2 - Anesthesia Mechanisms and Care Flashcards
What are the five components of anesthesia?
Unconsciousness
Amnesia
Analgesia
Immobility
Attenuation of Autonomic Responses
What is neural inertia?
It takes a much higher concentration of anesthetic to induce anesthesia than to maintain it
What is the definition of MAC?
Minimum Alveolar Concentration
The alveolar pressure of a gas at which 50% of humans do not respond to a surgical incision
MAC measurement only apply to _______ anesthetics, not to ______ anesthetics
gas
parenteral
What is the MAC equivalent in parenteral anesthetics?
The plasma concentration required to prevent a response to a noxious stimuli in 50% of subjects
What are three limitations of MAC?
- Quantal, not graded
- Not helpful with parenteral drugs
- highly dependent on the endpoint used to define it (verbal response, noxious stimuli)
Meyer-Overton Rule
Unitary Theory of Anesthetics
Strong correlation between lipid solubility and MAC
all anesthetics are likely to act at the same molecular site
Exceptions to Meyer-Overton Rule
- Many compounds that are structurally and chemically similar are not anesthetics (some halogenated compounds are anesthetics, some are anticonvulsants, some are neither)
- Anesthetic potency increases with chain length until a critical chain length is reached (cutoff effect), but their oil/gas partition does not exhibit this cutoff
- Enantiometers (mirror-image compounds) which have the exact same solubility do not have the same effect. Other properties like size and shape must also be important.
Lipid theories of anesthesia
Postulates that anesthetics dissolve in the lipid bilayers and produce anesthesia when they reach a critical concentration
Why is the lipid theory of anesthesia not considered the most likely?
No lipid theory can plausibly explain all anesthetic pharmacology
Aside from lipid solubility, the Meyer Overton Rule could also be explained by ___________
the direct interaction of anesthetics with hydrophobic sites on proteins!
Firefly Luciferase
purified water soluble protein that could be inhibited by general anesthetics
Strong evidence that anesthetics bind to proteins
What are four remaining mysteries concerning anesthesia binding?
- Do many anesthetic molecules interact with a single protein molecule or only a few?
- Do anesthetics compete with endogenous ligands?
- Do all anesthetics bind to the same protein pocket?
- How many proteins have hydrophobic pockets that anesthetics can bind to?
What is neuronal excitability?
the propensity of a neuron to generate and propogate action potentials
Is neuronal excitability effected by anesthetics?
Slightly hyperpolarizes, but may nevertheless contribute significantly to the action of anesthetics
What is the most likely subcellular site of general anesthetic action?
synaptic transmission
What is the difference between glutamatergic nuerons and GABAergic neurons?
Glutamatergic neurons rely on glial-secreted signals to establish synaptic transmission
GABAergic neurons establish functional synaptic transmission in the absence of glia
What are glial cells?
cells in the nervous system that support and protect neurons
What is GABA?
The chief inhibitory neurotransmitter in the brain
What is glutamate?
The primary precursor of GABA
How does GABA inhibit neurons?
It binds with ligand gated Cl ion channels and allows Cl to pour into the cell, hyperpolarizing the cell and preventing excitability
What is the MOA of volatile anesthetics at the presynaptic level?
Inhibit release of glutamate
Interfere with sodium channel activity
What is the MOA of volatile anesthetics at the postsynaptic level?
Potentiate GABA receptor activity
How do volatile anesthetics affect neurotransmission?
Inhibit excitatory neurotransmission
Enhance inhibitory neurotransmission
How are ion channels affected by volatile anesthetics?
- Voltage dependent calcium channels : minimal sensitivity to anesthetics
- Some Na channels are inhibited
- Tp/4TM K channels may be involved
- HCN channels may be involved
What are NMDA channels?
Glutamate-activated ion channels that conduct Na, K, and Ca
Which anesthetics inhibit NMDA-type glutamate receptors?
Ketamine
N20
Xenon
What is GABA potentiation?
Which drugs cause it?
Makes it easier for GABA to elicit a Cl current
Halothane, Enflurane
What is direct gating of GABA channels?
Ability of a gas to activate GABA(a) channels when GABA is absent
What is the main site of at which anesthetics inhibit motor response to noxious stimuli?
The spinal cord. Not the brain.
What is a plausible anesthetic target that accounts for amnesiac effect?
GABA(a) receptors in the Hippocampus and Amygdala
What is the difference between arousal and awareness?
Awareness is the ability to process and store information
Arousal is the state of receptivity to the external environment
What is the RAS?
Reticular Activating System
Diffuse collection of brainstem neurons that mediate arousal
What is the reticular formation?
Collection of neurons in the midbrain and pons responsible for arousal and sleep
Likely the site of arousal ablation under anesthesia
What does the thalamus regulate?
cortical excitability
likely a site of ablation of arousal and awareness
What is the incidence of intraop awareness?
0.1-0.4%
What is the Brice Questionnaire?
accepted tool for detecting awareness postop
- Last thing you remember before sleep
- First thing you remember waking up
- Did you remember anything in between
- Did you dream during your procedure
- What was the worst thing about your operation?
When does awareness occur most?
Least?
Maintenance
Emergence
What are risk factors for awareness?
Females
Young adults
obesity
after normal hours
Emergency procedure
obstetric, cardiac, thoracic sx
use of nondepolarizing relaxants
Does BIS monitoring prevent awareness?
No
Are children more or less likely to develop PTSD from awareness?
Less
What is the difference between the elimination half life and the context-sensitive half-time?
C-S HT describes the time required for the plasma drug concentration to decrease by 50% after the termination of an infusion
As infusion duration increases, the context-sensitive HT _________
also increases
Fentanyl has a shorter half life than sufentanil, but after a two hour infusion fentanyl has double the context-sensitive HT. Why?
Fentanyl is stored in the compartments, so once the plasma concentration is cleared by the kidney, it is re-supplied by fentanyl returning from the periphery
What is t1/2ke0?
the half time of equilibration between drug concentration in the blood and effect on the target
“lag time”
Is t1/2ke0 more important with boluses or drips?
Why?
Boluses
Helps determine how far apart boluses should be given, and how big they should be
How does a decrease in CO (either iatrogenic or disease related) effect redistribution?
How should that change administration?
Redistribution will likely be impaired 2/2 poor perfusion to normal distribution sites.
Give small, well spaced doses. The timing of onset and duration will be increased. Be careful.
How does propofol interact with fentanyl?
Versed?
with fentanyl: reduces prop needed to suppress pain, but doesn’t effect amount needed for induction
versed: just the opposite
What is Cpss50?
Mac equivalent for IV drugs
Plasma concentration of a drug at steady state that is required to abolish purposeful movement at skin incision in 50% of patients
The effect of giving opiods and benzodiazepines together is not just _______, it is _________
additive
synergistic
Versed does not have significant respiratory effects alone.
What happens when it’s given with fentanyl?
WAAAYYY more respiratory depression/hypoxia/apnea than either of them alone
Why is propofol an ideal drug for MAC? (3)
context-sensitive HT short even with prolonged infusions
Short effect site equilibration (t1/2ke0)
Low incidence of PONV
Propofol is a _____-_____,
while versed is a ________.
sedative-hypnotic
sedative
How long does flumazenil effectively block benzos?
Up to 90 min, then symptoms may recur
What are 3 common adverse effects of narcotics?
- Resp Depression
- Muscle rigidity
- PONV
Are opiods significantly amnestic?
Nope
Bolus admin of remifentanil is associated with _____ and ______
Respiratory depression
chest wall rigidity
If respiratory depression develops and the remifentanil drip is decreased, how long will it take before you see a clinical change?
3 min
What is the most logical mode of remifentanil adminstration during MAC?
Constant infusion without boluses
Typical IV Dose:
Midazolam
1-2 mg prior to prop or remifent
Typical IV Dose:
Fentanyl
0.5-2 mcg/kg bolus 2-4 min prior to stimulus
Typical IV Dose:
Remifentanil
0.1 mcg/kg/min
What is frequently given with ketamine?
Why?
Antisialagogue
Fear of laryngospasm
Oral Ketamine
4-6 mg/kg
O 20-30 min
D 60-90 min
IM Ketamine
2-4 mg/kg
O 5-10 min
D 30-120 min
IV Ketamine
0.25-1 mg/kg increments
O 1-2 min
D 20-60 min
Precedex is a _______ agonist that produces _______ and ______
Alpha2 receptor
sedation
analgesia
Why is precedex useful in patients with OSA?
Hypercapnic arousal response remains intact
Precedex
Initial Bolus Dose:
Infusion Rate:
- 5-1 mcg/kg over 10-20 min
- 2-0.7 mcg/kg/hr
________ has amnestic properties at sub-hypnotic doses. _______ does not.
Propofol
Precedex
Why does the upper airway collapse during anesthesia?
During inspiration, the pressure within the upper airway is subatmospheric, creating a tendency to collapse
In awake patients this is prevented by upper airway dilator muscle tone
Why is airway obstruction a problem even when the patient has a normal respiratory drive?
The genioglossal mm and its counterparts are WAY more sensitive to sedatives than the diaphragm
MAC related adverse respiratory outcomes were overrepresented in which groups?
Elderly
ASA 3&4
Which MAC drug has a particularly suppressive effect on airway protective reflexes?
Propofol
A patient is receiving supplemental O2 and has a normal SpO2. Is alveolar ventilation adequate?
Impossible to know. Supp O2 can easily mask alveolar hypoventilation
What is the leading cause of death and severe injury during MAC?
Hypoxia d/t suppresion of spontaneous respiration by sedative-hypnotic drugs
What is the second most common cause of injury in MAC?
Cautery fires, particularly head and neck
How can fires in MAC be prevented?
- Don’t tent drapes
- Keep O2 as low as possible
- Use compressed air instead of O2
- Stop O2 flow 60 sec before cautery
- No alcohol prep
Where should a precordial stethoscope be placed?
sternal notch
When is respiratory depression more likely to be detected during MAC?
17.6x more likely to be identified when capnography is used
Who is more at risk for hypothermia: MAC or general?
Both are at risk. Studies show no difference.
Why does regional anesthesia tend to cause hypothermia?
Lower extremity vasodilation causes central cooling by moving blood into the periphery
Why should you be vigilant if a patient says it’s too hot under the drapes?
Feeling of hyperthermia may occur with hypoxia, hypercarbia, cerebral ischemia, local anesthetic toxicity, and MI
What are symtoms of low dose local anesthetic toxicity?
Sedation
Numbness of the Tongue and circumoral
Metallic taste
What are symptoms of high dose local anesthetic toxicity?
slurred speech
skeletal mm twitching
restlessness
vertigo
tinnitus
What MAC factors can increase local anesthetic toxicity?
Hypercarbia
Decrease hepatic blood flow
acidosis
hypoxia
