Vasopressin (argipressin) for septic shock (Critical Care Formulary)

For use in Critical Care Areas for Adults only.  Administer preferably via a CENTRAL line.

MECHANISM OF ACTION:

• Vasopressin, also known as argipressin, is antidiuretic hormone, an endogenous peptide hormone released by the pituitary gland.
• It is a vasoconstrictor and its mechanism of action includes binding to V₁ receptors on vascular smooth muscle to increase arterial blood pressure.
• Vasopressin plays a minimal role in blood pressure regulation in normotensive states.  In vasodilatory shock, administration may correct a relative endogenous vasopressin deficiency that develops when endogenous secretory stores become depleted.  It works synergistically with catecholamines and is commonly used as a noradrenaline sparing agent in septic shock.
• Half-life = 10 to 20 minutes.

USES:

• In resistant septic shock, where noradrenaline dose has reached 0.5 micrograms/kg/minute, with the aim of increasing the mean arterial pressure (MAP) or reducing noradrenaline requirements.  Consider also use of corticosteroids.
• Vasopressin should not be used as the first-line or sole agent in the management of septic shock.  Noradrenaline remains the first-line vasopressor as per Surviving Sepsis Guidelines.
• Use in organ donation: see separate guideline.

CAUTIONS:

• Vascular disease, particularly of the coronary arteries but also peripheral vascular disease.  Monitor for signs of ischaemia (see below).
• Avoid fluid overload.  Caution in conditions exacerbated by fluid overload eg heart failure, asthma and epilepsy.
• Patients with arrhythmias and those at risk of prolonged QTc interval.
• Low cardiac output states.
• Bradycardia.
• Intravascular depletion (correct hypovolaemia).

PRESENTATION:

• Ampoules containing argipressin (synthetic vasopressin) 20 units in 1mL.
• Stored in refrigerator.

ADMINISTRATION:

• Dilute one ampoule (20 units) to 50ml with glucose 5% to produce a concentration of 0.4 units per mL.

DOSE AND RATE:

• Usual starting dose is 0.03 units/minute = 1.8 units per hour as per Surviving Sepsis Guidelines.
• The dose may be titrated between 0.6 units per hour and 2.4 units per hour.
• Doses above 2.4 units per hour must be discussed with the Consultant Intensivist.  Higher doses have been associated with cardiac, digital and splanchnic ischaemia and cardiac arrhythmias, particularly if QTc prolonged.
• As the patient’s condition improves, the vasopressin must be weaned down slowly and stopped before the noradrenaline is stopped.  Consider stopping vasopressin when noradrenaline requirements <0.25 micrograms/kg/minute.  Reduce infusion by half every 30 minutes until 0.6 units per hour (1.5mL/hour) is reached, then stop.

STABILITY:

• 24 hours.
• Do not allow the syringe or infusion to run out.  A syringe or infusion can be made up to a maximum of one hour in advance and labelled clearly with contents and expiry.  Refer to local nursing guidelines for switching over infusions or syringes.
• However due to the half-life of vasopressin of 10 to 20 minutes, double pumping is not required when changing over syringes.

EXTRAVASATION:

• The infusion has a low pH and extravasation is likely to cause venous irritation and tissue damage.  If given peripherally, use a large vein with monitoring for phlebitis.  Resite catheter at first signs of inflammation.
• Please refer to NHS Highland Extravasation Protocol on intranet.  

SIDE EFFECTS:

• Reduced cardiac output, chest pain due to angina, cardiac arrest.
• Fluid retention with resulting hyponatraemia.
• Peripheral ischaemia and gangrene.
• Nausea and vomiting, diarrhoea.
• Bronchospasm.

MONITORING:

• Ensure ECG and blood pressure monitoring is in place. Invasive blood pressure monitoring is preferred as in hypoperfused or shock states with cool peripheries, non-invasive BP recordings are less reliable.
• Renal function and urine output/fluid balance.
• Monitor for signs of peripheral ischaemia.