Critically evaluate the role of vasopressin in septic shock.

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College Answer

Introductory statement:

Vasopressors have a role in septic shock to offset hypotension caused by vasoplegia. Vasopressin is an endogenous neuroendocrine peptide that acts on multiple receptors with multiple effects including potent vasoconstriction

Rationale for use of vasopressin in septic shock:

Low levels of vasopressin have been demonstrated in patients with septic shock (compared to cardiogenic shock).

Infusion of vasopressin reduces the need for other vasoactive medication and increases both urine output and creatinine clearance.

In septic shock, exogenous vasopressin appears to act preferentially on V1 receptors on the smooth muscle of the vasculature rather than the renal V2 receptors.

Patients with septic shock may be relatively catecholamine resistant and not respond well to nor-adrenaline and potentially respond better to vasoactive agents acting at different receptors.

Evidence:

The largest study to date is an International RCT (VASST) Patients: Septic shock on low dose nor-adrenaline infusion

Intervention: Vasopressin vs. Comparator: Noradrenaline (Other doses of open-label vasopressors given according to clinical indication)

Outcome: No effect on the primary outcome of 28-day mortality. Subgroup of those with less severe shock appeared to benefit.

Potential adverse effects:

  • Ischaemia: Cardiac/Gastrointestinal/Cutaneous 
  • Reduction in cardiac output 
  • Liver function abnormalities 
  • Platelet dysfunction

Opinion:

  • Vasopressin may benefit patients when it is started early, but the subgroup benefit may be a chance finding and needs to be interpreted with caution.
  • Higher doses of vasopressin (fixed dose infusion used in the studies) may be needed for patients with more severe shock.
  • Either way there is a clear need to monitor closely for adverse effects if vasopressin is used for septic shock.

Discussion

An extensive elaboration of vasopressin and its properties can be found elsewhere.

  • Introduction / definition:
    • Vasopressin is an important adjunct to the management of septic shock, and works synergistically with catecholamine vasopressors.
  • Rationale:
    • Vasopressin 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 form catecholamine vasopressors, thus decreasing catecholamine requirements.
    • 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.
    • 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.
  • Evidence: what the recent trials say
    • The VASST trial had demonstrated that vasopressin alone is not inferior to noradrenaline as a vasopressor in septic shock
  • Advantages
    • Decreased catecholamine requirements
    • Maintained activity in severe acidosis
    • Non-arrhythmogenic
    • Promotes the retention of resuscitation fluid
  • Disadvantages
    • Causes splanchnic vasoconstriction, which may promote anastomotic breakdown and worsening of gut ischaemia.
    • Causes increased peripheral vasoconstriction, which may result in ischaemia of the extremities
    • May cause cardiac ischaemia due to coronary vasoconstriction
    • Requires central venous access to administer
  • Own practice:
    • Vasopressin is useful as an adjunct in severe shock states which feature low peripheral vascular resistance, and should be added to catecholamine vasopressors in situations of increased catecholamine requirements or catecholamine resistance.
 

References

Landry, Donald W., et al. "Vasopressin deficiency contributes to the vasodilation of septic shock." Circulation 95.5 (1997): 1122-1125.

Sharshar, Tarek, et al. "Depletion of neurohypophyseal content of vasopressin in septic shock*." Critical care medicine 30.3 (2002): 497-500.

Dünser, Martin W., et al. "Arginine Vasopressin in Advanced Vasodilatory Shock A Prospective, Randomized, Controlled Study." Circulation 107.18 (2003): 2313-2319.