1. General Anesthetics Michael G. Haske, Jr. MD
Assistant Professor of Anesthesiology
Stritch School of Medicine
Loyola University Medical Center
Maywood, IL

2. IV Agents History Pharmacokinetics
Why do more soluble anesthetics take longer to cause sleep?
Why does an increase in cardiac output slow induction?
IV Agents

3. Anesthesia First sedative? Alcohol (Neolithic period?) vs. Analgesics
Opium – poppy (3400 B.C.) “Joy Plant”
Nitrous Oxide – Davy “Laughing Gas”
1800: Described in text its possible surgical use

4. http://www. dentalposterart

5. “America’s Greatest Medical Discovery”
William T. G. Morton
Dentist – ether frolics
tooth extraction
1846 invited to MGH
Ether Dome
Crawford W. Long MD
Ether
1842 Georgia
Neck Tumor

6. Anesthesia Oliver Wendell Holmes, Sr. “Without Sensation”
Goals of General Anesthesia?
Surgeon:
Don’t Move!
Patient:
Don’t Remember! Don’t make me puke! No Pain!
Anesthesiologist:
Unconsciousness, amnesia, immobility, no PONV, retention or improvement of preoperative organ systemic functions…

7. Inhalational Anesthetics
How do they work?
Nobody Knows!
Meyer-Overton hypothesis
Higher lipid solubility = higher potency
(less movement on incision)
GABAA Chloride channel IPSP

8. Inhibitory Post-Synaptic Potential

9. Safety 1st Too little? Too much? No antidote Remember cutting
Stop breathing, stop circulating
No antidote

10. Stages to a General Anesthetic
Preop anxiolytic +/- analgesic
Preoxygenate (de-nitrogenate)
Induction
Maintenance
Emergence
Recovery

11. Potency MAC – Side Effect
Minimum Alveolar 1ATM that prevents movement during a skin incision in 50%.
Bell-shaped curve
x 1.3 for ED95
Influenced by
Temp, Age, Rx
Not influenced by
Sex, O2, pH, BP

12. Pharmacokinetics How do most drugs work?
IV/PO → Blood → Organ of interest
Induction of anesthesia
Inhalational anesthetics are weird.
↑ C.O. → Slower induction

13. Pharmacokinetics Goal organ: Brain. How’s it get there?
Machine → Alveoli → Arterial Blood →Brain
How do we measure what’s in the brain?
Brain → Venous Blood → Alveoli → Machine
FA/FI
End-tidal / Inspired

14. Cascade
The faster the agent gets from one compartment to the next, the slower it reaches equilibrium

15. Machine → Alveoli Uptake and Distribution Volatile anesthetic is a gas
↑Delivery → ↑ Speed of induction
↑Concentration of agent
↑Minute volume

16. After delivery to alveoli, 3 main factors determine uptake into blood:
1. Solubility
2. Partial Pressure Difference
3. Cardiac Output

17. FA/FI End-tidal / Inspired
FA, or the end-tidal partial pressure is the brain partial pressure
Nitrous Oxide is not soluble
Halothane is very soluble in blood

18. 1. Solubility: Alveoli → Arterial Blood
Blood/Gas partition coefficient: λ
More soluble agents reach equilibrium slower than less soluble agents
The blood “compartment” is larger for a more soluble agent:

19. After delivery to alveoli, 3 main factors determine uptake into blood:
1. Solubility
2. Partial Pressure Difference
3. Cardiac Output

20. Alveolus vs. mixed venous partial pressure
Vessel-rich organs 1st, not just brain
BHLK
Partial pressure drives movement, not concentration
During maintenance, skin & muscle start uptake
Then fat

21. After delivery to alveoli, 3 main factors determine uptake into blood:
1. Solubility
2. Partial Pressure Difference
3. Cardiac Output

22. Cardiac Output Arterial Blood → Brain
Increased blood flow near alveolus slows equilibrium because it increases uptake
Therefore, it also slows FA/FI
Cerebral blood flow is regulated - increase CO should not bring extra agent to the brain

27. Emergence Turn off the gas
More fat soluble agent may lead to prolonged awakening
100% 0xygen
Breathe
Extubate
Recover

28. Side Effects Cardio- Vascular Pulmonary Skeletal muscle Brain
CO & O2 consumption
Vascular
Systemic, Pulmonary, Intracranial
Pulmonary
Respiratory rate, Status asthmaticus
Skeletal muscle
Brain
Uncoupling

30. Intravenous Anesthetic Agents
Propofol
A.K.A.
Uses:
Induction, Maintenance, sedation – OR, procedures, ICU
Mechanism:
IPSP – how?

31. Propofol organs CNS Veno- and Arterio- dilator Respiratory Depression
Decreased CMRO2 & ICP
Veno- and Arterio- dilator
Preload & Afterload reductions
Respiratory Depression
Context-sensitive half time:

32. Intravenous Agents
Induction vs. general IV agents

33. Thiopental Barbiturate - GABA
Was most-used induction Rx until propofol
Not available in U.S.
Arterial vasoconstrictor
Put brain to sleep
Vasoconstrictor and ↓ CMRO2

34. Ketamine ↑BP, HR Bad dreams, salivation, twitchy AKA
NMDA N-Methyl-D-aspartate receptor antagonist
Dissociative anesthesia
Induction & short procedures, gtt for pain
Keep breathing, BRONCHODILATOR
↑ CMRO2, cerebral blood flow & ICP
↑BP, HR
Bad dreams, salivation, twitchy

35. Etomidate Least cardiovascular side effects GABA again
Vasoconstrictor and ↓ CMRO2
Adrenal suppression

36. Summary

37. Reference