title: The effects of terlipressin on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.
abstract: OBJECTIVE
  Although terlipressin (TP) may improve renal function in cirrhotic patients, its use in sepsis remains controversial due to concerns about regional ischemia. We investigated the effects of TP on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.
  
  
  METHODS
  We studied thirteen merino ewes in a university physiology laboratory using a randomized controlled cross over design. We implanted flow probes around the pulmonary, circumflex coronary, superior mesenteric, renal and iliac arteries. We injected live Escherichia coli and induced hyperdynamic sepsis. We treated animals with either bolus vehicle or a single dose of TP (sTP = 1 mg). In a second group, after 1 mg of TP, two additional bolus injections (mTP) of 0.5 mg were given at 2 hourly intervals.
  
  
  RESULTS
  sTP (1 mg) significantly increased mean arterial pressure (MAP) (74 to 89 mmHg; P<0.0001) creatinine clearance (31 to 85 mL/min; P<0.0001) and urine output (24 to 307 mL/hr) (P<0.0001). However, it decreased CO (5.7 to 3.9 L/min; p<0.0001), coronary blood flow (CBF) (43 to 32 mL/min; p<0.0001) and mesenteric blood flow (MBF) (944 to 625 mL/min; p = 0.004) and increased blood lactate (2.1 to 4.0 mmol/L; p<0.0001). Extra doses of TP caused little additional effect.
  
  
  CONCLUSIONS
  In hyperdynamic sepsis, bolus TP transiently improves MAP and renal function, but reduces CO, CBF and MBF, and increases blood lactate. Caution should be applied when prescribing bolus TP in septic patients at risk of coronary or mesenteric ischemia.
authors.affiliation: Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.forename: Paolo
authors.initials: P
authors.lastname: Calzavacca
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Clive N
authors.initials: CN
authors.lastname: May
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects*; D012756:Sheep; D012772:Shock, Septic / Q000188:drug therapy* / Q000382:microbiology; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D008236:Lypressin; D000077585:Terlipressin