Isoflurane

Isoflurane is a drug that belongs to a group of agents used in anesthesiology. Its use is justified when there is a need for inhalation administration of a drug to reduce sensitivity to pain by putting the patient into deep sleep. Reversible inhibition of the central nervous system, which occurs under the influence of anesthesia, causes temporary loss of consciousness and memory, a noticeable decrease in some reflexes, muscle relaxation and complete loss of sensitivity, which is necessary in the case of surgical intervention.

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Indications Isoflurane

"Isoflurane" is an inhalation anesthetic. It may be required during surgical operations requiring general anesthesia. Inhalation anesthesia is also often used in obstetrics, for example, pain relief during cesarean section, as well as when minor surgical interventions are performed that do not require loss of consciousness.

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Release form

The drug is produced as a 100% isoflurane solution for inhalation in dark glass bottles of 100 and 250 ml. Both forms of release of a strong painkiller used in surgery and obstetrics are bottles filled with a transparent, thick, non-flammable liquid that does not have a specific color.

Inhalations are carried out using special calibrated anesthetic vaporizers, which provide and maintain the required concentration of the solution supplied to the patient’s body, depending on the stage of anesthesia.

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Pharmacodynamics

Isoflurane is an inhalation anesthetic used for general anesthesia that is equally effective in providing induction of anesthesia, patient support during surgery, and rapid recovery from anesthesia.

Under its influence, there is a rapid loss of sensitivity in patients, a decrease in pharyngeal and laryngeal reflexes, a release of muscle tension and their relaxation, which is necessary for many abdominal surgeries.

The use of isoflurane for inhalation anesthesia allows for easy control of the depth (level) of anesthesia, which is very important during surgery, since exceeding the dose and effectiveness of the drug can lead to tragic consequences, and insufficient anesthesia can lead to premature return of sensitivity or awakening of the patient.

The depth of anesthesia has a significant effect on arterial pressure. The pressure decreases during the induction stage due to the expansion of arterial and venous vessels, while in the surgical phase the blood pressure normalizes. A further increase in the depth of anesthesia can lead to a proportional decrease in pressure, up to the development of arterial hypotension.

The drug significantly weakens spontaneous breathing, but does not affect the heart rate and blood ejection during myocardial contraction. An increase in heart rate during artificial ventilation of the lungs, provided that the tension of carbon dioxide in arterial blood is normal, is caused by the need to maintain the cardiac output.

With superficial anesthesia, the drug does not affect the blood flow of the brain, but with the deepening of anesthesia, the blood flow can increase, causing an increase in the pressure of the cerebrospinal fluid. Stabilization of the condition is achieved by reducing hyperventilation the day before or during the action of anesthesia. Hyperventilation should also be used if the patient has increased intracranial pressure.

Isoflurane has a slight irritating effect due to the barely perceptible pungent smell of ether, which can negatively affect the induction of a gaseous substance; however, the rate of development of processes during induction of anesthesia and at the final stage remains quite high.

The EEG and vascular activity indices remain normal during isoflurane anesthesia. Their changes are observed only in isolated cases.

The use of the drug does not cause an increase in the secretion of salivary and tribronchial glands (saliva and sputum).

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Pharmacokinetics

The active substance of the drug is very poorly soluble in body fluids. This leads to the rapid development of partial pressure in the alveoli, which is necessary for anesthesia.

Isoflurane is excreted from the body quite quickly through the respiratory tract, and only a small amount (less than 0.2%) is excreted by the kidneys in the form of metabolites. The concentration of organic and inorganic fluorides formed as a result of the metabolization and breakdown of isoflurane is quite low and is considered safe for the kidneys; however, patients diagnosed with severe renal impairment should be given anesthesia with particular caution.

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Dosing and administration

Anesthesia using the drug "Izufloran", both introductory and at all subsequent stages, is carried out using special evaporators.

Preliminary preparation of patients for anesthesia is carried out using medications corresponding to the selected type of anesthesia. When choosing Isufloran for anesthesia, it is necessary to take into account the ability of the latter to have a depressing effect on breathing. Drugs that inhibit the conduction of nerve impulses can be used to reduce salivation (which is not at all necessary in the case of isufloran), but it must be taken into account that they can enhance the effect of Isufloran in terms of increasing the heart rate.

Induction anesthesia. The recommended initial dose of isufloran in the anesthesia mixture is 0.5%. To avoid coughing during inhalation of isufloran, anesthesia should be started not with the inhalation method, but with intravenous administration of short-acting barbiturates or other painkillers used in anesthesia. Coughing may occur in both adult patients and children, which is associated with an increase in saliva secretion.

To achieve a surgical level of anesthesia, the concentration of the drug must be brought to 1.5-3%. In this case, the operation can begin after 8-10 minutes.

Surgical stage of anesthesia. A sufficient level of anesthesia is achieved with an isoflorane concentration of 1 to 2.5% in a mixture of oxygen with 70% nitric oxide. When using oxygen alone or with a low content of nitric oxide, the isoflorane concentration should be increased to 1.5-3.5%.

The decrease in blood pressure at this stage of anesthesia depends on the depth of anesthesia. If a strong decrease in pressure is observed during deep anesthesia, the isoflurane dose must be adjusted. Controlled hypotension during artificial ventilation is achieved with an isoflurane concentration of 2.5-4%. The isoflurane dose required in this case can be reduced by prophylactic administration of Clonidine.

During the recovery stage, the concentration of isoflurane gradually decreases from 0.5% at the time of closure of the surgical wound to 0 at the end of the operation. At this stage, it is necessary to make sure that the action of muscle relaxants and various blockers used during anesthesia has also ceased.

When the effect of all anesthetic drugs is over, the patient's airways are ventilated with pure oxygen for some time to end the anesthesia. The end of the anesthesia occurs quite quickly and easily.

The activity of anesthetics is usually measured in MAC (minimum alveolar concentration). This is the smallest effective dose of the drug, which depends on the patient's age.

The highest MAC rate is found in children aged one to six years (first month of life – 1.6%, in 1-6 months the rate increases to 1.87, then up to one year it decreases slightly and is 1.8%, and from one year to six years it returns to the level of 1.6%). At the same time, MAC is lower in premature babies (in 6-7 months – 1.28%, in 8 months – 1.41%). In children over 6 years old, teenagers and in adolescence the MAC rate is 1.25%.

In adults, the minimum concentration values are relatively low. For young people aged 20 to 40, the MAC will be within 1.18%, for middle-aged people (approximately up to 60 years) this value decreases to 1.15%, and for the elderly it is 1.05%.

These figures are valid if isoflurane is used in combination with oxygen, but if the main component is a mixture of oxygen with 70% nitrous oxide (for children - with 75% nitrous oxide), the concentration of isoflurane should be significantly reduced (more than 2 times). For example, for middle-aged people, the MAC indicator will be equal to 0.50%, for young people - 0.56%, for elderly people it will decrease to 0.37%.

At first glance, the numbers are so small that they hardly differ from each other, but in medicine, and especially in anesthesiology, every hundredth of a percent is a value equal to a person's life. The above are only approximate figures that anesthesiologists use to calculate the necessary concentration of isoflurane in the gas. In fact, this value may depend on the patient's health and some physiological characteristics of his body, in particular, on the tolerance of the drug.

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Use Isoflurane during pregnancy

As for the use of Isoflurane during pregnancy, there are no precise instructions in the manufacturer's instructions. It is not recommended to use isoflurane in the first trimester of pregnancy. This is due to the possible toxicity of the drug and its negative impact on reproductive function. Research in this area has only been conducted on animals; no impact on humans has been established.

In general, it is considered better not to use anesthetics during pregnancy. If there is an extreme need, the use of isoflurane should be carried out taking into account all the risks to the health and life of the mother and fetus.

When performing birth operations under anesthesia (for example, cesarean section), a mixture of oxygen and nitric oxide should be used, then the recommended dose of isoflurane will be from 0.5 to 0.75%.

It is not recommended to use Isoflurane for gynecological surgeries (e.g. gynecological cleaning) performed under general anesthesia, as this increases the risk of major blood loss.

During breastfeeding, the use of anesthesia with isoflurane is not prohibited. However, breastfeeding will have to be interrupted until all the anesthesia leaves the mother's body.

Contraindications

Like most medical drugs, Isoflurane has its own contraindications for use. One of these contraindications is malignant hyperpyrexia (or otherwise, hyperthermia), which manifests itself in a sharp increase in body temperature during anesthesia, which threatens the patient's life. This pathology is hereditary and occurs under the influence of drugs used for anesthesia.

For this reason, the use of isoflurane is unacceptable in patients who have already experienced similar manifestations or have a hereditary predisposition to the disease. The latter applies to both cases of the disease in the family and the development of diseases that can lead to increased muscle metabolism (various types of myopathy, myotonia, King's syndrome, muscle dystrophy, etc.).

Isoflurane anesthesia is not used in cases of jaundice and severe liver damage. Also, if a person has a very high temperature accompanied by fever (fever).

It is unacceptable to use Isofloran if a person has increased sensitivity to this solution or to anesthetic drugs containing halogens. The same applies to cases of eosinophilia, when under the influence of the above-described drugs the level of eosinophilic cells in the blood, which perform a protective function in the leukocyte formula, increases.

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Side effects Isoflurane

The use of the drug "Isoflurane" for anesthesia is sometimes accompanied by undesirable symptoms related to the side effects of this drug. The most common reactions, characteristic of all halogen-containing drugs used in anesthesiology, include heart rhythm disturbances, increased blood pressure and depression of the respiratory center.

"Isoflurane", like any other anesthetic, can cause such unpleasant symptoms as nausea accompanied by vomiting, short-term changes in the blood composition towards an increase in leukocytes, chills, intestinal obstruction, loss of consciousness after the completion of the operation and the effects of anesthesia.

Sometimes patients experience a slowing of the heart rate (bradycardia) or an increase in it (tachycardia), hemorrhages in various organs, an increase in the level of carboxyhemoglobin (a compound of hemoglobin with carbon monoxide), and the development of an extreme degree of myopathy (rhabdomyolysis). Mood swings due to anesthesia are common, but bronchospasms caused by the use of Isoflurane are quite rare.

Sometimes doctors have to deal with such a side effect of the drug as the development (during its use) of liver dysfunctions of varying severity, from jaundice and hepatitis to liver tissue necrosis and death. In childhood, cases of laryngospasm caused by increased salivation are not uncommon.

Rarely, reactions associated with malignant hyperthermia, increased levels of potassium in the blood plasma and other changes in its composition, anaphylactic reactions, and cardiac arrest have occurred.

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Overdose

An incorrectly calculated isoflurane level can lead to an overdose of the drug, which is manifested in significant depression of the respiratory function and a decrease in blood pressure to critical values. The decrease in blood pressure in this case is also associated not with myocardial depression, but with the vasodilatory effect of isoflurane.

If an overdose is established, the drug is immediately stopped and preventive ventilation of the lungs with pure oxygen is performed to remove residual anesthesia. This is a very unpleasant situation, considering that it can happen during surgery. In this case, oxygen ventilation is replaced by controlled ventilation with small doses of isoflurane.

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Interactions with other drugs

The use of Isoflurane for anesthesia should be carried out taking into account information on drug interactions with other drugs.

To relax muscles, which is necessary in case of abdominal and some other surgeries, the effect of isoflurane is sometimes supplemented with drugs from the muscle relaxant group. In this case, isoflurane enhances their effect, which means that the doses of muscle relaxants, taking this into account, should be relatively small. To reduce the effectiveness of non-depolarizing drugs for relaxing skeletal muscles, "Proserin" is used (the active substance is neostigmine methylsulfate), which does not react with isoflurane.

The simultaneous effect of isufloran and adrenaline or amphetamines on the human body can lead to the development of arrhythmia. If the patient has no heart problems, the dose of adrenaline should be no more than 3 micrograms per kilogram of weight, but if there are heart rhythm disturbances, the dosage will have to be significantly reduced. It is even better to stop taking drugs belonging to the class of beta-sympathetics, at least a couple of days before the expected date of surgery.

Concomitant use of isoflurane and vasodilators can lead to a significant decrease in blood pressure.

It is not allowed to take anesthesia drugs and MAO inhibitors at the same time. This is because the latter increase the effect of isufloran and other similar drugs. You should stop taking MAO inhibitors at least 2 weeks before the scheduled date of surgery.

Some drugs, in particular beta blockers, can protect the patient's heart from possible arrhythmia caused by isoflurane. If necessary, the heart rate can be increased and the necessary vasoconstriction can be achieved using appropriate sympathomimetics, a list of which should be available to every anesthesiologist.

The drug "Isomyazid", used in the treatment and prevention of tuberculosis, can increase the susceptibility of the liver to the toxic effects of isoflurane, so it is advisable to stop taking the above-mentioned drug at least 7 days before the date of surgery to protect the liver from destruction.

Opioid (narcotic) analgesics (Morphine, Omnopon, Isopromedol, Methadone and others), used in parallel with isoflurane, contribute to increased respiratory depression, which can be life-threatening for the patient.

When CO2-absorbents used in anesthesia machines dry out _, the introduction of isoflurane can cause an increase in carboxyhemoglobin in the blood, which has a strong toxic effect, which in turn leads to the destruction of liver cells.

In order to prevent liver dysfunction, it is not recommended to perform repeated anesthesia using the same halogen-containing drugs, which include Isufloran.

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Storage conditions

Halogen-containing drugs for anesthesia retain their properties at a temperature of no more than 30 degrees. And the safety of the drug and those around is ensured by storing the drug "Isoflurane" in places inaccessible to children with their enormous cognitive abilities.

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Shelf life

The shelf life of the drug, provided it is stored sealed in its original packaging, is 5 years.