title: Somatostatin infusion increases intestinal ischemia and does not improve vasoconstrictor response to norepinephrine in ovine endotoxemia.
abstract: Hemodynamic support of patients with septic shock is often complicated by a tachyphylaxis against exogenous catecholamines. Because an increase in somatotropic hormones may play a pivotal role in the regulation of the inflammatory response to endotoxin, intravenous supplementation of the neuroendocrine hormone somatostatin (SOMA) may attenuate hemodynamic dysfunction resulting from endotoxemia. The objective of the present study was to assess the short-term effects of SOMA alone and in combination with norepinephrine (NE) on cardiopulmonary hemodynamics, global oxygen transport, plasma nitrate/nitrite levels, and intestinal integrity compared with single NE therapy in ovine endotoxemia. After a baseline measurement in healthy sheep (n = 16) had been performed, Salmonella typhosa endotoxin was centrally infused (10 ng x kg(-1) x min(-1)) to induce a hypotensive-hyperdynamic circulation using an established protocol. Animals surviving 16 h of endotoxemia were randomly assigned to one of the two groups (each n = 6). Sheep allocated to the SOMA + NE group received SOMA as a loading dose of 10.5 microg x kg(-1) x min(-1) for 1 h, followed by a continuous infusion of 3.5 microg x kg(-1) x min(-1) for the next 2 h. After the SOMA loading dose had been given, NE was concurrently infused (0.3 microg x kg(-1) x min(-1)) for 2 h. In the NE group (control), NE (0.3 microg x kg(-1) x min(-1)) was continuously infused for 3 h. Endotoxemia caused a decrease in MAP and systemic vascular resistance index in both groups, but to a greater extent in the NE group. Arterial hypotension persisted despite administration of the study drugs. Infusion of SOMA alone and in combination with NE did not significantly increase systemic vascular resistance index. Neither SOMA nor NE infusion alone affected pulmonary vasoregulation. Plasma nitrate/nitrite levels did not differ between groups. However, combined infusion of SOMA and NE significantly increased arterial lactate concentrations, oxygen consumption index, and oxygen extraction rate (P < 0.05) and aggravated ileal mucosal injury. In conclusion, short-term treatment with SOMA failed to attenuate cardiocirculatory shock resulting from endotoxemia and did not improve vasopressor response to NE. In addition, combined SOMA and NE therapy resulted in intestinal injury. Therefore, SOMA does not seem to represent a therapeutic option to treat arterial hypotension resulting from sepsis and systemic inflammatory response syndrome.
authors.affiliation: Department of Anesthesiology and Intensive Care, University Hospital of Muenster, Muenster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lauer
authors.forename: Fritz
authors.initials: F
authors.lastname: Daudel
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Traber
authors.forename: Jerzy-Roch
authors.initials: JR
authors.lastname: Nofer
authors.forename: Christian
authors.initials: C
authors.lastname: Ertmer
authors.forename: Andrea
authors.initials: A
authors.lastname: Morelli
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Matthias
authors.initials: M
authors.lastname: Lange
authors.forename: Sebastian
authors.initials: S
authors.lastname: Rehberg
authors.forename: Björn
authors.initials: B
authors.lastname: Ellger
authors.forename: Henning D
authors.initials: HD
authors.lastname: Stubbe
authors.forename: Claudius
authors.initials: C
authors.lastname: Kruse
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bone
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007022:Hypotension; D007511:Ischemia / Q000503:physiopathology*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D012756:Sheep; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D009566:Nitrates; D009573:Nitrites; D014662:Vasoconstrictor Agents; D013004:Somatostatin; D009638:Norepinephrine