Neuro: Hupka - General Anesthesia

Front 1

Ok again Hupka will give us some questions and we will do his objectives.....

Back 1

let's begin

Front 2

Preanesthetic medications - drugs given generally prior to anesthesia (includes drugs given during or after) in order to:

Decrease anxiety without producing excessive drowsiness

Facilitate a rapid, smooth induction without prolonging emergence

Provide amnesia for the perioperative period

Relieve pre-and post-operative pain

Minimize undesirable side effects of anesthetics (e.g. PONV)

Back 2

Common Preanesthetic Agents
Drug Class Benzodiazepine:
Generic Name: Diazepam and Modazolam

Common Preanesthetic Agents
Drug Class: Antihistamines
generic name: Hydroxyzine
Desired Effect: Sedation

Desired Effect: Reduce anxiety, Sedation, Amnesia, “Conscious sedation”

Front 3

Common Preanesthetic Agents
Drug Class: Opioid Analgesics
Generic Name: Morphine, Meperidine, Fetanyl, Remifentanil

Dersired Effect: Sedation to decrease tension, anxiety, and provide analgesia

Back 3

Common Preanesthetic Agents
Drug Class: Phenothiazines
Generic Name: promethazine

Desired Effect: Sedation, antihistaminic, antiemetic, decreased motor activity

Front 4

Common Preanesthetic Agents
Drug Class: Anticholinergics
Generic name: atropine and glycopyrollate

Desired effect: Inhibit secretions, bradycardia, vomiting, and laryngospasms

Back 4

Common Preanesthetic Agents
Drug Class: GI Drugs
generic name: ondansetron, cimetidine, & metoclopramide

Desired Effect: Antiemetic,
Decrease gastric acidity,
Decrease stomach contents

Front 5

Which Anticholinergic is better at crossing the BBB and causing effects: Inhibit secretions, bradycardia, vomiting, and laryngospasms:

Atropine or Glycopyrollate?

EXAM*****

Back 5

Atropine

Front 6

know this picture....EXAM

Back 6

Molecules have to disolve to get to the brain.

The alveoli drug should match the brain drug

Have to fill up the blood compartment.

smaller compartments are easier to fill up

If NOT blood soluble have faster effect

Front 7

Uptake, Distribution and Elimination of Anesthetic Gases
During administration of an anesthetic

The concentration rises most rapidly in tissues with high blood flow (brain), and lags in tissues with lower flow (fat and muscle)
Many tissues don’t reach an equilibrium status during surgery

EXAM****

Back 7

Safety, Potency, and Efficacy:
Potency:
Relative potency of anesthetic gases expressed as MAC
EXAM******

MAC (minimal alveolar concentration)
MAC = the Minimal Alveolar Concentration that will block movement in response to incision in 50% of patients (sort of like an ED50)
MAC expressed as % of inspired air
MAC best correlates inversely with lipid/gas partition coefficient (the greater the lipid solubility the lower the MAC)
The MAC for most inhalation anesthetics is < 2% of inspired air
Relative potency = 1/MAC
Smaller the MAC the more potent the anesthetic is
MAC values are additive

Front 8

At what stage of anethesia are most surgeries done?

Back 8

Stage 3

EXAM*****

Front 9

With Inhalation Anesthetic Agents
What do you need to be really careful about?

EXAM****

Back 9

General pharmacological effects
Cardiovascular: myocardial depressants

Front 10

With Inhalation Anesthetic Agents
What drug will NOT cause Malignant Hyperthermia?

Back 10

triggered by exposure to volatile gaseous inhalation anesthetics and succinylcholine -

N2O is not a trigger****

EXAM*****

Front 11

What Inhalation Anesthetic Agents drug is most likely to cause Hepatotoxicity?

Back 11

Halothane

EXAM*****

Front 12

What drug's main unwanted effects is Adrenocortical suppression?

Back 12

Etomidate

EXAM****

Front 13

What Intravenous Anesthetic Agents can be used as a Antiemetic (An antiemetic is a drug that is effective against vomiting and nausea.)

Back 13

Propofol


EXAM****

Front 14

what Intravenous Anesthetic Agents main unwanted effects are Psychotomimetic effects following recovery?

Back 14

Ketamine

EXAM*****

Front 15

What Intravenous Anesthetic Agent produces good analgesia and amnesia. Also causes Bronchodilation?

Back 15

Ketamine

EXAM*****

Front 16

What Intravenous Anesthetic Agents Is good for Amnesia?

Back 16

Midazolam

EXAM*****

Front 17

IV anesthetic drug mechanisms:

What drug primarily produces its effects by binding non-competively to the NMDA receptor site to inhibit the excitatory NT glutamate

Back 17

Ketamine = glutamate antagonist

EXAM*****

Front 18

How do IV anesthetic drugs thiopental, midazolam, propofol, etomidate work?

Back 18

thiopental, midazolam, propofol, etomidate
primarily produce their anesthetic effects by enhancing the efficacy of GABA at GABAA chloride ionophore


EXAM*****

Front 19

What drug causes:

Causes a direct cerebral vasoconstriction that results in decrease CBF and CMRO2 and as a result an elevated ICP is lowered

Back 19

Etomidate

EXAM****

Front 20

What drug will you see Myoclonic movements are common is association with induction and emergence?

Back 20

Etomidate

EXAM*****

Front 21

What drug has Good amnesic properties and is Often combined with opioid for ‘conscious sedation’
Availability of specific receptor antagonist = flumazenil

Back 21

Midazolam

EXAM*****

Front 22

1. Explain what is meant by MAC, indicate its significance, and the physical characteristic it best correlates with

Back 22

Relative potency of anesthetic gases expressed as MAC

MAC (minimal alveolar concentration)

MAC = the Minimal Alveolar Concentration that will block movement in response to incision in 50% of patients (sort of like an ED50)
MAC expressed as % of inspired air

Front 23

MAC best correlates inversely with lipid/gas partition coefficient
(the greater the lipid solubility the lower the MAC)

The MAC for most inhalation anesthetics is < 2% of inspired air

Back 23

Relative potency = 1/MAC

Smaller the MAC the more potent the anesthetic is

MAC values are additive

Front 24

Image of MAC and Lipid Solubility

Back 24

Front 25

Combining agents to reduce the MAC of each

Back 25

Front 26

What are some factors that may increase MAC?

Back 26

Hyperthermia

Hypernatremia

Hyperthyroidism

Chronic alcohol abuse

Increased CNS norepinephrine levels

(MAO inhibitors, cocaine, ephedrine, acute amphetamine intoxication)

Front 27

Some factors that decrease MAC

Back 27

Increasing age
Metabolic acidosis
Certain Drugs
Hypothermia
Hypotension
Hyponatremia

Front 28

2. Indicate which of the inhalation anesthetics has significant analgesic properties

Back 28

Anesthetic gases – only one is Nitrous Oxide which has good analgesic properties (others don’t)

Front 29

3. Explain induction and recovery times and potency based upon physical properties of general anesthetics.

Back 29

speed of induction and emergence (recovery)
determined by the rate of change of the partial pressure (concentration) of the gas in the brain

Speed of induction best correlated with blood/gas partition coefficient (inverse correlation)

determined by the partial pressure of the gas in arterial blood which is related to alveolar concentration

So concentration in brain related to alveolar concentration

Front 30

Uptake, Distribution and Elimination of Anesthetic Gases

Image

Back 30

Rate of induction faster for N2O than desflurane because it is usually given in much higher concentration (50 – 70% versus 3 – 9%)

Front 31

Summary:

During administration of an anesthetic:
its concentration in blood rises toward that in the inspired gas

Tissue concentrations rise to approach the concentration in the arterial blood

Back 31

The concentration rises most rapidly in tissues with high blood flow (brain), and lags in tissues with lower flow (fat and muscle)

Many tissues don’t reach an equilibrium status during surgery

Front 32

4. Describe the proposed mechanism(s) of action of inhalation anesthetics

Back 32

don't know how they work

Anesthesia probably has no unitary mechanism but may involve
Sufficient enhancement of inhibition
Inhibition of excitation
A combination of the two

Front 33

The GABAA receptor complex seems to be the primary target for most of GA and many IV anesthetics

They may
act indirectly to enhance GABA’s effect to increase chloride conductance at lower concentrations

Act directly as agonists to open the chloride channel

Back 33

Inhalation anesthetic
Primary agents used today:

Nitrous oxide (N2O)*
Sevoflurane**

Front 34

Theories of Anesthetic Action:
GABAA-Chloride channel complex (GABAA )
Common specific target for
Anxiolytics hypnotics general and IV anesthetics, antiepileptics

Back 34

All don’t fit the mechanism

Spinal glycine receptors targets for some GA effects

Actions to increase chloride conductance to produce hyperpolarization


Ketamine and nitrous oxide seem to act by inhibiting glutamate NMDA receptors or central acetylcholine receptors

Front 35

5. Indicate the physiological indices for "surgical" anesthesia (Stage III plane 3) and anesthetic overdose (Stage IV).

Back 35

Depth of Anesthesia
Signs and stages of anesthesia originally developed for diethyl ether
Stage III: Used for most Sx
Pupillary light reflex present
no eye movement
still breathing
No response to skin incision

Stage IV: Imminent death
Apnea appears
Pupil is completely dialated
muscle tone is flaccid

Front 36

6. Compare and contrast the pharmacological properties, and uses of etomidate, ketamine, propofol and midazolam. Consider mechanisms, induction and recovery, as well as potential adverse effects

Back 36

etomidate:
Fast onset, fairly fast recovery
Excitatory effects during induction and recovery, Adrenocortical suppression
No significant effects on cardiovascular and respiratory system. Injection site pain

Propofol
Fast onset, very fast recovery
Cardiovascular and respiratory depression. Pain at injection site
Most common induction agent. Rapidly metabolized; possible to use as continuous infusion. Injection pain. Antiemetic

Front 37

Ketamine

Slow onset, after-effects common during recovery

Psychotomimetic effects following recovery, Postoperative nausea, vomiting and salivation

Produces good analgesia and amnesia. Bronchodilation. Increased HR, BP, CO. No injection site pain

Back 37

Midazolam

Slower onset than other agents

Minimal CV and resp effects

Little respiratory or cardiovascular depression. No injection pain. Good amnesia.

Front 38

Etomidate.....most likely to cause PONV

Also..........

Myoclonic movements are common is association with induction and emergence

Back 38

7. Explain the concept of balanced anesthesia
Combination or balanced anesthesia

no single anesthetic agent meets the ideal
so, a combination of drugs is used to
take advantage of their best properties
minimize the undesirable side effects

Front 39

8. Define "dissociative" anesthesia and name the drug used to produce it.

Back 39

Dissociative – ketamine
Produces a ‘dissociative anesthesia’
Chemically related to PCP
Analgesia, immobility, amnesia

No loss of consciousness but like in a trance with eyes open and cataleptic
Patient may appear to be awake but does not respond to sensory stimuli
Used for minor surgical and diagnostic procedures especially in children

Front 40

Ketamine

Almost no respiratory depression with significant bronchodilation properties

Unique =unlike other IV anesthetic drugs stimulates CV system

Unlike other anesthetic agents can be given by IM route (useful for anesthetizing children who resist IV or inhalation)

Back 40

9. Compare isoflurane, desflurane, and sevoflurane in respect to: recovery time, extent of metabolism, heart rate, and respiratory irritation. Which agents are most likely to produce emergence delirium in children?

isoflurane (Forane) – commonly used anesthetic for adults, inexpensive, pungent odor, inexpensive

Front 41

desflurane (Suprane) – similar to isoflurane except for more rapid emergence, and more irritating to airway, expensive

Back 41

sevoflurane (Ultane) – similar to desflurane except not irritating to airway, one of the best!! Expensive!

Isoflurane:
recovery time,- moderate
extent of metabolism, - 0.2%
heart rate,- increased
respiratory irritation - significant

Front 42

Desflurane
recovery time - very fast
extent of metabolism, - 0.02&
heart rate,- increased
respiratory irritation - significant

Back 42

Sevoflurane
recovery time, - FAST
extent of metabolism, - 3-6%
heart rate, - Stable

Ketamine...........
Delirium, hallucinations, vivid dreams and irrational behavior during recovery (emergence delirium)
respiratory irritation - NO

Front 43

10. Know which substance of abuse ketamine is related to.

Back 43

Chemically related to PCP

Front 44

11. Explain what is meant by "induction anesthesia" and name the IV agents primarily used for this procedure

Back 44

Propofol

Most frequently used induction agent
Good induction and maintenance agent
Rapid onset of action and short recovery time
Possesses antiemetic properties

Front 45

12. Explain the mechanism behind propofol’s brief duration of CNS effects following IV bolus administration

Propofol
Short recovery time attributed to redistribution and rapid clearance from plasma by metabolism (mainly glucuronidation)
little hangover
Considered safe for use in pregnant women
Propofol and opioids thought to act synergistically

Back 45

13. Explain why in spite of the fact that the general inhalation anesthetics have a low Therapeutic Index they still can be safely used to produce anesthesia.

Therapeutic indices (TI)
for most general anesthetics is among the lowest of drugs (2- 4)
accurate control of dosage is necessary for safe use

Front 46

14. Explain what is meant by "incomplete anesthetic", indicate which anesthetic gas is considered and incomplete anesthetic.

Back 46

Nitrous oxide is an incomplete anesthetic

it can’t produce all stages of anesthesia without producing hypoxia (MAC = 105)

N2O has less efficacy than a complete anesthetic

Front 47

15. Compare propofol, etomidate, and ketamine for their effects on systemic blood pressure and heart rate.

Back 47

propofol, - decrease systemic BP, Decrease HR

etomidate, - No change in systemic BP, No change in HR

ketamine - Increase in systemic BP, increase in HR

Front 48

16. Describe the use of pre anesthetic medications. Be able to list the most commonly used agents and their desired effects

Back 48

See earlier

Front 49

17. Describe malignant hyperthermia and relate it to general anesthetics. Indicate which of the neuromuscular blocking agents is also capable of triggering this adverse effect. Indicate the drug most frequently used to manage MH. Indicate which inhalation anesthetic does not trigger MH.

Back 49

Malignant Hyperthermia (MH):

Rare life-threatening emergency condition
Management involves:
IV administration of dantroline
discontinuation of triggering agents
supportive
treatment must be instituted quickly


triggered by exposure to volatile gaseous inhalation anesthetics and succinylcholine -
N2O is not a trigger
Signs and symptoms usually develop in an hour after exposure and include
hyperthermia (110+ degrees)
muscle rigidity
metabolic acidosis

Front 50

All drugs can cause MH

Back 50

18. Explain what is meant by ‘irregularly descending anesthesia’ and the importance of this concept.

General pharmacological effects

CNS: dose - dependent depression of all portions of CNS
Order of sensitivity (most to least) is RAS and cortex → hippocampus → basal ganglia → cerebellum → spinal cord → medulla (irregularly descending anesthesia)

Front 51

19. Indicate for which of the IV anesthetics flumazenil would be most useful to recover from overdosage

Back 51

Midazolam

Front 52

20. Indicate the pros and cons of the inhalation anesthetics isoflurane, desflurane, sevoflurane, and N2O.

Back 52

Isoflurane:
Pros: Inexpensive
Little metabolism
No significant systemic tox
Maintains CO because of vasodilation
Con: Pungent odor
Airway irritant
Trigger of MH

Desflurane
Pros:Fast uptake and eliminate
Stable molecules
Little metabolism
No significant systemic tox
Cons:
airway irritant
Sympathetic stimulant
Expensive
Rapid increase in inspired conc may trigger tachycardia and hypertension
Trigger of MH

Front 53

sevoflurane

Pros: Fast uptake and eliminate
Nonpungent
Good for inhalation induction
CV effects similar to isoflurane

Cons:3 – 5% metabolized but no hepatic or renal tox
Reacts with soda lime
Increases serum fluoride conc
Expensive
Trigger of MH

Back 53

N2O

Pros: Analgesic
Fast uptake
Fast eliminate
Nonpungent
Little CV or respiratory depression

Cons: High conc. Required
Teratogenic
Diffusion hypoxia
Expands into closed air spaces

Front 54

21. Given blood/gas partition coefficients, lipid/gas partition coefficients indicate which anesthetic is most likely to induce anesthesia most rapidly and which is most potent.

Back 54

Smaller the MAC the more potent the anesthetic is
Most Potent: halothane
Most Rapid: N20

speed of induction and emergence (recovery)
determined by the rate of change of the partial pressure (concentration) of the gas in the brain
determined by the partial pressure of the gas in arterial blood which is related to alveolar concentration
So concentration in brain related to alveolar concentration
Speed of induction best correlated with blood/gas partition coefficient (inverse correlation)

Front 55

22. Dexmedetomidine is an IV agent that has a unique mechanism of action. Indicate that mechanism of action and indicate some of the unique properties of this agent as compared to propofol and ketamine

Back 55

Dexmedetomidine:

Central acting α2 agonist
Profound sedation with anxiolytic and analgesic properties
Slower onset and longer acting than midazolam and propofol
Minimal respiratory depression but has potential for bradycardia and hypotension
Changes in respiration similar to those observed during natural sleep
Wake up with clear clear consciousness

Decreases propofol, opioid, inhalation anesthetic dose requirements