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Severe vagal response after endotoxin administration in humans
Lucas T G J van Eijk1, Peter Pickkers, Paul Smits
1Department of Intensive Care Medicine (519), University Medical Centre St. Radboud, PO box 9101, 6500 HB Nijmegen, The Netherlands.
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.