1. Severe vagal response after endotoxin administration in humans
- Author
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Eijk, Lucas T. G. J., Pickkers, Peter, Smits, Paul, Bouw, Martijn P. W. J. M., and van der Hoeven, Johannes G.
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Endotoxins -- Dosage and administration ,Endotoxins -- Complications and side effects ,Endotoxins -- Research ,Fainting -- Risk factors ,Bradycardia -- Risk factors ,Health care industry - Abstract
Byline: Lucas T. G. J. Eijk (1,2), Peter Pickkers (1,2), Paul Smits (2), Martijn P. W. J. M. Bouw (1), Johannes G. van der Hoeven (1) Keywords: Endotoxin/lipopolysaccharide; Endotoxemia; Human; Adverse effects; Bezold-Jarisch reflex; Vasovagal syncope Abstract: Objective Endotoxin administration to humans is a common means to study systemic inflammation. Worldwide, thousands of volunteers have received endotoxin, and adverse events are rarely reported. The aim of this report was to increase awareness of specific risks of the intravenous administration of endotoxin to human volunteers. Design Report of four cases who developed severe bradycardia or protracted asystole after administration of endotoxin. Interviews with investigators at three large centers that conduct normal volunteer endotoxin studies. Setting Clinical research unit. Cases Four subjects developed severe bradycardia or protracted asystole, approximately 1 h after administration of endotoxin. Further analyses revealed that the subjects had a history of vasovagal syncope or a positive head-tilt test, indicating increased vagal sensitivity. Relative volume depletion associated with fasting overnight may have predisposed these subjects to this condition. Conclusions These responses are very rare and are likely due to the cardioinhibitory Bezold-Jarisch reflex. A thorough screening regarding a history of vagal sensitivity and liberal oral or intravenous fluid administration prior to and during the endotoxin challenge may decrease the risk of these events. Author Affiliation: (1) Department of Intensive Care Medicine (519), University Medical Centre St. Radboud, PO box 9101, 6500 HB, Nijmegen, The Netherlands (2) Department of Pharmacology-Toxicology, University Medical Centre St. Radboud, Nijmegen, The Netherlands Article History: Registration Date: 24/09/2004 Received Date: 17/02/2004 Accepted Date: 13/09/2004 Online Date: 26/10/2004 Article note: P. Pickkers is a recipient of a Clinical Fellowship grant of the Netherlands Organisation for Scientific Research (ZonMw)
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- 2004