Volatiles

Question 1

Factors affects gas Inspired concentration

Answer 1

There are three major things: gas flow rate, breathing circuit (circle system) volume, and breathing circuit absorption.

A simplified way to think of it is this: imagine that the circle system is a sink for volatile anesthetic, like a sponge. The more sponge you have, the more anesthetic that will be absorbed before you reach the patient, therefore decreasing the size of the circle system (smaller/ shorter tubing) will lead to less absorption. Therefore the gas that leaves the circle system (at the Y-connector) will more closely resemble the gas that leaves the fresh gas outlet (where you attach the circle system circuit)

Question 2

The avidity to which the anesthetic is taken up from the alveolus to the venous blood depends on two major factors …

Answer 2

(1) solubility of the agent.
The more soluble the agent is in blood, the more anesthetic that will be taken from the alveoli. The partition coefficient describes this in terms of how much agent will be in the blood versus the alveolus (blood / gas partition coefficient). The higher the coefficient, the higher the concentration in the blood as compared to the alveolus (it’s a simple ratio).

(2)The difference in partial pressures between the alveolus and the venous blood.
The lower the partial pressure of the agent in the blood and the higher the partial pressure in the alveolus results in the greatest pressure difference between the alveoli and pulmonary venous blood.

Question 3

What is meaning of Induction? And what’s considered fast or slow induction?

Answer 3

Induction occurs when the alveoli concentration reaches a certain level (lets say 1 MAC). The speed in which that occurs is described by the alveolar concentration (FA) to inhalation concentration (FI) plot over time. In other words, the faster FA reaches FI, the faster the induction.

Question 4

Induction is faster with more soluble or insoluble gases?

Answer 4

Insoluble volatiles

increasing the blood/ gas coefficient means that we are increasing the solubility of the agent in blood. Therefore, the higher the solubility, the more anesthetic that will be taken out of the alveoli. The more anesthetic that is taken out of the alveoli, the longer it will take for the alveolar concentration (FA) to reach the inhaled concentration (FI) (answer B). If the gas is less soluble, then less anesthetic will removed from the alveolus, and the FA will reach the FI concentration (partial pressure) quicker! The related subject is pulmonary venous blood concentration (see question 2). With insoluble agents (that means only a little bit is taken up by blood), the circulation is saturated with the anesthetic much quicker.

Question 5

Speed of induction increased with …. cardiac output

Answer 5

Low CO = fast induction.

The higher the cardiac output, the more anesthetic that is removed from the alveolus, and therefore FA lags behind FI. Decreasing cardiac output leads to less alveolar anesthetic removal and FA approaches FI more quickly. The exception to this is shunt.

Question 6

Speed of induction increased with …. MV

Answer 6

Increasing MV

Increasing ventilation means that the agent in the alveoli that was taken up by the blood is replaced quicker. This speeds FA (right!). Since FI (the inhalation concentration doesn’t change) the FA/ FI ratio increases, meaning that induction is sped up.

Question 7

Mainstem intubation will … the speed of induction

Answer 7

Slow

By mainsteming the patient, shunt has increased. Therefore there is a bunch of blood that does not participate in gas exchange (or anesthetic uptake) and dilutes the concentration of anesthetic in the arterial blood leaving the alveoli (post capillary blood). Therefore, the anesthetic concentration in the mixed venous blood is also decreased. The decreased concentration in mixed venous blood means that there will be a greater concentration difference from alveoli to venous blood, and therefore more anesthetic will be pulled from the alveoli into the blood BUT less blood is being exposed to the lungs with a net effect of decreased uptake. Therefore, altogether FA continues to approximate FI, yet the arterial partial pressure of the volatile agent is decreased.

Question 8

The speed of induction is slower/faster for soluble or insoluble gases in mainstem intubation or shunt in general?

Answer 8

Faster than insoluble

Soluble agents are less effected by shunts than insoluble agents. The best explanation that I have seen essentially says that because the blood concentration of an insoluble agent is so low, the shunted blood that has not taken up any volatile agent will dilute out this small concentration of insoluble agent as compared to a soluble agent. But the real reason is essentially this: the shunt fraction blood will increase its concentration of volatile anesthetic over time and as this proportion of blood increases its concentration with continued induction closer to that of the post-capilary blood, the dilutional effects will be less. Soluble agents will saturate this portion of unventilated blood quicker than insoluble agents

Question 9

Speed of induction vs cardiac shunt (Rt to left vs Left to Rt)?

Answer 9

Induction will be quicker in the ‘left to right’ shunt

left to right shunts do not slow induction.

Question 10

Desflurane’s Blood/ Gas partition coefficient of 0.42 means that

Answer 10

Blood will have 42% as much desflurane when compared to alveolar gas

At equilibrium at 37 C, desflurane because of its low partition coefficient will have a higher concentration in alveolar gas than in blood. Therefore, blood has only 42% the capacity for desflurane as does alveolar gas (per unit).

Question 11

Induction is faster with (soluble or insoluble) in presence of right to left shunt?

Answer 11

Soluble (Isoflurane).

Normally the insoluble is faster due to faster FI/FA equilibrium

Where if shunt present then the unventilated shunted fraction will equilibrate with the post-capillary blood quicker with a soluble agent as opposed to an insoluble agent.

Question 12

Name a factor that would speed up the induction of gases but at the same time it would slow the gas elimination?

Answer 12

None

Factors that speed induction also speed elimination. In fact, elimination is essentially induction backwards. Using high fresh gas flows, low volume and absorbency breathing circuits speed induction by maintaining FI close to the concentration delivered by the machine (at the fresh gas outlet) during induction (see question 1). During elimination, these factors keep the inspired gases as close to the fresh gas outlet as well, except its typically 100% oxygen plus the very small amount of residual anesthetic that was absorbed into the circuit. Decreasing cardiac output is counterintuitive, but remember that brain levels of sevoflurane parallel that at the alveolus. When cardiac output is low, the alveolus can better rid itself of residual anesthetic.

Question 13

The potency of volatiles correlates to their …

Answer 13

Lipid solubility

This principle is known as the Meyer-Overton rule, and demonstrates that inhalation agents’’ potency correlates with lipid solubility. There are multiple theories of anesthetic mechanism of action from disturbing lipid membrane form and conductivity and stimulating actual receptors (answer B), but this possible mechanism does not explain potency. Aromatic rings may allow for lipid solubility, but are not possessed by any anesthetics in clinical use. Increasing the concentration of an agent does not make it more potent (answer A). More potent volatile anesthetics have LOWER MACs (sevoflurane and isoflurane are very potent, whereas N20 is not very potent at all). Blood/ Gas partition coefficients describe solubility, which in turn can explain time to induction (answer D). Blood/ Gas coefficients do not correlate with potency, as N2O with a very low coefficient (0.47) is not potent, whereas Desflurane (0.42) is more potent and sevoflurane (0.65) still more potent again.

Potency describes how concentration and effect are related. Highly potent drugs exert their effect at lower concentrations than less potent drugs. In terms of volatiles. this means that a low MAC, which has a linear correlation (not perfect, but strong correlation) to increased lipid solubility describes potency.

Question 14

What’s the ED95 for patients movement following surgical stimulation?

Answer 14

ED50 = At 1.0 MAC 50% of patients will move in response to a surgical incision, and at

ED95 = 1.3 MAC only 5% of patients will. Remember this means without any other anesthetics on board either (residual propofol, fentanyl, midazolam, lidocaine, etc).

Question 15

A 70 year old man will likely have what % reduction in MAC compared to a 40 year old man:

Answer 15

One expects a 6% decrease in MAC per decade of life after age 40. Therefore, 70-40 = 30 (3 decades); 3 X 6% = 18%.

Question 16

Most metabolic disturbances decrease MAC, except for

Answer 16

hypernatraemia,

which can increase MAC. Hypoxia can be a powerful “anaesthetic,” perhaps as decreased oxygen supplies to the CNS lead to decreased arousal. Likewise, extreme anaemia, may not provide enough oxygen to the brain with the same clinical effect. More common than hypoxia, is hypercarbia as a cause of decreased MAC and delayed emergence.

Question 17

Do infants have increased or decreasesd MAC?

Answer 17

Increased MAC is often required for young patients, and depending on the specific agent, peaks very early in life and progressively decreases (pretty much linearly) after age of 1 year

Question 18

Do thyroid abnormalities increases or decreases MAC requirement

Answer 18

Neither hyper nor hypothyroidism have effect MAC*.

*Some sources state that hyperthyroidism does increase MAC, including Miller (based on animal data)

Question 19

Temp effect on MAC requirement?

Answer 19

Hypothermia decreases MAC whereas moderate/ severe (but not very severe) hyperthermia increases MAC.

Question 20

Acute drug abuse would … MAC requirement except for 2 ….

Answer 20

In general acute drug abuse leads to a decrease in MAC with the exception of sympathomimetics (cocaine, methamphentamine, etc).

Also, in general, chronic drug use (without acute intoxication) leads to resistance (increased MAC); again with sympathomimetic drugs leading to the opposite effect: decreased MAC.

Question 21

Would low pH or high decreases MAC? How about hypo or hyper osmolality? And NMB?

Answer 21

There’s a mess of things that decrease MAC.

Pretty much anything that you use for sedation or analgesia will decrease MAC, including lidocaine will have major effects on MAC.

Anything that is the opposite of those factors that increase MAC will decrease MAC (old age, hyponatraemia, hypothermia, decreased neurotransmitter levels (drugs, etc)).

Anything that decreases oxygen to the brain (hypoxia, hypotension, and extreme anaemia).

Some other random stuff like hypoosmolality, maybe muscle relaxants (especially pancuronium), reversal agents (at insanely high doses), and acidaemia also will decrease MAC.

But before you start running your patients at 0.9 sevo, its important to realize that most of these effects are rather minor and only at extremes (like hypoxia where you need to get down to a pO2 of 38, for example). And don’t think that your pancuronium will decrease MAC more than a hair’s turn on your vaporizer either!

Question 22

Electrolytes increases MAC requirement?

Answer 22

High sodium blood levels will increase MAC and hyponatraemia will decrease MAC.

Other than the extremes (and I mean extremes) of magnesium, other normally measured electrolyte abnormalities do not affect MAC.

Question 23

MAC requirement increases with

Answer 23

• Increased neurotransmitter levels (medication or illicit drug induced),
• chronic drug abuse (especially alcohol)
• hypernatraemia
• hyperthermia
• young age

Question 24

Regarding commonly used modern halogenated volatile anesthetics (isoflurane, sevoflurane, & desflurane) at 1 MAC:

Answer 24

At 1 MAC, SVR and subsequently MAP decreases with a (compensatory?) increase in heart rate and no significant change in cardiac output (in healthy volunteers). Stroke volume is minimally effected and may decrease. Dysrhythmias are not common in healthy volunteers (exception halothane). QT intervals typically widen, probably without clinical significance.

Question 25

What effect of volatiles at 1% MAC on TV, Mv, RR, HPV?

Answer 25

bronchodilation
decreased airway resistance

Tidal volume decreases
minute volume decreases mildly (hence respiratory rate increases) leading to an increase in dead space ventilation. (and pCO2 is mildly increased).

Hypoxic pulmonary vasoconstriction is mildly blunted

Remember all drugs including volatile agents’ effects are dose dependent. Therefore as dose increases, the various effects change. In general its nice to understand what happens at 1 MAC and at high levels (“stage 4 anesthesia”). High levels of volatile anesthetics (classically) lead to flaccid muscle tone, respiratory arrest, and cardiovascular collapse. Pupils are fixed and dilated.

Question 26

N2O effect on heart?

Answer 26

N2O at 50-70% tends to stimulate the sympathetic nervous system:
leading to a small increase (or no change) in heart rate
mean arterial blood pressure,
and cardiac output.

N2O has mild myocardial depressing effects that are outweighed by the sympathetic stimulation

PVR predictably increases, which can exacerbate pulmonary hypertension.

Question 27

N2O differ than halogenated volatiles in its affect on MV & panic threshold?

Answer 27

Halogenated volatile anesthetics lead to decreased minute ventilations and increased apneic thresholds.

N2O, on the other hand, has a preserved minute ventilation and no rise in the apneic threshold (the PaCO2 at which apnea occurs).

Dead space ventilation (from decreased tidal volumes and increased respiratory rates) occurs with all inhaled anesthetics.

Question 28

All gases produce & potentiate muscle relaxation except …

Answer 28

Sevoflurane, like other halogenated anesthetics) produce and potentiate muscle relaxation whereas N2O does not. Therefore volatile anesthetics produce a degree of muscle relaxation when used alone as well as potentiate that of muscle relaxants.

Question 29

All gases causes decrease CMRO2 except …

Answer 29

N2O

Cerebral metabolic rate (CMRO2) slightly increases with N2O and significantly decreases with sevoflurane

Question 30

All gases cases decrease in SVR except ..

Answer 30

Sevoflurane will predictably decrease SVR, whereas N2O has no significant effect.

Question 31

The only gas effect PVR?

Answer 31

N2O

Question 32

One gas that dose not trigger MH?

Answer 32

N2O

N2O is not a trigger for malignant hyperthermia, unlike the halogenated inhaled anesthetics.

Question 33

N2O (prolonged exposure!) has been shown to cause …

Answer 33

peripheral neuropathies, pernicious anaemia, megaloblastic anaemia, and depressed bone marrow production due its effects on vitamin B12

N2O oxidizes cobalt in vitmin B12 leading to inhibition of multiple enzymes including the (often tested) methionine synthetase (used for myelin formation) and thymidylate synthetase (used for DNA synthesis).

Question 34

Procedure contraindicated to use N2O?

Answer 34

(1) vowel obstruction? Some controversy exists using N2O based on bowel distention (which is more of a closed space) making the surgery more technically difficult.
(2) pneumothorax can expand and produce a tension pneumothorax
(3) The same concept is true for pneumocephalus after the dura is closed.
(4) Following placement of a tympanic membrane graft, the pressure in the middle air can rise and cause graft failure with N2O.
(5) Intraocular air bubbles placed for retinal detachment (for example) can expand with N2O and lead to retinal injury.

Question 35

Is laparoscopic procedure contraindicated for N2O use?

Answer 35

N2O is 35 times more soluble than nitrogen (N2) in blood, and thus can diffuse into air filled spaces (remember air is mostly N2) quicker than N2 can diffuse out, thus increasing the size of the air cavities. With laparoscopic surgery the pneumoperitoneum is created by carbon dioxide (CO2) which is pressure regulated (additional volume of gas is removed from the patient when the pressure raises above a certain point (such as 15 mm Hg)), and is not actually a closed cavity.

Question 36

A modern variable-bypass vaporizer of sevoflurane at 25 C and sea level is set to 2% and anesthetic concentration at the fresh gas outflow with pure oxygen flow rate of 2 liters per minute. Following this, the carrier gas is changed to oxygen at 0.6 L/ min and nitrous oxide (N2O) at 1.4 L/ min (30% O2/ 70% N2O) with no other changes made (sevoflurane vaporizer is still set at 2%). As measured at the fresh gas outlet, which of the following is true:

Answer 36

The partial pressure of sevoflurane is decreased and there is also a decrease in the concentration of sevoflurane

N2O is more soluble in volatile anesthetics than oxygen, and when the carrier gas is changed from pure O2 to 70% N20, more of the carrier gas will be absorbed into the volatile anesthetic solution, (transiently) decreasing output (out of the vaporizer). The net effect of this is a decrease in vaporizer output as the carrier gas (N2O) dissolves into the sevoflurane as N2O is more soluble in liquid sevoflurane than oxygen. In modern vaporizers there is a decrease in concentration of sevoflurane being delivered (see equipment Q 17 for more discussion on this very confusing topic, as older vaporizers the exact opposite is true!). Since the ambient conditions of both experiments were identical (altitude, temperature), partial pressure of sevoflurane would also be decreased by the same proportion. The relationship between concentration and partial pressure is:

Gas Concentration = (Gas Partial Pressure)/(Ambient Pressure)

I like to think of concentration as how much effect the drug will have (a high concentration of sevoflurane will have more effect than a low concentration). Think of partial pressure as the determination of how the anesthetic gas moves around in the body. Gas will flow from a high partial pressure to a low partial pressure. Therefore, when the partial pressure of sevoflurane is high in the alveolus and low in venous blood, it will move from lung to blood.

Question 37

Which of the following volatile anesthetics is metabolized to the greatest extent:

Answer 37

Sevoflurane is metabolized to 5%, isoflurane 0.2%, and desflurane and N2O, even less than that. Halothane, which likely will NOT be on the boards is metabolized 20%.

Question 38

Which of the following produces the greatest extent of coronary vasodilatation:

Answer 38

Isoflurane has been shown to dilate coronary arteries, whereas the others have not. The dilatory effects are not terribly pronounced and less than nitroglycerin. There have been unfounded concerns regarding coronary steal due to isoflurane by the scientist types; whereas in clinical practice this has not been shown.

Question 39

At which level of MAC does isoflurane tend to produce burst suppression on EEG:

Answer 39

At 1.5 MAC of isoflurane the EEG tends to start showing burst suppression. At levels as low as 2.0 MAC electrical silence can be seen. Remember this is assuming no other agents are being used (such as medications that bind to and potentiate GABA-A, such as barbiturates, benzodiazepines, propofal, and etomidate) which could possibly lead to burst suppression at even lower MAC. The effects of sevoflurane and desflurane are probably very similar.

Question 40

Which 2 volatiles causes increase sympathetic tone with increase their concentration?

Answer 40

Although more pronounced with desflurane, rapid increases in concentration levels of isoflurane or desflurane can lead to transient tachycardia and blood pressures.

Question 41

Following three hours of general anesthesia using 7% desflurane the carboxyhaemoglobin levels increase by 150%. Which of the following is most likely:

Answer 41

Desiccated (dried out) CO2 absorbent

Desflurane can be degraded by desiccated CO2 absorbent, leading to the production of carbon monoxide.

The classic situation this problem occurs is when anesthesia machines are left running high oxygen flows over the weekend and the CO2 absorbent is not changed out. This is most classic with barium hydroxide lime.

Carbon monoxide can be produced from volatile anesthetic degredation in the presence of desiccated CO2 absorbents, and is more common with desflurane.

Question 42

Compound A produced by …

Answer 42

Desiccated carbon dioxide (CO2) absorbent such as barium hydroxide lime (Baralyme) or soda lime (but not calcium hydroxide!) can lead to the production of Compound A, a chemical at supratherapeutic levels was found to be nephrotoxic in animals. This has lead to recommendations that gas flows should be kept at 2 L/ min or greater when using sevoflurane for more than 2 hours. At clinically produced levels of Compound A, nephrotoxicity has not been seen in humans. Sevoflurane is metabolized (5%) to free fluoride atoms, which has been shown to rise above 50 micromoles/L, which is considered dangerous. Despite this, there is no evidence that sevoflurane, even with long cases, lead to nephrotoxicity.

Older anesthetics such as methoxyflurane have been associated with fluoride associated nephrotoxicity which presents as high urine output renal failure. Sevoflurane can form the strong acid hydrogen fluoride when processed with certain impurities and improper storage conditions (which has been addressed and resolved).

Question 43

Which volatiles associated with fluoride associated nephrotoxicity

Answer 43

Older anesthetics such as methoxyflurane have been associated with fluoride associated nephrotoxicity which presents as high urine output renal failure.