Chapter 8: Inhalation Anesthesia and Neuromuscular Blocking Agents

8. When is administration of N2O sedation contraindicated in an asthmatic patient?

There are no absolute contraindications for the use of N2O sedation in asthmatic patients. Because anxiety is a stimulus for an asthmatic attack, N2O sedation is actually beneficial for these patients.

3. How long can oxygen at 2 L/min be delivered from an E cylinder with a reading of 500 psi?

A full E cylinder of oxygen (O2) contains approximately 600 L at a pressure of 2000 psi. At 2 L/min, a full E cylinder will deliver O2 for approximately 300 minutes, or 5 hours. A reading of 500 psi will therefore give you approximately 1 hour and 15 minutes of O2.

17. What is partition coefficient? How can it influence the speed of induction?

A partition coefficient is defined as a distribution ratio of a volatile anesthetic as it distributes itself between two phases at equilibrium when the temperature, pressure, and volume are the same. A blood-to-gas coefficient therefore describes the distribution of anesthetic between blood and gas. High blood solubility requires a greater concentration of inhaled anesthetic to be dissolved in the blood before equilibrium can occur. The blood acts as an inactive reservoir that prevents the anesthetic from reaching the site of action, thereby slowing induction. Gases with low solubility in blood and adipose equilibrate more rapidly. Nitrous oxide has very low solubility and therefore achieves equilibration most rapidly. This explains why nitrous oxide has the fastest onset among inhalation agents. Relative onset of effect is directly proportional to solubility, when all other factors are equal (e.g., alveolar concentration, cardiac output). The lower solubility of sevoflurane compared with isoflurane explains why sevoflurane is a more rapid induction agent.

7. Can inhalational anesthetics be administered to patients with chronic obstructive pulmonary disease (COPD)?

Administration of volatile anesthetics (desflurane, isoflurane, and sevoflurane) is safe for patients with COPD (asthmatic bronchitis, emphysema, and chronic bronchitis). Volatile anesthetics are potent bronchodilators and, therefore, beneficial to patients with COPD. N2O, however, should be used cautiously. Carbon dioxide (CO2) is a respiratory stimulus for patients with normal respiratory physiology. Patients with COPD retain larger amounts of CO2 in their lungs and, over time, lose their respiratory drive. COPD patients thus develop a hypoxic drive. The potential for the hypoxic drive to cease with the severe chronic patient exists when O2 is >21% room air (i.e., N2O-O2 at 70/30%). Patients with COPD have increased incidence of pulmonary bullae or blebs (combined alveoli). Because of N2O's low blood solubility, it can increase the volume and pressure of these lung defects, which could create an increased risk of barotrauma and pneumothorax. Duration of exposure and concentration of N2O must be considered. During sedation with an open airway, keep patients breathing spontaneously, and do not take away their respiratory drive. O2 supplementation should be used with caution in patients with severe COPD. Supplemental O2 via nasal cannula delivers low FiO2, which should not affect hypoxic drive. It is recommended that oxygen concentrations not exceed an FiO2 of 40. Remember, 4 L through a nasal cannula equals 36% O2. Nasal cannula (3 to 6 L/min): FiO2 = 20 + 4 × L/min Face mask with reservoir (6 to 10 L/min): FiO2 = 10 × L/min Asthma or reactive airways may occur at any age and could easily be encountered in the office. Patients with debilitating emphysema and chronic bronchitis are often chronically ill and are not seen commonly in an office setting. They may, however, be encountered in nursing homes and hospitals.

19. What is diffusion hypoxia?

Although its existence has been questioned, diffusion hypoxia is postulated to occur when the administration of N2O has been discontinued with the spontaneous breathing of room air. The theory holds that N2O's low blood solubility allows it to leave the blood rapidly and enter the alveoli. Excessive N2O in the alveoli dilutes the O2 and makes the patient hypoxic. This phenomenon has been refuted by many studies. Nonetheless, because of side effects such as headaches, nausea, vomiting, and lethargy, administering O2 for 3 to 5 minutes following N2O use is recommended.

18. Which volatile anesthetic has the quickest wake-up potential after a long (>5 hours) surgical procedure?

Anesthetics take time to be distributed from the blood to the tissues (e.g., muscle, fat). As the length of time of a surgery increases and tissues become increasingly saturated with an anesthetic, wakeup times increase. The fat-to-blood partition coefficient for desflurane is the lowest for all volatile anesthetics, and it provides the quickest wake-up. A common misconception is that sevoflurane has a quick wake-up time because it has a quick onset. For short surgeries this is true, because tissue saturation has not had time to occur. For long surgeries, however, sevoflurane does not provide a quick wake-up.

36. How long does it take before changes in oxygen saturation are reflected in pulse oximeter readings?

Approximately 20 seconds. It takes time for O2 delivered to the lung to influence oxygenation at the fingertip. Pulse oximeter signals are also averaged over different periods. This is mainly to reduce spurious pulse oximeter readings, such as those caused by patient movement. The trade-off is that true reductions in pulse oximeter readings are delayed (a patient desaturating faster than the pulse oximeter indicates). Similarly, once adequate delivery of oxygen is restored, there will be a delay in recovery of the pulse oximeter readings. The period of signal averaging can often be changed in commonly used pulse oximeters.

25. What is the breakdown and elimination process of nondepolarizing NMBs?

Atracurium and cisatracurium are unique in that they undergo spontaneous breakdown at physiologic temperatures and pH (Hoffmann elimination), as well as ester hydrolysis. These properties allow safe delivery in patients with compromised hepatic or renal function Aminosteroid relaxants (pancuronium, vecuronium, pipecuronium, and rocuronium) are deacetylated in the liver, and their action may be prolonged in the presence of hepatic dysfunction. Vecuronium and rocuronium also have significant biliary excretion, and their action may be prolonged with extrahepatic biliary obstruction. Relaxants with significant renal excretion include tubocurarine, metocurine, doxacurium, pancuronium, and pipecuronium.

6. Should a patient with an upper respiratory infection (URI) be given N2O via a nasal hood?

Because a patient with a URI has nasal blockage, the delivery of the N2O is limited and the potential for leakage of N2O around the hood is more likely. In addition, patients with a URI are also more likely to have associated middle ear and sinus infections. Therefore the use of N2O with patients with URI is unwise.

13. Why are additive values of MAC for inhalational anesthetics beneficial?

Additive values are beneficial when a decrease in volatile anesthetics is desired. MAC values are additive; therefore the simultaneous administration of N2O with a volatile anesthetic will decrease the MAC of both agents. For example, using 0.5 MAC N2O (approximately 50%) with 0.5 MAC isoflurane (approximately 0.6%) results in a MAC of 1.0. The only inhalational anesthetics that would be administered simultaneously would be a volatile anesthetic (desflurane, halothane, isoflurane, and sevoflurane) and N2O. Fail-safe mechanisms exist on anesthetic machines to prevent the simultaneous administration of two volatile agents. N2O has a MAC >100% and therefore is not used as a sole anesthetic agent, because a minimum of 21% O2 is required at 1 atm. Typically, N2O concentrations of 20% to 70% are used.

21. What are neuromuscular blocking agents (NMBs)?

NMBs, commonly called muscle relaxants, are drugs that interrupt transmission at the neuromuscular junction. These drugs provide skeletal muscle relaxation and, consequently, can be used to facilitate tracheal intubation, assist with mechanical ventilation, and optimize surgical conditions. Occasionally, they may be used to reduce the metabolic demands of breathing; in the management of status epilepticus (although they do not diminish central nervous system activity), status asthmaticus, or tetanus; and to facilitate the treatment of raised intracranial pressure. These drugs inhibit the function of all skeletal muscle, including the diaphragm, and must be administered only by personnel skilled in airway management. NMBs should never be given without preparation to maintain the airway and ventilation. The concomitant use of sedative-hypnotic or amnestic drugs is indicated, because NMBs alone achieve complete paralysis while allowing the patient complete awareness.

32. Are clinicians accurate in determining arterial desaturation by "visual oximetry" (how red is the blood)?

No. Pulse oximetry should be regarded as the fifth vital sign.

29. How do we make muscle relaxants work faster if we need to secure the airway sooner?

By overwhelming the sites of action (receptors in the neuromuscular junction), one can provide a competitive advantage for the blocking drug over acetylcholine. This is exactly what is done with the standard intubating dose of a nondepolarizing relaxant. The usual intubating dose is approximately three times the ED95 (the dose expected to show 95% reduction in twitch height on electrical stimulation). For relaxants with cardiovascular stability, further increases in initial dose can provide some decrease in onset time without producing side effects. However, with the exception of the nondepolarizing NMB rocuronium, it is very difficult to decrease the onset time to that of SCh. For drugs with side effects such as histamine release, increases in dose usually increase side effects as well. Another method of decreasing onset time is the priming technique. By giving one-third of the ED95 at 3 minutes before the intubating dose, one can decrease onset time by as much as 1 minute. However, sensitivity to the paralyzing effects of these agents varies greatly among patients, and some patients may become totally paralyzed with a priming dose. Other patients may experience distressing diplopia, dysphagia, or the sensation of not being able to take a deep breath. For this reason, the practice of administering "priming" doses of relaxants is discouraged by many anesthesiologists. Once relaxants are administered at any dose, the anesthetist should be in the position to assist ventilation

11. What factors affect MAC?

Factors that decrease MAC: Higher altitudes (Ø barometric pressure) Pregnancy Hypothermia Hyponatremia Alcohol (acute use) Barbiturates Calcium channel blockers Opioids Factors that increase MAC: Increased central neurotransmitter levels (MAOIs, Cocaine, ephedrine, levodopa) Hypothermia Alcohol (chronic use) Hypernatremia

24. What are the indications for using SCh?

In clinical situations in which the patient has a full stomach and is at risk for regurgitation and aspiration when anesthetized, rapid paralysis and airway control are priorities. Such situations include diabetes mellitus, hiatal hernia, obesity, pregnancy, severe pain, and trauma. SCh provides the most rapid onset of any NMB currently available. In addition, the duration of blockade induced by SCh is only 5 to 10 minutes. Respiratory muscle function returns quickly should the patient prove difficult to intubate. SCh is indicated for the treatment of laryngospasm unresponsive to positive pressure ventilation.

12. How can MAC values be used to gauge awareness during surgery?

Intraoperative patient awareness is a concern with all patients undergoing a deep sedation or general anesthesia. Volatile anesthetics have amnestic properties at an adequate MAC. Intravenous medications are often used in conjunction with volatile anesthetics, which often cause a decrease in MAC. This decreased MAC may prevent an amnestic state. Although specific concentrations of volatile agents have not been established for the elimination of intraoperative recall, clinical studies show that awareness is eliminated between 0.4 and 0.6 MAC for isoflurane. Attaining a MAC of 0.8 has been recommended to guarantee unconsciousness and, therefore, lack of awareness. Awareness precautions need to be taken with certain anesthetic techniques. An anesthetist may be tempted to decrease the concentration of a volatile anesthetic when a paralytic has been used because surgical stimulation has been eliminated. The addition of midazolam, an amnestic benzodiazepine, can be used in situations where MAC has been reduced below 0.8. MAC is often reduced in patients who develop intraoperative hypotension because of volatile inhalational vasodilating properties. Vasopressors, such as ephedrine and phenylephrine, may be necessary to maintain a MAC of 0.8 when additional amnestic medications are not being used.

27. NMB reversal agents cause an increase in available acetylcholine. Is this a problem?

It is important to remember that the muscarinic effects of these drugs at cholinergic receptors in the heart must be blocked by atropine or glycopyrrolate to prevent bradycardia. The degree of bradycardia may be significant. Even asystole has been noted. The most common doses used for this purpose are 0.01 mg/kg of atropine and 0.005 to 0.015 mg/kg of glycopyrrolate. To prevent bradycardias associated with the anticholinesterases, it is important to administer an anticholinergic with a similar onset of action. Atropine is administered with edrophonium and glycopyrrolate with neostigmine.

26. Is it possible to reverse the effects of the nondepolarizing NMBs?

Just as competition at the receptor sites of the neuromuscular junction allows the relaxant to overcome the effects of acetylcholine, medications that increase the amount of acetylcholine at the neuromuscular junction facilitate reversal of relaxation. Reversal agents are acetylcholinesterase inhibitors and include neostigmine, pyridostigmine, and edrophonium. These drugs inhibit the enzyme that breaks down acetylcholine, making more of this neurotransmitter available at each receptor. Physostigmine, another acetylcholinesterase inhibitor, crosses the blood-brain barrier and is not used for reversal of muscle relaxants. Pyridostigmine is used in the management of patients with myasthenia gravis. The acetylcholinesterase inhibitors possess positively charged quaternary ammonium groups, are water-soluble, and are renally excreted.

10. What is minimal alveolar concentration (MAC)?

MAC is the concentration of an inhaled anesthetic at 1 atm that prevents skeletal muscle movement response to a painful stimulus (e.g., surgical skin incision) in 50% of patients (Table 8-1). A MAC of 1.3 prevents skeletal movement in approximately 95% of individuals undergoing surgery. The potency of anesthetic gases can be compared using MAC

20. What are the concerns to administration of N2O sedation to an obstetric patient?

N2O crosses the placenta and therefore has the potential to cause teratogenic effects to the fetus. The greatest potential for problems exists during the first trimester when organs are forming. Significant exposure during the first 6 weeks can inhibit DNA synthesis. Consequently, female surgeons and staff who are not aware that they are pregnant may be at greater risk than patients. Recent research has refuted the claim that N2O is dangerous to the fetus. Although N2O has been used safely for years in obstetrics, it would be wise to obtain a medical consult before its administration in pregnant women who are in their second or third trimesters. Even if N2O sedation is approved by the patient's obstetrician, it should be used only for short procedures, and no more than 50% N2O should be administered

5. Why is N2O use contraindicated in patients with conditions involving closed gas spaces?

N2O has a low blood-to-gas partition coefficient (0.46) and therefore low solubility. It can leave the blood and enter air-filled cavities 34 times more quickly than nitrogen can leave the cavity to enter the blood. The use of N2O can increase the expansion of compliant cavities, such as a pneumothorax, bowel gas in a bowel obstruction, and an air embolism. An increase in pressure will occur when N2O is used with noncompliant cavities, such as the middle ear or sinuses. The oral and maxillofacial surgeon needs to be cautious when treating the recent trauma patient (e.g., motor vehicle accident victim). An asymptomatic, undiagnosed closed pneumothorax can double in size in 10 minutes after the administration of 70% N2O. Nitrous oxide-oxygen sedation should be postponed in patients with gastrointestinal obstructions, middle ear disturbances, and, possibly, sinus infections

4. How long can nitrous oxide (N2O) at 2 L/min be delivered from an E cylinder that reads 750 psi?

N2O has a pressure of 750 psi, and approximately 1600 L of N2O is contained in an E cylinder. N2O is a compressed liquid and not a compressed gas like O2. A compressed liquid does not show a linear correlation between volume and pressure as does a compressed gas. N2O pressure will remain at 750 psi until all the liquid has been vaporized. Therefore an estimated time cannot be determined

30. What is plasma cholinesterase (pseudocholinesterase)?

Plasma cholinesterase is produced in the liver and metabolizes SCh as well as ester local anesthetics. A reduced quantity of plasma cholinesterase may be the result of liver disease, pregnancy, malignancies, malnutrition, collagen vascular disease, and hypothyroidism. This reduction could result in a prolonged duration of blockade with SCh.

34. What is the relationship between oxyhemoglobin saturation (SaO2) and partial pressure of oxygen (PaO2)?

Proper interpretation of pulse oximetry requires recall of the oxyhemoglobin dissociation curve A rightward shift (decreased hemoglobin affinity for oxygen) facilitates oxygen unloading at the tissue level. Increasing temperature, increasing PaCO2, increasing 2,3-diphosphoglycerate, and increasing hydrogen ion concentration—all "increases"—shift the curve to the right. When the PaO2 is >100 mm Hg, however, the curve is virtually flat. Consequently, a large drop in PaO2 (e.g., from 200 to 100 mm Hg) may occur with no discernible change in SaO2

33. Can any other environmental or clinical conditions result in inaccurate pulse oximetry values?

Reliability depends on a strong arterial pulse plus good light transmission. Inaccuracy results with hypotension (mean arterial pressure <50 mm Hg), hypothermia (<35° C), vascular disease (poor peripheral perfusion), and vasopressor therapy (vasoconstriction). Bright lights, intravenous dyes, nail polish, and excessive motion each may produce bad information.

23. What is the mechanism of action of SCh?

SCh is the only depolarizing agent to be used widely in clinical anesthetic practice. The depolarizing agent mimics the action of acetylcholine. However, because SCh is hydrolyzed by plasma cholinesterase (pseudocholinesterase), which is present only in the plasma and not at the neuromuscular junction, the length of blockade is directly related to the rate of diffusion of SCh away from the neuromuscular junction. Consequently, the resultant depolarization is prolonged when compared with acetylcholine. Depolarization gradually diminishes, but relaxation persists as long as SCh is present at the postsynaptic receptor.

28. The heart is a muscle. Do muscle relaxants decrease contraction of the myocardium?

The NMBs have their primary effect at nicotinic cholinergic receptor sites. The myocardium is a muscle with nerve transmission accomplished via adrenergic receptors using norepinephrine as the transmitter. Consequently, muscle relaxants have no effect on cardiac contractility. NMBs also have no effect on smooth muscle.

31. What is the importance of a dibucaine number?

The dibucaine number is used to identify individuals at risk for prolonged paralysis following administration of SCh. Dibucaine number is the percent of pseudocholinesterase (PChE) enzyme activity that is inhibited by dibucaine. Dibucaine inhibits normal plasma cholinesterase by 80%, whereas atypical plasma cholinesterase is inhibited by only 20%. A patient with normal SCh metabolism will have a dibucaine number of 80. If a patient has a dibucaine number of 40 to 60, then that patient is heterozygous for this atypical plasma cholinesterase and will have a moderately prolonged block with SCh. If a patient has a dibucaine number of 20, the patient is homozygous for atypical plasma cholinesterase and will have a very prolonged block with SCh. It is important to remember that a dibucaine number is a qualitative, and not quantitative, measurement. Consequently, a patient may have a dibucaine number of 80 but have prolonged blockade with SCh related to decreased levels of normal plasma cholinesterase.

15. What are the hemodynamic considerations of the combined use of a volatile anesthetic and the intravenous anesthetic propofol?

The inhalational anesthetics desflurane, isoflurane, and sevoflurane and the intravenous agent propofol are potent vasodilators. Additive effects causing hypotension from a decrease in systemic vascular resistance occur with simultaneous administration of these two anesthetic groups. Combining these agents should be done cautiously in elderly patients and patients taking hypertensive medications. Preoperative blood pressures are extremely important. Selection of an alternative intravenous anesthetic agent may be indicated. If propofol is used along with a volatile anesthetic, then vasopressors (e.g., ephedrine, phenylephrine) should be prepared and made readily available.

2. What is the mechanism of action of inhalational anesthetics?

The mechanism of action of volatile anesthetics, along with their molecular and cellular actions, remains elusive. Volatile anesthetics act on synaptic transmission in the central nervous system but proof remains a matter of debate. Inhalational anesthetics act in the central nervous system. They disrupt synaptic transmission, interfere with the release of neurotransmitters from presynaptic nerve terminals, alter reuptake of neurotransmitters, change binding of neurotransmitters to the postsynaptic receptor sites, and influence the ionic conductance. The Meyer-Overton theory postulates that anesthesia occurs when a sufficient number of inhalation anesthetic molecules dissolve in the lipid cell membrane. However, the Meyer-Overton theory does not describe why anesthesia occurs. The Critical Volume Hypothesis believes that the absorption of anesthetic molecules could expand the volume of a hydrophobic region within the cell membrane and subsequently distort channels necessary for sodium ion flux and the development of action potentials necessary for synaptic transmission. The protein interaction theory hypothesizes that anesthetics bind to specific proteins that affect ion flux during membrane excitation, resulting in either potentiation of inhibitory neurotransmitters (e.g., GABA, glycine) or inhibition of excitatory neurotransmitters (e.g., glutamate NMDA receptors). This is supported by a steep dose response curve.

22. How are NMBs classified?

These drugs are classified into two groups according to their actions at the neuromuscular junction: 1. Depolarizing NMB (succinylcholine [SCh]): SCh mimics the action of acetylcholine by depolarizing the postsynaptic membrane at the neuromuscular junction. The postsynaptic receptor is occupied/ depolarized and remains refractory to further stimulation. 2. Nondepolarizing NMBs: These agents act by competitive blockade of the postsynaptic membrane, so that acetylcholine is blocked from the receptors and cannot have a depolarizing effect.

9. What is the second gas effect?

This occurs when one gas speeds the rate of increase of the alveolar partial pressure of a second gas. This effect is normally associated with an inhalational induction involving a large volume of N2O and a volatile anesthetic. N2O's low blood solubility allows it to be absorbed quickly by the alveoli, thus causing an increase in the alveolar concentration of the concomitantly administered volatile anesthetic. In theory, a high concentration of one gas (e.g., 70% N2O) could speed the induction of a second gas (e.g., sevoflurane). Inhalational inductions are normally used in energetic pediatric patients. Obtaining intravenous access in children who cannot sit still is difficult, and a quick induction is desirable. The speed of induction with sevoflurane should be increased when it is used concurrently with 70% N2O.

1. What inhalational anesthetics are currently available, and how are they delivered in clinical use?

Three volatile liquids (desflurane, isoflurane, and sevoflurane) and one gas (nitrous oxide) are used clinically. The volatile liquids require a vaporizer for inhalational administration. Additionally, the desflurane vaporizer has a heating component to allow delivery at room temperature. Inhalational anesthetic delivery systems exist for the delivery of one or multiple agents. These delivery systems have mandatory scavenging and fail-safe mechanisms to optimize safety. Inhalation agents are administered in hospital operating rooms and outpatient environments, such as surgery centers and dental offices.

14. What are the hemodynamic effects of volatile anesthetics?

Volatile anesthetics depress the cardiovascular system, which results in a reduced mean arterial pressure. Desflurane, isoflurane, and sevoflurane cause primarily a decrease in systemic vascular resistance, which is reflected by a reduced blood pressure

16. What are the respiratory effects of volatile anesthetics?

Volatile anesthetics will cause a dose-dependent decrease in ventilation. Volatile anesthetics cause a decrease in tidal volume (TV) with a compensatory increase in respiratory rate (RR) but a net decrease in minute ventilation (mV). Volatile anesthetics: net ↓mV = ↑RR × ↓TV This decreased minute ventilation causes an increase in CO2. An increase in CO2 stimulates the respiratory drive in the unanesthetized patient. Inhalational anesthetics, however, shift the CO2 response curve to the right and lessen the ventilatory response to hypercarbia and hypoxia