Week 5 Inhalation Anesthetics Flashcards by Ashley Campbell

A single specific anesthetic receptor has yet to be found

True or false

True

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_______ sites of action and proteins targets probably exist

Multiple

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We do know that once a ________ _______ of a drug enters the brain and spinal cord, loss of consciousness ensues

Critical concentration

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Level of anesthesia is related to ______ concentration

Alveolar

(Measured through end tidal)

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Partial pressure of anesthetic in ______ is assumed to be the same as in the ______

This is why the dose of an individual drug is expressed in terms of ______ ______ ______ (_____)

Lungs, brain

(ex: end tidal sevo 1.8, assume its 1.8 in the brain)

Minimum alveolar concentration (MAC)

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MAC is the minimum alveolar concentration required to produce anesthesia in ____ % of the population upon surgical stimulation

Gauged by _________

50%

Lack of movement

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We start with a drug supplied as a ______, vaporizing it in an anesthesia machine, and delivering it to the patient’s _______ and other tissues via the ______

Liquid
Brain
Lungs

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Main factors influencing ability to anesthetize patients are (5)

Technical or machine specific
Drug related
Respiratory
Circulatory
Tissue related

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Primary factors that influence ABSORPTION of inhalation anesthetics (5)

SOLUBILITY of the anesthetic drug
in the blood
Uptake into the blood
Alveolar-to-venous blood partial-
pressure difference
Ventilation
Cardiac output

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Factors that may affect UPTAKE early in anesthetic administration (2)

-Drug solubility in the rubber and
plastic machine parts (minimal)
-Total machine liter FGF of gases
chosen

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How do FGFs affect uptake early in anesthetic administration?

-Low flows = slows delivery of anesthetic gases
-High flows = speeds process up

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What is FGF of 1L O2, 1L air?

2L FGF

Carrier gases (O2, air, N2O that flow through vaporizers to pickup and carry volatile anesthetics into patient)

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Blood/Gas solubility

An indicator of the _______ of uptake and elimination

Speed

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Blood/Gas solubility

Reflects proportion of anesthetic that will be ______ in the blood, and not readily enter the ________

Soluble, tissues

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Blood/Gas solubility

Increased solubility means anesthesia will be achieved________ (faster/slower)

Slower

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Blood/Gas solubility

The ______ soluble the drug, the slower the brain and spinal cord uptake drug, anesthesia is achieved slower

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Sevoflurane MAC

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Isoflurane MAC

1.15

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Nitrous oxide MAC

105

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Desflurane MAC

5.8

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Sevoflurane Blood/Gas Coefficient

0.6

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Isoflurane Blood/Gas Coefficient

1.4

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Nitrous oxide Blood/Gas Coefficient

0.47

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Desflurane Blood/Gas Coefficient

0.42

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Blood/Gas Solubility Agents with ____ solubility ( ____ blood/gas coefficient) leave the blood quickly and enter the tissues, producing a rapid anesthetic state

low, low ex: Desflurane (0.42- lower solubility) faster than Isoflurane (1.4- higher solubility)

The ventilation effect: The ______ and more _______ a patient breathes or is ventilated, the _______ the patient loses consciousness at the start of anesthesia and emerges at the end

faster, deep, faster (can get more volatile agent into and out of patient faster)

The ventilation effect __________ in pediatrics results in faster loss of consciousness

Crying

_______ -_______ deficits or poor lung function hinder inhalation drug administration

Ventilation-perfusion

During first minutes of gas administration, a higher concentration of drug, or loading dose, is delivered to speed initial uptake Commonly referred to as what?

Overpressuring or the concentration effect

__________ can speed the effect of slow agents (i.e. Isoflurane)

Overpressuring

In overpressuring, after the first few minutes the dose is ________ to the normal maintenance level

decreased

__________ administration of a relatively slow agent with a faster drug in high concentrations can speed the onset of the slower agent Referred to as what?

Simultaneous Second Gas Effect

Example of the Second Gas Effect

Isoflurane with nitrous oxide Sevoflurane with nitrous oxide (pedi induction)

Second Gas Effect Mechanism of second-gas effect not clearly definitive but traditionally explained as the _______ volume uptake of nitrous oxide concentrating the other alveolar gases

large

The second gas effect occurs during ____________ as well

emergence (if want to get agent off faster, can use second gas effect)

Oil/Gas Solubility Coefficient is an indicator of _________

potency

Oil/Gas Solubility Coefficient Higher the __________ the more potent the drug

solubility

Oil/Gas Solubility Coefficient High solubility reflects high _____ solubility

lipid

Oil/Gas Solubility Coefficient Highly ______ -soluble drugs tend to be the most potent

lipid

Oil/Gas Solubility Coefficient __________ (99) is the most potent, _________ (1.4) is the least

Isoflurane, nitrous oxide

Oil/Gas Solubility Coefficient Sevoflurane

Oil/Gas Solubility Coefficient Isoflurane

Oil/Gas Solubility Coefficient Nitrous Oxide

1.4

Oil/Gas Solubility Coefficient Desflurane

18.7

Two major influences on anesthetic uptake and distribution: 1. Blood leaving the lungs deliver anesthetic to _______ compartment first vs _______ compartment The _______ the administration the greater the saturation in all compartments 2. During induction, ________ in cardiac output slow onset _______ cardiac output removes more anesthetic from the lungs, which slows the rise in lung and brain concentrations

1. central, peripheral Longer, (the longer infused, closer to equilibrium in the central and peripheral compartments) 2. Increases Increased (removing volatile anesthetic from lungs will slow the rise in lung concentration, and ultimately brain concentration)

__________ metabolized

Minimally

Possible toxic _________ formation is not currently a clinical issue

metabolite

_______ was known to be hepatotoxic

Halothane (repeated exposure = higher risk for hepatitis)

Although sevoflurane is metabolized ___ - ___ % releasing free _____ ions, no related clinically significant toxicity has been noted

5-8% flouride

Anesthetic metabolism Sevoflurane: __ - __ metabolized Nitrous oxide: < __ % metabolized Isoflurane: < __ % metabolized Desflurane: < __ % metabolized

5-8% < 1% < 1% < 0.1%

Temperature _________ results in slow induction, with slower emergence due to increased tissue capacity and slower perfusion

Hypothermia

Temperature Hyperthermia ________ anesthetic requirements and cardiac output, leads to _______ induction

Increases, slower

Emergence In general the ______ an anesthetic is administered, the slower the patient emerges

longer

Emergence Greatest (slowest) with the _____ soluble agent, ________, and less with _______ and ________

most, isoflurane sevoflurane, desflurane

Emergence Residual anesthetic has been shown to remain in the body for ________ following a routine anesthetic

several days

Diffusion Hypoxia During emergence, when _____ concentrations of a rapid insoluble anesthetic (________) have been given and then stopped, the drug exits the body quickly through the _____ and is replaced by _____ soluble nitrogen in the air This results in a transient _______ of normal respiratory gases Administration of _____ % oxygen will prevent this potential problem

high Nitrous oxide lungs less (N20 leaves, nitrogen replaces it) dilution (brief hypoxic episodes) 100% ex: running 50% N20, turn off N2O, turn on 100% O2 = wont see diffusion hypoxia

________ diffuses into air-containing cavities in the body

Nitrous oxide

Examples of Nitrous oxide diffusing into air-containing cavities of in the body (7)

air embolism pneumothorax acute intestinal obstruction intraocular air bubbles pneumoperitoneum ENDOTRACHEAL TUBE LMA *If running N2O for prolonged time, check cuff pressures; can trend upward over course of case

uptake ________ in children than in adults

faster

child's ______ alveolar ventilation per weight accounts for faster uptake

higher

infants and children have higher cardiac outputs per weight than adults This would normally slow onset Cardiac output is distributed to __________ group in children, as well as ______ muscle mass, means more agent delivered to vital organs

Vessel-rich lower

Risk factors for emergence agitation (4)

Difficult parental separation behavior Anxiety Age 2-5 Postop pain

Drugs that reduce incidence of emergence agitation (4)

Fentanyl DEXMEDETOMIDINE (gold standard) Propofol Ketamine

Do midazolam, serotonin antagonists, or parental presence upon emergence have an effect on emergence agitation?

Obesity Some clinicians prefer __________ because of its low solubility and lipophilicity This appears to promote a slightly _______ recovery

desflurane faster

Obesity Long procedures and morbid obesity allow for an ______ in deposition of anesthetics into fat This may ________ recovery

increase prolong

Pregnant women have a ______ (higher/lower) minute ventilation

higher

Pregnant women have a ______ (higher/lower) cardiac output

higher

In pregnant women, uptake of anesthetics is ___________ to nonpregnant women

similar (Because higher minute ventilation [speeds up onset] and higher cardiac output [slows onset] cancel eachother out)

Right-to-left shunt ______ (speeds/slows) induction of anesthesia

Slows b/c shunted blood mixes with and dilutes blood coming from ventilated alveoli, resulting in reduction of alveolar partial pressure of anesthetic takes longer to build up concentration

Right-to-left shunt _______ or part of anesthetic ( ____ lung ventilation)

Pathologic (one )

Right-to-left shunt Shunted blood mixes with and ________ blood coming from ventilated alveoli resulting in ________ of alveolar partial pressure of the anesthetic

dilutes, reduction = slows induction of anesthesia (takes longer to build up concentration)

Left-to-Right shunt Causes anesthetic partial pressure in mixed venous blood to _______ (increase/decrease) more rapidly than it would in absence of shunt

increase

Left-to-Right shunt Slightly _________ rate of anesthetic delivery or uptake into the brain, muscle, and other tissue is a result

increased

Cardiopulmonary bypass ________ characteristics of modern membrane oxygenators are more limited than lungs

transfer

Cardiopulmonary bypass During bypass _______ concentrations of volatile anesthetic agent are given compared to that which is required when administered by normal lung inhalation

higher

Ether was made in ______ Sevoflurane was made in ______

1842 1995

All commonly used inhalation agents are ______ or _______ ________ with no more than 4 carbon atoms

ethers (R-O-R) aliphatic hydrocarbons

Halogenation of hydrocarbons and ethers influences: (4)

Anesthetic potency Arrhythmogenic properties Flammability Chemical stability

Halogenation entails the addition of: (4)

Fluorine Chlorine Bromide Iodine

Volatile anesthetics interact with main repolarizing cardiac ________ channels, as well as with _____ and _____ channels at slightly higher concentrations

potassium calcium sodium (cardiac depressants)

Inhibition of the ion channels by volatile anesthetics alters both ______ ______ shape (triangulation), and _______ _______ conduction This may facilitate arrhythmogenesis by volatile anesthetics per se, and is potentiated by _____________

action potential electrical impulse catecholamines

Flammability is reduced and chemical stability enhanced by substituting _____ atoms with ______

hydrogen, halogens

Desflurane contains _____ as its only halogen This results in a molecule that strongly resists _________

fluorine biodegradation (stable molecule)

Do we know the exact mechanism of action of inhalation anesthetics?

No, exact mechanisms remain elusive

A popular hypothesis of MOA proposes that general anesthesia results from direct multisite interactions with multiple and diverse _____ _______ in the brain

ion channels

MAC is useful to compare the _______ of inhalation agents

potencies

MAC is where ____ % of subjects will not respond to a painful stimulus A response is defined as _____, ______ movement of the head or extremities

50% gross, purposeful

The MAC represents the _____ dose of the anesthetic

required

MAC requirements is ____ dependent Peaks at ___ months of age, and gradually ______ with age

age 6 months, decreases (6 month old = highest MAC requirement)

The MAC at which 50% of subjects will respond to command "open your eyes"

MAC-awake (about 1/3 of MAC)

MAC necessary to block adrenergic response to skin incision

MAC-BAR (block adrenergic response) (About 1.6 times higher than MAC)

From a clinical standpoint patients usually require anesthetic concentrations that exceed the MAC by ___ - ____ % (____ - ____times MAC)

20-30% 1.2-1.3 (If running primarily on volatiles)

Increased age

Reduces MAC

Hypothermia

Reduces MAC

Administration of sedative hyptonics

Reduces MAC

Coadministration of other anesthetics

Reduces MAC

Alpha-agonists

Reduces MAC

Opioids

Reduces MAC

Acute ethanol consumption

Reduces MAC

Hypoxemia

Reduces MAC

Hyponatremia

Reduces MAC

Anemia (less than 4.3 mL O2/dL blood

Reduces MAC

Hypotension (MAP < 50 mmHg)

Reduces MAC

Pregnancy

Reduces MAC

Lithium

Reduces MAC

Young age

Increases MAC

Hyperthermia

Increases MAC

Hyperthyroidism

Increases MAC

Hypernatremia

Increases MAC

Acute administration of CNS stimulant drugs

Increases MAC

Red hair in females

Increases MAC

Chronic alcohol abuse

Increases MAC

Duration of anesthesia

No effect on MAC

Gender

No effect on MAC

Hypocapnia or hypercapnia

No effect on MAC

Metabolic alkalosis

No effect on MAC

Hypertension

No effect on MAC

Hyperkalemia or hypokalemia

No effect on MAC

Hypermagnesemia

Reduce MAC

MAC is expressed as a ___ of ___ atmosphere

% of 1 atmosphere

When combined with 60-70% N20, MAC ______

decreases

______ is the primary site of action of volatile anesthetics, which exhibit ____ -_______ effects with significant clinical considerations

CNS dose-dependent

Inhalation anesthetic (iso, sevo, des) effect on Cerebral metabolic rate of O2 (CMRO2) and cerebral blood flow (CBF)

Decrease CMRO2 Increase in CBF (dose-dependent)

N20 effect on Cerebral metabolic rate of O2 (CMRO2) and cerebral blood flow (CBF)

Increases CMRO2 Increases CBF

Volatile anesthetics produce dose dependent _____ in CBF This effect depends on the balance between vasoconstrictive properties, due to ____ -________ coupling, and the direct cerebral ________ action of the anesthetics

increase flow-metabolism vasodilatory (decreases in CMRO2 and increases in CBF = uncoupling occurs)

When vascular resistance is decreased, CBF, cerebral blood volume, and CSF pressure _______

increase (need to be aware of these changes in high risk patients)

Uncoupling of cerebral blood flow (CBF) and metabolism When ______ in CMRO2 are accompanied by _______ in CBF, uncoupling is said to occur

decreases, increases

Uncoupling of cerebral blood flow (CBF) and metabolism This response does not seem to occur with ___ MAC or less of ______ or _________

1.0 desflurane, isoflurane (if keep volatiles < 1 MAC can keep this phenomenon from occurring; use a "balanced technique" to prevent uncoupling, ex: volatile anesthetic with remifentanil or a different opioid of choice)

Cerebral vascular responsiveness to CO2 Normal physiologic response of the cerebral vasculature to CO2 is to _____ in the presence of hypocapnia and ___________ with hypercarbia

vasoconstrict vasodilate

Cerebral vascular responsiveness to CO2 In patients in which a reduction in intracranial volume is desired (ex: increased ICP) partial pressure of arterial carbon dioxide should be maintained around ____ to _____ mmHg Effective for approximately ____ -____ hours

30-35 mmHg 4-6 hours (decrease CO2 with hyperventilation = vasoconstriction) Done in neurosurgical patient population

Electroencephalogram (EEG) Volatile agents produce dose-dependent _______ of EEG activity

suppression

Electroencephalogram (EEG) Burst suppression can be achieved at ____ - _____ MAC with desflurane, and ____ MAC with isoflurane or sevoflurane (Burst suppression = EEG temporarily stops recording)

1.5-2 2

Evoked Potentials Volatile agents and N2O produce a dose-dependent _________ in evoked potentials ___________ evoked potentials most sensitive ___________evoked potentials most resistant

reduction Visual-evoked potentials Brainstem-evoked potentials

Evoked potentials An increase in latency or decrease in amplitude of evoked potentials can reflect _____, or may be secondary to the __________

ischemia volatile agent (issue b/c monitoring these as part of maintaining safety of patient during procedure = may actually reflect ischemia OR be result of volatiles anesthetic) Work to provide anesthetic that will allow for optimal monitoring without dampening signals more than necessary (balanced technique, TIVA)

Emergence and neurologic assessment in adults _______ emergence in neurosurgical patients can have devastating consequences Makes ___________ assessment difficult

Delayed Neurologic (ex: want to do a neuro assessment after wake-up from carotid endartectomy, craniotomy)

Emergence and neurologic assessment in adults Conflicting data on superiority of _____ vs _______ anesthetics

TIVA vs inhalation

Emergence and neurologic assessment in adults Are inhalation agents still widely used in most neurosurgical procedures?

Yes (want a technique that allows for prompt wakeup with minimal long term complicating effects of neuro assessment; ex: avoid benzos so not lingering around)

Developmental neurotoxicity FDA advised that repeated or lengthy use of general anesthetics and sedative drugs in children younger than _____ or in pregnant women during the ________ trimester may affect the development of the child's brain

3 third

Developmental Neurotoxicity Recommended to keep anesthesia and surgery as _____ as possible and to use _____-acting drugs and/or a combination of general anesthesia and multimodal anesthesia including systemic analgesics and local or regional anesthesia to ______ overall drug dosages

short, short reduce

Emergence phenomenon in children Occurs after ______ and ______ in preschool-aged children

sevoflurane, desflurane

Emergence phenomenon in children Usually lasts about ___ minutes and will ______ _______ once the child eliminates more of the anesthetic

15 resolve spontaneously

Treatment for Emergence phenomenon in children

Dexmedetomidine

Cardiovasular system All capable of altering _______ (dose-dependent)

Hemodynamics

Cardiovascular system Extent volatiles alter hemodynamics related to preoperative and intraoperative factors: - _______ status classification -Co-administration of: (4)

Physical status classification Co-administration of: vasoactive drugs opioids benzodiazepines propofol

Cardiovascular system Isoflurane, desflurane, sevoflurane all _______ CO and CI in a dose dependent fasion

reduce

Cardiovascular system Isoflurane, desflurane, and sevoflurane all _____ MAP via _____ in SVR N2O activates the ________ and increases _______

reduce, reduction symapthetic nervous system SVR (can have more stable hemodynamic pattern in certain patients if decrease volatile agent and use N20 as strategy to achieve full MAC of anesthesia for patient)

Cardiovascular system Dose dependent changes in heart rate noted Rapid increases in inhaled concentrations of _______, and especially _______ can lead to increase in HR and BP _______ activation due to an irritant effect

isoflurane desflurane symapthetic

Cardiovascular system Sevoflurane has _________ HR effects

Minimal

Cardiovascular system As MAC hours of anesthesia increase, CI and HR _____ slightly

increase (for long procedures, increase over time)

Cardiovascular system ____________ is a reduction in the perfusion of ischemic myocardium with simultaneous improvement of blood flow to ________ tissue

Coronary steal nonischemic

Cardiovascular system Coronary steal: Blood is taken from the "_____" and given to the "______"

Poor, rich

Cardiovascular system Coronary steal When _______ is maintained, a steal phenomenon is ablated Maintain within ___ % of baseline to avoid coronary steal

normotension 20% (coronary steal is not an ideal situation because want ischemic area to receive blood flow)

Cardiovascular system Arrhythmias Have both _________ and _________ actions

proarrhythmic and antiarrhythmic

Cardiovascular system Arrhythmias All ______ QT interval

prolong

Cardiovascular Arrhythmias All agents with the exception of _______ and probably ________ are conducive to the development of ________ and disturbances in ____ nodal conduction

isoflurane, desflurane bradycardia AV

Cardiovascular Arrhythmias When fibers become ischemic or injured, volatile agents are prone to producing ________ excitation

reentrant

Cardiovascular Arrhythmias Ability of volatile agents to reduce the quantity of catecholamines necessary to evoke arrhythmias is commonly, but inaccurately, called _______ More accurate to describe as an __________ Keep epinephrine dose less than _____ mcg/kg

sensitization adverse drug reaction 10

In normal adults, PVR has a small _____ with N2O May become clinically significant with preexisting ____________ which results in larger increases in PVR

Increase Pulmonary hypertension

Volatile agents ________ pulmonary artery pressure

decrease

Responsiveness to CO2 is _______

depressed

Tidal volume _______ as concentration of agent increases

reduces

Compensatory increases in RR as a response to decreased TV is not sufficient to prevent elevations in ______

CO2

___________ helps to overcome respitatory-depressant effects of volatile agents

Surgical stimulation

________ of renal circulation generally remains intact

Autoregulation

Reductions in SBP are accompanied by compensatory _______ in renal vascular resistance Can still result in ________ in GFR This may contribute to the commonly seen intraoperative _____ in urinary output

decreases decline reduction

FDA guidelines recommend caution with use of ___________ in renal insufficient patients Past concern with ___________'s degradation within anesthesia circuits by older CO2 absorbents This resulted in the production of potential toxin referred to as ________, and dictated fresh gas flow rates

sevoflurane sevoflurane's Compound A millions of sevoflurane anesthetics have failed to demonstrate any significant untoward renal outcomes

Volatile anesthetics have the potential to impair liver function ________ in particular is associated with significant risk of postoperative liver failure = __________

Halothane, halothane hepatitis (especially with repeat exposure)

Extremely rare for _______, _______, and ________ to produce clinically significant liver damage

isoflurane, sevoflurane, desflurane

All volatile agents produce dose-dependent ________ of skeletal muscle, as well as additive effect with ________ and _________ muscle relaxants

relaxation depolarizing and nondepolarizing

Neuromuscular sytems Multifactorial mechanism: _______ neural activity in the CNS ________and _________ effect at NMJ

Reduced Presynaptic and postsynaptic

Malignant hyperthermia Which volatile agents are capable of triggering?

All volatile agents except N2O

Medications used to treat malignant hyperthermia in adults and children

Raynodex and dantrolene

Pregnant patients have a ____ to ____ % chance of developing a medical condition that requires a general surgical intervention during pregnancy

0.2% to 0.75%

Elective surgery should be _______ until after delivery in pregnant women, and nonurgent surgery should be performed in the _____ trimester

delayed second

_____ exposure has been linked to both spontaneous abortion and _____ fertility in workers

N2O, reduced