General Anesthetics
Anesthesia

Author: Alessandro Meli
Date: 17/03/2009

Description

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Definition

General anesthesia is the induction of a state of unconsciousness with the absence of pain sensation over the entire body, through the administration of anesthetic drugs. It is used during certain medical and surgical procedures.

Purpose

General anesthesia has many purposes including:

  • pain relief (analgesia)
  • blocking memory of the procedure (amnesia)
  • producing unconsciousness
  • inhibiting normal body reflexes to make surgery safe and easier to perform
  • relaxing the muscles of the body

Anesthesia performed with general anesthetics occurs in four stages (defined by Guedel in 1920) which may or may not be observable because they can occur very rapidly (modern technologies tend to hide the different steps):

  • Stage One: Analgesia The patient experiences analgesia or a loss of pain sensation but remains conscious and can carry on a conversation.
  • Stage Two: Excitement The patient may experience delirium or become violent. Blood pressure rises and becomes irregular, and breathing rate increases. This stage is typically bypassed by administering a barbiturate, such as sodium pentothal, before the anesthesia.
  • Stage Three: Surgical Anesthesia During this stage, the skeletal muscles relax, and the patient's breathing becomes regular. Eye movements slow, then stop, and surgery can begin.
  • Stage Four: Medullary Paralysis This stage occurs if the respiratory centers in the medulla oblongata of the brain that control breathing and other vital functions cease to function. Death can result if the patient cannot be revived quickly. This stage should never be reached. Careful control of the amounts of anesthetics administered prevent this occurrence.

Methods of Action

General anesthesia works by altering the flow of sodium molecules into nerve cells (neurons) through the cell membrane. Exactly how the anesthetic does this is not understood since the drug apparently does not bind to any receptor on the cell surface and does not seem to affect the release of chemicals that transmit nerve impulses (neurotransmitters) from the nerve cells. It is known, however, that when the sodium molecules do not get into the neurons, nerve impulses are not generated and the brain becomes unconscious, does not store memories, does not register pain impulses from other areas of the body, and does not control involuntary reflexes. Although anesthesia may feel like deep sleep, it is not the same. In sleep, some parts of the brain speed up while others slow down. Under anesthesia, the loss of consciousness is more widespread.

Actual theories are based on:

  • Lipid theory

Overton and Meyer postulated that general anaesthetics exert their action by acting on the plasma membrane. This is supported by evidence that the potency of the drug has a direct, positive correlation with the lipid solubility of the blood.
The mechanism of action was proposed to be increased fluidity of the membrane. The interpretation of the Overton and Meyer finding has been challenged and discredited.
In 1978 a workgroup processed a conformational model
Pathological situations which alterate lipid membrane composition could decrease nervous response to anesthetics, as demonstrated for pentobarbital. See Anestesiology review.
In the last few years studies have been demonstrating the effectiveness of using statin terapy during perioperative period.

  • Ion Channels

General anaesthetics inhibit excitatory functions of some CNS receptors, such as glutamate or 5-HT receptors. Some general anaesthetics also excite inhibitory receptors, notably GABA-A receptors and TREK. GABAA is a major target of the intrevenous anaesthetics thiopental and propofol.
General anaesthetics may decrease transmitter release pre-synaptically or decrease excitability of post-synaptic neuron.
For previous theories see also: Outdated theories of anaesthetic action

Mode of administration

Agents used for general anesthesia may be either gases or volatile liquids that are vaporized and inhaled with oxygen, or drugs delivered intravenously. A combination of inhaled anesthetic gases and intravenous drugs are usually delivered during general anesthesia; this practice is called balanced anesthesia and is used because it takes advantage of the beneficial effects of each anesthetic agent to reach surgical anesthesia.
If necessary, the extent of the anesthesia produced by inhaling a general anesthetic can be rapidly modified by adjusting the concentration of the anesthetic in the oxygen that is breathed by the patient (MAC). The degree of anesthesia produced by an intravenously injected anesthesic is fixed and cannot be changed as rapidly.
Most commonly, intravenous anesthetic agents are used for induction of anesthesia and then followed by inhaled anesthetic agents.

Recommended dosage

The dosage depends on the type of anesthetic, the patient's age and physical condition, the type of surgery or medical procedure being done, and other medication the patient takes before, during, or after surgery.

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