Chapter 27
General Anesthetics
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
General Anesthetics
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General anesthetics are drugs that produce
unconsciousness and lack of responsiveness
to all painful stimuli
Local anesthetics do not reduce
consciousness, and they blunt pain only in a
limited area
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Pain
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Analgesia
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Loss of sensibility to pain
Anesthesia
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Loss of pain and loss of all other sensations
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General Anesthetics
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Two main groups
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Inhalation anesthetics
Intravenous anesthetics
Before 1846
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Surgery: brutal and excruciatingly painful
Strong people and straps used to restrain patient
Survival based on surgeon’s speed
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General Anesthetics
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Given only by licensed anesthesiologists
(physicians) and CRNAs (nurses)
Used to facilitate certain procedures
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Endoscopy, urologic procedures, radiation
therapy, electroconvulsive therapy, transbronchial
biopsy, various cardiologic procedures
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General Anesthetics
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Basic pharmacology of inhalation anesthetics
Properties of individual inhalation anesthetics
Intravenous anesthetics
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Basic Pharmacology of
Inhalation Anesthetics
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Properties of an ideal inhalation anesthetic
Balance anesthesia
Molecular mechanism of action
Minimum alveolar concentration
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Pharmacokinetics
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Uptake and distribution
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Uptake
• From the lungs
• The greater the concentration, the more rapid the uptake
Distribution
• To CNS and other tissues
• Determined largely by regional blood flow
Elimination
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Exported in the expired breath
• Inhalation anesthetics are almost entirely eliminated by the
lungs
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Metabolism
• Hepatic metabolism is minimal
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Pharmacokinetics
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Adverse effects
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Respiratory and cardiac depression
Sensitization of the heart to catecholamines
Malignant hyperthermia
Aspiration of gastric contents
Toxicity to operating room personnel
Hepatotoxicity
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Drug Interactions
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Analgesics, CNS depressants, and CNS
stimulants can influence the amount of
anesthetic required to produce anesthesia
Opioids allow for a reduction
CNS depressants add to the depressant
effects of anesthesia
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Adjuncts to Inhalation Anesthesia
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Preanesthetic medications
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Given to reduce anxiety, produce perioperative
amnesia, and relieve preoperative and
postoperative pain
• Benzodiazepines
• Opioids
• Clonidine, an alpha2-adrenergic agonist
• Anticholinergic drugs
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Neuromuscular Blocking Agents
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Surgical procedures require skeletal muscle
relaxation
NBAs reduce amount of anesthesia needed
NBAs prevent contraction of all skeletal
muscles, including diaphragm and muscles of
respiration (flaccid paralysis)
21 million patients undergo surgery
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20,000–40,000 wake up during the procedure
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Postanesthetic Medications
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Analgesics
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Antiemetics
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Mild pain: aspirin-like drugs
Severe pain: opioids
Ondansetron (Zofran)
Muscarinic antagonists
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Abdominal distention and urinary retention
Bethanechol
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Properties of Individual
Inhalation Anesthetics
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Halothane (no longer available in United
States)
Isoflurane
Enflurane
Desflurane
Sevoflurane
Nitrous oxide
Obsolete inhalation anesthetics
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Halothane
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Prototype for volatile inhalation anesthetics
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No longer available in United States
Anesthetic properties
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High-potency anesthetic
Time course: smooth and relatively rapid
Weak analgesia
Muscle relaxation generally inadequate for surgery
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Halothane
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Adverse effects
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Hypotension
Respiratory depression
• Requires support with oxygen-rich gas mixture
Promotion of dysrhythmias
• Epinephrine and catecholamines should be used with caution.
Malignant hyperthermia
• Genetically predisposed
Hepatotoxicity
• Rare
Other adverse effects
Elimination
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60%–80% by lungs and 20% hepatic
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Isoflurane
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Most widely used inhalation anesthetic
Properties much like those of halothane
Better muscle relaxant, but still requires NMB
Not associated with renal or hepatic toxicity
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Enflurane
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Has pharmacologic properties very similar to
those of halothane
Newer agents now preferred
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Desflurane (Suprane)
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Nearly identical in structure to isoflurane
Induction occurs more rapidly than with any
other volatile anesthetics
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Sevoflurane (Ultane)
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Similar to desflurane
Approved for induction and maintenance
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Nitrous Oxide
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Also known as “laughing gas”
Very low anesthetic potency
Very high analgesic potency
Never used as primary anesthetic
Frequently combined with other inhalation
agents to enhance analgesia
20% nitrous oxide = Pain relief of morphine
No serious side effects (nausea and vomiting)
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Obsolete Inhalation Anesthetics
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Ethylene
Cyclopropane
Diethyl ether (ether)
Vinyl ether
Ethyl chloride
Abandoned because they are explosive and
offer no advantage over newer anesthetics
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Intravenous Anesthetics
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Short-acting barbiturates (thiobarbiturates)
Benzodiazepines
Propofol
Etomidate
Ketamine
Neuroleptic-opioid combination: droperidol
plus fentanyl
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Short-Acting Barbiturates
(Thiobarbiturates)
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Administered intravenously
Used for induction of anesthesia
Two agents
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Thiopental sodium (Pentothal)
Methohexital sodium (Brevital)
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Benzodiazepines
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Diazepam
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Induction with intravenous diazepam (Valium)
Unconsciousness within a minute
Very little muscle relaxation
Midazolam
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Unconsciousness within 80 seconds
Can cause dangerous cardiorespiratory effects
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Propofol
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Most widely used anesthetic
Actions and uses
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Unconsciousness develops within 60 seconds and
lasts 3–5 minutes
Sedative-hypnotic for induction and maintenance
of analgesia
• Mechanical ventilation and procedures
Adverse effects
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Can cause profound respiratory depression
Can cause hypotension
Risk of bacterial infection
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Propofol
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Risks for abuse
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Not a controlled substance
Supplies are not closely monitored
Widely available in operating rooms, etc.
No “high”
Instantaneous but brief sleep period
Patients awaken “refreshed” and talkative, and
report feeling elated and even euphoric
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Fospropofol
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Fospropofol (Lusedra)
Intravenous prodrug
Conversion to propofol in the lever
Effects similar to propofol
Slower onset of sedation (4 min vs. 1 min)
Lower risk of bacteremia
Schedule IV drug
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Etomidate
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Potent hypnotic agent
Used for induction
Repeated administration can cause
hypotension, oliguria, electrolyte
disturbances, and high incidence of
postoperative nausea and vomiting
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Ketamine
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Anesthetic effects
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Adverse psychologic reactions
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Dissociative anesthesia
Sedation, immobility, analgesia, and amnesia
Hallucinations, disturbing dreams, and delirium
Soothing environment
Therapeutic uses
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Anesthesia for young children with minor
procedures
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Neuroleptic-Opioid Combination:
Droperidol Plus Fentanyl
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Quiescence
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Indifference to surroundings
Patient appears to be asleep but is not in a state
of complete loss of consciousness.
Used for diagnostic and minor procedures
Adverse effects
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Prolongs the QT interval, hypotension, and
respiratory depression
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