General Anesthetics Michael G. Haske, Jr. MD Assistant Professor of Anesthesiology Stritch School of Medicine Loyola University Medical Center Maywood, IL https://www.youtube.com/watch?v=Oo44FkFDyhg

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

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

http://www. dentalposterart http://www.dentalposterart.com/Resources/Images/Dental-Posters/Dental-Poster-Nitrous-Oxide.jpg

“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

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… https://www.youtube.com/watch?v=Oo44FkFDyhg

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

Inhibitory Post-Synaptic Potential

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

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

Potency MAC – Side Effect Minimum Alveolar Concentration @ 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

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

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

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

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

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

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

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:

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

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

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

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

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

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

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

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:

Intravenous Agents Induction vs. general IV agents

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

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

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

Summary

Reference https://www.youtube.com/watch?feature=player_embedded&v=K4qADFNsDxE