Friday, December 14, 2012

More C-Spine "Doom and Gloom"

If you haven't been paying attention to the literature, then you're practicing completely unawares of an epidemic of missed spinal cord injuries.  From the literature that suggests CT isn't adequately sensitive and the final common pathway for c-spine clearance should be MRI, to this new article that says all of those studies in summary aren't enough – and patients might also need "erect cervical spine radiographs".

This is a case series – the authors bill it as a retrospective review, but the methods are laughably absent, at best – of four patients the authors identified as having cervical spine instability missed through traditional diagnostic methods.  These patients, aged 61 through 87, received Emergency Department evaluation for cervical spine injury, were treated conservatively initially, and eventually needed operative intervention.  The ED work-up of these patients can probably best be described as "interesting" – e.g., a 61 year-old female thrown from horse whose initial work-up involved only three-view radiographs of the cervical spine.  Or, a seventy-five year old man with a cervical fracture on CT who was managed initially in a semi-rigid collar without other assessment for ligamentous injury.

Regardless, each of these patients had some combination of eventual CT or MRI that failed to adequately describe the extent of cervical spine instability, but a simple erect radiograph demonstrated subluxation.  Interestingly, this is a little bit of full circle back to the days of flexion/extension films.  While other studies have demonstrated MRI picks up signal abnormalities not detected on CT imaging, the clinical significance of this is debatable.  Conversely, these dynamic/load-bearing plain radiographs offer a true functional test without precisely describing the injury – akin to the difference between cardiac stress testing and coronary angiograms.

These injuries are quite rare, and not every patient needs an MRI or dynamic testing for cervical stability.  However, in the end, these tests have a role and should be utilized as necessary in the appropriate clinical situation.

"Erect Radiographs to Assess Clinical Instability in Patients with Blunt Cervical Spine Trauma"

Wednesday, December 12, 2012

Next Up – Apixaban!

The latest installment of propaganda in the NEJM comes from Pfizer and Bristol-Meyers Squibb, the joint venture behind apixaban.  Along with rivaroxaban, apixaban is an oral Factor Xa inhibitor, another option in the procession of potential warfarin replacements.  The Xa inhibitors, while they've had their problems, improve upon their main competitor – dabigatran – because they can be reversed in the emergency setting using prothrombin concentrate complexes (PCCs).  Dabigatran, as we all know, has no practical reversal strategy.

This is AMPLIFY-EXT, the extended treatment option from AMPLIFY – where apixaban is continued for an additional 12 months for prophylaxis against recurrent venous thromboembolism.  In isolation, looks great!  The placebo group had an 8.8% VTE recurrence in the study period vs. 1.7% in either of the two apixaban doses.  And, major bleeding in the placebo group exceeded the apixaban groups – 0.5% vs. 0.2% and 0.1%.  More effective and safer than a sugar pill!

So, what's the problem?  Well, this is the third apixaban trial to be published in the NEJM in the last two years.  The first one, apixaban for acute coronary syndrome, showed no benefit and increased bleeding.  The next, apixaban for stroke prevention in non-valvular atrial fibrillation (ARISTOTLE), showed non-inferiority to warfarin – but the rate of major bleeding in that study was 2.1% per year.  Then, the NEJM also has a recent article regarding aspirin for the prevention of recurrent VTE – where the placebo group only had a VTE recurrence risk of 6.5% rather than the 8.8% observed in AMPLIFY-EXT.

You can't directly compare trial populations, of course, but it doesn't make any sense that bleeding would be reduced compared to placebo.  And, it's a straw man comparison with placebo – the correct comparison is rather head-to-head against a potentially efficacious agent, such as low-dose aspirin.  After all, low-dose ASA is pennies a day, rather than the ~$10 per day for apixaban.

Can't blame the pharmaceutical companies for selling, can only blame the suckers for buying.

"Apixaban for Extended Treatment of Venous Thromboembolism"

Monday, December 10, 2012

End-Tidal to Predict Operative Intervention in Trauma

In penetrating trauma, sometimes it's very simple to predict operative intervention.  However, sometimes, the perfusion states of our patients are less easy predict – vital signs frequently obfuscate the underlying clinical picture as the body compensates.

This is a prospective study that indirectly aims to validate end-tidal CO2 as a predictor of operative intervention in penetrating trauma by correlating it to serum lactate levels.  And, as their primary outcome, these investigators observed a strong correlation between ETCO2 and lactate levels (R^2 = 0.74).  For secondary endpoints – unsurprisingly, considering it was correlated with lactate – ETCO2 was also predictive of operative intervention.  In fact, the authors report ETCO2 was more predictive of intervention than lactate, although it seems a little odd to significantly outperform lactate, given the strength of their linear correlation.

Compared with systolic blood pressure, the test performance characteristics essentially tell us what we already know: normal blood pressure isn't helpful, low blood pressure is obviously helpful (98% specificity).  Lactate and ETCO2 are more sensitive to hypoperfusion states not reflected in vital signs, although, in this small study, even elevated ETCO2 would miss 1 in 5 operative interventions (sensitivity 82%) and would incorrectly predict 1 operative intervention for every 4 correct predictions (specificity 82%).

If prospective study confirms that ETCO2 outperforms lactate levels as an indicator of hypoperfusion, perhaps it adds something to the trauma bay evaluation.  Otherwise, it seems the most useful function might be to add to prehospital triage protocols – an environment where lactate wouldn't be available.

"Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: A prospective cohort study"