Inhaled Anesthetics Flashcards

Question

Anesthetic partitioning into blood (blood solubility) increases after ingestion of fatty foods and may decrease in anemic or malnourished patients T or F

Answer 1

(1) alveolar ventilation, (2) cardiac output, and (3) anesthetic solubility in blood. Increased ventilation delivers more anesthetic from circuit to alveoli and increases Palv/Pcirc. Importantly, increased pulmonary blood flow removes more anesthetic from alveoli, thereby decreasing the rate of increase in alveolar concentration of anesthetic (Palv/Pcirc). Indeed, significant decreases in cardiac output are suspected when end-tidal CO2 (ETCO2) decreases and end-tidal concentration of VA increases. The more soluble an anesthetic is in blood (i.e., the higher its λb/g), the greater is the capacity for each volume of blood to take up anesthetic from alveolar gases (i.e., the larger the effective blood flow). Thus as λb/g increases, Palv/Pcirc increases more slowly

Answer 2

Dead space (ventilated but not perfused pulmonary regions) reduces effective alveolar ventilation, and thus slows anesthetic uptake

Answer 3

Pulmonary right to left shunting can be physiologic, pathologic, or iatrogenic, such as during one-lung ventilation. Right-to-left shunting results in a difference between Palv and the partial pressure of anesthetic in arterial blood (Part). This is because arterial blood represents a mixture of shunted mixed venous blood combined with blood that has equilibrated with alveolar gases. Because such shunts also reduce transcapillary gas exchange in the lung and slow anesthetic uptake, right-to-left shunting sustains Pcirc, an effect that is more pronounced for highly soluble drugs compared with insoluble anesthetics. Thus shunt reduces the ratio of Part:Palv more for insoluble anesthetics, such as N2O

Answer 4

When the anesthetic represents a large fraction of the inhaled gas mixture, its rapid uptake results in a smaller relative alveolar anesthetic concentration drop, because the volume of alveolar gas also decreases. This is known as the concentration effect. The second gas effect is a consequence of the concentration effect. Ex.: After an initial inspiratory breath, alveoli are filled with the gas mixture in the circuit (66% N2O, 33% O2, 1% Isoflurane) at their normal end-inspiratory volume. After half of the N2O and isoflurane are absorbed into pulmonary blood, the alveolar gas volume is reduced by 33.5%. At this point, the volume of N2O equals the volume of O2 and the gas mixture is 49.6% N2O, 49.6% O2, 0.8% isoflurane. Inflow of additional inspired gas mixture returns alveolar volume to its original value, resulting in a gas mixture of 55.1% N2O, 44.1% O2, 0.8% isoflurane. The alveolar partial pressure of N2O falls much less than the fractional uptake (the concentration effect). In addition, the partial pressure of O2 increases relative to the inspired gas O2 content, and the partial pressure of isoflurane is sustained close to the inspired value, increasing its rate of uptake (the second gas effect)

Answer 5

1) The vessel-rich group (VRG): the heart, brain, lungs, spinal cord, liver, and kidney. Together, these organs compose approximately 10% of the adult human body mass; however, they receive approximately 70% of cardiac output under normal resting conditions. As a result, time constants for anesthetic equili- bration between blood and these organs are typically only a few minutes 2) skeletal muscle: Muscle composes approximately 40% of body mass in a healthy adult, making muscle the largest single compartment based on weight. Moreover, most inhaled anesthetics partition into muscle more than into brain, resulting in an increased effective volume for anesthetic uptake into this compartment. At rest, muscle receives about 10% to 15% of cardiac output (20 mL/kg/min), but this value can increase dramatically during exercise, stress, fever, or other states associated with high cardiac output. Taken together, these factors generally result in slow equilibration between anesthetic in blood and muscle, with typical time constants of hours. 3) fat: in a healthy adult composes less than 25% of body mass and receives approximately 10% of cardiac output. Potent VAs partition avidly into fat; therefore, fat represents the largest effective volume for uptake of these drugs. The extremely large effective volume coupled with low blood flow results in very slow equilibration of anesthetics between blood and fat, with time constants approaching days 4) vessel poor tissues: skin, cortical bone, and connective tissue

Answer 6

In pediatric patients, the balance of cardiac output to various tissue beds differs from that in adults. Thus, although cardiac output per kilogram body weight is larger in children than in adults, anesthetic induction in young children is more rapid than in adults, because a disproportionate amount of perfusion goes to the vessel rich organs, such as the brain.

Answer 7

The alveolar anesthetic concentration preventing percep- tive awareness in 50% of subjects. MAC-awake for potent VAs is typically 0.34 × MAC-immobility, whereas MAC- awake for N2O is approximately 0.7 × MAC-immobility

Answer 8

local blood flow and the surface to volume ratio of the space surface/volume ratios relative flow of blood containing dissolved N2O

Answer 9

F increased cardiac output slows clearance, because more gas-exchange volumes are required to remove anesthetic from the larger blood flow

Answer 10

Diffusion hypoxia is another sequelae of rapid outgassing from the tissues of patients anesthetized with N2O. During the initial 5 to 10 minutes after discontinuation of anesthesia, the flow of N2O from blood into the alveoli can be several liters per minute, resulting in dilution of alveolar oxygen. Another effect of rapid outgassing is reduction of alveolar PCO2, which may also reduce respiratory drive. If the patient does not receive supplemental oxygen during this period, then the combined effects of respiratory depression from anesthesia, reduced alveolar PCO2, and reduced alveolar PO2 can result in hypoventilation and oxyhemoglobin desaturation

Answer 11

This outcome is avoided by routinely providing supplemental O2 for the first 5 to 10 minutes of recovery, together with vigilant attention to respiration and oxygenation

Answer 12

Extent of tissue metabolism (%) Halothane 25 Methoxyflurane 70 Enflurane 2.5 isoflurane 0.2 Desflurane 0.02 Sevofluarane 5

Answer 13

Halotane +++++ Enflurane ++ Isoflurane + Desflurane +

Answer 14

CYP2E1 ethanol and isoniazid disulfiram

Answer 15

1) Subclinical hepatotoxicity: occurs in 20% of adults who receive halothane. It is characterized by mild postoperative elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), but is reversible and innocuous. Anaerobic halothane reduction by CYP2A6 to a 2-chloro-1,1,1-trifluoroethyl radicalis thought to mediate this mild hepatic injury. 2) Fulminant form of hepatotoxicity, commonly known as halothane hepatitis: Is characterized by elevated ALT, AST, bilirubin, and alkaline phosphatase levels, and massive hepatic necrosis following the administration of halothane. Halothane hepatitis is rare (1 in 5000-35,000 administrations in adults) but is fatal in between 50% to 75% of cases. Because of the potential for fatal hepatitis, halothane is no longer used in adult patients in most countries. Halothane hepatitis is caused by a hypersensitivity reaction associated with oxidative metabolism of halothane. The highly reactive trifluoroacetyl chloride metabolite of halothane oxidation can react with nearby liver proteins. In most patients who developed hepatic necrosis after halothane anesthesia, antibodies against trifluoro-acetyl-modified proteins were detected, suggesting that the hepatic damage is linked to an immune response against the modified protein, which acts as a neoantigen.

Answer 16

hexafluoroisopropanol and inorganic F− Hexafluoroisopropanol

Answer 17

polyuric renal insufficiency

Answer 18

50 μM (microMol/liter)

Answer 19

(1) their lower tissue solubilities, particularly in kidney, resulting in lower intrarenal fluoride production; (2) lower overall degrees of biotransformation; (3) more rapid respiratory clearance from the body

Answer 20

sodium hydroxide (NaOH) and potassium hydroxide (KOH) ------ a haloalkene [fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether], known as compound A

Answer 21

proximal tubular necrosis

Answer 22

5 CO, trifluoromethane (CF3H), and hydrogen fluoride (HF)

Answer 23

KOH > NaOH>>Ba(OH)2, Ca(OH)2

Answer 24

desflurane enflurane isoflurane Sevoflurane, methoxyflurane, and halothane

Answer 25

N2O is unique among anesthetics in irreversibly inhibiting cobalamins (vitamin B12) by oxidizing the Cobalt (I) ligand. Cobalamins are ingested or produced by bacteria in the gut and are critical cofactors together with 5-methyltetrahy-drofolate in the activity of methionine synthase. Methionine synthase catalyzes methylation of homocysteine to methionine, while demethylating 5-methlytetra-hydrofolate to tetrahydrofolate. Methionine, converted to S-adenosylmethionine, is the major substrate for methylation in biochemical pathways involved in the synthesis of DNA, RNA, myelin, and catecholamines. Chronic vitamin B12 deficiency (as in pernicious anemia) results in hematologic and neurologic dysfunction. Long-term N2O exposure, typically among individuals who frequently inhale it as a recreational drug, can also cause megaloblastic anemia, myelopathy (subacute combined degeneration), neuropathy, and encephalopathy, sometimes presenting as psychosis

Answer 26

pernicious anemia or other gastrointestinal malabsorption syndromes, extremes of age, alcoholism, malnutrition, a strict vegetarian diet, and inborn deficiencies in cobalamin or tetrahydrofolate metabolism. Inhibitors of folate metabolism, such as methotrexate, may also enhance sensitivity to N2O toxicity

Answer 27

homocysteine

Answer 28

It is most comparable to N2O, but superior in a number of ways. Xenon is present as a minor constituent of air (50 parts per billion), and is isolated by distillation of liquefied air, along with liquefied nitrogen and oxygen. Xenon is entirely unreactive in the biosphere and is the only inhaled anesthetic that is not an environmental pollutant, although its distillation from air uses considerable energy and thus creates CO2 and other pollutants as byproducts. It is odorless, tasteless, nonflammable, and has a limitless shelf-life. Its solubility in blood (λb/g = 0.14) and body tissues is lower than that of any other inhaled anesthetic, including N2O. As a result, it has extraordinarily rapid onset and respiratory clearance, with emergence times 2- to 3-fold faster when it replaces N2O in clinical settings. It undergoes no biotransformation or reactions with CO2 absorbents or ultraviolet light. Moreover, xenon has favorable pharmaco-dynamic effects in comparison to most inhaled anesthetics. It produces minimal cardiovascular depression and is not arrhythmogenic. As with N2O, xenon has analgesic activity and reduces intraoperative opioid requirements. It does not trigger malignant hyperthermia or produce any known toxicity. In fact, xenon has been shown to have cardioprotective and neuroprotective activities in preclinical models. Clinical trials in adult cardiac surgery patients, partial nephrectomy patients, and comatose survivors of cardiac arrest have demonstrated that xenon reduces pressor requirements and modestly reduces the extent of organ damage, relative to other anesthetics. However, in these clinical settings and in others, xenon does not improve neurocognitive function or survival

Answer 29

It’s expensive: more than $15/L in the gas form, xenon is greater than 100-fold more expensive than N2O and far more expensive per patient than either desflurane or sevoflurane, which are currently the most expensive VAs. Xenon has a MAC-immobility of 0.61 atm, and even with a strict closed- circuit technique, greater than 10 L are needed to anesthetize a typical patient. To perform closed circuit anesthesia with xenon-oxygen also requires lengthy preanesthetic denitrogenation to prevent N2 from accumulating in the rebreathing circuit. Transitioning from 100% oxygen during denitrogenation to closed circuit xenon-oxygen anesthesia is another slow process because xenon is added to the circuit as oxygen is metabolized in the patient at 200 to 250 mL/min. High-flow xenon is otherwise necessary to make this transition short Xenon gas has a much higher density (5.9 g/L) than either N2O (1.9 g/L) or air (1.2 g/L), resulting in increased flow resistance and work of breathing. Thus it may be a poor choice for patients with compromised respiratory function. As with N2O, high xenon partial pressures needed for anesthesia cause expansion of trapped air spaces and vascular air emboli. Compared with propofol infusion or sevoflurane inhalation, xenon anesthesia results in a higher incidence of nausea and vomiting

Answer 30

sensory afferents in the nucleus of the solitary tract (NTS), projecting to vagal preganglionic neurons (VPN)

Answer 31

dilation decreases in cytoplasmic ionized calcium concentration and/or a reduction in calcium sensitivity of airway smooth muscle pulmonary airway resistance

Answer 32

desflurane

Answer 33

pharyngeal airway collapse

Answer 34

F In healthy children, sevoflurane slightly decreased airway resistance, but desflurane had the opposite effect, presumably via reduced airway size. Children with documented airway susceptibility, such as those with asthma or a recent upper respiratory tract infection, exhibit significant increases in airway resistance. In these pediatric patients, desflurane should be avoided

Answer 35

enhancement of IP3 and ryanodine-receptor channel activities

Answer 36

F Halothane, sevoflurane, and, minimally, isoflurane exert direct effects on muscarinic receptor–mediated contraction of isolated airway smooth muscle. The inhibitory effects of volatile agents on the biochemical coupling between the M3 muscarinic receptor and the Gαq heterotrimeric G protein is completely REVERSIBLE with time

Answer 37

brainstem preganglionic cholinergic nerves in the lung

Answer 38

Volatile anesthetics and nitrous oxide diminish the rates of mucous clearance by decreasing ciliary beat frequency, disrupting metachronism, and altering the physical characteristics or quantity of mucus

Answer 39

sevoflurane

Answer 40

Although inhibition of hypoxic pulmonary vasoconstriction by volatile anesthetic is an overall small effect, it can contribute to worsening of hypoxemia in patients with underlying pulmonary disease

Answer 41

1 1 tidal volume increases xenon reduction

Answer 42

Volatile anesthetics impair peripheral chemoreceptor responses to hypoxia and hypercarbia in a dose dependent manner. In the presence of volatile anesthetic concentrations of 1 MAC or higher, breathing in humans is entirely dependent on the automatic control from the pontomedullary respiratory center and afferent excitatory inputs from the central chemoreceptors. These anesthetic concentrations lead to a complete depression of the peripheral chemoreflex loop with further respiratory depression rather than stimulation in response to hypoxia. Even very low concentrations of the agent (0.1 MAC of isoflurane and sevoflurane) depress the peripheral chemoreflex loop, without affecting the central chemoreflex loop

Answer 43

F Volatile anesthetics, such as halothane, depress various respiratory muscles differently. The diaphragm, as the main inspiratory muscle, is unique in that regard because it is relatively spared from the respiratory depression by volatile anesthetics

Answer 44

1-1.3 paradoxically enhance and prolong the duration of

Answer 45

Desflurane and isoflurane

Answer 46

F Xenon is a SYMPATHETIC stimulant and better maintains systolic, diastolic, and mean arterial blood pressures and reduces heart rate

Inhaled Anesthetics Flashcards

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