General Anesthetics Flashcards
Minimum Alveolar Concentration (MAC)
A measure of anesthetic potency
1.0 MAC is defined as the minimal alveolar concentration of anesthetic which produces insensitivity to painful stimulation in 50% of patients
MAC is inversely proportional to potency (Potency = 1/MAC)
How do volatile anesthetics work?
Volatile anesthetics partition into the lipid bilayer of the nerve cell membrane, interacting with hydrophobic pockets in various membrane proteins including:
GABA-A receptor - increases duration of IPSPs
Glycine receptor - potentiates inhibitory Cl- influx
nAChR receptor - decreases CNS excitation
TASK-1 K+ channels - depresses neuronal excitability
Nitrous Oxide - Potency and Uses
Low Potency - MAC of 105% means that its impossible to achieve surgical anesthesia with N2O alone
Used as an adjunctive anxiolytic/analgesic in balanced anesthesia
Balanced anesthesia
Nitrous oxide + Barbiturate + Opioid
N2O Concentration Effect
Because of its high MAC, N2O is administered at high % inspired air (up to 75%); the large volume of N2O taken out of the lung into the blood sucks more gas into the lung by negative partial pressure effect causing faster than expected uptake
N2O Diffusion Hypoxia Effect
When anesthetic administration is terminated the large N2O volume leaving the blood expands the lung and dilutes alveolar O2 concentration, causing hypoxia
N2O Second Gas Effect
Occurs with concurrent administration of N2O and another gaseous anesthetic; the huge volume uptake of N2O sucks more of both gasses into the lung increasing the rate of uptake of the second agent over its expected value alone
Which hypothetical anesthetic agents are NOT used clinically?
Xenon
Diethyl Ether - flammable, excessive respiratory respirations, slow induction and recovery
Chloroform - risk of cardiac arrhythmias and hepatotoxicity
Halothane - Advantages
Relatively low blood : gas partition coeffcient leading to efficient induction and recovery
Moderate-high potency
Non-irritant (reduced respiratory secretions)
Halothane - 3 major risks
- Respiratory / cardiovascular failure
- Hepatotoxicity
- Malignant Hyperthermia
Halothane-induced hepatotoxicity
Occurs in 1/10,000 patients with death secondary to hepatic failure in 50%
Presents as fever, anorexia, nausea, and vomiting developing 2-5 days after anesthesia
Malignant Hyperthermia
Occurs in patients with inherited mutations in skeletal muscle RyRs upon administration of Halothane
Presents as rapid onset muscle rigidity and fever
Treated with Dantrolene, which causes muscle relaxation by blocking Ca2+ release from the RyR
Flourinated ether anesthetics - 4 agents
Enflurane
Isoflurane
Desflurane
Sevoflurane
Isoflurane
Most widely used inhalational anestetic
Potent with rapid induction and recovery; good muscle relaxant
Less risk of hepatotoxicity, renal toxicity, and seizures
Disadvantage: Pungent odor
Enflurane
Excellent analgesic with fast induction and recovery; good muscle relaxant
Lower hepatotoxocity than halothane but higher than isoflurane; can trigger seizures
Desflurane
Rapid onset and recovery; not hepatotoxic
Not suitable for induction due to pungent odor, irritation, and coughing; contraindicated in patients with risk of malignant hyperthermia
Sevoflurane
High potency; MAC = 2%
Rapid onset / recovery
Does not cause coughing or airway irritation; therefore suitable for induction
Major disadvantage is renal toxicity
Uptake: Phase I
Lung factors
Rate of increase in partial pressure of anesthetic gas in alveoli and pulmonary capillary blood is proportional to the rate of ventilation
Uptake: Phase II
Uptake by blood from alveoli determined by:
- Solubility of anesthetic agent in blood - lower solubility causes faster approach to equilibrium
- Pulmonary blood flow - increased CO slows the rate of uptake because the blood has less time to equilibrate with the alveoli
Anesthetic solubility
Determined by the blood:gas partition coefficient
The higher the anesthetic solubility in blood, the slower the approach to equilibrium and the slower the induction of anesthesia
Ex Halothane (more soluble) exhibits a slower induction than N2O (less soluble)
Uptake: Phase III
Uptake from arterial blood to brain depends on:
- Solubility of anesthetic gas in tissue, expressed as the tissue:blood partition coefficient; ~1 for lean tissues (brain) and > 1 for fatty tissues
- Tissue blood flow - increased blood flow causes faster uptake of anesthetic within tissue
- Partial pressure of anesthetic in blood and tissues - initially high but decreases as concentrations equilibrate
Uptake: Phase IV
Tissue distribution depends on vascularization and tissue:blood solubility
Vessel-rich group (brain, heart, kidney, etc,) exhibit fast uptake due to good perfusion
Muscle & skin exhibit uptake over 2-4 hours due to relatively less perfusion
Fat exhibits slow uptake due to high lipid solubility of anesthetic agents and low perfusion; fat serves as a huge storage resevoir for anesthetic
Stages of general anesthesia
Stage I: Analgesia
Stage II: Excitement, delirium
Stage III: Surgical anesthesia
Stage IV: Medullary paralysis
Planes of Stage III Anesthesia
Plane I: Regular, metronomic respirations
Plane II: Onset of muscular relaxation, fixation of pupils
Plane III: Complete muscular relaxation, depressed intercostal excursion during respiration
Plane IV: Diaphragmatic breathing, dilated pupils
Characteristics of Stage IV Anesthesia
Respiratory failure
Circulatory Failure
Death within minutes
Thiopental
Ultra short-acting barbituate; potentiates GABA-A receptor activity, prolonging IPSP duration and depressing CNS excitability
High lipid solubility leads to rapid-on rapid-off effect; good for induction of anesthesia
Major disadvantage is disorientation
Ketamine
NMDA Glutamate receptor antagonist
Produces dissociative anesthesia characterized by catatonia, amnesia, and analgesia
Major disadvantages are disorientation, hallucination
Propofol
Non-barbituate; potentiates GABA-A receptor activity
Useful due to rapid onset, faster recovery than thiopental, less post-op nausea
Etomidate
Nonbarbituate hypnotic; potentiates GABA-A receptor activity but lacks analgesic properties
Useful due to rapid induction and recovery with larger safety margin than thiopental
Disadvantages: Involuntary movement during induction, post-op nausea/vomiting
Ondansetron
5HT3-type serotonin receptor antagonist
Treats post-op nausea/vomiting
