Severe vagal response after endotoxin administration in humans

Eijk, L.T.G.J. van; Pickkers, Peter; Smits, Paul; Bouw, Martijn P.W.J.M.; Hoeven, Johannes G. van der

doi:10.1007/s00134-004-2477-0

Cited by 28 publications

(19 citation statements)

References 9 publications

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“…In the previous 3 decades, small doses of endotoxin (2-4 ng/ kg, equivalent to 14-28 EU in a 70-kg adult), administered intravenously to thousands of volunteers to study acute inflammatory responses, have generally been found to be safe, although 4 cases of severe bradycardia or protracted asystole have been reported [12]. A study of patients with septic shock showed median plasma endotoxin loads of 13,000 EU [13], and a self-administered intravenous endotoxin dose of 1 mg (100,000 EU) resulted in shock and multiple-organ dysfunction in a patient [14].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Bacterial Load, Species Virulence, and Transfusion Reaction with Transfusion of Bacterially Contaminated Platelets

Good²,

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Relationship between Bacterial Load, Species Virulence, and Transfusion Reaction with Transfusion of Bacterially Contaminated Platelets

Good²,

et al. 2008

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“…Besides the decrease in symptoms, it is also believed that prehydration decreases the risk of a severe vagal response during human endotoxemia. 22 It is advisable to administer prehydration in human endotoxemia experiments, but when used as a model to measure inflammation or the effects of therapeutic interventions on cytokine responses, a standardised protocol should be applied.…”

Section: Discussionmentioning

confidence: 99%

Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia

Dorresteijn¹,

Eijk²,

Netea³

et al. 2005

J. Endotoxin Res.

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Clinical experience suggests that the administration of fluids in human endotoxemia reduces symptoms. In the present study, the effects of a standardised fluid protocol on symptoms, inflammatory and hemodynamic parameters in human endotoxemia are determined. With approval of the local ethics committee, 16 healthy volunteers received 2 ng/kg of Escherichia coli endotoxin (O:113). After an overnight fast, nine subjects received 1.5 l of 2.5% glucose/0.45% NaCl the hour prior to the endotoxin administration and 150 ml/h during the course of the experiment ('prehydrated group'). Seven subjects only received a continuous infusion of 75 ml/h during the experiment ('non-prehydrated group'). The course of inflammatory parameters and symptoms were determined and mean arterial pressure, heart rate and forearm blood flow were measured. In the prehydrated group, TNF-alpha increased to 522 +/- 63 pg/ml (mean +/- SEM) while the maximum in the non-prehydrated group was 927 +/- 187 pg/ml (P < 0.04). IL-10 increased similarly in both groups (non-prehydrated 117 +/- 18 pg/ml and prehydrated 99 +/- 18 pg/ml; P = NS). The prehydrated group had a significantly lower (P < 0.004) symptom score and recovered sooner (P = 0.004). Endotoxin-induced changes in hemodynamics revealed no significant differences between groups. We demonstrate that prehydration in experimental human endotoxemia significantly shifts the cytokine balance towards a more anti-inflammatory pattern. This effect is associated with a reduction in symptoms, whereas the changes in hemodynamic parameters are not influenced by prehydration.

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“…To prevent vasovagal responses subjects were prehydrated by infusion of 1.5 L glucose 2.5%/NaCl 0.45% in one hour28. Purified lipopolysaccharide (LPS, US Standard Escherichia coli O:113 endotoxin) was obtained from the Pharmaceutical Development Section of the National Institutes of Health (Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin

Kiers

Koch

Hamers

et al. 2017

Sci Rep

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Investigating the systemic inflammatory response in patients with critical illness such as sepsis, trauma and burns is complicated due to uncertainties about the onset, duration and severity of the insult. Therefore, in vivo models of inflammation are essential to study the pathophysiology and to evaluate immunomodulatory therapies. Intravenous bolus administration of endotoxin to healthy volunteers is a well-established model of a short-lived systemic inflammatory response, characterized by increased plasma cytokine levels, flu-like symptoms and fever. In contrast, patients suffering from systemic inflammation are often exposed to inflammatory stimuli for an extended period of time. Therefore, continuous infusion of endotoxin may better reflect the kinetics of the inflammatory response encountered in these patients. Herein, we characterize a novel model of systemic inflammation elicited by a bolus infusion of 1 ng/kg, followed by a 3hr continuous infusion of 1 ng/kg/h of endotoxin in healthy volunteers, and compared it with models of bolus administrations of 1 and 2 ng/kg of endotoxin. The novel model was well-tolerated and resulted in a more pronounced increase in plasma cytokine levels with different kinetics and more prolonged symptoms and fever compared with the bolus-only models. Therefore, the continuous endotoxin infusion model provides novel insights into kinetics of the inflammatory response during continuous inflammatory stimuli and accommodates a larger time window to evaluate immunomodulating therapies.

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Severe vagal response after endotoxin administration in humans

Cited by 28 publications

References 9 publications

Relationship between Bacterial Load, Species Virulence, and Transfusion Reaction with Transfusion of Bacterially Contaminated Platelets

Relationship between Bacterial Load, Species Virulence, and Transfusion Reaction with Transfusion of Bacterially Contaminated Platelets

Iso-osmolar prehydration shifts the cytokine response towards a more anti-inflammatory balance in human endotoxemia

Characterization of a model of systemic inflammation in humans in vivo elicited by continuous infusion of endotoxin

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