Vasopressin and its analogues in the CICM Second Part Exam

Substance

Physiology

Uses in critical care

• An endogenous nonapeptide, with a ring-shaped molecule
• Product of the posterior pituitary
• Plays a major role in the homeostatic mechanisms in defence of tonicity, by increasing the absorption of water in the collecting duct (V2 receptors)
• At higher doses, acts as a vasoconstrictor  by acting on V1 receptors.

Use in septic shock:

• Used in septic shock as an adjunct to noradrenaline. Theoretically, the use of vasopressin in septic shock overcomes the pituitary vasopressin depletion which tends to occur in such patients.
• Together with noradrenaline,  vasopressin reduces the amount of noradrenaline required. (VASST) 
• In meta-analysis (Neto et al, 2012), there was an associated small improvement in mortality (RR = 0.87) when vasopressin was compared with noradrenaline.

Use in cardiac arrest:

• In a meta-analysis of 5 randomised controlled trials (Aung et al, 2005) there was no clear advantage of vasopressin over adrenaline in the treatment of cardiac arrest.

• Synthetic analogue of vasopressin: a dodecapaptide
• Structurally similar to vasopressin: the dodecapeptide contains a nonapeptide chain identical to lysine vasopressin (same as the porcine vasopressin molecule)- where the lysine is substituted for arginine,
• Has its own intrinsic vasoconstrictor activity and also acts as a pro-drug for lysine vasopressin (when it undergoes hepatic metabolism)
• Selective for the splanchnic circulation

Use in hepatorenal syndrome

• According to meta-analysis by Israelsen et al, 2015, terlipressin is more effective than placebo, and  equal with noradrenaline in efficacy. It reduces mortality from HRS-AKI (previously known as Type 1 HRS) and  is presently the recommended drug of choice for this condition.

Use in variceal haemorrhage

• Terlipressin reduces bleeding from varices by decreasing portal venous pressure.
• In terms of mortality and re-bleeding rates, there seem to be no difference between terlipressin, somatotatin and octreotide (Seo et al, 2014).

Use in septic shock

• When compared to vasopressin, terlipressin infusion appears to be equivalent in efficacy (Morelli et al, 2009)

• Synthetic analogue of vasopressin: with a deaminated cysteine molecule, and the substitution of a D-stereoisomer for L-arginine.
• Duration of action is 6 to 14 hours.
• Greater selectivity for V2 receptors, with little V1 activity
• The effect is therefore largely limited to increasing water retention
• A pleasing side-effect is the improvement in platelet function and the increases in the plasma levels of factor VIII and vWF, as desmopressin causes them to be released from their storage sites in the vascular endothelium (Manucchi, 1997)

Use in diabetes insipidus

• Desmopressin is the standard of care for DI since its introduction in the early 1980s.

Use in haemostasis

• According to Massimo (2007), the following haemostatic disorders benefit from desmopressin:
  • von Willebrands disease
  • Haemophilia A (mild)
  • Uraemic platelet dysfunction
  • Platelet dysfunction due to antiplatelet agents
  • Bleeding during cardiac surgery