General Anesthetics

Question 1

Surgical Anesthesia

Answer 1

Eliminates sensation of pain to permit operation

Question 2

Non-Anesthetics

Drugs

Answer 2

• Narcotics
  (morphine, fentanyl, meperidine)
  
  • ↓ Dysphoria associated with pain
  • ↑ Pain tolerance
  • Do not produce surgical anesthesia
• Sedatives
  (diazepam, midazolam, alcohol)
  
  • ↓ Anxiety
  • Can produce amnesia
  • Provides no analgesia
  • Cannot produce surgical anesthesia
• Muscle relaxants
  (pancuronium, curare, succinylcholine)
  
  • Prevent movement in response to pain
  • Produce neither amnesia nor analgesia

Question 3

Properties of Anesthesia

Answer 3

• Unconsciousness and amnesia: no response to command, no recall
• Analgesia: no response to surgical incision
• Blunting of protective reflexes: no response to non-surgical stimulus (e.g. laryngoscopy)
• Reduced muscle tone: allows entry into abdomen

Question 4

Depth of Anesthesia

Answer 4

Stage 1: Analgesia ⇒ Patient is conscious, ↑ pain tolerance (only nitrous oxide and ketamine)

Stage 2: Excitement ⇒ Disinhibition, patient unresponsive to command, thrashing even without stimulation

Stage 3: Surgical anesthesia ⇒ Patient still, not responsive to command or surgical stimulation

State 4: Medullary depression ⇒ Life-threatening CV and respiratory depression

Question 5

Anesthesia Goals

Answer 5

• Maintain homeostasis
  
  • Oxygenation and ventilation
  • CO and arterial pressure
  • Protect the unconscious patient from injury
• Provide optimal conditions for the surgeon ⇒ a still bloodless field
• Perioperative care ⇒ optimize patient’s condition before and after operation

Question 6

Inhaled Anesthetic Drugs

Answer 6

All are administered via inspired gas and eliminated via exhaled gas

Unique pharmacokinetics

• Nitrous oxide ⇒ gas at room temperature
• Halogenated hydrocarbons ⇒ most are volatile liquids at room temperature
  
  • Isoflurane (“Forane”)
  • Sevoflurane (“Ultane”)
  • Desflurane (“Suprane”)
  • Enflurane ⇒ used infrequently
  • Halothane ⇒ used infrequently

Question 7

Inhaled Anesthetics

Pharmacokinetics

Answer 7

• Dissolved anesthetic agents tend to come out of solution ⇒ partial pressure
• ↑ Solubility ⇒ ↑ molecules required to achieve a given partial pressure
• Anesthetic effect is produced by partial pressure, not by concentration
• Highly soluble agents ⇒ require more dissolved molecules (i.e., more time) to produce anesthesia
• Agents with low solubility produce faster induction and faster recovery

Question 8

Inhaled Anesthetics

Solubility Assessment

Answer 8

Blood:Gas Coefficient ⇒ ratio of blood concentration to gas concentration

Low B/G = low solubility = faster acting

Question 9

Inhaled Anesthetics

Adequacy of Anesthesia

Answer 9

Partial pressure of agent in the brain to produce absence of movement in response to surgical incision.

(Measured in % of inspired gas at sea level)

• Measure partial pressure in exhaled gas ⇒ approximation of alveolar gas ⇒ approximates blood gas ⇒ approximates brain partial pressure
• For each anesthetic agent, clinical studies determine the minimum alveolar concentration to prevent movement in response to surgical incision

Question 10

Minimum Alveolar Concentration (MAC)

Answer 10

The alveolar concentration at which 50% of healthy patients do not move.

• A statistical property
• Each patient responds differently
• MAC differs among different populations
• ↓ in the elderly, pregnancy, and sickness
  
  • Less anesthetic is required
• All anesthetics are titrated to effect

Question 11

Alveolar Concentration

Factors

Answer 11

• During induction:
  
  • Solubility of agent ⇒ low solubility = faster rise
  • Anesthetic concentration ⇒ higher concentration = faster rise
  • Ventilation ⇒ normal is optimal for induction
  • CO ⇒ low CO = faster rise
  • Concentration in venous blood ⇒ high = faster rise
• During emergence:
  Same factors, with exceptions
  
  • Inspired concentration cannot be lower than zero
  • Long anesthetic time means higher venous concentration ⇒ slower drop in alveolar concentration

Question 12

Inhaled Anesthetics

Mechanism of Action

Answer 12

Exact mechanism unknown

Question 13

Inhaled Anesthetics

Physiologic Effects

Answer 13

• ↓ Cellular metabolism
  
  • ↓ O₂ consumption
  • ↓ Myocardial O₂ consumption
  • ↓ O₂ demand ⇒ ↓ O₂ supply in response
• ↓ Sympathetic tone
  
  • Arteries dilate
  • Veins dilate
  • ↓ Contractility and HR
• Direct cardiovascular effects
  
  • Some ↓ in contractility
  • ∆ SA node rate
  • Some directly dilate arteries
• Respiratory effects
  
  • Bronchodilation
  • ↓ TV, ↑ RR, ↓ alveolar ventilation
  • ↓ Response to hypercarbia
  • NO response to hypoxemia
  • ↑ CO₂ apnea threshold
• CNS effects
  
  • All functions ↓
  • ↑ Cerebral blood flow; a concern with ↑ ICP
  • Exceptions: nitrous oxide, intravenous anesthetics
• Other organs
  
  • ↓ Muscle tone
  • ↓ Renal GFR
  • ↓ Hepatic blood flow with ↓ CO

Question 14

Inhaled Anesthetics

Toxicity

Answer 14

• Renal: fluoride ion with enflurane? Not as much of a problem with sevoflurane
• Hepatic: halothane; via metabolites? Antibodies?
• Respiratory: sevoflurane interactions with soda lime in anesthesia circuit
• Malignant hyperthermia: genetic predisposition to a hypermetabolic response to volatile anesthetics and/or succinylcholine
  
  • Leads to ↑ temperature, acidosis, hyperkalemia, hypercarbia
  • Fatal if untreated

Question 15

IV Anesthetic Drugs

Answer 15

• Thiopental (“Pentothal”)
• Methohexital (“Brevital”)
• Etomidate
• Propofol (“Diprivan”)
• Ketamine

Question 16

IV Anesthetics

Pharmacokinetics

Answer 16

Conventional ⇒ concentration proportional to drug effect

• Rapid ↑ in concentration with bolus ⇒ rapid onset
• Rapid redistribution after bolus ⇒ short duration
• Large doses/long duration fill volume of distribution ⇒ prolonged effect

Question 17

IV Anesthetics

Pharmacodynamics

Answer 17

Same as inhaled

• ↓ Oxygen consumption
• ↓ CO and arterial pressure
• ↓ Ventilation
• ↓ Cerebral blood flow (only difference from inhaled)

Question 18

Benzodiazepines

Answer 18

• Sedatives, not anesthetics
• Produce amnesia and unconsciousness, not analgesia
• Reverse w/ Flumazenil (a partial antagonist)
  
  • Difficult to reverse respiratory depression

Question 19

Opioids

Answer 19

• Analgesics, not anesthetics
• Produce intense pain relief
• Can ↓ anesthetic agents required
• Cannot produce surgical anesthesia alone
• All effects (including respiratory depression) 100% reversible

Question 20

Propofol

Answer 20

• Can be used as the sole anesthetic agent
  
  • Unconsciousness
  • Surgical anesthesia
  • Cardiac and respiratory depression
  • Death
• No muscle relaxation
• Like other IV anesthetics: high doses or long infusions fill volume of distribution
  
  • Requires metabolism to end effect

Question 21

Ketamine

Answer 21

• Produces dissociative anesthesia
  
  • Patient remains responsive
• Low doses provide analgesia
• Stimulates cardiovascular system
• Preserves airway reflexes
• Short elimination half-life
• ↑ cerebral blood flow

Question 22

Inhaled Anesthetics

Summary

Answer 22

• Nitrous oxide: low solubility, rapid induction
• Iso-, sevo-, and desflurane: Not metabolized, hepatic and renal safety
• Enflurane: renal toxicity from fluoride
• Halothane: hepatoxicity
• Malignant hyperthermia: rare side effect of inhaled anesthetics, treat with dantrolene

Question 23

IV Anesthetics

Summary

Answer 23

• Thiopental: rapid induction
• Propofol: rapid induction, short procedure, anti-emetic
• Ketamine: dissociative anesthesia, cardiovascular stimulant, ↑ cerebral blood flow, disorientation, hallucination, bad dreams
• Benzodiazepine: sedative, used adjunctively with general anesthetics, respiratory depression, amnesia
• Narcotics: analgesics, can ↓ anesthetics necessary, respiratory depression