Induction agents Flashcards
Mechanism of action of Propofol, Etomidate, Barbiturates, benzos and Ketamine?
Propofol - GABA A Etomidate - GABA A Barbiturates - GABA A Benzos - GABA A Ketamine - NMDA receptor antagonist
After how long after being drawn up should propofol be discarded?
After 12 hrs (was 6 hrs but now it is 12!)
This is because of bacterial contamination (sepsis and bacteraemia) so you should also replace the syringe and tubing
If someone has allergy to eggs, what is the likely reaction to propofol exposure?
Most likely…no reaction. BUT, the manufacturer still recommends against its use in an egg allergy.
Egg lecithin (yolk) is in propofol. Most egg allergies are due to the egg whites (albumin).
Why would premedication of a patient with an infusion of propofol followed by propofol bolus lead to increased time of apnea?
Propofol has a short half life after bolus more due to redistribution, no metabolism. A preexisting infusion of propofol would allow the tissues to have more propofol in them. Then, following a bolus, redistribution would be limited causing apnea
What are the physiologic effects of Etomidate? Mortality in critically ill? Side effects?
Effects: minimal effects on hemodynamics, mild decrease in SVR and respiratory drive, can maintain spontaneous ventilation
Prolonged infusions in criticially ill is associated with increase mortality (likely 2/2 adrenal insufficiency)
Side effects: myotonic movements and jaw clenching. Adrenal suppression occurs in all patients.
Ketamine:
1) Physiologic effects
2) Side effects (what about in CHF?)
1) Activates sympathetic nervous system –> Increased HR, CO, Stroke volume.
2)
a) Direct myocardial depression (usually masked by the sympathetic activation).
- In severe CHF the sympathetic system is fully ramped up so this allows the direct myocardial depression to be significant
b) Psychotomimetic effects (dissociated amnesia)
- Vivid nightmares (this can be avoided with coadministration of benzos)
How and in what amounts are propofol, etomidate, midazolam and fentanyl
Propofol: completely metabolized by liver on a single pass
Etomidate: 50% is unmetabolized when passing liver
Fentanyl and Midazolam: incompletely metabolized when passing liver
G protein pathways?
Pathway 1 (Gs): increased cAMP --> increased protein Kinase A --> decreased Calcium -Ex: beta receptors
Pathway 2 (Gi): Decreased cAMP --> decreased protein kinase A --> decreased Calcium -Ex: alpha 2, Muscarinic ACh2
Pathway 3 (Gq):
What are the effects of propofol?
CV
- Vasodilation (venous/arterial —> decreased pre and after load) –> hypotension
- Baroreflex blunting prevents increase in HR
Resp
- narrow window for causing hyponsis without apnea
- Blunts airway reflexes
Neuro
- Hypnotic effect
- NO Analgesic effect
- Pain on injection (prevent with lidocaine or using a larger vein)
Pancreatitis during long infusions
What accounts most for the termination of action of propofol?
1) Mostly due to redistribution from central compartment to vessel rick peripheral compartments
2) Hepatic Metabolism
3) Lung metabolism (largest extrahepatic site of elimination)
What is Fospropofol?
Effects and side effects?
Prodrug that is metabolized by liver first to release propofol (and formaldehyde).
- due to this, it has a slower onset of action and recovery.
- Large doses causes apnea
- Water soluble, does not require a lipid emulsion
- Decreased pain on injection, no risk of sepsis or hypertriglyceridemia.
Effects of Barbiturates?
- Injection into artery? –> classically causes prolonged vasoconstriction and could potentially lead to lib loss. Classically treat this with stellate ganglion block
- Vasodilation with significant baroreceptor blunting –> hypotension
- Resp depression, apnea
- gold standard for decreasing brain oxygen consumption, cerebral blood flow and ICP
Properties of Ketamine?
- Analgesic effect (somatic)
- Hypnotic effect, termed a dissociative anesthetic with the patient’ sconsciousness unaware of the surroundings
- Less effects on amnesia and no effect on muscle relaxation BUT it does potentiate non depolarizing muscle relaxants.
- Emergence reactions with vivid out of body nightmares.
Properties of Thiopental
- Most likely to cause myocardial depression
- Avoid use in Porphyria.
- Avoid mixing in IV tubing with opioids, cateholamines or NMBs.
- If injected intra arterially can cause arterial spasm potentially causing loss of limb. Treat with stellate ganglion block, heparin, intra-arterial lidocaine.
- No pain in injection
Properties of Dexmedetomidine
-No amnestic effects, resp depression, no renal effects on clearance
-decreases shivering
-Tachyphylaxis after 24hrs use
-Mechanism: activates central and peripheral alpha 2 receptors (much more potent than clonidine)
Side effects: Bradycardia and hypotension
-Metabolized by liver
-Off all commonly used sedating gtts in ICU, most resembles normal sleep
