VTE prevention in surgical settings: A top priority in clinicians checklist. Episode 2 - Dr. Abhay Bhave and Prof. Juan Arcelus

This edition of the podcast will focus upon: 
•    Differences in the incidence of VTE among laparoscopic and open surgery: What does the data suggest?
•    Role of mechanical & pharmacological VTE prophylaxis: Do these two approaches compliment or contradict each other?
•    Pre-op vs. post-op initiation of pharmacological prophylaxis: When is the right time to initiate?

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Transcription

00:06 - 00:40

Unknown

Welcome to VTE Unplugged, a brand new podcast series curated by Sanofi. The aim of VTE Unplugged is to bring latest in the field of Venous Thromboembolism management delivered by renowned experts in this field. Today, let's listen to our ongoing discussion on VTE prevention in surgical settings, a top priority in clinician's checklist.

In the previous episode, our experts discussed about the incidence of VTE in surgical patients and also about the risk of VTE and bleeding among different surgical settings. Now we will take this discussion forward.

00:44 - 00:57

Dr. Abhay Bhave

Will the type or the nature of surgery make -- make a difference to your thoughts about thromboprophylaxis? By that I mean an open surgery versus laparoscopic surgery, is there a difference in the incidence of VTE?

00:58 - 05:17

Professor Juan Arcelus

Well, here we have two phases. I would say that in the first 20 years of laparoscopic, you know, that we, general surgeons, jumped into laparoscopy much later than our gynecological colleagues. And we started with a -- in Paris with the cholecystectomies, then Olsen and Reddick in Nashville and Joe Caprini by the way was -- was I think the first academic surgeon in Chicago doing lap collis. So at the beginning, we thought that this was less aggressive, less painful. We didn't have a large incision. So we didn't have the tissue factor release of a large incision. And we thought that well, this is going to be less, less thrombogenic.

We published one study with Joe Caprini. And we presented several abstracts where we were showing hypercoagulability in both groups open and laparoscopic cholecystectomies. And then we realized that these potential advantages of less aggression, early mobility, early discharge could be counterbalanced in some degree by the fact of the high pressure in the abdomen, the insufflation of CO2 to create a pneumoperitoneum to see what we're doing in some patients the position of the person in a reverse trendelenburg like biliary surgery or hiatus surgery, upper abdominal surgery usually requires in some times of the operation reverse trendelenburg. So that means stasis.

Also as I said at the beginning as operations done laparoscopically became being more and more complex, bariatrics, abdominal wall, hernia repair, liver surgery, pancreatic surgery. So we were going to procedures five six seven hours. And at the beginning during the learning curve, the surgeons were taking a lot of time to conduct them. That meant that the risk would be equivalent in the open and the laparoscopic approach.

However, recent data are showing that trained surgeons, very skillful surgeons that do the operations almost at the same time that they would do open, in those cases, yeah, the rate tends to be lower. I'm seeing recent studies colorectal, esophagus etc., the risk could be lower than in the open. But at the time being, and I concur with the ASCO and ITAC guidelines that I was happy to participate. Even I was a collaborator in the recent ITAC guidelines in cancer. I think this is a very pragmatic and valid recommendation at the time being do the same prophylactic approach irrespective of the minimally invasive access or classical open access. Because as I said still we -- at the beginning things were very similar. Now could be better for laparoscopy, but we shouldn't forget the Italian study by Vedavati providing a 10% post-discharge VTE rate. Patients that didn't have a VTE at the time of discharge in Italy colorectal, laparoscopic surgery were randomized to three additional weeks of low molecular weight heparin or non -- or -- or controls. And there were 10% DVTs at one month identified by duplex ultrasound in those that prophylaxis was interrupted as opposed to one case in those that were prolonged. So, and guess what was the rate at the time of discharge in Italy when they did the duplex to randomize the patient 17%, which I considered very difficult to believe a 17% DVT rate in patients with prophylaxis. But what am I telling this story? To show that laparoscopic colorectal surgery for cancer is associated with very high, very, very high DVT rate.

05:19 - 05:54

Dr. Abhay Bhave

Uh, those are really interesting points Professor Celis. Thank you for that. So, so far we've identified the group of patients. We've done a risk assessment model. We have also looked at the bleeding tendency. And now the time has come where you've identified a patient who have a higher risk. So we would now like to know your views on the pharmacological thromboprophylaxis, which drug and how to use it? And would you combine it with the mechanical thromboprophylaxis? Or is that not used today?

05:55 - 14:40

Professor Juan Arcelus

Well, I think that's one of the most critical questions you have made. All the questions you made were very, very important. But I think this is the most practical, I mean, so far we have talked about the incidence. This is a problem still killing people. We have talked about the risk assessment for thrombosis and bleeding. So assuming that we have a patient at high risk for thrombosis, but with non particularly high risk for bleeding, what do we do? Of course, use prophylaxis. And the first methods of prophylaxis, the first trial, probably one of the most important trials in recent history of medicine was published in Lancet by Professor Vijay Kakkar as you know came from your country, the father of Lord Kakkar who remains a very active researcher and speaker, good friend. Both of them are good friends of mine. But the father Vijay Kakkar led a multi-center trial comparing unfractionated heparin with nothing in several hundred patients in Europe mainly. And with postmortem outcome, the outcome was fatal PE. They identified a significant reduction in mortality related to PE using unfractionated heparin. So that was a seminal very important study showing that for every 120 patients undergoing general surgery that you would provide heparin, you would save one life, one out of seven. So I think that's, that's very important.

Then in Italy, and many people don't know that study Perugia published one study with 4,000 patients in Italy that were receiving low molecular weight heparin or none or nothing. And they found a significant reduction in all cause of mortality again confirmed by postmortem studies. So in the 70s, the main -- the main method I would say for 15 years until 1989 unfractionated heparin was the gold standard. Then in France, low molecular weight heparin is designed at the Choay Center, and then came another heparin, Enoxaparin, Dalteparin, Tinzaparin. And low molecular weight heparins remain the gold standard. Several meta-analyses in global surgical patients like mismatches or cancer patients like Leonardis have shown that low molecular weight heparin has the best efficacy, safety profile, and at the time being should be the first option for patients with high risk for thrombosis. So that's the preferred option provided that the patient is not at high risk for bleeding, high risk or provided that the patient is not bleeding in the post-operative period. Actually, the rate of severe bleeding so that you could associate with pharmacological prophylaxis is less than 1%. So it's very, very low. Actually, in Leonardis meta-analysis the rate of bleeding severe enough to reoperate patients was 0.7% in patients without any anticoagulant, 1% in patients with low molecular weight heparin, and close to 2% in patients with unfractionated heparin. So they are very safe.

However, with pharmacological prophylaxis we address hypercoagulability, one of the main Verhofstadt legs, hypercoagulability, stasis, endothelial injury. Stasis is very important. Although today with today's management we know with the era approach and the fast track patients go home almost before being operated, they go very, very early. But stasis remains an issue in many patients. For that reason mechanical methods, and here I want to differentiate active methods like intermittent pneumatic compression, which is very effective, and passive methods like graduated elastic stockings that are less effective. What are the main indications today of mechanical methods? Well, there are really two. Number one, it is a resource. It is your alternative when a patient has a high risk for thrombosis. But that patient is in the list of contraindications to use anticoagulants. In that case, you have to rely on, you have to recur to the mechanical methods. And what is the rate of patients in large studies dropping, falling in this category? Well, almost 10% in indoors. In indoors with more than 68,000 patients, we identified in the 30,000 surgical patients that 10% considered at high thrombotic risk would have some contraindication to use mechanical methods. In that case, mechanical methods are an option.

The second indication could be in patients or very particularly high risk of thrombosis where you want to combine the best of the two worlds because we should consider pharmacological and mechanical as complementary, not competitors. They complement each other from the ethiopathogenic perspective as I mentioned. What is the real impact, benefit of adding stockings to heparin with the stockings minimal? There is a very interesting study from the UK probably in a good journal showing by, by Shalhoub showing that the addition of a stocking to low molecular weight heparin didn't provide much advantage.

However, there are other studies from Japan particularly, showing that the addition of intermittent pneumatic compression to low molecular weight heparin, then you get a reduction in the rate of DVT. What is the advantage of this combination? That you don't increase any complication on any of the both or any of the methods. The mechanical method is not going to increase the bleeding potential, and some of the control complications associated to the mechanical method nerve policy, scheme breaking in elderly patient, inappropriate adjusting of the stockings or sizing, that's very important with stocking.

So what do we do in my -- or before I say my experience, very important, this is universal. The fact that you prescribe mechanical methods does not imply -- it does not imply that they are properly used. And now I'm referring to nurses, and nurse extenders, and auxiliary personnel. When I was in Chicago, we sent students, medical students during the summer to check the correct use, application of both stockings and IPC. And almost 40, 50% of the times they had been cleaning the patient, removing the stockings, nobody put it back. Or the patient went to the radiology department and when came back, nobody connected the pump again. So if you have to rely in ICU trauma patients, neurosurgery situations where mechanical methods have a very good niche, they have a very good indication. Please ensure that your personnel is properly trained to keep them working the stockings applied and the pumps being active. Otherwise, it's not going to work, could be even worse. Our experience, we use mainly IPC. The stockings are really we are not so happy these days based on recent data in stockings. Of course, if you don't have IPC, and you have a very high thrombosis risk, and you cannot use temporarily or permanently during the early post-operative period that you cannot use pharmacological, well, you can rely on the stockings. Better than nothing. But they're not that efficient.

14:43 - 15:10

Dr. Abhay Bhave

Thank you. That was loud and clear, and a clear message for the use of these thromboprophylaxis agents or methods. But now that we've decided to use a thromboprophylactic agent, especially a pharmaceutical or pharmacological, when should we initiate this therapy? Should it be before the surgery? Should it be during? Or how many hours post-op? Is there a set of patients who needs it before surgery as opposed to the others?

15:10 - 20:52

Professor Juan Arcelus

Another excellent question, Dr. Bhave. Well, the first thing is that you have to follow the package insert. That's very important. You know, whatever is in your packet insert, your country has been approved by the regulators based on the evidence, although it takes a while sometimes from the evidence comes to the regulators. But anyway, so try to avoid starting post-operatively heparins that are evaluated in trials and approved for pre-op and the opposite. So, number one, that's very important. Do follow the protocol. Try to avoid going off label as possible. Second, emergency and elective surgery are different situations. I never recommend preoperative prophylaxis in patients that are admitted and are going to be operated in the next 12 hours. No, no, because that could cause bleeding. Elective surgery is different as I will mention.

So in a high risk patient, let's focus on Enoxaparin as an example. Enoxaparin in non-orthopedic surgery is based on the pre-operative administration either two hours before or the night before. But that will depend on the dose. The moderate risk dose for Enoxaparin would be 20 milligrams is only used I think in Japan or in western countries in patients with renal failure. But what we consider by convention, all the thrombosis community, we consider that any dose higher than 3400 units of any low molecular weight heparin is a high risk dose, high risk thrombosis dose.

So what do we recommend for elective surgery? What do we do in our oncologic surgery, in our bariatric surgery, you know, all risks high-risk thrombosis patients? We indicate the injection the night before 10 to 12 hours before the scheduled time for surgery. That would allow you to operate without any anti-Xa effect at the time of surgery provided that the renal function is normal, and that would also allow for any neuraxial technique, subarachnoid, anesthesia, or the insertion of an epidural catheter, which are very good advantages. There are some products like the DOGS like Bemiparin one heparin that was designed in Spain, and it's catching up in some countries or even the selective indirect anti-Xa Fondaparinux, the only synthetic anticoagulant before the DOGS. Well, those products have approval in some countries to start post-operatively. However, for those who start post-operatively, don't wait 24 hours, don't wait 36 hours, like our colleagues do in the US. Provided that the hemostasin seems to be assured, never inject any anticoagulant in the -- in the first eight hours after an operation. But after that you can start. So I would be pragmatic and recommend for those who do not want to use preoperative prophylaxis, start 10, 12, 8 to 12 hours after the end of the operation. That's very important.

I would like to see comparative trials. We have cohorts we have administrative databases bases. There are recent data even from liver surgery showing that pre-op is better than post-op. Then the ortho colleagues, orthopedic colleagues, they have jumped into the post-op. But think of this, which is interesting. When we were using in Europe 40 milligrams of Enoxaparin in total hips, starting the night before, and the North Americans decided to start Enoxaparin in this major orthopedic surgery. They decided to start post-operatively, but not 40 milligrams once a day, but 30 milligrams twice a day. Why do they did that? Because they knew that patients were unprotected during the operation. Some of them could come from the operating room with some small clot. So from a philosophical, physiopathological, and ethiopathogenic perspective, I prefer preoperative prophylaxis with these precautions I mentioned. Of course, in talking of other, other populations as I mentioned, emergency surgery, you shouldn't use anything pre-op. Trauma surgery is a situation that sometimes you need some days using mechanical methods, and then once the liver hematoma or the spleen is stable despite hemoperitoneum, you can add gradually post-operatively, neural surgery, intracranial surgery, although there are some brave studies giving pre-operative, a low molecular weight heparin in intracranial surgery. If I were operated of the brain, I would rather prefer having mechanical methods in the operating room, in the recovery unit. And after 48 hours, then, you know, they could consider heparins. So those are my comments about this, this very, very important question.

20:53 - 20:59

Dr. Abhay Bhave

Thank you very much, Professor Celis. Those are very well accepted then. Thank you very much for making it clear.

21:00 - 21:05

Unknown

Thank you for joining us today. Watch out this space as we bring to you next part of the ongoing discussion between Professor Juan Arcellus and Dr. Abhay Bhave.

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