Induction Drugs: Propofol, Ketamine, Fentanyl, Midazolam
CA-1 · draft
CA-1 Bootcamp day 1. Authored from cited abstracts; every claim carries a PMID.
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Before induction
Propofol produces unconsciousness by positively modulating the inhibitory action of GABA at the GABA-A receptor, and the price it charges for that is a relatively high incidence of apnoea together with a fall in blood pressure.
Patients under 60 needed 2.25 to 2.5 mg/kg of propofol to lose consciousness while those over 60 needed only 1.5 to 1.75 mg/kg, and in the elderly doses above 1.75 mg/kg caused significant hypotension and apnoea - so age changes the dose before anything else does.
About 60% of adults have pain when propofol is injected, and across 177 trials the two most effective preventives were using an antecubital rather than a hand vein (relative risk 0.14) and pretreating with lidocaine under venous occlusion (relative risk 0.29).
Ketamine's central sympathetic stimulation and its blockade of neuronal catecholamine uptake normally mask its direct negative inotropic effect, but in a failing myocardium that direct depression is unmasked and cardiac performance deteriorates.
Fentanyl 2 micrograms/kg given before induction significantly attenuated the rise in arterial pressure and heart rate at laryngoscopy and intubation, and 6 micrograms/kg abolished the response altogether.
Midazolam works by potentiating GABA at the GABA-A receptor and buys you sedation, anxiolysis and anterograde amnesia, along with dose-dependent ventilatory depression and a modest fall in arterial pressure with a rise in heart rate driven by falling systemic vascular resistance.
Questions in the room
Which of these four drugs will drop his pressure, and is it the vessels, the heart, or the sympathetic tone doing it?
Why does the fentanyl go in before the propofol rather than after it?
He grimaces as the propofol runs in - what caused that, and what would have prevented it?
If this were a hypotensive trauma patient instead, which syringe would you reach for first, and what would still worry you about that choice?
Oral boards stem
A 62-year-old man is on your table for an open cholecystectomy. He is hypertensive on lisinopril, has taken nothing by mouth since midnight, and arrives at 148/86 with a heart rate of 74. Four syringes are laid out in front of you - propofol, ketamine, fentanyl, midazolam - and your attending asks which ones you are giving, in what order, and what you expect each of them to do to his blood pressure over the next three minutes.
Sources
Trapani et al., Current Medicinal Chemistry 2000
PMID 10637364
Dundee et al., Anaesthesia 1986
PMID 3487990
Jalota et al., BMJ 2011
PMID 21406529
Bovill, Seminars in Cardiothoracic and Vascular Anesthesia 2006
PMID 16703233
Peltoniemi et al., Clinical Pharmacokinetics 2016
PMID 27028535
Kautto, Acta Anaesthesiologica Scandinavica 1982
PMID 7113629
Olkkola et al., Handbook of Experimental Pharmacology 2008
PMID 18175099
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