Anesthesia is a combination of the endpoints (discussed above) that are reached by drugs acting on different but overlapping sites in the central nervous system. General anesthesia (as opposed to sedation or regional anesthesia) has three main goals: lack of movement (paralysis), unconsciousness, and blunting of the stress response. In the early days of anesthesia, anesthetics could reliably achieve the first two, allowing surgeons to perform necessary procedures, but many patients died because the extremes of blood pressure and pulse caused by the surgical insult were ultimately harmful. Eventually, the need for blunting of the surgical stress response was identified by Harvey Cushing, who injected local anesthetic prior to hernia repairs. This led to the development of other drugs that could blunt the response leading to lower surgical mortality rates.
The most common approach to reach the endpoints of general anesthesia is through the use of inhaled general anesthetics. Each anesthetic has its own potency which is correlated to its solubility in oil. This relationship exists because the drugs bind directly to cavities in proteins of the central nervous system, although several theories of general anesthetic action have been described. Inhalational anesthetics are thought to exact their effects on different parts of the central nervous system. For instance, the immobilizing effect of inhaled anesthetics results from an effect on the spinal cord whereas sedation, hypnosis and amnesia involve sites in the brain.
The potency of an inhalational anesthetic is quantified by its minimum alveolar concentration or MAC. The MAC is the percentage dose of anesthetic that will prevent a response to painful stimulus in 50% of subjects. The higher the MAC, generally, the less potent the anesthetic.
Syringes prepared with medications that are expected to be used during an operation under general anesthesia maintained by sevoflurane gas:
- Propofol, an hypnotic
- Ephedrine, in case of hypotension
- Fentanyl, for analgesia
- Atracurium, for neuromuscular blockade
- Glycopyrronium bromide (here under trade name “Robinul”), reducing secretions
The ideal anesthetic drug would provide hypnosis, amnesia, analgesia, and muscle relaxation without undesirable changes in blood pressure, pulse or breathing. In the 1930s, physicians started to augment inhaled general anesthetics with intravenous general anesthetics. The drugs used in combination offered a better risk profile to the person under anesthesia and a quicker recovery. A combination of drugs was later shown to result in lower odds of dying in the first 7 days after anesthetic. For instance, propofol (injection) might be used to start the anesthetic, fentanyl (injection) used to blunt the stress response, midazolam (injection) given to ensure amnesia and sevoflurane (inhaled) during the procedure to maintain the effects. More recently, several intravenous drugs have been developed which, if desired, allow inhaled general anesthetics to be avoided completely.:720