Inotropic Support During Experimental Endotoxemic Shock: Part I. The Effects of Levosimendan on Splanchnic Perfusion

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Abstract

BACKGROUND: Septic shock may cause splanchnic hypoperfusion. We hypothesized that levosimendan would improve systemic and hepatosplanchnic perfusion during endotoxemic shock. METHODS: In 16 anesthetized pigs (31.4 +/- 3.4 kg), a jugular vein, a carotid artery, the Pulmonary artery (thermodilution), the portal vein, and a hepatic vein were cannulated for hemodynamic monitoring and blood sampling. Ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery (SMA). In addition to 30 mL/kg of dextran 70 given before baseline, all animals received 1.0 mL . kg(-1) . h(-1) of IV fluids throughout the experiment. An endotoxin infusion (2 mu g . kg(-1) . h(-1)) was given for 300 min; 100 min after the start of endotoxin, the pigs were randomized to receive levosimendan (50 mu g . kg(-1) . h(-1), n = 8) or placebo (n = 8). To evaluate the isolated effects of endotoxemia, all data before randomization were pooled into one group. Data were analyzed by analysis of variance and presented as mean +/- SEM. RESULTS: Endotoxemia (t = 90 min, pooled data) decreased systemic vascular resistance (SVR, 2526 +/- 203 to 1946 +/- 122 dyn . s . cm(-5), P = 0.003) and mean arterial blood pressure (MAP, 109 +/- 6 to 84 +/- 3 mm Hg, P < 0.05), whereas heart rate (66 +/- 4 to 98 +/- 8 bpm), and mean pulmonary arterial pressure (MPAP, 20 +/- 1 to 38 +/- 2 mm Hg) increased (P < 0.001). Cardiac output (CO, 3.4 +/- 0.2 L/min) and systemic oxygen delivery (414 +/- 33 mL/min) were unchanged, but blood flows in the SMA (575 +/- 34 to 392 +/- 38 mL/min) and the portal vein (881 +/- 62 to 568 +/- 39 mL/min) decreased (P < 0.001). Although hepatic arterial blood flows increased (36 +/- 8 to 219 +/- 38 mL/min), gut (114 +/- 11 to 84 +/- 7 mL/min) and hepatic (94 +/- 11 to 67 +/- 8 mL/min) oxygen deliveries decreased (P < 0.05). At t = 300 min, the levosimendan group showed lower MPAP (39 +/- 3 vs 49 +/- 2 mm Hg, P = 0.025), lower SVR (2158 +/- 186 vs 3069 +/- 370 dyn . s . cm(-5), P = 0.052), and lower MAP (55 +/- 9 vs 87 +/- 9 mm Hg, P < 0.001) than the control group. In both groups, CO, portal vein, and hepatic arterial blood flows decreased (P < 0.001); the mean values for the levosimendan group at t = 300 min were 2.0 +/- 0.4 L/min, 390 +/- 83 mL/min, and 36 +/- 12 mL/min, respectively. SMA blood flow decreased only in the levosimendan group (432 +/- 40 to 320 +/- 78 mL/min, P < 0.001), whereas gut oxygen delivery decreased in the levosimendan (85 +/- 12 to 63 +/- 12 mL/min, P < 0.001) and in the control (83 +/- 6 to 59 +/- 3 mL/min, P = 0.03) groups. CONCLUSION: Levosimendan administered after the establishment of endotoxemic shock to pigs receiving moderate fluid resuscitation prevented further increases in MPAP and maintained a low SVR. There were, however, no improvements in CO, MAP decreased, and levosimendan neither prevented the development of circulatory shock nor improved hepatosplanchnic perfusion. (Anesth Analg 2009:109:1568-75)

Details

Authors
  • Doris Cunha Goncalves
  • Valéria Perez de Sá
  • Edgars Grins
  • Peter Dahm
  • Johan Thörne
  • Sten Blomquist
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Anesthesiology and Intensive Care
Original languageEnglish
Pages (from-to)1568-1575
JournalAnesthesia and Analgesia
Volume109
Issue number5
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes