Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 27 General Anesthetics

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. General Anesthetics  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

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pain  Analgesia  Loss of sensibility to pain  Anesthesia  Loss of pain and loss of all other sensations

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. General Anesthetics  Two main groups  Inhalation anesthetics  Intravenous anesthetics  Before 1846  Surgery: brutal and excruciatingly painful  Strong people and straps used to restrain patient  Survival based on surgeon’s speed

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. General Anesthetics  Given only by licensed anesthesiologists (physicians) and CRNAs (nurses)  Used to facilitate certain procedures  Endoscopy, urologic procedures, radiation therapy, electroconvulsive therapy, transbronchial biopsy, various cardiologic procedures

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.  Basic pharmacology of inhalation anesthetics  Properties of individual inhalation anesthetics  Intravenous anesthetics General Anesthetics

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Pharmacology of Inhalation Anesthetics  Properties of an ideal inhalation anesthetic  Balance anesthesia  Molecular mechanism of action  Minimum alveolar concentration

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics  Uptake and distribution  Uptake From the lungs From the lungs The greater the concentration, the more rapid the uptake The greater the concentration, the more rapid the uptake  Distribution To CNS and other tissues To CNS and other tissues Determined largely by regional blood flow Determined largely by regional blood flow  Elimination  Exported in the expired breath Inhalation anesthetics are almost entirely eliminated by the lungs Inhalation anesthetics are almost entirely eliminated by the lungs  Metabolism Hepatic metabolism is minimal Hepatic metabolism is minimal

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics  Adverse effects  Respiratory and cardiac depression  Sensitization of the heart to catecholamines  Malignant hyperthermia  Aspiration of gastric contents  Toxicity to operating room personnel  Hepatotoxicity

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Interactions  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

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adjuncts to Inhalation Anesthesia  Preanesthetic medications  Given to reduce anxiety, produce perioperative amnesia, and relieve preoperative and postoperative pain Benzodiazepines Benzodiazepines Opioids Opioids Clonidine, an alpha 2 -adrenergic agonist Clonidine, an alpha 2 -adrenergic agonist Anticholinergic drugs Anticholinergic drugs

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Neuromuscular Blocking Agents  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  20,000–40,000 wake up during the procedure

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Postanesthetic Medications  Analgesics  Mild pain: aspirin-like drugs  Severe pain: opioids  Antiemetics  Ondansetron (Zofran)  Muscarinic antagonists  Abdominal distention and urinary retention  Bethanechol

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Properties of Individual Inhalation Anesthetics  Halothane (no longer available in United States)  Isoflurane  Enflurane  Desflurane  Sevoflurane  Nitrous oxide  Obsolete inhalation anesthetics

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Halothane  Prototype for volatile inhalation anesthetics  No longer available in United States  Anesthetic properties  High-potency anesthetic  Time course: smooth and relatively rapid  Weak analgesia  Muscle relaxation generally inadequate for surgery

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Halothane  Adverse effects  Hypotension  Respiratory depression Requires support with oxygen-rich gas mixture Requires support with oxygen-rich gas mixture  Promotion of dysrhythmias Epinephrine and catecholamines should be used with caution. Epinephrine and catecholamines should be used with caution.  Malignant hyperthermia Genetically predisposed Genetically predisposed  Hepatotoxicity Rare Rare  Other adverse effects  Elimination  60%–80% by lungs and 20% hepatic

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Isoflurane  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

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Enflurane  Has pharmacologic properties very similar to those of halothane  Newer agents now preferred

19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Desflurane (Suprane)  Nearly identical in structure to isoflurane  Induction occurs more rapidly than with any other volatile anesthetics

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sevoflurane (Ultane)  Similar to desflurane  Approved for induction and maintenance

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nitrous Oxide  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)

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Obsolete Inhalation Anesthetics  Ethylene  Cyclopropane  Diethyl ether (ether)  Vinyl ether  Ethyl chloride  Abandoned because they are explosive and offer no advantage over newer anesthetics

23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Intravenous Anesthetics  Short-acting barbiturates (thiobarbiturates)  Benzodiazepines  Propofol  Etomidate  Ketamine  Neuroleptic-opioid combination: droperidol plus fentanyl

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Short-Acting Barbiturates (Thiobarbiturates)  Administered intravenously  Used for induction of anesthesia  Two agents  Thiopental sodium (Pentothal)  Methohexital sodium (Brevital)

25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Benzodiazepines  Diazepam  Induction with intravenous diazepam (Valium)  Unconsciousness within a minute  Very little muscle relaxation  Midazolam  Unconsciousness within 80 seconds  Can cause dangerous cardiorespiratory effects

26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propofol  Most widely used anesthetic  Actions and uses  Unconsciousness develops within 60 seconds and lasts 3–5 minutes  Sedative-hypnotic for induction and maintenance of analgesia Mechanical ventilation and procedures Mechanical ventilation and procedures  Adverse effects  Can cause profound respiratory depression  Can cause hypotension  Risk of bacterial infection

27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propofol  Risks for abuse  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

28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fospropofol  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

29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Etomidate  Potent hypnotic agent  Used for induction  Repeated administration can cause hypotension, oliguria, electrolyte disturbances, and high incidence of postoperative nausea and vomiting

30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ketamine  Anesthetic effects  Dissociative anesthesia  Sedation, immobility, analgesia, and amnesia  Adverse psychologic reactions  Hallucinations, disturbing dreams, and delirium  Soothing environment  Therapeutic uses  Anesthesia for young children with minor procedures

31Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Neuroleptic-Opioid Combination: Droperidol Plus Fentanyl  Quiescence  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  Prolongs the QT interval, hypotension, and respiratory depression