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Chapter: Modern Pharmacology with Clinical Applications: General Anesthesia: Intravenous and Inhalational Agents

Intravenous Anesthetic Agents

Among the barbiturates , three com-pounds, thiopental sodium (Pentothal Sodium), thiamy-lal sodium (Surital), and methohexital sodium (BrevitalSodium), are useful as induction agents, as supplemen-tal drugs only during short periods when surgery re-quires increased depth of anesthesia, or as maintenance hypnotics for short surgical procedures.

INTRAVENOUS ANESTHETIC AGENTS

Important pharmacological characteristics for anes-thetic management using IV anesthetics are shown in Table 25.1. The principal use of these drugs is to induce anesthesia. In typical anesthetic management, the last event that the patient remembers is the insertion of the needle. Patients are often unaware that other anesthet-ics, most frequently in the form of inhalational drugs, are necessary to maintain the anesthesia.


Ultra–Short-Acting Barbiturates

Among the barbiturates , three com-pounds, thiopental sodium (Pentothal Sodium), thiamy-lal sodium (Surital), and methohexital sodium (BrevitalSodium), are useful as induction agents, as supplemen-tal drugs only during short periods when surgery re-quires increased depth of anesthesia, or as maintenance hypnotics for short surgical procedures. These drugs are termed ultra–short-acting agents, since their rapid entry into the CNS is followed by relatively rapid redistribu-tion of the drug to indifferent tissues, such as skeletal muscle. Because of their slow rate of metabolism, these agents, when used in large repeated doses or by contin-uous infusion, cause persistent hypnosis or subtle men-tal cloudiness.

Pharmacological Actions

All three IV barbiturates rapidly produce unconscious-ness. Since unconsciousness is attended by amnesia without either analgesia or skeletal muscle relaxation, anesthetized patients may react to painful stimuli but are unaware and do not remember the procedure. For example, patients undergoing short surgical procedures with thiopental alone may respond to surgical maneu-vers with facial grimaces or arm and leg movements and with potentially dangerous changes in blood pressure and heart rhythm. Consequently, induction of anesthe-sia may be nearly the only indication for thiopental. However, if thiopental is to be used to maintain anes-thesia for short operative procedures, analgesia should be provided with other drugs.

Thiopental remains the most popular IV induction agent. Its rapid and pleasant induction of anesthesia and its relatively low cost are among the reasons for its high acceptance rate by both the patient and the practi-tioner. Also, it does not induce obstructive secretions in the airway, produces little or no emesis, and does not sensitize the myocardium to endogenous cate-cholamines that may be released in response to the stress of surgery. It can, however, cause cardiovascular depression.

Although the pharmacological actions of the IV bar-biturates are similar, methohexital in particular may provide some advantages in selected situations. Its du-ration of action is only half as long, and it exerts fewer cumulative effects than does thiopental. The occasional requirement of intraoperative communication between the patient and surgeon is easily satisfied with metho-hexital because of its short duration of action. For ex-ample, it can be used for basal sedation in the few mo-ments that a very painful stimulus is applied, and then, as consciousness is quickly regained, the surgeon can as-sess the results by talking to the patient.

Adverse Effects

Cardiovascular depression may occur after the admin-istration of barbiturates by IV bolus. The hemodynamic changes are transient in the healthy patient with good cardiovascular reserve, but they may be prolonged and/or not well tolerated in elderly patients or those with poorly compensated myocardial function. For ex-ample, thiopental decreases myocardial contractility and dilates capacitance vessels, thereby reducing ve-nous return to the heart. The healthy normovolemic patient may compensate for these changes by an in-crease in heart rate to maintain stroke volume and blood pressure. The patient with myocardial disease or hypovolemia may not be capable of appropriate com-pensation. Serious ischemic impairment of the my-ocardium may occur in patients with coronary artery disease.

Respiratory depression also may occur after the ad-ministration of barbiturates by IV bolus. Respiration may be further compromised by barbiturate-induced laryngospasm, as it is with most anesthetics.

There is some tendency of the ultra–short-acting bar-biturates to precipitate at biological pH once they are in-jected, especially if the injection solution is not given slowly enough to allow the drug to be diluted by the ve-nous blood. If inadvertent intraarterial injection occurs and drug precipitates are formed, arterial thrombosis, vasospasm, local ischemia, and possibly tissue sloughing may occur. Methohexital precipitation is less common, since it is a more potent barbiturate and can be provided in a more dilute solution. Barbiturate solutions must not be coadministered with acidic solutions, such as those containing meperidine, morphine, or ephedrine.

Most of the adverse reactions associated with the use of the intravenous barbiturates are predictable and therefore can be controlled or avoided. Some reactions, such as hypersensitivity, are entirely unpredictable. Particularly patients with asthma, urticaria, or an-gioedema may acquire allergic hypersensitivity to the barbiturates. Acute intermittent porphyria is an ab-solute contraindication to the use of barbiturates.

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