Anna S P Meyer1, Per I Johansson2, Jesper Kjaergaard3, Martin Frydland4, Martin A S Meyer5, Hanne Hee Henriksen6, Jakob H Thomsen7, Sebastian C Wiberg8, Christian Hassager9, Sisse R Ostrowski10. 1. Section for Transfusion Medicine, Blood Bank, Rigshospitalet, 2034, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; Dept. of Cardiology, Rigshospitalet, 2143, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Electronic address: anna.sina.pettersson.meyer.02@regionh.dk. 2. Section for Transfusion Medicine, Blood Bank, Rigshospitalet, 2034, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; Dept. of Surgery, University of Texas Health Medical School, 6410 Fannin Street UPB 1100, Houston, TX 77030, USA. Electronic address: per.johansson@regionh.dk. 3. Dept. of Cardiology, Rigshospitalet, 2143, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Electronic address: jesper.kjaergaard.05@regionh.dk. 4. Dept. of Cardiology, Rigshospitalet, 2143, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Electronic address: martin.frydland.01@regionh.dk. 5. Section for Transfusion Medicine, Blood Bank, Rigshospitalet, 2034, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: martin.as.meyer@gmail.com. 6. Section for Transfusion Medicine, Blood Bank, Rigshospitalet, 2034, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: hanne.hee.henriksen@regionh.dk. 7. Dept. of Cardiology, Rigshospitalet, 2143, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Electronic address: Jakob.hartvig.thomsen@regionh.dk. 8. Dept. of Cardiology, Rigshospitalet, 2143, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Electronic address: sebastian.christoph.wiberg@regionh.dk. 9. Dept. of Cardiology, Rigshospitalet, 2143, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. Electronic address: christian.hassager@regionh.dk. 10. Section for Transfusion Medicine, Blood Bank, Rigshospitalet, 2034, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: sisse.rye.ostrowski@regionh.dk.
Abstract
OBJECTIVE: An increasingly recognized prognostic factor for out-of-hospital-cardiac-arrest (OHCA) patients is the ischemia-reperfusion injury after restored blood circulation. Endothelial injury is common in patients resuscitated from cardiac arrest and is associated with poor outcome. This study was designed to investigate if iloprost infusion, a prostacyclin analogue, reduces endothelial damage in OHCA patients. METHODS:50 patients were randomized in a placebo controlled double-blinded trial and allocated 1:2 to 48-hours iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Endothelial biomarkers (soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), vascular endothelial cadherine (VEcad), nucleosomes) and sympathoadrenal activation (epinephrine/norepinephrine) from baseline to 48 and 96-hours were evaluated. RESULTS:Iloprost infusion did not influence endothelial biomarkers by the 48-hour endpoint. A rebound effect was observed with higher biomarker plasma values in the iloprost group (sTM p=0.02; Syndecan p=0.004; nucleosomes p<0.001; VEcad p<0.03) after 96-hours. There was a significant difference in 180-day mortality in favor of placebo. There was no difference regarding total adverse events between groups (p=0.73). Two patients were withdrawn in the iloprost group due to hypotension. CONCLUSIONS: The administration of low-dose iloprost (1ng/kg/min) to OHCA patients did not significantly influence endothelial biomarkers as measured by the 48- hour endpoint. A rebound effect was however observed in the 96-hour statistical model, with increasing endothelial biomarker levels after cessation of the iloprost-infusion.
RCT Entities:
OBJECTIVE: An increasingly recognized prognostic factor for out-of-hospital-cardiac-arrest (OHCA) patients is the ischemia-reperfusion injury after restored blood circulation. Endothelial injury is common in patients resuscitated from cardiac arrest and is associated with poor outcome. This study was designed to investigate if iloprost infusion, a prostacyclin analogue, reduces endothelial damage in OHCA patients. METHODS: 50 patients were randomized in a placebo controlled double-blinded trial and allocated 1:2 to 48-hours iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Endothelial biomarkers (soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), vascular endothelial cadherine (VEcad), nucleosomes) and sympathoadrenal activation (epinephrine/norepinephrine) from baseline to 48 and 96-hours were evaluated. RESULTS: Iloprost infusion did not influence endothelial biomarkers by the 48-hour endpoint. A rebound effect was observed with higher biomarker plasma values in the iloprost group (sTM p=0.02; Syndecan p=0.004; nucleosomes p<0.001; VEcad p<0.03) after 96-hours. There was a significant difference in 180-day mortality in favor of placebo. There was no difference regarding total adverse events between groups (p=0.73). Two patients were withdrawn in the iloprost group due to hypotension. CONCLUSIONS: The administration of low-dose iloprost (1ng/kg/min) to OHCA patients did not significantly influence endothelial biomarkers as measured by the 48- hour endpoint. A rebound effect was however observed in the 96-hour statistical model, with increasing endothelial biomarker levels after cessation of the iloprost-infusion.
Authors: Martin Abild Stengaard Meyer; Sebastian Wiberg; Johannes Grand; Anna Sina Pettersson Meyer; Laust Emil Roelsgaard Obling; Martin Frydland; Jakob Hartvig Thomsen; Jakob Josiassen; Jacob Eifer Møller; Jesper Kjaergaard; Christian Hassager Journal: Circulation Date: 2021-03-22 Impact factor: 29.690
Authors: Christoph Schriefl; Christian Schoergenhofer; Florian Ettl; Michael Poppe; Christian Clodi; Matthias Mueller; Juergen Grafeneder; Bernd Jilma; Ingrid Anna Maria Magnet; Nina Buchtele; Magdalena Sophie Boegl; Michael Holzer; Fritz Sterz; Michael Schwameis Journal: Front Med (Lausanne) Date: 2021-06-09
Authors: Martin A S Meyer; Sebastian Wiberg; Johannes Grand; Jesper Kjaergaard; Christian Hassager Journal: Trials Date: 2020-10-20 Impact factor: 2.279
Authors: Nicolai Rytter; Howard Carter; Peter Piil; Henrik Sørensen; Thomas Ehlers; Frederik Holmegaard; Christoffer Tuxen; Helen Jones; Dick Thijssen; Lasse Gliemann; Ylva Hellsten Journal: J Am Heart Assoc Date: 2020-07-29 Impact factor: 5.501