Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial- and brain injury
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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. / Meyer, Martin Abild Stengaard; Bjerre, Mette; Wiberg, Sebastian; Grand, Johannes; Obling, Laust Emil Roelsgaard; Meyer, Anna Sina Pettersson; Josiassen, Jakob; Frydland, Martin; Thomsen, Jakob Hartvig; Frikke-Schmidt, Ruth; Kjaergaard, Jesper; Hassager, Christian.
In: Resuscitation, Vol. 184, 109676, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Modulation of inflammation by treatment with tocilizumab after out-of-hospital cardiac arrest and associations with clinical status, myocardial- and brain injury
AU - Meyer, Martin Abild Stengaard
AU - Bjerre, Mette
AU - Wiberg, Sebastian
AU - Grand, Johannes
AU - Obling, Laust Emil Roelsgaard
AU - Meyer, Anna Sina Pettersson
AU - Josiassen, Jakob
AU - Frydland, Martin
AU - Thomsen, Jakob Hartvig
AU - Frikke-Schmidt, Ruth
AU - Kjaergaard, Jesper
AU - Hassager, Christian
N1 - Publisher Copyright: © 2022 The Author(s)
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1016/j.resuscitation.2022.109676
DO - 10.1016/j.resuscitation.2022.109676
M3 - Journal article
C2 - 36572373
AN - SCOPUS:85147376278
VL - 184
JO - Resuscitation
JF - Resuscitation
SN - 0300-9572
M1 - 109676
ER -
ID: 341276506