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25 General Anesthetics
C H A P T E R

Helge Eilers, MD, & Spencer Yost, MD

C ASE STUD Y

An elderly man with type 2 diabetes mellitus and ischemic The nurse in the preoperative holding area obtains the
pain in the lower extremity is scheduled for femoral-to- following vital signs: temperature 36.8°C (98.2°F), blood
popliteal artery bypass surgery. He has a history of hyper- pressure 168/100 mm Hg, heart rate 78 bpm, oxygen
tension and coronary artery disease with symptoms of stable saturation by pulse oximeter 96% while breathing room
angina. He can walk only half a block before pain in his legs air, and pain 5/10 in the right lower leg after walking into
forces him to stop. He has a 50-pack-year smoking history the hospital. What anesthetic agents will you choose for his
but stopped 2 years ago. Medications include atenolol, anesthetic plan? Why? Does the choice of anesthetic make
atorvastatin, and hydrochlorothiazide. a difference?

For centuries, humans relied on natural medicines and physical minor superficial surgery or invasive diagnostic procedures, oral
methods to control surgical pain. Historical texts describe the sedative or parenteral sedatives can be combined with local anesthetics in
effects of cannabis, henbane, mandrake, and opium poppy. Physical a technique termed monitored anesthesia care (MAC) (see Box:
methods such as cold, nerve compression, carotid artery occlusion, Sedation & Monitored Anesthesia Care, and Chapter 26). These
and cerebral concussion were also employed, with variable effect. techniques provide profound analgesia, with retention of the
Although surgery was performed under ether anesthesia as early as patient’s ability to maintain a patent airway and to respond to ver-
1842, the first public demonstration of surgical general anesthesia in bal commands. For more invasive surgical procedures, anesthesia
1846 is generally accepted as the start of the modern era of anesthe- may begin with a preoperative benzodiazepine, be induced with
sia. For the first time, physicians had a reliable means to keep their an intravenous agent (eg, thiopental or propofol), and be main-
patients from experiencing pain during surgical procedures. tained with a combination of inhaled (eg, volatile agents, nitrous
The neurophysiologic state produced by general anesthetics is oxide) and/or intravenous drugs (eg, propofol, opioid analgesics).
characterized by five primary effects: unconsciousness, amnesia,
analgesia, inhibition of autonomic reflexes, and skeletal mus-
cle relaxation. None of the currently available anesthetic agents MECHANISM OF GENERAL ANESTHETIC
when used alone can achieve all five of these desired effects well. ACTION
An ideal anesthetic drug should also induce rapid, smooth loss
of consciousness, be rapidly reversible upon discontinuation, and General anesthetics have been in clinical use for more than
possess a wide margin of safety. 170 years, but their mechanism of action remains unknown. Ini-
The modern practice of anesthesiology relies on the use of tial research focused on identifying a single biologic site of action
combinations of intravenous and inhaled drugs (balanced anes- for these drugs. In recent years, this “unitary theory” of anesthetic
thesia techniques) to take advantage of the favorable properties action has been supplanted by a more complex picture of molecu-
of each agent while minimizing their adverse effects. The choice lar targets located at multiple levels of the central nervous system
of anesthetic technique is determined by the type of diagnostic, (CNS). Ongoing research has focused on molecular, cellular, and
therapeutic, or surgical intervention that the patient needs. For network effects to identify the mechanism of general anesthesia.

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