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Chapter: Basic & Clinical Pharmacology : General Anesthetics

General Anesthetics

For centuries, humankind has relied on natural medicines and physical methods to control surgical pain.

General Anesthetics


For centuries, humankind has 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 surgi-cal general anesthesia in 1846 is usually considered to be the start of a new era of anesthesia. For the first time physicians had a reli-able 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 mus-cle relaxation. None of the currently available anesthetic agentswhen used alone can achieve all five of these desired effects. In addition, an ideal anesthetic drug should 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 com-binations 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 anes-thetic technique is determined by the type of diagnostic, therapeu-tic, or surgical intervention to be performed. For minor superficial surgery or for invasive diagnostic procedures, oral or parenteral sedatives can be used in combination with local anesthetics, so-called monitored anesthesia care techniques 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 extensive surgical procedures, anesthesia may begin with preoperative benzodiazepines, be induced with an intravenous agent (eg, thiopental or propofol), and be maintained with a com-bination of inhaled (eg, volatile agents, nitrous oxide) or intrave-nous (eg, propofol, opioid analgesics) drugs, or both.


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


This patient has significant underlying cardiac risk involving major stressful surgery. Balanced anesthesia would begin with intravenous agents that cause minimal changes in blood pressure and heart rate such as propofol or etomidate, com-bined with potent analgesics such as fentanyl  to block undesirable stimulation of autonomic reflexes. Main-tenance of anesthesia could incorporate inhaled anesthetics that ensure unconsciousness and amnesia, additional intra-venous agents to provide intraoperative and postoperative analgesia, and, if needed, neuromuscular blocking drugs  to induce muscle relaxation. The choice of inhaled agent(s) would be made based on the desire to maintain sufficient myocardial contractility, systemic blood pressure, and cardiac output for adequate perfusion of criti-cal organs throughout the operation. Rapid emergence from the combined effects of the chosen anesthetic drugs would facilitate the patient’s return to a baseline state of heart func-tion, breathing, and mentation.

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