Expert: Dr Ian Jackson - please note UK based - 9/21/2004

Question
Hi,
I have a very urgent question. I'm student in PhD (physics), I worked on the antioxidant properties of propofol and I defend my thesis tomorrow. A member of my jury suggests me a question but I'm not a doctor so, I don't have any idea of the answer. The question is:
You write in your manuscript that propofol induce sedation within 40 second and after that the blood-brain equilibrium is reached in 2.9 min. This is not a contradiction?

I have another question? Do you know if PPF is less toxic than other anaesthetic agent? I know that chloroform is cancerous, but why?

Thank you for your help.

Belinda Heyne


Answer
Belinda

Wow! Now that is a question and for tomorrow - no pressure then!

What you need is a pharmacologist not a jobbing anaesthetist - however I will do my best.

What you write is not a contradiction, brain equilibrium with the blood level (that is what you are talking about I assume) does take time BUT the concentration required in the brain to achieve sedation occurs long before this point.

Experimental work shows that a effector site (ie brain)concentration of between 4-6 micrograms/ml is required to induce anaesthesia. Sedation would occur below this level. In real life anaesthetists give an 'induction dose' of propofol that induces anaesthesia in under a minute. We achieve this by giving a much larger dose than is necessary. Indeed it is a trick of mine when teaching to give the propofol extremely slowly and demonstrate how little it takes to anaesthetise someone. However this does take a long time - several minutes, and anaesthetists aren't very good at waiting! So we use a larger dose.

Propofol is less toxic than several agents
- sodium thiopentone causes severe anaphylaxis in about 1 in 25,000 patients (this is life threatening)
- halothane can cause halothane hepatitis if given repeatedly over a short period
- chloroform killed people by causing cardiac arrhythmias during anaesthesia
- methoxyflurane caused problems with renal failure due to release of fluoride ions in the body.

I hope some of this makes sense and helps.

Best of luck
Ian