The “diuretic combination” of furosemide with dobutamine is a common form of medication in cardiology, but its irrationality has been raised as early as 40 years ago. Can “diuretic combination” be used or not?
- Why should “diuretic combination” be used?
Based on clinical experience, furosemide is easily tolerated during long-term use, and it is difficult to achieve good results with a single diuretic in cardiology, such as in acute heart failure patients.
Small doses of dopamine can increase urine output by agonizing dopamine receptors, dilating renal blood vessels, and increasing renal blood flow.
The two are configured into a diuretic combination, which is a perfect match pharmacologically, and many clinical experiences have confirmed its effectiveness. But is this really the right way to use the drug?
- Incompatibility of furosemide + dopamine
Let’s start with a table to understand the different manufacturers of furosemide injection and dopamine injection.
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Why are the two incompatible? It can be explained by David W. Newton’s view that acid-base reactions are the most common cause of drug incompatibility.
When organic drugs in salt or ionic form, diluted or mixed lead to precipitation, the most likely cause is the formation of the non-ionic form of the drug.
Based on this theory, let’s look specifically at furosemide injection and dopamine injection.
- If the pH of the mixed solution is acidic, then furosemide injection will precipitate furosemide out of the mixed solution.
How to understand this statement? Furosemide API itself is insoluble weak acid, because it is insoluble in water and soluble in alkali, so the sodium salt of soluble furosemide is made from sodium hydroxide, so furosemide injection is alkaline.
When a certain acid is added, it disrupts the acid-base balance of the soluble sodium salt of furosemide injection, and a certain acid competes with furosemide (weak acid) to form salt with base, and finally precipitates furosemide. So the cloudiness seen in the infusion tube is water-insoluble furosemide.
Aurélie Foinard et al. suggest that even in the absence of visible particles, the precipitation of furosemide results in an estimated drug loss of between 10% and 15%, with tachyzoate being more susceptible to interactions.
As an example: furosemide injection + 5% GS 250 mL, the solvent glucose injection is acidic, so furosemide is easily precipitated in the glucose solvent.
Isn’t it common to encounter accelerated clouding of urine injections in glucose solutions in clinical practice? Then why is it not cloudy in some cases? It may be because the pH of the final configuration of the medium does not reach the acid value for furosemide precipitation.
For example, the dose of furosemide injection added is large enough to cause the pH to rise, bringing the final configuration to a neutral or alkaline solution, or the dose of glucose solvents may be small enough to reduce the overall pH of the solvents toward acidity. In addition, it is also related to the different pH of drug solvents from different manufacturers.
Therefore, it is recommended to use saline as the solvent to dissolve furosemide injection clinically and to control the amount of saline because the pH of saline may also vary from manufacturer to manufacturer.
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Therefore, the addition of furosemide injection into acid is turbid in terms of compatibility and is contraindicated for compatibility.
- If the pH of the mixed solution is alkaline, then dopamine will be degraded to a melanin-like polymer.
Why is this? Actually, the dopamine used in clinical applications is its hydrochloride form, dopamine hydrochloride, so dopamine hydrochloride is acidic.
Because dopamine contains phenolic hydroxyl groups (catecholamines), it is easily oxidized under air or light conditions, especially in an alkaline environment, which accelerates its oxidation. Therefore, the addition of alkali to dopamine injection tends to oxidize dopamine to a melanin-like polymer. This is why the antioxidant sodium bisulfite is added to the dopamine drug excipients.
As an example: dopamine injection + furosemide injection (dopamine in small doses), mixing the two their final solution is likely to be alkaline, so dopamine undergoes oxidative discoloration.
In the experiments of Lu et al. on diuretic combination, it was concluded that dopamine hydrochloride solution is stable at pH < 8.0 for 3 hours. Therefore, it is likely that the black polymer was produced when the pH of the mixed solution was > 8.0.
Gardella LA et al. in “Stability of Intravenous Mixtures of Dopamine Hydrochloride” mention that dopamine is chemically and physically stable for at least 48 hours at pH 6.85 or below.
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Therefore, the addition of dopamine to alkali can cause discoloration in terms of compatibility and is contraindicated. In addition, dopamine should preferably be dissolved in sugar water rather than salt water.
- Can “diuretic combination” be used?
As mentioned above, furosemide injection is alkaline and dopamine injection is acidic, so there are contraindications to mixing dopamine injection and furosemide injection directly.
If they must be combined, they need to be dosed separately, and it is recommended that furosemide be dissolved in saline and dopamine in sugar water.
If you still do not understand, then use the author’s own jingle to do a summary of it.
acid with acid, base with base
tachyonine, it is appropriate to use salt
Doba acid, it is appropriate to use sugar
acid-base with, insoluble salt
Anti-oxidation, add antioxidant
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