Oropharyngeal angioedema can be one of the true Emergency Department airway disasters. Massive and rapidly progressive edema can engulf all usable landmarks and views, necessitating surgical intervention. No one enjoys these cases – least of all the patient.
This small trial, replete with heavy sponsor involvement, details the utility of icatibant, a selective bradykinin receptor antagonist, for treatment of ACE inhibitor-induced angioedema. 27 patients were randomized either to icatibant or steroids plus an antihistamine. The mean times to symptom relief were reduced substantially by use of icatibant – with reported total symptom resolution reduced from 27 hours to 8 hours.
Of course, for the three placebo patients meeting the protocol definition of worsening clinical status, the authors arbitrarily set their time to symptom resolution to 61.8 hours – exaggerating (unnecessarily) the difference measured for the primary outcome. Finally, bizarrely, 4 of these 27 patients were lost to follow-up – all in the placebo cohort. What sort of effect this would have on the integrity of the results is uncertain.
But, all such misbehaviors aside, icatibant probably works, along with C1-esterase inhibitor and ecallantide. However, each use of these medications costs between ~$7,000-$10,000 per administration. Therefore, restraint is necessary to prevent indication creep – and such medications should not be given to all perioral angioedema presentations, and be reserved only as a final option to fend off impending upper airway obstruction.
“A Randomized Trial of Icatibant in ACE-Inhibitor–Induced Angioedema”
http://www.ncbi.nlm.nih.gov/pubmed/25629740
Or try FFP as an alternative http://www.pulmcrit.org/2015/02/treatment-of-acei-induced-angioedema.html
Agree – FFP makes sense. The lack of evidence in support is almost certainly a result of funding available in support of trials (such as this one). Much easier to promote something being added to formulary/protocol when there's a NEJM publication instead of case-series! Great write-up, by the way. Puts mine to shame!
In our consensus statement we published in AEM on the treatment of angioedema, we did not recommend FFP for theoretical reasons that it may worsen laryngeal edema since it has a significant amount of bradykinin substrate. No RCT has ever been performed to demonstrate benefit or harm with FFP. All of the allergist who contributed to the statement were on board with this recommendation more so than the emergency physicians.
It will be interesting for the multicenter trial that Shire is sponsoring to see if there is benefit for severe angioedema(ISHOO class 3-4 – posterior tongue and laryngeal) especially in light of the ecallantde (Dyax) trial just published in Annals which had been prematurely halted since it showed no benefit at least in mild angioedema. In Cincinnati, we actually lead the very first trial (physician initiated) trial exploring ecallantide for ace – inh angioedema with 50 patients which like the annals trial showed no significant benefit in mild angioedema but for more severe angioedema, we started to get signal. If they (Lewis et al) would have continued on, there might have been signal in more severe angioedema similar to our trial which would be obviously more cost effective to use in such patients i.e $8000.00 is not justifiable to observe someone's lip shrink in 8 hrs vs 22 hrs but could be helpful to prevent those in need of intubation/ icu admission.
Just my opinion