For centuries, humans relied on natural medicines and physical methods to control surgical pain. Historical texts describe the sedative effects of cannabis, henbane, mandrake, and opium poppy. Physical methods such as cold, nerve compression, carotid artery occlusion, and cerebral concussion were also employed, with variable effect. Although surgery was performed under ether anesthesia as early as 1842, the first public demonstration of surgical general anesthesia in 1846 is generally accepted as the start of the modern era of anesthesia. For the first time, physicians had a reliable means to keep their patients from experiencing pain during surgical procedures.
The neurophysiologic state produced by general anesthetics is characterized by five primary effects: unconsciousness, amnesia, analgesia, inhibition of autonomic reflexes, and skeletal muscle relaxation. None of the currently available anesthetic agents when used alone can achieve all five of these desired effects well. An ideal anesthetic drug should also induce rapid, smooth loss of consciousness, be rapidly reversible upon discontinuation, and possess a wide margin of safety.
The modern practice of anesthesiology relies on the use of combinations of intravenous and inhaled drugs (balanced anesthesia techniques) to take advantage of the favorable properties of each agent while minimizing their adverse effects. The choice of anesthetic technique is determined by the type of diagnostic, therapeutic, or surgical intervention that the patient needs. For minor superficial surgery or invasive diagnostic procedures, oral or parenteral sedatives can be combined with local anesthetics in a technique termed monitored anesthesia care (MAC) (see Box: Sedation & Monitored Anesthesia Care, and Chapter 26). These techniques provide profound analgesia, with retention of the patient’s ability to maintain a patent airway and to respond to verbal commands. For more invasive surgical procedures, anesthesia may begin with a preoperative benzodiazepine, be induced with an intravenous agent (eg, thiopental or propofol), and be maintained with a combination of inhaled (eg, volatile agents, nitrous oxide) and/or intravenous drugs (eg, propofol, opioid analgesics).
General anesthetics have been in clinical use for more than 170 years, but their mechanism of action remains unknown. Initial research focused on identifying a single biologic site of action for these drugs. In recent years, this “unitary theory” of anesthetic action has been supplanted by a more complex picture of molecular targets located at multiple levels of the central nervous system (CNS). Ongoing research has focused on molecular, cellular, and network effects to identify the mechanism of general anesthesia.
Anesthetics affect neurons at various cellular locations, but the primary focus has been on the synapse. A presynaptic action may alter the release of neurotransmitters, whereas a postsynaptic effect may change the frequency or amplitude of impulses exiting the synapse. The cumulative effect of these actions may produce strengthened inhibition or diminished excitation within key areas of the CNS. Studies on isolated spinal cord tissue have demonstrated that excitatory transmission is impaired more strongly by anesthetics than inhibitory effects are potentiated.