Research
Comparison of cardiac, hepatic, and renal effects of arginine vasopressin and noradrenaline during porcine fecal peritonitis: a randomized controlled trial
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* Corresponding author: Peter Radermacher peter.radermacher@uni-ulm.de
- † Equal contributors
1 Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für Anästhesiologie, Universitätsklinikum, Steinhövelstrasse 9, 89075 Ulm, Germany
2 Abteilung Thorax- und Gefäßchirurgie, Universitätsklinikum, Steinhövelstrasse 9, 89075 Ulm, Germany
3 Instituto di Anestesiologia e Rianimazione dell'Università degli Studi di Milano, Azienda Ospedaliera, Polo Universitario San Paolo, Via di Rudin 8, 20142 Milan, Italy
4 Abteilung Pathologie, Universitätsklinikum, Albert-Einstein-Allee 11, 89081 Ulm, Germany
5 Laboratoire HIFIH, UPRES-EA 3859, IFR 132, Universitè d'Angers, Département de Réanimation Médicale et de Médecine Hyperbare, Centre Hospitalo- Universitaire, 4, rue Larrey, 49933 Angers cedex 9, France
6 Abteilung für Anästhesiologie und Schmerztherapie, Landeskrankenhaus Sterzing, Margarethenstraße 24, 39049 Sterzing, Italy
7 Ferring Research Institute Inc., 3550 General Atomics Court, Bldg 2 Room 444, San Diego, CA 92121, USA
8 Semmelweis Egyetem, Aneszteziológiai és Intenzív Terápiás Klinika, Kútvölgyi út 4., 1125 Budapest, Hungary
Critical Care 2009, 13:R113 doi:10.1186/cc7959
Published: 10 July 2009Abstract
Introduction
Infusing arginine vasopressin (AVP) in vasodilatory shock usually decreases cardiac output and thus systemic oxygen transport. It is still a matter of debate whether this vasoconstriction impedes visceral organ blood flow and thereby causes organ dysfunction and injury. Therefore, we tested the hypothesis whether low-dose AVP is safe with respect to liver, kidney, and heart function and organ injury during resuscitated septic shock.
Methods
After intraperitoneal inoculation of autologous feces, 24 anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned to noradrenaline alone (increments of 0.05 μg/kg/min until maximal heart rate of 160 beats/min; n = 12) or AVP (1 to 5 ng/kg/min; supplemented by noradrenaline if the maximal AVP dosage failed to maintain mean blood pressure; n = 12) to treat sepsis-associated hypotension. Parameters of systemic and regional hemodynamics (ultrasound flow probes on the portal vein and hepatic artery), oxygen transport, metabolism (endogenous glucose production and whole body glucose oxidation derived from blood glucose isotope and expiratory 13CO2/12CO2 enrichment during 1,2,3,4,5,6-13C6-glucose infusion), visceral organ function (blood transaminase activities, bilirubin and creatinine concentrations, creatinine clearance, fractional Na+ excretion), nitric oxide (exhaled NO and blood nitrate + nitrite levels) and cytokine production (interleukin-6 and tumor necrosis factor-α blood levels), and myocardial function (left ventricular dp/dtmax and dp/dtmin) and injury (troponin I blood levels) were measured before and 12, 18, and 24 hours after peritonitis induction. Immediate post mortem liver and kidney biopsies were analysed for histomorphology (hematoxylin eosin staining) and apoptosis (TUNEL staining).
Results
AVP decreased heart rate and cardiac output without otherwise affecting heart function and significantly decreased troponin I blood levels. AVP increased the rate of direct, aerobic glucose oxidation and reduced hyperlactatemia, which coincided with less severe kidney dysfunction and liver injury, attenuated systemic inflammation, and decreased kidney tubular apoptosis.
Conclusions
During well-resuscitated septic shock low-dose AVP appears to be safe with respect to myocardial function and heart injury and reduces kidney and liver damage. It remains to be elucidated whether this is due to the treatment per se and/or to the decreased exogenous catecholamine requirements.