scholarly journals Tocilizumab reduces cardiac injury after out-of-hospital cardiac arrest primarily in patients without acute revascularization - Results from a randomized trial, The IMICA trial

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
M Meyer ◽  
S Wiberg ◽  
J Grand ◽  
ASP Meyer ◽  
L Obling ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Systemic Inflammation ◽  
Marked Reduction ◽  
Myocardial Dysfunction ◽  
Geometric Mean ◽  
Cardiac Injury ◽  
Temperature Management ◽  
Significant Group ◽  
Biomarker Analysis ◽  
Hospital Cardiac Arrest

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation (Reference no. 19-R135-A9302-22125) Lundbeck Foundation (Reference no. R186-2015-2132) BACKGROUND Patients remaining comatose after the initial resuscitation from out-of-hospital cardiac arrest (OHCA) have a high risk of morbidity and mortality as part of the ensuing post cardiac arrest syndrome (PCAS). Systemic inflammation and myocardial dysfunction are constituents of PCAS. The cytokine Interleukin-6 (IL-6) is associated with PCAS severity and poor outcome. Also, the extend of cardiac injury is a prognostic marker. We have recently shown that the IL-6 receptor antagonist tocilizumab dampens systemic inflammation and cardiac injury after cardiac arrest. PURPOSE To investigate if the reduction in cardiac injury by tocilizumab is differentiated in patients undergoing acute coronary revascularization compared to those who do not. METHODS Eighty comatose OHCA patients were randomized 1:1 in a double-blinded placebo-controlled trial to a single infusion of tocilizumab or placebo in addition to standard of care including targeted temperature management. Trial registration: Clinicaltrials.gov NCT03863015. Blood samples were sequentially drawn for biomarker analysis. Endpoints were markers of cardiac injury and inflammation:  Troponin T (TnT), N-terminal pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP). Continuous variables were log2 transformed and analyzed using mixed models; values shown as geometric mean with 95%-confidence limits [95%CL] after back-transformation. RESULTS Thirty-nine patients were randomized to treatment with tocilizumab and 41 to placebo. In the tocilizumab group 15 (39%) patients underwent acute revascularization (all PCI), and this was 22 (54%) for placebo. Patients not undergoing acute revascularization had a marked reduction by treatment with tocilizumab in TnT at 6h, as well as NT-proBNP at 48h (Figure). For patients treated with acute revascularization there was no significant group difference in TnT at 6h, whereas there was a marked reduction in NT-proBNP at 48h. There was a substantial reduction in CRP by treatment with tocilizumab irrespective of whether acute revascularization was performed. CONCLUSION Treatment with tocilizumab resulted in a significant reduction in myocardial injury as measured by TnT primarily in patients not undergoing acute revascularization, whereas the reduction in NT-proBNP, as well as CRP, was seen irrespective of whether acute revascularization was performed. Abstract Figure. Acute vs. NO acute revascularization

scholarly journals Tocilizumab mitigates hypercoagulability after out-of-hospital cardiac arrest – results from a randomized controlled trial (IMICA)

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Meyer ◽  
S Wiberg ◽  
J Grand ◽  
A S P Meyer ◽  
L Obling ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Platelet Count ◽  
Placebo Group ◽  
Systemic Inflammation ◽  
Controlled Trial ◽  
Maximum Amplitude ◽  
Standard Of Care ◽  
Temperature Management ◽  
Coagulation Parameters ◽  
Hospital Cardiac Arrest

Abstract Background Systemic inflammation constitutes a key element of the post cardiac arrest syndrome (PCAS) which affects initially comatose resuscitated cardiac arrest patients. We have recently shown that treatment with tocilizumab, an IL-6 receptor antagonist, reduces systemic inflammation and myocardial injury after out-of-hospital cardiac arrest (OHCA). Inflammation and coagulation are interconnected, and changes in coagulation often accompany inflammatory states. Purpose To investigate if conventional coagulation parameters or a viscoelastic hemostatic assay differ in patients treated with tocilizumab compared to placebo. Methods Eighty comatose OHCA patients were randomized 1:1 in a double-blinded placebo-controlled trial to a single infusion of tocilizumab or placebo in addition to standard of care including targeted temperature management. Trial registration: Clinicaltrials.gov NCT03863015. Endpoints were plasma fibrinogen, platelet count, and Thrombelastography (TEG) variables. TEG analysis was performed utilizing whole blood in a citrated kaolin assay with heparinase (to neutralize any unfractionated or low molecular weight heparin that had been administered), and the following variables were analyzed: reaction time (R), angle, maximum amplitude (MA), and lysis at 30 minutes (Ly30) which represents clot initiation, propagation, strength and dissolution respectively. Data reported as median (Q1; Q3), statistical analysis performed by constrained linear mixed models, and a p<0.05 was considered statistically significant. Results Admission median levels of the investigated coagulation parameters were within normal levels for both the tocilizumab and placebo group. At 48 hours, for the placebo group, fibrinogen levels (figure 1) had risen to supra-normal levels, TEG angle had increased from 64 (10; 67) till 72 (69; 74), and TEG MA (figure 2) had increased to the hypercoagulable range (all p<0.05), while for the tocilizumab group fibrinogen levels and TEG MA remained within normal values. Both groups had a significant fall in platelet count from admission till 48h [placebo: from 252 109/L (208; 282) till 151 (126; 189); tocilizumab from 217 (183; 260) till 152 (127; 183)], with no group differences. Also for both groups there was significant shortening of the TEG R time [placebo: from 8 min (6; 10) till 6 (6; 8); tocilizumab from 8 (6; 9) till 7 (6; 8)], again with no difference between groups. Ly30 did not change over time or differ between groups. Conclusion Treatment with tocilizumab following resuscitated OHCA aids in maintaining a normo-coagulable state, whereas placebo patients developed supra-normal fibrinogen levels and a hypercoagulable TEG clot strength. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Danish Heart Foundation (Reference no. 19-R135-A9302-22125); Region Hovedstadens Forskningsfond til sundhedsforskning (CapitalRegion Research Foundation, Denmark; reference no. A6030) Figure 1. Fibrinogen Figure 2. Thrombelastography MA

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.

Abstract 12933: Myocardial Dysfunction After In-Hospital Cardiac Arrest in COVID-19 Patients

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Abhishek Bhardwaj ◽  
Mahmoud Alwakeel ◽  
Siddharth Dugar ◽  
sudhir krishnan ◽  
Xiaofeng Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Median Time ◽  
Systolic Function ◽  
Myocardial Dysfunction ◽  
Systolic Dysfunction ◽  
Cleveland Clinic ◽  
Case Series ◽  
Apache Ii Score ◽  
Lv Function ◽  
Hospital Cardiac Arrest

Introduction: Post resuscitation myocardial dysfunction (PRMD) is common after out-of-hospital cardiac arrest. While PRMD is a known cause of post-resuscitation circulatory failure, few studies have reported associations between PRMD and neurologic outcome or survival. Further, little is known about PRMD after in-hospital cardiac arrest (IHCA) nor on the incidence and prognosis of PRMD in COVID-19 IHCA. We sought to evaluate the incidence of PRMD in a multicenter cohort of resuscitated COVID-19 IHCA patients. Study Population and Methods: We included adult patients (≥18 y) admitted to multiple hospitals of Cleveland Clinic Health System. Patients who attained ROSC with an initial echocardiogram (EC) in the 72 hours post-arrest were included. Data were extracted from a data registry and electronic medical records. Results: From 03/2020-10/2020, 58 patients with COVID-19 had IHCA. ROSC was noted in 35 patients (60.3%), 27 (46.6%) were alive at 24 h and 13 patients (22.4%) survived to hospital discharge. Of the 35 patients who had ROSC, 14 patients (40%) had an EC within 72 h. The median age of this cohort was 67 y (IQR 47 - 73); 71% were male, and median BMI of 28 (IQR 27 - 34), and admission APACHE II score was 13 (IQR 11 - 19). One third of the patients (36%) were mechanically ventilated before arrest and 43% were on vasopressors. Initial arrest rhythms were: PEA/Asystole, 79%; and VF/VT, 21%. Most patients (93%) received manual chest compression with median CPR duration of 5 min (IQR 2 - 10). The median time of obtaining first EC post-ROSC in these 14 patients was 22 hours (IQR 6 - 62). 7/14 (50%) of the patient had systolic dysfunction on initial EC (6 had global dysfunction, 1 with regional wall motion abnormality, and 4/7 had combined LV and RV systolic dysfunction). 5/14 patients had a follow up EC with a median time of 43 days. 2/5 had normal initial EC and 3 out of these 5 patients who initially had PMRD showed complete recovery in their LV and RV systolic function. Conclusion: We report a case series of PRMD in COVID-19 patients who experienced IHCA. We found that PMRD is seen in half of the patients. Most patients with PMRD recovered to normal RV and LV function, consistent with prior studies of non-COVID-19 arrest EC.

Abstract 407: Utility of Abnormal Head Computed Tomography in Predicting Outcome in Out of Hospital Cardiac Arrest Victims Resuscitated and Subsequently Placed on Targeted Temperature Management

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Michael Bernett ◽  
Robert A Swor
Keyword(s):  
Computed Tomography ◽  
Cardiac Arrest ◽  
Survival Analysis ◽  
Interrater Reliability ◽  
Targeted Temperature Management ◽  
Neurologic Outcome ◽  
Temperature Management ◽  
Radiology Reports ◽  
Head Computed Tomography ◽  
Hospital Cardiac Arrest

Introduction: Head computed tomography (HCT) is often performed to assess for hypoxic-ischemic brain injury in resuscitated out of hospital cardiac arrest (OHCA) patients. Our primary objective was to assess whether cerebral edema (CE) on early HCT is associated with poor survival and neurologic outcome post OHCA. Methods: We included subjects from a prospectively collected cardiac arrest database of OHCA adult patients who received targeted temperature management (TTM) at two academic suburban hospitals from 2009-Sept-2018. Cases were included if a HCT was performed in the emergency department (ED). Patient demographics and cardiac arrest variables were collected. HCT results were abstracted by study authors from radiology reports. HCT findings were categorized as no acute disease, evidence of CE, or excluded (bleed, tumor, stroke). Outcomes were survival to discharge or cerebral performance scores (CPC) at discharge of three or four (poor neurologic outcome). Descriptive statistics, univariate, multivariate, survival, and interrater reliability analysis were performed. Results: During the study period, there were 425 OHCA, 277 cases had ED HCTs performed; 254 cases were included in the final survival analysis. Patients were predominately male, 189 (65.0%), average age 60.9 years, average BMI of 30.5. Of all cases, 44 (15.9%) showed CE on CT. Univariate analysis demonstrated that CE was associated with 9.2-fold greater odds of poor outcome (OR: 9.23; 95% CI 1.73, 49.2), and 9.1-fold greater odds of death (OR: 9.09: 95% CI 2.4 33.9). In adjusted analysis, CE was associated with 14.9-fold greater odds of poor CPC outcome (AOR: 14.9, 95% CI, 2.49, 88.4), and 13.7-fold greater odds of death (AOR: 13.7, 95% CI, 3.26, 57.4). Adjusted survival analysis demonstrated that patients with CE on HCT had 3.6-fold greater hazard of death than those without CE (HR: 3.56: 95% CI 2.34, 5.41). Interrater reliability demonstrated excellent agreement between reviewers for CE on HCT (κ = 0.86). Conclusion: The results identify that abnormal HCTs early in the post-arrest period in OHCA patients are associated with poor rates of survival and neurologic outcome. Prospective work is needed to confirm whether selection bias or other variables confound this association.

Abstract 18656: The Effect of Targeted Temperature Management is Dependent Upon the Duration of Out-of-hospital Cardiac Arrest

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ian R Drennan ◽  
Steve Lin ◽  
Kevin E Thorpe ◽  
Jason E Buick ◽  
Sheldon Cheskes ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Hospital Discharge ◽  
Spontaneous Circulation ◽  
Targeted Temperature Management ◽  
Neurologic Outcome ◽  
Temperature Management ◽  
Neurologic Injury ◽  
Good Neurologic Outcome ◽  
The Impact ◽  
Hospital Cardiac Arrest

Introduction: Targeted temperature management (TTM) reduces neurologic injury from out-of-hospital cardiac arrest (OHCA). As the risk of neurologic injury increases with prolonged cardiac arrests, the benefit of TTM may depend upon cardiac arrest duration. We hypothesized that there is a time-dependent effect of TTM on neurologic outcomes from OHCA. Methods: Retrospective, observational study of the Toronto RescuNET Epistry-Cardiac Arrest database from 2007 to 2014. We included adult (>18) OHCA of presumed cardiac etiology that remained comatose (GCS<10) after a return of spontaneous circulation. We used multivariable logistic regression to determine the effect of TTM and the duration of cardiac arrest on good neurologic outcome (Modified Rankin Scale (mRS) 0-3) and survival to hospital discharge while controlling for other known predictors. Results: There were 1496 patients who met our inclusion criteria, of whom 981 (66%) received TTM. Of the patients who received TTM, 59% had a good neurologic outcome compared to 39% of patients who did not receive TTM (p< 0.001). After adjusting for the Utstein variables, use of TTM was associated with improved neurologic outcome (OR 1.60, 95% CI 1.10-2.32; p = 0.01) but not with survival to discharge (OR 1.23, 95% CI 0.90-1.67; p = 0.19). The impact of TTM on neurologic outcome was dependent on the duration of cardiac arrest (p<0.05) (Fig 1). Other significant predictors of good neurologic outcome were younger age, public location, initial shockable rhythm, and shorter duration of cardiac arrest (all p values < 0.05). A subgroup analysis found the use of TTM to be associated with neurologic outcome in both shockable (p = 0.01) and non-shockable rhythms (p = 0.04) but was not associated with survival to discharge in either group (p = 0.12 and p = 0.14 respectively). Conclusion: The use of TTM was associated with improved neurologic outcome at hospital discharge. Patients with prolonged durations of cardiac arrest benefited more from TTM.

Abstract 86: Association Between Hospital Postresuscitative Performance and Clinical Outcomes in Patients with Out-of-Hospital Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Dion Stub ◽  
Robert H Schmicker ◽  
Monique L Anderson ◽  
Eric D Peterson ◽  
Clifton W Callaway ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Functional Status ◽  
Performance Metrics ◽  
Treatment Guidelines ◽  
Hospital Performance ◽  
Temperature Management ◽  
Performance Score ◽  
Resuscitation Guidelines ◽  
Care Guidelines ◽  
Hospital Cardiac Arrest

Context: Whilst performance measures have been extensively evaluated in conditions such as myocardial infarction, it remains unclear if adherence to post-resuscitation guidelines is associated with better outcome in patients hospitalized after out-of-hospital cardiac arrest (OHCA). Objectives: To assess whether survival and good functional status at discharge are associated with post-resuscitation performance score based on treatment guidelines for patients with OHCA, comprised of a) initiation of temperature management; b) target temperature 32 0 -34 0 C achieved; c) temperature management continued for more than 12 hours; d) coronary angiography performed within 24 hrs; e) life sustaining treatment not withdrawn prior to day 3. Methods: An observational analysis of hospital care in 111 North American hospitals, including 3252 patients enrolled in the Resuscitation Outcomes Consortium (ROC-PRIMED) study, between 2007 and 2009, following OHCA. Performance scores were calculated, utilizing opportunity based scoring, with each factor weighted equally and scaled from 0-1. Scores for individual patients were grouped at the hospital level, with hospitals divided for descriptive purposes into quartiles based on their median opportunity composite score. Results: Performance score varied widely (median [IQR] scores from lowest to highest hospital quartiles, 21% [20%-25%] vs 59% [55%-64%]. Adjusted survival to discharge increased with each quartile of performance score (lowest to highest: 16.2%, 20.8%, 28.5%, 34.8%, P <0.01). Similarly adjusted rates of good functional outcome improved (lowest quartile to highest: 8.3%, 13.8%, 22.2%, 25.9%, P<0.01). Hospital performance score were significantly associated with outcome after risk adjustment for established prehospital resuscitative factors (Highest versus lowest adherence quartile: adjusted OR of survival 1.64; 95% CI 1.13, 2.38) Conclusions: Increased survival and improved functional status at discharge are associated with greater adherence to recommended hospital based post-resuscitative care guidelines. Measuring, reporting and improving hospital adherence to guideline-based performance metrics could improve outcomes following OHCA.

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