ARTICLE REVIEW
Septic shock is a ubiquitous condition treated in intensive care. Vasopressin at low doses is currently recommended [1] as a third line vasopressor in order to either increase the blood pressure or to reduce the dose of catecholamines. Clinical trials such as the VANISH trial, recently presented at the Annual Congress of ESICM, have been performed to elucidate the clinical effect of arginine vasopressin (AVP) in comparison with Noradrenaline in septic shock.
Vasopressin (AVP) is a stress hormone that stimulates AVPR1a, AVR1b, AVPR2 and purinergic receptors. Stimulation of endothelial V2-receptors causes vasodilation, leukocyte migration and pro-coagulant effects while V1a-receptors stimulation causes vasoconstriction.
The effect of a new selective V1a receptor agonist, Selepressin (FE 202158), was investigated in a ovine model of peritonitis-induced septic shock in a recently published study.
He X. and colleages designed a randomised animal study [2] with 46 adult sheep. The whole sample was divided into two large groups: early-intervention (where the vasopresor was started when arterial pressure had decreased by 10% from baseline) and late-intervention (where the vasopressor was started when the mean arterial pressure (MAP) remained less than 70 mmHg despite fluid challenge). Each group, in turn, was divided in three to compare either IV Selepressin (1pmol/Kg/min), AVP (0.25 pmol/kg/min) or norepinephrine (3 nmol/kg/min). An additional control group was also observed, and all animals were observed until death or a maximum of 30 hours.
In the early intervention group, Selepressin maintained MAP and importantly, cardiac index, SVRI and LVSWI, slowed the increase in blood lactate levels and was associated with less lung oedema, lower accumulative fluid balance, and lower interleukin-6 and nitrite/nitrate levels than AVP or norepinephrine. Renal blood flow and creatinine clearance was higher and oliguria ocurred later in the Selepressin group. Also, Selepressin blunted the increases in PT and aPTT compared with AVP and control groups.
In the late-intervention groups, Selepressin delayed the decrease in MAP and was associated with less lung oedema than in the other two groups, but there were no differences in cardiac index, SVR index, or LVSWI, and no effect on coagulation times. Overall, Selepressin treated animals survived longer than the other animals.
The authors conclude that Selepressin is superior to AVP and Norepinephrine in the treatment of septic shock, particularly in the early stages of this condition, therefore as a first line vasopressor.
These results are in line with previous studies. Maybauer et al. [3] demonstrated that Selepressin was as effective as AVP to maintain blood pressure and more effective to reduce vascular leak in an ovine model of pneumonia.
Rehberg S. et al. showed that a selective stimulation of V1a-receptors with a titrated infusion of Phe2-Orn8-Vasotocin (POV) were more effective than AVP in attenuating vascular and cardiopulmonary dysfunction in an ovine model of sepsis.
This data is pointing out a pathway of future research in humans. Experimental and clinical investigations on new selective V1 agonists in patients suffering septic shock are required.
Article review prepared and submitted by ESICM Journal Review Club member Hollmann D. Aya on behalf of the Cardiovascular Haemodynamics section.
References
1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41(2): 580-637.
2. He X, Su F, Taccone FS, et al. A Selective V1A Receptor Agonist, Selepressin, Is Superior to Arginine Vasopressin and to Norepinephrine in Ovine Septic Shock. Crit Care Med 2016; 44(1): 23-31.
3. Maybauer MO, Maybauer DM, Enkhbaatar P, et al. The selective vasopressin type 1a receptor agonist selepressin (FE 202158) blocks vascular leak in ovine severe sepsis*. Crit Care Med 2014; 42(7): e525-33.
