (34 °C) group with normothermia (36 °C) group . Single and multivariable logistic regression analysis was performed. Results: The study included 9930 patients. Of these, 1184 (11.9%) patients received TTM. Favorable neurological outcome was more present in TTM group than in no TTM group (39.7% vs. 4.3%, odds ratio [OR] 14.6, 95% confidence interval [CI] 12.5-17.1, p&lt;0.001). Multivariable analysis showed TTM was associated with favorable neurological outcome (OR 1.6, 95%CI 1.1-2.3, p&lt;0.001). Of TTM group, 801 (68.5%) patients received hypothermia management and 242 (20.7%) patients received normothermia management. Favorable neurological outcome was more present in the hypothermia group than in the normothermia group (42.6% vs. 34.3%, OR 1.42, 95% CI 1.1-1.9, p=0.022). However, the neurological outcome did not differ between these two groups (OR 0.84, 95%CI 0.46-1.5, p&lt;0.57). Conclusions: TTM was significantly associated with favorable neurological outcome. However, neurological outcome was not associated with target temperature on TTM.

Abstract 346: Targeted Temperature Management is Associated with Improved Neurological Outcomes in Witnessed Out-of-hospital Cardiac Arrest Patients Who Achieve Early Return of Spontaneous Circulation

Background: Previous randomized controlled trials demonstrated the efficacy of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA) patients with both shockable and non-shockable rhythm. Real-world evidence for TTM using large OHCA database are scarce, and no study has investigated the relationship between TTM and time-to-return of spontaneous circulation (ROSC). Methods: The Japanese Association for Acute Medicine - out-of-hospital cardiac arrest (JAAM-OHCA) Registry is a multicenter, prospective, observational registry including 34,754 OHCA patients between 2014 and 2017. Patients with witnessed non-traumatic OHCA who had been resuscitated and were in a coma were included. Eligible patients were divided into two groups according to the use of TTM. The primary outcome was defined as a Cerebral Performance Categories (CPC) Scale 1-2 at 30 days after OHCA. The propensity score matching analysis was used. The cubic spline analysis of the odds ratio of CPC 1-2 for TTM use by time-to-ROSC was performed. Results: Out of 34,754 patients with OHCA, 5,261 patients were included. The mean age was 70.3 years, and 3,417 (65.0%) were male. CPC 1-2 was more frequently observed in the TTM group in propensity score matching analysis (15.1% vs. 8.5%; odds ratio 1.92; 95% confidence interval 1.04-3.53; P=0.037). The cubic spline analysis showed that TTM was associated with CPC 1-2 in witnessed OHCA patients, which did not reach statistical significance in patients with time-to-ROSC longer than 50 min. Conclusions: TTM was associated with better neurological outcomes in witnessed OHCA patients, especially when patients were resuscitated within 50 min after collapse.

The Clinical Usefulness of Targeted Temperature Management in Acute Ischemic Stroke with Malignant Trait After Endovascular Thrombectomy.

Targeted temperature management (TTM) may be more beneficial after endovascular treatment (EVT) in patients with a large ischemic core. Therefore, we assessed the usefulness of TTM for such patients from a multicenter endovascular registry. Anterior circulation stroke patients who underwent endovascular recanalization were included; acute ischemic stroke with malignant traits was designated as (1) baseline Alberta Stroke Program Early CT Score (ASPECTS) below 6 and (2) diffusion-weighted imaging (DWI) lesion volume measurement (> 82ml) or National Institutes of Health Stroke Scale score > 20 and item Ia > 0. TTM (34.5°C) was maintained for at least 48h. We evaluated baseline demographics, risk factors, EVT parameters, and clinical outcomes between the TTM and non-TTM groups. Among the 548 patients, the TTM group (n = 91) significantly had a lower baseline ASPECTS (p < 0.001) and a higher DWI volume (p < 0.001) than the non-TTM group (n = 457). TTM group had a lower prevalence of favorable outcome (0-2 of modified Rankin Scale at 3months; p = 0.008) than the non-TTM group. In a subgroup analysis of malignant trait patients (n = 80), TTM patients (n = 28) had more favorable outcome (32.1% vs. 7.7% p = 0.009) and less hemorrhagic transformation (none vs. any hemorrhage, p = 0.007) than non-TTM patients (n = 52). After adjusting for potential outcome predictors, TTM (odds ratio [OR] 4.63; confidence interval [CI] 1.20-17.89; p = 0.026) and hypertension (OR 0.18; CI 0.04-0.74; p = 0.018) were found to be independent determinants. Our data suggest that TTM attenuates impending hemorrhagic transformation and leads to favorable clinical outcomes in EVT patients with malignant trait.