Inhalational Agents Flashcards
What is added on modern anesthetic agents?
diethyl group
the 3 A’s of inhalational general anesthesia
amnesia, analgesia, areflexia
Action of general anesthesia agents
altered transmission in the cerebral cortex
additional effects on: brain stem arousal center, central thalamus, spinal cord
What makes them cross blood brain barrier quickly?
carbon based
Stage 1 of Anesthesia
Amnesia and Anesthesia
initiation of anesthesia: LOC, follow simple commands, protective reflexes, eyelid reflex intact
Stage 2 of Anesthesia
Delirium and Excitation
LOC and eyelid reflex, irregular breathing, dilated pupils, extremely hypersensitive - vomiting, laryngospasm, cardiac arrest, emergence delirium, avoid manipulating!
Stage 3 of Anesthesia
Surgical Anesthesia - where we want them!
cessation of spontaneous respiration, absence of eyelash response and swallowing reflex
should get benefit of 3 A’s here
Who do we see stage 2 exaggerated in?
young kids
Stage 4 of Anesthesia
anesthetic overdose!
cardiovascular collapse
Are we hyperdynamic or hypodynamic in stage 2?
hyperdynamic (elevated BP and HR)
choice of anesthesia based on
proposed surgery
comorbidities
provider experience
surgeon
When was nitrous oxide discovered and by who?
1793 by Joseph Priestley
When was nitrous oxide successfully used in a dental procedure and by who?
1842 by Horace Wells
when was diethyl ether first used in medicine and by who?
1842 by Crawford Long
What day is ether day and why is it that day?
October 16.. on this day in 1846 William TG Morton removed a tumor from a jaw using diethyl ether
When was chloroform discovered and by who?
1831 by Dr. Samuel Guthrie
When was chloroform first used as an anesthetic and by who?
1847 by Sir James Young Simpson
What is unique about chloroform?
nonflammable, highly potent
When did Dr. John Snow use chloroform?
in 1853 on Queen Victoria during child birth
but had developed the first vaporizer
When was Halothane developed?
1956
Significance of Halothane?
first halogenated anesthetic agent, non flammable, metabolized in liver, causes hepatoxicity
How does an inhalation agent work?
it starts in liquid form, gets vaporized, and breathed in and delivered to the brain
absorption of inhalational agents are related to
ventilation, blood uptake, cardiac output, blood solubility, and alveolar to blood partial pressure difference
the concentration or partial pressure of gas in the lungs is assumed to be ____
be equal in the brain
Definition of MAC
minimum alveolar concentration (%) required to produce anesthesia (lack of movement) in 50% of population
the faster the lung concentration rises
the faster anesthesia is achieved
Increase MAC if
hyperthermia, increase in CNS activity, hypernatremia, chronic alcohol abuse
Decrease MAC if
hypothermia, increased age, alpha 2 agonists (dex), acute alcohol ingestion, pregnancy, hyponatremia
rubber and plastic pieces and CO2 absorbent can ___
retain gas delaying initial uptake
all inhalational agents except ____ can trigger ___
nitrous oxide ; malignant hyperthermia
ways to avoid triggering malignant hyperthermia in at risk patient
flush 10mL/min for 20 minutes, replace all breathing circuits and CO2 absorbent, remove all vaporizers, charcoal filters
increasing liter flow during induction ____ agent intake
accelerates
Definition of Blood:Gas Solubility
describes amount of gas that will dissolve or bind to blood vs the amount that will diffuse into tissues
isoflurane solubility coefficient
1.4
there is 1.4x more gas soluble in the blood than available to the tissues
desflurane solubility coefficient
0.42
only .42 stays in blood for every molecule that is available to the tissues (put to sleep quicker and awake faster)
Which is more potent isoflurane or desflurane?
isoflurane
Over-pressuring or Concentration Effect
administration of higher concentration of gas than necessary to speed up initial uptake
greater effect on high solubility gases
Second gas effect
co-administering a 2nd agent with NO to speed the onset of the slower agent
also used in emergence to quickly remove slower gas
Why don’t we use nitrous oxide with Desflurane often?
can cause tachycardia/arrhythmia if over-pressurized, toxic to environment
oil:gas solubility
ability to get into tissues, indicator of potency
higher lipid soluble drugs tend to be ___
more potent
the circulatory system has 2 major influences on anesthetic gases
- uptake
2. distribution
an increase in cardiac output
slows uptake
approximately 5-8% of sevoflurane is metabolized
by the liver
decreases in temperature results in
increased potency and solubility
hypothermia decreases
tissue perfusion = slowed induction
how can decreased tissue perfusion in hypothermia be overcome?
increase gas concentration, warm the patient if able
hypothermia increases
tissue anesthetic capacity (slow recovery)
hyperthermia increases
cardiac output and anesthetic requirement (slows induction)
a patient receiving nitrous oxide during a case should receive
100% oxygen on emergence
the longer an anesthetic gas is used during the case
the slower the emergence
the higher the solubility
the slower the emergence
emergence phase 1
cessation of anesthetic, reversal, apnea to breathing, increased alpha and beta waves on EEG
emergence phase 2
increased HR and BP, return of autonomic responses, responsiveness to pain, salivation, tearing, grimacing, swallowing and gagging, defensive posturing
emergence phase 3
eye opening, response to verbal commands, awake EEG, extubation possible
nitrous oxide is ___ soluble than nitrogen
34 times more
when nitrous oxide is being administered what can happen
increased volume in air containing cavities (abdominal distension)
anesthetic agents are ___ soluble and ___ uptake in kids over adults
less; greater
right to left shunt
ex. PE
shunted blood mixes and dilutes blood reducing anesthetic partial pressure and slows induction
left to right shunt
ex. septal defect
increases uptake
What are all of the modern inhalation agents based off of?
ether
What is the basic structure of ether?
R-O-R
What is fresh gas flow determined by?
vaporizer and flowmeter settings
Fi stands for and is determined by
inspired gas concentration, determined by FGF rate, breathing circuit volume, and circuit absorption
FA stand for and is determined by
alveolar gas concentration, uptake, ventilation, concentration effect and second gas effect
Fa stand for and is determined by
arterial gas concentration, affected by ventilation/perfusion mismatching
What could cause V/Q mismatch in terms of intubation
right bronchial intubation, PFO
What do inhalational agents most likely target?
NMDA receptors, tandem pore potassium channels, VGNaCh, glycine receptors, GABA receptors
According to the Meyer Overton theory…
lipophilicity equals potency
CMRO2 is ____ with inhalational agents
decreased
Cerebral blood flow is ___ with inhalational agents
increased
What happens with “uncoupling”
CMRO2 decreased, CBF increased except for NO it increases both
cerebral vascular responsiveness to CO2 is
vasodilate
When does Burst suppression occur with inhalational agents?
1.5 MAC of desflurane, 2 MAC with isoflurane and sevoflurane
In terms of evoked potentials, inhalational agents
decrease amplitude (height) and increase latency (how often response is occuring)
What is the proposed mechanism of developmental neurotoxicity?
activation of extrinsic and intrinsic apoptic cell death pathways
What does PANDA stand for in PANDA study
pediatric anesthesia neuorodevelopment analysis
What does GAS stand for in the GAS trial
general anesthesia vs spinal
Who should we be concerned about postoperative cognitive dysfunction with?
the elderly
who should we be concerned with emergence delirium with?
children
what inhalational agents is more common with emergence delirium?
sevoflurane and desflurane (insoluble, get in quick, get out quick)
all volatile inhalational agents ___ CO
reduce
as MAC hours increase, ____ CI and HR
slight increase
reduced MAP secondary to
SVR reduction
how do inhalational agents induce HR changes?
via SA node antagonism, modulation of baroreflex activity, SNS activity (blunting)
all inhalational agents produce
vasodilation (SVR)
in hypotensive patients vasodilation can result in
reverse Robinhood syndrome (steal from poor give to the rich)
which inhalational agent is most associated with reverse robinhood syndrome?
isoflurane
preconditioning
the heart is exposed to intracellular events that protect it from ischemic and reperfusion insult
sensitization
volatile agents reduce the quanity (desensitize) of catecholamines necessary to evoke arrhythmias
safe epi dosing
10mL of 1:100,000 (10mcg/mL) in a 10 minute period or up to 30 mL in one hour
nitrous oxide causes a slight increase in
PVR , worsens with patients with pulmonary HTN
volatile agents decrease
pulmonary artery pressure
hypoxic pulmonary vasoconstriction is
depressed
which drug has the greatest effect on HPV?
isoflurane
volatile agents cause decreases in
tidal volume and responsiveness to CO2
how is decreased tidal volume compensated for?
increased RR (not sufficient to offset TV)
which causes the least bronchodilation?
desflurane
which has least impact of renal function?
desflurane
use of older absorbents can increase likelihood
nephrotoxicity with sevoflurane
should not exceed 2 MAC hours at flows ___
<2L per minute
Halothane has what affect on hepatic function?
is associated with Halothane Hepatitis
what causes halothane hepatitis?
metabolites binding to proteins and forming antibodies, re-exposure to Halothane antibodies mediate massive hepatic necrosis
Advantage of fluorination
resists hepatic degradation
which drug undergoes the most metabolism?
sevoflurane (5-8%)
is sevoflurane toxic to liver?
no, can be toxic to kidneys though d/t fluoride ions
volatile agents have additive effect with
nondepolarizing NMBDs
an ideal anesthetic agent
nonirritating to respiratory tract rapid induction and emergence chemically stable (nonflammable) produce amnesia, analgesia, areflexia potent not metabolized and excreted by respiratory tract free of toxicity and allergic reactions minimal systemic changes uses a standardized vaporizer affordable
what four properties affect how agents work
vapor pressure, boiling point, partial pressure, solubility
what is vapor pressure
pressure exerted inside a container between liquid and vapor
as long as liquid is present, vapor pressure is
independent of volume
vapor pressure is directly proportional to
temperature
boiling point
temperature at which vapor pressure exceeds atmospheric pressure in an open container
partial pressure
fraction of pressure within a mixture (Dalton’s Law)
solubility
tendency of a gas to equilibrate with a solution (Henry’s Law)
the concentration of anesthetic in tissue is dependent on
the partial pressure and solubility
what is used instead of partial pressure
inspired concentration or fractional volumes
for most drugs, concentration is measured as
mass (mg/mL) but can be expressed in percent by weight or volume
MAC awake
MAC in which 50% opens eyes to command
MAC bar
the MAC necessary to block adrenergic response to stimulation
MAC ___ with age
decreases
How much should MAC decline with age?
6% each decade after age 40
6% of 6% for example
how do vaporizers facilitate movement of anesthetic from machine to patient
by fresh gas flow, pressure, and temperature
isoflurane (general facts)
halogenated methyl ethyl ether most potent, most soluble slow onset and recovery dilates coronary arteries - reverse robinhood minimal cardiac depression pungent, not used for induction
desflurane (general facts)
least potent
quicker induction and emergence
heated and pressurized to maintain constant
can boil at room temp
rapid increase in gas can increase HR and BP
very pungent
avoid in pts with reactive airway disease
bad for the environment
sevoflurane (general facts)
fluorinated methyl isopropyl ether moderate potency rapid induction and emergence may prolong QT interval nonpungent preferred agent for induction small percent metabolized by CYP soda lime can degrade into Compound A (nephrotoxic)
safety factors for sevoflurane
calcium hydroxide absorbent, flows 2lpm, avoid in renal dysfunction
nitrous oxide (general facts)
not volatile, colorless and odorless gas at room temp nonflammable NMDA receptor antagonist have to weigh it stimulates SNS, increases RR, decreases hypoxic drive increases CMRO2 and CBF increases risk of PONV
absolute and relative contraindications for NO
absolute: methionine synthase pathway deficiency, expansion of gas filled space
relative: PONV, 1st trimester pregnancy, increased ICP, pulmonary HTN, prolonged surgery
Xenon (general facts)
noble gas, odorless, colorless, naturally occuring, acts on NMDA and glycine receptors, minimal effects
rare and hard to get
ideal agent
malignant hyperthemia triggered by
succinylcholine and volatile anesthetics
stress
malignant hyperthermia receptor
ryanodine receptor gene mutation (chromosome 19)
S/S of malignant hyperthemia
incease in CO2 production, muscle rigidity, metabolic acidosis, high temp, urine color darkens, tachycardia, tachypnea
treatment of malignant hyperthermia
dantrolene sodium or ryanodex**
dose of dantrolene sodium (w/ mannitol and sodium hydroxide)
1 mg/kg
*70mL vials containing 20mg
administer until side effects subside or up to 10mg/kg
takes forever to mix!!
ryanodex
requires fewer vials and less reconstituion, shorter half life, requires supplementation of mannitol
