How does vasopressin work in the treatment of sepsis/septic shock?

Updated: Oct 07, 2020
  • Author: Andre Kalil, MD, MPH; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, FAPS, MCCM  more...
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Answer

Vasopressin is synthesized in the hypothalamus and excreted by the posterior pituitary. In contrast to endogenous catecholamines (eg, norepinephrine), whose serum levels are universally high in septic shock, vasopressin stores are limited and its levels are low. [91] Furthermore, catecholamine effectiveness on vascular smooth muscle cells is inhibited by the activation of ATP-dependent potassium channels and NO.

Exogenous administration of vasopressin results in vasoconstriction via activation of V1 receptors on vascular smooth muscle cells that have the effect of inhibiting ATP-dependent potassium channels and, in theory, restoring the effectiveness of catecholamines. Vasopressin is also thought to inhibit NO synthase and therefore counteract the vasodilatory effect of NO. In addition, vasopressin increases renal perfusion by causing vasodilation of afferent renal arterioles, in contrast to the renal vasoconstriction caused by catecholamines.

Several small clinical trials have shown that low-dose vasopressin increases MAP and decreases the requirement for catecholamines while maintaining mesenteric and renal perfusion. [91] However, a large, randomized trial (the Vasopressin and Septic Shock Trial [VASST]) did not find mortality to be significantly lower in patients who received vasopressin in addition to norepinephrine than in those who received norepinephrine alone, even though vasopressin reduced the requirement for norepinephrine. [92]

Overall, the major adverse effects attributed to vasopressin (myocardial ischemia, cardiac arrest, mesenteric, and digital ischemia) were not significantly increased in the trial; however, patients with known coronary artery disease or congestive heart failure were excluded from the study. [92] The incidence of digital ischemia was higher with vasopressin use. Because the mean time to receiving the drug in VASST was 12 hours, this study does not address the use of vasopressin in early sepsis resuscitation.


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