Document Detail

Hemodynamic effects of titrated norepinephrine in healthy versus endotoxemic sheep.
MedLine Citation:
PMID:  17621546     Owner:  NLM     Status:  MEDLINE    
In patients with sepsis and systemic inflammatory response syndrome, hemodynamic support is often complicated by a vascular hyporesponsiveness to exogenously administered norepinephrine. Although norepinephrine tachyphylaxis represents a significant clinical problem, the relationship between norepinephrine dosages and mean arterial pressure (MAP) in the presence of systemic inflammation is still not fully understood. This study was, therefore, designed as a prospective, controlled laboratory trial to elucidate the hemodynamic response to incremental norepinephrine doses in healthy and endotoxemic sheep. ANOVA demonstrated that a significantly higher mean infusion rate of norepinephrine was needed to increase MAP by 20 mmHg in endotoxemic versus healthy control sheep (P = 0.007). Whereas the goal-MAP was reached in 100% of healthy controls, it was achieved in only 80% during endotoxemia. Cardiac index increased significantly in healthy, but not in endotoxemic, sheep. Our findings confirm the presence of vascular hyporesponsiveness to norepinephrine in endotoxemia. In addition, this study demonstrates that the presence of systemic inflammation leads to an early hyporesponsiveness against norepinephrine which was caused by a drug-independent mechanism rather than a tachyphylaxis due to long-term administration of norepinephrine.
Matthias Lange; Katrin Bröking; Christoph Hucklenbruch; Christian Ertmer; Hugo Van Aken; Martin Lücke; Hans-Georg Bone; Martin Westphal
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of endotoxin research     Volume:  13     ISSN:  0968-0519     ISO Abbreviation:  J. Endotoxin Res.     Publication Date:  2007  
Date Detail:
Created Date:  2007-07-10     Completed Date:  2007-07-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9433350     Medline TA:  J Endotoxin Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  53-7     Citation Subset:  IM    
Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany. lange-m@anit.uni
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MeSH Terms
Blood Pressure / drug effects*,  physiology
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Administration Schedule
Endotoxemia / chemically induced,  drug therapy*,  physiopathology
Endotoxins / pharmacology
Norepinephrine / administration & dosage,  pharmacology*
Prospective Studies
Salmonella typhimurium
Vascular Resistance / drug effects*
Vasoconstrictor Agents / administration & dosage,  pharmacology*
Reg. No./Substance:
0/Endotoxins; 0/Vasoconstrictor Agents; 51-41-2/Norepinephrine

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