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General Anesthesia
Jason Ryan, MD, MPH
General Anesthesia
• Anesthesia: insensitivity to pain
• Anesthetic drugs produce:
• Loss of consciousness
• Analgesia
• Amnesia
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• Muscle relaxation
• Inhaled
• Intravenous
• Neuromuscular blockers
• Local

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Inhaled General Anesthetics

Diethyl Ether
• Desflurane
• Halothane
• Isoflurane
• Enflurane
• Sevoflurane
Isoflurane
• Methoxyflurane
• Nitrous oxide
• Two key gas properties determine clinical effects:
• Blood solubility
• Lipid solubility
Blood Solubility
• Determines onset and offset time of inhaled anesthetics
• Molecules dissolved in blood: no anesthetic effect
• Molecules not dissolved: anesthetic effect
• Need to saturate blood before undissolved molecules accumulate
• High solubility = longer to take effect
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Gas
Good effect

Blood
No effect
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Blood Solubility
Inhaled Anesthetics
Partial
Pressure
Partial Pressure
Amount of
undissolved gas

Anesthesia
Gas from
Lungs
Blood Solubility
Inhaled Anesthetics
• High blood solubility
• Higher tendency to stay in blood
• Longer time to saturate blood
• Longer time for partial pressure to rise Gas
• SLOWER induction and washout time Good effect
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• Low blood solubility
• Quickly saturates blood
• Partial pressure rises rapidly
• Quickly exerts effects on brain Blood
• SHORTER induction and washout time
No effect
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Blood Solubility
Inhaled Anesthetics
• Blood solubility described by blood/gas partition coefficient
• Isoflurane: 1.4
• [blood]1.4 > [alveoli]
• High partition coefficient = high solubility
• Low partition coefficient = low solubility
Gas
Good effect

Blood
No effect
Blood Solubility
Inhaled Anesthetics

Blood : Gas
Gas
Partition Coefficient
Halothane 2.3
Isoflurane AfraTafreeh.com 1.4
Sevoflurane 0.69
Nitrous Oxide 0.47
Desflurane 0.42

Halothane → SLOW induction/washout

Nitric Oxide → FAST induction/washout
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Lipid Solubility
Inhaled Anesthetics
• Affinity of gas for lipids
• Lipid soluble gasses easily diffuse into brain
• ↑ lipid affinity = more potent (Meyer-Overton rule)
• Lower gas concentration required to produce anesthetic effect
• Described by the oil/gas partition coefficient
Lipid Solubility
Inhaled Anesthetics

Oil:gas
Gas
Partition Coefficient
Halothane 224
Enflurane AfraTafreeh.com 99
Isoflurane 98
Sevoflurane 47
Desflurane 28
Nitrous Oxide <10
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Minimum Alveolar Concentration

• Gas concentration (1%, 5%, 10%)
• Prevents movement in 50% of subjects in response to pain
• Useful parameter in clinical practice
• Determines concentration of gas to administer to patient
• Low MAC = low gas concentration needed = high potency
• High MAC = high gas concentration needed = low potency
• MAC related to lipid solubility

1
Lipid Solubility =
MAC
Minimum Alveolar Concentration
Inhaled Anesthetics

Gas MAC (%) Oil:gas PC

Halothane 0.8 224
Enflurane 1.8
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Isoflurane 1.3 98
Sevoflurane 2.5 47
Desflurane 7.2 28
Nitrous Oxide >100 <10
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Minimum Alveolar Concentration

Additive Properties
• When using multiple drugs, MACs are additive
• Allows use of lower concentration of each drug
• Example:
• Sevoflurane ½ MAC – 25% efficacy
• Nitrous oxide ½ MAC – 25% efficacy
• Combination: 1 MAC, 50% efficacy
• Patient exposed to less of each drug
• Lower risk of adverse effects
Minimum Alveolar Concentration
Inhaled Anesthetics
• Decreases with age
• Also decreases in pregnancy

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Inhaled Anesthetics Summary

• Onset of action and washout
• Blood : gas partition coefficient (higher = slower)
• Solubility in blood (higher = slower)
• Potency
• Oil : gas partition coefficient (higher = more potent)
• Solubility in lipids (higher = more potent)
• MAC (lower = more potent)

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Inhaled Anesthetics
Physiologic Effects
• ↑ cerebral blood flow
• Cerebral vasodilation
• Blood flow goes up
• ICP goes up
• Dose-dependent hypotension
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• Vasodilation:
• ↓ SVR and ↓ MAP
• Decreased GFR

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Inhaled Anesthetics
Physiologic Effects
• Respiratory depression
• ↓ tidal volume
• ↑ CO2
• Myocardial depression
• ↓ Cardiac output
• Minimal with sevoflurane and isoflurane
Specific Inhaled Anesthetics
• Desflurane, isoflurane, and sevoflurane
• Most commonly used agents
• Least adverse effects
• Minimal myocardial depression
• Nitrous oxide
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• Low potency
• Cannot deliver more than 0.75 MAC
• Rapid onset/offset
• Can switch to this gas toward end of case
• Frequent nausea and vomiting

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Nitrous Oxide Collapsed Lung

Normal Lung
• Diffuses rapidly into air spaces
• Will increase volume
• Cannot use:
• Pneumothorax
• Abdominal distention
Special Adverse Effects
• Halothane: hepatotoxicity
• Liver toxicity: rare, life-threatening
• Massive necrosis, increased AST/ALT
• Still used outside US in resource-poor settings
• Methoxyflurane: nephrotoxicity
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• Renal-toxic metabolites
• Enflurane: seizures
• Lowers seizure threshold

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Malignant Hyperthermia
• Rare, dangerous reaction to anesthesia drugs
• Associated with inhaled anesthetics
• Also succinylcholine (paralytic)
• Presents as fever and muscle rigidity
• Diffuse muscle damage: ↑ CK and hyperkalemia
• Tachycardia and hypertension
• Treatment:
• Stop offending drug
• Administer oxygen
• Dantrolene (muscle relaxant)
Stages of Anesthesia
• Induction
• Drugs used to put patient to sleep
• Usually IV propofol with an opioid (Fentanyl)
• Once asleep, paralytic agent used prior to intubation
• Maintenance
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• Drugs to keep patient asleep
• Inhaled or intravenous anesthetics (or combination)
• Sometimes ongoing use of paralytics
• Emergence
• Discontinuation of anesthetics
• Reversal of neuromuscular blockade
• Extubation