Knowledge
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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 A pholcodine containing cough syrup has been withdrawn from the market in Norway because of this (and levels of sensitisation seem to be dropping although it is still too early to draw conclusions).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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Why the excitement?
Since the landmark 2017 WOMAN trial (collected below) showed that tranexamic acid (TXA) may reduce mortality in post-partum haemorrhage, TXA has increasingly been found in close proximity to where obstetric spinal anaesthetics are commonly performed.
TXA's operating theatre ubiquity has also been enhanced by it's replacement of aprotonin in cardiac surgery (Myles 2017, Koster 2015), after the former's associated mortality bump, along with the increasingly routine use of TXA in major joint surgery to reduce bleeding and transfusion (Ho 2003, Poeran 2014).
Recent reviews have identified 21 case reports of mistaken intrathecal administration of TXA over 60 years of anaesthetic publications – although it is likely many cases have been unreported.
Seems rare - why should I be concerned?
- Intrathecal TXA has a 50% mortality, and frequently leaves survivors with permanent neurological injury.
- Once recognised, immediate, aggressive management may improve outcome (particularly, CSF lavage).
- Although rarely published, the increased use of intra-operative TXA may bring it into close proximity with common intrathecal drug ampoules, increasing the risk of this devastating error. Case report publication dates support the increasing incidence.
- Knowing the potential for this error is the first step to avoiding it both personally and systemically.
- Almost all cases involve drug swap errors with major human factor contributions.
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