Chapter 8: Inhalation Anesthetics

Fresh gas flow (FGF) is determined by ___________ and __________.

the vaporizer and flowmeter settings

MAC-awake is a concentration that is associated with awakening from anesthesia when the inhaled drug is the only agent maintaining anesthetic (a rarity); it is also the concentration required to block voluntary reflexes and control perceptive awareness. What's MAC-awake?

0.3-0.4 MAC

Fresh gas leaving the anesthesia machine mixes with gases in the breathing circuit, thus the patient isn't really breathing the concentration you set the vaporizer at. Name 3 factors affecting Fi (inspiratory concentration) that will clinically result in FASTER induction and recovery times.

1) Higher FGF rate (high rate) 2) A smaller breathing circuit volume (small volume) 3) Lower circuit absorption (low absorption)

The second factor that affects anesthetic uptake is alveolar blood flow. In the absence of pulmonary shunting, flow is equal to Cardiac Output. Therefore, if CO increases, so does uptake, and induction is delayed. How does a low output stat affect 1) insoluble agents and 2) soluble agents?

1) Insoluble agents won't be really affected by a change in output since so little is taken up into the blood anyway. 2) Soluble agents in a low output state will be prone to overdosage because less will need to be in blood thus alveolar concentration will increase faster.

[Remember: Uptake is 1 of 3 factosr that affects FA] Name 3 factors that affect anesthetic uptake.

1) Solubility, 2) Alveolar blood flow, 3) Difference in partial pressure between alveolar gas and venous blood.

What MAC is equivalent to ED 95, i.e. a level at which 95% of patients had no movement to a standardized stimulus?

1.3 MAC

MAC-BAR is the concentration required to block autonomic reflexes to nociceptive stimuli. What's MAC-BAR?

1.7-2.0 MAC

How much does MAC decrease with age?

6% decrease in MAC per decade of life after age 40.

Nitrous Oxide: Respiratory effects? What is the concern for breathing in the PACU?

Resp: Like all inhalation anesthetics, RR increases and tidal volume decreases. Minute ventilation is unchanged. However, with NO2, peripheral chemoreceptors' activity in the carotid body is markedly depressed, so YOU LOSE YOUR HYPOXIC DRIVE. Thus ensure these patients get supplemental oxygen regardless.

Isoflurane, Desflurane, and sevoflurane: Cerebral effects? Renal effects? Neuromuscular?

All increase cerebral blood flow causing increased ICP, however, each of these agents can be treated with hyperventilation. Unlike halothane, you don't have to pre-treat before administering the agent. Note, each of these agents decrease cerebral metabolic rate so not as much oxygen is required either. These agents all decrease renal blood flow, but isoflurane decreases it more than des and sevo. All 3 of these agents cause skeletal muscle relaxation and potentiate NM blockade. (Note: Sevo produces enough SkM relaxation during induction of children that you don't require a paralytic.)

Nitrous Oxide Drug Interactions: If you use NO2 in addition to volatile agents, how does it change requirements?

The addition of NO2 decreases the requirements of volatile agents. Using 65% NO2 decreases the MAC of volatile anesthetics by 50%!

The 3 phases of general anesthesia:

1) Induction, 2) Maintenance, and 3) Emergence

Name 3 factors that affect alveolar concentration (FA).

1) Uptake 2) Ventilation 3) Concentration effect + Augmented inflow effect

Halothane: Neuromuscular? renal? Hepatic?

Halothane relaxes skeletal muscle, which also potentiates NM blocking agents. Like all other volatile agents, it can trigger malignant hyperthermia. Halothane reduces renal and hepatic blood flow (note: think about the CV effects).

Isoflurane vs Desflurane physical property difference? What's this do to its vapor pressure?

Isoflurane's Chlorine atom is substituted with a Fluoride atom. This minor difference has profound effects on the physical properties of the drug. Desflurane requires a specialized vaporizer because of how high the vapor pressure is.

Xenon: MOA? Effects on CV/Hepatic/Renal? Cerebral? MOA for cerebral effect?

NMDA antagonist (like NO2, but it is a natural element thus it is scarce and thus expensive, limiting its widespread use). Xenon has little effect on the CV, hepatic and renal systems. On the brain, it has been found to be protective against neuronal ischemia. Xenon is anti-apoptotic that inhibits influx of Ca2+ following cell injury.

Nitrous Oxide Contra-indications: Name them and explain why it can't be used.

NO2 can't be used in any surgery where there is an air-containing cavity, i.e. bowel obstruction, pneumothorax, ENT surgeries, intracranial air, air embolism, pulmonary air cysts. This is because nitrous oxide will diffuse into the air cavity faster than the air (i.e. mostly composed of nitrogen) will diffuse out.

Desflurane: CV effects? What about if you rapidly increase desflurane's concentration? How can you attenuate these effects?

CV effects are generally like isoflurane's, in that CO is essentially unchanged at a 1-2 MAC. Increasing the dose at a normal rate will cause a decrease in systemic vascular resistance, thus a drop in BP. However, if you do a rapid increase in [des] it will lead to transient, worrisome elevations in HR, BP, and catecholamine levels especially in patients with CV disease. These effects can attenuated by fentanyl, esmolol, or clonidine.

What is desflurane's Blood:Gas partition coefficient? (What's NO2's? How much more potent is desflurane than NO2?) What's this tell you about induction/emergence? Compare wake-up times of iso vs desflurane.

Desflurane's B:G is 0.42, the lowest of all volatile agents; NO2 is second lowest at 0.47. Des is 17x more potent than NO2. Des's coefficient means it has very low solubility making induction and emergence very rapid/ultra short-acting. Wake up times are approximately 50% less than those observed for isoflurane.

Desflurane Toxicity: What's the main risk? How can you clinically diagnose? What's really important to do with the breathing circuit when using Desflurane as an anesthetic?

Desflurane, more than other volatile anesthetics, is degraded by dessicated CO2 absorbent into potentially clinically significant levels of carbon monoxide. CO poisoning is hard to diagnose under general anesthesia, so getting an ABG would be helpful. You would also look at the pulse ox, which would be low but still falsely high. It's important to make sure you change out the soda lime so it's not dried out!

Exhalation is the most important route of elimination of inhalation anesthetics. Know that many factors that speed induction also speed recovery. Name some.

Elimination of re-breathing. High fresh gas flow. Low circuit volume. Low circuit absorption. Decreased solubility. High cerebral blood flow. Increased ventilation.

Recovery from anesthesia depends on lowering the concentration of anesthetic in brain tissue. Name the 3 ways inhalation anesthetics are eliminated and describe each.

Exhalation (main route), biotransformation (minimal, but more important for soluble agents via CYP-2E1 metabolism), and transcutaneous loss (insignificant).

If you have greater Uptake, what happens to FA:Fi ratio? How will this affect the induction rate?

Greater uptake means that you're going to have a lower alveolar concentration, therefore the ratio will be low, i.e. FA/Fi < 1.0. This will slow the rate of induction.

Halothane: Cerebral effects (2)? Ways to fix it?

Halothane causes 2 things, increase in CBF and blunting of autoregulation. Therefore, you often get ICP with this but you can prevent a rise in ICP by establishing hyperventilation PRIOR to administration of halothane. Either way, halothane (like all inhalation anesthetics) should be used very cautiously in patients with inc ICP.

Halothane: CV effects? Comment on myocardial perfusion and halothane-induced arrhythmias as well.

Halothane causes direct myocardial depression. A 2.0 MAC in patients not undergoing surgery results in 50% decrease in BP and CO! Adequate myocardial perfusion is usually maintained, as oxygen demand also drops. Further, halothane sensitizes the heart to arrhythmia if >1.5 mg/kg epinephrine is used.

Halothane toxicity: Who is most at risk for Halothane hepatitis?

Halothane hepatitis is extremely rare (1 of 35,000). Patients most at risk are those who have had 1) multiple halothane exposures, 2) at short intervals, 3) who are middle-aged/obese/women, and 4) have a family or personal pre-disposition to halothane toxicity.

Halothane Toxicity: Explain "Halothane hepatitis"

Halothane is oxidized to its principal metaboliate, tri-fluroacetic acid (TFAA). It appears that disulfiram inhibits this formation, and enzyme inducers like barbiturates increase production of TFAA. Further, hypoxia creates more hepatotoxic end products. Despite all of this, it looks like "halothane hepatitis" is best explained by auto-immune attack with TFAA being the triggering antigen causing antibody formation.

Halothane is very water soluble with a Blood:Gas partition coefficient of 2.4, versus a relatively water soluble agent like Nitrous Oxide, with a Blood:Gas partition coefficient of 0.47. What does this mean for alveolar concentrations between the two, and thus the induction rate?

Halothane with a B:G coefficient of 2.4 will obviously like to be blood 2.4 more times than in the alveoli as a gas (note: the higher the coefficient, the greater the solubility). Given, NO2s B:G coefficient is 0.47... this means that the alveolar concentration of Nitrous Oxide will rise faster than halothane, and will have a faster induction rate.

What's faster... inhalation vs IV anesthetics? Why?

Inhalation anesthetics are taken up via pulmonary circulation and thus have a more rapid appearance in arterial blood compared to IV administered anesthetics.

Isoflurane: Effects on CV? Explain coronary steal.

Isoflurane decreases systemic vasc resistance (thus dec BP) but HR increases to compensate, thus CO is maintained. Also, isoflurane dilates coronary arteries, which theoretically divert blood away from fixed stenotic lesions, i.e. "coronary steal"--this has largely been forgotten

Desflurane: Respiratory effects? Should des be used for induction?

Like other inhalation anesthetics, RR increases and TV decreases. MV decreases overall. And like the other volatile agents, apneic threshold is increased and doesn't respond to the higher PaCO2 like the body would normally. Des would be poor for induction because it causes salivation, breath-holding, coughing, and laryngospasm.

Ventilation is another factor, in addition to Uptake, that affects FA. Knowing that uptake lowers alveolar partial pressure, what can you do to ventilation to counter this? How does increasing ventilation affect soluble vs insoluble agents?

Lowering of alveolar partial pressure by uptake can be countered by INCREASING ventilation. In other words, constantly replacing anesthetic taken up by the pulmonary circulation results in better maintenance of alveolar concentration. Increasing ventilation while using SOLUBLE agents will help counter uptake by raising the FA/FI ratio. However, increasing ventilation while using INSOLUBLE agents will have a minimal effect.

Define MAC. Also, by definition, MAC is equivalent to what? Clinically, MAC is also a useful measure because it mirrors what? Nonetheless, what should you always remember about MAC (i.e. during induction)?

MAC (minimal alveolar concentration) = the anesthetic concentration that prevents movement in 50% of subjects to a standardized stimulus, i.e. surgical incision. MAC by definition is equivalent to the ED50 of a drug. MAC is a useful measure because it mirrors the brain partial pressure. However, always remember it is a median value with limited usefulness in individual patients, especially during induction because of rapidly changing alveolar concentrations.

Are MAC values for different anesthetics roughly additive for both CNS depression and myocardial depression?

MAC values are roughly additive for CNS depression, i.e. using 0.5 MAC of Nitrous Oxide + 0.5 MAC of halothane. This is not necessarily true for myocardial depression though so be aware, i.e. 0.5 MAC of halothane produces more myocardial depression than that of 0.5 MAC of nitrous oxide.

Nitrous Oxide: MOA? What are it's CV effects?

MOA: NMDA receptor antagonist CV: no change essentially, maybe slight increase because NO2 is known to stimulate sympathetics. Know that NO2 directly depresses the heart's contractility, so use cautiously (if at all) in patients with CAD or severe hypovolemia

Explain the second gas effect.

Most often explained with NO2. A high concentration of nitrous oxide will augment not only its own uptake, but theoretically the uptake of a concurrently administered volatile anesthetic. Clinically this is probably insignificant.

Nitrous Oxide: What makes NO2 a less attractive use for neuroanesthesia?

NO2 causes a mild increase in ICP because it vasodilates cerebral vessels, causing an increase in cerebral blood flow and volume. It also increases cerebral oxygen consumption (CMRO2). Both of these makes it unattractive for neuro use.

Explain what happens if you're using NO2 as part of your anesthesia regimen and you're beginning emergence. What do you need to do clinically?

NO2 diffuses very quickly from the alveoli and causes a dilution of both CO2 and O2 in the alveoli, resulting in DIFFUSION HYPOXIA. Clinically, this is prevented by administering 100% oxygen for 5-10 minutes after discontinuing the nitrous oxide.

Nitrous Oxide: Effects on Neuromuscular? Renal? GI?

NO2 does NOT provide any significant muscle relaxation, but does potentiate NM blockade (but less so than volatile agents). NO2 tends to increase renal vasculature resistance, so you do see a decrease GFR slightly (thus less UOP). Lastly, NO2 is known to cause post-op nausea/vomiting.

Nitrous Oxide Toxicity: Name 2 consequences of NO2's interactions with Vitamin B12. Also, is it safe to use in pregnant patients?

NO2 irreversibly oxidizes vitamin B12 rendering it inactive. Thus any enzyme that requires B12 can't work, including methionine synthetase (used in myelin formation) and thymidylate synthetase (used in DNA synthesis). Therefore, 2 consequences are peripheral neuropathy and megaloblastic anemia 2/2 bone marrow depression. Finally, NO2 is a teratogen so it is often avoided in pregnant patients who are not yet in their 3rd trimester.

Halothane contra-indications: Name 2. Also, name 2 drug classes that you need to be very careful with.

Patients who are hypovolemic may not tolerate the drastic decrease in cardiac output caused by halothane. Thus, you should not use BB or CCBs in these patients. Also, patients with increased ICP because of the possibility of intracranial hypertension 2/2 inc cerebral blood flow and volume. Remember you must hyperventilate these patients PRIOR to giving halothane (unlike the other volatile agents).

Halothane: Respiratory effects ? Comment on minute ventilation, hypoxic drive, and the several effects it has on the bronchial tree. Any concerns for breathing in the PACU?

RR increases, but not enough to compensate for a largely decreased TV therefore MV is decreased and resting PaCO2 rises. Know that the APNEIC THRESHOLD also rises, so even though PaCO2 is elevated you're not taking a breath when you need it. Hypoxic drive is severely depressed (more so than NO2) with very low concentrations of halothane, i.e. 0.1 MAC. Also, halothane is a potent bronchodilator (can reverse asthma-induced bronchospasm), but attentuates airway reflexes and depresses mucus clearance... this can promote post-op hypoxia and atelectasis.

Normally, alveolar and arterial anesthetic partial pressures are assumed to be equal, however the arterial pressure is consistently less than expected. Name 4 factors that could affect arterial concentration.

Reasons for a decreased arterial partial pressure compared to alveolar partial pressure include 1) venous admixture, 2) alveolar dead space, 3) non-uniform alveolar gas distribution, and 4) ventilation/perfusion mismatch.

Isoflurane: Respiratory effects?

Respiratory depression with isoflurane also decrease TV, and you do produce an increased RR but not as much as the other volatile anesthetics therefore MV is reduced. Also, despite being a bronchoirritant, it is also a bronchodilator with the same strength as sevo (note: halothane is stronger though).

Desflurane contra-indications: name 3 (which are common to the other modern inhalation anesthetics as well).

Severe hypovolemia, intracranial hypertension, and malignant hyperthermia.

Sevoflurane: CV effects? Any specific effects on EKG?

Sevo mildly depresses myocardial contractility. Sevo causes a decrease in BP with no compensatory increase in HR so CO declines a little. Interestingly, sevo is known to cause prolonged QT which doesn't really have any clinical significance--but it doesn't show up for infants until an hour after emergence.

Sevoflurane: What is it's blood:gas coefficient? What makes it useful for induction in both kids and adults?

Sevo's B:G coefficient is 0.65, so it is still soluble and allows for a more rapid induction than isoflurane, but less than desflurane. Further it is sweet smelling making it an excellent choice for inhalation induction.

Name 2 inhalation anesthetics used in pediatric patients.

Sevoflurane and halothane

Sevoflurane Toxicity: Most concerning is it's interaction with Soda Lime. Explain. Talk about 5 factors that can increase this problem. What patient population should Sevo be avoided in?

Soda lime or Barium OH- lime (but not CaOH) can degrade sevo into Compound A, a nephrotoxic agent. Accumulation of compound A increases with 1) Inc respiratory gas temperature, 2) low-flow anesthesia (always put to at least 2L), 3) dried out soda lime, 4) high sevo concentrations, and 5) long duration of receiving Sevo. It's recommended that patients with pre-existing renal dysfunction not receive Sevo.

Ventilation/perfusion mismatch is 1 of 4 factors that could affect arterial concentration. The mismatch acts as a restriction. Explain how alveolar pressure before and after the mismatch will be affected.

The mismatch increase the alveolar-arterial pressure difference. The mismatch will act as a restriction to flow, so not only will it reduce flow through the restriction, it will also raise the alveolar pressure in front of the restriction and lower the pressure beyond it.

Factors affecting Alveolar Concentration include uptake, ventilation, and lastly--INSPIRED CONCENTRATION. The slowing of induction due to uptake from alveolar gas can be reduced by doing what to the inspired gas concentration? This actually has 2 effects on the alveolar concentration... what are they?

The slowing of induction due to uptake from alveolar gas can be reduced by INCREASING inspired gas concentration. Interestingly, increasing FI not only 1) increases [FA], but it also 2) increases the rate of rise of [FA]... this is called the "concentrating effect." Simply put, a higher inspired concentration results in a disproportionately higher alveolar concentration.

Inhaled anesthetic uptake and distribution depends on tissue solubility and tissue blood flow. Name the 4 groups (and what organs they include).

Vessel rich group (brain/heart/lungs/kidneys/and endocrine organs) is the the first group to encounter the anesthetic and the first to reach steady state, i.e. arterial and tissue partial pressures are equal. Muscle/skin is group 2 and is well perfused but slower than the vessel rich. 3rd group is the fat, but steady state would take days to achieve because anesthetics are lipid soluble. And last group is Vessel-poor group, i.e. bones/ligaments/cartilage/ teeth/and hair, has insignificant uptake.

Factors affecting MAC: Age (young/old), Alcohol intoxication (acute/chronic), Temperature, Anemia, Hypoxia, Hypocarbia, Thyroid, and Hypotension? Electrolyte imbalances? Pregnancy -- how much does it affect MAC?

Young age, chronic alcohol abuse, HyperNa+, and ephedrine use are the only 4 factors that increase MAC. All others decrease it except the thyroid, which has no effect either way. For pregnancy, MAC is decreased by 1/3 at 8 weeks but returns to normals a few days after delivery.