Induction Drugs-(Propofol) (Ex 2)

Question 1

For Propofol, what are the doses for:
1. Induction
2. Maintenance
3. Conscious sedation

Answer 1

1. Induction = 1.5 - 2.5 mg/kg IV
2. Maintenance = 100 - 300 μg/kg/min
3. Conscious sedation = 25 - 100 μg/kg/min

Question 2

What is the concentration of a 1% solution?

Answer 2

• 10mg/mL

Question 3

What are the inactive ingredients in propofol? Why is one particularly important?

Answer 3

• 1.2% Lecithin (from egg yolks) can cause anaphylaxis with egg allergies.
• 2.25% glycerol
• 10% soybean oil

Question 4

What are the disadvantages of propofol’s inactive ingredient composition?

Answer 4

• ↑ bacterial growth
• ↑ plasma triglycerides with prolonged infusions
• Pain on injection

Question 5

Differentiate Ampofol and Aquavan.

Answer 5

• Ampofol - low-lipid, no preservative that burns on injection more often.
• Aquavan - prodrug with less injection pain but causes dysesthesias. Slower onset, larger Vd, and high potency.

Question 6

What is the mechanism of action of propofol?

Answer 6

• GABA-A receptor modulator that increases Cl⁻ conductance.

Question 7

How does propofol cause immobility through spinal cord-depression?

Answer 7

• Trick question. Immobility from propofol is not from drug-induced spinal cord depression.

Question 8

What are the clearance characteristics of propofol?

Answer 8

The clearance of propofol from plasma exceeds hepatic blood flow.

Question 9

What metabolizes propofol?

Answer 9

• Hepatic CYP450 enzymes and excreted by kidneys.

Question 10

What is the E ½ time of propofol?

Answer 10

• 30 - 90 minutes

Question 11

What is the context-sensitive half-time of propofol? Is this a relatively low or high context half-time?

Answer 11

• 40 minutes (for an 8 hour infusion)
• Low CS ½ time.

Question 12

What are the following characteristics of propofol:
1. Elimination ½ time.
2. Volume of distribution
3. Clearance (mL/kg/min)

Answer 12

1. E ½ time = 30 - 90 minutes
2. Vd = 3.5 - 4.5
3. Clearance = 30 - 60 mL/kg/min

Question 13

Differentiate blood pressure and heart rate changes that occur with propofol vs thiopental.

Answer 13

• Propofol: ↓BP & ↓HR
• Thiopental: ↓BP & ↑HR

Question 14

Does propofol cross the placenta? What are the consequences of this?

Answer 14

• Yes but is rapidly cleared from neonatal circulation.

Question 15

Do cirrhosis and renal dysfunction have significant effects on propofol metabolism?

Answer 15

No significant impact

Question 16

What drug is the induction drug of choice?

Answer 16

Propofol

Question 17

What is the induction dose of propofol in adults? Children?

Answer 17

• Adults: 1.5-2.5 mg/kg IV
• Pediatrics: higher doses due to larger central volume and clearance rate.

Question 18

What is the induction dose of propofol in the elderly?

Answer 18

25 - 50% lower than regular adult

Question 19

What plasma propofol levels would correlate with unconsciousness?
What about awakening?

Answer 19

• Unconscious: 2 - 6 μg/mL
• Awake: 1 - 1.5 μg/mL

Question 20

What is the conscious sedation dose of propofol?

Answer 20

• 25 - 100 μg/kg/min

Question 21

What are the anesthetic characteristics of propofol in the context of conscious sedation?

Answer 21

• Minimal analgesia but has anti-convulsive and amnestic properties.
• Prompt recovery w/ low residual sedation
• ↓ risk of PONV
• Midazolam or opioids as adjuncts.

Question 22

What are the anti-emetic properties of propofol?
Why is this thought to occur?

Answer 22

• Very anti-emetic (more effective than ondansetron)
• Direct depressant of vomiting center

Question 23

What is the sub-hypnotic dosing for propofol?

Answer 23

• 10 - 15 mg IV, followed by 10 mcg/kg/min

Question 24

What is the anti-pruritic dosing of propofol?

Answer 24

• 10 mg IV

Question 25

What is the anti-convulsant dosing of propofol?

Answer 25

1mg/kg IV

Question 26

What are “other” category benefits of propofol?

Answer 26

• Bronchodilation
• Anti-emetic
• Anti-pruritic
• Anti-convulsant
• Low dose analgesia
• Antioxidant
• Does not trigger MH

Question 27

What are propofol’s effects on CMRO₂, CBF, and ICP?

Answer 27

• ↓ CMRO₂, CBF, and ICP

Question 28

Large doses of propofol may ______ cerebral perfusion pressure.

Answer 28

decrease

Question 29

Though propofol will not produce seizures, it will produce _______.

Answer 29

myoclonus (originates from the muscle)

Question 30

Between thiopental, propofol, and isoflurane, which is the least EEG suppressive?

Answer 30

• Propofol

Question 31

Which would decrease blood pressure more, thiopental or propofol?

Answer 31

Propofol

Question 32

What is the mechanism for propofol-induced hypotension?
What conditions will exaggerate this effect?

Answer 32

• SNS inhibition causing ↓SVR and ↓ intracellular Ca⁺⁺.
• Hypovolemia, elderly, and LV compromise

Question 33

How is propofol-induced hypotension from induction usually counteracted?

Answer 33

• Intubation (from laryngeal stimulation).

Question 34

Why is bradycardia seen with propofol?
What would occur with propofol overdose?

Answer 34

• ↓SNS response & baroreceptor reflex
  depression.
• Profound bradycardia & eventual asystole.

Question 35

What are the pulmonary effects of propofol?
How does this change with opioids?

Answer 35

• Dose-dependent depression of ventilation.
• Synergistic resp depression with opioids

Question 36

What severe condition(s) can occur with prolonged propofol infusions?

Answer 36

• Hepatocellular injury or Propofol Infusion Syndrome.

Question 37

What is Propofol Infusion Syndrome?

Answer 37

• Metabolic acidosis thought to occur from poisoning of electron transport chain and impaired oxidation of fatty acids.

Question 38

What relatively benign condition(s) can occur from prolonged propofol infusions?
Why does this happen?

Answer 38

Green and cloudy urine from phenols and uric acid crystals.

Neither alters renal function.

Question 39

What sort of infusion dosing can result in propofol infusion syndrome?

Answer 39

• > 75 μg/kg/min for longer than 24 hours

Question 40

What is the worst side effect in children who have propofol infusion syndrome?

Answer 40

• Severe, refractory, fatal bradycardia

Question 41

What are the symptoms of propofol infusion syndrome?
How is propofol infusion syndrome diagnosed?

Answer 41

• Urine changes, lactic acidosis, brady-dysrhythmias, and rhabdomyolysis.
• ABG & serum lactate concentrations.

Question 42

What are the “other” organ system effects of propofol?(5)

Answer 42

• Injection pain (lido before)
• ↓ IOP
• Plt aggregation inhibition
• Allergic reactions (lecithin)
• Prolonged myoclonus