Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest.Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as "Cerebral Performance Category."Thirty-six sites in Europe and Australia.All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial.Targeted temperature management at 33°C or 36°C.Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3-5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03-1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group.Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.
Sevoflurane sample data in a standard single patient ICU room, VieCuri Medical Centre. Physical data of the ICU room: 52 m3, air refreshing rate minimum 6/hr
Background: An increasing number of cardiac centres are using immediate percutaneous coronary intervention (PCI) and extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out of hospital cardiac arrest (r-OHCA). Published evidence regarding PCI in OHCA has been mainly reporting to patients with early return of spontaneous circulation and the influence of PCI and ECPR on survival in the population of patients with r-OHCA and acute coronary syndrome (ACS) remains unclear. Methods: In this post hoc analysis of the randomized r-OHCA trial, all patients with ACS as a cause of r-OHCA were included. The effect of successful PCI and ECPR on 180-days survival was examined using Kaplan-Meier estimates and multivariable Cox regression. Results: In total, 256 patients were evaluated in Prague OHCA study and 127 (49.6 %) had ACS as the cause of r-OHCA constituting current study population. The mean age was 58 years (46.3-64) and duration of resuscitation was 52.5 minutes (36.5-68). ECPR was used in 51 (40.2 %) of patients. Immediate PCI was performed in 86 (67.7%) patients and TIMI flow 2 or 3 was achieved in 75 (87.2%) patients. The overall 180-days survival of patients with successful PCI was 40 % compared to 7.7 % with no or failed immediate PCI (log-rank p < 0.001). After adjustment for confounders, successful PCI was associated with a lower risk of death (HR 0.47, CI 0.24-0.93, p = 0.031). Likewise, ECPR was associated with a lower risk of death (HR 0.11, CI 0.05-0.24, p< 0.001). Conclusion: In this post hoc analysis of the randomized r-OHCA trial, successful immediate PCI as well as ECPR were associated with improved 180-days survival in patients with r-OHCA due to ACS.
Extracorporeal cardiopulmonary resuscitation (ECPR) is a challenging approach for treating refractory out-of-hospital cardiac arrest (OHCA).The authors describe a case of a 40-year-old Caucasian female who suffered from refractory OHCA, was admitted to a hospital while receiving ongoing cardiopulmonary resuscitation, and was connected to venoarterial extracorporeal membrane oxygenation 73 minutes after collapse. Ventricular tachyarrhythmias alternating with pulseless electrical activity resolved after eight hours. Following complete cardiac and neurological recovery, only adenoviral genome was found in myocardial biopsy. After 11 months, another episode of identical arrhythmias was rescued by an implantable cardioverter-defibrillator.Adequate prehospital and early hospital logistics is a prerequisite for successfully implementing extracorporeal cardiopulmonary resuscitation for refractory OHCA.
Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain.
Objective
To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival.
Design, Setting, and Participants
Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021).
Interventions
In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132).
Main Outcomes and Measures
The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours).
Results
The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, −1.3% to 20.1%];P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%];P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, −2.5% to 21%];P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively).
Conclusions and Relevance
Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference.
Despite the significance of proteins containing iron‐sulfur cluster (Fe–S proteins), the processes of Fe–S cluster assembly and maturation of Fe–S proteins are poorly understood. However, several key proteins involved in the assembly have been identified, notably IscS, a cystein desulfurase, which provides sulfur for Fe–S cluster and IscU, a metallochaperone acting as a scaffold for cluster assembly. In this work, we studied the process of Fe–S cluster biosynthesis in Trypanosoma brucei by identifying the homologue of IscS in the T. brucei (TbIscS). To address the function of TbIscS, we inhibited its expression by means of RNA interference (RNAi). After RNAi induction, generation time of the TbIscS knock‐down cell line was significantly prolonged. All types of mitochondrial ATP production in the cells were severely affected. Analysis of glucose metabolism end products determined pyruvate as major excreted metabolite of the induced cells, while the uninduced cells produced only small amount of this glycolytic end product. These data demonstrate that mitochondrial metabolism is impaired in cells with TbIscS knocked down. To test whether the observed phenomena were results of Fe–S cluster assembly disruption, we examined the Fe–S cluster‐dependent activity of aconitase. This enzyme is localized in its active form in mitochondrion as well as in cytosol of T. brucei . After RNAi induction we observed the reduction of aconitase activity in both compartments (approx. 70% reduction in cytosol, approx. 30% in mitochondria). Western blots together with the EPR analysis showed that the reduction in cytosolic activity was due to impaired Fe–S cluster formation, while decrease in aconitase activity in mitochondria corresponded to the reduced level of the protein.