Propofol Injection Pain

Propofol is an intravenous anesthetic agent commonly used for procedural anesthesia, in which a patient is given a sedating medication along with an analgesic medication before an operation, and as an induction agent for general anesthesia.¹ Propofol is an alkylphenol: the molecule contains a benzene ring (six carbons arranged in a hexagon) attached to an –OH group, both of which are bound to an additional chain of carbon molecules. Phenol-containing drugs often cause pain on injection, but injections of propofol are notoriously painful. Approximately 70% of patients who do not receive a pretreatment report propofol injection pain.² For comparison, the incidence of pain on injection for other anesthetic agents like thiopentone and midazolam is below 10%.³ 

Several theories have been suggested for the cause of propofol injection pain. One postulates that propofol interacts with sensory nerve fibers located in the outermost walls of blood vessels. Certain ion channels, such as transient receptor potential ankyrin 1 (TRPA1) release neuropeptides upon interacting with propofol, which induce vascular leakage, vasodilation, and inflammation, all of which can cause pain at the site of injection.⁴ This theory accounts for the finding that pain is lower when propofol is injected into a large vein: the medication on average makes less contact with the endothelial walls of the vein.⁴  

Other factors affecting the pain caused by a propofol injection include the speed and location of injection. Slower injections cause more pain, possibly due to the prolonged exposure to propofol (whereas a faster injection would clear propofol out of the vein more quickly). Additionally, when administered in the antecubital fossa (the inner region of the arm connecting the forearm and bicep), propofol typically causes a smaller amount of pain, while much greater pain is experienced when propofol is injected into the dorsum (back) of the hand.⁵ 

 Due to its popularity as an anesthetic agent, several strategies for mitigating propofol injection pain have been developed. The most popular is to administer lidocaine, a local anesthetic, either with or before propofol injection. The propofol injection is an emulsion (mixture of two immiscible liquids) of the molecule with water, and lidocaine destabilizes the emulsion, which can reduce the potency of the anesthetic but also the pain it causes. One study found that lidocaine administration both before and simultaneous with propofol injection did not affect the dose of propofol required for loss of consciousness.⁶ 

In a more recent study conducted by a team of Chinese researchers, the ability of the medication dexmedetomidine to reduce propofol injection pain was evaluated.⁷ The study consisted of three groups of patients: a lidocaine only group, a dexmedetomidine group, and a third that received both medications prior to propofol injection. While patients in the combination group experienced pain, its incidence (51%) was significantly lower than that of the dexmedetomidine only (67%), lidocaine only (71%), and placebo groups (94%).  The authors speculate that dexmedetomidine has a greater impact on pain relief due to its ability to raise the pain threshold as an agonist for receptors involved in pain signaling.⁸ Studies such as this will help ensure the comfort of patients receiving propofol. 

References 

1. Procedural Sedation. https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/procedural-sedation (2019).
2. Kang, H.-J. et al. Clinical factors affecting the pain on injection of propofol. Korean J. Anesthesiol. 58, 239–243 (2010), DOI: 10.4097/kjae.2010.58.3.239
3. Tan, C. H. & Onsiong, M. K. Pain on injection of propofol. Anaesthesia 53, 468–476 (1998).
4. Desousa, K. A. Pain on propofol injection: Causes and remedies. Indian J. Pharmacol. 48, 617–623 (2016), DOI: 10.4103/0253-7613.194845
5. Scott, R. P., Saunders, D. A. & Norman, J. Propofol: clinical strategies for preventing the pain of injection. Anaesthesia 43, 492–494 (1988), DOI: 10.1111/j.1365-2044.1988.tb06641.x
6. Tan, L.-H. & Hwang, N.-C. The Effect of Mixing Lidocaine with Propofol on the Dose of Propofol Required for Induction of Anesthesia. Anesth. Analg. 97, 461–464 (2003), DOI: 10.1213/01.ANE.0000066357.63011.75
7. Lu, Y. et al. Intravenous Dexmedetomidine Administration Prior Anesthesia Induction With Propofol at 4°C Attenuates Propofol Injection Pain: A Double-Blind, Randomized, Placebo-Controlled Trial. Front. Med. 8, (2021), DOI: 10.3389/fmed.2021.590465
8. Kaur, M. & Singh, P. M. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth. Essays Res. 5, 128–133 (2011), DOI: 10.4103/0259-1162.94750