Major components and anesthesia

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Analgesia

Amnesia

Hypnosis

Immobility

Stages of anesthesia

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Analgesia then amnesia

Excitement: delirious, amnesic with abnormal respiration

Surgical anesthesia: apnea, analgesia, hemodynamic depression

 Medullary depression: circulatory and respiratory depression

Vapor pressure level of ether required for one to overcome excitement phase:

Vapor pressure level of ether given over long time:

>150mm

50mm

Normal response to verbal stimulation

Unaffected airway

Unaffected spontaneous ventilation

Unaffected CV function

Purposeful response to verbal or tactile stimulation

No intervention required for airway

Adequate spontaneous ventilation

CV usually maintained

Deep sedation 

Arexiolysis

Purposeful response following repeated painful stimulation

Intervention may be required for airway

Spontaneous ventilation may be inadequate

CV usually maintained

Unarousable even with painful stimulus

Airway intervention often required

Spontaneous ventilation frequently inadequate

CV function may be impaired

Ideal anesthetic drug 

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Loss of consciousness smoothly and rapidly

Prompt recovery of cognitive fct after is admin is d/c

Wide margin of safety devoid of adverse effects

Potency of anesthetic__________with lipid solubility

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Used to describe mechanism of volatile anesthetics

Linear relationship btwn potency and lipid solubility

No longer generally accepted

Appears in different levels of CNS integration

Molecular, subcellular, cellular 

Site of action of anesthetics

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GABA_a Receptor

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Located in the neuronal membrane at synapse

GABA is endogenous compound that binds to receptor (alpha and beta: need to GABA) and causes receptor to open via a conformational change

This leads to influx on Cl^- ions down the EC gradient

CNS desired effects of Anesthesia

Unconsciousness

Unconsciousness: Cerebral cortex, thalamus, reticular formation

High density of GABA_a, NMDA, and Ach receptors

Hemodynamic: Decrease in systemic arterial BP

Respiratory: Reduce both ventilatory drive and reflexes maintaining airway (May need to keep airway open another way)

Hypothermia

Nausea and Vomiting via CTZ

Immobility: Sensory and motor neurons (GABA_a, Glycine (augmentation), AMPA (inhibited), NMDA glutamate receptor (inhibited))

Analgesia: spinal cord (blocking at glutamate, GABA, or micro receptors)

Amnesia: Inhibition of neuronal Ach receptors (hippocampus, amygdala, prefrontal cortex)

Implicit memory is target (recalled unconsciously)

Explicit memory is not target (recalled consciously)

Both use NMDA and non NMDA receptors

MAC

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Minimal anesthetic concentration

The concentration required to produce immobility in 50% of the subjects exposed to the stimulus

Causes of a decreased MAC

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Nitrous oxide

Premedication

Age (increased age)

R'OH intoxication

Hypothermia

Hypotension

Hypercarbia (has its own anesthetic effect)

Causes of increased MAC

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Age (highest at 6 mos)

Chronic Alcoholic abuse (increased enzyme activity)

Sympathetic increase (ephedrine, amphetamine, cocaine, hypermetabolic states like thyrotoxicosis, pyrexia)

The higher the CNS target is the _______  the MAC

Therefore the spinal cord requires the ______ MAC

Lower 

Highest

higher

higher

Basically Intubation is very invasive and needs a high level on anesthesia.

KNOW THIS

Green cord for oxygen connected to pipe in hospital. Then you have oxygen flow meter to regulate flow rate of oxygen that comes out of outlet. Oxygen delivered to vaporizer. On the bottom of vaporizer you have the volatile anesthetic. Can’t put different anesthetic drugs in same vaporizer. Most vaporize at RT. There is always portion of liquid in vapor. The more you open the more flow gets vaporized. This increases concentration at outlet. There are some temp regulating components because temp dependent. Regulate flow through chamber by turning wheel.  The higher the flow you regulate the quicker you can deliver the volatile anesthetic. 

Solubility: λ

Cardiac output: Q

Alveolar to venous partial pressure difference: p_A-p_v

Uptake= λ* Q*(p_A- p_v)

F_a

F_i

Fa: Alveolar anesthetic concentration 

Fi: inspired anesthetic concentration

The higher the Fa originally the more lipid soluble and the longer it will take to reach equilibrium

Nitrous oxide, desflurane and sevoflurane are ______ lipid soluble and achieve equilibriation between the alveoli and blood _____

Halothane and methoxyflurane are ______ lipid soluble and achieve equilibriation between the alveoli and blood ____

not

quickly

very

slowly or not at all

Quicker

Seen with Nitrous oxide, Desflurane and Sevoflurane

Nitrous oxide, Sevoflurane, Desflurane and Xenon have ______ blood:gas partition coefficients and _____  brain:blood partition coefficients

Leading to ___ onset and recovery

Low

High

Rapid

high

Low

moderate

Rank level of metabolism from highest to lowest

Nitrous oxide, Halothane,

Enflurane, Isoflurane, Sevoflurane, Desflurane, Xenon

Rises rapidly

decreases (delayed effect): Decreases alveolar concentration by augmenting uptake

Desflurane and Sevoflurane recovery happens _____ than for isoflurane

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Much faster

Desflurane (8 min)

Sevoflurane (30 min)

Isoflurane (off the chart)

By the time anesthesia has ended we want a ___% decrease in the anesthetic concentration

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Effects of volatile anesthetics on the heart

Halothane and Enflurane:

Sevoflurane, Desflurane and Isoflurane:

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All depress CV fct in a dose-dependent manner

Halothane and Enflurane: act directly and also reduce HR

Desflurane, Sevoflurane, Isoflurane: Depress by causing a reduction in SVR --> increased HR

All reduce myocardial oxygen consumption and act AGAINST MYOCARDIAL REPERFUSION INJURY

Volatile anesthetic effects on Respiratory system

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Dose-dependent decrease in tidal volume and increase in respiratory rate.

Increase apneic threshold (PaCO2 level below which apnea occurs through lack of CO2-driven respiratory stimulation) and decreased the ventilatory response to hypoxia.

Depress mucociliary fct (risk of atelectasis and post op respiratory infections)

Depression of contractility of diaphragm

Bronchodilation

NO EFFECT ON HYPOXIC PULMONARY CONSTRICTION at normal doses.

Volatile anesthetics effect on Kidney

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Reduce RBF and GFR

Impairment of autoregulation of RBF

Reduction of hepatic BF (15-45% of baseline)

Permanent changes of liver function are rare

May decrease metabolism of other drugs

Reduction of cerebral metabolic rate (might cause increase in blood flow by reduction in resistance)

Enflurane may lead to spike- and -wave pattern and mild generalized mm twitches at higher concentrations

Halothane hepatitis

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Halothane is metabolized to trifluoroacetyl chloride. By adding water you get Trifluoroacetic acid (TFAA). Keep this in mind because TFAA can bind to hepatocytes. Immune system recognizes and causes inflammatory response to hepatocytes. Happens after numerous times with halothane treatment. 

Sevoflurane nephrotoxicity

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Effects on Uterine Smooth mm

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Effects on the uterine smooth muscle

Nitrous oxide appears to have little effect on uterine musculature, however, the other halogenated anesthetics are potent uterine muscle relaxants and produce a dose-dependent relaxation

Hypercarbia, sinus tach, masseter spasm, temp abnormalities

Respiratory acidosis and mm abnormalities follow

Volatile anesthetics (halothane, enflurane, isoflurane, sevoflurane, desflurane)

Depolarizing mm relaxante (succinylcholine, 4-chloro-m-cresol)

Stress and temp 

Normal: dihydropyridine receptor on transverse tubule couples with ryanodine receptor on sarcoplasmic reticulum--> opened channel and outflow of Ca into cytoplasm.

Ca binds to troponin-->contraction 

Then Ca is pumped back into SR

Hyperthermia: mutation on RyR (chrom 18) with anesthetic agents--> alterations of hydrophilic, amino-terminal portion of RyR-->uncontrolled Ca efflux (3*)--> tetany, increased SKM metab and heat production

1. Declare MH emergency

2. D/C triggering agents and give 100% Oxygen at high flow

3. Give dantrolene: muscle relaxant that cools patient (titrate to effect)

4. Cool patient

Thiopental

Onset and recovery

Side effect

Contraindication

Rapid with bolus, slow recovery with infusion

CV depression

porphyria

Propofol

Onset and recovery

Use

Side effects

Rapid

Antiemetic, induction and maintenance of anesthetic

Hypotension

Ketamine (arylcyclohexylamine)

Onset and recovery

Use

Moderately rapid

CV stimulant and increase in CBF

Reactions impair recovery

Doesn't drop BP as much as others

Etomidate (carboxylated imidazole)

Onset and recovery

Use

Side effect

Rapid onset with moderately fast recovery

CV stabilizer, inhibit steroidogenesis

Good for patient with low Ejection Fraction

Causes involuntary mm movement

Midazolam (benzodiazapine)

Onset and recovery

Use

Side effect

Slow

Balanced anesthesia and conscious sedation, CV stability

Side effect: marked amnesia

Thiopental:

lipid solubility

plasma:brain

half life

termination

Fct

high

fast

8-10 hours

redistribution (NOT metabolism)

Activate GABA_A and inhibit AMPA

Propofol and Midazolam are used for ______

Etomidate and Ketamine are used for _______

Normal anesthesia

Trauma/CHF

Why can it take days for a patient to wake up from thiopental?

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Accumulates in fat tissue

Blood-->brain-->lean tissues-->fat

Propofol

Route

Mechanism of Action

Half life

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Parenteral: small, hydrophobic, substituted aromatic compound that partitions into lipophilic tissue of spinal cord and brain

Fast working 

MOA: Binds to special site on GABA_A receptor. Inhibits response to pain by binding to ß3 on GABA_A and causes sedation by binding to ß₂ on GABAA(point mutation can eliminate fct)

Half life: 1.8 hours (hydrophobic)

2-4 minute distribution to entire body because EXTREMELY LIPID SOLUBLE

Why is diazepam not a good choice for long term sedation 

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Context sensitive half time

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The longer you give the drug the longer it takes to get rid of it. 

Net transfer into compartments is a guide as to when to stop infusion

Urine excretion: 88%

Hepatic conjugation of inactive glucuronide metabolites. 

Etomidate

Plasma concentration

Half life

Termination

Side effects

Biphasis

Initial: 3 min, Intermediate: 29 min

Redistribution

Adrenal insufficiency, hemodynamic

Ketamine

Use

Solubility

MOA

Metabolism

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Only induction drug with analgesic effect. Dissociative anesthesia: still awake, breathe spontaneously (good for patients with respiratory syndromes), catabolic

Water soluble with 2 isomers (US uses racemic mixture)

S is more potent that R and has less side effects (KNOW)

Binds to NMDA receptor, opioid receptor, monaminergic receptor, muscarinic receptor, voltage-sensitive calcium channels

DOES NOT INTERACT WITH GABA

Hepatic enzyme metabolism

Diazepam, Lorazepam, Midolazam

Agonist: Bind to benzodiazepine receptor (GABA_r)  leading to increased opening of channel

Flumezanil is antagonist of GABAr