title: Cardiac effects of induction agents in the septic rat heart.
abstract: BACKGROUND
  The current debate about the side effects of induction agents, e.g. possible adrenal suppression through etomidate, emphasizes the relevance of choosing the correct induction agent in septic patients. However, cardiovascular depression is still the most prominent adverse effect of these agents, and might be especially hazardous in septic patients presenting with a biventricular cardiac dysfunction--or so-called septic cardiomyopathy. Therefore, we tested the dose-response direct cardiac effects of clinically available induction agents in an isolated septic rat heart model.
  
  
  METHODS
  A polymicrobial sepsis was induced via cecal ligation and single puncture. Hearts (n = 50) were isolated and randomly assigned to five groups, each receiving etomidate, s(+)-ketamine, midazolam, propofol, or methohexitone at concentrations of 1 x 10-8 to 1 x 10-4 M. Left ventricular pressure, contractility and lusitropy, and coronary flow were measured. Cardiac work, myocardial oxygen delivery, oxygen consumption, and percentage of oxygen extraction were calculated.
  
  
  RESULTS
  All of the induction agents tested showed a dose-dependent depression of cardiac work. Maximal cardiac work dysfunction occurred in the rank order of s(+)-ketamine (-6%) <etomidate (-17%) <methohexitone (-31%) <midazolam (-38%) <propofol (-50%). In addition, propofol showed a maximum decrease in contractility of -38%, a reduction in lusitropy of -44%, and a direct vasodilator effect by increasing coronary flow by +29%.
  
  
  CONCLUSIONS
  Overall, this study demonstrates that these tested drugs indeed have differential direct cardiac effects in the isolated septic heart. Propofol showed the most pronounced adverse direct cardiac effects. In contrast, S(+)ketamine showed cardiovascular stability over a wide range of concentrations, and might therefore be a beneficial alternative to etomidate.
authors.affiliation: Department of Anaesthesiology and Critical Care, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93053, Germany. york.zausig@klinik.uni-regensburg.de
authors.forename: York A
authors.initials: YA
authors.lastname: Zausig
authors.forename: Hendrik
authors.initials: H
authors.lastname: Busse
authors.forename: Dirk
authors.initials: D
authors.lastname: Lunz
authors.forename: Barbara
authors.initials: B
authors.lastname: Sinner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zink
authors.forename: Bernhard M
authors.initials: BM
authors.lastname: Graf
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005858:Germany; D006321:Heart / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008723:Methohexital / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008874:Midazolam / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D018686:Anesthetics, Intravenous; D007649:Ketamine; D008723:Methohexital; D008874:Midazolam; D015742:Propofol