Mild Therapeutic Hypothermia Group Research Articles

Circulating Galectin-3 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Sub-Study of the SHOCK-COOL Trial.

Background: Galectin-3 (Gal-3) is considered a potential cardiovascular inflammatory marker that may provide additional risk stratification for patients with acute heart failure. It is unknown whether mild therapeutic hypothermia (MTH) impacts Gal-3 levels. Therefore, this biomarker study aimed to investigate the effect of MTH on Gal-3. Methods: In the randomized SHOCK-COOL trial, 40 patients with cardiogenic shock (CS) complicating acute myocardial infraction (AMI) were randomly assigned to the MTH (33 °C) or control group in a 1:1 ratio. Blood samples were collected on the day of admission/day 1, day 2, and day 3. Gal-3 level kinetics throughout these time points were compared between the MTH and control groups. Additionally, potential correlations between Gal-3 and clinical patient characteristics were assessed. Multiple imputations were performed to account for missing data. Results: In the control group, Gal-3 levels were significantly lower on day 3 than on day 1 (day 1 vs. day 3: 3.84 [IQR 2.04−13.3] vs. 1.79 [IQR 1.23−3.50] ng/mL; p = 0.049). Gal-3 levels were not significantly different on any day between the MTH and control groups (p for interaction = 0.242). Spearman’s rank correlation test showed no significant correlation between Gal-3 levels and sex, age, smoking, body mass index (BMI), and levels of creatine kinase-MB, creatine kinase, C-reactive protein, creatinine, and white blood cell counts (all p > 0.05). Patients with lower Gal-3 levels on the first day after admission demonstrated a higher risk of all-cause mortality at 30 days (hazard ratio, 2.67; 95% CI, 1.11−6.42; p = 0.029). In addition, Gal-3 levels on day 1 had a good predictive value for 30-day all-cause mortality with an area under the receiver operating characteristic curve of 0.696 (95% CI: 0.513−0.879), with an optimal cut-off point of less than 3651 pg/mL. Conclusions: MTH has no effect on Gal-3 levels in patients with CS complicating AMI compared to the control group. In addition, Gal-3 is a relatively stable biomarker, independent of age, sex, and BMI, and Gal-3 levels at admission might predict the risk of 30-day all-cause mortality.

Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL Trial

Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating AMI were enrolled and assigned to MTH (33 °C) for 24 h or normothermia at a 1:1 ratio. Blood samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3. Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed. Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results: There were differences in MCP-1 levels over time between patients in MTH and normothermia groups (P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group (day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL; p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range, 87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming. Trial registration: NCT01890317.

The impact of mild therapeutic hypothermia on platelet reactivity in comatose survivors of cardiac arrest with acute myocardial infarction treated with ticagrelor.

The aim of the study was to assess the antiplatelet effect of ticagrelor in patients with myocardial infarction (MI) after out-of-hospital cardiac arrest (OHCA) treated with percutaneous coronary intervention (PCI) and mild therapeutic hypothermia (MTH) vs. MI patients without OHCA treated with PCI. The study was designed and performed as a phase IV, single-center, investigator-initiated, prospective, observational study assessing the early pharmacodynamic effect (within first 24 h) of a ticagrelor loading dose (180 mg) in both groups of patients (MTH group vs. MI group). For assessment of ticagrelor pharmacodynamics Multiple Electrode Aggregometry (MEA) was applied. Compared with the MTH group, platelet inhibition was persistently stronger in the MI group over the entire observation period (up to 24 h), with the highest difference at 4 hours after loading with ticagrelor (25.8 ± 26.4 vs. 75.8 ± 40.9 U, p = 0.002). As a consequence, there was a higher prevalence of high platelet reactivity in the MTH group, with the most explicit difference at 6 hours after the loading dose of ticagrelor (78% vs. 7%, p < 0.001). In comparison with patients treated with primary PCI for uncomplicated MI, the antiplatelet effect of ticagrelor in patients with MI complicated with OHCA, undergoing MTH and primary PCI, is attenuated and delayed.

Pre-hospital mild therapeutic hypothermia for patients with severe traumatic brain injury

ABSTRACT Background We aimed to assess the effects of pre-hospital mild therapeutic hypothermia (MTH) on patients with severe traumatic brain injury (sTBI). Methods Eighty-six patients with sTBI were prospectively enrolled into the pre-hospital MTH group and the late MTH group (initiated in hospital). Patients in the pre-hospital MTH group were maintained at a tympanic temperature of 33°C–35°C before admission and continued to be treated with a therapeutic hypothermia device for 4 days. Patients in the late MTH group were treated with the same MTH parameters. Intracranial pressure (ICP), complications and Glasgow Outcome Scale (GOS) scores were monitored. Results ICP was significantly lower for patients in the pre-hospital MTH group 24, 48, and 72 h after treatment (17.38 ± 4.88 mmHg, 18.40 ± 4.50 mmHg, and 16.40 ± 4.13 mmHg, respectively) than that in the late MTH group (20.63 ± 3.00 mmHg, 21.80 ± 6.00 mmHg, and 18.81 ± 4.50 mmHg) (P < .05). The favorable prognosis (GOS scores 4–5) rate in the pre-hospital MTH group was higher tha n the late MTH group (65.1% vs. 37.2%, respectively; P < .05) without complications . Conclusion Pre-hospital MTH for patients with STBI can reduce ICP and improve neurological outcomes.

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. Nineteen hospitals in The Netherlands. The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. None. After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Mild Therapeutic Hypothermia Alters Hemostasis in ST Elevation Myocardial Infarction Patients.

Background and Rationale: Mild therapeutic hypothermia (MTH) is a concept to reduce infarct size and improve outcome after ST-segment elevation myocardial infarction (STEMI). In the STATIM trial, we investigated MTH as an additional therapy for STEMI patients. In the intention-to-treat set, 101 patients were included. No difference in primary and secondary endpoints measured by cardiac magnetic resonance imaging was found. Platelet activation and plasmatic coagulation are key in the pathophysiology of STEMI. In the present study, we investigated the effect of MTH on primary and secondary hemostasis in STEMI patients.Methods and Results: Platelet function and morphology were assessed by routine blood count, aggregometry testing, and flow cytometry. Soluble platelet markers were determined by enzyme-linked immunosorbent assay (ELISA) testing. Plasmatic coagulation was measured throughout the study. Platelet count remained unchanged, irrespective of treatment, whereas platelet size decreased in both patient groups. Platelet aggregometry indicated increased platelet reactivity in the MTH group. Furthermore, higher adenosine diphosphate (ADP) plasma levels were found in MTH patients. Expression of glycoprotein IIb/IIIa was increased on platelets of STEMI patients treated with MTH. Lower patient temperatures correlated with longer clotting times and resulted in reduced pH. Lower pH values were positively correlated with longer clotting times.Conclusion: Present data indicate longer clotting times and higher platelet reactivity in STEMI patients treated with MTH. These changes did not correspond to clinical bleeding events or larger infarct size.

Impact of mild therapeutic hypothermia on bioavailability of ticagrelor in patients with acute myocardial infarction after out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest (OHCA) frequently occurs in the early phase of acute myocardial infarction (MI). Survivors require percutaneous coronary intervention (PCI) with concomitant dual antiplatelet therapy. Target temperature management, including mild therapeutic hypothermia (MTH), should be applied in comatose patients after resuscitation. However, an increased risk of stent thrombosis in patients undergoing hypothermia is observed. The aim of this study was to assess the impact of MTH on pharmacokinetics of ticagrelor in cardiac arrest survivors with MI treated with MTH and PCI. In a prospective, observational, single-center study pharmacokinetics of ticagrelor were evaluated in 41 MI patients, including 11 patients after OHCA undergoing MTH (MTH group) and 30 MI patients without OHCA and MTH (no-MTH group). Blood samples were drawn before administration of a 180 mg ticagrelor loading dose, and 30 min, 1, 2, 4, 6, 12, and 24 h after the loading dose. In patients treated with MTH total exposure to ticagrelor during the first 12 h after the loading dose and maximal plasma concentration of ticagrelor were significantly lower than in the no-MTH group (AUC(0-12): 3403 ± 2879 vs. 8746 ± 5596 ng·h/mL, difference: 61%, p = 0.01; Cmax: 475 ± 353 vs. 1568 ± 784 ng/mL, p = 0.0002). Time to achieve maximal ticagrelor plasma concentration was also delayed in the MTH group (tmax for ticagrelor: 12 [6-24] vs. 4 [2-12] h, p = 0.01). Bioavailability of ticagrelor was substantially decreased and delayed in MI patients treated with MTH after OHCA. ClinicalTrials.gov Identifier: NCT02611934.

Mild Hypothermia in Cardiogenic Shock Complicating Myocardial Infarction.

Experimental trials suggest improved outcome by mild therapeutic hypothermia for cardiogenic shock after acute myocardial infarction. The objective of this study was to investigate the hemodynamic effects of mild therapeutic hypothermia in patients with cardiogenic shock complicating acute myocardial infarction. Patients (n=40) with cardiogenic shock undergoing primary percutaneous coronary intervention without classic indications for mild therapeutic hypothermia underwent randomization in a 1:1 fashion to mild therapeutic hypothermia for 24 hours or control. The primary end point was cardiac power index at 24 hours; secondary end points included other hemodynamic parameters and serial measurements of arterial lactate. No relevant differences were observed for the primary end point of cardiac power index at 24 hours (mild therapeutic hypothermia versus control: 0.41 [interquartile range, 0.31-0.52] versus 0.36 [interquartile range, 0.31-0.48] W/m2; P=0.50; median difference, -0.025 W/m2; 95% CI, -0.12 to 0.06). Similarly, all other hemodynamic measurements were not statistically different. Arterial lactate levels at 6, 8, and 10 hours were significantly higher in patients in the mild therapeutic hypothermia group with a slower decline ( P for interaction=0.03). There were no differences in 30-day mortality (60% versus 50%; hazard ratio, 1.27; 95% CI, 0.55-2.94; P=0.55). In this randomized trial, mild therapeutic hypothermia failed to show a substantial beneficial effect on cardiac power index at 24 hours in patients with cardiogenic shock after acute myocardial infarction. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01890317.

Therapeutic hypothermia in patients with coagulopathy following severe traumatic brain injury

BackgroundCoagulopathy in traumatic brain injury (TBI) has been associated with poor neurological outcomes and higher in-hospital mortality. In general principle of trauma management, hypothermia should be prevented as it directly worsens coagulopathy. Therefore, we examined the safety of mild therapeutic hypothermia (MTH) in patients with coagulopathy following severe TBI.MethodsWe re-evaluated the brain hypothermia (B-HYPO) study data based on coagulopathy and compared the Glasgow Outcome Scale scores and survival rates at 6 months using per protocol analyses. Coagulopathy was defined as an activated partial thromboplastin time (APTT) > 60 s and/or fibrin/fibrinogen degradation product levels (FDP) > 90 μg/mL on admission. Baseline characteristics, coagulation parameters, and outcomes were compared between the control and MTH groups with or without coagulopathy.ResultsIn patients with coagulopathy, 12 patients were allocated to the control group (35.5–37.0 °C) and 20 patients to the MTH group (32–34 °C). In patients without coagulopathy, 28 were allocated to the control group and 59 patients were allocated to the MTH group.In patients with coagulopathy, favorable neurological outcomes and survival rates were comparable between the control and MTH groups (33.3% vs. 35.0%, P = 1.00; 50.0% vs. 60.0%, P = 0.72) with no difference in complication rates. On admission, no significant differences in APTT or FDP levels were observed between the two groups; however, APTT was significantly prolonged in the MTH group compared to the control group on day 3.DiscussionBased on our study, MTH did not seem to negatively affect the outcomes in patients with coagulopathy following severe TBI on admission; therefore, the present study indicates that MTH may be applicable even in patients with severe TBI and coagulopathy.ConclusionsOur study suggests that in comparison to control, MTH does not worsen the outcome of patients with coagulopathy following severe TBI.Trial registrationUMIN-CTR, No. C000000231, Registered 13 September 2005.

Influence of argon on temperature modulation and neurological outcome in hypothermia treated rats following cardiac arrest

Aim of the studyCombining xenon and mild therapeutic hypothermia (MTH) after cardiac arrest (CA) confers a degree of protection that is greater than either of the two interventions alone. However, xenon is very costly which might preclude a widespread use. We investigated whether the inexpensive gas argon would enhance hypothermia induced neurologic recovery in a similar manner. MethodsFollowing nine minutes of CA and three minutes of cardiopulmonary resuscitation 21 male Sprague-Dawley rats were randomized to receive MTH (33°C for 6h), MTH plus argon (70% for 1h), or no treatment. A first day condition score assessed behaviour, motor activity and overall condition. A neurological deficit score (NDS) was calculated daily for seven days following the experiment before the animals were killed and the brains harvested for histopathological analysis. ResultsAll animals survived. Animals that received MTH alone showed best overall neurologic function. Strikingly, this effect was abolished in the argon-augmented MTH group, where animals showed worse neurologic outcome being significant in the first day condition score and on day one to three and five in the NDS in comparison to MTH treated rats. Results were reflected by the neurohistopathological analysis. ConclusionOur study demonstrates that argon augmented MTH does not improve functional recovery after CA in rats, but may even worsen neurologic function in this model.

Plasma Potassium Concentration on Admission Correlates with Neurologic Outcome in Traumatic Brain Injury Patients Treated with Targeted Temperature Management: A Post Hoc Analysis of a Multicenter Randomized Controlled Trial

Recent studies have focused on the association between plasma electrolytes, particularly potassium level and neurologic outcomes in patients with traumatic brain injury (TBI). We hypothesized that potassium level on admission is an indicator for initiation of targeted temperature management in patients with severe TBI. We re-evaluated the Brain Hypothermia Study data based on the potassium levels on admission (i.e.,hypokalemia [<3.5 mEq/L] or normokalemia [3.5-5 mEq/L]) and compared these values and Glasgow Outcome Scale scores at 6 months by per protocol analysis. Consequently, 135 patients were enrolled. Finally, groups 50 and 23 patients with hypokalemia and 34 and 23 patients with normokalemia were allocated to mild therapeutic hypothermia (MTH) and fever control groups, respectively. Baseline characteristics, complication rates, and favorable neurologic outcome rates were compared between the two groups. In the normokalemia patients, fever control management was associated with a significant increase in favorable neurologic outcome compared with those in the MTH group (68.2% vs. 35.3%; P= 0.03). The complication rate was significantly higher in the MTH group than in the fever control group for patients with normokalemia (23.4% vs. 0%; P= 0.03). Conversely, hypokalemia patients in the MTH group revealed relatively better favorable neurologic outcomes compared with those in the fever control group (52.0% vs. 39.1%; P= 0.33). The initial potassium level may be an indicator in determining appropriate targeted temperature management for patients with TBI. Fever control may be considered instead of MTH for normokalemia patients with TBI on admission.

Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi-Center, Randomized Controlled Trial.

In our prospective, multi-center, randomized controlled trial (RCT)-the Brain Hypothermia (B-HYPO) study-we could not show any difference on neurological outcomes in patients probably because of the heterogeneity in the severity of their traumatic condition. We therefore aimed to clarify and compare the effectiveness of the two therapeutic temperature management regimens in severe (Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the present post hoc B-HYPO study, we re-evaluated data based on the severity of trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled. Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15 patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and fever control groups, respectively. No significant intergroup differences were observed with regard to age, gender, scores on head computed tomography (CT) scans, and surgical operation for traumatic brain injury (TBI), except for Injury Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p = 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p = 0.26) in patients with AIS 3-4, although the latter was not statistically significant. There was no difference in mortality or favorable outcome in patients with AIS 5. Fever control may be considered instead of MTH in patients with TBI (AIS 3-4).

Abstract 17314: Impact of Mild Therapeutic Hypothermia on Platelet Inhibition in Acute Coronary Syndrome

Background: Mild therapeutic hypothermia (MTH) improves outcome for patients with acute coronary syndrome (ACS) after cardiac arrest (CA). Previous data point to an interaction between hypothermia and drug metabolism, thus potentially impacting on platelet function under antiplatelet therapy. Purpose: The aim of the study is to determine clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with mild hypothermia (33°C, n=12) compared with ACS patients (troponin positive) with normal body temperature (n=14). Methods: Platelet function was measured by light transmittance aggregometry (LTA), multiple electrode platelet aggregometry (MEA) and VASP phosphorylation analysis before, 2h, 4h and 24h after administration of a 600 mg clopidogrel loading dose. Furthermore, plasma concentrations of clopidogrel, the active thiol metabolite and the inactive carboxyl metabolite were determined. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. Mild hypothermia was carried out according to current guidelines for 24 hours at a target temperature of 33°C. Results: Plasma concentration of clopidogrel and metabolites were lower in the MTH group after 2h and 4h, respectively (all p&lt;0.005). All platelet function tests showed an attenuated response to clopidogrel with respect to baseline platelet activity in the MTH group. This was significant for VASP analysis and LTA (p&lt;0.05). Moreover, there was no difference in genotype and platelet function determined ex vivo with 33°C and 37°C, respectively. Conclusion: Inhibition of platelet function is decreased under MTH, presumably due to a diminished clopidogrel absorption and metabolization. Thus, these patients might have a higher risk for cardiovascular events despite antiplatelet therapy.

Abstract 291: Interaction Between Diabetes and Hypothermia on Outcomes After Out-of-Hospital Cardiac Arrest: A Nationwide Observational Study

Objective: To determine whether diabetes mellitus (DM) has an interaction effect with the mild therapeutic hypothermia (MTH) on brain recovery after emergency medical services (EMS) assessed out-of-hospital cardiac arrest (OHCA) survivors. Methods: We included all OHCA patients survived to admission with presumed cardiac etiology (Jan. 2009 to Dec. 2012) from Korean national OHCA registry, excluding cases without available outcome data. The primary exposure was MTH which included all kinds of cooling methods. The endpoints were hospital discharge and discharge with brain recovery (cerebral performance category 1 or 2). DM was defined as PDM-positive when the patient has clinical treatment history or positive at blood laboratory test, NDM- negative in history and test, and UDM- if there is no available laboratory test and history. We compared outcomes between MTH versus non-MTH group using multivariable logistic regression with interaction term between MTH and DM for calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for individual, Utstein, post-resuscitation factors, and comorbidities. Results: We included 7,516 OHCAs survived to admission. MTH was performed in 14.6% and showed better outcomes than non-MTH group; 54.1% vs. 36.4% in survival discharge and 22.6% vs. 14.1% in good brain recovery (Ps&lt;0.001). Survival to discharge with good brain recovery of all and DM group was 15.3% of all (n=7,516), 17.7% of NDM (n=4,129), 9.7% of PDM (n=1,952), and 16.1% of UDM (n=2,382), respectively. MTH performed has increased by year; 8.6% (2009), 9.9% (2010), 16.1% (2011), and 21.1% (2012). Adjusted OR (95% CI) by MTH for survival to discharge was 1.66 (1.42-1.95) in non-interaction model and 2.08 (1.55-2.81) in NDM, 1.24 (0.88-1.75) in PDM, 1.84 (1.23-2.61) in UDM in interaction model, respectively. Adjusted OR (95% CI) by MTH for discharge with brain recovery was 1.29 (1.04-1.56) in non-interaction model and 1.33 (0.87-2.02) in NDM, 0.59 (0.34-1.04) in PDM, and 0.62 (0.36-1.03) in UDM in interaction model, respectively. Conclusions: The MTH was associated with better outcomes and is significantly associated with survival to discharge in non-diabetes group, not in diabetes group.

Feasibility and Cardiac Safety of Inhaled Xenon in Combination With Therapeutic Hypothermia Following Out-of-Hospital Cardiac Arrest*

Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892). A multipurpose ICU in university hospital. Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm. Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n=18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon+mild therapeutic hypothermia group, n=18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n=17; Xenon+mild therapeutic hypothermia group, n=16). Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group=5.30 mg vs Xenon+mild therapeutic hypothermia group=2.95 mg, p=0.06). Heart rate was significantly lower in Xenon+mild therapeutic hypothermia patients during hypothermia (p=0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon+mild therapeutic hypothermia group (p=0.04). Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.

Mild Therapeutic Hypothermia After Out‐Of‐Hospital Cardiac Arrest Complicating ST‐Elevation Myocardial Infarction: Long‐term Results in Clinical Practice

Recently, mild therapeutic hypothermia (MTH) has been integrated into the European resuscitation guidelines to improve outcomes after out-of-hospital cardiac arrest (OHCA). Data on long-term results are limited, especially in patients with acute ST-elevation myocardial infarction (STEMI). Invasive MTH influences long-term prognosis after OHCA due to STEMI. We analyzed 48 patients who underwent emergency coronary angiography for STEMI after witnessed OHCA. In 24 consecutive patients, MTH was performed via intravascular cooling (CoolGard System, 34°C maintained for 24 hours) after initialization by rapid infusion of cold saline. Clinical, procedural, and mortality data were compared to 24 historical controls. Neurological recovery was assessed using the Cerebral Performance Category score (CPC) at 30-day and 1-year follow-up. Median time delay until arrival of emergency medical service was 6 minutes (MTH group) vs 6.5 minutes (controls) (P = 0.16). Initial rhythm was ventricular fibrillation in 75% vs 66.7% (P = 0.75). There were no differences regarding baseline characteristics, angiographic findings, and success of cardiac catheterization procedures. MTH was not associated with a higher frequency of bleeding complications or of pneumonia. Thirty-day mortality was 33.3% in both groups. One-year mortality was 37.5% (MTH group) vs 50% (controls) (P = 0.56). At 1 year, favorable neurological outcome (CPC ≤2) was significantly more frequent in the MTH group (58.3% vs 20.8%, P = 0.017). Multivariate analysis identified MTH as independent predictor of favorable neurological outcome (P < 0.02, odds ratio: 12.73). MTH via intravascular cooling improves neurological long-term prognosis after OHCA due to STEMI and is safe in clinical practice.

Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention*

Mild therapeutic hypothermia (MTH) has been integrated into international resuscitation guidelines. In the majority of patients, sudden cardiac arrest is caused by myocardial infarction. This study investigated whether a combination of MTH with primary percutaneous coronary intervention (PCI) is feasible, safe, and potentially beneficial in patients after cardiac arrest due to acute myocardial infarction. Single-center observational study with a historical control group. University clinic. Thirty-three patients after cardiac arrest with ventricular fibrillation as initial rhythm and restoration of spontaneous circulation who remained unconscious at admission and presented with acute ST elevation myocardial infarction (STEMI). In 16 consecutive patients (2005-2006), MTH was initiated immediately after admission and continued during primary PCI. Seventeen consecutive patients who were treated in a similar 2-yr observation interval before implementation of MTH (2003-2004) served as a control group. Feasibility, safety, mortality, and neurologic outcome were documented. Initiation of MTH did not result in longer door-to-balloon times compared with the control group (82 vs. 85 mins), indicating that implementation of MTH did not delay the onset of primary PCI. Target temperature (32-34 degrees C) in the MTH group was reached within 4 hrs, consistent with previous trials and suggesting that primary PCI did not affect the velocity of cooling. Despite a tendency to increased bleeding complications and infections, patients treated with MTH tended to have a lower mortality after 6 months (25% vs. 35%, p = .71) and an improved neurologic outcome as determined by a Glasgow-Pittsburgh Cerebral Performance Scale score of 1 or 2 (69% vs. 47% in the control group, p = .30). MTH in combination with primary PCI is feasible and safe in patients resuscitated after cardiac arrest due to acute myocardial infarction. A combination of these therapeutic procedures should be strongly considered as standard therapy in patients after out-of-hospital cardiac arrest due to STEMI.