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

Abstract 13686: Variation in Time in Therapeutic Range for Cooling for Out-of-Hospital Cardiac Arrest

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Kevin M Wheelock ◽  
Lian Chen ◽  
Saket Girotra ◽  
Paul S Chan ◽  
Rohan Khera
Keyword(s):  
Cardiac Arrest ◽  
Clinical Practice ◽  
Therapeutic Range ◽  
Interpolation Method ◽  
Controlled Trial ◽  
Linear Interpolation ◽  
Temperature Management ◽  
Level Variation ◽  
Time In Therapeutic Range ◽  
Hospital Cardiac Arrest

Introduction: For comatose survivors of out-of-hospital cardiac arrest (OHCA), targeted temperature management (TTM) is strongly recommended with a goal temperature of 32-36C for a period of at least 24 hours. However, adherence to this target in clinical practice remains unknown. We developed time-in-therapeutic range (TTR) as a treatment metric for patients receiving TTM and evaluated patient- and site-level variation in TTR. Methods: We used data from the Resuscitation Outcomes Consortium-CCC trial which included patients with OHCA across 10 North American sites during 2011-2015. We identified patients who underwent TTM for >12 hours. Serial temperature measures were evaluated between hypothermia start and end times with temperatures between consecutive measures imputed using a linear interpolation method. TTR was defined as percent of time between 32C and 36C during TTM (Fig A). Site was defined based on trial clusters, which represented hospitals served by the same EMS agency. Site-level variation in TTR<90% was evaluated in hierarchical logistic regression using median odds ratio (OR), after adjustment for patient-level factors. Results: A total of 2,695 patients across 49 clusters were included with a median of 45 (IQR: 34 - 52) patients per cluster. The median duration of hypothermia was 23 (IQR: 21 - 24) hours with a median time outside therapeutic range of 0.9 (IQR: 0.0 - 4.2) hours. The median TTR was 96.1% but 1,654 (61%) patients had at least one temperature outside the therapeutic range and 991 (37%) patients had a TTR <90%. There was large variation across sites in the proportion of patients with TTR<90%, ranging from 10% to 68%, with a median OR of 1.74 (Fig B). Conclusions: Within a large randomized controlled trial, more than 1 in 3 OHCA patients treated with TTM had a TTR <90%, with large variation in TTR across sites. These findings highlight an urgent need to focus on improving quality of TTM in clinical practice.

scholarly journals P075: Targeted temperature management was associated with worse outcomes of non-shockable out of hospital cardiac arrest

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S91-S91
Author(s):  
T. Kawano ◽  
B. Grunau ◽  
F. Scheuermeyer ◽  
C. Fordyce ◽  
R. Stenstrom ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Hospital Admission ◽  
Hospital Discharge ◽  
Neurological Outcome ◽  
Controlled Trial ◽  
Targeted Temperature Management ◽  
Temperature Management ◽  
Entire Cohort ◽  
Favorable Neurological Outcome ◽  
Hospital Cardiac Arrest

Introduction: We sought to assess the effect of in-hospital targeted temperature management (TTM) on outcomes of non-shockable out-of-hospital cardiac arrest (OHCA). Methods: This is a secondary analysis of a randomized controlled trial “A Randomized Trial of Continuous Versus Interrupted Chest Compressions in Out-of-Hospital Cardiac Arrest” (NCT01372748). We included non-traumatic comatose OHCAs with non-shockable rhythm who survived to hospital admission. Outcomes of interest were survival at hospital discharge and favorable neurological outcome (modified Rankin scale 0-3). We performed multivariable logistic regression, adjusting for baseline characteristics to determine the association between TTM and outcomes, compared to no TTM, for the entire cohort as well as for the propensity matched cohort. Results: Of 1,985 OHCAs who survived to hospital admission, 780 (39.3%) were managed with TTM. In TTM patients, 7.3 % patients survived to hospital discharge and 3.9 % had a favorable neurological outcome in contrast to 10.2 % and 6.1 %, respectively, in no TTM patients. Multivariable analyses demonstrated an association between TTM and decreased probability of both outcomes, compared to no TTM (adjusted ORs for survival: 0.67 95% CI 0.48–0.93, and for favorable neurological outcome: 0.57 95% CI 0.37–0.90). Propensity score matched analyses demonstrate the similar results. Conclusion: TTM might decrease the probability of neurologically intact survival for non-shockable OHCAs.

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 Extracorporeal life support in adult patients with out-of-hospital cardiac arrest

2021 ◽  
Vol 62 (08) ◽  
pp. 433-437 ◽  
Author(s):  
JH Lim ◽  
MJ Chakaramakkil ◽  
BKK Tan
Keyword(s):  
Cardiac Arrest ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Controlled Trial ◽  
Advanced Life Support ◽  
Adult Patients ◽  
Temperature Management ◽  
Randomised Controlled ◽  
Hospital Cardiac Arrest ◽  
Extracorporeal Cpr

The use of extracorporeal life support in cardiopulmonary resuscitation (CPR) of adult patients experiencing out-of-hospital cardiac arrest by the application of veno-arterial extracorporeal membrane oxygenation (ECMO) during cardiac arrest has been increasing over the past decade. This can be attributed to the encouraging results of extracorporeal CPR (ECPR) in multiple observational studies. To date, only one randomised controlled trial has compared ECPR to conventional advanced life support measures. Patient selection is crucial for the success of ECPR programmes. A rapid and organised approach is required for resuscitation, i.e. cannula insertion with ECMO pump initiation in combination with other aspects of post-cardiac arrest care such as targeted temperature management and early coronary reperfusion. The provision of an ECPR service can be costly, resource intensive and technically challenging, as limited studies have reported on its cost-effectiveness.

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