General anesthetics are drugs that induce general anesthesia and are most commonly used to induce anesthesia during surgical procedures. General anesthetics are given only under controlled situations by anesthesiologists or nurse anesthetists. General anesthesia is achieved by the use of one or more drugs. Often a synergistic combination of drugs is used, which allows for smaller doses of each drug and better control of the patient’s anesthetized state. Inhalational anesthetics are volatile liquids or gases that are vaporized or mixed with oxygen to induce anesthesia. For a historical perspective on general anesthesia, see Box 11-1.

Parenteral anesthetics (Table 11-1) are given intravenously and are used for induction and/or maintenance of general anesthesia, induction of amnesia, and as adjuncts to inhalation-type anesthetics (Table 11-2). The specific goal varies with the drug. Common intravenous anesthetic drugs include drugs classified solely as general anesthetics, such as etomidate and propofol.

Adjunct anesthetics or simply adjuncts are also used. Adjunct is a general term for any drug that enhances clinical therapy when used simultaneously with another drug. Adjunct drugs can be thought of as “helper drugs” when their use complements the use of any other drug(s). They are used simultaneously with general anesthetics for anesthesia initiation (induction), sedation, reduction of anxiety, and amnesia. Adjuncts include neuromuscular blocking drugs (NMBDs; see Neuromuscular Blocking Drugs later in the chapter), sedative-hypnotics or anxiolytics (see Chapter 12) such as propofol (this chapter), benzodiazepines (e.g., diazepam, midazolam), barbiturates (e.g., thiopental, methohexital; see Chapter 12), opioid analgesics (e.g., morphine, fentanyl, sufentanil; see Chapter 10), anticholinergics (e.g., atropine; see Chapter 21), and antiemetics (e.g., ondansetron; see Chapter 52). Note that propofol can be used as a general anesthetic and/or sedative-hypnotic, depending on the dose. The simultaneous use of both general anesthetics and adjuncts is called balanced anesthesia. Common adjunctive anesthetic drugs are listed in Table 11-3.

Many theories have been proposed to explain the actual mechanism of action of general anesthetics. The drugs vary widely in their chemical structures, and their mechanism of action is not easily explained by a structure-receptor relationship. The concentrations of various anesthetics required to produce a given state of anesthesia also differ greatly. The Overton-Meyer theory has been used to explain some of the properties of anesthetic drugs since the early days of anesthesiology. In general terms, it proposes that, for all anesthetics, potency varies directly with lipid solubility. In other words, across a continuum of drug potency, fat-soluble drugs are stronger anesthetics than water-soluble drugs. Nerve cell membranes have high lipid content, as does the blood-brain barrier (see Chapter 2). Lipid-soluble anesthetic drugs can therefore easily cross the blood-brain barrier to concentrate in nerve cell membranes.

The overall effect of general anesthetics is a progressive reduction of sensory and motor CNS functions. The degree and speed of this process varies with the anesthetics and adjuncts used along with their dosages and routes of administration. General anesthesia initially produces a loss of the senses of sight, touch, taste, smell, and hearing, along with loss of consciousness. Cardiac and pulmonary functions are usually the last to be interrupted, because they are controlled by the medulla of the brainstem. These are the classical “stages” of anesthesia. Mechanical ventilatory support is absolutely necessary. In more extensive surgical procedures, especially those involving the heart, pharmacologic cardiac support involving adrenergic drugs (see Chapter 18) and inotropic drugs (see Chapter 24) may also be required.

The reactions of various body systems to general anesthetics are further described in Table 11-4.

General anesthetics are used to produce unconsciousness as well as relaxation of skeletal and visceral smooth muscles for surgical procedures as well as in electroconvulsive therapy for severe depression (see Chapter 16).

Contraindications to the use of anesthetic drugs include known drug allergy. Depending on the drug type, contraindications may also include pregnancy, narrow-angle glaucoma, and known susceptibility to malignant hyperthermia (see Adverse Effects) from prior experience with anesthetics.

With the development of newer drugs, many of the unwanted adverse effects characteristic of the older drugs (such as hepatotoxicity and myocardial depression) are now a thing of the past. In addition, many of the bothersome adverse effects such as nausea, vomiting, and confusion are less common since balanced anesthesia is widely used. Substance abuse (e.g., alcohol abuse; see Chapter 17) can predispose a patient to anesthetic-induced complications (e.g., liver toxicity). A positive history of substance abuse may lead to dosage adjustments in one or more of the drugs used. A drug-abusing patient with a high tolerance for street drugs may require larger doses of anesthesia-related drugs (e.g., benzodiazepines, opioids) to achieve the desired sedative effects.

Malignant hyperthermia is an uncommon, but potentially fatal, genetically linked adverse metabolic reaction to general anesthesia. It is classically associated with the use of volatile inhalational anesthetics as well as the depolarizing NMBD succinylcholine (see Neuromuscular Blocking Drugs later in this chapter). Signs include rapid rise in body temperature, tachycardia, tachypnea, and muscular rigidity. Patients known to be at greater risk for malignant hyperthermia include children, adolescents, and individuals with muscular and/or skeletal abnormalities such as hernias, strabismus, ptosis, scoliosis, and muscular dystrophy. Malignant hyperthermia is treated with cardiorespiratory supportive care as needed to stabilize heart and lung function along with the skeletal muscle relaxant dantrolene (see Chapter 12). In fact, by law, all facilities that provide general anesthesia must maintain a certain amount of dantrolene on hand in case of malignant hyperthermia.