Neonatal Intensive Care Drug Manual

1. 
   Treatment of refractory hypotension.
   
2. 
   Adjunctive treatment of pulmonary hypertension.
   
3. 
   Acute antidiuretic hormone (ADH) replacement when diagnosis of diabetes insipidus established. [The drug of choice for the treatment of diabetes insipidus is desmopressin (dDAVP). An argipressin infusion should be considered in the initial management of post-surgical or post-traumatic DI.]
   
4. 
   Adjunct in acute massive haemorrhage of gastrointestinal tract or oesophageal varices (specialist use only) [Terlipressin or octreotide preferred].
   

Argipressin provokes vasodilatation in some vascular beds via its action on oxytocin receptors.

0.01 to 0.05 units/kg/hour infusion

For pulmonary hypertension:

0.01 to 0.02 units/kg/hour (can be commenced at 0.006 units/kg/hour to a maximum 0.07 units/kg/hour)

For diabetes insipidus:

Starting dose: 0.5 milliunits/kg/hour

Dose range: 0.5 to 1.0 milliunits/kg/hour. May increase to 2.0 milliunits/kg/hour.

The final wean may be from 0.5 to 0.25 milliunits/kg/hour

For acute massive gastrointestinal bleeding:

May not be best agent for this indication.

Commence argipressin 0.12 units/kg/hour. Increase (titrate) over 2 hours to maximal dose of 0.6 units/kg/hour. Monitor carefully for side effects including fluid retention, electrolyte abnormalities, hypertension and cardiac arrhythmias. If bleeding not controlled at dose < 0.6 units/kg/hour (0.01 units/kg/minute) then unlikely to be controlled at higher doses and other measures should be used.

For acute massive gastrointestinal bleeding: 0.6 units/kg/hour (0.01 units/kg/min).

Single strength continuous IV infusion

Draw up 0.125 mL/kg argipressin (2.5 units/kg) and dilute in 50 mL sodium chloride 0.9% or glucose 5% = 0.05 units/kg/mL solution.

Infusing at a rate of 1 mL/hour = 0.05 units/kg/hour.
DOUBLE STRENGTH continuous IV infusion

Infusion strength	Prescribed amount
1 mL/hour = 0.1 units/kg/hour	5 units/kg argipressin and make up to 50 mL

Dilution: draw up 0.25 mL/kg argipressin (5 units/kg) and dilute in 50 mL sodium chloride 0.9% or glucose 5% = 0.1 units/kg/mL solution.

Infusing at a rate of 1 mL/hour = 0.1 units/kg/hour.
QUADRUPLE STRENGTH continuous IV infusion

Infusion strength	Prescribed amount
1 mL/hour = 0.2 units/kg/hour	10 units/kg argipressin and make up to 50 mL

Dilution: draw up 0. 5 mL/kg argipressin (10 units/kg) and dilute in 50 mL sodium chloride 0.9% or glucose 5% = 0.2 units/kg/mL solution.

Infusing at a rate of 1 mL/hour = 0.2 units/kg/hour.
FOR DIABETES INSIPIDUS

Continuous IV infusion

Step 1: Add 0.1 mL (2 units) of argipressin (20 unit/mL ampoule) to 500 mL bag of 0.9% sodium chloride to make a 4 milliunit/mL solution (SOLUTION A). Mix it well.

FOR GASTROINTESTINAL BLEEDING

QUADRUPLE STRENGTH continuous IV infusion

Infusion strength	Prescribed amount
1 mL/hour = 0.2 units/kg/hour	10 units/kg argipressin and make up to 50 mL

Draw up 0. 5 mL/kg argipressin (10 units/kg) and dilute in 50 mL sodium chloride 0.9% or glucose 5% = 0.2 units/kg/mL solution.

Infusing at a rate of 1 mL/hour = 0.2 units/kg/hour.

Assess urine output and peripheral perfusion frequently.

Observe IV site closely for blanching and extravasation.

For diabetes insipidus:

The dose of this is titrated (usual dose range 0.0005 to 0.001 units/kg/hour (0.5 to 1.0 milliunits/kg/hour), aiming for:

• 
  urine output 2–4 mL/kg/hour,
  
• 
  neutral fluid balance,
  
• 
  maintain plasma sodium 145–150 mmol/L
  

Argipressin causes water retention and hyponatraemia.

May cause ischaemia related to infusion site.

Acute ECG or biochemical evidence of myocardial ischaemia.

Previously documented chronic and/or severe liver dysfunction (INR > 2, direct bilirubin > 50 micromol/L) or clinical evidence of portal hypertension.

Documented or high suspicion of mesenteric ischaemia.

Use in diabetes insipidus:

The mainstay of initial therapy is accurate fluid and electrolyte management. ADH administration should only be considered after a reasonable period of observation establishes that DI is persistent (at least 4–6 hours, but preferably longer in acute situations). Early or over vigorous ADH administration may provoke cerebral oedema,

Prior to starting the infusion, it is advisable to allow the patient to drift into a slightly negative fluid balance. This can be easily achieved by not replacing all the previous hour(s) urine output. Once the argipressin infusion has commenced, continue the fluid regimen of replacement of previous hour’s losses plus insensible losses.