General Anesthetics DSA

Question 1

List the general inhaled anesthetics

Answer 1

Desflurane
Enflurane
Halothane
Isoflurane
Nitrous oxide
Sevoflurane

Question 2

List the general intravenous anesthetics

Answer 2

Dexmedetomidine
Diazepam (Valium)
Etomidate
Fentanyl
Fospropofol
Ketamine
Lorazepam (Ativan)
Methohexital
Midazolam (Versed)
Propofol (Diprivan)
Thiopental

Question 3

The anesthetic state produced by general anesthetics is a collection of component changes in behavior or perception that include?

Which agent can be used alone to achieve all five?

Answer 3

Unconsciousness
Amnesia
Analgesia
Attenuation of autonomic reflexes to noxious stimulation
Immobility in response to noxious stimulation (skeletal muscle relaxation)

None

Question 4

Describe the modern practice of anesthesiology

Answer 4

Relies on the use of combinations of intravenous and inhaled drugs (balanced anesthesia) to take advantage of favorable properties of each agent while minimizing their adverse effects

Utilizes sedatives, neuromuscular blocking agents, local anesthetics, and analgesics in addition to general anesthetics to induce anesthesia

Question 5

Describe monitored anesthesia care

Answer 5

Sedation-based anesthetic techniques
Utilized for diagnostic and/or minor therapeutic surgical procedures
Performed without general anesthesia
Typically involves the use of midazolam for a premedication (to provide anxiolysis, amnesia, and mild sedation) followed by a titrated propofol infusion (to provide moderate to deep levels of sedation)
Potent opioid analgesic or ketamine may be added to minimize the discomfort associated with injection of local anesthesia and surgical manipulations

Question 6

Describe conscious sedation

Answer 6

Used primarily by nonanesthesiologists (dentists)
The patient retains ability to maintain a patent airway and is responsive to verbal commands
Benzodiazepines and opioid analgesics (fentanyl) in conscious sedation protocols have the advantage of being reversible by specific receptor antagonist drugs (flumazenil and naloxine)

Question 7

Describe deep sedation

Answer 7

Similar to light state of general (intravenous) anesthesia involving decreased consciousness from which the patient is not easily aroused
Transition from deep sedation to general anesthesia is fluid and sometimes difficult to clearly determine where transition is
Accompanied by a loss of protective reflexes, an inability to maintain a patent airway, and lack of verbal responsiveness to surgical stimuli
Intravenous agents used in deep sedation protocols mainly include sedative-hypnotics propofol and midazolam, sometimes in combination with potent opioid analgesics or ketamine, depending on level of pain associated with surgery or procedure

Question 8

Dsecribe intensive care unit (ICU) sedation

Answer 8

Patients who require mechanical ventilation for prolonged periods
Sedative-hypnotic drugs and low doses of IV anesthetics

Question 9

Describe mechanism of general anesthetic action

Answer 9

Anesthetics affect neurons at various cellular locations, but the primary focus has been on synapse
Presynaptic action may alter release of neurotransmitters, whereas a postsynaptic effect may change frequency or amplitude of impulses exiting synapse
At organ level, effect of anesthetics may result from strengthening inhibition or from diminishing excitation within CNS (studies on isolated spinal cord tissue have shown that excitatory transmission is impaired more strongly by anesthetics than inhibitor effects are potentiated)
Chloride channels (gamma-aminobutyric acid-A (GABAa) and glycine receptors) and potassium channels (K2p, possibly Kv, and Katp channels) remain primary inhibitory ion channels considered legitimate candidates of anesthetic action
Excitatory ion channel targets include those activated by acetylcholine (nAChRs and mAChRs) by excitatory amino acids (amino-3-hydroxy-5-methyl-4-isoxazol-proprionic acid (AMPA), kainite, and N-methyl-D-aspartate (NMDA) receptors), or by serotonin (5-HT2 and 5-HT3 receptors)

Question 10

Describe volatile anesthetics

Answer 10

Halothane, enflurane, isoflurane, desflurane, sevoflurane
Have low vapor pressures and thus high boiling points so that they are liquids at room temperature and sea-level ambient pressure

Question 11

Describe gaseous anesthetics

Answer 11

Nitric oxide

Have high vapor pressures and low boiling points and are in gas form at room temperature

Question 12

Describe pharmacokinetics of inhaled anesthetics

Answer 12

Volatile and gaseous inhaled anesthetics are taken up through gas exchange in alveoli
Uptake from alveoli into blood and distribution and partitioning into the effect

Question 13

Describe uptake and distribution of inhaled anesthetics

Answer 13

Driving force for uptake of an inhaled anesthetic is alveolar concentration

Two factors that determine how quickly alveolar concentration changes:

1. Inspired concentration or partial pressure
2. Alveolar ventilation

Increases in either inspired partial pressure or in ventilation will increase rate of rise in alveoli and will accelerate induction

Partial pressure in alveoli is expressed as ratio of alveolar concentration (Fa) over inspired concentration (Fi); the faster Fa/Fi approaches 1, the faster anesthesia will occur during an inhaled induction

Question 14

What coefficients affect solubility?

Answer 14

Blood:gas partition coefficient
Brain:blood partition coefficient

Question 15

Describe the blood:gas coefficient

Answer 15

Defines the relative affinity of an anesthetic for blood compared with that of inspired gas (blood solubility)
There is an inverse relationship between blood:gas partition coefficient values and the rate of anesthesia onset
Agents with low solubility (nitrous oxide, desflurane) reach high arterial pressure rapidly, which in turn results in rapid equilibration with brain and fast onset of action
Agents with high solubility (halothane) reach high arterial pressure slowly, which results in slow equilibration with brain and slow onset of action

Question 16

Describe the brain:blood partition coefficient

Answer 16

Values for inhaled anesthetics are relatively similar and indicate that all agents are more soluble in brain than in blood

Question 17

Describe blood:gas coefficient, brain:blood coefficient, MAC (vol%), metabolism (%), and comments about nitrous oxide

Answer 17

0.47
1.1
>100
None
Incomplete anesthetic; rapid onset and recover

Question 18

Describe blood:gas coefficient, brain:blood coefficient, MAC (vol%), metabolism (%), and comments about desflurane

Answer 18

0.42
1.3
6-7

Question 19

Describe blood:gas coefficient, brain:blood coefficient, MAC (vol%), metabolism (%), and comments about sevoflurane

Answer 19

0.69
1.7
2
2-5
Rapid onset and recovery

Question 20

Describe blood:gas coefficient, brain:blood coefficient, MAC (vol%), metabolism (%), and comments about isoflurane

Answer 20

1. 4
2. 6
3. 4

Question 21

Describe blood:gas coefficient, brain:blood coefficient, MAC (vol%), metabolism (%), and comments about enflurane

Answer 21

1.8
1.4
1.7
8
Medium rate of onset and recovery

Question 22

Describe blood:gas coefficient, brain:blood coefficient, MAC (vol%), metabolism (%), and comments about halothane

Answer 22

2.3
2.9
0.75
>40
Medium rate of onset and recovery

Question 23

Why is induction of anesthesia slower with more soluble anesthetic gases?

Answer 23

For a given concentration or partial pressure of two anesthetic gases in inspired air, it will take much longer for blood partial pressure of more soluble gas (halothane) to rise to same partial pressure as in alveoli.
Since concentration of anesthetic agent in brain can rise no faster than concentration in blood, onset of anesthesia will be slower with halothane than with nitrous oxide

Question 24

The alveolar anesthetic concentration (Fa) approaches inspired anesthetic concentration (Fi) fastest for ___

Answer 24

Least soluble agents

Nitrous oxide>desflurane>sevoflurane>isoflurane>halothane

Question 25

Describe cardiac output effect on uptake of inhaled anesthetics

Answer 25

Increase in pulmonary blood flow (increased cardiac output) will increase uptake of anesthetic and decrease rate by which Fa/Fi rises, which will decrease rate of induction of anesthesia (Fa decreases because of increased pulmonary blood flow, which essentially dilutes drug in alveoli) An increase in cardiac output and pulmonary blood flow will increase uptake of anesthetic into blood, but the anesthetic taken up will be distributed and diluted into all tissues, not just CNS This results in slower rise in partial pressure in blood due to greater volume of distribution

Question 26

Describe alveolar-venous partial pressure difference effect on uptake of inhaled anesthetics

Answer 26

Anesthetic partial pressure difference between alveolar and mixed venous blood is dependent mainly on uptake of anesthetic by tissues, including nonneural tissues The slower the rate and extent of tissue uptake, the greater the difference in anesthetic gas tensions between arterial and venous blood, the more time it will take to achieve equilibrium with brain tissue Since anesthetics must be carried from tissues to lungs for primary elimination, larger A-V concentration differences means less drugs are returning for elimination, which may increase time for awakening

Question 27

Describe distribution of inhaled anesthetics

Answer 27

1. Concentrations of anesthetics in blood will increase as rate and depth of ventilation is increased 2. Depression of respiration by opioid analgesics slows onset of anesthesia of inhaled anesthetics if ventilation is not manually or mechanically assisted 3. Increasing pulmonary blood flow (cardiac output) slows rate of increase in arterial concentration of anesthetic because a larger volume of blood is exposed to anesthetic. Thus, blood capacity increases, and anesthetic concentration rises slowly (Reverse is true: decreasing pulmonary blood flow will increase rate of rise of arterial anesthetic concentration) 4. Brain, heart, liver, kidneys, and splanchnic bed are highly perfused and receive over 75% of resting cardiac output and have higher immediate concentrations of anesthetic 5. Although muscle and skin constitute about 50% of total body mass, anesthetics accumulate more slowly in these tissues than highly perfused tissues because they receive only one-fifth of resting cardiac output

Question 28

Describe elimination of inhaled anesthetics

Answer 28

1. Many of the processes of anesthetic transfer during recovery are the reverse of those that occur during induction 2. Inhaled anesthetics that are relatively insoluble in blood and brain are eliminated at faster rates than more soluble anesthetics 3. Clearance of inhaled anesthetics via lungs is major route of elimination from body, although some agents are metabolized by liver to varying degrees 4. Duration of exposure to anesthetic can have a significant effect on recovery time, especially in case of more soluble anesthetics - accumulation of anesthetics in muscle, skin, and fat increases with prolonged exposure (especially in obese patients), and blood tension may decline slowly during recovery as anesthetic is slowly eliminated from these tissues - although recovery may be rapid with more soluble agents following a short period of exposure, recovery is slow after prolonged administration of halothane or isoflurane

Question 29

Describe minimal alveolar concentration (MAC) required to prevent response to a surgical incision

Answer 29

1. Concentration of inhalation anesthetics that prevents movement in response to surgical stimulation in 50% of subjects (measure of potency, ED50) 2. Values are expressed as volume %, the percentage of atmosphere that is anesthetic at MAC 3. Dose of 1 MAC of any anesthetic prevents movement in response to surgical incision in 50% of patients (individual patients may require 0.5-1.5 MAC) Ex: 1 MAC of isoflurane is 1.4 volume %, while 1 MAC of halothane is 0.75 volume % 4. MAC values greater than 100% indicate that even if 100% of inspired air at barometric pressure is the anesthetic, the MAC value would still be less than 1, and other agents must be supplemented to achieve full surgical anesthesia (nitrous oxide) 5. Since nitrous oxide lacks potency to produce surgical anesthesia, it is combined with volatile or intravenous anesthetics to produce a state of balanced general anesthesia (using nitrous oxide to produce 40% MAC in combination with 70% of a volatile agent's MAC would yield a total of 110% MAC, sufficient for surgical anesthesia in most patients)

Question 30

Describe the stage of analgesia of CNS depression

Answer 30

Stage 1 Initially patient experiences analgesia without amnesia Both analgesia and amnesia are produced at end of stage

Question 31

Describe stage of excitement of CNS depression

Answer 31

Stage II Patient often appears delirious Respiration is irregular in both volume and rate Retching and vomiting may occur if patient is stimulated Regular breathing is established at end of this stage

Question 32

Describe stage of surgical anesthesia of CNS depression

Answer 32

Stage III Begins with regular breathing and extends to complete cessation of spontaneous respiration (apnea) Reliable indication that this stage has been achieved is loss of responsiveness to painful stimuli (trapezius muscle squeeze) and reestablishment of regular breathing (EEG cerebral indices are monitored as well)

Question 33

Describe stage of medullary depression of CNS depression

Answer 33

Stage IV, deepest stage Includes severe depression of vasomotor center in medulla as well as respiratory center Death will occur without circulatory and respiratory support

Question 34

Inhaled anesthetics decrease the ___ of the brain and increase ___. Not beneficial in what patients?

Answer 34

Metabolic rate Cerebral blood flow Patients with increased intracranial pressure

Question 35

Describe inhaled anesthetic effects on respiratory system

Answer 35

All volatile anesthetics are respiratory depressants (body has reduced response to increased levels of carbon dioxide) Depression of mucociliary function in airway can result in pooling of mucus and postoperative respiratory infections

Question 36

Describe toxicity of inhaled anesthetics

Answer 36

Common side effects include nausea and vomiting Halothane may cause hepatitis with or without previous exposure (symptoms include anorexia, nausea, myalgias, arthralgias, and rash, eosinophilia, hepatomegaly, and jaundice. Develops 2 days to 3 weeks after exposure) Agents metabolized to products including fluoride ions may cause renal toxicity (enflurane and sevoflurane) In combination with succinylcholine, inhaled volatiles anesthetics may cause malignant hyperthermia, which consists of rapid onset tachycardia and hypertension, severe muscle rigidity, rhabdomyolysis, hyperthermia, hyperkalemia, and acid-base imbalance with acidosis (dantrolene is antidote)

Question 37

Describe intravenous anesthetics

Answer 37

Nonopioid IV anesthetics are widely used to facilitate rapid induction of anesthesia and have replaced inhalation as preferred method of anesthesia induction in most settings (except for pediatric anesthesia) Similar to inhaled anesthetics, IV agents do not produce all and only five desired changes in behavior or perception (unconsciousness, amnesia, analgesia, inhibition of autonomic reflexes, and skeletal muscle relaxation) Therefore, balanced anesthesia with multiple drugs (inhaled anesthetics, sedative-hypnotics, opioids, neuromuscular blocking drugs) is used to minimize unwanted side effects IV anesthetics are highly lipophilic and preferentially partition into highly perfused lipophilic tissues (brain, spinal cord), which accounts for their quick onset of action

Question 38

Describe induction, recovery, and comments of etomidate

Answer 38

Rapid onset and moderately fast recovery | Provides CV stability, causes decreased steroidogenesis, and involuntary muscle movements

Question 39

Describe induction, recovery, and comments of ketamine

Answer 39

moderately rapid onset and recovery | CV stimulation, increased cerebral blood flow, and emergence reactions that impair recovery

Question 40

Describe induction, recovery, and comments of methohexital

Answer 40

Rapid onset and rapid recovery | Preferred over thiopental for short ambulatory procedures

Question 41

Describe induction, recovery, and comments of midazolam

Answer 41

Slow onset and recovery. Flumazenil reversal available | Used in balanced anesthesia and conscious sedation. Provides CV stability and marked amensia

Question 42

Describe induction, recovery, and comments of propofol

Answer 42

Rapid onset and rapid recovery | Used in induction and for maintenance, can cause hypotension, has useful antiemetic action

Question 43

Describe induction, recovery, and comments of thiopental

Answer 43

Rapid onset and rapid recovery (bolus dose). Slow recovery following infusion Standard induction agent, causes CV depression, avoid in porphyrias

Question 44

Describe induction, recovery, and comments of fentanyl

Answer 44

Slow onset and recovery. Naloxone reversal available | Opioid used in balanced anesthesia and conscious sedation, produces marked analgesia

Question 45

Describe propofol

Answer 45

Most commonly used parenteral anesthetic in US PK properties allow for continuous infusions and maintenance of anesthesia, sedation in ICU, conscious sedation and short-duration general anesthesia in locations outside operating room (interventional radiology suites, emergency department, dental offices, etc) Poor solubility in water and is formulated as emulsion containing soybean oil, glycerol, and lecithin (major component of egg yolk phosphatide fraction), making allergic reactions possible in susceptible patients (solution appears milky white and slightly viscous)

Question 46

Describe MOA of propofol

Answer 46

Most likely targets GABAa receptors as agonist and potentiates chloride current (other receptors likely involved)

Question 47

Describe pharmacokinetics of propofol

Answer 47

Rapidly metabolized in liver (phase I and II reactions (glucuronide and sulfate conjugates)) with extensive extrahepatic metabolism (lung tissue may account for elimination of up to 30% of bolus dose) Low "hangover" effect likely due to high plasma clearance Rapid rate of onset, rapid recovery, and patients are able to ambulate quickly after use Time of onset (as determined by time to unconsciousness) is 15-30 seconds

Question 48

Describe context-sensitive half-life of propofol

Answer 48

Describes elimination half-time after a continuous infusion as a function of duration of infusion Key factor in suitability of a drug for use as maintenance anesthetic Context sensitive half-life for propofol is brief, even after a prolonged infusion, and recovery remains relatively prompt

Question 49

Describe context-sensitive half-life of common intravenous anesthetics

Answer 49

Duration of action of single intravenous doses of anesthetic/hypnotic drugs is similarly short for all and is determined by redistribution of drugs away from their active sites However, after prolonged infusions, drug half-lives and durations of actions are dependent on factors such as rate of redistribution of drug, amount of drug accumulated in fat, and drug's metabolic rate. Half-lives of some drugs such as etomidate, propofol, and ketamine increase only modestly with prolonged infusions. Others (diazepam and thiopental) increase dramatically

Question 50

CNS effects of propofol

Answer 50

General suppression of CNS activity even though excitatory effect such as twitching or spontaneous movement are occasionally observed during induction No analgesic properties Decreases cerebral blood flow and cerebral metabolic rate for oxygen (CMRO2), which decreases intracranial pressure (ICP) and intraocular pressure Produces burst suppression in EEG when administered in large doses, which conveys a neuroprotective effect during neurosurgical procedures (as does decreased CMRO2)

Question 51

Describe cardiovascular effects of propofol

Answer 51

Compared with other induction agents produces most pronounced decrease in systemic blood pressure due to profound vasodilation in both arterial and venous circulation leading to reductions in preload and afterload Hypotensive effects are augmented by inhibition of normal baroreflex response

Question 52

Describe respiratory effects of propofol

Answer 52

Potent respiratory depressant, generally produces apnea after an induction dose Causes a greater reduction in upper airway reflexes than thiopental does, which makes it well suited for instrumentation of airway, such as placement of a laryngeal mask airway

Question 53

Pain on injection of propofol is common, so premedicate with ___

Answer 53

Opioid or coadminister lidocaine

Question 54

Describe fospropofol

Answer 54

Water-soluble prodrug of propofol that is rapidly metabolized by alkaline phosphatase, producing propofol, phosphate, and formaldehyde (metabolized by aldehyde dehydrogenase in liver and in erythrocytes) Effects are similar to propofol, but onset and recovery are prolonged because prodrug must first be converted into active form Less pain on administration than propofol Common adverse effect is experience of paresthesias (including perineal discomfort or burning sensation) and pruritus (including genital, perineal, and generalized pruiritus) are mostly limited to first 5 minutes of administration and usually described as mild-moderate in intensity (mech unknown. No pretreatment helpful)

Question 55

Describe etomidate

Answer 55

Hypnotic but not analgesic effects MOA: enhances actions of GABA on GABAa receptors Causes minimal cardiovascular and respiratory depression, useful in patients with impaired CV and respiratory systems Produces rapid loss of consciousness and less rapid recovery rate compared to propofol Extensively metabolized by liver and in plasma

Question 56

CNS effects of etomidate

Answer 56

Potent cerebral vasoconstrictor, decreases cerebral blood flow and ICP

Question 57

CV and respiratory effects of etomidate

Answer 57

CV system stability is maintained even after bolus injection Minimal change in heart rate and cardiac output Respiratory depressant effects are less pronounced compared to barbiturates

Question 58

Describe endocrine effects of etomidate

Answer 58

Causes adrenocortical suppression by producing a dose dependent inhibition of 11beta-hydroxylase (necessary for conversion of cholesterol to cortisol) Suppression lasts 4-8 hours after induction dose Endocrine adverse effects limit use for continuous infusion

Question 59

Describe ketamine

Answer 59

MOA: NMDA receptor antagonist Produces a dissociative anesthetic state characterized by catatonia amnesia, analgesia with or without loss of consciousness (pt's eyes remain open with a slow nystagmic gaze) Similar in structure to phencyclidine (PCP) Lacrimation and salivation are increased upon administration, and premedication with anticholinergic may be indicated Only IV anesthetic to produce profound analgesia, stimulation of sympathetic nervous system, bronchodilation, and minimal respiratory depression

Question 60

Describe CNS effects of ketamine

Answer 60

Increases cerebral blood flow as well as CMRO2, not recommended for use in patients with intracranial pathology, especially increased ICP Unpleasant emergence reactions after administration are main factor limiting ketamine's use (vivid colorful dreams, hallucinations, out-of-body experiences, increased and distorted visual, tactile, and auditory sensitivity) May induce a euphoric state, which explains potential abuse

Question 61

Describe CV effects of ketamine

Answer 61

Can increase systemic blood pressure, heart rate, and cardiac output, presumably by centrally mediated sympathetic stimulation Ketamine is considered to be a direct myocardial depressant, a property masked by stimulation of sympathetic nervous system (depressant actions of ketamine may be more apparent in critically ill patients with limited ability to increase their sympathetic nervous system activity)

Question 62

Describe dexmedetomidine

Answer 62

MOA: alpha-2 adrenergic agonist that produces hypnosis presumably from stimulation of alpha-2 receptors in locus ceruleus and analgesic effects at level of spinal cord Sedative effect more completely resembles physiologic sleep state through activation of endogenous sleep pathways Infusion results in moderate decreases in heart rate and systemic vasucular resistance and systemic blood pressure, bradycardia may require treatment Principally used for the short-term sedation of intubated and ventilated patients in an ICU setting or as adjunct to general anesthesia

Question 63

What are anesthetic adjuncts used for?

Answer 63

To augment specific components of anesthesia, permitting lower doses of general anesthetics with fewer side effects

Question 64

Describe opioid analgesics

Answer 64

Have been used in combination with large doses of benzodiazepines to achieve a general anesthetic state Common agents: IV fentanyl, sufetanil, remifentanil, morphine MOA: agonists at opiate receptors Due to adverse effects (impaired ventilation, tolerance after surgery, awareness during anesthesia) opiates are often used as premedication and as an adjunct to both IV and inhaled anesthetics to provide perioperative analgesia

Question 65

Describe barbiturates

Answer 65

Thiopental (prototype) and methohexital Highly lipophilic and quick plasma: brain equilibrium Cause dose-dependent CNS depression ranging from sedation to general anesthesia (no analgesia) Cause respiratory depresssion MOA: acts on GABAa receptor to increase duration of channel opening (agonist) and enhances inhibitory neurotransmission Methohexital may be preferred over thiopental for short ambulatory procedures due to its rapid elimination Induce cytochrome P450 enzymes Largely replaced as induction agents by propofol

Question 66

Describe benzodiazepines

Answer 66

Common agents: diazepam, lorazepam, midazolam MOA: acts on GABAa receptor to increase receptor sensitivity to GABA (agonist) and enhances inhibitory neurotransmission Commonly used in perioperative period because of their anxiolytic properties and ability to produce anterograde amnesia. Actions can be terminated by antagonist flumazenil Midazolam is water-soluble (diazepam and lorazepam are not) and is considered drug of choice for parenteral administration Midazolam is frequently administered intravenously before patients enter operating room because it has a more rapid onset, shorter elimination half-life (2-4hrs), and steeper dose-response curve than other benzodiazepines Potent anticonvulsant properties, used in treatment of status epilepticus, alcohol withdrawal, and local anesthetic-induced seizures