Uptake is specific to inhaled anesthetics and is the same as absorption. It is the movement of the anesthetic from alveoli into the pulmonary capillary blood (to the circulation)
What is distribution?
Transport of the anesthetic to the sites of action (CNS)
Inhaled agents undergo limited metabolism, T or F?
How are inhaled anesthetics eliminated for the most part?
Via the lungs (exhalation)
What is FA/FI?
Ratio of concentration of anesthetic in the alveoli (A) and the concentration of anesthetic that's inspired (I). How quickly FA = FI is important in determining how quickly the agent will have an effect.
Describe the route of the inhaled anesthetic from the anesthesia machine to the CNS.
Vaporizer thru fresh gas flow thru breathing circuit to FI to lungs to alveolar gas to arterial blood to vessel rich group (brain is part of VRG)
What drives the distribution of an inhaled anesthetic from inhaled gas to the to CNS?
Partial pressure gradient.
How is FI expressed?
In vol %, which means ml / ml
What does a volume % of 2% mean?
2 ml sevo in 100 ml gas
How does solubility relate to uptake and distribution of an inhaled anesthetic?
Increased solubility means the agent will take longer to reach an equilibrium between FA and FI. This is because there is more dissolved in the inhaled portion and FA doesn't build up as quickly.
What does a blood gas partition coefficient of 1.8 for enflurane mean?
Enflurane is 1.8 x more soluble in the blood than in gas.
How does a higher blood gas partition coefficient affect uptake and distribution of an inhaled anesthetic?
A higher blood gas partition coefficient means the agent is very soluble in the blood and will take longer to build up a partial pressure and take effect.
How does increasing the inhaled partial pressure affect alveolar partial pressure? What is this called?
Increasing the inhaled partial pressure (increased concentration) off-sets uptake speeding up the rise in Palveolar (uptake into blood means it's "lost" and unable to build up partial pressure and have an effect).
This is called over pressurization, it's like giving a bolus.
What are determinants of alveolar partial pressure? (There are 8)
1) inh PP 2) alv vent 3) spont vs mech vent 4) CO 5) Alv to venous pp diff 6) conc effect
7) 2nd gas effect 8) solubility
How does alveolar ventilation affect alveolar partial pressure?
Increased ventilation promotes input to offset uptake. If we don't ventilate the alveolar the drug can't get there.
Effect is less with an agent less soluble in blood.
How could hyperventilation affect the clinical effect of an inhaled agent?
With hyperventilation CO2 level decreases, this decreases cerebral blood flow, thus there is less delivery of the agent to the brain, and a slower clinical effect.
How do volatile agents affect respiration (TV and RR) and how does this affect alveolar partial pressure?
Volatile agents decrease TV and increase RR. Inhaled anesthetics affect their own uptake by dose dependent respiratory depression (spontaneous vent), this can be overridden with mechanical ventilation.
How does CO affect alveolar partial pressure?
Increased CO will decrease the rate of equilibration (more rapid uptake into the blood) and a decrease in Palveolar and rate of induction. Less of an issue with a less soluble agent.
With a high CO there is not enough time for a partial pressure to build up.
How do alveolar to venous partial pressure differences affect alveolar partial pressure?
Reflects tissue uptake of anesthetic. The fraction of anesthetic removed from the blood as it passes thru the tissues depends on: solubility of anesthetic in tissue, blood flow, and PP difference. VRG equilibrates rapidly with arterial PP. There needs to be a PP gradient for the agent to get into the tissue. So the solubility of the agent in the various tissue groups is important.
What is the concentration effect?
The higher the inspired partial pressure, the more rapidly the alveolar partial pressure approaches inspired. FA approaches FI.
Explained by Fick's Law.
What are the 2 components to the concentration effect?
1) Concentrating effect
2) Augmentation of tracheal inflow
Explain the concentratING effect.
After uptake of 50% of gas, the anesthetic gas is concentrated in a smaller total volume (smaller denominator). The higher the concentration used, the faster FA approaches FI. Compares differences in inhaled concentrations (2% sevo vs. 1% sevo)
What is augmentation of tracheal inflow?
In the next breath (after the 1st breath which involves the concentrating effect), the absorbed gas must be replaced by an equal volume of the gas mixture, this pulls in more inspired gas. Again a higher concentration increases the rate by which FA approaches FI.
What is the second gas effect? What gas is always involved?
Concentration effect of 1 gas on another. High concentration of 1 gas (N20) augments the uptake of another gas (a volatile).
Always involves N20 (1st gas) and a volatile (2nd gas).
It is weak and likely insignificant.
How does solubility affect alveolar partial pressure?
Various coefficients for different compartments. Gives an indication as to uptake of anesthetic into tissues.
What is a time constant?
An estimate of the amount of anesthetic that can be dissolved in the tissue divided by the tissue blood flow.
Pertains to tissue: blood coefficient.
What is the formula to calculate a time constant?
Capacity / Flow = TC
Capacity = volume of tissue (ml) / tissue blood flow
What does a large time constant indicate?
Increased capacity, low flow, it will take longer for the agent to equilibrate in that tissue. Ex: fat tissue.
How many time constants does it typically take to see a 95-98% change in a vaporizer setting?
What factors will increase the rate of rise of FA / FI ?
Low blood solubility, low CO, high alveolar ventilation. Opposite is true as well.
Which tissue group has the greatest % of body mass?
Most- muscle group
Which tissue group receives the greatest % of blood flow? The least?
What are the BG partition coefficients of N20 and des?
What's the BG partition coefficient of sevo?
What's the BG partition coefficient of halothane?
What's the BG partition coefficient of enflurane and iso?
How does solubility affect recovery from anesthesia?
Less soluble agent = faster recovery time (faster washout)
Combination of tissue-blood and BG partition coefficients determines how quickly the patient will wake up
What's a context sensitive half time for inhaled agents?
Time to 50% decrease in anesthetic concentration INDEPENDENT of duration
What is diffusion hypoxia?
N20 dilutes O2 as it comes out of the tissues quickly when the case is over and trying to wake up pt. Hence we give 100% O2 after the N20 is d/c.
What happens when Cl is substituted with F (substitute higher MW with lower MW)?
Potency decreases (MAC increases)
How much MAC do we want for tracheal intubation?
What about to get immobility?
Tracheal intubation- more than 1 MAC
To prevent movement in ALL pts (not just 50%), exceed MAC by 10-30%
How does adding N20 to a volatile decrease the MAC of the volatile? Is this the second gas effect?
Adding N20 can decrease the MAC of the volatile by 50% (makes it more potent). This is NOT the 2nd gas effect, it's the effect of giving 2 medications that effect the CNS.
What is a benefit of using N20 with a volatile?
N20 does not cause vasodilation.
How is MAC calculated?
MAC = 150 / oil gas partition coefficient
What is MAC awake? How does it compare to MAC?
Avg concentration permitting voluntary response to a command. Less than MAC
1/3 MAC for sevo, iso, and des
1/2 MAC for halothane
More than 60% MAC N20
A pt at MAC awake level is able to protect their airway, T or F?
F! normal pharyngeal function requires the anesthetic conc to be at 0.1 MAC or less (lower than MAC awake)
What is MAC-BAR? How does this compare to MAC?
MAC- Blocks Autonomic Reflexes
Prevents response to surgical stim, considerable in excess of MAC
What factors don't affect MAC?
Duration of anesthesia, MAP > 50 mmhg, gender, size
How does T affect MAC?
Both hyper and hypothermia DECREASE MAC. Unless T > 42 C, then MAC INCREASES
How do extremes of age affect MAC?
Young (<1yr)- INCREASED MAC
Elderly- DECREASED MAC
How does increased PCO2 or decreased PO2 affect MAC?
How does MAP < 40 mmHg affect MAC
How do hyper and hypothyroid affect MAC?
They don't. But they do affect CO, so it may appear that MAC has changed.
How do hypercalcemia and hyponatremia affect MAC?
How do opioids, local anesthetics, ketamine, barbituates, benzos, verapamil, lithium, sympatholytics (methyldopa and clonidine), acute intoxication, and chronic amphetamine use affect MAC?
All decrease MAC
How does chronic alcohol use, acute amphetamine use, ephedrine, and cocaine affect MAC?
With normocapnia, how do the volatiles affect CBF? Which agents have the most affect? The least affect?
They produce vasodilation and thus increase CBF. Greatest effect with halothane, least with iso and des.
It is time and dose dependent.
How do the volatiles affect cerebral metabolic rate?
They produce dose-dependent decreases in cerebral metabolic O2 requirements (a good thing).
Decr. cerebral metab = less CO2 prod = opposition to vasodilation.
Cerebral protection during periods of ischemia from hypotension.
Greater with iso than halothane.
When could the increased CBF be harmful?
With space occupying lesions, increased ICP.
We hyperventilate to a PCO2 of about 30 mmHg to offset.
How does halothane affect the CV system? BP, CO, HR
Halothane decreases CO, decreases contractility, causes myocardial depression. It also decreases HR, this causes a decrease in BP.
What is a common affect on the CV system from all the volatiles? How can we counteract this (what anesthetic agent)?
Dose dependent hypotension. But different mechanisms of different agents. We can add N2O as it produces no change or a slight increase in BP, get additive anesthesia without vasodilation.
By what mechanism do all volatiles (except halothane) affect BP?
They reduce BP by reducing SVR.
What agents are known to increase HR?
iso and des (especially immediately after a change in settings)
Other than halothane, do the other volatiles affect CO?
Does halothane affect SVR?
How do the volatiles affect arrhythmias?
The myocardium is sensitized to epi. This occurs more with halo and less with iso, des, and sevo. When using iso, des, and sevo we should not exceed 6 mcg / kg of epi.
What is "steal"?
Coronary vasodilation of small resistance vessels, "steal" occurs when blood is redirected from ischemic to non ischemic areas. This is probably offset by negative inotropy, so only pt's with steal prone anatomy are at risk.
What is steal prone anatomy?
Total occlusion of major coronary artery.
90% stenosis of collateral distal to occlusion.
What agent is thought to cause coronary "steal"?
Iso. However, in practice if adequate hemodynamics are maintained, it doesn't occur.
How do volatiles affect the respiratory system?
Increased RR, decreased TV, however, increased RR is not enough to offset decreased TV, so decreased MV. Thus an increase in PaCO2.
How do volatiles affect the body's response to hypercarbia and hypoxemia?
Dose dependent decrease in response.
T or F, volatiles increase airway resistance?
F, they reduce airway resistance.
Hepatic effects are most severe from which agent?
Halothane. 2 types of hepatotoxicity.
What types of hepatotoxicity can occur ?
1) mild self limited postop liver toxicity (bump in enzymes, fever, lethargy, occurs in 20% of adults)
2) halothane hepatitis, immune mediated response, massive hepatic necrosis and death possible, kids less susceptible.
What is the major effect of the volatiles on the kidneys?
Decreased blood flow to the kidneys, decreased GFR, decreased UO.
What is fluoride induced nephrotoxicity? What agents cause it?
Polyuria, hypernatremia, inability to concentrate urine. Clinical toxicity occurs when plasma F conc. > 80 micromol / L.
Methoxyfluorane caused this and this is why we don't use it any longer.
Also assoc enflurane, but that's not why it's rarely used any longer, it's just no better than anything else.
What is compound A? What agent is it associated with?
Compound A is a dose dependent nephrotoxin (vinyl halide nephrotoxicity). Associated with sevo. Formed when sevo reacts with CO2 absorbants.
What does the manufacturer recommended to avoid compound A toxicity? Is it something to be worried about?
Manufacturer recommends using FGF of at least 2L when using sevo. However, the amt of compound A produced is less than the amount found to cause nephrotoxicity in rats, so the concerns are more theoretical.
How do the volatiles affect skeletal muscle relaxation?
All but halothane enhance NMB, but don't replace them.
What agent is the most potent trigger for MH? The least?
What is the only inorganic anesthetic gas? When is it contraindicated?
Contraindicated with ENT surgery (lasers) as it will support combustion. Also with air embolism, pneumothorax, intestinal obstruction. Pulm HTN (may increase PVR).
How does N20 affect SNS, contractility, and hemodynamics?