scholarly journals The complement lectin pathway protein MAp19 and out-of-hospital cardiac arrest: Insights from two randomized clinical trials

2019 ◽  
Vol 9 (4_suppl) ◽  
pp. S145-S152
Author(s):  
John Bro-Jeppesen ◽  
Anni Nørgaard Jeppesen ◽  
Simon Haugaard ◽  
Anne Troldborg ◽  
Christian Hassager ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Randomized Clinical Trials ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Lectin Pathway ◽  
Healthy Controls ◽  
Target Temperature ◽  
Potent Inducer ◽  
Randomized Controlled Studies ◽  
Hospital Cardiac Arrest

Aim: Activation of the complement system is known to be a potent inducer of systemic inflammation, which is an important component of post-cardiac arrest syndrome. Mannan-binding-lectin associated protein of 19 kDa (MAp19) is suggested to be a regulatory component of the lectin pathway of complement activation. The aims of this study were to describe serial levels of MAp19 protein in comatose survivors of out-of-hospital cardiac arrest (OHCA), to evaluate the effect of two different regimes of targeted temperature management and to investigate the possible association between levels of MAp19 and mortality. Methods: In this post-hoc study, we analysed data from two large randomized controlled studies: ‘Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest’ (TTM) and ‘Targeted temperature management for 48 versus 24 h and neurological outcome after out-of-hospital cardiac arrest’ (TTH). We measured serial levels of MAp19 in 240 patients within 72 h after OHCA and in 82 healthy controls. The effect of targeted temperature management on MAp19 levels was analysed according to temperature allocation in main trials. Results: MAp19 levels were significantly lower in OHCA patients within 48 h after OHCA ( p-values <0.001) compared with healthy controls. A target temperature at 33°C compared with 36°C for 24 h was associated with significantly lower levels of MAp19 (–57 ng/mL (95% confidence interval (CI): –97 to −16 mg/mL), p=0.006). Target temperature at 33°C for 48 h compared with 24 h was not associated with a difference in MAp19 levels (–31 ng/mL (95% CI: –120 to 60 mg/mL), p=0.57). Low MAp19 levels at admission were associated with higher 30-day mortality (12% vs. 38%, plog-rank =0.0008), also in adjusted analysis (two-fold higher, hazard ratio =0.48 (95% CI: 0.31 to 0.75), p=0.001). Analysis of MAp19 levels at 24–72 h showed they were not associated with 30-day mortality. Conclusion: Survivors after OHCA have lower levels of MAp19 protein compared with healthy controls. A targeted temperature management at 33°C compared with 36°C was associated with significantly lower MAp19 levels, whereas target temperature at 33°C for 48 h compared with 24 h did not influence MAp19 protein levels. Low MAp19 levels at admission were independently associated with increased mortality.

scholarly journals Mitochondrial dysfunction in adults after out-of-hospital cardiac arrest

2019 ◽  
Vol 9 (4_suppl) ◽  
pp. S138-S144
Author(s):  
Sebastian Wiberg ◽  
Nis Stride ◽  
John Bro-Jeppesen ◽  
Mathias J Holmberg ◽  
Jesper Kjærgaard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Arrest ◽  
Mitochondrial Function ◽  
Complex I ◽  
Targeted Temperature Management ◽  
System Capacity ◽  
Temperature Management ◽  
Healthy Controls ◽  
Muscle Biopsies ◽  
Hospital Cardiac Arrest

Background: While preclinical studies suggest that mitochondria play a pivotal role in ischaemia–reperfusion injury, the knowledge of mitochondrial function in human out-of-hospital cardiac arrest remains scarce. The present study sought to compare oxidative phosphorylation capacity in skeletal muscle biopsies from out-of-hospital cardiac arrest patients to healthy controls. Methods: This was a substudy of a randomised trial comparing targeted temperature management at 33°C versus 36°C for out-of-hospital cardiac arrest patients. Skeletal muscle biopsies were obtained from adult resuscitated comatose out-of-hospital cardiac arrest patients 28 hours after initiation of targeted temperature management, i.e. at target temperature prior to rewarming, and from age-matched healthy controls. Mitochondrial function was analysed by high-resolution respirometry. Maximal sustained respiration through complex I, maximal coupled respiration through complex I and complex II and maximal electron transport system capacity was compared. Results: A total of 20 out-of-hospital cardiac arrest patients and 21 controls were included in the analysis. We found no difference in mitochondrial function between temperature allocations. We found no difference in complex I sustained respiration between out-of-hospital cardiac arrest and controls (23 (18–26) vs. 22 (19–26) pmol O2/mg/s, P=0.76), whereas coupled complex I and complex II respiration was significantly lower in out-of-hospital cardiac arrest patients versus controls (53 (42–59) vs. 64 (54–68) pmol O2/mg/s, P=0.01). Furthermore, electron transport system capacity was lower in out-of-hospital cardiac arrest versus controls (63 (51–69) vs. 73 (66–78) pmol O2/mg/s, P=0.005). Conclusions: Mitochondrial oxidative phosphorylation capacity in skeletal muscle biopsies was reduced in out-of-hospital cardiac arrest patients undergoing targeted temperature management compared to age-matched, healthy controls. The role of mitochondria as risk markers and potential targets for post-resuscitation care remains unknown.

Abstract 158: Association Between Initial Body Temperature and Neurologic Outcomes of Out-Of-Hospital Cardiac Arrest Undergoing Targeted Temperature Management

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jong Hwan Kim ◽  
Jeong Ho Park ◽  
Sun Young Lee ◽  
Sang Do Shin ◽  
Jieun Pak ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Body Temperature ◽  
Spontaneous Circulation ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Target Temperature ◽  
Multivariable Logistic Regression Model ◽  
Neurologic Recovery ◽  
Neurologic Outcomes ◽  
Hospital Cardiac Arrest

Objectives: Targeted temperature management (TTM) is the core post-resuscitation care to minimize neurologic deficit after out-of-hospital cardiac arrest (OHCA). Uncontrolled body temperature of patients may reflect the thermoregulation ability which can be associated with neurologic damage during arrest. The aim of this study was to investigate the association between initial body temperature (BT) and neurologic outcomes in OHCA patients who underwent TTM. Methods: We used nationwide OHCA database from January 2016 to December 2017. Adult OHCA patients with presumed cardiac etiology who underwent TTM after return-of-spontaneous circulation (ROSC) were included. The main exposure was a BT at initiation of TTM which was categorized into 3 groups: low (-35.5°c), middle(35.6°c-37.4°c), and high BT (37.5°c-). The primary outcome was good neurologic outcome (cerebral performance categories (CPC) 1 or 2). Adjusted ratios (AORs) and 95% confidence intervals (CIs) were estimated to evaluate association between initial BT of TTM and outcome in multivariable logistic regression model. Stratified subgroup analyses were according to the target temperature of TTM (hypothermia vs normothermia). Results: Of a total of 744 patients, 208 (28.0%) patients were low initial BT group and 471 (63.3%) patients were normal initial BT group and 65 (8.7%) patients were high initial BT group. Good neurological recovery rate was 13.9% in low initial BT group, 41.8% in middle initial BT group and 36.9% in high initial BT group. The adjusted odds ratios for good neurologic recovery were 0.281 (95% confidence interval [CI] 0.17-0.47) in low BT group and 0.65 (95% CI 0.34-1.27) in high BT group compared with normal initial BT group. Similar results were also found regardless of target temperature of TTM. Conclusion: Low initial BT of TTM was associated with unfavorable neurologic recovery for OHCA patients who underwent TTM after ROSC.

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

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Takeshi Iyonaga ◽  
Ken-ichi Hiasa ◽  
Nobuyuki Enzan ◽  
Masaaki A Nishihara ◽  
Kenzo Ichimura ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neurological Outcome ◽  
Multivariable Analysis ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Target Temperature ◽  
Neurological Outcomes ◽  
Favorable Neurological Outcome ◽  
The Relationship ◽  
Hospital Cardiac Arrest

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 < 18 and Glasgow Coma Scale score > 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<0.001). Multivariable analysis showed TTM was associated with favorable neurological outcome (OR 1.6, 95%CI 1.1-2.3, p<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<0.57). Conclusions: TTM was significantly associated with favorable neurological outcome. However, neurological outcome was not associated with target temperature on TTM.

scholarly journals Targeted temperature management: It is not yet time to change your target temperature

CJEM ◽  
2015 ◽  
Vol 17 (6) ◽  
pp. 706-708 ◽  
Author(s):  
David Clinkard ◽  
Andrew Cameron ◽  
Daniel Howes ◽  
Ian Ball
Keyword(s):  
Cardiac Arrest ◽  
Targeted Temperature Management ◽  
Lower Mortality ◽  
Temperature Management ◽  
Clinical Question ◽  
Target Temperature ◽  
Neurologic Function ◽  
Unconscious Patients ◽  
Hospital Cardiac Arrest

Clinical questionIn unconscious patients of out-of-hospital cardiac arrest, does targeted temperature management to 36°C (96.8°F) improve outcomes compared to the standard target of 32°C–34°C (89.6°F–93.2°F)?Article chosenNielson N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med 2013;369:2197-2206.ObjectiveTo determine which temperature, 33°C (91.4°F) or 36°C (96.8°F), is associated with lower mortality and better neurologic function after cardiac arrest.

scholarly journals Echocardiographic parameters during prolonged targeted temperature Management in out-of-hospital Cardiac Arrest Survivors to predict neurological outcome – a post-hoc analysis of the TTH48 trial

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Thomas Hvid Jensen ◽  
Peter Juhl-Olsen ◽  
Bent Roni Ranghøj Nielsen ◽  
Johan Heiberg ◽  
Christophe Henri Valdemar Duez ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Neurological Outcome ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Left Ventricular Ejection ◽  
Secondary Outcome ◽  
Ventricular Ejection Fraction ◽  
Hospital Cardiac Arrest

Abstract Background Transthoracic echocardiographic (TTE) indices of myocardial function among survivors of out-of-hospital cardiac arrest (OHCA) have been related to neurological outcome; however, results are inconsistent. We hypothesized that changes in average peak systolic mitral annular velocity (s’) from 24 h (h) to 72 h following start of targeted temperature management (TTM) predict six-month neurological outcome in comatose OHCA survivors. Methods We investigated the association between peak systolic velocity of the mitral plane (s’) and six-month neurological outcome in a population of 99 patients from a randomised controlled trial comparing TTM at 33 ± 1 °C for 24 h (h) (n = 47) vs. 48 h (n = 52) following OHCA (TTH48-trial). TTE was conducted at 24 h, 48 h, and 72 h after reaching target temperature. The primary outcome was 180 days neurological outcome assessed by Cerebral Performance Category score (CPC180) and the primary TTE outcome measure was s’. Secondary outcome measures were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), e’, E/e’ and tricuspid annular plane systolic excursion (TAPSE). Results Across all three scan time points s’ was not associated with neurological outcome (ORs: 24 h: 1.0 (95%CI: 0.7–1.4, p = 0.98), 48 h: 1.13 (95%CI: 0.9–1.4, p = 0.34), 72 h: 1.04 (95%CI: 0.8–1.4, p = 0.76)). LVEF, GLS, E/e’, and TAPSE recorded on serial TTEs following OHCA were neither associated with nor did they predict CPC180. Estimated median e’ at 48 h following TTM was 5.74 cm/s (95%CI: 5.27–6.22) in patients with good outcome (CPC180 1–2) vs. 4.95 cm/s (95%CI: 4.37–5.54) in patients with poor outcome (CPC180 3–5) (p = 0.04). Conclusions s’ assessed on serial TTEs in comatose survivors of OHCA treated with TTM was not associated with CPC180. Our findings suggest that serial TTEs in the early post-resuscitation phase during TTM do not aid the prognostication of neurological outcome following OHCA. Trial registration NCT02066753. Registered 14 February 2014 – Retrospectively registered,

Effects of Targeted Temperature Management in Patients with Post-Cardiac Arrest Syndrome after an Out-Of-Hospital Cardiac Arrest Caused by Hanging: A Prospective Observational Cohort Study in Japan

2021 ◽  
Author(s):  
Ryuichiro Kakizaki ◽  
Naofumi Bunya ◽  
Shuji Uemura ◽  
Takehiko Kasai ◽  
Keigo Sawamoto ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cardiac Arrest ◽  
Propensity Score ◽  
Multivariate Logistic Regression Analysis ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Matched Cohort ◽  
Neurological Outcomes ◽  
Post Cardiac Arrest Syndrome ◽  
Hospital Cardiac Arrest

Abstract Background: Targeted temperature management (TTM) is recommended for unconscious patients after a cardiac arrest. However, its effectiveness in patients with post-cardiac arrest syndrome (PCAS) by hanging remains unclear. Therefore, this study aimed to investigate the relationship between TTM and favorable neurological outcomes in patients with PCAS by hanging.Methods: This study was a retrospective analysis of the Japanese Association for Acute Medicine out-of-hospital cardiac arrest (OHCA) registry between June 2014 and December 2017 among patients with PCAS admitted to the hospitals after an OHCA caused by hanging. A multivariate logistic regression analysis was performed to estimate the propensity score and to predict whether patients with PCAS by hanging receive TTM. We compared patients with PCAS by hanging who received TTM (TTM group) and those who did not (non-TTM group) using propensity score analysis.Results: A total of 199 patients with PCAS by hanging were enrolled in this study. Among them, 43 were assigned to the TTM group and 156 to the non-TTM group. Logistic regression model adjusted for propensity score revealed that TTM was not associated with favorable neurological outcome at 1-month (adjusted odds ratio [OR]: 1.38, 95% confidence interval [CI]: 0.27–6.96). Moreover, no difference was observed in the propensity score-matched cohort (adjusted OR: 0, 73, 95% CI: 0.10–4.71) and in the inverse probability of treatment weighting-matched cohort (adjusted OR: 0.63, 95% CI: 0.15–2.69).Conclusions: TTM was not associated with increased favorable neurological outcomes at 1-month in patients with PCAS after OHCA by hanging.

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