1/ Tweetorial alert 🚨🚨
Why does propofol burn so much?
It turns out the answer is not what you might expect. We'll cover some literature exploring the question and some evidence-based strategies to prevent it.
#Tweetorial #medtwitter
Why does propofol burn so much?
It turns out the answer is not what you might expect. We'll cover some literature exploring the question and some evidence-based strategies to prevent it.
#Tweetorial #medtwitter
2/
Propofol was developed by John Glen, a veterinarian and researcher at the Imperial Chemical Industries. Yes, that's him down there.
Propofol was developed by John Glen, a veterinarian and researcher at the Imperial Chemical Industries. Yes, that's him down there.
3/
Propofol was originally formulated with a castor oil (Cremophor EL).
This formula was withdrawn due to anaphylactic reactions and re-formulated into a soybean emulsion.
Propofol was originally formulated with a castor oil (Cremophor EL).
This formula was withdrawn due to anaphylactic reactions and re-formulated into a soybean emulsion.
4/ The current formula includes...
10% w/v soya bean oil
1.2% w/v purified egg phosphatide
2.25% w/v glycerol
0.005% disodium edetate
Sodium hydroxide
10% w/v soya bean oil
1.2% w/v purified egg phosphatide
2.25% w/v glycerol
0.005% disodium edetate
Sodium hydroxide
5/
Before we discuss propofol specifically, why does injection of anything intravenously cause pain?
It turns out that “unphysiological” osmolality and pH have both been studied as causes.
Before we discuss propofol specifically, why does injection of anything intravenously cause pain?
It turns out that “unphysiological” osmolality and pH have both been studied as causes.
6/
Klement and Arndt injected saline or glucose of different osmolalities (0 to 6 osmol per kg) and pH (2 to 13) into veins on the dorsum of the hands of seven volunteers.
Klement and Arndt injected saline or glucose of different osmolalities (0 to 6 osmol per kg) and pH (2 to 13) into veins on the dorsum of the hands of seven volunteers.
7/
As you might have suspected, the volunteers included the authors and medical students.
They found that pain occurred at 1.0 osmol per kg (with infusion) and 3.0 osmol per kg (with injection). In addition, extremes of pH < 4 or > 11 evoked pain.
As you might have suspected, the volunteers included the authors and medical students.
They found that pain occurred at 1.0 osmol per kg (with infusion) and 3.0 osmol per kg (with injection). In addition, extremes of pH < 4 or > 11 evoked pain.
8/
Does propofol have a high osmolality or extreme of pH?
Does propofol have a high osmolality or extreme of pH?
9/
The answer is surprisingly no!
Sodium hydroxide is added to maintain a pH between 6 and 8.5 and the published osmolality seems to be ~ 0.3 osmol per kg.
So now what? 🧐
The answer is surprisingly no!
Sodium hydroxide is added to maintain a pH between 6 and 8.5 and the published osmolality seems to be ~ 0.3 osmol per kg.
So now what? 🧐
10/
Klement and Arndt might be able to help us again.
This time, they recruited one more medical student than before and studied propofol evoked pain through serial dilutions in Intralipid and 5% glucose.
Klement and Arndt might be able to help us again.
This time, they recruited one more medical student than before and studied propofol evoked pain through serial dilutions in Intralipid and 5% glucose.
11/
Two 14-gauge cannulae were inserted from down- and upstream puncture sites to study pain with IV perfusion. Ouch.
A 28-gauge cannula was used to inject into the skin of the forearm to study pain with intracutaneous injection. Ouch.
Two 14-gauge cannulae were inserted from down- and upstream puncture sites to study pain with IV perfusion. Ouch.
A 28-gauge cannula was used to inject into the skin of the forearm to study pain with intracutaneous injection. Ouch.
12/
Propofol evoked pain was concentration-dependent in 6 of 8 subjects during IV perfusion.
Pain was related specifically to the aqueous concentration of propofol (dilutions with Intralipid were less painful than dilutions with 5% glucose).
Propofol evoked pain was concentration-dependent in 6 of 8 subjects during IV perfusion.
Pain was related specifically to the aqueous concentration of propofol (dilutions with Intralipid were less painful than dilutions with 5% glucose).
13/
It seems there's something inherent to the drug that elicits the pain.
There are a ton of speculated molecular etiologies including irritation of the venous endothelium through molecules including TPRV1 and TRPA1 that I won’t go into further.
It seems there's something inherent to the drug that elicits the pain.
There are a ton of speculated molecular etiologies including irritation of the venous endothelium through molecules including TPRV1 and TRPA1 that I won’t go into further.
14/
Here are links to some basic science theories.
ncbi.nlm.nih.gov/pubmed/20826794
ncbi.nlm.nih.gov/pubmed/18574153
ncbi.nlm.nih.gov/pubmed/11578842
Here are links to some basic science theories.
ncbi.nlm.nih.gov/pubmed/20826794
ncbi.nlm.nih.gov/pubmed/18574153
ncbi.nlm.nih.gov/pubmed/11578842
15/
Now, what are the most efficacious methods of preventing burning with propofol injection?
A systematic review and meta-analysis from 2011 studied 177 randomized controlled trials.
Now, what are the most efficacious methods of preventing burning with propofol injection?
A systematic review and meta-analysis from 2011 studied 177 randomized controlled trials.
16/
The overall risk of pain was about 60%.
The two most efficacious interventions were use of the antecubital vein or pretreatment with lidocaine in conjunction with venous occlusion for hand veins.
The overall risk of pain was about 60%.
The two most efficacious interventions were use of the antecubital vein or pretreatment with lidocaine in conjunction with venous occlusion for hand veins.
17/
In summary...
💉 Pain on injection of propofol is not related to osmolality or pH
💉 Mechanisms continue to be speculative but seem to be related to the aqueous concentration
💉 Injection into the AC or pretreatment with lidocaine and venous occlusion are effective
In summary...
💉 Pain on injection of propofol is not related to osmolality or pH
💉 Mechanisms continue to be speculative but seem to be related to the aqueous concentration
💉 Injection into the AC or pretreatment with lidocaine and venous occlusion are effective
