What is catheter-directed therapy? (EKOS)

Catheter-directed lysis therapy delivers thrombolytics (like tPA) via a catheter. Consider it for extensive DVT or submassive or massive PE when you have concerns about bleeding risks.

EKOS (EndoWave Catheter Infusion System) is a device that is supposed to enhance catheter-directed therapy with the use of ultrasonic waves. Ooh! There are several parts of the EKOS experience to be aware of:

  • Control unit–the pump. Can adjust settings and infusion rates. Beeps at you when there are problems.
  • Catheter/drug delivery device–infuses the thrombolytic at a set rate
  • Ultrasound core–supposedly increases thrombolytic efficacy, decreases fibrin clotting
  • Coolant (usually normal saline or heparin-infused normal saline)–to prevent the ultrasound core from overheating/causing tissue damage

A video is worth a thousand pictures: check out the EKOS inservice video on YouTube.

This review goes into some of the nitty-gritty of managing EKOS. The thrombolytic of your choice is usually set to an infusion rate of 1-5 mg/hour. The catheter usually stays in for 18-24 hours. Consider stopping thrombolysis once a maximum dose has been given (like 18-24 mg), 18-24 hours has passed, or repeat ECHO or CTA shows improvement. Once the clinical goal is achieved, the catheters may be removed without repeat imaging. Trend fibrinogen levels: most conservative protocols would reduce or stop the infusion when fibrinogen <200 mg/dL.

While there are studies proving the efficacy and relative safety of EKOS (such as SEATTLE II), there are no high-quality studies that compare EKOS with other kinds of catheter-directed therapy, or against the oldie goodie systemic tPA. Therefore, EKOS seems promising, but people are reluctant to recommend it over other kinds of therapy.

Tangent: not all contraindications to tPA are created equal; see this review on the absolute and relative contraindications to thrombolytics. In addition, even when there are contraindications to tPA, you might still be able to use it and get lucky, as in this interesting case report.

What’s the deal with contrast-induced nephropathy?

How is contrast-induced nephropathy (CIN) diagnosed? 

Generally speaking, CIN is thought of as a more quickly reversible form of ATN: muddy brown casts and tubular epithelial cells can be seen in the urine. You should not see features of glomerulonephritis or AIN (RBC casts or WBC casts) or large urine output a la post-ATN diuresis. The surprise twist is that CIN is associated with a FeNa of <1%, which is more consistent with prerenal physiology.  Core IM podcast did a great episode on CIN that discusses that what we know about CIN is largely based on animal models, and so there is much about this condition that remains poorly understood. Importantly, they note that biopsy is not helpful because lesions in CIN are non-specific.

Should I give pre- and post-contrast hydration? 

Wyatt et al, in this commentary on the 2017 AMACING trial, a Dutch study looking at about 400 patients with CKD stage III getting contrast and risk of CIN, makes clear that the patient’s pretest probability for CIN, as well as the pretest probability for complications from fluid overload, matter a lot. Patients who have diabetes, hypertension, and obviously, CKD that borders on ESRD, are at higher risk. In addition, patients with ESRD who still make urine could be at risk, and giving contrast could worsen their renal function even more. Age (>60 years) may be associated but it’s not clear.if you’re working in an inpatient setting and have a patient with borderline renal function who is at risk of intra-op hypotension and low risk of flashing/pulmonary edema, it’s probably safer to give fluids. A 500 mL NS/LR bolus 30-60 minutes before/after is adequate.

On the other hand, there is very limited evidence to support yes fluids/no fluids. Previous studies that showed reduced risk of AKI with fluids might have shown this benefit because fluids prevented hypotension and ATN, rather than CIN itself. The PRESERVE trial, published in 2018, did not show differences in mortality, dialysis requirement, or persistent worsened kidney function, or CIN in patients receiving preventive IV sodium bicarbonate, oral acetylcysteine, normal saline, or placebo. But, there is always debate in the renal world…if you have a patient with CHF and an EF of 20%…giving fluids or sodium bicarbonate might not be a great idea.

Does the kind of contrast and procedure matter? 

Yes.Interventional studies, like coronary angiography, are higher-risk than diagnostic studies. In addition, according to the Core IM podcast, arterial contrast carries a higher risk of inducing CIN compared to venous contrast, although there are issues with differentiating CIN from atheroembolic showers, selection bias, and lack of control groups in these studies.



Can I give contrast to a patient with end stage renal disease or who’s on dialysis?

The short answer: almost certainly yes. And you don’t need to schedule urgent dialysis afterwards to remove the contrast.

Radiologists will tell you all the time that you can’t order a study with contrast because of someone’s creatinine, and so you may have to argue back, and advocate for your patient to get the study they need. I was inspired to write this post after our radiologist refused to perform a CTA on a patient on HD who turned out to have an actively bleeding 18-cm  hematoma. That’s a problem!

Think about it this way: a patient who is on dialysis does NOT have working kidneys, right? That’s why they’re on dialysis. Therefore, you do not have to protect their kidneys from contrast. The same is most likely true for patients on peritoneal dialysis, although I’m not sure if there are guidelines on this. There is an argument for preserving even residual renal function in ESRD patients, but…most of the time we are ordering CT scans for acute or urgent reasons, so you can do that risk-benefit assessment.

What you DO want to avoid is giving a patient on the cusp of needing dialysis, with CKD-IV or V, a huge contrast load. You don’t want to push them over the edge. Before giving them a CT torso with contrast, or sending them for cardiac catheterization, think about giving a little fluid beforehand and discussing with the renal experts. If it is a life/death situation, I’d probably lean towards giving contrast and hoping they don’t need dialysis permanently afterwards–but make sure there are no other alternatives and your consultants are on the same page as you.

What about MRI contrast? 

Most radiology departments have low-dose gadolinium protocols these days to avoid the feared nephrogenic systemic fibrosis (NSF). Anecdotally, nephrologists are more wary of approving gadolinium, and may be more likely to recommend dialysis after gadolinium load, but again, if there is a truly urgent need for an MRI study, the benefits likely outweigh the risks.

Do you need to schedule urgent dialysis after your patient gets contrast? 

Probably not, but the data is mixed. For example, this prospective study from NEJM suggests CVVH may help (in ICU patients), while other, small studies (here and very small study here) for HD. According to the American College of Radiology’s own 2016 guidelines:  “Unless an unusually large volume of contrast medium is administered or there is substantial underlying cardiac dysfunction, there is no need for urgent dialysis after intravascular iodinated contrast medium administration.”

Fun fact: a recent study from Hopkins in Annals of Emergency Medicine showed that contrast itself was not associated with higher incidence of AKI in patients getting CT scans, even in patients with CKD and on dialysis. (Of course, the doctors were more judicious with ordering CT scans in patients with CKD, and tended to give them fluids beforehand.)

Can I give contrast to a patient with a shellfish allergy?

The short answer: yes!

There is a longstanding theory that because shellfish has a lot of iodine in it, patients who have anaphylactic reactions to shellfish should not be given iodinated radiocontrast because that will set off anaphylaxis as well. This is kind of hand-wavy pathophysiology, as Jennifer Gunter notes on KevinMD: the substance patients do react to in contrast is the hyperosmolar agent in contrast, which tends to be irritating, and there are now low-osmolar alternatives. Iodine itself is an element in the periodic table that is in fact, essential for life, so saying you have an iodine allergy is like saying you’re allergic to water. Which, hopefully, you’re not.

This is an entertaining piece on Clinical Correlations that gives a great evidence-based explanations for why it is absolutely okay to give contrast. A review in the Journal of Emergency Medicine reports that severe reactions (the kind we care about) only occur in 0.02-0.5% of patients, and that patients with higher risk of any kind of reaction tend to be more atopic, that is, have asthma, multiple food allergies, etc.

A few cool points about ultrasound

There are different shapes of transducers:

  • curvilinear (good for mashing down fat)
  • linear (legs, arms, whatever)
  • hockey stick (good for thyroid, breast, and superficial structures)
  • endocavital (mouth, rectum, vaginal)
  • cardiac (for TEE)

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If you REALLY want to get into the nitty-gritty, this article goes into more detail about different ultrasound probes.

Different frequencies are good for different purposes:

  • 1 is good for fat
  • 8 is soft tissue range, like liver or kidney
  • 15 is like breast, thyroid
  • You can increase the “gain” on the ultrasound, and make proteinaceous material move around 😀

There are certain organs that tend to get over-imaged. See this editorial that argues for fewer thyroid ultrasounds.

On CT physics:

the Hounsfield unit describes the radiodensity of objects. The higher, the more radiodense it is, the lower, the less radiodense it is.

-400——- -50——0——- 80 —————————-800

air———– fat– water— soft tissue—————— bone

Do I order this image with or without IV contrast?

The American College of Radiology recommends that unenhanced CT images be used for the following indications through the  ABIM’s Choosing Wisely campaign:

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In addition:

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When contrast is required or will allow for best visualization, RadConsult has made a super-helpful chart organized by rule-out diagnosis:

Contrast required Best with IV contrast, but not required  No IV contrast needed
-any CT angiography (aorta, PE study, carotids/vertebrals, brain)
-adrenal mass assessment*
-aortic dissection*
-cardiac CT (except calcium scoring)
-liver mass assessment*
-pancreatic mass assessment*
-renal mass assessment*
-abdominal pain generally
-any time infection is suspected
-follow-up malignancy exam (usually)
-mediastinal mass (usually)
-postoperative (usually)
-aortic aneurysm size assessment (for intraluminal detail, contrast needed)
-pulmonary nodule followup
-fractures and many osseous lesions
-brain (nearly always; talk to your radiologist if you have questions)
-renal colic
-suspicion for intra-abdominal, retroperitoneal, or other large hemorrhage
-ventral hernia (oral contrast may be helpful)

* Be sure to understand that for these studies, a non-contrast scan is usually part of the protocol, exposing your patient to at least double the radiation dose.




What is the “sniff test?”

Don’t worry, it’s not the “whiff” test.

“Sniff test” can actually refer to two different phenomena. It could be a test used to see in real-time if a patient has unilateral diaphragm paralysis–sniffing is essentially the opposite of a Valsalva maneuver and you would expect both halves of the diaphragm to flatten appropriately. If they don’t, that’s a problem.

It can also refer to duplex ultrasound, and trying to identify the subclavian vein. Eyeballing veins can be tricky. But if you ask the patient to do a “sniff test,” the subclavian should collapse, which can be a helpful way to identify it. Conversely, if you ask the patient to Valsalva, the subclavian should expand.