Vasopressin

Vasopressin (antidiuretic hormone, ADH) controls water excretion in kidneys via V2 receptors and produces constriction of vascular smooth muscle via V1 receptors. In normal subjects vasopressin infusion has no effect on blood pressure but has been shown to significantly increase blood pressure in septic shock.The implication is that in septic shock there is a deficiency in endogenous vasopressin, and this has been confirmed by direct measurement of endogenous vasopressin in patients with septic shock requiring vasopressors. In vitro studies show that catecholamines and vasopressin work synergistically.

Anecdotally, use of 3 units per hour is usually very effective and not associated with a reduction in urine output.

As its pseudonym antidiuretic hormone implies, vasopressin infusion might be expected to decrease urine output, but the opposite is the case at doses required in septic shock.This may be due to an increase in blood pressure and therefore perfusion pressure. It is also worth noting that, whereas noradrenaline constricts the afferent renal arteriole, vasopressin does not, so may be beneficial in preserving renal function. It has been shown that doses as high as 0.1 units/min (6 units/h) do reduce renal blood flow, so should be avoided.A dose of 0.04 units/min (2.4 units/h) is often efficacious in septic shock and does not reduce renal blood flow. The VAAST study (N Engl J Med 2008; 358: 877–87) found that lowdose vasopressin (0.01–0.03 units/min) in addition to noradrenaline did not reduce mortality compared with noradrenaline alone.However,benefit was seen in less severe septic shock, where mortality was lower in the vasopressin group.The less severe group were identified as those stabilized on noradrenaline at doses of 5–15 μg/min

Vasopressin does not cause vasoconstriction in the pulmonary or cerebral vessels, presumably due to an absence of vasopressin receptors. It does cause vasoconstriction in the splanchnic circulation, hence the use of vasopressin in bleeding oesophageal varices.The dose required in septic shock is much lower than that required for variceal bleeding.

Uses
In septic shock: reserve its use in cases where the noradrenaline dose exceeds 0.3 μg/kg/min (unlicensed)

Contraindications
Vascular disease, especially coronary artery disease

Administration
IV infusion: 1–4 units/h
Dilute 20 units (1 ml ampoule of argipressin) in 20 ml glucose 5% (1 unit/ml) and start at 1 unit/h, increasing to a maximum of 4 units/h

Do not stop the noradrenaline, as it works synergistically with vasopressin. As the patient’s condition improves, the vasopressin should be weaned down and off before the noradrenaline is stopped

Available as argipressin (Pitressin)
Stored in fridge between 2 and 8°C

How not to use vasopressin
Doses in excess of 5 units/h

Adverse effects
Abdominal cramps
Myocardial ischaemia
Peripheral ischaemia

Cautions
Heart failure
Hypertension