Test 1: Propofol

Question 1

What is the MOA of Propofol?

Answer 1

Potentiates the endogenous GABA-mediated responses in neurons AND directly activates GABAA receptor function.
-Alpha, Beta, and gamma subunits (predominantly Beta 2)

Low dose: Allosteric activator
High dose: Direct acting stimulator

No analgesic properties (does cause amnesia according to Nagelhout)

Question 2

What is an emulsion?

Answer 2

A fine dispersion of minute droplets of one liquid in another in which it is not soluble.

Question 3

Why is it necessary to formulate propofol in a lipid emulsion?

Answer 3

Because of its extremely poor water solubility.
-The most commonly available propofol formulations today involve a mixture of soybean oil, glycerol, and purified egg phospholipid to solubilize the drug.

Question 4

Why can you give Propofol to someone with an egg allergy?

Answer 4

Despite initial concerns that the egg-derived lecithin might precipitate anaphylaxis in egg-allergic individuals, it appears that propofol can be safely used in egg-allergic patients.
-Most egg allergies are related to egg albumin (in egg whites) as opposed to lecithin (primarily in the egg yolk), and a small study revealed no hypersensitivity to propofol in egg-allergic patients undergoing skin prick testing.

Yolk allergy/Lecithin allergy is a contraindication for Propofol

Question 5

What causes the infections related to Propofol?

Answer 5

-The Lipid emulsion state is the perfect environment for bacterial growth
-Has caused both sepsis and death, leading to a 2007 FDA mandate that propofol must have an antimicrobial agent added.
-Diprivan: EDTA
-Generic: Sodium Metabisulfite or Benzyl alcohol

Question 6

How long until a propofol syringe should be discarded? A vial?

Answer 6

Syringe - 6 hours
Vial - 12 hours

Question 7

What factors influence pain on injection?

Answer 7

-the temperature of the drug
-the site of administration
-the size of the vein
-the speed of injection
-the rate of infusion of the carrier fluid
-pH of the drug
-Concentration of the drug

Use the AC if you can and administer Lidocaine with it to reduce injection pain.

Question 8

What are ways that we can reduce the infection risk with Propofol? (Blue Box!)

Answer 8

The contents of an opened ampule, vial or syringe must be discarded if not used within 6 hours.

Minimize the time between preparing the dose to administering the dose.

When preparing a syringe, label appropriately with initials, date and time of expiration.

Question 9

What is important to know regarding Sodium Metabisulfite (additive in generic form of Propofol)? (Blue Box!)

Answer 9

Blue Box: Propofol with metabisulfite preservative increases bronchial tone and does not blunt the vagally mediated effects leading to bronchoconstriction.

Extra info:
-Preservative that contributes to the incidence of bronchospasms in susceptible patients.
-Can potentially irritate asthmatics and/or those allergic to sulfa drugs.

Question 10

What is important to know regarding mixing Lidocaine and Propofol? (Blue Box!)

Answer 10

-No more than 20mg of Lidocaine with 20mL of Propofol
-Starts to separate after 1 hour = Risk of microscopic fat emboli

Question 11

What are the pharmacokinetics associated with Propofol?

Answer 11

-Onset: 9-51 sec (avg 30 sec)
-Highly lipophillic, Protein bound 97-99%
-Metabolism: Hepatic via biotransformation to inactive metabolites, extra-hepatic clearance, and pulmonary uptake
-1/2 life: initial is 40 min, terminal is 4-7 hours
-DOA = 3-10 minutes

Question 12

What is the induction dose of Propofol?

Answer 12

Adults: 1-2 mg/kg
Children: 2.5 - 3.5 mg/kg

Question 13

Why do you decrease the dose of Propofol in elderly?

Answer 13

Decrease the dose in the elderly 2/2 reduced metabolic clearance abilities and general dehydration (decreased volume of the central compartment)

Question 14

Why do you increase the dose of Propofol in pediatrics?

Answer 14

Central compartment is larger and their metabolism is greater

Question 15

What is important to know regarding the metabolism of Propofol and liver failure patients?

Answer 15

Metabolic clearance is not dependent on hepatic blood flow. Can be used in Liver Failure patients.
-Extra hepatic sites of metabolism (lungs, kidneys)

Question 16

What are the CNS effects related to Propofol administration?

Answer 16

-Decreased CBF, CMRO2, ICP, and CPP and IOP
-Decreased arterial pressure and cerebral vasoconstriction
-Cerebral autoregulation is preserved
-EEG slowing to burst suppression
-Anticonvulsant (used in tx of status epilepticus)
-Sedation, hypnosis, anxiolysis, amnesia
-Anti-emetic
-May be “neuro-protective” due to preservation of cerebral perfusion

Question 17

What are the CV effects related to Propofol administration?

Answer 17

-Decreased MAP, BP, and CO with induction doses due to systemic vasodilation and decrease in SNS tone.
-Normal induction dose causes a 25-40% reduction in SBP independent of cardiac status (worse with age > 50 years, ASA III-IV, baseline MAP < 70 mmHg, and when given with high dose fentanyl)
-Peripheral venous dilation from inhibition of SNS vasoconstrictor nerve activity
-SVR decreases 15-25 % (decreased vascular resistance)
-Negative inotropic effect from inhibition of intracellular Ca uptake
-Decreased CO 35-40% (myocardial Depression)
-CV effects can often be reversed due to laryngeal stimulation of intubation.

Question 18

What are the Respiratory effects related to Propofol administration?

Answer 18

-Dose dependent respiratory depression
-Apnea is common with induction doses (dec Vt and RR)
-Minimal bronchial tone alteration (safe for asthmatics) UNLESS sodium metabisulfite is present
-Depression of airway muscle reflexes and tone (concern with OSA)

Question 19

What are the Misc effects related to Propofol administration?

Answer 19

-Decrease dose in age > 50 years
-Less “hangover” effect when compared to other agents
-Effects are altered with age, debilitating conditions, cardiac compromise, and weight
-Give slow IV push to decrease impact of hypotension (hypotension is increased with hypovolemia)
-Anti-emetic, anti-pruritic
-Pain on injection (use AC or pretreat with Lido)
-Inc triglycerides with prolonged infusion

Question 20

What are C/I to the use of Propofol?

Answer 20

-Be very cautious in patients with critical aortic stenosis or cardiac tamponade or poor LV function (can mix with ketamine, have vasopressors available)
-C/I in known hypersensitivity or disorder of lipid metabolism
-Caution in elderly, debilitated, and CV compromised

Question 21

What is Propofol Infusion Syndrome?

Answer 21

Result of prolonged, high dose infusions.
Risk increases: Dose > 5 mg/kg/hr, duration > 48 hours, critical illness, concomitant catechol infusion, and steroid administration
-Most likely due to defect in production of ATP
Symptoms:
-Hypertriglyceridemia
-Metabolic acidosis
-Rhabdomyolysis
-Renal failure (AKI)
-Hemodynamic instability (persistent bradycardia refractory to tx, hypotension)
-Hepatomegaly and elevated LFTs

Associated with infusions for > 48 hours

Tx: D/c Propofol, improve gas exchange, pace for bradycardia, PDE Inhibitors, glucagon, ECMO, CRRT

Question 22

What is the induction, maintenance, and conscious sedation doses of Propofol? From Nagelhout

Answer 22

The induction dose is 1–2 mg/kg followed by a maintenance infusion of 100–200 mcg/kg/min. Conscious sedation doses are 25–75 mcg/kg/min.

Question 23

What is important to know regarding the metabolism of Propofol?

Answer 23

Plasma clearance is high and exceeds hepatic blood flow, indicating the importance of extrahepatic metabolism, which presumably occurs in the lungs and may account for the elimination of up to 30% of a bolus dose of the drug.
-Less hangover effect is due to high plasma clearance.

Question 24

Why is propofol a preferred choice for IV maintenance of anesthesia?

Answer 24

Even after a prolonged infusion, the context sensitive half-time of propofol is relatively short, which makes propofol the preferred choice for intravenous maintenance of anesthesia. Ketamine and etomidate have similar characteristics, but their use is limited by other effects.

Question 25

What is the dose of propofol used to treat PONV?

Answer 25

10-20 mg IV as a bolus or 10 mcg/kg/min as an infusion