Icatibant for ACE-Inhibitor Angioedema

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”

TMJ Dislocations: A Better Mousetrap?

Anterior temporomandibular dislocations are generally quite satisfying closed reductions.  Patients, understandably, are exceedingly grateful to have their function restored.  However, it typically requires parenteral analgesia, sometimes procedural sedation, and puts the practioner at risk of injury from inadvertent biting.

This interesting pilot describes a technique in which the patient, essentially, self-reduces the TMJ dislocation by using a syringe held between the posterior molars as a rolling fulcrum.  I’d describe it in more detail, but I think, from the image reproduced here, you’ll get it:

These authors used this technique for 31 cases, and only one was ultimately unsuccessful.

While this is not the intended use for a syringe, I can’t hardly imagine any terrible harmful adverse effects from materials failure – and they don’t exceed the risks of procedural sedation.  I certainly find it reasonable to experiment with this technique.

“The ‘Syringe’ technique: a hands-free approach for the reduction of acute nontraumatic temporomandibular dislocation in the Emergency Department.”

The Myth of “Sinus Headache”

Here’s a simple truth to take away: incidentally-noted “chronic sinusitis” on CT should not be used as a scapegoat for acute atraumatic headache symptoms in the ED.

This is a retrospective review of non-contrast head CT at a single center in Boston, comparing 234 patients undergoing CT for atraumatic headache and 266 undergoing CT for minor head injury.  22.2% of atraumatic headache patients received radiologic diagnoses of “chronic sinusitis”, while 17.7% of minor head injury patients had a similar radiologic finding.  The authors conclude, within the limitations of this retrospective review, that findings of “chronic sinusitis” are purely incidental, and unlikely to be related to an Emergency Department visit for acute atraumatic headache, and should not be diagnosed with “sinus headache”.

This fits in with multiple other investigations demonstrating most “sinus headaches” outside the context of acute upper respiratory infection meet criteria for migrane, and respond to serotonin-receptor agonists.  Do not treat these patients with antibiotics, and do not correlate these incidental radiologic findings with acute pathology.

“Findings of chronic sinusitis on brain computed tomography are not associated with acute headaches.”

Kids with Tubes and Otitis Media Get Drops not Pills

A guest post by Anand Swaminathan (@EMSwami) of EM Lyceum and Essentials of EM fame.

Over the last decade, researchers have sought to determine the usefulness, or lack there of, for systemic antibiotics in a number of infectious etiologies previously thought to require antibiotics for resolution. This includes strep throat, sinusitis, bronchitis and, more recently, diverticulitis. Acute otitis media (AOM) has long been a target for such studies and recently, the guidelines have changed. The American Academy of Pediatrics now endorses a “wait and see” approach for many children with AOM while also recommending a more stringent definition of the disease.

What about for patients with tympanostomy tubes who present with signs of AOM? These patients typically present with otorrhea (pus from the tympanostomy tube). Is the presence of drainage adequate to treat or should these patients be placed on oral or topical antibiotics? Small trials have shown good efficacy of topical antibiotics but Pediatricians and Emergency Physicians continue to prescribe oral antibiotics in the face of inadequate evidence.

The researchers here attempt to answer this question. They performed a fairly large study of 230 children who were randomized to either observation, oral antibiotics or topical antibiotic-glucocortocoid drops in an open-label fashion. The primary endpoint was resolution of otorrhea at 2 weeks. The results are surprising. Resolution was seen in 95% in the group given drops, 56% in the oral antibiotic group and 45% in the observation group. These numbers yield a miniscule NNT = 3 for resolution of otorrhea with topical antibiotics-glucocortocoids vs. oral antibiotics.

A couple of notes are important. All of the patients had otorrhea for up to 7 days prior to entering the study and the presence of a fever excluded them from the study. Additionally, tubes couldn’t be recently placed (< 2 weeks) there couldn’t be recent antibiotic use (< 2 weeks) or otorrhea (< 4 weeks).

As evidence mounts to the harms of inappropriate and unnecessary systemic antibiotic use, it’s important to tailor therapy based on the available literature. Many patients with tympanostomy tubes that develop otorrhea will resolve with simple observation. However, treatment with topical antibiotic-glucocortocoid drops should be the first line treatment as they are superior to oral antibiotics with fewer side effects.

“A trial of treatment for acute otorrhea in children with tympanostomy tubes.” 

Tranexamic Acid for Epistaxis

Well, it’s not the major hemorrhage of CRASH-2 – but, as every Emergency Physician knows, refractory epistaxis is burdensome and significantly irritating to all involved.  Luckily, there are a variety of methods available to manage bleeding, mostly successful.

You may now add tranexamic acid to this list.  TXA, an antifibrinolytic agent, already used to reduce hemorrhage-associated coagulopathy, has been used in many different forms for minor bleeding as well.  These folks from Iran randomized, in unblinded fashion due to differences in odor, folks presenting with severe epistaxis to “conventional control” with cotton pledgets soaked in lidocaine + epinephrine versus pledgets soaked with 500mg of TXA.  Sadly, they do not declare a primary outcome – rather, the authors list several “efficacy variables” – but, whichever they would have chosen, it would have favored the TXA group.  71% of TXA patients had cessation of bleeding within 10 minutes, versus 31% with lidocaine+ epinephrine, faster discharge from the ED, less rebleeding in 24 hours, and less rebleeding at a week.

It seems physiologically plausible, in any event, considering lidocaine+epinephrine isn’t truly directly therapeutic for hemostasis.  As any Emergency Physician knows, it’s all about Plan B, C & D for every situation – and TXA seems another reasonable tool for the box.

“A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial”