Does FEIBA Work for NOACs?

“Maybe”?

The novel oral anticoagulants – dabigatran, rivaroxaban, apixaban, edoxaban – have spread in use quite rapidly. There is weak evidence supporting the use of idarucizumab for emergency reversal of dabigatran, and even weaker evidence regarding the use of adenxanet alfa. Prothrombin concentrate complexes seem to be efficacious for the Factor Xa inhibitors – but what about factor eight inhibitor bypassing agent?

This small case series from Pittsburgh addresses this question in the least helpful fashion: 11 patients and no comparison group. These 11 patients, most of whom were on rivaroxaban, received 20mg/kg of FEIBA for emergency reversal of anticoagulation in the setting of traumatic intracranial hemorrhage. The authors report 6 of these 11 had stable ICH on repeat CT following initial diagnosis, and, therefore, FEIBA is a potentially safe reversal option.

Of course, the full accounting requires us to mention the remainder of patients had radiographic progression of their injuries despite FEIBA. Most injuries were minor and not expected to have elevated 30-day mortality – and, unsurprisingly then, most survived. In the patients demonstrating substantial derangement of laboratory measures of coagulation, most showed profound improvement of the PT following FEIBA administration. Two patients also suffered subsequent thromboembolic events.

So, yes, FEIBA may be a treatment option for the Factor Xa inhibitors – but this hardly supports routine use outside a study setting as these authors seem to be doing.

“Factor Eight Inhibitor Bypassing Agent (FEIBA) for Reversal of Target-Specific Oral Anticoagulants in Life-Threatening Intracranial Bleeding”

https://www.ncbi.nlm.nih.gov/pubmed/28007364

Opiates Versus NSAIDs, the Battle Continues

HealthDay says: “Opioids No Better Than Ibuprofen for Pain After Car Crash: Study”, leading with an assertion that prescription painkillers are no more effective than non-steroidal anti-inflammatory drugs. This was also picked up by the daily American College of Emergency Physicians e-mail newsletter.

So – no?

Despite the best of intentions, there is simply no reliable conclusion to be drawn from the cited publication. In the citation, the authors perform a propensity score-matching secondary analysis of prospectively collected observational data on patients discharged from the Emergency Department following a motor vehicle collision. There were 948 patients in their initial study cohort, with approximately half receiving a prescription at ED discharge. Propensity score matching then further excluded approximately 100 more, and finally patients lost to follow-up reduce their ultimate sample to 284. Their primary outcome was the presence of persistent self-reported moderate to severe pain six weeks after their MVC.

Unsurprisingly, with the wide confidence intervals mandated by their small sample, there was some overlap between the number in each group having persistent pain at six weeks. Thus, this leads the authors to make a guarded, but clearly anti-opiate, conclusion the evidence does not exist to recommend opiate therapy at ED discharge.

The bias in any underpowered study is to commit Type II error, which, as a reminder, is to retain the false null hypothesis in failing to detect an effect. Furthermore, as the authors note in their extensive methods section, in non-randomized studies, the measured and unmeasured confounders ultimately guide group assignment, which can bias the downstream results. The adjustments of propensity matching attempt to control for these, but tend to depend on large sample sizes and robust feature sets to reduce the magnitude of systematic bias – neither of which are present here. The need to impute missing data further reduces the reliability of under foundational data. Lastly, is their primary outcome relevant and related to the interventions examined? I am doubtful that six week persistent pain accurately reflects the scope of benefit (or lack thereof) relating to analgesic pharmacotherapy following MVC.

Avoiding the adverse effect of opiates is certainly important. However, this article should add little to the discussion – despite its lay medical press coverage.

“Persistent pain after motor vehicle collision: comparative effectiveness of opioids versus non-steroidal anti-inflammatory drugs prescribed from the emergency department—a propensity matched analysis”
http://journals.lww.com/pain/Abstract/publishahead/Persistent_pain_after_motor_vehicle_collision__.99393.aspx

When Is An Extremity CTA Necessary?

Here’s another piece regarding low-value testing in trauma, focusing on another topic: the use of CT angiograms for evaluation of extremity vascular injury.

This single-center, retrospective series looks at use of the extremity computed tomography angiogram in the setting of orthopedic and multi-system trauma. For what it’s worth, at least, there were only 275 scans identified during their 10-year study period. However, the bad news, of course: only 16 (6%) of those scans identified an injury requiring treatment.

Of greatest interest to those trying to eradicate low-value care comes the entirely unsurprising observation that 109 (40%) of patients received CTAs despite the absence of hard or soft signs of vascular injury – and all were normal. Additionally, all 16 cases requiring treatment had diminished or absent distal pulses on presentation.

I do anedcotally see the clinical examination being devalued, especially in trauma – it shouldn’t be!

“When are CT angiograms indicated for patients with lower extremity fractures? A review of 275 extremities”
http://journals.lww.com/jtrauma/Abstract/publishahead/When_are_CT_angiograms_indicated_for_patients_with.99386.aspx

From Way Too Many CTs to Many CTs

I am always keen to hear reports of successful imaging reduction interventions – and, even moreso, in trauma. The typical, modern, approach to trauma involves liberal use of advanced imaging – almost to the point of it being a punch line.

This single-center before-and-after report details their experiences between 2006 and 2013. Before 2010, there was no specific protocol regarding CT in trauma – leading to institutional self-examination in the setting of rampant overuse. After 2010, the following protocol was in effect:

trauma algorithm

There isn’t much besides good news presented here. Their primary imaging use outcome, abdominopelvic CT, decreased from 76.7% to 44.6% of all presentations. This was related to an increase in mean ISS for those undergoing CT. When free fluid from non-traumatic causes was individually accounted for, the rate of positivity of these CT rose from 12.3% to 17.5%. Finally, mortality was unchanged – 3.1% vs. 2.7%.

No doubt, any reduction in imaging will miss some important findings. The net counterbalancing effect, however, is likely a massive reduction in costs and harms from further evaluation of false-positives, renal contrast injury, and radiation. And, after all, they’re still performing CTs on nearly half their patients!

“Effect of an Institutional Triaging Algorithm on the Use of Multidetector CT for Patients with Blunt Abdominopelvic Trauma over an 8-year Period”

http://pubs.rsna.org/doi/abs/10.1148/radiol.2016152021

The Extra Head CTs in Trauma, Estimated

In the world of academia and residency training, the spirited debate in trauma is usually regarding the merits of the “pan-scan” – and whether we can all agree it is probably safe to reduce costs and resource utilization by selective scanning. In community practice, it’s about picking up the needle in a haystack – and, hence, preventing the innumerable unnecessary CTs.

This is a retrospective review using electronic health record data to estimate the number of potentially unnecessary head CTs in the setting of trauma. These authors pulled records for all patients for whom a head CT was obtained, and for whom recorded EHR values suggested an encounter for trauma. This cohort was then evaluated for appropriateness of a CT by retrospectively determining the presence of high-risk or exclusion criteria for the Canadian CT Head Rule.

Among 27,240 patients extracted, 11,432 (42.0%) were “discordant” with the CCHR by structured EHR content. However, upon manual review of the chart narrative, the structured EHR content misclassified the CCHR recommendation 12.2% (95% CI 5.6-18.8%) of the time. Thus, the authors then estimate approximately 36.8% (95% CI 34.1-39.6%) of CT head for trauma in a community setting is inappropriate.

This is probably a reasonable research strategy, warts and all. Due to EHR limitations, they actually only filtered for 3 of the 5 high-risk criteria – basilar skull fracture and open skull fracture are such rare findings in their cohort the impact on overall results would be negligible. Then, Kaiser is probably more aggressive at minimizing CT use than the general community ED population, as routine quality improvement monitors individual and group rates of CT usage.

Bottom line: at least a third of head CTs for trauma in the community can probably be obviated by use of validated criteria.

“Computed Tomography Use for Adults with Head Injury: Describing Likely Avoidable ED Imaging based on the Canadian CT Head Rule”

http://www.ncbi.nlm.nih.gov/pubmed/27473552

Pan-Scans Don’t Save Lives

Humans are fallible.  We don’t always make good choices, and our patients – bless their hearts – can sometimes be time bombs wrapped in meat.  Logically, then, as many trauma services have concluded, the solution is to eliminate the weak link: don’t let the human chose which parts of the body to scan – just scan it all.

This is REACT-2, a randomised [sic] trial evaluating precisely the limits to human judgment in a resource-utilization versus immediacy context.  In this multi-center trial, adult trauma patients wth suspected serious injury were randomized to either imaging guided by clinical evaluation or total-body CT.  The primary outcome was in-hospital mortality, with secondary outcomes relating to timeliness of diagnosis, to mortality in other time frames, morbidity, and costs.

This was a massive undertaking, with 1,403 patients randomly assigned to one of the arms, with ~540 in each arm successfully allocated and included in their primary analysis.  Each cohort was well-matched on baseline characteristics, including all physiologic markers, although the Triage Revised Trauma Score was slightly lower (worse) for the total-body CT group.  The results, in most concise form, weakly favor selective scanning.  There was no difference in mortality nor complications nor length-of-stay nor virtually any reliable secondary outcome.  Costs, as measured in European terms, were no different, despite the few scans obviated.  Time-to-diagnosis was slightly faster in the total-body CT group, owing to skipping initial conventional radiography, while radiation exposure was slightly lower in the selective scanning group.

In some respects, it is not surprising there were no differences found – as CT was still frequently utilized in the selective CT cohort, including nearly half that ultimately underwent total-body CT.  There were some differences noted in in-hospital Injury Severity Score between groups, and I agree with Rory Spiegel’s assertion this is probably an artifact of the routine total-body CT.  This study can be used to justify either strategy, however – with selective CT proponents focusing on the lack of differences in patient-oriented outcomes, and total-body CT proponents noting minimal resource and radiation savings at the expense of timeliness.

“Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial”
http://www.ncbi.nlm.nih.gov/pubmed/27371185

Trauma is Still Trauma the Next Day

Acute closed head trauma is easy enough – and challenging enough.  There are validated decision instruments and guidelines, yet still plenty of CTs performed absent sound indications.  However, the question this study addresses is slightly different: what to do with those who present in a delayed fashion following minor head trauma?

The authors probably sum it up best in a reasonably concise fashion:

“Patients presenting after 24h of injury are a potentially distinct subpopulation. They could be at lower risk, as there is evidence that patients with mild/minor head injury who have injuries requiring neurosurgery will deteriorate within 24h. Alternatively, they could be a self-selecting higher-risk group attending due to the worsening or persistence of symptoms.”

These authors reviewed 2,240 patient encounters resulting in a CT scan of the head, with a goal of winnowing it down to just those performed for a traumatic indication.  Of those, 549 were performed within 24 hours of injury and 101 were delayed presentations.  There were 46 (8.4%) CTs positive for traumatic injury in the acute presentations and 10 (9.9%) in delayed, while 5 and 3 patients each underwent neurosurgical intervention, respectively.  So, the answer to their research question, at least in pragmatic terms, may be that the two forces balance each other out.

These authors also present “sensitivity” statistics regarding the utility of guidelines at predicting the presence of an important TBI, and quote a sensitivity of 70% based on chart review.  The denominator for sensitivity would more appropriately the entire population of presentations for trauma, not simply those who underwent CT scanning.  It is also probably more likely, given these patients had important TBI on CT, there may have been undocumented, guideline-compliant, indications not abstracted by chart review.

While our decision instruments for closed head injury were derived in typically an acute population, I would not yet draw any conclusions refuting their generalizability to delayed presentations.

“CT head imaging in patients with head injury who present after 24 h of injury: a retrospective cohort study”
https://www.ncbi.nlm.nih.gov/pubmed/27076439

Hello, Have You Heard of NEXUS/CCR?

In the same vein as my previous post inappropriate imaging despite the presence of PERC, this next article takes our evaluation of minor trauma to task.

This brief retrospective series looked only at presentations to the Emergency Department following “ground level fall” leading to a CT of the cervical spine.  These authors defined a “ground level fall” as fall of fewer than 3 feet or 5 stairs.  These authors then reviewed the documentation associated with each case for criteria specifically excluding the case from NEXUS or CCR and appropriate for CT imaging.

Of the 760 patients with ground-level falls included in this study, there were 7 cervical spine fractures – 6 stable, and 1 unstable.  All patients with a cervical spine fracture had documented criteria supporting appropriate CT imaging.  However, based on their retrospective review, 22.0% and 20.7% of encounters specifically documented criteria meeting NEXUS and CCR, and should not have led to CT imaging.  An additional 9.3% and 29.9% of patients had insufficient documentation of NEXUS or CCR criteria needed to determine appropriateness.

These authors posit there may be substantial cost savings to the healthcare system if these decision instruments are appropriately applied.  I tend to agree – although, there are obvious limitations to this sort of retrospective review.  It does, at least, back up my own anecdotal experience witnessing clinically questionable use of advanced imaging in minor trauma.

“Utility of computed tomography imaging of the cervical spine in trauma evaluation of ground level fall”
https://www.ncbi.nlm.nih.gov/pubmed/27032009

Survival of the Intoxicated

We are mostly all familiar with the beneficial social outcomes associated with occasional alcohol use.  However, we also see the detrimental effects of chronic use in the context of comorbid disease states.

But, it’s apparently not all bad news in a medical sense.

This retrospective evaluation of patients admitted to medical and surgical critical care units in teaching hospitals in Boston simply tracked outcomes segregated by admission blood alcohol level.  Evaluating 11,850 admissions, most admitted patients had undetectable BAC, while 638, 703, and 1,226 patients fell into their three strata of increasing BAC.

Unsurprisingly, as most patients with the highest BAC had the fewest comorbid factors and were overwhelmingly admitted due to trauma, they had the lowest mortality in the unadjusted analysis.  However, across several different types of multivariate adjustment and propensity scoring, the same survival advantage held, although substantially weakened.

There is some school of thought alcohol confers a neuroprotective and anti-inflammatory effect in the setting of acute illness.  These retrospective data, fraught with potential confounders, are inadequate to conclusively confirm or refute such a hypothesis – but it is reasonable to suggest further study of underlying mechanisms may be warranted.

“Association between blood alcohol concentration and mortality in critical illness”
http://www.ncbi.nlm.nih.gov/pubmed/26483354

Don’t Hospitalize Warfarin & Minor TBI

There have been a few retrospective, observational studies evaluating the outcomes of anticoagulated patients with minor head injury.  The incidence reported by such series ranges from 6% in observation with mandatory repeat CT, to 0.6% with discretionary CT.

This series from Singapore reports: 0.3%.
In this series, all patients taking warfarin and having minor head trauma underwent protocolized initial CT and hospitalization for observation.  Repeat CT was performed, however, only at the discretion of the treating physicians.  Of the 295 patients hospitalized, only 11 underwent repeat CT, and only 1 abnormality was identified.  That one patient underwent neurosurgical intervention.  Of the remainder, no patients returned within two weeks of the initial incident with a further episode of delayed bleeding.  Thus, 0.3%.
Is it the difference between mandatory and discretionary repeat CT resulting in the wide range of reported incidence of delayed hemorrhage?  But, if there aren’t any symptomatic changes, are the extra hemorrhages detected clinically important?
Interestingly enough, they also reported three deaths from nosocomial pneumonia.  So, yes, the risk of delayed hemorrhage is non-zero – but likely lower than the risks associated with hospitalization.
“Outcomes of warfarinized patients with minor head injury and normal initial computer tomographic scan”