• What is the significance of Pholcodine for anesthesia?


    Daniel Jolley.

    16 articles.

    Created March 8, 2019, last updated 4 months ago.

    Collection: 95, Score: 2152, Trend score: 0, Read count: 2151, Articles count: 16, Created: 2019-03-08 23:34:17 UTC. Updated: 2023-02-28 22:37:01 UTC.



    Pholcodine is an opioid anti-tussive (ie. cough suppressant). It is a common component of over-the-counter cough medications. However it has a special significance to anesthesiologists in relation to anaphylaxis risk, particularly related to neuromuscular agents.

    Florvaag et al's 2009 review covers this issue very comprehensively. Earlier 2006 research from Florvaag et al attempting to explain some of the regional variability in anaphylaxis rates showed that exposure to pholcodine causes an 60-105 times increase in IgE levels!

    Countries where pholcodine use is common (eg Norway) seem to have experienced higher levels of anaphylaxis to neuromuscular blocking agents than countries where it is not common (eg Sweden). In fact, in Norway rocuronium anaphylaxis was such a problem that its use was restricted to modified rapid sequence inductions. A pholcodine containing cough syrup has been withdrawn from the market in Norway because of this (and levels of sensitisation seem to be dropping although it is still too early to draw conclusions). It will be interesting to see if there are other compounds that have a similar effect on IgE sensitisation and whether other countries will consider withdrawing pholcodine products.

    In addition to the two articles from Florvaag that specifically look at Pholcodine and it's effects, there is also an interesting review looking at recent insights into anaphylaxis in the anaesthetic setting from Dewachter and team.

    Also interesting is Lee et al.'s 2016 case report describing two patients with pholcodine anaphylaxis who then when tested also showed NMBD sensitivity.

    Helen Crilly & Michael Rose's 2014 review in Australian Prescriber Anaphylaxis and anaesthesia – can treating a cough kill? is another great summary of the issue.

    Daniel Jolley  Daniel Jolley

    Opioid anti-tussive pholcodine is a potent IgE stimulator, increasing the risk of perioperative anaphylaxis, and possibly contributing to observed regional variations in rocuronium anaphylaxis.

    Daniel Jolley  Daniel Jolley

    As of February 28th 2023, pholcodine has FINALLY been banned in Australia by the Therapeutic Goods Administration (TGA).

    Press release here: TGA - Pholcodine

    It's very sad that it took 14 years after Florvaag & Johansson's landmark 2009 paper describing the connection between pholcodine and NMBD anaphylaxis, for this problem to be addressed.

    How many patients were exposed to avoidable harm?

    Daniel Jolley  Daniel Jolley

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