Anesthesia causes insensitivity to pain through local or general agents. It was introduced in 1847 and the first public demonstration used ether. Anesthetics act through various cellular systems in the brain and spinal cord to depress excitability and movement. Their potency correlates with lipid solubility. Factors like concentration, flow rates, and solubility determine how fast anesthesia takes effect. Adequate depth is assessed through movement, breathing, eye signs and monitoring. Anesthetics depress breathing and the heart at doses below full unconsciousness and can cause problems if not carefully managed. They lower blood pressure and kidney function through these cardiovascular effects.

1. What is Anesthesia?
Franklin Scamman, MD

2. Topics to Cover This Lecture
1. What is “anesthesia”
2. History and mechanism of anesthesia
3. Uptake and distribution of inhaled anesthetics
4. CNS effects of anesthesia
5. Minimal alveolar concentration (MAC)
6. Properties of inhaled anesthetics
7. System effects of inhaled anesthetics
8. Delivery systems for inhaled anesthetics

3. “Anesthesia”
• Insensitivity to pain
• May be from local or general agents
• Term introduced by Oliver Wendell Holmes
in 1847 in response to work by WTG
Morton using ether

4. History of Anesthesia
• Greeks and Romans: aware of opium and
derivatives; oral ethanol
• Japan: 1820s, mandrake causing
cholinergic crisis and unconsciousness
• TWG Morton, MGH, October 16, 1846
using diethyl ether
• However, Crawford Long in 1849
described his use of it in 1842

5. MGH “Ether Dome” 1846

6. Mechanisms of Anesthesia
• No single macroscopic site of action
• Specific brain areas affected by inhalational
Anesthetics causing amnesia
– Reticular activating system,
– Cerebral cortex
– Cuneate nucleus
– Olfactory cortex
– Hippocampus
• Anesthetics depress excitatory transmission in
the spinal cord supressing movement

7. Mechanisms of Anesthesia
• General anesthetic action could be due to
alterations in any one of several cellular systems
including ligand-gated ion channels, second
messenger functions, or neurotransmitter
receptors.
• Many anesthetics (the potent agents) enhance
(GABA) inhibition of the central nervous system.
• Other agents (nitrous oxide and xenon) are
NMDA agonists with good pain relief, just like
ketamine
• Potency of inhalation agents correlates directly
with their lipid solubility (Meyer–Overton rule)

10. Rate of Rise of Alveolar
Concentration

11. Factors Determining the Speed
of Induction
• Vaporizer setting (concentration)
• Fresh gas flow
• Alveolar minute ventilation
• Blood-gas partition coefficient (solubility)
• Cardiac output
• Alveolar-to-venous partial-pressure difference
• Brain-blood partition coefficient
• Cerebral blood flow

12. How fast do you go asleep?
The higher the blood/gas coefficient

The greater the anesthetic's solubility

The greater its uptake by the pulmonary
circulation.

Alveolar partial pressure rises more slowly

Slow induction

13. Many of the factors that speed
induction also speed recovery
• Elimination of rebreathing
• High fresh gas flows,
• low anesthetic-circuit volume,
• low absorption by the anesthetic circuit,
• Decreased solubility,
• High cerebral blood flow,
• Increased ventilation.

14. Minimal Alveolar Concentration
• Percent alveolar concentration to prevent
purposeful movement in 50% of individuals
• Corresponds to the ED-50 of oral or IV drugs
• Lower at extremes of age
• Lower with other depressant drugs
• Lower in pregnancy
• Maximum at 37-39 degrees
• Maximum age 2-24 (roughly)

15. Properties of the Vapors
Desflurane Nitrous
Oxide
Isoflurane Sevoflurane
Blood/Gas 0.42 0.47 1.43 0.69
Brain/Blood 1.29 1.1 1.57 1.70
Fat/Blood 27.2 2.3 44.9 47.5
MAC % 6.0 104 1.2 2.0

16. Depth of Anesthesia
• Anesthesia depth can be assessed by
– Lack of movement in non-paralyzed state
– Respiration rate and pattern
– Respiratory depression (ET CO2 and VE )
– Eye signs
– BP and P less valuable
– BIS and Entropy analysis

17. Respiratory Effects
• Abolish the hypoxic response at less than
half MAC concentrations
• Fantastic bronchodilators by direct action
on smooth muscle

18. Cardiovascular Effects (1)
• All cause cardiac depression
• Cardiac depression causes an increased
rate of concentration rise
• An increased concentration causes more
cardiac depression
• Positive feedback -> cardiac arrest if not
careful

19. Cardiovascular Effects (2)
• Isoflurane and desflurane cause increased
heart rate which may mask depression
• Systemic vascular resistance
– Isoflurane and desflurane decrease (great for
starting IVs)
– Halothane and nitrous oxide do not change

20. Renal Effects
• All decrease arterial pressure
• RBF and GFR will be maintained until
threshold of autoregulation, absent other
influences (sympathetic tone, renin)
• Urine output is variable, depending on
ADH and aldosterone and other humeral
agents
• Creatinine clearance not effected by UO