Inhalational Anesthetics principals Flashcards
What is methoxyflurane?
A potent halogenated anesthetic with high solubility and low vapor pressure
How was methoxyflurane metabolized?
50% by cytochrome P450 into nephrotoxic compounds
What was prolonged anesthesia with methoxyflurane associated with?
Vasopressin resistant, high output renal failure
What are the effects of enflurane?
Depressed myocardial contractility
Increased CSF
Decreased CSF output
Seizures
What is the ultimate effect of inhalation all anesthetics?
Therapeutic tissue concentration in the brain
What is the inspired gas concentration determined by?
The fresh gas flow rate
Breathing circuit volume
Circuit absorption
What is the concentration of a gas directly proportional to?
It’s partial pressure
Why is the alveolar partial pressure of a gas important?
Because it determines the partial pressure of anesthetic in the blood and ultimately the brain.
What is the relationship between uptake and alveolar concentration?
The greater the uptake, the greater the difference between inspired and alveolar concentration and SLOWER rate of induction.
What 3 factors affect anesthetic uptake?
Solubility in the blood
Alveolar blood flow
The difference in partial pressure between alveolar gas and venous blood.
What does it mean if something is less soluble?
Means that it is not taken up in the blood as avidly, meaning that the alveolar concentration will be higher and induction much faster (nitrous oxide)
What is the partition coefficient?
The ratio of the concentrations of the anesthetic gas in each of two phases at steady state
What is the blood/gas coefficient of nitrous oxide?
0.47 so the blood has 47% capacity of nitrous oxide as alveolar gas
What is the blood/gas coefficient of halothane?
2.4
If the blood/gas coefficient is bigger, what does this mean for the anesthetic’s solubility and uptake by the pulmonary circulation?
It means it is more soluble and has higher uptake in the pulmonary circulation meaning that the alveolar partial pressure will take awhile to rise, thereby causing slower induction
What is alveolar uptake(blood flow) equal to?
Cardiac output
What are the first organs to reach steady state and why?
Brain, heart, liver, kidney, and endocrine because they have the high blood flow
How can you increase the alveolar concentration?
By increasing the concentration of inspired gas
What is augmented inflow effect?
The absorbed gas has be replaced by an equal volume of the mixed gas to prevent alveolar collapse
What is the second gas effect?
A high concentration of one gas will augment its own uptake and another volatile anesthetic (nitrous oxide does this)
How does ventilation affect the alveolar partial pressure?
It will increase it by constantly replacing anesthetic that is being taken up
What does VQ mismatch doe to alveolar partial pressure?
It increases it, thus making onset faster for soluble agents
What happens with the elimination of nitrous oxide?
It diffuses so fast that oxygen and co2 are diluted causing a diffusion hypoxia?
How do you treat diffusion hypoxia?
By administering 100% oxygen for 5-10 minutes after stopping nitrous oxide
How are inhalational agents cardio protective?
They open the K ATP channel, preventing the influx of calcium and reducing ROS. Therefore reducing ischemia-reperfusion injury
What protective property does Xenon have?
An anti-apoptotic effect that may be secondary to its inhibition of calcium ion influx following cell injury
What happens to MAC as you age per decade?
The MAC decreases by 6% regardless of volatile anesthetic
What is a MAC of 1.3 correlated with in any of the volatile anesthetics?
Prevention of movement in 95% of patients
What is a Mac of 0.3-0.4 associated with?
Awakening
What factors decrease MAC?
Temperature (hypo or hyperthermia) Old Acute alcohol intoxication Hypoxemia Hypercapnia Hypotension Hypercalcemia Hyponatremia Pregnancy
What factors increase Mac?
Hypernatremia Cocaine Ephedrine Chronic alcohol use Young age Temperature over 42 Celsius
What is the principal mechanism by which halothane decreases blood pressure?
By decreasing cardiac output
How do isoflurane, sevoflurane, and desflurane decrease blood pressure?
Through decreasing SVR
Cause dose dependent changes in arterial bp, SVR, and co
Which anesthetic is metabolized to hexafluoroisopropanolol?
Sevoflurane
How is sevoflurane metabolized to hexafluoroisopropanolol ?
Through p450 enzymes
How are desflurane, isoflurane, and sevoflurane mainly eliminated?
Unchanged when exhaled out of the lungs
What is the order of volatile that undergoes liver metabolism from greatest to least?
Halothane > sevoflurane > isoflurane > desflurane
What enzyme family is responsible for volatile metabolism in the liver?
P450 (CYP2E1)
What do desflurane and isoflurane get metabolizes to in the liver?
Trifluoroacetic acid
What does Trifluoroacetic acid do?
Binds hepatocellular proteins and acts as a happen –> immune response
What is a rare complication from isoflurane or desflurane?
Hepatic necrosis and liver failure from subsequent exposure after immune response on first exposure
What 2 types of liver injury are associated with halothane?
- Mild form : free radical formation by reductive metabolism (CYP2A6 and CYP3A4) (under conditions of hypoxia or decreased flow
- Oxidative metabolism and the immunologic response from TFA
What does the rate of rise of the FA:Fi ratio depend on?
The blood gas solubility
The inspired concentration of gas
Therefore the speed at which the alveolar anesthetic (FA) equilibration with that being delivered to the lungs (Fi).
How much inactivation of methionine synthetase do you get from nitrous oxide at 70% for 46 minutes?
50%
What does halothane do to catecholamines effects on the heart?
Sensitized the heart to them so causes arrhythmias
Which inhalational agents will have a longer induction with one-lung ventilation
Desflurane and nitrous oxide because they have the lowest blood/gas solubility.
One lung ventilation creates a shunt. Less blood is there to take the volatile to the brain. The less soluble agents will just stay in the ventilated lung
When cardiac output is doubled what happens to the rate of rise of FA/Fi of a soluble agent?
It will slow the rate of rise
What happens to rate of rise for insoluble agents in a shunt?
Slow the rise
