*Drug dilution simplified*
To make a solution of Norepinephrine, should I take Normal Saline or 5D? –the nurse asked.
Which solution NS or 5D to take to make Amiodarone infusion?
Is it better to write the solvent in the prescription? And does it matter?
This is an everyday happening and how to solve the diluents errors forever.
A patient is septic shock is getting Norepi single strength @ 4 ml per hour. The nurse prepares a new dilution of the same drug at the same strength and runs at the same rate. After 10 minutes she calls you and informs that BP has increased above target and asks for advice. What is the reason behind this?
To understand this whether we can do an error on choosing the diluent- let us first go to the basics.
Traditionally we have four solutions which can be used as a vehicle or diluent:
1. Normal Saline (NS)
2. Dextrose 5% (5D)
3. Ringer Lactate (LR)
4. Sterile water for injection
All medicines are chemical substances with its tendency to react chemically to other reactive molecules. To simplify -we can consider this property in terms of pH. The common injectable medicines can have pH ranging from 4 to 12.
According to one study there can be 25 -40 % incidence of drug- drug or drug solvent incompatibilities since there are more injectable, more injectable given simultaneously and more need of medicines being delivered quickly.
pH of normal saline is 5.5, 5D is 4.3, LR is 6.5 and sterile water for injection is close to 7.0.
This means that sterile water is least reactive and best diluent for all medicines – but there is a problem with it. Its osmolality is Zero mOsmol/L. More than a small quantity injected into the body will cause hemolysis.
Normal saline (NS) is best in terms of osmolality and most common diluent in the history of medicine- but the reactive molecules can reduce their potency due to oxidative stress of Cl- ion.
There is also risk of sodium load in high quantity.
Dextrose 5% (5D) is the next best and most commonly used diluent – if the risk of dextrose load and free water load is considered.
LR is the only buffer solution which will resist change in pH and is least reactive solution. It was never used so commonly as a diluent without any scientific rationale. Although, most manufacturers recommend this alternatively to NS or 5D.
*Possible outcomes of incompatibilities leading to inactivation of the drugs*
2. Ionic reactions
3. Denaturation of biological molecules (e.g. interferons etc.)
4. Evolution of gas
*Drugs which cannot be diluted*
Diazepam is supplied in solvent propylene glycol (50%) and ethanol (10%). Dilution in aqueous phase results in precipitation.
*Manufacturers of the following IV medications are recommended to be dissolved in 5D only:*
1. Amphotericin B
2. Liposomal Amphotericin B
5. Vasoactive drugs such as Noradrenalin, Dobutamine (due to inactivation by oxidation)
*Manufacturers of the following IV medications are recommended to be dissolved in NS only:*
4. Iron sucrose
Therefore to simplify this – we can presume that normal saline can be good *default diluent* except for exclusions. Drugs.com lists only two drugs which are incompatible with normal saline:
However there is no harm in taking the other two solutions as default diluents except for their exclusions.
• Reconstitution of medicines should be done just before the administration. More time means more chemical reaction.
• No two medicines should be mixed- or given at the same time though Y-Connector- unless the compatibilities are known. The simpler method is to check for precipitation on mixing.
• The choice of diluent is not absolute- since no diluent is ideal.
• Normal saline seems to be the best diluent – considering the ease of availability –if the exceptions are well known in the Unit.
• Best source of recommended diluent is the product leaflet.
_*Please share which one do you consider as default diluents in your Unit.*_