Experimental sepsis in pigs—effects of vasopressin on renal, hepatic, and intestinal dysfunction

Abstract

IntroductionLow-dose arginine vasopressin (AVP) has been proposed as an adjunctive vasopressor for the treatment of advanced vasodilatory shock. However, its effects on renal, hepatic, and intestinal dysfunction during sepsis remain controversial.MethodsFecal peritonitis was induced in 20 anesthetized, invasively monitored, mechanically ventilated female pigs. Following the time point of septic shock (defined as mean artery pressure (MAP) ≤65 mmHg), animals were randomly assigned to the following groups (n = 10): 1) a norepinephrine group with MAP between 65 and 75 mmHg; and 2) an AVP group with a constant infusion rate of 0.5 mU.kg-1.min-1.ResultsMAP, pulmonary capillary wedge pressure, hematocrit, TNF-α, IL-6, and IL-10 were similar in the two groups during the 28-h observation period. Infusion of AVP was associated with lower total norepinephrine and fluid requirements. There was a statistically significant improvement in renal function as assessed by increased urine output and renal blood flow, and decreased serum creatinine, in the AVP group when compared with the norepinephrine group (P < 0.05). Histological analyses of the intestine, liver, and kidney showed similar light microscopical appearance of the two groups. Apoptotic cells in the liver were significantly fewer in the AVP group when compared with the norepinephrine group (P < 0.05).ConclusionAn adjunctive AVP to norepinephrine infusion exhibits a favorable impact on renal function without deleterious effects on the liver and intestine in a porcine model of experimental sepsis when compared with norepinephrine infusion alone.

Development of a large animal model of lethal polytrauma and intra-abdominal sepsis with bacteremia

“…Others have used models of isolated hollow viscous injury, 15 16 or attempted to replicate Gram-negative sepsis with endotoxin infusion. 17 While these models do create uncontrolled intra-abdominal sepsis, there is no transition to a period of source control that would be clinically realistic.…”

Neural injury after use of vasopressin and adrenaline during porcine cardiopulmonary resuscitation

“…VA group) also tended to cause higher troponin I concentrations in systemic blood, but the difference did not attain statistical significance as only half of the animals had very high troponin I values, and transiently greater protein S-100β levels in jugular venous blood, implying a tendency towards greater cerebral and cardiac injury. This might explain the post-resuscitation myocardial dysfunction observed after adrenaline administration during CPR ( 37 ) in contrast to the beneficial visceral effects of the vasopressin-noradrenaline combination observed ( 38 ) in experimental septic shock. In addition, cerebral cortical blood flow (CCBF) was numerically (36%) higher after ROSC in the V group, indicating difficulties in maintaining cerebral perfusion after ROSC in the VA group.…”

Controversies regarding choice of vasopressor therapy for management of septic shock in animals

“…There have been numerous small noncontrolled trials using vasopressin for the treatment of hypotension in septic patients since the first report of its success by Landry et al An example of 1 such trial examined 24 human patients with septic shock that were given a low dose of vasopressin (median 0.06 U/min) and found that their dose of norepinephrine could be decreased while the mean arterial blood pressure and cardiac index were maintained . This finding has also been seen in an experimental, randomized porcine peritonitis septic shock model . The administration of vasopressin was associated with a lower total norepinephrine and fluid requirement in order to maintain mean arterial pressure and pulmonary capillary wedge pressure in the target range.…”