Septic shock: The Vasopressin Drip
HOW does vasopressin work?
• Released by pituitary ➡️ activates V1 receptors on vascular smooth muscle ➡️ increases phospholipase C causing calcium ion release ➡️ causing arterial vasoconstriction ➡️ thus raising blood pressure and SVR.
• Promotes water retention via activation of V2 receptors (by adenyl cyclase). Hence ADH effect.
• Lowers HR
Name the trial that studied vasopressin in shock
• VASST trial (Vasopressin and Septic Shock Trial, NEJM. 2008.
• Multi-center, randomized, double-blind trial comparing low-dose vasopressin (0.01 to 0.03 units/min) to norepinephrine (5 to 15 μg/min) in patients with septic shock
WHY is Vasopressin drip dosed at a fixed rate of 0.03 units per minute in the ICU?
• "Higher doses of vasopressin have been associated with cardiac, digital, and splanchnic ischemia"
• Supported by CHEST (ACCP), IDSA and SCCM and Surviving Sepsis Campaign Guidelines.
Primary endpoint of VASST?
• 28-day mortality, which showed no significant difference between the vasopressin and norepinephrine groups (35.4% vs. 39.3%, respectively; P=0.26)
WHEN and WHY is vasopressin ordered concomitant to norepinephrine drip?
- A prospectively defined subgroup analysis revealed that patients with less severe septic shock (requiring 5 to 14 μg/min of norepinephrine) had a lower 28-day mortality when treated with vasopressin compared to norepinephrine (26.5% vs. 35.7%, P=0.05)
- Vasopressin demonstrated a catecholamine-sparing effect, reducing the need for norepinephrine to maintain target blood pressure.
WHY is there relative vasopressin deficiency in septic shock?
- Impaired baro-reflex mediated secretion. Despite hypotension, vasopressin is not released.
- Apoptosis if vasopressenergic neurons. Sepsis activates blood-brain microglia as well as the apoptotic pathway in the hypothalamus.
- V1A receptor downregulation by cytokines. This happens to liver, lung, kidney, and heart through efforts of IL-1 beta, TNF-alpha, IFN-gamma.
- Inducible Nitric Oxide Synthase Pathway. iNOS pathway inhibits release of vasopressin.
- Depletion of vasopressin in neurohypophysis.
REFERENCES
Russell JA, Walley KR, Singer J, et al. Vasopressin Versus Norepinephrine Infusion in Patients With Septic Shock. The New England Journal of Medicine. 2008;358(9):877-87. doi:10.1056/NEJMoa067373
Russell JA, Walley KR, Gordon AC, et al. Interaction of Vasopressin Infusion, Corticosteroid Treatment, and Mortality of Septic Shock. Critical Care Medicine. 2009;37(3):811-8. doi:10.1097/CCM.0b013e3181961ace.
Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Critical Care Medicine. 2021;49(11):e1063-e1143. doi:10.1097/CCM.0000000000005337.
Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of Vasopressin Relevant to Management of Septic Shock. Chest. 2001;120(3):989-1002. doi:10.1378/chest.120.3.989.
Landry DW, Levin HR, Gallant EM, et al. Vasopressin Deficiency Contributes to the Vasodilation of Septic Shock. Circulation. 1997;95(5):1122-5. doi:10.1161/01.cir.95.5.1122.
da Costa LHA, Júnior NNDS, Catalão CHR, et al. Vasopressin Impairment During Sepsis Is Associated With Hypothalamic Intrinsic Apoptotic Pathway and Microglial Activation. Molecular Neurobiology. 2017;54(7):5526-5533. doi:10.1007/s12035-016-0094-x.
Bucher M, Hobbhahn J, Taeger K, Kurtz A. Cytokine-Mediated Downregulation of Vasopressin V(1A) Receptors During Acute Endotoxemia in Rats. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2002;282(4):R979-84. doi:10.1152/ajpregu.00520.2001.
Giusti-Paiva A, De Castro M, Antunes-Rodrigues J, Carnio EC. Inducible Nitric Oxide Synthase Pathway in the Central Nervous System and Vasopressin Release During Experimental Septic Shock. Critical Care Medicine. 2002;30(6):1306-10. doi:10.1097/00003246-200206000-00025.
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