Sonothrombolysis in Stroke
The current state of play in hyper-acute stroke care mirrors the evolution of acute STEMI care over a decade ago. There is now beginning a very slow and gradual transition from systemic thrombolysis to neuro-interventional, catheter directed therapies. Whilst this is a wonderful thing, there remains significant barriers to accessing clot retrieval for most patients. Further, both primary percutaneous coronary intervention (pPCI) and clot retrieval are not just currently inaccessible to the majority of the world’s population, but, due to cost and expertise, will likely remain so for decades to come.
Could ultrasound hold the key to future low-cost interventional therapies?
Trans-Cranial Ultrasound, as its name suggests, involves placing the probe over the thinnest portion of the temple and scanning through the skull to visualise the brain.
Trans-Cranial Ultrasound can allow visualisation of various aspects of the brain, particularly the circle of Willis (most importantly the Mid- Cerebral Artery (MCA)) using Doppler, as well the ventricles, in B-mode. This technology has been around for a while and is finally starting to gain rapid traction as a diagnostic modality (1).
While its diagnostic use continues to grow, another avenue of possibility has opened up. Through exploring the effects of focussed ultrasound technology on tissues, ultrasound as an interventional modality is undergoing an evolution. The impact of sound waves on tissue causes rarefaction and compression; a kind of expansion and contraction. This vibration (movement) also causes some heat and has traditionally been viewed in a negative light; being the reason the ALARA (As Low As Reasonably Achievable) principle was introduced, and MI (Mechanical Index) and TI (Thermal Index) values are displayed on all machines. Interventional ultrasound is harnessing this effect to target lesions; and in the case of endovascular pathology, to target clots.
Roughly 80-90% of the population have skulls thin enough for Transcranial Doppler to penetrate them; however in the remaining 10-20% of people (2,3), a microbubble contrast is required for visualisation. This microbubble contrast is a non-reactive substance of micro-gas particles trapped in a synthetic fatty-fluid, and a critical component to only excellent visualisation, but also intervention.
When microbubbles are exposed to an ultrasound beam, they alter the attenuation of sound through the fluid inside a vessel. An effect known as Inertial Cavitation occurs(4) (i.e. the formation and violent collapse of gas-filled bubbles in a fluid) which causes short lived micro-jetting of surrounding fluid, structurally weakening the clot(5). Stable cavitation also causes microstreaming, which enlarges the size of the microbubbles and might compress the thrombus against the vessel wall, creating small pores in its surface(3).
By focussing the ultrasound beam on the thrombosed vessel for between 30-60 minutes, preliminary research is suggesting that rarefaction and compression work to affect a combination of an acoustic radiation force, stable cavitation, and inertial cavitation, of the microbubble contrast. We still don’t know which effect is most important, nonetheless, combined they effectively “shake up” and dislodge the fibrin structures of the clot, causing it’s proximal edges to weaken and degrade(3). This then paves the way for either the body’s endogenous lytic process, or an introduced lytic agent, to begin further disintegrating the thrombus.
Already three separate observational studies suggest that Trans-Cranial Doppler might accelerate vessel recanalization in combination with r-tPa (recombinant tissue plasminogen activator) (6–10).
Sonothrombolysis might also be effective in occlusive myocardial infarction, and initial trials are underway at the University of Alberta to test the effect of pre-pPCI microbubble contrast sonothrombolysis (NCT03092089)(11).
It sounds rather magical and far-fetched, and frankly the science still has a way to go, but sonothrombolysis is pitching to hit serious research soon, and when it does, it’s going to make waves.
Images Credit (12,13)
1. Lau VI, Arntfield RT. Point ‑ of ‑ care transcranial Doppler by intensivists. Critical Ultrasound Journal. 2017;
2. Bahner DP, Blickendorf JM, Bockbrader M, Adkins E, Vira A, Boulger C, et al. Language of Transducer Manipulation. Journal of Ultrasound in Medicine [Internet]. 2016 Jan;35(1):183–8. Available from: http://doi.wiley.com/10.7863/ultra.15.02036
3. Bader KB, Bouchoux G, Holland CK. Sonothrombolysis. Adv Exp Med Biol. 2016;339–62.
4. Everbach EC, Francis CW. Cavitational mechanisms in ultrasound-accelerated thrombolysis at 1 MHz. Ultrasound in medicine & biology [Internet]. 2000 Sep;26(7):1153–60. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11053750
5. Meairs S. Sonothrombolysis. Translational Neurosonology. 2015;36:83–93.
6. Eggers J. Sonothrombolysis for treatment of acute ischemic stroke: Current evidence and new developments. Perspectives in Medicine [Internet]. 2012 Sep;1(1–12):14–20. Available from: http://linkinghub.elsevier.com/retrieve/pii/S2211968X12000290
7. Rubiera M, Alexandrov A V. Sonothrombolysis in the Management of Acute Ischemic Stroke. American Journal Cardiovascular Drugs [Internet]. 2010 Feb;10(1):5–10. Available from: http://link.springer.com/10.2165/11316850-000000000-00000
8. Lu Y, Wang J, Huang R, Chen G, Zhong L, Shen S, et al. Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic Microembolism-Induced Acute Ischemic Stroke. Stroke [Internet]. 2016 May;47(5):1344–53. Available from: http://stroke.ahajournals.org/lookup/doi/10.1161/STROKEAHA.115.012056
9. Ricci S, Dinia L, Sette M Del, Anzola GP, Mazzoli T, Cenciarelli S, et al. Sonothrombolysis for Acute Ischemic Stroke. Stroke. 2013;6–8.
10. Controlled R, Sonothrombolysis C. NOR-SASS ( Norwegian Sonothrombolysis in Acute. Stroke. 2017;1–8.
11. Becher H. Clinical Trials: Sonothrombolysis in Patients With STEMI [Internet]. NCT. 2017 [cited 2018 Jun 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03092089
12. Phillips. Microbuble Cavitation [Image] [Internet]. 2017. Available from: http://thefutureofthings.com/3805-ultrasound-activated-microbubbles-fight-cancer/
13. Radiologykey.com. Use of transcranial Doppler ultrasonography in the pediatric intensive care unit [Internet]. radiologykey.com; 2016. p. 1. Available from: https://radiologykey.com/use-of-transcranial-Doppler-ultrasonography-in-the-pediatric-intensive-care-unit-consultant-level-examination
In collaboration with Developing EM, our core partners ISTIH and our partners at AIU, we are proud to announce Dr Nilanka Wickramaratne and Dr Harendra Cooray from Sri Lanka as recipients of the 2018 EMUGs Developing Countries Scholarship.
Dr Wickramaratne and Dr Cooray were nominated and selected in collaboration with The Critical Care Society of Sri Lanka. They have both demonstrated a sincere commitment to quality improvement in Sri Lanka. Their participation in this scholarship will enable significant training opportunities for Emergency Medicine doctors in training in Sri Lanka under their leadership.
The students will be attending AIU's 5 day Advanced Emergency Medicine Ultrasound (POCUS) course compliments of our generous partners at AIU.
They will also be attending as many of EMUGs Regional Events as possible either in person or via video conference so please join us in making them feel welcome and a part of our amazing EMUGs community of passionate POCUS professionals.
When I learned how to use ultrasound, I thought - wow, now I have this tool, I’ll never miss an IV again! I mean, you can see what you’re doing in real time - what could possibly go awry?
Well… plenty, as it turns out. And through trial and error (not to mention the guidance of some people cleverer than myself), I’ve refined my technique… here are some tips that you may find useful.
A word of caution: sometimes getting the cannula in is the easiest part - getting it to STAY IN is the challenge. In patients with a lot of loose, fatty, or freely mobile subcutaneous tissue (ie, elderly patients, or patients with a lot of adipose tissue), by the time you’ve traversed 4cm of soft tissue, only a few millimetres of cannula is in the vein. As soon as the subcut tissue moves - that cannula will be pulled out of the vein. A PICC or long line is your best bet here.
2) Comfort is key
Set up your workspace to maximise comfort - yours and the patient’s! (Take a tip from our anaesthetic colleagues - they are the masters of a good set up, as they know it’s key to the success of any procedure). A comfortable patient will stay still and hold a required position for longer. A comfortable doctor will have better fine motor control and better chance at success.
For patient comfort - use towel rolls, pay attention to positioning and use an assistant to steady the limb if available. For doctor comfort - swing the screen of the ultrasound machine to an optimal position, sit down to do the procedure (or crank the bed up so you’re not having to lean over)... and, most important of all… eat and/or go to the bathroom before you start!
My preference is to use use local anaesthetic drawn up in an insulin syringe (or 1mL syringe with 25G needle) whenever I’m doing ultrasound-guided IV cannulae. Personally, I get very distracted by patient pain, and I can work better if the patient isn’t flinching, wincing or swearing. Also, I figure that by the time I come along, there have already been several attempts at cannulation, and it’s a nice thing to do. A word of warning - if you’re using local anaesthetic, ensure that you get all the air out of the syringe before your infiltrate. Any air introduced into your field will destroy your ultrasound picture!
3) Choose your weapons wisely
This is my list of equipment for inserting IV cannulae:
4) Use whatever view suits your needs
Long axis? Short axis? What’s the best approach to cannulation? In my mind - both! Here’s a description of my technique:
After my preparations are complete and I’m comfortably seated, I insert the needle and approach the vein using a short-axis approach, with my eyes on the screen until I reach the vessel. Once on top of the vessel, I bounce the needle a little so I can confirm that the needle is indenting the vessel. I then look down at the needle and advance it into the vessel, so I can spot a flashback as soon as it occurs. Once I get a flashback, I then rotate the probe into long axis view, and reduce the angle of the needle (ie, so it’s more shallow). I then advance a millimetre or so more, so I can see I’m in the centre of the vein, and watch on the screen as I slide the cannula off and into the vessel.
(May need to put a video link or graphics link here).
5) Secure that cannula! You’ve got it in… now make sure it stays in: tape that sucker down! Dry off the area thoroughly and secure it like you would a paediatric cannula. Hint: a bit of Friar’s Balsam (tincture of benzoin) or Cavilon (™) is particularly useful on sweaty skin, to help things to stick down.
6) Practice, practice, practice! This is just my technique - different things work best for different people. Practice this skill, ask people for tips, and try them out! It takes practice,a little experimentation and active learning to be a master at this skill.
Acknowledgements: Many thanks to Dr Adrian Goudie, Dr Leanne Hartnett and Dr Lindsay Bridgford, for their tips and tricks which have helped me refine my IV cannulation technique!
Welcome to the future where apps, AI, handheld devices and robots are taking over ultrasound education and scanning.
I’d like to introduce you to Clip De-identifier. Preparing a talk? Posting on a blog? or just storing your logbook images - This nifty program developed by Ben Smith from Ultrasound of the Week allows you to crop patient information and unnecessary data from your ultrasound images or clips as well as removing the metadata embedded in the clip.
It is simple to use with a drag and drop interface, compatible with MAC and PC and allows you to preview your images before clipping. It will save you loads of time especially with batch conversion being possible when you want to de-identify more than one ultrasound clip. Best of all it's free and open access!
Email me your tips or leads on any new or amazing ultrasound tech/apps/blogs and I will review them in the future - Luke Phillips (Victoria Co-chair).
EMUGs was created to advocate for the use of POCUS in the Emergency Department and to form a collaborative learning network for all POCUS users. We believe that The EMUGs Doppler, EMUGs first digital newsletter, will allow us to further develop that network, with the latest in POCUS arriving directly to your inbox.
The Doppler is released quarterly and includes information on upcoming EMUGs and other POCUS-focused events, case studies, the latest information on POCUS technology and more.
To read Issue 1 - CLICK HERE. To subscribe - CLICK HERE
The team at Royal Prince Alfred's Emergency Department are proud to announce their upcoming Critical Care Sonography Course...
DATES: 26/02 to 01/03, 2018
LOCATION: Kerry Packer Building, RPAH
For more details email the team at firstname.lastname@example.org
After nearly three years of preparation and regional meetings the Emergency Medicine Ultrasound Groups regional teams are coming together for the first time!
Months of planning has brought together an excellent gathering of Australian, New Zealand and international speakers to deliver a new wave of POCUS training and educational topics and approaches.
The EMUGS sessions are part of the ACEM ASM so to join one or all of our sessions register via acem2017.com/ and also via the following eventbrite registration for logistical/organisation reasons:
NOTE: The EMUGs sessions are free to all ACEM ASM attendees. Any EMUGs donations are appreciated. This enables the Admin Team to provide essential support for all EMUGs projects.
Point of Care Ultrasound is now an essential skill of Fellowship trained Emergency Physicians. It is widely supported in national and international guidelines for a host of clinical settings, most notably expediting the appropriate care of both traumatically injured and critically unwell patients as well as in the performance of needle-guided techniques such as central line insertion.
A 35 female was brought to ED by ambulance following a sudden collapse at home. At the scene – skin cold, Blood Pressure un-recordable, semi-conscious.
Blogs are written by our EMUGs Team from across Australasia.