General Anesthetics

Question 1

how do we describe potency of anesthesia?

Answer 1

MAC: minimum alveolar concentration = concentration of anesthetic required to keep half of the people from moving

Question 2

1/2 MAC of NO + 1/2 MAC of sevoflourine = ?

Explain this concept

Answer 2

= 1 MAC

MACs are additive, even through different classes of drugs

Question 3

Supposing that MAC of sevofluorine is 2%, and we give 1% of sevo, how much of a MAC of sevo would that be?

Answer 3

1/2 a MAC of sevoflourine

Question 4

What determines whether the anesthetic will put you to sleep or not?

Answer 4

The PARTIAL PRESSURE of the anethetic (not the %)

MAC of cevo is 2% in Farmington. Suppose we go to Mt. Everest, where partial pressure there is 1/2 of what it is in Farmington, then we would need to give 4% of cevoflouroine.

Question 5

if your atmostpheric pressure decreases, you need to give a (lower/higher) % to get the same partial pressure to get you to sleep.

Answer 5

higher.

Question 6

What is the potency of an anesthetic directly related to? What is the relationship with MAC?

Answer 6

The potency is directly related to the anesthetics lipid solubility; the more lipid soluble, the more potent.

High potent anesthetics = low MAC (need less % for one MAC)

If you have a low lipid solublity anesthetic (low potency), it will be a high MAC (needs more % for one MAC)

Question 7

What is a comon receptor that is involved in sedative drugs?

Answer 7

GABA-A receptor. Anesethetics may act here to. GABA receptors increase chloride conductance, hyperpolarizes membranes so they dont depolarize readily.

Question 8

While we are not sure how anesthetics work, we know what they do. What are the 2 important actions?

Answer 8

1. Act on CNS: cause unconsciousness, slowing of EEG (>2MAC will give you electrical silence). Myocardial and respiratory depression
2. Cerebral vasodilators: Increase cerebral blood flow (decrease cerebral metabolic demand). Bad if you have brain tumor, because intracranial pressure will go up. Can avoid this by hyperventilating (to decrease Co2 to brain, causing vasoconstriction because brian doesnt want too much oxygen)

Question 9

CO x SVR = BP

Explain the effects of Halothane

Answer 9

• decreases CO
• no effect on SVR
• causes a drop in BP
• causes decreased HR and decreased AV conductivity (Acts like a beta-blocker) and sensitizes the heart to catecholamines. If injected with Epi, pt would get runs of PVCs and V tach. Halothane + epi = ventricular arrhythmias

Question 10

CO x SVR = BP

Explain effects of Isoflurane

Answer 10

• increases CO
• decreases SVR
• BP remains stable
• causes SNS activation: causes increase in HR and contractiliy, which is why CO goes up in those drugs. Can cause tachycardia, so bad for patients with angina.
• Desflurane works the same way

Question 11

CO x SVR = BP

Explain effects of Sevoflurane

Answer 11

• CO constant
• decreases SVR
• lowers BP
• no change in HR really

Question 12

CO x SVR = BP

Explain effects of NO

Answer 12

• slight decrease in CO
• stable SVR
• stable BP
• some sympathetic stimulation

Question 13

How do these general anesthetics affect respiratory system? What are the two control systems of respiration?

Answer 13

All except N2O are bronchodilators

Respirations tends to become rapid and shallow, and also affects your control of breathing

Two control systems: 1) CO2 response 2) lack of oxygen (hypoxia)

Question 14

All of the general anesthetics (Except NO) can cause malignant hyperthermia. Explain this. What is the treatment?

Answer 14

• caused by a defect in the ryanodine receptor: if defect, Ca gets released and doesn’t get taken back up, so muscles are in a constant state of contraction
• temp goes sky high, end up with rhabdomyolysis, myoglobin can cause renal failure and you basically die
• treatment: Dantrolene: blocks Ca release, muscles relax.

Question 15

What are general anesthetics effects on the liver? Which drug was phased out due to liver complications?

Answer 15

• All decrease hepatic blood flow, but maintain adequate hepatic oxygenation
• Halothane: went away because small number would receive massive hepatic necrosis, Associated with allergic reactions

Question 16

which general anesthetic can cause you to develop pernicious anemia (megaloblastic) and how?

Answer 16

• NO
• its an oxidizing agent, and will oxidize the cobalt in Vitamin B12. If you oxidize the cobalt, VB12 doesn’t do its job.

Question 17

6 conditions for an ideal inhalation anesthetic:

Answer 17

1. not very soluble in blood and tissues (can get it in and out of the body quickly)
2. adequate potency
3. blunts reflexes (larynx closes off to protect airway, not good in surgery becuase you’ll get hypoxic; if abdominal muscles arent relaxed, the guts will flop all over the place)
4. acceptable side effects
5. chemically stable
6. easy to administer

Question 18

What is the driving force for transfer of gases between comparments?

Answer 18

Partial pressure: gas molecules move from comparment of higher partial pressure to compartments with lower partial pressure

analogy: care tire with hole will release air to atmosphere, even though the atmosphere has a higher concentration of air, the tire has a higher _partial pressure. _

Question 19

equation for figuring out the concentration of a gas in blood

Answer 19

concentration of the gas phase x blood gas solubility coefficient

ex. Halotahen is 1%, 99% oxygen, coefficient of 2.5

(1/100 cc) x 2.5 = 2.5 of halothane gase will dissolve in each 100 cc of blood

Question 20

what are the 3 important vessel rich tissue compartments?

Answer 20

brain, heart, kidney

Question 21

Solubility of anesthetics in fat

Answer 21

VERY soluble in fat, therefore it takes a lot of anesthetic to raise the partial pressure even a little bit in the blood.

Question 22

If anesthetic is insoluble in tissue vs if its really soluble

Answer 22

doesnt take many molecules to raise the partial pressure. if really soluble, then like a sponge the tissue sops it up and the partial pressure never rises, so you need alot of molcules of gas anesthetic to raise the partial pressure.

Question 23

difference in vessel size in vessel rich groups, fat groups, and muscle groups

Answer 23

vessel rich group: fat pipes, sot he [] in the vessel rich group rises quickly (not a large capcity for the anesthetic, so partial pressure rises quickly)

fat group: not many blood vessels, thin pipes, anesthetics soluble in fat, takes a ton to raise the partial pressure

muscles: in between these two extreme s

Question 24

The greater the tissue solubility, the (less/more) molecules of anesthetic are required to increase the partial pressure by a given amounts.

What is the relationship between partial pressure rate and tissue blod flow and concentration of anesthetic?

Answer 24

more molecules

Rate of increase of pp directly proportional to the tissue blood flow and [anesthetic] in the blood. It will be inversely proportional to the solubility fo the anesthetic in the tissue

Question 25

What is the first stage of uptake of anesthetics? What is the equation?

Answer 25

LUNGS

The ratio of alveolar concentration : inspired concentration

(FA/FI) = 1-e ^{<span>-(V_A/FRC) x t</span>}

tells us the speed at which alveolar concentration (FA) approaches the inspired, as time goes on, this expression gets smaller. if you have a big FRC, the exponent doesn’t get big very fast, therefore this doesn’t approach inspired concentration as fast.

note: this equation measuring first stage of uptake tells us how quickly you get to plateau, but it has NOTHING to do with the type of anestheti (no solubility coeff in the equation)

Question 26

What does the rate of increase in alveolar concentration depend on? (2)

Answer 26

1. Alveolar ventilation
2. Functional residual capacity
   i. e. emphysema pt has large FRC and small tidal volume; pregnant lady has small FRC (baby pushing up on lungs) and large breaths

Question 27

Second stage of uptake and equation. How does change in CO affect it?

note: equation assumes theres no anesthetic goign back from tissues to lungs.

Answer 27

BLOOD

F_A/F_I = V_A /(V_A + lambdaB-G x CO)

if low CO (shock), then F_A will rapidly approach F_I, resulting in potentially lethal [] of anesthetic delivered to heart and brain.

lambdaB-G is anesthetic solubility coefficient, this equation also tells you height of plateau of inspired concentration at 1.

note: while first stage of uptake tells us hoq quickly you get to plateau of concentration, this second equation tells us how high it is, and DOES have to do with the type of anesthetic.

Question 28

what is the heigh of halothane’s plateau [] if normal ventilation = 5, CO = 5, and blood gas solubility of halothane is 2.5?

What does this imply for MAC?

Answer 28

5/(5+2.5 x 5) = a little less than 1/3

the height of this plateau is a little less than 1/3 of the inspired []

This means that if you give a MAC, you only will get 1/3 of the MAC. say the MAC of halothane is 3/4 of 1%. If you were to inspire 3/4, the alveolar concentration would be about 1/4. If pt needs to fall asleep, you’d need to give a lot more, so you’d have to give 3 or 4%. Giving an extra dose/loading dose is called overpressure.

Question 29

Partial pressure in vessel rich organs closely parallels what partial pressure?

Answer 29

Partial pressure in blood

Question 30

partial pressure in blood usually parallels that in lungs except for these 2 conditions:

Answer 30

1. Right to left shunt: decreased uptake of insoluble agents (partial pressure in lung normally increases quickly; less pulmonary blood flow to remove anesthetic and deliver to tissue)
2. Dead-space ventilation: decreased uptake of soluble agents (rate of delivery very dependent on alveolar ventilation, blood takes up every molecule it sees!)

Question 31

What is overpressure, and when is it used

Answer 31

acts as a loading dose; use relatively high concentrations of anesthetic agent for induction.

Question 32

Advantages of use of NO for induction of anesthesia

Answer 32

• low solubility – partial pressure in lungs rises quickly, not very soluble in blood and tissues so has a high plateau
• second gas effect– since high [] are used (50-80%), large volumes are taken up in first few minutes. Inspired volumes exceed expired volumes. Oher anesthetic agents in inspired mix (e.g. halothane) carried along for the ride. Has to do with the fact that you can take up about 1 L fo NO in first few minutes

Question 33

Maintenance of anesthesia

Answer 33

gradually derease amount you’re giving because venous blood is bringing more BACK to the lungs, so you don’t need to give as much as time goes on. (gradual saturation of tissue stores leads to increased venous concentration of anesthetic with proportionally less uptake of anesthetic from lungs)

Also, incision is most painful part of surgery, so don’t need as much after that.

Question 34

In terms of waking up from anesthesia, decrease in arterial blood levels depends on what 2 factors?

Answer 34

1. alveolar ventilation (if you increase ventilation, you get it out more quickly, but the problem is too much ventilation with decrease cerebrale blood flow, and in order for pt to wake up, you need to get the anesthesia out of the braine)
2. Redistribution of anesthetic from vessel righ croup to muscle and at groups
   - concentration of agents in muscles and fat continue to increase even after anesthetic turned off
   - after long operation, most tissues fully saturated, therefore, serve as a *source, *rather than a sink for anesthetic agent.

(In short operation, partial pressure in vessel rich group is higher than in muscle group, so some anesthetic is going to redistribute from vessel rich group to the muscle group and will help wake them up. In long operation, musle and fat are already filled with anesthetic, so when you turn anesthetic off, it will be leaching out from muscle and fat and keeping vessel rich group higher than it otherwise would be. In this case, redistribution keeps them sleepy)