Chapter 4: Stoelting Inhaled Anesthetics Flashcards
What were the characteristics of inhaled anesthetics before the 1950s?
- Before 1950, except for nitrous oxide, inhaled anesthetics were either flammable or potentially toxic to the liver
What was the significance of introducing fluroxene?
- Introduced in 1951
- Fluroxene was the first halogenated hydrocarbon anesthetic
- Developed to decrease flammability
- It was withdrawn due to potential flammability and organ toxicity
When was halothane synthesized, and what was a concern associated with it?
- Synthesized in 1951
- Used clinically in 1956
- Had a tendency to enhance the arrhythmogenic effects of epinephrine.
What are the key features and drawbacks of methoxyflurane?
- Introduced in 1960
- Methoxyflurane didn’t enhance epinephrine’s arrhythmogenic effects
- Caused hepatic toxicity, and nephrotoxicity due to high fluoride levels
- Prolonged induction, and slow recovery
- It still sees limited use in Australia.
What are the characteristics of enflurane?
- Introduced in 1973
- Enflurane doesn’t enhance epinephrine’s arrhythmogenic effects or cause hepatotoxicity
- It can lead to inorganic fluoride metabolism
- Lower the seizure threshold.
Why was isoflurane introduced, and what are its benefits?
- Introduced in 1981 as a structural isomer of enflurane
- Isoflurane is resistant to metabolism
- Reduce the likelihood of organ toxicity
What was the focus in the development of inhaled anesthetics after isoflurane?
- Post-isoflurane, the focus was on creating more pharmacologically “perfect” anesthetics.
- This led to the development of nonflammable, poorly lipid-soluble, and metabolism-resistant anesthetics by excluding all halogens except fluorine.
When were desflurane and sevoflurane introduced, and what are their characteristics?
- Desflurane 1992
- Sevoflurane 1994
- Both totally fluorinated ethers
- Have low solubility in blood
- Enables rapid anesthesia induction
- Precise control during maintenance
- Prompt recovery.
How did market forces influence the development of desflurane and sevoflurane?
- Acceptance of desflurane and sevoflurane were driven more by market forces like ambulatory surgery and the desire for rapid awakening than by significant pharmacologic improvements over isoflurane.
What challenges arise with the use of desflurane and sevoflurane?
- Airway irritation
- Sympathetic nervous system stimulation
- Carbon monoxide production (desflurane)
- Compound A production (sevoflurane)
- Dealing with increased manufacturing and administration costs.
What factors influence the cost of new inhaled anesthetics?
The cost is influenced by the price per milliliter of liquid, anesthetic characteristics like:
- Vapor pressure
- Potency
- Solubility
- Fresh gas flow rate used for delivery.
How do low fresh gas flow rates affect the cost of inhaled anesthetics?
- Decreases costs.
- Less soluble anesthetics, like desflurane and sevoflurane, are suited for low flow rates due to better control of delivered concentration and less depletion from inspired gases.
How does the potency of desflurane compare to isoflurane, and what does this mean for their delivery?
- Desflurane is one-fifth as potent as isoflurane
- Only slightly more than threefold the amount of isoflurane is needed to sustain the minimal alveolar concentration (MAC).
Compare the MAC of sevoflurane to isoflurane and its implications on usage.
- The MAC of sevoflurane is 74% greater than isoflurane
- Only 30% more sevoflurane is needed to sustain MAC.
Physical and chemical properties of the inhaled anesthetic- table
What are the commonly administered inhaled anesthetics as of the current clinical practice?
- Nitrous oxide
- Isoflurane
- Desflurane
- Sevoflurane
Halothane and enflurane are used infrequently but are important for comparative pharmacology studies
How are volatile liquid anesthetics like diethyl ether and chloroform administered?
- Are administered as vapors after vaporization in devices known as vaporizers.
- Diethyl ether and chloroform are now mostly used in veterinary medicine.
What are the characteristics and clinical uses of nitrous oxide?
- Is a low-potency
- Poorly blood-soluble gas
- Analgesic and sedative effects
- Most commonly used with opioids or other volatile anesthetics for general anesthesia.
- It supports combustion
- Causes minimal muscle relaxation
- Can increase the risk of postoperative nausea and vomiting.
What are the concerns and clinical trial findings regarding nitrous oxide?
- Concerns with nitrous oxide include its effect on gas-containing spaces
- Vitamin B12 inactivation
- increased postoperative nausea and vomiting.
- The IMPACT trial highlighted that the risk of nausea and vomiting with nitrous oxide needs to be weighed against its alternatives, like volatile anesthetics or propofol.
What are the key characteristics of halothane?
- Halogenated alkane derivative
- Exist as a clear, nonflammable liquid at room temperature
- Sweet, bland odor
- It has intermediate solubility in blood
- High potency
- Allows for intermediate onset and recovery from anesthesia.
Why was halothane developed, and what are its chemical properties?
- Halothane was developed for its intermediate blood solubility, anesthetic potency, and molecular stability.
- Its structure includes carbon-fluorine bonds (decreasing flammability), trifluorocarbon (contributing to stability), and carbon-chlorine/bromine bonds plus a hydrogen atom (ensuring potency).
What are the stability concerns with Halothane, and how is it stored?
- Halothane can decompose into harmful compounds.
- It is stored in amber-colored bottles with thymol added as a preservative.
- Residual thymol in vaporizers after halothane vaporization can malfunction vaporizer mechanisms.
What are the general characteristics of enflurane?
- A Halogenated methyl ethyl ether
- Is a clear, nonflammable volatile liquid at room temperature with a pungent, ethereal odor.
- It has intermediate solubility in blood and high potency,
- Allowing for intermediate onset and recovery from anesthesia.
What are the notable effects of enflurane and its typical usage?
- Lowers the seizure threshold
- Metabolized in the liver
- Produce nephrotoxic inorganic fluoride ions.
- Primarily used in procedures where a low seizure threshold is desired, like electroconvulsive therapy.
Is enflurane commonly used in the United States currently?
Enflurane is no longer in common use in the United States.
What are the general characteristics of isoflurane?
- Is a halogenated methyl ethyl ether.
- existing as a clear, nonflammable liquid at room temperature
- with a pungent, ethereal odor
- It has intermediate solubility in blood and high potency, facilitating intermediate onset and recovery from anesthesia.
What distinguishes isoflurane in terms of physical stability?
- Extremely stable
- showing no detectable deterioration over 5 years of storage, even when exposed to carbon dioxide absorbents or sunlight.
- Its stability negates the need for preservatives like thymol in its commercial form.
What distinguishes desflurane’s chemical structure from isoflurane?
- Desflurane, a fluorinated methyl ethyl ether
- Has a fluorine atom instead of a chlorine atom on its alpha-ethyl component.
- This fluorination increases vapor pressure
- Enhances molecular stability
- Decreases potency
How does the vapor pressure of desflurane affect its use, and what technology addresses this?
- Its high vapor pressure is three times that of isoflurane
- Would cause it to boil at normal operating room temperatures.
- Special heated and pressurized vaporizers that require electrical power are used to regulate its concentration.
How is Desflurane metabolized, and what is its potency compared to isoflurane?
- Desflurane is minimally metabolized, with serum and urinary concentrations of trifluoroacetate
- Significantly lower than those from isoflurane metabolism.
- Its potency, as indicated by MAC, is about fivefold less than isoflurane.
What are the clinical considerations and side effects of using Desflurane?
- Desflurane’s pungency makes inhalation induction unpleasant
- Cause airway irritation
- Increasing the risk of salivation, breath holding, coughing, or laryngospasm
- It also produces the highest carbon monoxide concentrations when degraded by strong bases in desiccated carbon dioxide absorbents.
Why is intraoperative detection of carbon monoxide challenging?
- Pulse oximetry can’t differentiate between carboxyhemoglobin and oxyhemoglobin,
- Making it difficult to detect carbon monoxide exposure intraoperatively.
- Low pulse oximetry readings despite adequate arterial oxygen may suggest carbon monoxide exposure.
What are indirect indicators of carbon monoxide formation during anesthesia?
- Decreased pulse oximeter readings
- Erroneous gas analyzer readings (indicating mixed gases or enflurane when desflurane is used)
- Can be early warnings of carbon monoxide formation attributed to trifluoromethane production.
How can carbon monoxide exposure be confirmed intraoperatively?
- Carboxyhemoglobin can be measured acutely with CO-oximetry
- A technology that is routinely available, to confirm carbon monoxide exposure
What delayed effects can occur due to carbon monoxide poisoning?
Delayed neurophysiologic sequelae such as:
- Cognitive defects
- Personality changes
- Gait disturbances
- May occur 3 to 21 days after anesthesia due to carbon monoxide poisoning.
What are the solubility characteristics and potency of desflurane, and how do they impact its use?
- Desflurane has a blood:gas partition coefficient of 0.42
- MAC of 6.6%, allowing for rapid achievement of the necessary alveolar partial pressure for anesthesia
- Prompt awakening upon discontinuation.
What are the key characteristics of sevoflurane?
- Sevoflurane, a fluorinated methyl isopropyl ether
- Has vapor pressure similar to halothane and isoflurane
- Allowing use with conventional vaporizers.
- Its solubility ensures quick induction and recovery.
- It is nonpungent, minimally odorous, and causes less airway irritation.
How does recovery from sevoflurane anesthesia compare to isoflurane?
- Recovery from sevoflurane is 3 to 4 minutes faster than isoflurane
- Especially noticeable in surgeries longer than 3 hours
What are the metabolism characteristics and safety profile of sevoflurane?
- Sevoflurane undergoes more metabolism than desflurane (3% to 5% biodegradation),
- Produce inorganic fluoride and hexafluoroisopropanol.
- It doesn’t form reactive acyl halide intermediates or stimulate antitrifluoroacetylated protein antibodies, reducing hepatotoxicity risk.
Is sevoflurane likely to form carbon monoxide?
- Is least likely to form carbon monoxide when exposed to carbon dioxide absorbents.
- However, it breaks down to form toxic compounds in animals, primarily compound A
- Although levels in humans are below speculated toxic levels even at low gas flows.
What are the key characteristics and potency of Xenon as an inhaled anesthetic?
- Xenon is an inert gas
- MAC of 63% to 71%
- More potent than nitrous oxide.
- It is nonexplosive, odorless, chemically inert, environmentally friendly
- Has a blood:gas partition coefficient of 0.115.
What are the cost considerations and potential use of xenon in anesthesia practice?
- Xenon’s high cost limits its use, though this could be offset by low fresh gas flow rates and xenon-recycling systems.
- Its acceptance depends on demonstrating special properties or significantly lower morbidity
- Mortality during anesthesia.
How does xenon affect gas exchange conditions?
- Xenon can favor air bubble expansion, which may exacerbate neurologic injury from venous air embolism.
- It has a minimal effect on bowel expansion compared to nitrous oxide.
How does the emergence of xenon anesthesia compare to other anesthetics?
- Is 2 to 3 times faster than from equal-MAC nitrous oxide plus isoflurane or sevoflurane.
- Xenon is a potent hypnotic and analgesic without causing hemodynamic depression.
What makes xenon’s neuroprotective effects unique among NMDA antagonists?
- Offers neuroprotection without psychotomimetic behavioral changes
- It does not stimulate dopamine release from the nucleus accumbens, unlike ketamine or nitrous oxide.
Identify the below chemical structure
Identify the chemical structures below
Identify the inhaled gases on the graph below
What does the FA/FI ratio signify in the induction of anesthesia with inhaled anesthetics?
- Indicates the ratio of end-tidal anesthetic concentration (FA) to inspired anesthetic concentration (FI)
- Describes the uptake of inhaled anesthetics during induction.
- It reflects how quickly the anesthetic reaches equilibrium in the lungs.
How does the solubility of anesthetics affect the FA/FI ratio?
- Anesthetics with lower blood:gas partition coefficients have a more rapid increase in their FA/FI ratio compared to more soluble anesthetics,
- Indicates faster pulmonary uptake and equilibrium.
Lower blood:gas partition coefficients: nitrous oxide, desflurane, and sevoflurane
What does a decrease in the rate of change in the FA/FI ratio after 5 to 15 minutes indicate?
- Suggests decreased tissue uptake as vessel-rich group tissues become saturated with the anesthetic.
What are the four key aspects of inhaled anesthetic pharmacokinetics?
- Absorption from alveoli to blood
- Distribution in the body
- Metabolism
- Elimination (mainly via lungs)
How does aging affect the pharmacokinetics of volatile anesthetics?
- Aging leads to changes in body composition (less lean mass, more fat)
- Affects the volume of distribution
- It may also impair pulmonary gas exchange
- Reduce cardiac output
- Alter tissue perfusion and anesthetic distribution.
How are inhaled anesthetics propelled to their action sites in the CNS?
- A series of partial pressure gradients, starting at the anesthetic machine, move the anesthetic across alveoli, capillaries, and cell membranes to the CNS.
What is the principal objective of inhalation anesthesia?
- The main goal is to achieve a constant and optimal brain partial pressure of the inhaled anesthetic, correlating with PA (alveolar partial pressure) and PBRAIN (brain partial pressure).
Why is the alveolar partial pressure (PA) of inhaled anesthetics a crucial index?
- Indicates the depth of anesthesia, recovery from anesthesia
- Anesthetic equal potency (MAC)
- It mirrors PBRAIN at a steady state
- allows for control of anesthetic doses to the brain
What is the difference between equilibration and equality of concentrations in biophases?
- Equilibration means equal partial pressures in two phases, not equal concentrations.
- This concept is key in controlling doses of volatile anesthetics.
What factors determine the alveolar partial pressure (PA) of inhaled anesthetics?
The balance of input (delivery) into alveoli and uptake (loss) from alveoli into arterial blood.
Input depends on:
- The inhaled partial pressure (PI)
- Alveolar ventilation
- Characteristics of the anesthetic breathing system.
What influences the input of anesthetics into alveoli?
Anesthetic input into alveoli depends on:
- The inhaled partial pressure (PI) of the anesthetic
- The rate of alveolar ventilation
- The design of the anesthetic delivery system
What factors affect the uptake of inhaled anesthetics from alveoli into pulmonary capillary blood?
- The solubility of the anesthetic in body tissues
- Cardiac output
- The alveolar-to-venous partial pressure differences (A-vD)
Why is a high inhaled partial pressure (PI) important during initial anesthetic administration?
- To offset anesthetic uptake accelerating anesthesia induction.
- This quickens the rate of rise in the PA and PBRAIN.
- As uptake decreases over time, PI should be reduced to maintain a constant and optimal PBRAIN.
What is the concentration effect in the context of inhaled anesthetics?
- States that a higher PI leads to a more rapid increase in PA
- As the higher concentration offsets uptake, speeding up the PA’s rise.
- It results from a concentrating effect and augmentation of tracheal inflow.
What mechanisms contribute to the concentration effect?
- Concentrating the anesthetic in a smaller lung volume due to gas uptake
- while increased tracheal inflow fills the space produced by gas uptake
What is the second gas effect, and how does it work?
- Occurs when the high-volume uptake of a primary gas (first gas) accelerates the PA rise of a secondary gas (second gas)
- It’s due to increased tracheal inflow and concentration of the second gas in a reduced lung volume from the high-volume uptake of the first gas
What is a common misconception about gas volume compensation in the lungs?
- It’s misleading to suggest that extra gas is routinely drawn into the lungs to compensate for lost lung volume.
- Compensatory changes may include decreased expired ventilation or a decrease in lung volume, not just increased inspired ventilation.
How does increased alveolar ventilation affect the induction of anesthesia?
- Accelerates the input of anesthetics, raising the PA more rapidly towards the PI.
- speeds up anesthesia induction.
- Hyperventilation can decrease cerebral blood flow (CBF), which might offset the increased anesthetic delivery to the brain.
What is the effect of decreased alveolar ventilation on anesthesia induction?
- Reduces anesthetic input
- Slows the establishment of the necessary PA and PBRAIN for anesthesia induction.
How does the alveolar ventilation to functional residual capacity (FRC) ratio affect anesthesia induction?
- A higher alveolar ventilation to FRC ratio leads to a faster rate of increase in PA.
- Neonates have a higher ratio (about 5:1) compared to adults (1.5:1)
- Results in quicker anesthesia induction in neonates due to their higher metabolic rate.
How do inhaled anesthetics affect alveolar ventilation?
- Have a dose-dependent depressant effect on alveolar ventilation
- Creates a negative feedback mechanism
- Prevents excessive anesthesia depth during spontaneous breathing
- Decrease anesthetic delivery when ventilation is reduced.
What happens to the anesthetic distribution when ventilation decreases during spontaneous breathing?
- Anesthetics redistribute from high-concentration tissues (like the brain) to low-concentration tissues (like skeletal muscles).
- When brain concentration drops below a threshold, ventilation increases, raising anesthetic delivery to the lungs
What protective mechanism is lost during mechanical ventilation?
- Mechanism against excessive anesthesia depth, which is present during spontaneous breathing
- This is because mechanical ventilation maintains consistent anesthetic delivery regardless of the brain’s anesthetic concentration.
Mechanism against excessive anesthesia depth, which is present during spontaneous breathing, is lost during mechanical ventilation.
How does the solubility of an anesthetic in the blood affect the impact of alveolar ventilation changes on the PA?
- Changes in alveolar ventilation influence the PA of soluble anesthetics (like halothane, and isoflurane)
- More than poorly soluble ones (like nitrous oxide, desflurane, sevoflurane).
- Poorly soluble anesthetics have a rapid PA increase regardless of ventilation changes due to limited uptake.
What is the difference in uptake between more blood-soluble and poorly soluble anesthetics?
- More blood-soluble anesthetics have greater uptake; thus, increasing alveolar ventilation accelerates the PA’s approach to the PI.
- Conversely, uptake of poorly soluble anesthetics is limited, so their PA rises rapidly regardless of ventilation changes.
How does changing from spontaneous to mechanical ventilation affect anesthesia depth?
- Increased alveolar ventilation, likely increases the depth of anesthesia (PA) for more blood-soluble anesthetics.
- Due to faster PA rise towards the PI.
What characteristics of the anesthetic breathing system influence the PA rate of increase?
- The system’s volume (acting as a buffer).
- Solubility of anesthetics in the system’s materials.
- Gas inflow rate from the anesthetic machine.
- High gas inflow rates can negate the buffering effect of the system’s volume.
How does the volume of the anesthetic breathing system affect anesthetic PA?
- Slows the achievement of the target PA by acting as a buffer.
- High gas inflow rates can counteract this buffering effect.
What is the impact of anesthetic solubility on breathing system components?
- Initially slows the PA’s rate of increase.
- At the end of anesthetic administration, the reverse gradient causes anesthetic elution, slowing the PA’s rate of decrease.
Which anesthetic gas is the only soluble among others?
Methoxyflurane
Which anesthetic gases are immediately soluble?
- Halothane
- Enflurane
- Isoflurane
Which anesthetic gases are poorly soluble?
- Nitrous Oxide
- Desflurane
- Sevoflurane
- Xenon
What is a partition coefficient in the context of inhaled anesthetics?
- Is a distribution ratio that describes how an inhaled anesthetic distributes itself between two phases (like blood and gas) at equilibrium.
- It indicates the concentration relationship of the anesthetic in these phases when their partial pressures are equal.
How do you interpret a blood:gas partition coefficient for inhaled anesthetics?
- Blood:gas partition coefficient of 0.5 means the concentration of the anesthetic in the blood is half that in alveolar gases when their partial pressures are equal.
- It indicates the solubility and distribution of the anesthetic between blood and gas.
What does a brain:blood partition coefficient indicate?
- A brain:blood partition coefficient of 2 means the concentration of anesthetic in the brain is twice that in the blood when their partial pressures are equal.
- It shows the relative concentration of anesthetic in the brain versus blood.
How does temperature affect partition coefficients?
- Partition coefficients are temperature-dependent.
- The solubility of a gas in a liquid decreases as the temperature of the liquid increases.
How does the solubility of an anesthetic in blood affect the rate of increase of the PA towards the PI?
- The rate of PA increase towards the PI is inversely related to the anesthetic’s solubility in blood.
- Highly soluble anesthetics like methoxyflurane require more anesthetic to be dissolved in blood for PA to equilibrate with PI, leading to slower induction.
What is the overpressure technique in anesthesia, and when is it used?
- The technique involves delivering a higher PI than required for the maintenance of anesthesia to speed up induction.
- Particularly with highly soluble anesthetics.
- Sustained high PI can result in overdose.
How does low blood solubility of anesthetics like nitrous oxide, desflurane, or sevoflurane affect anesthesia induction?
- Low blood solubility means minimal anesthetic needs to be dissolved for equilibration.
- Results in rapid PA increase.
- Quicker onset of effects ( anesthesia induction).
What are the unique effects of nitrous oxide due to its high-volume absorption?
- At concentrations of 60-70%, leads to unique effects when used with volatile anesthetics or in air-containing cavities.
How do individual variations affect blood:gas partition coefficients?
Vary with individual differences in:
- Water.
- Lipid Protein content.
- Hematocrit levels.
For example, lower hematocrit or a recent fatty meal can affect the solubility of volatile anesthetics in blood.
How does age affect the solubility of inhaled anesthetics in blood?
- The solubility of certain anesthetics like halothane, enflurane, methoxyflurane, and isoflurane is about 18% less in neonates and the elderly.
- For less soluble anesthetics like sevoflurane, there’s no significant difference in solubility between neonates and adults.
What role do tissue:blood partition coefficients play in anesthetic administration?
- Determines the uptake of anesthetics into tissues.
- The time needed for tissues to equilibrate with the arterial partial pressure of anesthetics (Pa).
How is the time for equilibration of tissues with Pa estimated?
- Is estimated by calculating a time constant, defined as the amount of inhaled anesthetic that can be dissolved in the tissue divided by tissue blood flow.
- One time constant represents 63% equilibration.
- Three time constants equal 95% equilibration.
How long does it take for the brain to equilibrate with volatile anesthetics?
- Usually requires 5 to 15 minutes, or about three time constants, depending on the anesthetic’s blood solubility.
What is the estimated equilibration time of fat with isoflurane?
- Is based on its fat:blood partition coefficient
- Assumed fat blood flow, is estimated to be 25 to 46 hours for three time constants.
How does fasting before surgery affect anesthetic uptake?
- Fasting leads to the transport of fat to the liver
- potentially increasing anesthetic uptake by the liver
- modestly slowing the rate of increase in the alveolar partial pressure (PA) of a volatile anesthetic during induction.
How are oil:gas partition coefficients related to anesthetic requirements?
- Are directly related to anesthetic requirements.
- An anesthetic’s MAC (Minimum Alveolar Concentration) can be estimated as 150 divided by the oil:gas partition coefficient.
How can you calculate the estimated MAC for an anesthetic?
- Divide 150 by the anesthetic’s oil:gas partition coefficient.
150 is a constant representing the average product of oil:gas solubility and MAC for various anesthetics
What would be the calculated MAC for an anesthetic with an oil:gas partition coefficient of 100?
For an anesthetic with an oil:gas partition coefficient of 100, the calculated MAC would be 1.5% (150 divided by 100).
How does nitrous oxide accumulate in closed gas spaces, and what are the consequences?
Nitrous oxide has a high blood:gas partition coefficient (0.46) compared to nitrogen (0.014), allowing it to rapidly accumulate in air-filled cavities, increasing volume or pressure, potentially leading to damage.
How does nitrous oxide affect different types of body cavities?
- In compliant cavities (like intestinal gas or pneumothorax), nitrous oxide causes expansion.
- In noncompliant cavities (like the middle ear or cerebral ventricles), it increases intracavitary pressure.
What factors influence the impact of nitrous oxide in closed spaces?
- Partial pressure of nitrous oxide.
- Blood flow to the cavity.
- The duration of nitrous oxide administration.
- In high-flow areas, volume increases can be rapid.
How does nitrous oxide affect middle ear pressure?
- Diffuses into the middle ear faster than nitrogen leaves, potentially increasing ear pressure
- Especially if the Eustachian tube is blocked
- Leads to tympanic membrane rupture or serous otitis after anesthesia.
What is the effect of nitrous oxide on intraocular gas bubbles used in eye surgeries?
- Can rapidly increase the volume of intraocular gas bubbles, enough to compress the retinal artery.
- Potentially cause visual loss, especially critical in the weeks following ocular surgery.
How does cardiopulmonary bypass affect blood-gas solubility?
- Changes in blood-gas solubility, influenced by the priming solution and temperature.
- The overall effect of hypothermic bypass and a crystalloid prime on solubility is about 2%
How does cardiopulmonary bypass affect the equilibration of volatile anesthetics?
- Volatile anesthetics initiated take longer to equilibrate.
- If the anesthetics are already present when the bypass begins, they may be diluted, potentially reducing anesthesia depth.
How does cardiac output influence anesthetic uptake and the rate of increase in the PA?
Increased cardiac output:
- rapid uptake of anesthetic from the alveoli.
- Slowing the increase in PA and anesthesia induction.
Decreased cardiac output:
- Speeds up PA increase due to less anesthetic uptake.
Why does increased cardiac output paradoxically lower Pa despite hastening equilibration in tissues?
- While increased cardiac output hastens the equilibration of tissue anesthetic partial pressures with Pa, it actually lowers the Pa than if cardiac output were normal, due to increased anesthetic uptake.
How do changes in cardiac output affect soluble vs. poorly soluble anesthetics?
- Changes in cardiac output significantly influence the PA rate of increase for soluble anesthetics
- Have little effect on poorly soluble anesthetics like nitrous oxide, regardless of cardiac output variations.
How can volatile anesthetics impact cardiac output and what is the feedback response?
- May depress cardiac output, leading to a positive feedback response where decreased output raises PA
- Deepening anesthesia and further depressing cardiac function.
How does the distribution of cardiac output affect the PA of an anesthetic?
- Increases in cardiac output may not proportionally increase blood flow to all tissues.
- Preferential perfusion of vessel-rich tissues can lead to a faster increase in PA than if the increased cardiac output were evenly distributed.
How does a right-to-left shunt affect the PA and Pa of inhaled anesthetics?
- Dilutes anesthetic partial pressure in blood from ventilated alveoli
- Decrease Pa
- Slows anesthesia induction.
- It creates a gradient where PA underestimates Pa, similar to its effect on PaO2.
How does the solubility of an anesthetic influence its rate of increase in Pa in the presence of a right-to-left shunt?
- A right-to-left shunt slows the rate of increase of Pa for poorly soluble anesthetics
- Soluble anesthetics’ uptake offsets the dilutional effects of shunted blood
- Uptake of poorly soluble anesthetics is minimal.
How does the impact of a shunt contrast with changes in cardiac output and alveolar ventilation?
The impact of solubility in the presence of a right-to-left shunt is opposite to that observed with changes in cardiac output and alveolar ventilation.
What is the effect of left-to-right tissue shunts on anesthetic Pa?
Left-to-right shunts (like arteriovenous fistulas) deliver blood with a higher anesthetic partial pressure to the lungs, offsetting the dilutional effects of a right-to-left shunt on Pa.
How do right-to-left and left-to-right shunts interact to influence the PA of anesthetics?
- Right-to-left shunt on slowing PA increase is maximal without a left-to-right shunt.
- Left-to-right shunts can only offset right-to-left shunt effects if both types of shunts are present.
What does the A-vD indicate in the context of inhaled anesthetics?
- The A-vD reflects tissue uptake of inhaled anesthetics.
- It affects lung uptake by controlling the rate of increase of the mixed venous partial pressure of the anesthetic, influenced by tissue solubility, blood flow, and arterial-to-tissue pressure differences.
How do vessel-rich group tissues affect anesthetic uptake?
- Equilibrate rapidly with arterial anesthetic pressure (Pa) due to high blood flow and low mass.
- After three time constants, venous blood pressure equilibrates with alveolar pressure (PA), decreasing anesthetic uptake.
What is the role of skeletal muscles and fat in sustained anesthetic uptake?
- Skeletal muscles and fat, comprising a large body mass but receiving less cardiac output
- Continue to take up anesthetics for an extended period, maintaining the A-vD and continuous uptake from the lungs.
How does equilibration time for vessel-rich group tissues differ in neonates and infants compared to adults?
- Is faster in neonates and infants due to greater cardiac output to these tissues and decreased solubility of anesthetics in their tissues.
- Skeletal muscle mass is a smaller fraction of body weight in the very young.
What factors influence the rate of recovery from anesthesia?
- Rapid washout from the brain
- Low solubility in brain tissue
- High cardiac output to the brain.
The rate of decrease in the brain’s partial pressure (PBRAIN) as reflected by the alveolar partial pressure (PA).
How do induction and recovery from anesthesia differ?
- Unlike induction, which can be accelerated by the concentration effect, recovery can’t be sped up similarly since you can’t administer less than zero.
- Tissue concentrations at recovery’s start depend on the anesthetic’s solubility and administration duration.
How does tissue equilibrium with PA affect the recovery rate?
Since some tissues (like skeletal muscles and fat) may not equilibrate with PA during maintenance, the PA decrease rate during recovery is faster than its increase rate during induction. These tissues continue taking up anesthetic, aiding PA decrease.
How do the solubility of the anesthetic and duration of anesthesia impact recovery?
- Recovery time is prolonged for soluble anesthetics (like halothane, isoflurane) in proportion to anesthesia duration.
- For poorly soluble anesthetics (like sevoflurane, desflurane), duration has minimal impact on recovery time
How does anesthetic absorption into breathing system components affect recovery?
- Will pass back into the breathing circuit gases at anesthesia’s end slowing the PA decrease rate.
- Increasing fresh gas flow rates at conclusion can help mitigate rebreathing of exhaled anesthetics.
What is the context-sensitive half-time in relation to inhaled anesthetics?
- Refers to the pharmacokinetics of the elimination of inhaled anesthetics, which depends on the duration of administration and the blood-gas solubility of the anesthetic.
- It varies for different anesthetics and increases with the duration of anesthesia.
How do recovery times differ among desflurane, sevoflurane, and isoflurane?
- Recovery is fastest with desflurane (most insoluble) and
- Slowest with isoflurane (most soluble).
- For short procedures (around 30 minutes), there’s little difference in recovery time among these anesthetics.
- The difference becomes appreciable in longer procedures.
How can sevoflurane be managed to ensure rapid recovery in longer procedures?
In longer procedures (3-4 hours), turning off sevoflurane about 30 minutes before the end and replacing it with 70% nitrous oxide can ensure rapid recovery by allowing adequate time for a 90% decrease in sevoflurane concentration.
What characterizes the initial phase of anesthetic elimination?
- The initial phase of elimination, primarily driven by alveolar ventilation,
- Reflected in the 50% decrement time of various anesthetics,
- which is typically less than 5 minutes and doesn’t increase much with anesthesia duration.
How do 80% and 90% decrement times vary among different anesthetics?
- Desflurane and sevoflurane have 80% decrement times under 8 minutes
- Enflurane and isoflurane, these times increase after 60 minutes.
- The 90% decrement time of desflurane increases slightly with longer anesthesia but remains significantly less than for other anesthetics after 6 hours.
What is diffusion hypoxia, and how is it related to nitrous oxide?
- Occurs when nitrous oxide is abruptly discontinued
- Causes it to rapidly leave the blood and enter the alveoli, diluting the PAO2 (alveolar oxygen partial pressure)
- Potentially lowering the PaO2 (arterial oxygen partial pressure).
What are the consequences of diffusion hypoxia?
- Can dilute both PAO2 and PACO2 (alveolar carbon dioxide partial pressure).
- Reduces the stimulus to breathe.
- Exacerbates the decrease in PaO2.
How is diffusion hypoxia managed at the end of anesthesia?
- Administer oxygen to fill the lungs at the end of anesthesia,
- It counteract the dilution of PAO2 by nitrous oxide.
What is the MAC of an inhaled anesthetic?
- Is the concentration of an inhaled anesthetic at 1 atm that prevents movement in response to a painful stimulus in 50% of patients.
- It’s considered the anesthetic 50% effective dose (ED50) for immobility.
What part of the nervous system is primarily affected by inhaled anesthetics as measured by MAC?
- The MAC primarily reflects the effects of inhaled anesthetics on the spinal cord, with a minor component resulting from cerebral effects.
Why is the MAC concept important in anesthetic pharmacology?
- MAC provides a uniform measure of potency for inhaled anesthetics
- allows for standardization of dosages
- comparison of drugs
- investigation into mechanisms of anesthetic action.
What are the variable that influence Pharmacologic effect of Inhaled Anesthetics?
- Anesthetic concentration
- Rate of increase in anesthetic concentration
- Spontaneous versus controlled ventilation
- Variations from normocapnia
- Surgical stimulation
- Patient age
- Coexisting disease
- Concomitant drug therapy
- Intravascular fluid volume
- Preoperative medication
- Injected drugs to induce and/or maintain anesthesia or skeletal muscle relaxation
- Alterations in body temperature
How do different volatile anesthetics affect the susceptibility to epinephrine-induced ventricular cardiac dysrhythmias?
Halothane, an alkane derivative, greatly increases the sensitivity to epinephrine-induced ventricular dysrhythmias. In contrast, ether derivatives like isoflurane, desflurane, and sevoflurane have minimal to no effect in increasing this susceptibility.
Proteins involved in Cardiac protection.
How does surgical stimulation impact minute ventilation and PaCO2?
- Increases minute ventilation by approximately 40% due to rises in both tidal volume and frequency of breathing
- PaCO2 decreases by only about 10% (4-6 mm Hg) despite this increase in minute ventilation.
- This is thought to be due to heightened carbon dioxide production from sympathetic nervous system activation in response to the pain of surgical stimulation, which offsets the effects of increased minute ventilation.
