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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Martich GD, Boujoukos AJ, Suffredini AF (1993) Response of man to endotoxin. Immunobiology 187:403–416
Suffredini AF, Fromm RE, Parker MM, Brenner M, Kovacs JA, Wesley RA, Parrillo JE (1989) The cardiovascular response of normal humans to the administration of endotoxin. N Engl J Med 321:280–287
Williams WV, Fullerton T, Fox JC, Enslin MB, Murray L, Jorkasky D (2000) Asystole following endotoxin administration. J Endotoxin Res 6:303–306
Richardson RP, Rhyne CD, Fong Y, Hesse DG, Tracey KJ, Marano MA, Lowry SF, Antonacci AC, Calvano S (1989) Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Influence of elicited hormones and cytokines. Ann Surg 210:239–245
Abboud FM (1989) Ventricular syncope: is the heart a sensory organ? N Engl J Med 320:390–392
Ottaway CA, Fong IW, da Silva B, Singer W, Karrass L (1998) Integrative aspects of a human model of endotoxemia. Can J Physiol Pharmacol 76:473–478
Oberg B, Thoren P (1972) Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat. A possible cause of the vaso-vagal reaction. Acta Physiol Scand 85:164–173
Barriot P, Riou B (1987) Hemorrhagic shock with paradoxical bradycardia. Intensive Care Med 13:203–207
Brignole M, Alboni P, Benditt D, Bergfeldt L, Blanc JJ, Bloch Thomsen PE, van Dijk JG, Fitzpatrick A, Hohnloser S, Janousek J, Kapoor W, Kenny RA, Kulakowski P, Moya A, Raviele A, Sutton R, Theodorakis G, Wieling W (2001) Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 22:1256–1306
Acknowledgments
We would like to thank Dr. T. van der Poll, Academic Medical Centre Amsterdam, The Netherlands; Dr. A.F. Suffredini, National Institutes of Health, Bethesda, USA; and Dr. R. Noveck, MDS Pharma Services, New Orleans, USA, for their helpful advice, sharing the data of their subjects, and critical review of the manuscript
Author information
Authors and Affiliations
Corresponding author
Additional information
P. Pickkers is a recipient of a Clinical Fellowship grant of the Netherlands Organisation for Scientific Research (ZonMw)
Rights and permissions
About this article
Cite this article
van Eijk, L.T.G.J., Pickkers, P., Smits, P. et al. Severe vagal response after endotoxin administration in humans. Intensive Care Med 30, 2279–2281 (2004). https://doi.org/10.1007/s00134-004-2477-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-004-2477-0