Vasopressin in resuscitation of septic shock

An extensive elaboration of vasopressin and its properties can be found elsewhere. This is a brief summary, to help one answer questions like Question 22 from the second paper of 2013.

In short

What is vasopressin and why would it be useful in sepsis

• Vasopressin is an endogenous nonapeptide hormone
• It acts on V1 and V2 receptors, of which the V1 receptors are responsible for its vasoconstrictor properties.
• Activation of these receptors leads to vasoconstriction which is synergistic with the vasoconstriction from catecholamine vasopressors, thus decreasing catecholamine requirements.
• There is also a concept of "relative vasopressin insufficiency" which suggests that in states of severe shock the endogenous secretion of vasopressin is inadequate, and vasopressin needs to be supplemented in order to maintain an adequate vasopressor response.

Advantages of vasopressin

• Vasopressin does not have proarrhythmic properties of catecholamine agents, and may be used as a catecholamine-sparing agent
• Vasopressin receptor sensitivity is unchanged in the setting of severe acidosis, while catecholamine receptors lose their sensitivity.
• Unlike catecholamines, it does not cause arrhythmias.
• The antidiuretic effect promotes the retention of resuscitation fluid
• As a first-line agent in sepsis, it may have a protective effect on renal function.

Disadvantages of vasopressin

• That retention of fluid also leads to the dilution of sodium, and hyponatremia
• Vasopressin needs to be administered into central veins, and thus requires a CVC.
• It causes splanchnic vasoconstriction, which may promote anastomotic breakdown and worsening of gut ischaemia.
• It causes increased peripheral vasoconstriction, which may result in ischaemia of the extremities
• It may cause cardiac ischaemia due to coronary vasoconstriction
• It increases afterload, which may be counterproductive
• It may promote platelet aggregation and thus produce thrombocytopenia

Evidence behind the use of vasopressin in septic shock

• Vasopressin together with noradrenaline seems to be better than noradrenaline alone in small studies which looked at hemodynamic parameters rather than survival. On its own high dose vasopressin was no better than noradrenaline alone.
• The VASST trial from 2008, on a substrate of 778 recruited patients, demonstrated that vasopressin didn’t change 28th day mortality when compared to noradrenaline (except maybe in "mild" septic shock, where it seemed to be slightly better).
  • In 2013, the VASST investigators also took a look at the cardiac safety of vasopressin in septic shock, and concluded that it does not have a detrimental effect on the hearts of septic shock patients.
• The VANISH trial from 2016 looked at using vasopressin early in septic shock, and what effect this might have on renal function (the hypothesis was that the use of vasopressin as the first-line pressor agent would be somehow renally protective). 
  • Turns out, vasopressin had little effect on the dvelopment of "biochemical" renal failure: the rate was 43% in the vasopressin group and 40.8% in the noradrenaline group. 
  • However, dialysis rates were much lower in the vasopressin group (25.4% vs. 35.3%)
  • Serious adverse events related to pressor use (eg. mesenteric ischaemia, fingers falling off, that sort of thing) were marginally higher in the vasopressin group (10.7% vs. 8.3%)
  • These things did not have any effect on the 28 day mortality.
  • Conclusion? Negative study. Cannot recommend vasopressin as a replacement for noradrenaline as the first-line agent.