Propofol Pharmacology

Question 1

What is Propofol’s Mechanism of Action?

Answer 1

Propofol causes global CNS depression, presumably through

1. Agonism of GABAA receptors
2. Reduced Glutamatergic activity through NMDA receptor blockade.

Question 2

What is the Dose of Propofol for induction?

Assume Healthy Adults ASA 1-2

Answer 2

IV: 2 to 2.5 mg/kg

~40 mg every 10 seconds until onset of induction

Question 3

What is the Dose of Propofol for induction?

Assume Elderly/Debilitated ASA 3/4

Answer 3

1 to 1.5 mg/kg

~20 mg every 10 seconds until onset of induction

Question 4

Propofol Maintenance of general anesthesia dose in Healthy Adults ASA 1-2 <55 years?

Include Initial infusion and then maintence infusion rates (Dose per minute and Dose per Hour)

Answer 4

IV infusion:
Initial: 100 to 200 mcg/kg/minute
(or 6 to 12 mg/kg/hour) for 10 to 15 minutes

Usual maintenance infusion rate: 50 to 100 mcg/kg/minute (or 3 to 6 mg/kg/hour) to optimize recovery time.

IV intermittent bolus: 25 to 50 mg increments as needed

Question 5

What is the dose for Monitored Care Anesthesia Sedation for Healthy Adults ASA 1-2 <55 years?

Answer 5

Slow IV infusion:

100 to 150 mcg/kg/minute (or 6 to 9 mg/kg/hour) for 3 to 5 minutes or slow injection:

0.5 mg/kg over 3 to 5 minutes followed by IV infusion of 25 to 75 mcg/kg/minute (or 1.5 to 4.5 mg/kg/hour) or

incremental bolus doses: 10 mg or 20 mg

Question 6

What is the dose for Monitored Care Anesthesia Sedation for ASA 3-4?

Answer 6

80% of below

Slow IV infusion:

100 to 150 mcg/kg/minute (or 6 to 9 mg/kg/hour) for 3 to 5 minutes or slow injection:

0.5 mg/kg over 3 to 5 minutes followed by IV infusion of 25 to 75 mcg/kg/minute (or 1.5 to 4.5 mg/kg/hour) or

incremental bolus doses: 10 mg or 20 mg

Question 7

Propofol Dose:

ICU sedation in intubated mechanically ventilated patients?

mcg/kg/min
mg/kg/hour
Usual Dose?

Answer 7

Initial:

1. 5.0 mcg/kg/minute
2. 0.3 mg/kg/hour

Increase by:
5 to 10 mcg/kg/minute
or
0.3 to 0.6 mg/kg/hour 
every 5 to 10 minutes until desired sedation level is achieved

Usual maintenance:
5 to 50 mcg/kg/minute
0.3 to 3 mg/kg/hour

Question 8

Propofol Dose for Postoperative nausea and vomiting (PONV), rescue therapy?

Answer 8

IV 15-20 mg, May be repeated

Question 9

Propofol Loading Dose for Status Epilepticus?

Answer 9

Loading dose:

1 to 2 mg/kg with initiation of a continuous infusion.

Question 10

Propofol Maintenance Dose for Status Epilepticus?

Answer 10

Initial:

20 mcg/kg/minute
or
1.2 mg/kg/hour

Question 11

What is the cautionary dose maximum for propofol in Status epilepticus?

Answer 11

> 80 mcg/kg/minute (>4.8 mg/kg/hour) for >48 hours.

Question 12

Are there any dosage adjustments for Propofol For Renal Impairment?

Answer 12

No dosage adjustment necessary.

Question 13

Are there any dosage adjustments for Propofol For Hepatic Impairment?

Answer 13

No dosage adjustment necessary.

Question 14

What Dose adjustments should be made with Propofol with Chronic vs. Acute Alcohol ingestion?

Answer 14

Increase dose in patients with chronic alcoholism (Fassoulaki 1993)

Decrease dose with acutely intoxicated (alcoholic) patients.

Question 15

What is not compatible with propofol regarding line compatibility?

Answer 15

Blood or Plasma

Question 16

What drug can be used with propofol for pain with injection?

Answer 16

To reduce pain associated with injection, use larger veins of forearm or antecubital fossa; lidocaine IV (1 mL of a 1% solution) may also be used prior to administration or it may be added to propofol immediately before administration

Question 17

What is the max dose allowable for Lidocaine 1% with Propofol for induction?

Answer 17

In a quantity not to exceed 20 mg lidocaine per 200 mg propofol.

Question 18

Propofol Excretion

List Percentages

Answer 18

Urine (~88% as metabolites, 40% as glucuronide metabolite);

Feces (<2%)

Question 19

What specific subtype of Half-Life Elimination is Propofol?

Answer 19

Biphasic

1. STEEP (initial) part of curve —> initial distribution of the drug in the body.
2. SHALLOW part of curve —> ultimate excretion of drug, which is dependent on the release of the drug from tissue compartments into the blood.

Question 20

Propofol Has a Biphasic Half Life, what is the initial half tife and what is the terminal half life?

Answer 20

Initial: 40 minutes

Terminal: 4 to 7 hours

Question 21

After a 10 day infusion of propofol, what may the half life become?

Answer 21

After 10-day infusion, may be up to 1 to 3 days

Question 22

Propofol

Metabolism

Answer 22

Hepatic to water-soluble sulfate and glucuronide conjugates (~50%)

Question 23

Propofol

Protein Binding

Answer 23

97% to 99%

Question 24

Propofol

1. Adult Volume of Distribution?
2. Does Vd change after infusion?

Answer 24

1. Adults:
   2 to 10 L/kg;
2. After a 10-day infusion, Vd approaches 60 L/kg; decreased in the elderly

Question 25

Propofol

1. Children 4-12 years:

Volume of Distribution?

Answer 25

Children 4 to 12 years:

5 to 10 L/kg

Question 26

Propofol

Duration of Action?

Answer 26

3 to 10 minutes depending on the dose, rate and duration of administration

Question 27

Propofol

Onset of Action?

Answer 27

Onset of action:

Anesthetic: Bolus infusion (dose dependent):

9 to 51 seconds (average 30 seconds)

Question 28

What are some signs and symptoms for Propofol Relation Infusion Syndrome?

Answer 28

“CHARK”
CK and Renal, Hepatomegaly, Acidosis, Renal, K

Metabolic acidosis

Hyperkalemia

Rhabdomyolysis or elevated CPK

Hepatomegaly

Progression of cardiac and renal failure.

Question 29

Propofol Pregnancy Indications

Answer 29

Propofol Present in Breast Milk

Not recommended by the manufacturer

In studies where propofol is used prior to cesarean delivery, exposure to the infant is low due to low concentrations in breast milk and low volume of breast milk produced within 24 hours’ postpartum. When measurable, concentrations decrease quickly over time

Question 30

Does Propofol Cross Placenta?

Answer 30

Propofol crosses the placenta and may be associated with neonatal CNS and respiratory depression.