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Effects of vasopressin and terlipressin in ovine septic shock on mesenteric blood flow and survival
Critical Care volume 11, Article number: P19 (2007)
Vasopressin agonists, such as arginine vasopressin (AVP) and terlipressin (TP), are increasingly used to stabilize haemodynamics in catecholamine refractory hyperdynamic septic shock. However, it is still not fully understood if and how low-dose infusion of both drugs impacts on mesenteric blood flow (Qma) and outcome. The present study was conducted as a prospective, randomized, controlled laboratory experiment to compare the effects of AVP and TP on Qma and mortality in an established model of ovine septic shock.
Materials and methods
Fifteen ewes were anaesthetized and instrumented for chronic haemodynamic monitoring. A median laparotomy was performed to place a flow-probe around the superior mesenteric artery and to take faeces from the caecum under sterile conditions. After the gut and abdomen had been closed and baseline measurements (BL1) taken, the faeces were injected into the peritoneal cavity. After the onset of septic shock (defined as mean arterial pressure (MAP) < 60 mmHg), a second set of measurements (BL2) was taken. The animals were then randomly assigned to receive either AVP (0.5 mU/kg/min) or TP (1 μg/kg/hour). The control group received only the vehicle (normal saline). Norepinephrine was titrated to maintain MAP at 70 ± 5 mmHg in all groups. Systemic haemodynamics, global oxygen transport including arterial lactate concentrations, gas exchange, electrolytes and Qma were determined at baseline and following every hour after the onset of septic shock. Animals surviving the 12-hour study period were deeply anaesthetized and killed by an overdose of saturated potassium solution. Mortality was analyzed by the Kaplan–Meier survival analysis. All the other variables were compared using two-way analysis of variance with appropriate post-hoc comparisons.
The Qma and electrolytes were similar between groups. However, systemic haemodynamics and global oxygen transport were stabilized more effectively in both treatment groups versus control animals. Notably, continuous infusion of AVP and TP significantly prolonged survival as compared with the control group (P < 0.05 each; Figure 1). There were no differences between the treatment groups.
In this clinically relevant large animal model of septic shock, low-dose infusion of AVP and TP did not impair the Qma, but stabilized systemic haemodynamics and prolonged survival. Our data suggest that early infusion of AVP or TP may be beneficial in catecholamine-refractory septic shock.
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Rehberg, S., Ertmer, C., Lange, M. et al. Effects of vasopressin and terlipressin in ovine septic shock on mesenteric blood flow and survival. Crit Care 11, P19 (2007). https://doi.org/10.1186/cc5998
- Septic Shock
- Mean Arterial Pressure
- Superior Mesenteric Artery