Journal Feed Weekly Wrap-Up
- Feb 19th, 2022
- Clay Smith
We always work hard, but we may not have time to read through a bunch of journals. It’s time to learn smarter.
Originally published at JournalFeed, a site that provides daily or weekly literature updates.
The Controversy | Topical TXA for Epistaxis
An 83-year-old male with history of dementia and atrial fibrillation on warfarin comes in with bleeding from the nose for the past 90 minutes. Direct pressure doesn’t seem to have helped, but his caregiver really wants to avoid packing if possible, since he became extremely agitated last time he received it. Your attending says to pull out the vial of TXA, but you ask: “Wait, wasn’t there a recent study that found TXA didn’t help?”
The Case for TXA
TXA is a fixture in algorithms for epistaxis, including a recent one promulgated by the New England Journal of Medicine. This is based on multiple smaller studies showing promising efficacy.
For instance, a 2018 RCT included 124 patients with epistaxis on antiplatelet agents and compared topical TXA (500 mg) on a pledget to topical lidocaine-epinephrine on a pledget followed by nasal packing. Patients were only eligible for inclusion if 20 minutes of direct pressure failed to resolved their symptoms. The primary outcome was cessation of bleeding within 10 minutes, which occurred 73% of the time in the TXA group vs 29% in the lidocaine-epinephrine/nasal packing group.
Another RCT in 2019 took 135 patients and split them between three arms: atomized TXA (500 mg) with compression, nasal packing with Merocel, and compression alone. Primary outcome was cessation of bleeding within 15 minutes. This occurred 91.1% of the time in the TXA arm vs 93.3% in the Merocel packing arm and 71.1% in the compression alone group. On analysis, both TXA and Merocel were significantly better than placebo, though they were not different from each other.
The Argument Against
However, the largest RCT (NoPAC, 2021) on TXA in epistaxis comes to a different conclusion. It was a double-blinded multicenter RCT which enrolled 496 patients with epistaxis that failed to resolve with 10 minutes of direct pressure followed by topical vasoconstrictor application and then another 10 minutes of direct pressure. Patient were randomized between TXA or saline delivered via cotton wool dental rolls (the UK’s equivalent to pledgets). The protocol called for 200 mg TXA soaked into the dental roll which was held in place in the nare via nasal clip for ten minutes. If this did not control the bleeding, the treatment would be repeated once. Primary outcome in this trial was need for anterior nasal packing, which was placed at the discretion of the treating clinician. There was no significant difference in rates of packing between the groups, with 43.7% of the TXA undergoing packing vs. 41.3% of the placebo group.
My Take and Recommendations
So where does this leave us? We want to be evidence-based, and the largest study on the topic calls into question whether TXA in epistaxis improves outcomes. On the other hand, we know our 83-year-old won’t tolerate packing well, and we would like to spare him (and us) that experience if possible.
Digging into the NoPAC trial reveals a few differences that might contribute to its divergent findings. For one, TXA was given as a 200 mg dose x 2 rather than the single 500 mg used elsewhere. Moreover, all patients enrolled in NoPAC had to first fail a topical vasoconstrictor, which potentially selects a somewhat different patient population. Finally, NoPAC was conducted in the UK, which may limit generalizability to the US given practice variation (e.g. UK patients who undergo nasal packing are admitted for an average of three days).
A 2021 systematic review of topical TXA in epistaxis included 1,299 patients across 8 studies (including NoPAC). Unfortunately, NoPAC was excluded from the analysis of bleeding cessation because its outcome was avoiding packing, but the remaining trials showed that TXA had 3.5 times greater odds of bleeding control at first reassessment.
Thus, the evidence isn’t clear. But as with all treatments we provide to our patients, we have to weigh the risks and benefits. On the benefit side of the ledger, it is unclear if TXA will help this patient to avoid packing. Conversely, topical TXA has minimal adverse effects, is quite inexpensive and won’t take long to trial. Given the negligible downsides of TXA and the known harms of packing this patient, let’s give TXA a try!
An abstruse composite outcome encompassing both clinical response and adverse effects of antibiotics was superior in children who received 5 vs 10 days of antibiotics for pediatric community acquired pneumonia (CAP).
Why does this matter?
Standard duration for pediatric CAP is 10 days. But with increasing antibiotic resistance and the potential side effects of treatment, would a shorter duration do as well?
Just putting SCOUT-CAP on your RADAR
This was a RCT with 380 children with CAP who were treated as outpatients with either 5 or 10 days of antibiotics (mostly amoxicillin). All received either real drug or matching placebo for days 6-10 to maintain blinding. They used a wonky composite primary outcome called RADAR* (response adjusted for duration of antibiotic risk ), which is, “a composite end point that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR).” You know it’s obscure when there is an acrostic within an acronym (sorry…I just got a little DOOR in my RADAR). Anyway, for this composite outcome, there was a 69% probability of a more favorable RADAR in the short-term group.
They also swabbed the oropharynx of 171 of the children, about half in each group, about 3 weeks after diagnosis and found more resistance genes among the prokaryotes in the 10-day group than the 5-day group. The clinical significance of this is not known, but it may indicate a greater chance of resistance with longer duration of antibiotic exposure.
Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial. JAMA Pediatr. 2022 Jan 18. doi: 10.1001/jamapediatrics.2021.5547. Online ahead of print.
*What’s odd is that there were no differences in any of the individual components for clinical response or adverse effects in the short or long term groups, yet the “RADAR” was better in the short-duration group. After reading a paper explaining RADAR and DOOR, I finally understood that a shorter duration of therapy is ranked higher. In other words, if you get the same clinical response (with the same or better adverse effects) using a shorter course of antibiotic therapy, this is objectively better and yields a better RADAR rank. I just found it a little frustrating to have to read a paper in order to understand the primary outcome of this paper.
Delayed intracranial hemorrhage for patients on direct oral anticoagulant therapy with minor traumatic brain injury is rare (~1.5%) after a negative initial head CT.
Why does this matter?
Patients taking direct oral anticoagulant therapy (DOACs) have increased risk of bleeding after minor traumatic brain injury (mTBI). However, recent evidence suggests that the overall risk of intracranial hemorrhage (ICH) for patients taking DOACs after mTBI is low. Furthermore, studies of patients taking vitamin K antagonists report only a small risk of delayed ICH after mTBI (less than 2%), but can this data be extrapolated to patients taking DOACs? Are these patients at high risk for delayed ICH, and do they all need repeat CT scan after 24 hours to ensure a safe discharge?
Waiting 24 hours for a repeat head CT scan is such a headache…
This was a retrospective, multicenter, observational study of 5 EDs in northern Italy from January 1, 2016 to February 1, 2020. The study included patients on DOACs with mTBI defined as “any closed trauma of the craniofacial region associated with a Glasgow Coma Scale (GCS) score of 14–15 at presentation regardless of loss of consciousness immediately after the trauma.” A total of 1,426 patients taking DOACs were included in the study. Most patients included in the study were taking direct factor Xa inhibitor therapy (67.3%), and apixaban and rivaroxaban were the most commonly prescribed DOACs. Atrial fibrillation was the most common reason for DOAC use (90.3%), and accidental fall was the most common modality of trauma (74.9%).
Initial CT head was positive for ICH in 6% of patients (85/1426). Of the patients with an initial negative head CT (n = 1,341), 68.3% (916/1341) underwent a second CT after 24 hours of observation. Overall, only 1.5% of patients (14/916) who had a repeat head CT scan were found to have delayed ICH, and no patients with delayed ICH required neurosurgical intervention or died. Risk factors associated with diagnosis of delayed ICH were post-traumatic loss of consciousness and post-traumatic amnesia. None of the patients evaluated 8 hours after trauma with a negative initial head CT developed delayed ICH.
This study had several limitations given its retrospective design and potential confounders. In addition, a repeat CT was not performed on all patients with a negative initial CT. Instead, the decision to perform a repeat CT was left to the treating physician. However, this could mean that the patients who had a repeat head CT scan were thought to be higher risk than those who did not have a repeat scan.
This study suggests that delayed ICH after mTBI for patients taking DOACs with a negative initial head CT is rare and not associated with death or the need for neurosurgical intervention. Therefore, repeat head CT does not seem to significantly affect patient outcome and may be unnecessary in most instances. Clinical risk factors associated with delayed ICH such as post-traumatic loss of consciousness and post-traumatic amnesia could help determine the need for repeat imaging or observation.
Risk of delayed intracranial haemorrhage after an initial negative CT in patients on DOACs with mild traumatic brain injury. Am J Emerg Med. 2022 Jan 15;53:185-189. doi: 10.1016/j.ajem.2022.01.018. Online ahead of print.