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Basic principles of infusion solvent selection
A doctor at a grassroots hospital asked:
When on duty, patients with heart failure who often encounter diabetes mellitus are used with salt water with sodium nitroprus or sugar water?
I have also been struggling with this problem for a long time, saline with nitroprus sodium is an over-label drug, and may increase the workload of the heart, but the use of sugar water with a conflict with the patient's diabetes history.
So, in such a situation, how should we choose the infusion solvent?
Clinically, the drug is often administered in the form of infusion. Some injections available for intravenous infusion require the solvent (also known as the carrier) to dissolve and dilute and then infuse.
If the solvent selection is not appropriate, it will not only affect the stability of the drug or the occurrence of physicochemical reactions, resulting in reduced drug efficacy, or adverse reactions, but also serious risks to the safety of patients' lives.
For example, ceftriaxone sodium can lead to vascular embolic death if continuous infusion is added to calcium-containing infusions (e.g., Ringer's solution, Hartmann's solution).
The choice of infusion solvent is directly related to the safety and efficacy of medication and cannot be ignored. Next, with the small medicine of the world, we will talk about the 3 basic principles of infusion solvent selection.
01
The solvent is selected strictly according to the drug instructions
The drug instructions are legal documents containing important information about drugs, are the statutory guidelines for the use of drugs, and the drug methods recorded in the drug instructions are scientifically verified according to the physical and chemical properties of drugs and solvents, the compatibility of compatibility, and the stability after compatibility.
Taking penicillin for injection as an example, they are relatively stable in near-neutral (pH = 6-7) solutions, and the acidic or alkaline solutions accelerate their decomposition. It is best to dissolve penicillins with 0.9% sodium chloride injection when applied, but the instructions also state that when injecting intramuscularly, more than 500,000 units need to add 2 ml of sterile injection water, and sodium chloride injection should not be used as a solvent [1].
If glucose injection (pH = 3.5-5.5) is used as the solvent, the stability of penicillins decreases and there is a certain degree of decomposition, so it is clinically required to use a small volume of liquid (100 ml) for rapid instillation, but the speed of administration of intravenous infusion cannot exceed 500,000 units per minute, so as to avoid the toxic reaction of the central nervous system [1].
In addition, penicillins decompose extremely quickly in alkaline solutions. Therefore, it is strictly forbidden to match alkaline liquids (sodium bicarbonate, aminophylline, etc.) with them.
The antibacterial efficacy of macrolide antibiotics can be enhanced in the pH environment, so it is recommended to choose 0.9% sodium chloride injection as a solvent. It has also been reported that the addition of sodium bicarbonate to the 5% glucose injection solvent (5% sodium bicarbonate injection 0.1 ml in 500 ml of liquid) has also been reported to increase the pH.
As long as you carefully read the drug instructions, you will find that the solvent selection of some injections is strictly limited, either with glucose injection or with 0.9% sodium chloride injection.
For example, the instructions for injecting fluroxacin indicate that this product should not be combined with sodium chloride injection or glucose sodium chloride injection [2].
Fluroxacin is made by taking advantage of the fact that its molecular structure has both acidic and alkaline groups, and can be combined with amino acids to form soluble salts. In electrolyte solutions such as 0.9% sodium chloride injection, the solubility of the same ion effect is reduced, resulting in the agglutons formed in a short period of time to agglutinate and form a precipitate.
Similarly, injections like enoxacin and pefloxacin can only be dissolved and diluted with 5% or 10% glucose injections.
Another example is that furosemide injection (pH 8.5 ~ 9.5) and glucose injection (pH 3.5 ~ 5.0) are compatible, after mixing the pH value changes, furosemide precipitation, resulting in turbidity and easy precipitation of the solution, so furosemide injection uses sodium chloride injection as a solvent [3].
02
The lysate is selected according to the patient's pathological condition
The selection of infusion solvent according to the drug instructions is the preferred principle for clinical medication. However, the clinical needs are changeable, and it is also necessary to select the solvent according to the patient's pathological situation.
In general, there are the following situations to consider:
If the patient has a history of diabetes and the heart and kidney function is acceptable, saline can be used;
If the patient has hypertension, coronary heart disease and cardiac insufficiency, the intake of saline should be reduced to reduce the burden on the heart;
If the patient has renal insufficiency, it is necessary to reduce the intake of saline to reduce sodium water retention.
In addition, if the patient's examination of electrolytes results are hyponatremia, saline should be selected, and sugar water should be selected instead;
Evaluate cardiac function according to the patient's heart muscle enzymes and other indicators to decide the choice of saline or sugar water;
If the patient has pulmonary encephalopathy (type 2 respiratory failure), it is best to use saline, because the use of glucose increases the retention of carbon dioxide and aggravates pulmonary encephalopathy;
If the patient is in shock, neither saline nor sugar water is preferred. Because insulin secretion decreases during shock, the use of glucose is prone to hyperglycemia, and saline contains more sodium and chlorine than normal intercellular fluid, and the renal function during the shock phase will hinder the excretion of sodium and chlorine and cause hyperchlorinemia. At this time, it is best to use an equilibrium salt solution for volume expansion.
03
How should I deal with a conflict?
Clinically, it is often encountered that the drug instructions require glucose injection as a solvent, but patients with diabetes must avoid the contradiction of sugar intake.
For example, if a patient with sinus tachycardia with diabetes needs to use amiodarone injection, the drug label states that the solvent can only choose sugar water and not saline.
Image source: Clinical Decision Assistant app
Because amiodarone is a diiodo substitute on the benzene ring, in general, the iodine substitute is unstable and prone to spontaneous deiodine degradation, while the acidic environment can inhibit the degradation of amiodarone.
Moreover, the pH of amiodarone injection is 2.5-4.0, the pH of 5% glucose injection is 3.2-5.5, and the pH of normal saline is 4.5-7.0, so amiodarone is easily degraded in normal saline, plus chloride ions in NaCl solution will replace the iodine on the benzene ring, resulting in precipitation.
Of course, in order to avoid excessive glucose intake clinically, non-glucose solutions such as fructose and xylitol can also be selected as solvents. However, this kind of solution is more expensive, and there are compatibility contraindications with many drugs, and it is not a solvent recommended in the drug instructions, so it is recommended not to be selected as a conventional solvent.
In fact, diabetics are not completely unable to use glucose, just not in excess. Under the premise of not changing the conventional treatment and eating of diabetic patients, insulin can be used clinically to flush the glucose in the infusion (generally 1U insulin is against 4-5g of glucose), and pay attention to the use of process blood glucose monitoring. The same is true of the doctor's lysate selection of sodium nitroprusside earlier in the article.
For another example, patients with heart failure with gastric ulcers need to use pantoprazole for injection, and the intake of normal saline must be controlled due to the significant increase in sodium retention in heart failure.
From the perspective of drug stability, pantoprazole solvent for injection must use brine, what to do at this time?
This requires analysis to determine that the average heart failure patient limits sodium intake < 2g per day to reduce the burden on the heart. Calculated by infusion of normal saline:
100 mL NaCl contains 0.9 g of sodium × [23/(23 + 35.5)] = 0.35 g. Then 2g of sodium per day is equivalent to (2/0.35) × 100 = 570mL of normal saline, as long as it does not exceed this amount, saline can still be used as a solvent.
When necessary, sodium intake is also dynamically controlled based on the sodium levels suggested by blood gas analysis to maintain electrolyte balance.
In summary, the use of medicine such as the use of soldiers, the use of proper use, the medicine to the disease; improper use, loss of soldiers, delay in the disease. The same is true of the solvent selection for infusions.
Regarding the choice of solvent, what other drug doubts do you have, come to the comment area to tell us ~
bibliography:
[1] Penicillin sodium for injection drug instructions.
[2] Fluroxacin injection drug instructions.
[3] Furosemide injection drug instructions.
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Source: Clinical Pharmacy Channel of the Medical Community
Author: Wang Shuping Chief Pharmacist
Editor-in-charge: Zheng Huaju
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