title: Enoximone in contrast to dobutamine improves hepatosplanchnic function in fluid-optimized septic shock patients.
abstract: OBJECTIVE
  To investigate the impact of dobutamine and enoximone on hepatosplanchnic perfusion and function in fluid-optimized septic patients.
  
  
  METHODS
  Prospective, randomized, double-blinded interventional study.
  
  
  METHODS
  Intensive care unit of a university hospital.
  
  
  METHODS
  Forty-eight septic shock patients were examined within 12 hrs after onset of septic shock. Patients were conventionally resuscitated, achieving an optimal pulmonary artery occlusion pressure at which the left ventricular stroke work was on the maximal plateau. Liver blood flow was estimated by venous suprahepatic catheterization using the continuous indocyanine green infusion technique. Microsomal liver function was assessed by the plasma appearance of monoethylglycinexylidide, and release of hepatic tumor necrosis factor-alpha (TNF-alpha) was measured to estimate the severity of hepatic ischemia-reperfusion syndrome.
  
  
  METHODS
  Patients were randomly treated with dobutamine or enoximone. Within the first 10 hrs after baseline measurements, the dosage was increased until no further increase in the left ventricular stroke work index occurred. Then, positive inotropes were kept constant throughout the study.
  
  
  RESULTS
  Measurements were performed at baseline and after 12 and 48 hrs after baseline measurements. Cardiac index, systemic oxygen delivery, systemic oxygen consumption, and liver blood flow increased significantly in both groups during treatment (p <.01) without a significant difference between groups. Fractional liver blood flow (liver blood flow/cardiac index) did not change in the enoximone group and showed a significant but only minor (median, 10%) decrease in the dobutamine group (p <.05 after 12 hrs and p <.01 after 48 hrs vs. baseline). After 12 hrs of enoximone treatment, monoethylglycinexylidide kinetics and hepatosplanchnic oxygen consumption demonstrated a significant increase (p <.05). The release of hepatic TNF-alpha after 12 hrs of dobutamine treatment was twice as high (p <.05) as during enoximone.
  
  
  CONCLUSIONS
  The increase in hepatosplanchnic oxygen consumption, together with an increased lignocaine metabolism and decreased release of hepatic TNF-alpha, indicates improved hepatosplanchnic function and antiinflammatory properties after 12 hrs of enoximone treatment. Therefore, if the inflammatory response should be attenuated in high-risk patients, administration of enoximone in fluid-optimized septic shock patients may be favorable compared with dobutamine.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, the University Hospital Charité, Campus Mitte, Humboldt-University of Berlin, Schumannstr. 20/21, 10098 Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kern
authors.forename: T
authors.initials: T
authors.lastname: Schröder
authors.forename: M
authors.initials: M
authors.lastname: Kaulfuss
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: W J
authors.initials: WJ
authors.lastname: Kox
authors.forename: C D
authors.initials: CD
authors.lastname: Spies
mesh_terms: D018806:APACHE; D000368:Aged; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use*; D004311:Double-Blind Method; D017335:Enoximone / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008012:Lidocaine / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D013152:Splanchnic Circulation / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D014409:Tumor Necrosis Factor-alpha; D004280:Dobutamine; D008012:Lidocaine; D017335:Enoximone