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Mechanism of action
Haemodynamic effects
- vasoconstriction mediated by effects on peripheral vasopressin receptors
- in contrast to catecholamine mediated vasoconstriction effects are
preserved during hypoxia and severe acidosis
- effects greatest in splanchnic, muscular and cutaneous vessels
- paradoxical vasodilatation may be seen in pulmonary, coronary and
vertebrobasilar circulation
- not known whether responsiveness to vasopressin varies between
distributive, hypovolaemic and cardiogenic shock
- reverses arginine vasopressin deficiency seen in prolonged shock. Whether
this is important in its mechanism of action is unclear
- additional mechanisms which may be important in septic shock:
- blockade of activated ATP-sensitive K channels in vascular smooth
muscle facilitating myocyte depolarization and vasoconstriction
- attenuates stimulation of NO generation by endotoxin and IL-1ß
inhibiting excessive vasodilatation
- directly decreases intracellular concentrations of NO second messenger
cGMP
- enhances adrenergic responsiveness in endotoxaemia
- stimulates synthesis of endothelin-I (potent endogenous
vasoconstrictor)
Haemostatic effects
- facilitates platelet aggregation and release of platelets from bone marrow
- prostacyclin generation stimulated
- increased tissue type plasminogen activator activity, factor VIII-related
antigen activity, factor VIII coagulant activity and von Willebrand factor
multimeres
- arginine vasopressin and desmopressin induce
pro-coagulant activity in healthy patients, haemophiliacs, and patients with
renal and hepatic disease and after cardiac surgery. Whether or not arginine
vasopressin causes clinically relevant haemostatic effects in the doses used
for vasodilatory shock is unclear
Hepatocytes
Increases:
- glycolysis
- gluconeogenesis
- esterification and oxidation of free fatty acids
- production of ketone bodies
Kidney
- increased resorption of free water
- increased urine output during continuous arginine vasopressin infusion for
distributive shock
- mechanism may be selective (V1-mediated)
vasoconstriction of efferent arterioles resulting in increased
glomerular filtration pressure. Alternative explanation is V2 -mediated
natriuresis and diuresis
Hypothalamic-pituitary-adrenal function
- stimulation of V3 receptors on anterior hypophysis stimulates
release of ACTH and hence increased cortisol secretion
Clinical uses
Distributive shock
- in distributive shock increases vasoconstriction,
increasing SVR and decreasing cardiac output and allowing a reduction in
norephinephrine dose
- in a randomized controlled trial use of vasopressin 0.01-0.03
IU/min in addition to norepinephrine was not
associated with an improved outcome compared to patients given
norepinephrine alone
- subgroup analysis suggests that there may be a survival benefit for
vasopressin in patients with less severe septic shock
Post cardiotomy shock
- vasoconstriction resulting in increased SVR and MAP
- variable effect on cardiac output
Adverse effects
- animal studies have shown both coronary vasoconstriction and
vasodilatation
- in high doses in humans (5-20 times dose given in distributive shock)
causes myocardial ischaemia
- cutaneous and lingual ischaemia is common in patients with distributive
shock treated with vasopressin but appears to be related to the underlying
disease rather than the vasopressin
- decreases splanchnic blood flow to a greater degree than norepinephrine
- ?increased risk of sudden death when given at high doses
Further reading
Dünser MW et al. Management of vasodilatory shock. Defining
the role of arginine vasopressin. Drugs, 2003;63(3):237-56
Russell JA et al. Vasopressin versus
norepinephrine infusion in patients with septic shock. New Engl J Med 2008; 358:
877–887
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