• Anesthesiology · Aug 2015

    Cyclopropyl-methoxycarbonyl Metomidate: Studies in a Lipopolysaccharide Inflammatory Model of Sepsis.

    • Peter Santer, Ervin Pejo, Yan Feng, Wei Chao, and Douglas E Raines.
    • From the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.
    • Anesthesiology. 2015 Aug 1; 123 (2): 368-76.

    BackgroundCyclopropyl-methoxycarbonyl metomidate (CPMM) is a rapidly metabolized etomidate analog that is currently in clinical trials. The goal of this study is to assess CPMM's potential value as an anesthetic agent for use in patients with sepsis by defining its actions in an acute inflammatory model of sepsis.MethodsEscherichia coli lipopolysaccharide (1 mg/kg) was injected intravenously into Sprague-Dawley rats. Thirty minutes later, CPMM, etomidate, or vehicle (n = 8 per group) was infused for 1 h. Plasma adrenocorticotropic hormone, corticosterone, and cytokine (interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α) concentrations were measured before, during, and after infusion.ResultsAfter lipopolysaccharide injection, adrenocorticotropic hormone concentrations changed similarly over time in all three groups. Compared with vehicle group rats, CPMM group rats had significantly lower corticosterone concentrations at only a single study time point during infusion and no significant differences in cytokine concentrations at any time during the study period. Compared with etomidate group rats, CPMM group rats had significantly higher corticosterone concentrations (up to nine-fold) during and after hypnotic infusion. Cytokine concentrations in CPMM group rats and vehicle group rats were not significantly different, but they were significantly lower than those in etomidate group rats. Postinfusion mortality was 40% in etomidate group rats and 0% in CPMM and vehicle group rats.ConclusionCompared with etomidate, CPMM produces less adrenocortical suppression, lower plasma cytokine concentrations, and improved survival in a lipopolysaccharide inflammatory model of sepsis. These results suggest that CPMM may be a safer alternative to etomidate in patients with sepsis.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…