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Advances In Research Of Effects Of Anesthetic Drugs On Antibiotic Metabolism
May 14, 2018

With the development of surgical techniques, more and more surgeries have been carried out, antibiotics have become an important part of the prevention of surgical infections, and the irrational application of antibiotics has also become one of the prominent problems in China. With the continuous deepening of the study of antibiotics, many previous reports of many factors affecting antibiotic metabolism such as age, liver and kidney function, operation time and surgical blood loss, urine volume and urine pH, according to previous domestic and international literature reported general anesthesia Will affect the body's metabolism, anesthetic drugs will affect the body's circulation, liver and kidney function and intraoperative use of anesthetics will interact with antibiotics affect each other's efficacy, but under general anesthesia, antibiotic half-life will not change and what kind of changes occur It is rarely proposed, so we will review the research on the effects of antibiotic metabolism under general anesthesia in order to facilitate the rational use of antibiotics in surgical anesthesia and further reduce the surgical infection rate.


1. The effect of inhalation anesthetics on body circulation

The effect of inhaled anesthetics on the circulation of the body, as described in the general literature, is that inhaled anesthetics can lower the mean arterial pressure and weaken the myocardial contractility. The antihypertensive effects of inhaled anesthetics are mainly through: 1) inhibition of cardiac contractility and thus reduction of cardiac output. The order of inhibition of myocardial contractility is: halothane> enflurane> isoflurane = sevoflurane. 2) Decrease blood pressure by expanding peripheral blood vessels to reduce the resistance of peripheral blood vessels.


2. The effect of intravenous injection of anesthetic on body circulation

The effects of intravenous injections of anesthetics on the circulation vary with the type of drug, but most of the intravenous anesthetics described in the literature have inhibitory effects on the circulatory system, and the degree of inhibition is related to the depth of anesthesia.

1) After intravenous injection of thiopental, myocardium inhibited the markedly decreased cardiac index, and the heart index decreased by about 25% during deep anesthesia, and the cardiac output decreased in different degrees. 2) Myocardial contractility decreased by 38% after intravenous injection of propofol. 3) Etomidate had no significant effect on the circulatory system. Some arterial pressures slightly decreased, and cardiac output increased or remained unchanged.


3. The effect on renal function under anesthesia

The effect of anesthesia on renal function is mainly related to the effect on the circulation. In general, under the anesthesia, the renal blood perfusion decreases and the glomerular filtration rate decreases. We know that for most drugs after the liver is metabolized, it will be excreted by the kidneys. Therefore, when the blood flow in the kidneys is reduced, the excretion volume of the drug will decrease with the urine. The drug will accumulate in the body and the plasma concentration of the drug will decrease. Therefore, the half-life of the drug is reduced. Correspondingly it will also be extended. For example, aminoglycoside antibiotics, polymyxin antibiotics, etc., in the renal blood perfusion reduced when the drug half-life significantly extended, for the penicillin antibiotics, chloramphenicol and erythromycin drug half-life, when renal blood perfusion is reduced only Slightly longer, but for some drugs that are not excreted by the kidneys, such as doxycycline, macrolides, rifamycin, etc., or antibiotics with less than 15% excretion from the urine when renal blood is perfused The half-life is not affected when it is reduced.


4. The effect on liver function under general anesthesia

The effect of general anesthesia on the liver. On the one hand, it changes the blood flow of the liver. Most general anesthetics reduce the blood flow in the portal vein of the liver. This is mainly related to changes in cardiac output, but the changes in the flow of the hepatic artery are related to the drugs used and can increase or decrease. Or does not change, and the increase of hepatic arterial blood flow compensates for the limited portal vein blood flow. Therefore, under general anesthesia, the total blood flow of the liver is reduced, and the distribution of the drug in the liver is also reduced. Slow down. On the other hand, general anesthetic drugs can lead to a decrease in the activity of drug-metabolizing enzymes in the liver, as indicated by the Anesthesiology School and the Pharmacology Institute of the Vanderbilt University School of Medicine in Nashville in 1991, where all known volatile anesthetics are known to date. Most of the drug metabolism has inhibitory effects, such as pethidine, lidocaine, and propranolol, and its inhibitory effects on other drugs are mainly through affecting the distribution of tissues and organs and drug metabolism enzyme activity.


It is known that the metabolism of most drugs is basically carried out in the liver through a series of reactions such as oxidation, reduction, hydrolysis, etc. Therefore, no matter what causes liver metabolism dysfunction, metabolism of drugs metabolized by the liver will be reduced, so the half-life of drugs will also be extended. . In an article published in 2013 by the foreign scholar Sarani, he pointed out that the reduction of liver metabolic function will affect the half-life of drugs that are mainly metabolized by the liver, such as ceftriaxone, and the hepatic metabolic dysfunction of ceftriaxone is prolonged. Hoffmann et al. (1970) found that the normal half-life of carbenicillin was 1 hour. In patients with liver disease, the half-life of carbenicillin was prolonged to 1.9 hours due to a decrease in liver metabolic function.


5. The Interaction between anesthetic drugs and antibiotics

Narcotic drugs interact with most antibiotics and affect each other's efficacy. In 1975, CECIL pointed out that under the condition of general anesthesia, antibiotics and anesthetic drugs react to each other. The interaction between drugs mainly affects two aspects. On the one hand, it influences the pharmacokinetics, such as affecting drug absorption and distribution. Metabolism, metabolism, and excretion interact, and on the other hand, it influences the efficacy of one drug over another. Min CH pointed out that when anesthetic muscle relaxants are combined with antibacterial drugs, most antibacterial drugs will increase muscle relaxation or prolong muscle relaxant action time, such as non-depolarizing muscle relaxants can be extended when combined with some aminoglycoside antibiotics Muscle relaxant action time.

The muscle relaxants produced by the combination of polymycin and muscle relaxants act by affecting the anterior and posterior membranes of the joint, and this effect cannot be antagonized by cholinesterase inhibitors or calcium ions. However, some antibiotics can only enhance non-depolarizing muscle relaxant efficacy such as lincomycin and clindamycin, and the synergistic effect produced when combined with non-depolarizing muscle relaxants can be inhibited by cholinesterase. Drugs or calcium ions are antagonistic. Condon in 1995 pointed out that some antibiotics do not have the effect of enhancing muscle relaxants such as penicillin-like piperacillin and the cephalosporin cefoxitin. Macrolide antibiotics are used in combination with anesthetic drugs, and adverse interactions are caused by macrolide antibiotics that inhibit hepatic metabolic enzymes. For example, when combined with benzodiazepines or opioids, they affect the body. The metabolic process extends its time effect.


In 1989, Bartkowski pointed out that when used with erythromycin, the elimination half-life of the narcotic analgesic alfentanil was extended from 84±8.2 minutes to 131±43 minutes, and the clearance rate was reduced from 3.9±0.8 ml/kg to 2.9±1.2. Ml/kg. Xu Lixian pointed out that erythromycin had no effect on the metabolic process of sufentanil. Patients who had been treated with erythromycin for oral administration for 1 week (500 mg/time, 3 times/day) received midazolam when they received midazolam. The AUC of midazolam was 4 times higher than that of the control group, and the plasma peak concentration was increased 3 times. The duration of its effects such as sedation and forgetfulness is also prolonged. In a clinical report by Hiller in 1990, in an 8-year-old boy adenoidectomy, erythromycin, a preoperative prophylactic antibiotic, interacts with midazolam, erythromycin and midazolam. The interaction between lunons is more extensive than we previously knew.


Ronald Miller pointed out that some cephalosporin antibiotics combined with anesthetic drugs and anesthesia-related drugs also have serious adverse reactions, such as cephradine and succinylcholine, phenytoin and meta-hydroxylamine and other drugs incompatibility exists. In summary, the metabolism of antibiotics in the body is very complex, affecting many factors of antibiotic metabolism, and the body circulation and liver and kidney function will be affected under anesthesia. At the same time, anesthetic drugs will interact with most antibiotics, and the body is in operation. In response to stress and trauma, liver and kidney blood flow is further reduced. Therefore, under general anesthesia, body metabolism slows down, and the half-life of antibiotics is correspondingly prolonged, as Ueda pointed out in a 1985 study. The plasma concentrations of cefotiam and ceftizoxime were measured during and 30 minutes, 60 minutes, 120 minutes, and 180 minutes at the time of surgery and during surgery. The plasma concentration was higher during surgery than during no operation. Blood concentration.


However, in the course of surgery, the surgeon will additionally use antibiotics during the operation because of special circumstances, such as long operation time, more intraoperative blood loss and local tissue damage and heavy pollution, etc. In the case of additional antibiotics during surgery, according to domestic and foreign literature reports The question of how to use additional antibiotics during surgery has not yet reached a uniform standard. According to the comprehensive domestic and international literature, most scholars believe that more than 1500 ml of intraoperative blood loss need to be used once more than 1500 ml, but some scholars believe that There is no need for additional antibiotics, and the use of a prophylactic antibiotic before surgery can prevent infection. According to the above-mentioned surgery, anesthesia will prolong the half-life of the drug. Therefore, it is necessary to further study the need for supplementation and how to correctly use antibiotics during surgery. This will further promote the rational use of antibiotics and reduce the infection rate during surgery.


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