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PDA Block 3 > General Anesthesia > Flashcards

General Anesthesia Flashcards

1
Q

Anesthetics

A
  • were introduces to American medicine 170 years ago; their importance is hard to over estimate
  • are used very frequently (over 20 million times per year)
  • are dangerous-very low therapeutic indices
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2
Q

General principles of surgical anesthesia

A
  • minimize potentially deleterious direct and indirect effects of anesthetic agents and techniques
  • sustain physiologic homeostasis during surgical procedures
  • improves postoperative outcomes through dampening of the surgical stress response
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3
Q

Clinical definition of general anesthesia

A
  • state of the patient in which no movement occurs in response to a painful stimuli; reversible
  • patient is usually not conscious; unaware of sensory input
  • what is conciousness
  • studies of the effects of anesthetic could help answer this question
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4
Q

components of general anesthetic

A

-amnesia
-unconsciousness
analgesia
immobility
attenuation of autonomic responses

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5
Q

amnesia

A

absence of memory during anesthesia

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6
Q

unconsiousness

A

not always necessary

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7
Q

analgesia

A

inability to interpret, respond to and remember pain

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8
Q

immobility

A

in response to noxious (painful) stimuli

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9
Q

attenuation of autonomic responses

A

to noxious stimuli

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10
Q

Measurement of anesthetic property

A
  • the dose of anesthetic that prevents movement in response to pain in 50% of patients
  • the dose of gaseous anesthetic are directly related to concentrations at the alveolus
  • gaseous anesthetic potency is quantified as the minimal alveolar concentration (MAC) that prevents movement in 50% of patients
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11
Q

advantages of MAC as a measure of anesthetic property

A
  • can measure it (concentration of anesthetic in the end-tidal expired air)
  • correlated well wth the concentration of drug at its site of action, the brain
  • end-point ( lack of movement to pain) is easy to measure and define
  • other “MAC” can be defined (MACawake)
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12
Q

Potency for intravenous anesthetics

A

-free plasma concentration that produces loss of response to a surgical incision in 50% of patients (EC50)

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13
Q

common effects shared by all general anesthetics

A
  • hyperpolarize neurons
  • particularly neurons that serve a pacemaker role
  • reduced excitability results in reduced probabbility of action potential
  • inhibit excitatory synaptic transmission and/or enhance inhibitory transmission
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14
Q

Targets of anesthetics

A
  1. GABA A receptors
  2. NMDA receptors
  3. other memebrane associated proteins are affected
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15
Q

GABA A receptors as a target for anesthetics

A
  • GABA regulated Cl channel
  • most anesthetics INCREASE GABA A opening via allosteric effects on the receptor protein
  • increased Cl conductance results in hyperpolarization (membrane potential becomes more negative)
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16
Q

NMDA as a target for anesthetics

A

some anesthetics inhibit NMDA receptors

  • results in reduced Na and Ca influx
  • some hyperpolarization of membrane potential
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17
Q

Other membrane associated proteins are affected as targets of anesthetics

A
  • anesthetics fill hydrophobi cavities in proteins

* can alter movement of proteins; alter transitions required for signaling and activation

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18
Q

3 stages of general anesthesia

A
  1. premedication
  2. induction
    * want something that will not be frightening or painful
    * parenterally (usually iv) anesthetic; only pain is establishing iv line
    * only induce with inhalational anesthetic in emergency
  3. maintenance
    * gaseous anesthetics have short half lives; need to administer continually
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19
Q

tell me generally about parenterally administered anesthetics

A
  • are all hydrophilic molecules
  • administered as intravenous bolus (all at once)
  • partition into the brain and spinal cord from the circulation during one pass; results in rapid induction of anesthesia
  • redistribution back out of the brain as blood levels drop
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20
Q

describe the relationship with the duration and half life

A

-duration of action is shorter than half-life; multiple dosing is complex as storage depots come in and out of equilibrium with blood

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21
Q

Barbiturate drugs

A

-sodium thiopental

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22
Q

sodium thiopental

A
  • barbituate
  • activates GABA-A receptors
  • used to induce anesthesia
  • occurs 10-30 sec after intravenous injection
  • duration of a single dose: 10 min at most
  • half life in body: 12 hours (can produce hang over)
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23
Q

Traits about barbituates

A
  • depressants are additive; reduce dose n combination with opiates, benzodiazepines, alpha 2 receptor agonists (all CNS depressants)
  • intraarterial injection is contraindicated bc can lead to inflammation and necrosis
  • can be given rectally to pediatric patients
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24
Q

Barbituates adverse effects

A
  • CNS depression
  • Cardiovascular
  • respiratory depression
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25
Q

Barbituates and CNS depression

A

decreases oxygen demand, therefore, decreases blood flow and decreases intracranial pressure

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26
Q

barbituates and cardiovascular effects

A
  • vasodilator-primarily venodilation
  • can be a problem in patients with already reduced preload or cardiomyopathy; results in severe drop in BP
  • since demand on the heart is reduced, barbituates are not contra indicated in patients with coronary artery disease; not arrythmogenic
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27
Q

Propofol

A
  • most commonly used parenteral general anesthetic in US
  • GABA A mechanism
  • used to both induce and maintain anesthesia
  • induction occurs 10-30 sec after intravenou sinjection
  • duration of a single dose=10 min
  • is antiemetic (an advantage since most patients are nauseated after surgery
  • half-life in the body: 3.5 hours ( much less than barbiturates)
  • this is an important advantage over thiopental; makes propofol very useful for out-patient surgery
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28
Q

unique adverse effects to Propofol

A
  • elicits pain on injection; often given with lidocaine or into a large veins
  • can cause initial excitation on induction
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29
Q

CNS effects of propofol

A
  • about the same as thiopental

- has demonstrated abuse liability

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30
Q

Cardiovascular side effect propofol

A
  • more severe reduction in BP than thiopental
  • vasodilation
  • AND depression of myocardial contractility
  • blunts baroreflexes (therefore, these changes are not opposed by vasoconstriction, HR increase)
  • therefore: used with caution in patients with intolerance to decreased blood ressure
  • respiratory : more depression than thiopental at equianesthetic dose
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31
Q

Etomidate

A
  • used to induce anesthesia in patients at risk for hypotension
  • etomidate produces little or no effect on blood pressure; only a small increase in heart rate
  • it is safer than propofol or thiopental in patients with hypotension or compromised baroreceptor function
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32
Q

adverse effects to etomidate

A
  • high incidence of pain on injection, myoclonus (use lidocaine for pain and pretreat with benzodiazepines or opiates for the second)
  • significant problems with nausea and vomiting
  • suppression of the adrenocortical response to stress; can result in mortality
  • worse during prolonged administration
  • therefore, only used to induce anesthesia in patients with hemodynamic problems
33
Q

CNS adverse events for etomidate

A
  • same as thiopental

- decreases oxygen demand, therefore, decreases blood flow and decreases intracranial pressure

34
Q

CV effects of etomidate

A

-MUCH less than thiopental

35
Q

respiratory effect etomidate

A

less than thiopental

36
Q

Ketamine

A
  • produces “dissociative anesthesia”
  • eyes open but patients are unresponsive to commands
  • profound analgesia
  • amnesia
  • does not affect respiration, is a bronchodilator
  • NMDA antagonist
  • can be used via multiple routes: iv, im, oral, rectal
  • these properties (primarly the analgesia; lack of effect on respiration and ability to use im) make it a useful agent
37
Q

adverse efect for ketamine

A
  • nystagmus, salivation, lacrimation, increased muscle tone and spontaneous movement
  • increased intracranial pressure due to increase cerebellar blood flow
  • emergence delirium (hallucinations, vivid dreams) not as bad in children as in adults
  • PCP is ketamine like
  • hypertension due to indirect sympathomimetic effect
38
Q

usefulness of ketamine

A
  • patients with bronchospasm (cannot be intubated)
  • ketamine is a bronchodilator due to indirect sympathomimetic effects
  • children undergoing short, painful procedures
39
Q

Midazolam

A
  • short acting benzodiazepine
  • GABA A activator
  • used for conscious sedation, anxiolysis, amnesia during short procedures
  • can also be used as an induction agent
  • adjunct during local anesthesia (eg during tooth extraction)
  • useful as a pre-operative medication decreases anxiety
40
Q

tell me about the induction time and duration for midazolam

A
  • slower induction time and longer duration of action than thiopental
  • metabolized by hydroxylation to an active metabolite
41
Q

adverse effect midazolam

A
  • can cause respiratory depression and respiratory arrest (especially when used intravenously)
  • used with caution in patients with neuromuscular disease; Parkinson’s disease; bipolar disorder
  • cardiovascular effects are similar to thiopental (depression in BP)
  • adverse effects reversed by flumazenil
42
Q

Flumazenil

A

can cause adverse effects

43
Q

thiopental usefulness and problems

A
  • U: induction for in patient surgery

- P: hypotension hang over

44
Q

propofol u&p

A

U- induction/maintenance especially for out patient

P- hypotension and respiratory depression

45
Q

Etomidate u&p

A

u-induction in patients at risk for hypotension

p-nausea/vomiting and adrenocortical suppression

46
Q

Ketamine u&p

A

u- bronchospasm and peds short painful procedures

p- increased intracranial pressure, delirium

47
Q

midazolam u&p

A
  • u- conscous sedation; anti-anxiety

- p- slow induction and respiratory depression

48
Q

commonalities among inhalation general anesthetics

A
  • very low therapeutic indices; LD50/ED50 can be as low as 2-4
  • pharmacokinetics are unique and important: gaseous or readily vaporized at room temperature
49
Q

Pharmacokinetics of gaseous anesthetics

A
  • for a gas, equilibrium between compartments is reached with the partial pressures (not concentrations) are the same
  • what matters to us are the partition coefficients of the gas at each of these compartment barriers
50
Q

partition coefficients

A
  • determine the relative amounts of anesthetic in two compartments
  • blood: gas
  • brain: blood
  • fat: blood
51
Q

Blood: gas partition coefficient

A

-partition coefficient determines the ease of absorption at the alveoli

52
Q

brain: blood

A

partition coefficient determines the anesthetic movement into the brain

53
Q

fat: blood

A

partition coefficient determines the redistribution to fat

54
Q

if the anesthetic had low blood: gas PC

A
  • needs high amounts in inspired air (bc it doesn’t want to go into the blood but you need to make it)
  • induction is quick ( bc equilibrium is reached quickly)
  • recovery will be quick ( drug will move readily out of the blood into gas)
55
Q

if anesthetic has a high Blood: gas partition coefficient

A
  • need less in inspired air

- induction and recovery are slow (equilibria are reached slowly

56
Q

if anesthetic has high fat: blood PC

A

-half life will be long (hang over) due to slow release into the blood, enough gets into the brain to make the patient feel sleep

57
Q

anesthesia occurs in the brain

A

-anesthesia is achieved when the brain partial pressure is equal to MAC
-anesthetics are all lipophillic and brain is highly perfused, so the brain gets a large share of the anesthetics in the circultion
-thus amnesia is achieved shortly after MAC is reached in the
alveolae

58
Q

define steady stae (equilibrium)

A
  • no net movement of gas at this stage
  • quick for gases with low blood: gas PC
  • slow for gases with high fat: blood PC
  • in clinical practice, instruments administering anesthetic measure the concentration of the anesthetic in expired air; end tidal concentration is an estimate of alveolar concentration
59
Q

elimination of drugs

A
  • reverse of induction; gas moves from the blood into the inspired air (which is now free of gas)
  • rate of elimination is dependent upon the blood: gas partition coefficient
  • lowest will be eliminated the fastest
  • but the gas needs to get into the blood to be eliminated
  • blood: fat PC of anesthetci determines half life
60
Q

recovery of anesthesia

A
  • agents that have a low solubility in blood and fat have rapid recovery
  • agents with high solubility in blood and fat, have slower recovery and the duration of the recovery will depend upon the length of time that the anesthetic was administered
61
Q

Malignant hypethermia

A
  • serious adverse effect of gaseous anesthetic exposure; rare but potentially fatal
  • heritable pockets of individuals in Wisconsin
  • skeletal muscle disorder, triggered by anesthetic
  • consists of muscle rigidity, hyperthermia, rapid onset of tachycardia and hyercapnia, hyperkalemia, metabolic acidosis
62
Q

Isoflurane

A
  • moderate blood: gas PC
  • moderate rates of induction and recovery
  • excreted unchanged in expired air
63
Q

clinical uses of isoflurane

A
  • commonly used inhalational anesthetic in US and (especially) worldwide
  • can be used to induce and maintain anesthesia; but is mostly used for maintenance
  • often used with nitrous oxide to reduce amount needed
64
Q

adverse effects of isoflurane- respiratory

A
  • respiratory
  • airway irritant
  • coughing
  • decreases tidal volume and increases respiratory rate
  • all anesthetics depress respiration (via effects in the CNS) and increase pCO2
65
Q

adverse effects isoflurane-cardiovascular

A
  • myocardial depression; results in decrease in BP
  • arrythmias (sensitization of the heart to catecholamines)
  • cerebral vessel vasodilation, can result in increase intracranial pressure
66
Q

Desflurane-pharmacokinetics

A
  • volatile liquid at room temperature
  • very low solubility in blood * very low blood: gas partition coefficient) therefore induction an recovery are rapid
  • excreted unchained in expired air
67
Q

clinical uses of deflurane

A
  • outpatient surgeries/maintenance
  • not used to induce because of respiratory irritation
  • skeletal relaxation is a good thing
68
Q

side effects of desflurane relative to isoflurane

A
  • cardiovascular-similar

- respiratory: worse irritant, can produce bronchospasm

69
Q

sevflurane-pharmacokinetics

A
  • very low blood: gas partition coefficient
  • about 5% of the administered dose is metabolized to fluoride ion in the liver
  • there is some concern that this can cause renal damage
  • is degraded to “compound A” by absorbants in the anesthesia administration apparatus
  • compound A is nephrotoxic in rats
70
Q

Sevoflurane clinical use

A
  • very popular
  • inpatient and outpatient
  • can but used to induce and maintain
  • children and adults
  • not a respiratory irritant
71
Q

side effects of sevoflurane

A

-similar to isoflurane

however not as much respiratory depression

72
Q

Nitrous oxide

A
  • a gas at atmospheric, not a volatile liquid
  • pharmacokinetics
  • very insoluble in blood; therefore rapidly equilibrates
  • uptake from air results in increased concentration of other anesthetics
  • so it is useful as an agent to enhance induction with isoflurane for example
  • during emergence can dilute oxygen so patients need to breath 100% oxgen
  • 99%excretion unchaged via lungs
73
Q

clinical uses nitrous oxide

A
  • weak anesthetic, cannot get enough into the air to produce MAC
  • good for sedation and analgesia at 50% concentration in inspired air
  • used together with other inhaled anesthetics to reduce dose needed
74
Q

nitrous oxide adverse effects

A
  • contraindicated in pneumothorax
  • negative inotrope but also sympathomimetic, cardiac output is preserved
  • respiratory effects are minimal, except for oxygen dilution issue
  • has abuse liability
  • prolonged exposure reduces methionine synthase activity, could cause megaloblastic anemia
75
Q

Isoflurane u&P

A

u- induction and maintenance inpatient

p- slowerl airway irritant

76
Q

desflurane u&p

A
  • u- outpatient maintenance only

- p- coughing bronchospasm

77
Q

sevoflurane

A

-u-all types induction and maintenance

p- oxygen dilution, abuse

78
Q

nitrous oxide

A

u-dentistry, adjunct

p-oxygen dilution, abuse

PDA Block 3 (16 decks)

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