Prevention of pain on injection of propofol: systematic review and meta-analysis
BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1110 (Published 15 March 2011) Cite this as: BMJ 2011;342:d1110
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
I have received colonoscopic polypectomies every 3 months this year. Numbers 2-4 were MAC anesthesia with Propofol via #22 angio in the right hand. The first administration was pain free. The second administration started like fire in my hand. The anesthesiologist offered lidocaine which I declined and asked that he go slowly and I would not care any more in 15 seconds or so. That is how we proceeded and the pain was 6/10 , remaining contained to the hand only.
On the third administration the pain was so severe in my hand that I jumped up in the bed. She did not slow the administration, and the "fire" rapidly went up my entire arm. I honestly thought someone had taken a blow torch to my arm. Fortunately, the pain was not sustained. I am not a "woose". I have endured trigeminal neuralgia, compartment syndrome and post-op rotator cuff repair pain. The pain of the Propofol RAPID administration made compartment syndrome look like a hangnail.
I have received Propofol 2 other times in my life outside of the situations listed above. They were totally pain free. I am absolutely convinced that administration rate is the is the key to whether Propofol is painfree or not. Obviously, using a 20g I.V. higher in the arm is going to be an even better choice than 22g. in the hand.
Competing interests: No competing interests
In the United Kingdom there are currently three companies which market propofol: AstraZeneca (Diprivan® LCT only emulsion), Fresenius (Propoven® LCT & MCT emulsion) and B-Braun (Propofol-Lipuro® LCT & MCT emulsion). Pain on injection is just one important characteristic of propofol formulations. Equivalence of potency, anti-microbial preservatives and difference in lipid loads are other under-studied aspects which complicates the comparison of propofol formulations.
We must therefore consider the issue in context. Although Jalota et al. review article makes measured recommendations, namely about using propofol emulsions with LCT & MCT when injecting in hand veins (see their figure 11), we must be careful not to embrace a particular propofol emulsion too early. This could affect drug availability, and even worsen the shortage issue. The ramifications of propofol shortage are not only confined to operating theatres. Intensive care units, endoscopy suites & critical care transfers would be equally affected. Until more clinical research can determine which propofol is the best for our patients, perhaps more discussions with pharmaceutical regulators and companies are warranted to ensure that at least the right drug remains available to our patients.
Dr Pierre-Antoine Laloë
Speciality Registrar in Anaesthesia
Yorkshire Deanery, Leeds, UK
References
1- Jalota L, Kalira V, George E, Shi Y-Y, Hornuss C, et al. Prevention of pain from propofol injection: systematic review and meta- analysis. BMJ 2011; 342: d1110
2- http://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm209227.htm accessed 22/5/11
Competing interests: No competing interests
Propofol is an iv general anaesthetic also used as sedative, that
besides hypotension and respiratory depression, frequently induces pain
after intravenous injection. Jalota et al(1). comparing several measures
to mitigate pain, interestling found that using the antecubital vein
instead of the hand vein was the most effective single intervention to
reduce pain. Other drugs (iv anaesthetics, diazepam, antibiotics,
anticancer drugs) may also induce pain after intravenous injection.
It seems worthy to look at the noxious mechanism of this pain.
Nociceptive pain is an alarm signal meaning an underlying lesion, which in
the case of an intravenous injection may correspond to a chemical or
osmotic aggression of the endothelium, especially when the venous flow is
small to dilute drugs. The lesion of the endothelium, which has
antithrombotic properties, sometimes results in the thrombosis of the vein
used for injection. Some caustic drugs must be administered in central
veins (with greater blood flow). I have seen many cases of phlebitis after
administration of diazepam trough catheters placed on hand's veins (low
blood flow).
The administration of drugs in the flow of a polyelectrolytic solution, is
another simple way to dilute drugs, remaining the solution more isosmotic
and likely less aggressive to vascular endothelium.
Besides the chemical/osmotic aggression provoked by drugs, it must also be
considered the lesion induced by the catheter itself.
Vascular endothelium is a very friable structure that in the lab is easily
removed from the vascular wall with a simple passage of cotton gauze. So,
is not surprising that the catheter may injure endothelium when its
diameter is similar to that of the vein, or when it is placed on mobile
zones (like the hand near the wrist) producing scrubbing movements inside
the vessel (2). The forearm length favours a much more stable catheter
than the short hand, and is less throbbing for patient activities like
eating or writing. It could be interesting to study a possible relation of
the catheter location with the phlebitis incidence.
Finally, it is also important to have in mind, that pain elicited by
catheter introduction is greater on hands, which are one of the most
sensitive areas (with a big cortical somatosensory projection), than on
the forearm.
These seem important reasons to prefer for intravenous injections an
antecubital catheter placement instead of their introduction on hands.
References.
1- Jalota L, Kalira V, George E, Shi Y-Y, Hornuss C, Radke O, et al.
Prevention of pain from propofol injection: systematic review and meta-
analysis. BMJ 2011;342:d1110.
2- Catheter associated thrombophlebitis and endothelium. Fernando
Martins do Vale. Rapid Responses for Webster et al.:
http://www.bmj.com/cgi/eletters/337/jul08_1/a339
Fernando Martins do Vale, MD, PhD.
Competing interests: No competing interests
Thank you for your comprehensive review, and for citing our
randomised controlled trial in Table 3 (your reference 267). However, I
note that you list our study under the category of Pretreatment, as
'Stimulant pretreatment'. Our study used ephedrine admixed with propofol,
not as pretreatment (1).
My compliments on an excellent and exhaustive paper!
James Austin
(1) Austin JD, Parke TJ. Admixture of ephedrine to offset side
effects of propofol: a randomized, controlled trial. J Clin
Anesth2009;21:44-9.
Competing interests: No competing interests
The mechanism of lidocaine-tourniquet method
Propofol is a commonly used intravenous anesthetic drug with the confused injection pain issue. Jalota et al. (1) reviewed several interventions to reduce pain on injection of propofol. They concluded that the two most efficacious interventions are using the antecubital vein, and pretreatment using lidocaine in conjunction with venous occlusion using a tourniquet.
The lidocaine-tourniquet method has been widely used for decades. Lidocaine is regarded as a local anesthetic and diffuses from the vascular endothelium to non-vascular nociceptors. Lidocaine blocks membrane-bound voltage-gated sodium channels thereby interrupting impulse transmission in axons. Pretreatment using lidocaine to prevent injection pain alone, however, is less efficient than the lidocaine-tourniquet method, which revealed that the application of tourniquet technique may contribute to reducing the risk of propofol injection pain.
Venous occlusion with a rubber tourniquet at the forearm may have several features. Physically, venous occlusion may cause venous diameter distension mimicking a larger vein. The increased blood volume related to venous occlusion may provide a better buffer system in contact with propofol. Subsequently, the ischemic /reperfusion conditioning by occluding and remove a rubber tourniquet in the forearm may increase expression and activation of transient receptor potential Vanilloid 4 (TRPV4) channels to induced endothelial relaxation (2). Rath et al. demonstrated the hypoxic preconditioning in restoring NO- and further improving endothelium-derived hyperpolarization (EDH)-mediated relaxation and vasodilatation through TRPV4. Thus, the ischemic/reperfusion of venous may maintain venous distention even after the remove of the tourniquet and reduce the concerned injection pain efficiently combined with lidocaine.
1. Jalota L, Kalira V, George E, Shi Y-Y, Hornuss C, et al. Prevention of pain from propofol injection: systematic review and meta- analysis. BMJ 2011; 342: d1110
2. Rath G, Saliez J, Behets G, Romero-Perez M, Leon-Gomez E, et al. Vascular hypoxic preconditioning relies on TRPV4 dependent calcium influx and proper intercellular gap junctions communication. Arteriosclerosis, Thrombosis, and Vascular Biology 2012; 32:2241–2249.
Competing interests: No competing interests