Vasopressin and terlipressin as first-line therapy in fulminant ovine septic shock

Introduction

Vasopressinergic V1 receptor agonists, such as arginine vasopressin (AVP) and terlipressin (TP), are increasingly used to stabilize haemodynamics in catecholamine-refractory hyperdynamic septic shock [1]. In the current sepsis guidelines, however, norepinephrine (NE) and dopamine are still recommended as vasopressors of choice [2]. The present study was designed as a prospective, randomized, controlled laboratory experiment to elucidate the effects of AVP and TP (when given as first-line therapy) on mesenteric blood flow (Qma) and mortality in an established model of ovine septic shock.

Methods

Twenty-four ewes were anaesthetized and instrumented for chronic study. 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 baseline measurements (BL1) had been performed, the faeces were injected into the peritoneal cavity. A second set of measurements (BL2) was taken after the onset of septic shock (defined as mean arterial pressure (MAP) <60 mmHg). The animals were then randomly assigned to receive either AVP (0.5 mU/kg/min; n = 8) or TP (1 μg/kg/hour; n = 8). The control group (n = 8) received only the vehicle (normal saline). NE was titrated to maintain MAP at 70 ± 5 mmHg in all groups.

Results

There were no differences between groups at baseline. Qma and electrolytes were similar between groups. However, systemic haemodynamics and global oxygen transport were stabilized more effectively in animals receiving AVP or TP versus control animals. In addition, continuous TP infusion prolonged survival as compared with the control and AVP group (P < 0.05).

Conclusion

In fulminant ovine septic shock, infusion of AVP or TP as first-line therapy is safe and efficacious. The notion that low-dose TP infusion may be superior to NE or AVP therapy needs to be confirmed in prospective clinical trials.