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 A pholcodine containing cough syrup has been withdrawn from the market in Norway because of this (and levels of sensitisation seem to be dropping although it is still too early to draw conclusions).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.summary
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The pressure to practice truly patient-focused, evidence-based medicine weighs on every anaesthetist and anaesthesiologist. Yet as the volume of evidence has grown, so has the expectation to always provide the highest quality care.
There is a trap of unknown knowns: evidence known in the greater medical-knowledge body but that we are naively ignorant of.
Bastardising William Gibson (1993), we risk that the evidence:
“…is already here – it's just not very evenly distributed.”
The greatest challenge for evidence-based anaesthesia continues to be the translation of research findings into actual practice change. The key to this is the intersection between quality, personal relevance, general significance, and credibility. But how can we achieve this?summary