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Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial- and brain injury

Authors :
Martin Abild Stengaard Meyer
Mette Bjerre
Sebastian Wiberg
Johannes Grand
Laust Emil Roelsgaard Obling
Anna Sina Pettersson Meyer
Jakob Josiassen
Martin Frydland
Jakob Hartvig Thomsen
Ruth Frikke-Schmidt
Jesper Kjaergaard
Christian Hassager
Source :
Meyer, M A S, Bjerre, M, Wiberg, S, Grand, J, Obling, L E R, Meyer, A S P, Josiassen, J, Frydland, M, Thomsen, J H, Frikke-Schmidt, R, Kjaergaard, J & Hassager, C 2023, ' Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial-and brain injury ', Resuscitation, vol. 184, 109676 . https://doi.org/10.1016/j.resuscitation.2022.109676, Abild Stengaard Meyer, M, Bjerre, M, Wiberg, S, Grand, J, Emil Roelsgaard Obling, L, Sina Pettersson Meyer, A, Josiassen, J, Frydland, M, Hartvig Thomsen, J, Frikke-Schmidt, R, Kjaergaard, J & Hassager, C 2023, ' Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial-and brain injury ', Resuscitation, vol. 184, 109676 . https://doi.org/10.1016/j.resuscitation.2022.109676
Publication Year :
2023

Abstract

Aim: To investigate how the inflammatory response after out-of-hospital cardiac arrest (OHCA) is modulated by blocking IL-6-mediated signalling with tocilizumab, and to relate induced changes to clinical status, myocardial- and brain injury. Methods: This is a preplanned substudy of the IMICA trial (ClinicalTrials.gov, NCT03863015). Upon admission 80 comatose OHCA patients were randomized to infusion of tocilizumab or placebo. Inflammation was characterized by a cytokine assay, CRP, and leukocyte differential count; myocardial injury by TnT and NT-proBNP; brain injury by neuron-specific enolase (NSE) and Neurofilament Light chain (NFL), while sequential organ assessment (SOFA) score and Vasoactive-Inotropic Score (VIS) represented overall clinical status. Results: Responses for IL-5, IL-6, IL-17, neutrophil as well as monocyte counts, and VIS were affected by tocilizumab treatment (all p < 0.05), while there was no effect on levels of NFL. IL-5 and IL-6 were substantially increased by tocilizumab, while IL-17 was lowered. Neutrophils and monocytes were lower at 24 and 48 hours, and VIS was lower at 24 hours, for the tocilizumab group compared to placebo. Multiple correlations were identified for markers of organ injury and clinical status versus inflammatory markers; this included correlations of neutrophils and monocytes with TnT, NSE, NFL, SOFA- and VIS score for the tocilizumab but not the placebo group. NT-proBNP, NFL and SOFA score correlated with CRP in both groups. Conclusions: Treatment with tocilizumab after OHCA modulated the inflammatory response with notable increases for IL-5, IL-6, and decreases for neutrophils and monocytes, as well as reduced vasopressor and inotropy requirements.

Details

Language :
English
Database :
OpenAIRE
Journal :
Meyer, M A S, Bjerre, M, Wiberg, S, Grand, J, Obling, L E R, Meyer, A S P, Josiassen, J, Frydland, M, Thomsen, J H, Frikke-Schmidt, R, Kjaergaard, J & Hassager, C 2023, ' Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial-and brain injury ', Resuscitation, vol. 184, 109676 . https://doi.org/10.1016/j.resuscitation.2022.109676, Abild Stengaard Meyer, M, Bjerre, M, Wiberg, S, Grand, J, Emil Roelsgaard Obling, L, Sina Pettersson Meyer, A, Josiassen, J, Frydland, M, Hartvig Thomsen, J, Frikke-Schmidt, R, Kjaergaard, J & Hassager, C 2023, ' Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial-and brain injury ', Resuscitation, vol. 184, 109676 . https://doi.org/10.1016/j.resuscitation.2022.109676
Accession number :
edsair.doi.dedup.....9a14cdc5c535e007b55e3599dc852155
Full Text :
https://doi.org/10.1016/j.resuscitation.2022.109676