Age-adjusted D-dimer to rule out PE: coming of age?

Put a CT scanner in every U.S. emergency department, add the non-specific signs and symptoms of pulmonary embolism, stir in its potential lethality and morbidity, and line up a few thousand lawyers on the sidelines ready to capitalize on any missed diagnoses, and it’s no wonder that the use of CT-angiograms to rule out pulmonary embolism has risen 11-fold [... read more]

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Think Surgical’s TSolution One Hip Replacement System

think surgical Think Surgicals TSolution One Hip Replacement System

tcat Think Surgicals TSolution One Hip Replacement System

THINK Surgical (Fremont, CA) won FDA clearance for its TSolution One Surgical System for performing total hip arthroplasties. The system relies on pre-operative CT scans and consists of the TPLAN surgical planning application and the TCAT computer guided mill that prepares the bone cavity and joint surface.

The TPLAN software provides 3D tools to analyze and set parameters for milling the bones, helps in selecting the optimal implant, and helps define the best placement and alignment for the implant.

During the operation, the TCAT drill is used to prepare bone with sub-millimeter accuracy according to the developed plan. This way the system permits the creation of multiple plans, selecting an optimal course of action, all without expanding extra surgical time and hopefully leading to optimal results.

Product page: TSolution OneTM Surgical System…

Press release: THINK Surgical™ Brings Precision and Accuracy to Total Hip Replacement with FDA Clearance for the TSolution One™ Surgical System…

A Secondary Examination of The Adventure of the Cardboard Box-Addendum

Screen Shot 2014-12-18 at 7.02.55 PM Screen Shot 2014-12-19 at 10.57.56 AM

Published in the NEJM on December 17th 2014, ushered in with the inflated fanfare only the medical industry capable of, MR CLEAN marks the first successful trial of interventional therapy for acute ischemic stroke. In direct contrast to IMS-3, SYNTHESIS and MR RESCUE, MR CLEAN is a significantly positive trial.  The authors demonstrated success in their primary outcome, “improved neurological outcomes at 90 days” with an adjusted odds ratio of 1.67  (95% confidence interval [CI], 1.21 – 2.30). (1). Why MR CLEAN was positive when the three trials that came before were negative is still unclear. As discussed in my previous post (as well as far more elegant posts on emlitofnote.com and stemlynsblog.org) it may be due to better equipment, faster symptom onset to recanulization times, and the incorporation of CT angiography to identify a cohort of patients who would truly benefit from these invasive interventional strategies. Conversely it may simply be due to the traditional therapy group performing so poorly.

A closer look at the results from MR CLEAN reveals that though the interventional group outperformed the placebo group by a significant amount (an absolute increase of the number of patients alive and independent by 13.5%) compared to its peers, its performance was far from exceptional. In the IMS-3 trial, 40.2% patients in the control arm (tPA alone) were alive and independent at 90 days compared to only 32.6% of the patients in the intervention arm of the MR CLEAN trial (1,2). Even the placebo groups in NINDS and ECASS-3 who received no reperfusion therapies had better outcomes than the patients receiving interventional therapies in the MR CLEAN trial. 26% and 45.5% of the control patients in the NINDS and ECASS 3 trials respectively had a mRS of 0 or 1 at 90 days (3,4). Compared to only 11.6% of the patients in the interventional arm of MR CLEAN.

Though it is difficult and not completely appropriate to compare groups from different trials it does call into question the reasons for MR. CLEAN’s staggering success. It may very well have been the patients in the MR CLEAN cohort were far sicker than the earlier stroke trials, (though both their presenting NIHSS and 90 day mortality rates seem quite similar). It may be that the utilization of CT angiography to select patients for recruitment excluded the majority of the stroke mimics who were included in these earlier trials, and will universally have good outcomes (This seems to be the answer given by the authors when queried by Dr. Ryan Radecki https://medstro.com/groups/nejm-group-open-forum/discussions/44). The subgroup analysis, which indicated only the patients with a NIHSS of greater than 20 demonstrated a statistically significant benefit from endovascular therapy, seems to support this supposition (1). The authors point to a meta-analysis of the six trials examining endovascular therapy for acute ischemic stroke as additionally poof (5). In this analysis by Fargen et al, published in the J NeuroIntervent Surg, the authors examine the subgroup of patients with radiographically confirmed large vessel occlusion (LVO). Similar to MR CLEAN, patients receiving endovascular therapy had better outcomes at 90 days (a mRS of 0-2 38.3% vs 25.8% respectively ). Even in this combined cohort with radiographically confirmed LVO, outcomes were not as dire  as those observed in the MR CLEAN trial.

MR CLEAN’s success may be attributed to the advancements in both procedural proficiency and technological prowess. But it is equally likely the whimsy of random chance was responsible for these impressive results. On a final note it is important to remember that all of these trials examining endovascular therapy in acute ischemic stroke where compared to a control group that included the administration of IV tPA, an intervention who’s own efficacy is very much in doubt. Although the rate of adverse events in the intervention arm of MR CLEAN did not differ significantly from those given only IV tPA, this is only because alteplase offers its own terrifying set unpleasantries. When compared to a true placebo group, I’m sure the rate of symptomatic intracranial hemorrhage and new ischemic stroke (7.7% and 5.6% respectively) would appear far more concerning.

Given the universal failure of the previous three trials examining the very same question surely more confirmatory evidence is required before investing the unimaginable resources required to support the vast infrastructure needed to make interventional therapy a reality. Since MR CLEAN success was announced at the 9th annual World Stroke Conference in Istanbul held in October 2014, two trials examining endovascular therapy in acute ischemic stroke, ESCAPE and EXTEND IA, have halted enrollment early for benefit. It will be interesting to see if these premature stoppages were because of preplanned interim analyses or if MR CLEAN’s success influenced their early termination. I hope we invest the time and resources required to answer these questions with the methodological rigor they deserves. It would be frustratingly tragic to once again be forced to practice with continual doubt because we halted all further investigations out of the fear of discovering reality is not as promising as the false-truth gained from interpreting only the data that pleases us.

 

Sources Cited:

  1. The MR CLEAN Investigators. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med, December 17, 2014
  2. Broderick JP, Palesch YY, Demchuk AM, et al. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368(10):893-903.
  3. .Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333(24):1581-7.
  1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008;359(13):1317-29.
  2. Fargen KM,
Neal D, Fiorella DJ, et al. J NeuroIntervent Surg Published Online First: [please include Day Month Year] doi:10.1136/ neurintsurg-2014-011543

 

 

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Ultrasound Clinical Case: Septic Thrombophlebitis

By Michael Macias

By Michael Macias

The Case 

A male presents to the emergency department with increasing pain to the left groin region for 3 days. He notes that he injects heroin daily and has been injecting into his femoral vein region for the past few weeks. He also notes fever and chills since last night.

Vitals: T 101.5  HR 120  BP 101/53  RR 14  O2 100% on room air

The patient's exam is notable for a 3 cm indurated, erythematous, and exquisitely tender mass directly over the femoral vessel complex at the level of the inguinal ligament. Trace edema is also noted in the left foot and ankle. A bedside ultrasound was performed:

Short axis view along femoral vessel complex over mass. Structures seen here were non compressible

Short axis view along femoral vessel complex over mass. Structures seen here were non compressible

Short axis view along femoral vessel complex over mass, with color doppler. 

Short axis view along femoral vessel complex over mass, with color doppler. 

Structure identification from previous ultrasound views.

Structure identification from previous ultrasound views.

As seen above, no abscess was identified and the two hypoechoic structures of interest were determined to be a reactive lymph node (superficial) and the femoral vein with clot (deep). Given fever and signs to suggest developing sepsis, the presumptive diagnosis of septic thrombophlebitis was made at this time and the patient was initiated on parenteral antibiotic therapy with vancomycin and zosyn. She was also resuscitated aggressively with fluids with excellent response. 

A formal lower extremity venous ultrasound study was obtained which then revealed significant femoral venous thrombosis with distal extension. Anticoagulation with Lovenox was initiated and the patient was admitted to the hospital for further management. The patient later grew out MSSA in his blood cultures which confirmed the diagnosis. 


Septic Thrombophlebitis

Septic thrombophlebitis is a condition that is characterized by venous thrombosis, inflammation and bacteremia. It has a wide range of presentation from local benign infection to septic shock. There are a multitude of distinct clinical conditions that have been described previously, depending on which venous structure is involved, however the basic pathophysiology  remains the same. The most common locations this entity is seen includes:

  • Peripheral veins: Predominately from skin breaks, phlebotomy or IV drug use.

  • Pelvic veins: Resulting from uterine infections such as endometritis or septic abortion.

  • Superior vena cava (SVC) or inferior vena cava (IVC): Often associated with indwelling central venous catheters

  • Internal jugular vein (Lemierre syndrome): Contiguous spread from oropharyngeal infection.

  • Dural sinuses: Contiguous spread from sinus infection. 

Let's focus specifically on this condition in the IV drug user.

Since IV drug users frequently inject smaller veins in their arms and legs, these vessels eventually become sclerosed and they turn to larger vessels such as the femoral, axillary and neck increasingly for injection preference. With repeated use, these vessels become injured, leading to hematoma formation, thrombosis and potentially superinfection. At this point septic thrombophlebitis can develop, however other complications can be seen such as mycotic aneurysm or traumatic arteriovenous fistula

Common bacterial flora: Gram-positive cocci, usually S. aureus (streptococci and enterobacteriaceae are also seen). Gram-negative pathogens, particularly P. aeruginosa, are not infrequently found. Polymicrobial infection is common. 

Clinical findings: Local pain, swelling and redness over injection site is predominately seen which can often appear as a simple abscess or cellulitis. Occasionally, these infections can be limited to deeper venous structures without considerable superficial skin changes. Fever is usually present in about 50% of these patients. 

Work up:

  • Labs: CBC, basic chemistry, lactic acid, coags
  • Blood cultures
  • Imaging: Ultrasound or CT with IV contrast

Treatment: The treatment of peripheral septic thrombophlebitis remains controversial. While parenteral antibiotic therapy is standard of care, the value of anticoagulation use has not been established. It may be reasonable to consider anticoagulation if there is significant clot burden or extension in a deep vessel.

The theoretical concern with anticoagulation is that if there has been septic embolic events to the lungs or brain, with subsequent mycotic aneurysm formation, then there is a potential risk for bleeding from these sites. The entire clinical picture must be taken into account, including complete physical exam, symptoms and comorbidities before considering anticoagulation. 


Conclusion

You always need to maintain a high suspicion for serious infection in the IV drug user, even when the infection may seem superficial and benign at first. Don't be afraid to slap on your ultrasound probe to get more information to assist with your clinical decision making and help guide you to the proper diagnosis.

I recommend listening to a great lecture by Andy Neill on Approach to the IV Drug User at Emergency Medicine Ireland for further learning on this topic. 

Learn how to perform ultrasound to evaluate for deep venous thrombosis at Ultrasound Podcast

Interested in Ultrasound? Check out our Ultrasound Leadership Academy Posts below: 


References

  • Bennett: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed.

  • [Guideline] Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. Jul 1 2009;49(1):1-45.

  • Baker CC, Petersen SR, Sheldon GF. Septic phlebitis: a neglected disease. Am J Surg. Jul 1979;138(1):97-103. [Medline].

  • Mertz D, Khanlari B, Viktorin N, Battegay M, Fluckiger U. Less than 28 days of intravenous antibiotic treatment is sufficient for suppurative thrombophlebitis in injection drug users. Clin Infect Dis. Mar 1 2008;46(5):741-4. [Medline].

Endovascular Therapy, Unproven Efficacy, Unproven Effectiveness

With the publication of MR-CLEAN two days ago, the medical world (especially Covidien, Stryker, and Penumbra) is ready to throw out all previous neutral trials – MR-RESCUE, SYNTHESIS, IMS-3 – and rush headlong into endovascular therapy for acute ischemic stroke as a new standard of care.

Nonsense, you say?  Not when financial and professional conflicts-of-interest coordinate to drown out the skeptics.

And, frankly, the reality is – despite trials failing to demonstrate benefit, endovascular therapy is already in widespread use.  The underlying tissue-reperfusion hypothesis upon which thrombolytic therapy is predicated is too compelling to wait for proof of efficacy or effectiveness.  Alas.

This is ICARO-3, essentially an ongoing prospective registry of patients considered by experts as optimal candidates for endovascular interventions.  These are all proximal internal carotid artery occlusions, having the among the least favorable rates of recanalization with IV tPA alone.  These authors obtained data on 324 cases between 2010 and 2013 receiving endovascular therapy and 324 matched controls (including 253 from the original ICARO study).  The endovascular cohort included a distribution of patients who received intra-arterial lysis, mechanical retrieval, systemic thrombolysis, or a combination of those treatments, while the tPA cohort received systemic thrombolysis alone.

Patients were generally well-matched on baseline characteristics, with an overall median NIHSS of the entire cohort of 16.  Ultimately, 18.2% of the IV tPA-only cohort had an mRS 0-1 at three months, compared with 20.7% of the endovascular cohort, and OR of 1.17 (95% CI 0.79-1.73).  However, 37% of the endovascular cohort experienced intracranial bleeding of which 6% was fatal, compared with 17.3% and 2.2% in the tPA-only cohort.  In summary, the outcomes – both positive and negative – were a wash.  The authors try to splice out an adjusted subgroup of specific types of endovascular interventions with improved outcomes compared with controls, but these statistical calisthenics are best left unmentioned given their limited validity.

So, until MR-CLEAN, all the randomized trials for efficacy have been neutral.  ICARO-3, a real-world effectiveness observation – also neutral.

Is it too late to derail the bandwagon?

“Intravenous thrombolysis or endovascular therapy for acute ischemic stroke associated with cervical internal carotid artery occlusion: the ICARO-3 study”
http://www.ncbi.nlm.nih.gov/pubmed/25451851