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New Gel Stops Severe Bleeding in Seconds
This video transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me today to discuss a novel, plant-based approach to stopping moderate to severe bleeding is Joe Landolina, CEO and cofounder of Cresilon. Welcome, Joe.
Joe Landolina, MS: Thank you so much for taking the time. It’s great to be here.
Educational Background and Inception of Cresilon
Glatter: It’s a pleasure to have you join me, and I want to congratulate you on your recent 510(k) FDA clearance for your novel product to save lives and stop bleeding. To begin with, can you explain how the idea for launching your company came about?
Landolina: The way that Cresilon came about was a little bit unorthodox, because I was 17 years old when I invented the technology behind the product that eventually became Traumagel®.
My grandfather was an ex-pharmaceutical executive, who later in life started a vineyard. I grew up on a vineyard with a winery chemistry lab across the street from my house and a grandfather who learned lab safety in the 60s. So, that meant that the day I learned how to walk, I was tossed into a lab and I fell head over heels in love with lab research.
That started experimentation and my academic pursuits. That led to discovering a blend of two plant-based polymers derived from algae that stop bleeding on contact, effectively creating a mechanical barrier and allowing anything from a gunshot wound to anything quite a bit more minor to stop in a matter of seconds.
Glatter: Your background is in biomedical engineering. How is it that you started tinkering and doing all this type of work?
Landolina: That’s correct. I did my undergrad in chemical engineering, and my graduate studies were in biomedical engineering. For me, that was supposed to be a pathway into medical school. I always wanted to be a surgeon myself, and I love the field of medicine.
As a freshman in college at NYU Engineering, I had this idea. I entered it into NYU’s business plan competition, and we won at the engineering school. That gave us just enough capital to start developing and researching Traumagel more, and Cresilon was born out of that research.
Techniques for Stopping Hemorrhage
Glatter: In terms of stopping hemorrhage, which takes so many lives in the United States and globally — certainly, uncontrolled hemorrhage — what are the techniques that you see, prior to the arrival of your product, as being effective? Can you elucidate some of these techniques?
Landolina: In emergency medicine, the primary mode of controlling hemorrhage is passive. It’s what, in Brooklyn, we like to call “pressure and a prayer”, where you have a material that’s either gauze or an impregnated gauze in most cases, where the mode of action is absorbing blood, with the adjunct of pressure by the first responder or by the clinician who’s providing aid.
These types of technologies are widespread. There are many versions of this technology carried by EMS agencies, trauma bays, US military soldiers, and soldiers across NATO countries. But these types of technologies tend to be relatively inefficient, meaning that they’re very difficult to get into wounds because of the gauze or the powder form of the devices, and it’s very hard to get them in contact with the form of bleeding.
On top of that, if the patient is clotting compromised or immunocompromised in some way, the ability to create a durable clot that will not be ripped off when you remove the product at the next level of care is also of concern. And so, this type of technology or the type of treatment of massive hemorrhage hasn’t changed in decades.
Current Applications and Potential Use
Glatter: I envision this product will be carried by paramedics, used on the battlefield at some point after your FDA clearance, and recently it went through.
Do you see any possibility that this could be an AED equivalent to Stop the Bleed? In other words, could the average lay person be trained to use your product if kits are available?
Landolina: To be very clear, Traumagel today is only approved or cleared under a “prescription-only” indication, which means that it will not initially be available OTC. However, that is our goal. Our goal is to make this product available and usable by someone with no medical training whatsoever.
The form factor of being a gel in a syringe lends itself well to that, meaning that we try to make it as easy as point and shoot to control hemorrhage, where there’s not as much technique to be learned in the application of a product like Traumagel as there is in current hemorrhage control techniques.
Mechanism of Action and Physiology
Glatter: Once you apply Traumagel, can you explain what happens to the product after it’s applied and the bleeding has stopped? Does it get reabsorbed by the body? What’s the process here?
Landolina: Under Traumagel’s indication, because it’s used in traumatic injury, it must be removed within 24 hours.
One of the big benefits of Traumagel is that when the patient produces a blood clot underneath Traumagel, it doesn’t become incorporated within the gel itself. To contrast that with the use of gauze, gauze is porous. The clot ends up wrapped around the fibers of the gauze, so if you peel the gauze away, it’s very likely that clot is coming off with it. The surgeon or the clinician at the next level of care is going to have to deal with the re-bleed.
You can remove Traumagel cleanly and entirely without disturbing the underlying clot. That’s a major benefit, not only to the patient but also to the next level of care, to the next clinician or physician that is required to remove the product.
Glatter: How is it possible to remove the substance without disturbing the clot? Can you explain in more detail?
Landolina: That’s one of the hallmarks of these plant-based polymers and the way that we design Traumagel itself. Traumagel is completely nonporous, and it has no fibrous nature to it. What that means is when the patient produces a blood clot or fibrin next to or on top of Traumagel, that fibrin ends up not incorporated within the polymers of Traumagel itself.
Over time, because Traumagel is a hydrogel, meaning that by weight it’s mostly water, you end up having less adhesion to the clot over time. When it’s time to remove Traumagel from the injury, it has lost almost all of its adhesive capabilities, meaning that when you peel it away, that clot is going to stick better to tissue than it will to the gel itself.
Glatter: Can you explain a little bit about the matrix that’s formed, the physiology, and how the polymers work to form this matrix?
Landolina: Sure. Traumagel is made of two polysaccharides that are plant derived. One polysaccharide is polyanionic, and the other is polycationic, meaning one has negative charges and the other has positive charges, which together create almost a Lego block effect, where when the material comes in contact with tissue, it adheres strongly and allows for itself to effectively create a mechanical barrier against bleeding.
Courtesy of Cresilon
Landolina: Even in the face of major arterial blood flow, Traumagel will stay where it needs to stay, and it’s not going to get washed away. This means that it is much more easily appliable to these types of surfaces and will allow the patient to produce their own endogenous fibrin clot at that location.
Like I mentioned before, when that fibrin clot is formed, because the gel itself has no pores or fibers, it doesn’t become incorporated within the fibrin clot. You can take the gel away, leaving that clot behind without the chance of a rebleed.
Testing With Major Bleeds
Glatter: In terms of bleeding itself, have you tested your product with major aortic bleeds or carotid bleeds in preclinical work?
Landolina: We have used the US military’s model for lethal hemorrhage, and the idea there is to create a model that is just that — lethal. These are the worst types of bleeds that you can possibly imagine, where the patients are clotting compromised, and where you have, in most cases, a very strong arterial component, so something like a femoral artery bleed.
We’ve also tested in carotid artery, aortic applications, as well as combinations of venous and arterial bleeds. The idea here is to show the use of the product in the absolute worst-case scenario so that when this translates into the clinic, the models that we’ve used for evaluation, hopefully, are worse than what actually rolls into the trauma bay.
Glatter: Excellent. What’s the mean time to stop an arterial vs a venous bleed? Are we talking a matter of seconds?
Landolina: In the case of a healthy patient, meaning a patient without clotting compromise, you’re in a matter of seconds. It’s less than 10 seconds.
In the case where you have clotting compromise, a deep, complicated wound geometry, we recommend holding a pressure bandage on for 3 minutes just because it increases the chance of Traumagel coming into contact with the bleed, especially when you can’t visualize the bleed in the bleed source. Because of that pressure time, that becomes the mean. But again, it’s highly dependent on the type of bleed and the style of application.
Failure Rates and Effectiveness
Glatter: As a segue to that, what is the failure rate based on your studies and internal research using Traumagel? Have there been cases where bleeding has not been able to be stopped?
Landolina: It depends on the study, but the failure rates are incredibly low with Traumagel, assuming that it’s correctly used. That’s one of the benefits to this product, where with proper technique, with overwrap with gauze, you nearly always get control of hemorrhage with a product like this.
Glatter: Is manual pressure required in that sense? From what you described earlier, manual pressure would not be required.
Landolina: It depends on the injury. What we recommend is that, if you have a very deep wound where you cannot visualize the source of bleed, you use pressure to seat Traumagel into the source of bleeding, meaning that you’re following Committee on Tactical Combat Casualty Care (Co-TCCC) regulations or requirements, where you’re over wrapping with gauze, and you’re providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it’s doing what it’s doing.
In most cases, it doesn’t hurt to apply pressure on top of Traumagel as well. In more surface level bleeds, you don’t need pressure at all.
Applications Beyond Trauma
Glatter: Interesting. In terms of further applications (eg, nose bleeds or GYN bleeding, which are life-threatening), do you see this coming as an application for the future?
Landolina: That’s where we’re working. Traumagel is the successor to an animal health product called Vetigel. The formulations of the gel behind Vetigel and Traumagel are identical. Vetigel has a full surgical indication, and that’s everything from epistaxis to neuro and spine procedures, into cardiovascular and soft tissue surgeries, orthopedic medicine, and so on.
Cresilon’s goal is to eventually expand the indication of our technology to include surgical indications and other indications where we can help any patient that’s bleeding.
Glatter: That’s important, because we use prehospital whole blood, low titer, specifically, when patients have life-threatening hemorrhage. With your product, that would reduce the amount of blood products that would need to be administered. This could be a real game changer.
Landolina: Definitely, that’s the goal we’re working on.
Infection Risks and Biocompatibility
Glatter: In terms of any risk for infection, has that been studied as well? Does Traumagel in any way lead to increased rates of infection?
Landolina: Traumagel is biocompatible. It’s a sterile product. We’ve done the full suite of biocompatibility testing as required by FDA. On top of that, remember that Vetigel, which is the same formulation, is an implantable product. As a result, that has even extended biocompatibility testing beyond what would be necessary for an external product.
In Vetigel’s use case, which has been used now in over 60,000 patients, primarily companion animals, dogs and cats, we haven’t seen instances of infection. There’s no reason to believe that we would see that clinically with Traumagel.
Research Collaborations and Future Applications
Glatter: In terms of other research that your company’s embarked on preclinically, I understand there were some studies done at Walter Reed Army Institute of Research. I was wondering if you could expand on these, specifically, in terms of traumatic brain injury (TBI) and hemorrhage related to that. For example, with shrapnel or even a gunshot wound.
Landolina: The Walter Reed collaboration with Cresilon is something that I’m particularly excited about, because it marks Cresilon’s first project that’s outside the scope of just hemostasis. Walter Reed came to us with this proposal where there’s a big challenge in a subset of TBI called penetrating ballistic-like brain injury, where the brain has been penetrated by a bullet, shrapnel, or some other projectile, and there’s an injury that exposes the brain to the outside.
Today, there is no standard of care to treat patients with those types of injuries. In many cases, mortality is caused through swelling of the brain, or collapse of the brain. What they came to us with was the potential of using our technology, not primarily as a hemostatic agent, but to be able to stabilize that patient enough to get to the next level of care to be treated by a neurosurgeon.
That study Walter Reed did was just a pilot that was done in small animals. In that pilot, they showed that over the period of treatment, there was no negative change in vital signs, no increase in edema or in swelling, or in any of the biomarkers that were being monitored at that time.
At the very least, this is not full indication that this indication will work for Cresilon, but it shows that there’s promise. It’s something that we’re working on and hopefully we’ll be able to bring to market soon.
Glatter: Certainly, maintaining intracranial pressure and cerebral perfusion pressures are very critical. In the future, do you think this product would be able to be deployed endovascularly? Imagine this in terms of stopping bleeding from some source, whether it’s from a stroke or another intracranial source.
Landolina: That’s been an area of interest for us. We have no evidence to prove that indication works at this point, but there’s also nothing to say that it wouldn’t be possible for our technology. At this point, we’ve only looked at a cursory level at those indications.
Glatter: Does the use of Traumagel obviate the need for a more definitive repair (eg, with sutures) or something that’s more permanent?
Landolina: I always say that Traumagel — and Vetigel, for that matter — is not a replacement for good surgical technique. The surgeon always needs to make his or her best judgment when reviewing the patient. That doesn’t mean that there won’t need to be sutures or vascular repair in most of these cases, especially in major trauma.
Final Takeaways
Glatter: Do you have some bullet points or pearls you could give our audience as a takeaway?
Landolina: When Cresilon looks at Traumagel — and for us, Traumagel is the next generation of hemostatic agent, especially in trauma care and in emergency medicine — it allows for a far-simplified application of the product and much faster control of hemorrhage with better patient outcomes.
As we roll this out through EMS agencies, trauma hospitals, military agencies, and eventually to the general public through a future indication, it’s something we’re very excited about. Personally, I started this business 14 years ago, and so it’s great to see our mission of saving lives transitioning to saving human lives.
Glatter: I look forward to seeing this product in the emergency department, but also in other settings, such as in the operating room where we can really help patients who are dying from hemorrhage, certainly on the battlefield, and the lay public. If someone were to come upon a patient who’s bleeding out, this could be certainly a game changer and a lifesaver.
I want to thank you for your time. This is a really important product that’s transformed the lives of so many animals, but also people in the future.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He reported no relevant conflicts of interest. Mr. Landolina is the CEO and co-founder of Cresilon, a biotechnology company specializing in plant-based solutions for emergency bleeding control.
A version of this article first appeared on Medscape.com.
This video transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me today to discuss a novel, plant-based approach to stopping moderate to severe bleeding is Joe Landolina, CEO and cofounder of Cresilon. Welcome, Joe.
Joe Landolina, MS: Thank you so much for taking the time. It’s great to be here.
Educational Background and Inception of Cresilon
Glatter: It’s a pleasure to have you join me, and I want to congratulate you on your recent 510(k) FDA clearance for your novel product to save lives and stop bleeding. To begin with, can you explain how the idea for launching your company came about?
Landolina: The way that Cresilon came about was a little bit unorthodox, because I was 17 years old when I invented the technology behind the product that eventually became Traumagel®.
My grandfather was an ex-pharmaceutical executive, who later in life started a vineyard. I grew up on a vineyard with a winery chemistry lab across the street from my house and a grandfather who learned lab safety in the 60s. So, that meant that the day I learned how to walk, I was tossed into a lab and I fell head over heels in love with lab research.
That started experimentation and my academic pursuits. That led to discovering a blend of two plant-based polymers derived from algae that stop bleeding on contact, effectively creating a mechanical barrier and allowing anything from a gunshot wound to anything quite a bit more minor to stop in a matter of seconds.
Glatter: Your background is in biomedical engineering. How is it that you started tinkering and doing all this type of work?
Landolina: That’s correct. I did my undergrad in chemical engineering, and my graduate studies were in biomedical engineering. For me, that was supposed to be a pathway into medical school. I always wanted to be a surgeon myself, and I love the field of medicine.
As a freshman in college at NYU Engineering, I had this idea. I entered it into NYU’s business plan competition, and we won at the engineering school. That gave us just enough capital to start developing and researching Traumagel more, and Cresilon was born out of that research.
Techniques for Stopping Hemorrhage
Glatter: In terms of stopping hemorrhage, which takes so many lives in the United States and globally — certainly, uncontrolled hemorrhage — what are the techniques that you see, prior to the arrival of your product, as being effective? Can you elucidate some of these techniques?
Landolina: In emergency medicine, the primary mode of controlling hemorrhage is passive. It’s what, in Brooklyn, we like to call “pressure and a prayer”, where you have a material that’s either gauze or an impregnated gauze in most cases, where the mode of action is absorbing blood, with the adjunct of pressure by the first responder or by the clinician who’s providing aid.
These types of technologies are widespread. There are many versions of this technology carried by EMS agencies, trauma bays, US military soldiers, and soldiers across NATO countries. But these types of technologies tend to be relatively inefficient, meaning that they’re very difficult to get into wounds because of the gauze or the powder form of the devices, and it’s very hard to get them in contact with the form of bleeding.
On top of that, if the patient is clotting compromised or immunocompromised in some way, the ability to create a durable clot that will not be ripped off when you remove the product at the next level of care is also of concern. And so, this type of technology or the type of treatment of massive hemorrhage hasn’t changed in decades.
Current Applications and Potential Use
Glatter: I envision this product will be carried by paramedics, used on the battlefield at some point after your FDA clearance, and recently it went through.
Do you see any possibility that this could be an AED equivalent to Stop the Bleed? In other words, could the average lay person be trained to use your product if kits are available?
Landolina: To be very clear, Traumagel today is only approved or cleared under a “prescription-only” indication, which means that it will not initially be available OTC. However, that is our goal. Our goal is to make this product available and usable by someone with no medical training whatsoever.
The form factor of being a gel in a syringe lends itself well to that, meaning that we try to make it as easy as point and shoot to control hemorrhage, where there’s not as much technique to be learned in the application of a product like Traumagel as there is in current hemorrhage control techniques.
Mechanism of Action and Physiology
Glatter: Once you apply Traumagel, can you explain what happens to the product after it’s applied and the bleeding has stopped? Does it get reabsorbed by the body? What’s the process here?
Landolina: Under Traumagel’s indication, because it’s used in traumatic injury, it must be removed within 24 hours.
One of the big benefits of Traumagel is that when the patient produces a blood clot underneath Traumagel, it doesn’t become incorporated within the gel itself. To contrast that with the use of gauze, gauze is porous. The clot ends up wrapped around the fibers of the gauze, so if you peel the gauze away, it’s very likely that clot is coming off with it. The surgeon or the clinician at the next level of care is going to have to deal with the re-bleed.
You can remove Traumagel cleanly and entirely without disturbing the underlying clot. That’s a major benefit, not only to the patient but also to the next level of care, to the next clinician or physician that is required to remove the product.
Glatter: How is it possible to remove the substance without disturbing the clot? Can you explain in more detail?
Landolina: That’s one of the hallmarks of these plant-based polymers and the way that we design Traumagel itself. Traumagel is completely nonporous, and it has no fibrous nature to it. What that means is when the patient produces a blood clot or fibrin next to or on top of Traumagel, that fibrin ends up not incorporated within the polymers of Traumagel itself.
Over time, because Traumagel is a hydrogel, meaning that by weight it’s mostly water, you end up having less adhesion to the clot over time. When it’s time to remove Traumagel from the injury, it has lost almost all of its adhesive capabilities, meaning that when you peel it away, that clot is going to stick better to tissue than it will to the gel itself.
Glatter: Can you explain a little bit about the matrix that’s formed, the physiology, and how the polymers work to form this matrix?
Landolina: Sure. Traumagel is made of two polysaccharides that are plant derived. One polysaccharide is polyanionic, and the other is polycationic, meaning one has negative charges and the other has positive charges, which together create almost a Lego block effect, where when the material comes in contact with tissue, it adheres strongly and allows for itself to effectively create a mechanical barrier against bleeding.
Courtesy of Cresilon
Landolina: Even in the face of major arterial blood flow, Traumagel will stay where it needs to stay, and it’s not going to get washed away. This means that it is much more easily appliable to these types of surfaces and will allow the patient to produce their own endogenous fibrin clot at that location.
Like I mentioned before, when that fibrin clot is formed, because the gel itself has no pores or fibers, it doesn’t become incorporated within the fibrin clot. You can take the gel away, leaving that clot behind without the chance of a rebleed.
Testing With Major Bleeds
Glatter: In terms of bleeding itself, have you tested your product with major aortic bleeds or carotid bleeds in preclinical work?
Landolina: We have used the US military’s model for lethal hemorrhage, and the idea there is to create a model that is just that — lethal. These are the worst types of bleeds that you can possibly imagine, where the patients are clotting compromised, and where you have, in most cases, a very strong arterial component, so something like a femoral artery bleed.
We’ve also tested in carotid artery, aortic applications, as well as combinations of venous and arterial bleeds. The idea here is to show the use of the product in the absolute worst-case scenario so that when this translates into the clinic, the models that we’ve used for evaluation, hopefully, are worse than what actually rolls into the trauma bay.
Glatter: Excellent. What’s the mean time to stop an arterial vs a venous bleed? Are we talking a matter of seconds?
Landolina: In the case of a healthy patient, meaning a patient without clotting compromise, you’re in a matter of seconds. It’s less than 10 seconds.
In the case where you have clotting compromise, a deep, complicated wound geometry, we recommend holding a pressure bandage on for 3 minutes just because it increases the chance of Traumagel coming into contact with the bleed, especially when you can’t visualize the bleed in the bleed source. Because of that pressure time, that becomes the mean. But again, it’s highly dependent on the type of bleed and the style of application.
Failure Rates and Effectiveness
Glatter: As a segue to that, what is the failure rate based on your studies and internal research using Traumagel? Have there been cases where bleeding has not been able to be stopped?
Landolina: It depends on the study, but the failure rates are incredibly low with Traumagel, assuming that it’s correctly used. That’s one of the benefits to this product, where with proper technique, with overwrap with gauze, you nearly always get control of hemorrhage with a product like this.
Glatter: Is manual pressure required in that sense? From what you described earlier, manual pressure would not be required.
Landolina: It depends on the injury. What we recommend is that, if you have a very deep wound where you cannot visualize the source of bleed, you use pressure to seat Traumagel into the source of bleeding, meaning that you’re following Committee on Tactical Combat Casualty Care (Co-TCCC) regulations or requirements, where you’re over wrapping with gauze, and you’re providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it’s doing what it’s doing.
In most cases, it doesn’t hurt to apply pressure on top of Traumagel as well. In more surface level bleeds, you don’t need pressure at all.
Applications Beyond Trauma
Glatter: Interesting. In terms of further applications (eg, nose bleeds or GYN bleeding, which are life-threatening), do you see this coming as an application for the future?
Landolina: That’s where we’re working. Traumagel is the successor to an animal health product called Vetigel. The formulations of the gel behind Vetigel and Traumagel are identical. Vetigel has a full surgical indication, and that’s everything from epistaxis to neuro and spine procedures, into cardiovascular and soft tissue surgeries, orthopedic medicine, and so on.
Cresilon’s goal is to eventually expand the indication of our technology to include surgical indications and other indications where we can help any patient that’s bleeding.
Glatter: That’s important, because we use prehospital whole blood, low titer, specifically, when patients have life-threatening hemorrhage. With your product, that would reduce the amount of blood products that would need to be administered. This could be a real game changer.
Landolina: Definitely, that’s the goal we’re working on.
Infection Risks and Biocompatibility
Glatter: In terms of any risk for infection, has that been studied as well? Does Traumagel in any way lead to increased rates of infection?
Landolina: Traumagel is biocompatible. It’s a sterile product. We’ve done the full suite of biocompatibility testing as required by FDA. On top of that, remember that Vetigel, which is the same formulation, is an implantable product. As a result, that has even extended biocompatibility testing beyond what would be necessary for an external product.
In Vetigel’s use case, which has been used now in over 60,000 patients, primarily companion animals, dogs and cats, we haven’t seen instances of infection. There’s no reason to believe that we would see that clinically with Traumagel.
Research Collaborations and Future Applications
Glatter: In terms of other research that your company’s embarked on preclinically, I understand there were some studies done at Walter Reed Army Institute of Research. I was wondering if you could expand on these, specifically, in terms of traumatic brain injury (TBI) and hemorrhage related to that. For example, with shrapnel or even a gunshot wound.
Landolina: The Walter Reed collaboration with Cresilon is something that I’m particularly excited about, because it marks Cresilon’s first project that’s outside the scope of just hemostasis. Walter Reed came to us with this proposal where there’s a big challenge in a subset of TBI called penetrating ballistic-like brain injury, where the brain has been penetrated by a bullet, shrapnel, or some other projectile, and there’s an injury that exposes the brain to the outside.
Today, there is no standard of care to treat patients with those types of injuries. In many cases, mortality is caused through swelling of the brain, or collapse of the brain. What they came to us with was the potential of using our technology, not primarily as a hemostatic agent, but to be able to stabilize that patient enough to get to the next level of care to be treated by a neurosurgeon.
That study Walter Reed did was just a pilot that was done in small animals. In that pilot, they showed that over the period of treatment, there was no negative change in vital signs, no increase in edema or in swelling, or in any of the biomarkers that were being monitored at that time.
At the very least, this is not full indication that this indication will work for Cresilon, but it shows that there’s promise. It’s something that we’re working on and hopefully we’ll be able to bring to market soon.
Glatter: Certainly, maintaining intracranial pressure and cerebral perfusion pressures are very critical. In the future, do you think this product would be able to be deployed endovascularly? Imagine this in terms of stopping bleeding from some source, whether it’s from a stroke or another intracranial source.
Landolina: That’s been an area of interest for us. We have no evidence to prove that indication works at this point, but there’s also nothing to say that it wouldn’t be possible for our technology. At this point, we’ve only looked at a cursory level at those indications.
Glatter: Does the use of Traumagel obviate the need for a more definitive repair (eg, with sutures) or something that’s more permanent?
Landolina: I always say that Traumagel — and Vetigel, for that matter — is not a replacement for good surgical technique. The surgeon always needs to make his or her best judgment when reviewing the patient. That doesn’t mean that there won’t need to be sutures or vascular repair in most of these cases, especially in major trauma.
Final Takeaways
Glatter: Do you have some bullet points or pearls you could give our audience as a takeaway?
Landolina: When Cresilon looks at Traumagel — and for us, Traumagel is the next generation of hemostatic agent, especially in trauma care and in emergency medicine — it allows for a far-simplified application of the product and much faster control of hemorrhage with better patient outcomes.
As we roll this out through EMS agencies, trauma hospitals, military agencies, and eventually to the general public through a future indication, it’s something we’re very excited about. Personally, I started this business 14 years ago, and so it’s great to see our mission of saving lives transitioning to saving human lives.
Glatter: I look forward to seeing this product in the emergency department, but also in other settings, such as in the operating room where we can really help patients who are dying from hemorrhage, certainly on the battlefield, and the lay public. If someone were to come upon a patient who’s bleeding out, this could be certainly a game changer and a lifesaver.
I want to thank you for your time. This is a really important product that’s transformed the lives of so many animals, but also people in the future.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He reported no relevant conflicts of interest. Mr. Landolina is the CEO and co-founder of Cresilon, a biotechnology company specializing in plant-based solutions for emergency bleeding control.
A version of this article first appeared on Medscape.com.
This video transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical adviser for Medscape Emergency Medicine. Joining me today to discuss a novel, plant-based approach to stopping moderate to severe bleeding is Joe Landolina, CEO and cofounder of Cresilon. Welcome, Joe.
Joe Landolina, MS: Thank you so much for taking the time. It’s great to be here.
Educational Background and Inception of Cresilon
Glatter: It’s a pleasure to have you join me, and I want to congratulate you on your recent 510(k) FDA clearance for your novel product to save lives and stop bleeding. To begin with, can you explain how the idea for launching your company came about?
Landolina: The way that Cresilon came about was a little bit unorthodox, because I was 17 years old when I invented the technology behind the product that eventually became Traumagel®.
My grandfather was an ex-pharmaceutical executive, who later in life started a vineyard. I grew up on a vineyard with a winery chemistry lab across the street from my house and a grandfather who learned lab safety in the 60s. So, that meant that the day I learned how to walk, I was tossed into a lab and I fell head over heels in love with lab research.
That started experimentation and my academic pursuits. That led to discovering a blend of two plant-based polymers derived from algae that stop bleeding on contact, effectively creating a mechanical barrier and allowing anything from a gunshot wound to anything quite a bit more minor to stop in a matter of seconds.
Glatter: Your background is in biomedical engineering. How is it that you started tinkering and doing all this type of work?
Landolina: That’s correct. I did my undergrad in chemical engineering, and my graduate studies were in biomedical engineering. For me, that was supposed to be a pathway into medical school. I always wanted to be a surgeon myself, and I love the field of medicine.
As a freshman in college at NYU Engineering, I had this idea. I entered it into NYU’s business plan competition, and we won at the engineering school. That gave us just enough capital to start developing and researching Traumagel more, and Cresilon was born out of that research.
Techniques for Stopping Hemorrhage
Glatter: In terms of stopping hemorrhage, which takes so many lives in the United States and globally — certainly, uncontrolled hemorrhage — what are the techniques that you see, prior to the arrival of your product, as being effective? Can you elucidate some of these techniques?
Landolina: In emergency medicine, the primary mode of controlling hemorrhage is passive. It’s what, in Brooklyn, we like to call “pressure and a prayer”, where you have a material that’s either gauze or an impregnated gauze in most cases, where the mode of action is absorbing blood, with the adjunct of pressure by the first responder or by the clinician who’s providing aid.
These types of technologies are widespread. There are many versions of this technology carried by EMS agencies, trauma bays, US military soldiers, and soldiers across NATO countries. But these types of technologies tend to be relatively inefficient, meaning that they’re very difficult to get into wounds because of the gauze or the powder form of the devices, and it’s very hard to get them in contact with the form of bleeding.
On top of that, if the patient is clotting compromised or immunocompromised in some way, the ability to create a durable clot that will not be ripped off when you remove the product at the next level of care is also of concern. And so, this type of technology or the type of treatment of massive hemorrhage hasn’t changed in decades.
Current Applications and Potential Use
Glatter: I envision this product will be carried by paramedics, used on the battlefield at some point after your FDA clearance, and recently it went through.
Do you see any possibility that this could be an AED equivalent to Stop the Bleed? In other words, could the average lay person be trained to use your product if kits are available?
Landolina: To be very clear, Traumagel today is only approved or cleared under a “prescription-only” indication, which means that it will not initially be available OTC. However, that is our goal. Our goal is to make this product available and usable by someone with no medical training whatsoever.
The form factor of being a gel in a syringe lends itself well to that, meaning that we try to make it as easy as point and shoot to control hemorrhage, where there’s not as much technique to be learned in the application of a product like Traumagel as there is in current hemorrhage control techniques.
Mechanism of Action and Physiology
Glatter: Once you apply Traumagel, can you explain what happens to the product after it’s applied and the bleeding has stopped? Does it get reabsorbed by the body? What’s the process here?
Landolina: Under Traumagel’s indication, because it’s used in traumatic injury, it must be removed within 24 hours.
One of the big benefits of Traumagel is that when the patient produces a blood clot underneath Traumagel, it doesn’t become incorporated within the gel itself. To contrast that with the use of gauze, gauze is porous. The clot ends up wrapped around the fibers of the gauze, so if you peel the gauze away, it’s very likely that clot is coming off with it. The surgeon or the clinician at the next level of care is going to have to deal with the re-bleed.
You can remove Traumagel cleanly and entirely without disturbing the underlying clot. That’s a major benefit, not only to the patient but also to the next level of care, to the next clinician or physician that is required to remove the product.
Glatter: How is it possible to remove the substance without disturbing the clot? Can you explain in more detail?
Landolina: That’s one of the hallmarks of these plant-based polymers and the way that we design Traumagel itself. Traumagel is completely nonporous, and it has no fibrous nature to it. What that means is when the patient produces a blood clot or fibrin next to or on top of Traumagel, that fibrin ends up not incorporated within the polymers of Traumagel itself.
Over time, because Traumagel is a hydrogel, meaning that by weight it’s mostly water, you end up having less adhesion to the clot over time. When it’s time to remove Traumagel from the injury, it has lost almost all of its adhesive capabilities, meaning that when you peel it away, that clot is going to stick better to tissue than it will to the gel itself.
Glatter: Can you explain a little bit about the matrix that’s formed, the physiology, and how the polymers work to form this matrix?
Landolina: Sure. Traumagel is made of two polysaccharides that are plant derived. One polysaccharide is polyanionic, and the other is polycationic, meaning one has negative charges and the other has positive charges, which together create almost a Lego block effect, where when the material comes in contact with tissue, it adheres strongly and allows for itself to effectively create a mechanical barrier against bleeding.
Courtesy of Cresilon
Landolina: Even in the face of major arterial blood flow, Traumagel will stay where it needs to stay, and it’s not going to get washed away. This means that it is much more easily appliable to these types of surfaces and will allow the patient to produce their own endogenous fibrin clot at that location.
Like I mentioned before, when that fibrin clot is formed, because the gel itself has no pores or fibers, it doesn’t become incorporated within the fibrin clot. You can take the gel away, leaving that clot behind without the chance of a rebleed.
Testing With Major Bleeds
Glatter: In terms of bleeding itself, have you tested your product with major aortic bleeds or carotid bleeds in preclinical work?
Landolina: We have used the US military’s model for lethal hemorrhage, and the idea there is to create a model that is just that — lethal. These are the worst types of bleeds that you can possibly imagine, where the patients are clotting compromised, and where you have, in most cases, a very strong arterial component, so something like a femoral artery bleed.
We’ve also tested in carotid artery, aortic applications, as well as combinations of venous and arterial bleeds. The idea here is to show the use of the product in the absolute worst-case scenario so that when this translates into the clinic, the models that we’ve used for evaluation, hopefully, are worse than what actually rolls into the trauma bay.
Glatter: Excellent. What’s the mean time to stop an arterial vs a venous bleed? Are we talking a matter of seconds?
Landolina: In the case of a healthy patient, meaning a patient without clotting compromise, you’re in a matter of seconds. It’s less than 10 seconds.
In the case where you have clotting compromise, a deep, complicated wound geometry, we recommend holding a pressure bandage on for 3 minutes just because it increases the chance of Traumagel coming into contact with the bleed, especially when you can’t visualize the bleed in the bleed source. Because of that pressure time, that becomes the mean. But again, it’s highly dependent on the type of bleed and the style of application.
Failure Rates and Effectiveness
Glatter: As a segue to that, what is the failure rate based on your studies and internal research using Traumagel? Have there been cases where bleeding has not been able to be stopped?
Landolina: It depends on the study, but the failure rates are incredibly low with Traumagel, assuming that it’s correctly used. That’s one of the benefits to this product, where with proper technique, with overwrap with gauze, you nearly always get control of hemorrhage with a product like this.
Glatter: Is manual pressure required in that sense? From what you described earlier, manual pressure would not be required.
Landolina: It depends on the injury. What we recommend is that, if you have a very deep wound where you cannot visualize the source of bleed, you use pressure to seat Traumagel into the source of bleeding, meaning that you’re following Committee on Tactical Combat Casualty Care (Co-TCCC) regulations or requirements, where you’re over wrapping with gauze, and you’re providing a pressure wrapping to ensure that the Traumagel is in contact with the bleed while it’s doing what it’s doing.
In most cases, it doesn’t hurt to apply pressure on top of Traumagel as well. In more surface level bleeds, you don’t need pressure at all.
Applications Beyond Trauma
Glatter: Interesting. In terms of further applications (eg, nose bleeds or GYN bleeding, which are life-threatening), do you see this coming as an application for the future?
Landolina: That’s where we’re working. Traumagel is the successor to an animal health product called Vetigel. The formulations of the gel behind Vetigel and Traumagel are identical. Vetigel has a full surgical indication, and that’s everything from epistaxis to neuro and spine procedures, into cardiovascular and soft tissue surgeries, orthopedic medicine, and so on.
Cresilon’s goal is to eventually expand the indication of our technology to include surgical indications and other indications where we can help any patient that’s bleeding.
Glatter: That’s important, because we use prehospital whole blood, low titer, specifically, when patients have life-threatening hemorrhage. With your product, that would reduce the amount of blood products that would need to be administered. This could be a real game changer.
Landolina: Definitely, that’s the goal we’re working on.
Infection Risks and Biocompatibility
Glatter: In terms of any risk for infection, has that been studied as well? Does Traumagel in any way lead to increased rates of infection?
Landolina: Traumagel is biocompatible. It’s a sterile product. We’ve done the full suite of biocompatibility testing as required by FDA. On top of that, remember that Vetigel, which is the same formulation, is an implantable product. As a result, that has even extended biocompatibility testing beyond what would be necessary for an external product.
In Vetigel’s use case, which has been used now in over 60,000 patients, primarily companion animals, dogs and cats, we haven’t seen instances of infection. There’s no reason to believe that we would see that clinically with Traumagel.
Research Collaborations and Future Applications
Glatter: In terms of other research that your company’s embarked on preclinically, I understand there were some studies done at Walter Reed Army Institute of Research. I was wondering if you could expand on these, specifically, in terms of traumatic brain injury (TBI) and hemorrhage related to that. For example, with shrapnel or even a gunshot wound.
Landolina: The Walter Reed collaboration with Cresilon is something that I’m particularly excited about, because it marks Cresilon’s first project that’s outside the scope of just hemostasis. Walter Reed came to us with this proposal where there’s a big challenge in a subset of TBI called penetrating ballistic-like brain injury, where the brain has been penetrated by a bullet, shrapnel, or some other projectile, and there’s an injury that exposes the brain to the outside.
Today, there is no standard of care to treat patients with those types of injuries. In many cases, mortality is caused through swelling of the brain, or collapse of the brain. What they came to us with was the potential of using our technology, not primarily as a hemostatic agent, but to be able to stabilize that patient enough to get to the next level of care to be treated by a neurosurgeon.
That study Walter Reed did was just a pilot that was done in small animals. In that pilot, they showed that over the period of treatment, there was no negative change in vital signs, no increase in edema or in swelling, or in any of the biomarkers that were being monitored at that time.
At the very least, this is not full indication that this indication will work for Cresilon, but it shows that there’s promise. It’s something that we’re working on and hopefully we’ll be able to bring to market soon.
Glatter: Certainly, maintaining intracranial pressure and cerebral perfusion pressures are very critical. In the future, do you think this product would be able to be deployed endovascularly? Imagine this in terms of stopping bleeding from some source, whether it’s from a stroke or another intracranial source.
Landolina: That’s been an area of interest for us. We have no evidence to prove that indication works at this point, but there’s also nothing to say that it wouldn’t be possible for our technology. At this point, we’ve only looked at a cursory level at those indications.
Glatter: Does the use of Traumagel obviate the need for a more definitive repair (eg, with sutures) or something that’s more permanent?
Landolina: I always say that Traumagel — and Vetigel, for that matter — is not a replacement for good surgical technique. The surgeon always needs to make his or her best judgment when reviewing the patient. That doesn’t mean that there won’t need to be sutures or vascular repair in most of these cases, especially in major trauma.
Final Takeaways
Glatter: Do you have some bullet points or pearls you could give our audience as a takeaway?
Landolina: When Cresilon looks at Traumagel — and for us, Traumagel is the next generation of hemostatic agent, especially in trauma care and in emergency medicine — it allows for a far-simplified application of the product and much faster control of hemorrhage with better patient outcomes.
As we roll this out through EMS agencies, trauma hospitals, military agencies, and eventually to the general public through a future indication, it’s something we’re very excited about. Personally, I started this business 14 years ago, and so it’s great to see our mission of saving lives transitioning to saving human lives.
Glatter: I look forward to seeing this product in the emergency department, but also in other settings, such as in the operating room where we can really help patients who are dying from hemorrhage, certainly on the battlefield, and the lay public. If someone were to come upon a patient who’s bleeding out, this could be certainly a game changer and a lifesaver.
I want to thank you for your time. This is a really important product that’s transformed the lives of so many animals, but also people in the future.
Dr. Glatter is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He reported no relevant conflicts of interest. Mr. Landolina is the CEO and co-founder of Cresilon, a biotechnology company specializing in plant-based solutions for emergency bleeding control.
A version of this article first appeared on Medscape.com.
Key Updates in Resuscitation Procedure After Drowning
New recommendations on rescuing adults and children who have drowned include an important update for healthcare professionals, trained rescuers, and untrained lay rescuers.
The American Heart Association (AHA) and the American Academy of Pediatrics (AAP) have issued recommendations that highlight delivering rescue breaths as well as calling 911 and performing chest compressions in cardiopulmonary resuscitation (CPR) as first steps when a person pulled from the water is in cardiac arrest.
This is the first collaboration between the two organizations on resuscitation after drowning. The recommendations were published simultaneously in Circulation and Pediatrics.
Included in the recommendations are two key principles:
- Anyone pulled from the water who has no signs of normal breathing or consciousness should be presumed to be in cardiac arrest.
- Rescuers should immediately start CPR that includes rescue breathing in addition to chest compressions. Multiple large studies show more people with cardiac arrest from noncardiac causes such as drowning survive when CPR includes rescue breaths, compared with hands-only CPR (calling 911 and pushing hard and fast in the center of the chest).
If someone is untrained, unwilling, or unable to give breaths, they can perform chest compressions until help arrives, the recommendations advise.
Reasoning Behind the Update
The authors, led by writing group cochair Tracy E. McCallin, MD, associate professor in the division of pediatric emergency medicine at Rainbow Babies and Children’s Hospital in Cleveland , Ohio, explained that drowning generally advances from initial respiratory arrest from submersion-related hypoxia to cardiac arrest, and therefore it can be difficult to distinguish respiratory arrest from cardiac arrest because pulses are difficult to accurately palpate within the recommended 10-second window.
“Therefore, resuscitation from cardiac arrest due to this specific circumstance must focus on restoring breathing as much as it does circulation,” the authors wrote.
Resuscitation after drowning may begin in the water with rescue breathing when safely provided by trained rescuers and should continue with chest compressions, once the drowned person and the rescuer are on land or in a boat, the report authors wrote.
“The focused update on drowning contains the most up-to-date, evidence-based recommendations on how to resuscitate someone who has drowned,” McCallin states in a press release.
In addition to the new guidance on rescue breaths, the update includes new topics that the AHA has not previously addressed with treatment recommendations, such as oxygen administration after drowning; automated external defibrillator use in cardiac arrest after drowning and public-access defibrillation programs.
Pediatricians Can Help Spread the Word
Alexandra Stern, MD, assistant professor in the Department of Pediatrics at University of Florida, Gainesville, who was not part of the update, said pediatricians can help disseminate this new information.
“Water safety is a topic frequently discussed as a pediatrician, with focus often being on primary prevention of drowning,” she said. “We stress the importance of the multiple layers of protection against drowning, such as touch supervision (staying within arm’s length); secure fencing, access to appropriate life jackets, and teaching our children to swim. Learning CPR is a large part of these measures and continuing these discussions with our patients and families is important.”
She added that updating the recommended procedures will likely require changes to all forms of education and community outreach regarding drowning from basic life support classes to more advanced lifeguard training. She noted that the update provides practical guidance not just for trained rescuers and healthcare professionals, but also for family members.
The paper notes that drowning is the third leading cause of death from unintentional injury globally, accounting for 7% of all injury-related deaths. In the United States, drowning is the leading cause of death in children aged 1-4 years and the second leading cause of death from unintentional injury in children aged 5-14 years.
The update is based on systematic reviews from 2021 to 2023 performed by the International Liaison Committee on Resuscitation related to the resuscitation of drowning.
The authors and Stern reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
New recommendations on rescuing adults and children who have drowned include an important update for healthcare professionals, trained rescuers, and untrained lay rescuers.
The American Heart Association (AHA) and the American Academy of Pediatrics (AAP) have issued recommendations that highlight delivering rescue breaths as well as calling 911 and performing chest compressions in cardiopulmonary resuscitation (CPR) as first steps when a person pulled from the water is in cardiac arrest.
This is the first collaboration between the two organizations on resuscitation after drowning. The recommendations were published simultaneously in Circulation and Pediatrics.
Included in the recommendations are two key principles:
- Anyone pulled from the water who has no signs of normal breathing or consciousness should be presumed to be in cardiac arrest.
- Rescuers should immediately start CPR that includes rescue breathing in addition to chest compressions. Multiple large studies show more people with cardiac arrest from noncardiac causes such as drowning survive when CPR includes rescue breaths, compared with hands-only CPR (calling 911 and pushing hard and fast in the center of the chest).
If someone is untrained, unwilling, or unable to give breaths, they can perform chest compressions until help arrives, the recommendations advise.
Reasoning Behind the Update
The authors, led by writing group cochair Tracy E. McCallin, MD, associate professor in the division of pediatric emergency medicine at Rainbow Babies and Children’s Hospital in Cleveland , Ohio, explained that drowning generally advances from initial respiratory arrest from submersion-related hypoxia to cardiac arrest, and therefore it can be difficult to distinguish respiratory arrest from cardiac arrest because pulses are difficult to accurately palpate within the recommended 10-second window.
“Therefore, resuscitation from cardiac arrest due to this specific circumstance must focus on restoring breathing as much as it does circulation,” the authors wrote.
Resuscitation after drowning may begin in the water with rescue breathing when safely provided by trained rescuers and should continue with chest compressions, once the drowned person and the rescuer are on land or in a boat, the report authors wrote.
“The focused update on drowning contains the most up-to-date, evidence-based recommendations on how to resuscitate someone who has drowned,” McCallin states in a press release.
In addition to the new guidance on rescue breaths, the update includes new topics that the AHA has not previously addressed with treatment recommendations, such as oxygen administration after drowning; automated external defibrillator use in cardiac arrest after drowning and public-access defibrillation programs.
Pediatricians Can Help Spread the Word
Alexandra Stern, MD, assistant professor in the Department of Pediatrics at University of Florida, Gainesville, who was not part of the update, said pediatricians can help disseminate this new information.
“Water safety is a topic frequently discussed as a pediatrician, with focus often being on primary prevention of drowning,” she said. “We stress the importance of the multiple layers of protection against drowning, such as touch supervision (staying within arm’s length); secure fencing, access to appropriate life jackets, and teaching our children to swim. Learning CPR is a large part of these measures and continuing these discussions with our patients and families is important.”
She added that updating the recommended procedures will likely require changes to all forms of education and community outreach regarding drowning from basic life support classes to more advanced lifeguard training. She noted that the update provides practical guidance not just for trained rescuers and healthcare professionals, but also for family members.
The paper notes that drowning is the third leading cause of death from unintentional injury globally, accounting for 7% of all injury-related deaths. In the United States, drowning is the leading cause of death in children aged 1-4 years and the second leading cause of death from unintentional injury in children aged 5-14 years.
The update is based on systematic reviews from 2021 to 2023 performed by the International Liaison Committee on Resuscitation related to the resuscitation of drowning.
The authors and Stern reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
New recommendations on rescuing adults and children who have drowned include an important update for healthcare professionals, trained rescuers, and untrained lay rescuers.
The American Heart Association (AHA) and the American Academy of Pediatrics (AAP) have issued recommendations that highlight delivering rescue breaths as well as calling 911 and performing chest compressions in cardiopulmonary resuscitation (CPR) as first steps when a person pulled from the water is in cardiac arrest.
This is the first collaboration between the two organizations on resuscitation after drowning. The recommendations were published simultaneously in Circulation and Pediatrics.
Included in the recommendations are two key principles:
- Anyone pulled from the water who has no signs of normal breathing or consciousness should be presumed to be in cardiac arrest.
- Rescuers should immediately start CPR that includes rescue breathing in addition to chest compressions. Multiple large studies show more people with cardiac arrest from noncardiac causes such as drowning survive when CPR includes rescue breaths, compared with hands-only CPR (calling 911 and pushing hard and fast in the center of the chest).
If someone is untrained, unwilling, or unable to give breaths, they can perform chest compressions until help arrives, the recommendations advise.
Reasoning Behind the Update
The authors, led by writing group cochair Tracy E. McCallin, MD, associate professor in the division of pediatric emergency medicine at Rainbow Babies and Children’s Hospital in Cleveland , Ohio, explained that drowning generally advances from initial respiratory arrest from submersion-related hypoxia to cardiac arrest, and therefore it can be difficult to distinguish respiratory arrest from cardiac arrest because pulses are difficult to accurately palpate within the recommended 10-second window.
“Therefore, resuscitation from cardiac arrest due to this specific circumstance must focus on restoring breathing as much as it does circulation,” the authors wrote.
Resuscitation after drowning may begin in the water with rescue breathing when safely provided by trained rescuers and should continue with chest compressions, once the drowned person and the rescuer are on land or in a boat, the report authors wrote.
“The focused update on drowning contains the most up-to-date, evidence-based recommendations on how to resuscitate someone who has drowned,” McCallin states in a press release.
In addition to the new guidance on rescue breaths, the update includes new topics that the AHA has not previously addressed with treatment recommendations, such as oxygen administration after drowning; automated external defibrillator use in cardiac arrest after drowning and public-access defibrillation programs.
Pediatricians Can Help Spread the Word
Alexandra Stern, MD, assistant professor in the Department of Pediatrics at University of Florida, Gainesville, who was not part of the update, said pediatricians can help disseminate this new information.
“Water safety is a topic frequently discussed as a pediatrician, with focus often being on primary prevention of drowning,” she said. “We stress the importance of the multiple layers of protection against drowning, such as touch supervision (staying within arm’s length); secure fencing, access to appropriate life jackets, and teaching our children to swim. Learning CPR is a large part of these measures and continuing these discussions with our patients and families is important.”
She added that updating the recommended procedures will likely require changes to all forms of education and community outreach regarding drowning from basic life support classes to more advanced lifeguard training. She noted that the update provides practical guidance not just for trained rescuers and healthcare professionals, but also for family members.
The paper notes that drowning is the third leading cause of death from unintentional injury globally, accounting for 7% of all injury-related deaths. In the United States, drowning is the leading cause of death in children aged 1-4 years and the second leading cause of death from unintentional injury in children aged 5-14 years.
The update is based on systematic reviews from 2021 to 2023 performed by the International Liaison Committee on Resuscitation related to the resuscitation of drowning.
The authors and Stern reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
From Pediatrics
Semiannual Time Changes Linked to Accidents, Heart Attacks
As people turn their clocks back an hour on November 3 to mark the end of daylight saving time and return to standard time, they should remain aware of their sleep health and of potential risks associated with shifts in sleep patterns, according to a University of Calgary psychology professor who researches circadian cycles.
said Michael Antle, PhD, head of the psychology department and member of the Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary, Alberta, Canada.
In an interview, Antle explained the science behind the health risks associated with time changes, offered tips to prepare for the shift, and discussed scientists’ suggestion to move to year-round standard time. This interview has been condensed and edited for clarity.
Why is it important to pay attention to circadian rhythms?
Circadian rhythms are patterns of physiologic and behavioral changes that affect everything inside the body and everything we do, including when hormones are secreted, digestive juices are ready to digest, and growth hormones are released at night. The body is a carefully coordinated orchestra, and everything has to happen at the right time.
When we start messing with those rhythms, that’s when states of disease start coming on and we don’t feel well. You’ve probably experienced it — when you try to stay up late, eat at the wrong times, or have jet lag. Flying across one or two time zones is usually tolerable, but if you fly across the world, it can be profound and make you feel bad, even up to a week. Similar shifts happen with the time changes.
How do the time changes affect health risks?
The wintertime change is generally more tolerable, and you’ll hear people talk about “gaining an hour” of sleep. It’s better than that, because we’re realigning our social clocks — such as our work schedules and school schedules — with daylight. We tend to go to bed relative to the sun but wake up based on when our boss says to be at our desk, so an earlier sunset helps us to fall asleep earlier and is healthier for our body.
In the spring, the opposite happens, and the time change affects us much more than just one bad night of sleep. For some people, it can feel like losing an hour of sleep every day for weeks, and that abrupt change can lead to car accidents, workplace injuries, heart attacks, and strokes. Our body experiences extra strain when we’re not awake and ready for the day.
What does your research show?
Most of my work focuses on preclinical models to understand what’s going on in the brain and body. Because we can’t study this ethically in humans, we learn a lot from animal models, especially mice. In a recent study looking at mild circadian disruption — where we raised mice on days that were about 75 minutes shorter — we saw they started developing diabetes, heart disease, and insulin resistance within in a few months, or about the time they were a young adult.
Oftentimes, people think about their sleep rhythm as an arbitrary choice, but in fact, it does affect your health. We know that if your human circadian clock runs slow, morning light can help fix that and reset it, whereas evening light moves us in the other direction and makes it harder to get up in the morning.
Some people want to switch to one year-round time. What do you advocate?
In most cases, the standard time (or winter time) is the more natural time that fits better with our body cycle. If we follow a time where we get up before sunrise or have a later sunset, then it’s linked to more social jet lag, where people are less attentive at work, don’t learn as well at school, and have more accidents.
Instead of picking what sounds good or chasing the name — such as “daylight saving time” — we need to think about the right time for us and our circadian clock. Some places, such as Maine in the United States, would actually fit better with the Atlantic time zone or the Maritime provinces in Canada, whereas some parts of Alberta are geographically west of Los Angeles based on longitude and would fit better with the Pacific time zone. Sticking with a year-round daylight saving time in some cities in Alberta would mean people wouldn’t see the sun until 10:30 AM in the winter, which is really late and could affect activities such as skiing and hockey.
The Canadian Society for Chronobiology advocates for year-round standard time to align our social clocks with our biological clocks. Sleep and circadian rhythm experts in the US and globally have issued similar position statements.
What tips do you suggest to help people adjust their circadian clocks in November?
For people who know their bodies and that it will affect them more, give yourself extra time. If your schedule permits, plan ahead and change your clocks sooner, especially if you’re able to do so over the weekend. Don’t rush around while tired — rushing when you’re not ready leads to those increased accidents on the road or on the job. Know that the sun will still be mismatched for a bit and your body clock will take time to adjust, so you might feel out of sorts for a few days.
Antle reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
As people turn their clocks back an hour on November 3 to mark the end of daylight saving time and return to standard time, they should remain aware of their sleep health and of potential risks associated with shifts in sleep patterns, according to a University of Calgary psychology professor who researches circadian cycles.
said Michael Antle, PhD, head of the psychology department and member of the Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary, Alberta, Canada.
In an interview, Antle explained the science behind the health risks associated with time changes, offered tips to prepare for the shift, and discussed scientists’ suggestion to move to year-round standard time. This interview has been condensed and edited for clarity.
Why is it important to pay attention to circadian rhythms?
Circadian rhythms are patterns of physiologic and behavioral changes that affect everything inside the body and everything we do, including when hormones are secreted, digestive juices are ready to digest, and growth hormones are released at night. The body is a carefully coordinated orchestra, and everything has to happen at the right time.
When we start messing with those rhythms, that’s when states of disease start coming on and we don’t feel well. You’ve probably experienced it — when you try to stay up late, eat at the wrong times, or have jet lag. Flying across one or two time zones is usually tolerable, but if you fly across the world, it can be profound and make you feel bad, even up to a week. Similar shifts happen with the time changes.
How do the time changes affect health risks?
The wintertime change is generally more tolerable, and you’ll hear people talk about “gaining an hour” of sleep. It’s better than that, because we’re realigning our social clocks — such as our work schedules and school schedules — with daylight. We tend to go to bed relative to the sun but wake up based on when our boss says to be at our desk, so an earlier sunset helps us to fall asleep earlier and is healthier for our body.
In the spring, the opposite happens, and the time change affects us much more than just one bad night of sleep. For some people, it can feel like losing an hour of sleep every day for weeks, and that abrupt change can lead to car accidents, workplace injuries, heart attacks, and strokes. Our body experiences extra strain when we’re not awake and ready for the day.
What does your research show?
Most of my work focuses on preclinical models to understand what’s going on in the brain and body. Because we can’t study this ethically in humans, we learn a lot from animal models, especially mice. In a recent study looking at mild circadian disruption — where we raised mice on days that were about 75 minutes shorter — we saw they started developing diabetes, heart disease, and insulin resistance within in a few months, or about the time they were a young adult.
Oftentimes, people think about their sleep rhythm as an arbitrary choice, but in fact, it does affect your health. We know that if your human circadian clock runs slow, morning light can help fix that and reset it, whereas evening light moves us in the other direction and makes it harder to get up in the morning.
Some people want to switch to one year-round time. What do you advocate?
In most cases, the standard time (or winter time) is the more natural time that fits better with our body cycle. If we follow a time where we get up before sunrise or have a later sunset, then it’s linked to more social jet lag, where people are less attentive at work, don’t learn as well at school, and have more accidents.
Instead of picking what sounds good or chasing the name — such as “daylight saving time” — we need to think about the right time for us and our circadian clock. Some places, such as Maine in the United States, would actually fit better with the Atlantic time zone or the Maritime provinces in Canada, whereas some parts of Alberta are geographically west of Los Angeles based on longitude and would fit better with the Pacific time zone. Sticking with a year-round daylight saving time in some cities in Alberta would mean people wouldn’t see the sun until 10:30 AM in the winter, which is really late and could affect activities such as skiing and hockey.
The Canadian Society for Chronobiology advocates for year-round standard time to align our social clocks with our biological clocks. Sleep and circadian rhythm experts in the US and globally have issued similar position statements.
What tips do you suggest to help people adjust their circadian clocks in November?
For people who know their bodies and that it will affect them more, give yourself extra time. If your schedule permits, plan ahead and change your clocks sooner, especially if you’re able to do so over the weekend. Don’t rush around while tired — rushing when you’re not ready leads to those increased accidents on the road or on the job. Know that the sun will still be mismatched for a bit and your body clock will take time to adjust, so you might feel out of sorts for a few days.
Antle reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
As people turn their clocks back an hour on November 3 to mark the end of daylight saving time and return to standard time, they should remain aware of their sleep health and of potential risks associated with shifts in sleep patterns, according to a University of Calgary psychology professor who researches circadian cycles.
said Michael Antle, PhD, head of the psychology department and member of the Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary, Alberta, Canada.
In an interview, Antle explained the science behind the health risks associated with time changes, offered tips to prepare for the shift, and discussed scientists’ suggestion to move to year-round standard time. This interview has been condensed and edited for clarity.
Why is it important to pay attention to circadian rhythms?
Circadian rhythms are patterns of physiologic and behavioral changes that affect everything inside the body and everything we do, including when hormones are secreted, digestive juices are ready to digest, and growth hormones are released at night. The body is a carefully coordinated orchestra, and everything has to happen at the right time.
When we start messing with those rhythms, that’s when states of disease start coming on and we don’t feel well. You’ve probably experienced it — when you try to stay up late, eat at the wrong times, or have jet lag. Flying across one or two time zones is usually tolerable, but if you fly across the world, it can be profound and make you feel bad, even up to a week. Similar shifts happen with the time changes.
How do the time changes affect health risks?
The wintertime change is generally more tolerable, and you’ll hear people talk about “gaining an hour” of sleep. It’s better than that, because we’re realigning our social clocks — such as our work schedules and school schedules — with daylight. We tend to go to bed relative to the sun but wake up based on when our boss says to be at our desk, so an earlier sunset helps us to fall asleep earlier and is healthier for our body.
In the spring, the opposite happens, and the time change affects us much more than just one bad night of sleep. For some people, it can feel like losing an hour of sleep every day for weeks, and that abrupt change can lead to car accidents, workplace injuries, heart attacks, and strokes. Our body experiences extra strain when we’re not awake and ready for the day.
What does your research show?
Most of my work focuses on preclinical models to understand what’s going on in the brain and body. Because we can’t study this ethically in humans, we learn a lot from animal models, especially mice. In a recent study looking at mild circadian disruption — where we raised mice on days that were about 75 minutes shorter — we saw they started developing diabetes, heart disease, and insulin resistance within in a few months, or about the time they were a young adult.
Oftentimes, people think about their sleep rhythm as an arbitrary choice, but in fact, it does affect your health. We know that if your human circadian clock runs slow, morning light can help fix that and reset it, whereas evening light moves us in the other direction and makes it harder to get up in the morning.
Some people want to switch to one year-round time. What do you advocate?
In most cases, the standard time (or winter time) is the more natural time that fits better with our body cycle. If we follow a time where we get up before sunrise or have a later sunset, then it’s linked to more social jet lag, where people are less attentive at work, don’t learn as well at school, and have more accidents.
Instead of picking what sounds good or chasing the name — such as “daylight saving time” — we need to think about the right time for us and our circadian clock. Some places, such as Maine in the United States, would actually fit better with the Atlantic time zone or the Maritime provinces in Canada, whereas some parts of Alberta are geographically west of Los Angeles based on longitude and would fit better with the Pacific time zone. Sticking with a year-round daylight saving time in some cities in Alberta would mean people wouldn’t see the sun until 10:30 AM in the winter, which is really late and could affect activities such as skiing and hockey.
The Canadian Society for Chronobiology advocates for year-round standard time to align our social clocks with our biological clocks. Sleep and circadian rhythm experts in the US and globally have issued similar position statements.
What tips do you suggest to help people adjust their circadian clocks in November?
For people who know their bodies and that it will affect them more, give yourself extra time. If your schedule permits, plan ahead and change your clocks sooner, especially if you’re able to do so over the weekend. Don’t rush around while tired — rushing when you’re not ready leads to those increased accidents on the road or on the job. Know that the sun will still be mismatched for a bit and your body clock will take time to adjust, so you might feel out of sorts for a few days.
Antle reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MDMA Is Off the Table, So What’s Next for PTSD?
It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.
Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.
“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.
Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
A Treatable Condition
So with MDMA-AT off the table, where does the field go next?
A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.
Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.
“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.
The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.
Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.
However, as the September meeting demonstrated, more therapies are needed.
“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.
There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.
Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.
“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.
“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.
The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.
One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.
The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.
The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.
Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.
Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
New Therapies on the Way
Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.
Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.
Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.
Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.
But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.
Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.
Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.
“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”
Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.
The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
The Potential of Psychedelics
Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.
The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.
Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.
Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”
Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.
London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.
Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.
“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.
Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.
Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.
“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.
Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
A Treatable Condition
So with MDMA-AT off the table, where does the field go next?
A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.
Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.
“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.
The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.
Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.
However, as the September meeting demonstrated, more therapies are needed.
“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.
There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.
Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.
“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.
“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.
The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.
One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.
The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.
The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.
Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.
Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
New Therapies on the Way
Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.
Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.
Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.
Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.
But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.
Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.
Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.
“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”
Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.
The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
The Potential of Psychedelics
Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.
The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.
Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.
Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”
Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.
London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.
Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.
“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.
Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
It has been 24 years since a pharmaceutical was last approved for posttraumatic stress disorder (PTSD). The condition is notoriously difficult to treat, with up to 40% patients finding no relief from symptoms through psychotherapy or current medications.
Many clinicians, advocates, and patients had pinned their hopes on the psychedelic drug midomafetamine with assisted therapy (MDMA-AT). However, in August, the US Food and Drug Administration (FDA) rejected it. At this point, it’s unclear when the therapy will be available, if ever.
“Not getting the FDA approval of any drug at this point is a setback for the field,” Lori Davis, MD, a senior research psychiatrist at the Birmingham Veterans Affairs (VA) Health Care System in Birmingham, Alabama, told Medscape Medical News.
Having an FDA-approved product would have helped increase public awareness of PTSD and driven interest in developing new therapies, said Davis, who is also adjunct professor of psychiatry at the Heersink School of Medicine, University of Alabama at Birmingham.
A Treatable Condition
So with MDMA-AT off the table, where does the field go next?
A public meeting in September hosted by the Reagan-Udall Foundation for the FDA in sought to answer that question. Agency officials joined representatives from the Department of Defense (DoD) and VA, patients, advocates, and industry representatives to discuss the current treatment landscape and what can be done to accelerate development of PTSD treatment.
Despite the common belief that PTSD is intractable, it “is a treatable condition,” Paula P. Schnurr, PhD, executive director of the VA National Center for PTSD, said at the meeting.
“There are effective treatments that work well for a lot of people, although not everyone has a satisfactory response,” she added.
The most effective psychotherapies are “trauma-focused,” and include cognitive processing therapy, eye movement desensitization and reprocessing, and prolonged exposure, according to the VA National Center for PTSD.
Three drugs have been approved by the FDA for PTSD: Venlafaxine (Effexor) in 1993, sertraline (Zoloft) in 1999, and paroxetine (Paxil) in 2000.
However, as the September meeting demonstrated, more therapies are needed.
“It’s clear to FDA and the federal government at large that there is an unmet need for safe and effective therapies to treat PTSD,” Bernard Fischer, MD, deputy director of the Division of Psychiatry in the Office of New Drugs at FDA’s Center for Drug Evaluation and Research, said at the meeting.
There is no shortage of research, Fischer added. Nearly 500 trials focused on PTSD are listed on clinicaltrials.gov are recruiting participants now or plan to soon.
Unsurprisingly, one of the primary drivers of PTSD therapeutics research is the VA. About 14% of the 5.7 million veterans who received care through the VA in 2023 had a diagnosis of PTSD.
“The US military is currently losing thousands of service members each year to PTSD- related disability discharges,” US Army Maj. Aaron Wolfgang, MD, a psychiatrist at the Walter Reed National Military Medical Center, said at the meeting. Only about 12%-20% of patients achieve remission with conventional therapies, added Wolfgang, who also is an assistant professor at the Uniformed Services University.
“For these reasons, establishing better treatments for PTSD is not only a matter of humanitarianism but also a pressing matter of national security,” he said.
The VA has committed at least $230 million to more than 140 active research projects in PTSD, Miriam J. Smyth, PhD, acting director of the clinical science, research and development service at the VA, said at the Reagan-Udall meeting.
One of the VA projects is the PTSD psychopharmacology initiative, which began in 2017 and now has 14 active clinical trials, said Smyth, who is also acting director for brain behavior and mental health at the VA. The first study should be finished by 2025.
The Million Veteran Program, with more than 1 million enrollees, has led to the discovery of genes related to re-experiencing traumatic memories and has confirmed that both PTSD and traumatic brain injury are risk factors for dementia, Smyth said.
The DoD has created a novel platform that establishes a common infrastructure for testing multiple drugs, called M-PACT. The platform allows sharing of placebo data across treatment arms. Drugs cycle off the platform if evidence indicates probability of success or failure.
Four trials are actively recruiting veterans and current service members. One is looking at vilazodone, approved in 2011 for major depressive disorder. It is being compared with placebo and fluoxetine in a trial that is currently recruiting.
Another trial will study daridorexant (sold as Quviviq), an orexin receptor antagonist, against placebo. The FDA approved daridorexant in 2022 as an insomnia treatment. A core issue in PTSD is sleep disruption, noted Davis.
New Therapies on the Way
Separately, Davis and colleagues are also studying methylphenidate, the stimulant used for attention-deficit/hyperactivity disorder. It may help with neurocognitive complaints and reduce PTSD symptoms, said Davis.
Because it is generic, few pharmaceutical manufacturers are likely to test it for PTSD, she said. But eventually, their work may lead a company to test newer stimulants for PTSD, she said.
Another potential therapeutic, BNC210, received Fast Track designation for PTSD from the FDA in 2019. Bionomics Limited in Australia will soon launch phase 3 trials of the investigational oral drug, which is a negative allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. In late July, the company announced “ favorable feedback” from the agency on its phase 2 study, which led to the decision to move forward with larger trials.
Researchers at Brigham and Women’s Hospital have just reported that they may have found a target within the brain that will allow for transcranial magnetic stimulation (TMS) to ameliorate PTSD symptoms. They published results of a mapping effort in Nature Neuroscience and reported on one patient who had improved symptoms after receiving TMS for severe PTSD.
But perhaps one of the most promising treatments is a combination of sertraline and the new psychiatric medication brexpiprazole.
Brexpiprazole was developed by Otsuka Pharmaceutical and approved in the United States in 2015 as an adjunctive therapy to antidepressants for major depressive disorder and as a treatment for schizophrenia. In 2023, the FDA approved it for Alzheimer’s-related agitation. However, according to Otsuka, its mechanism of action is unknown.
Its efficacy may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, antagonist activity at serotonin 5-HT2A receptors, as well as antagonism of alpha-1B/2C receptors, said the company.
“It is the combination, rather than either alone, that’s going to have that broad synergistic pharmacology that is obviously potent for ameliorating the symptoms of PTSD,” said Davis, who has received consulting fees from Otsuka. “That’s an exciting development.”
Otsuka and partner Lundbeck Pharmaceuticals reported results in May from the companies’ phase 2 and 3 randomized clinical trials. The therapy achieved a statistically significant reduction (P <.05) in PTSD symptoms compared with sertraline plus placebo. This was without any supplemental psychotherapy.
The FDA accepted the companies’ new drug application in June and is expected to make a decision on approval in February 2025.
The Potential of Psychedelics
Though Lykos Therapeutics may have to go back to the drawing board on its MDMA-AT, psychedelics still have potential as PTSD therapies, Smyth said, who added that the VA is continuing to encourage study of MDMA and other psychedelic agents.
The VA issued a call for proposals for research on psychedelics in January, focused on MDMA or psilocybin in combination with psychotherapy. The administration received the first wave of applications early in the summer.
Scientific peer review panels made up of research experts from within and outside the VA have reviewed the applications and funding announcements are expected this fall, Smyth said.
Wolfgang, the Army psychiatrist, said, “Under the psychedelic treatment research clinical trial award, we welcome investigators to apply to what we anticipate will usher in a new era of innovation and hope for service members and their families who need it the most.”
Psychedelic studies are also proceeding without VA funding, as they have for years, when most of the trials were backed by universities or foundations or other private money. Johns Hopkins University is recruiting for a study in which patients would receive psilocybin along with trauma-focused psychotherapy, as is Ohio State University.
London-based Compass Pathways said in May that it successfully completed a phase 2 trial of Comp360, its synthetic psilocybin, in PTSD. The company has started a phase 3 study in treatment-resistant depression but has not given any further updates on PTSD.
Davis said that she believes that the FDA’s rejection of Lykos won’t lead to a shutdown of exploration of psychedelics.
“I think it informs these designs going forward, but it doesn’t eliminate that whole field of research,” she said.
Davis reported receiving consulting fees from Boehringer Ingelheim and Otsuka and research funding from Alkermes, the Patient-Centered Outcomes Research Institute, and the VA. Schnurr, Fischer, Smyth, and Wolfgang reported no relevant disclosures.
A version of this article appeared on Medscape.com.
First Combined Face and Eye Transplant Performed
In a groundbreaking procedure, a team of surgeons from New York University Langone Health successfully performed the first combined face and eye transplant on a patient with extensive craniofacial tissue loss after an electrical accident.
The highly complex surgery lasted for 21 hours and involved more than 140 surgeons, nurses, and other healthcare professionals under the leadership of Eduardo D. Rodriguez. MD. It not only restored the patient’s facial features, but also integrated a functional eyeball, potentially setting a new standard for future treatments in similar cases.
The transplant took place in May 2023, and the case report was published on September 5 this year in JAMA.
The 46-year-old man lost a large part of his craniofacial tissue and his left eyeball. The approach was highly specialized. Advanced microsurgical techniques such as anastomoses of microscopic vessels and delicate suturing techniques were crucial for the transplant’s success.
Moreover, customized surgical devices, specific implants, and tissue manipulation tools were developed specifically for this case, thus ensuring the viability of the transplant and adequate perfusion of the transplanted ocular tissue.
The initial results are encouraging. Retinal arterial perfusion has been maintained, and retinal architecture has been preserved, as demonstrated by optical coherence tomography. Electroretinography confirmed retinal responses to light, suggesting that the transplanted eye may eventually contribute to the patient’s visual perception. These results are comparable to those of previous facial tissue transplants, but with the significant addition of ocular functionality, which is a notable advance.
“The successful revascularization of the transplanted eye achieved in this study may serve as a step toward the goal of globe transplant for restoration of vision,” wrote the authors.
The complexity of the combined transplant required a deep understanding of facial and ocular anatomy, as well as tissue preservation techniques. The surgical team reported significant challenges, including the need to align delicate anatomical structures and ensure immunological compatibility between the donor and recipient. Meticulous planning from donor selection to postoperative follow-up was considered essential to maximize the likelihood of success and minimize the risk for allograft rejection.
The patient will now be continuously monitored and receive treatment with immunosuppressants such as tacrolimus and prednisone, adjusted according to his response to the transplant. According to the researchers, further studies will be needed to assess the long-term functionality of the transplanted eye and its integration with the central nervous system.
Despite being the fifth facial transplant surgery performed under Dr. Rodriguez’s leadership, this is the first record of a whole-eye transplant. “The mere fact that we have successfully performed the first whole-eye transplant along with a face transplant is a tremendous achievement that many believed to be impossible,” the doctor said in a statement. “We have taken a giant step forward and paved the way for the next chapter in vision restoration.”
This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
In a groundbreaking procedure, a team of surgeons from New York University Langone Health successfully performed the first combined face and eye transplant on a patient with extensive craniofacial tissue loss after an electrical accident.
The highly complex surgery lasted for 21 hours and involved more than 140 surgeons, nurses, and other healthcare professionals under the leadership of Eduardo D. Rodriguez. MD. It not only restored the patient’s facial features, but also integrated a functional eyeball, potentially setting a new standard for future treatments in similar cases.
The transplant took place in May 2023, and the case report was published on September 5 this year in JAMA.
The 46-year-old man lost a large part of his craniofacial tissue and his left eyeball. The approach was highly specialized. Advanced microsurgical techniques such as anastomoses of microscopic vessels and delicate suturing techniques were crucial for the transplant’s success.
Moreover, customized surgical devices, specific implants, and tissue manipulation tools were developed specifically for this case, thus ensuring the viability of the transplant and adequate perfusion of the transplanted ocular tissue.
The initial results are encouraging. Retinal arterial perfusion has been maintained, and retinal architecture has been preserved, as demonstrated by optical coherence tomography. Electroretinography confirmed retinal responses to light, suggesting that the transplanted eye may eventually contribute to the patient’s visual perception. These results are comparable to those of previous facial tissue transplants, but with the significant addition of ocular functionality, which is a notable advance.
“The successful revascularization of the transplanted eye achieved in this study may serve as a step toward the goal of globe transplant for restoration of vision,” wrote the authors.
The complexity of the combined transplant required a deep understanding of facial and ocular anatomy, as well as tissue preservation techniques. The surgical team reported significant challenges, including the need to align delicate anatomical structures and ensure immunological compatibility between the donor and recipient. Meticulous planning from donor selection to postoperative follow-up was considered essential to maximize the likelihood of success and minimize the risk for allograft rejection.
The patient will now be continuously monitored and receive treatment with immunosuppressants such as tacrolimus and prednisone, adjusted according to his response to the transplant. According to the researchers, further studies will be needed to assess the long-term functionality of the transplanted eye and its integration with the central nervous system.
Despite being the fifth facial transplant surgery performed under Dr. Rodriguez’s leadership, this is the first record of a whole-eye transplant. “The mere fact that we have successfully performed the first whole-eye transplant along with a face transplant is a tremendous achievement that many believed to be impossible,” the doctor said in a statement. “We have taken a giant step forward and paved the way for the next chapter in vision restoration.”
This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
In a groundbreaking procedure, a team of surgeons from New York University Langone Health successfully performed the first combined face and eye transplant on a patient with extensive craniofacial tissue loss after an electrical accident.
The highly complex surgery lasted for 21 hours and involved more than 140 surgeons, nurses, and other healthcare professionals under the leadership of Eduardo D. Rodriguez. MD. It not only restored the patient’s facial features, but also integrated a functional eyeball, potentially setting a new standard for future treatments in similar cases.
The transplant took place in May 2023, and the case report was published on September 5 this year in JAMA.
The 46-year-old man lost a large part of his craniofacial tissue and his left eyeball. The approach was highly specialized. Advanced microsurgical techniques such as anastomoses of microscopic vessels and delicate suturing techniques were crucial for the transplant’s success.
Moreover, customized surgical devices, specific implants, and tissue manipulation tools were developed specifically for this case, thus ensuring the viability of the transplant and adequate perfusion of the transplanted ocular tissue.
The initial results are encouraging. Retinal arterial perfusion has been maintained, and retinal architecture has been preserved, as demonstrated by optical coherence tomography. Electroretinography confirmed retinal responses to light, suggesting that the transplanted eye may eventually contribute to the patient’s visual perception. These results are comparable to those of previous facial tissue transplants, but with the significant addition of ocular functionality, which is a notable advance.
“The successful revascularization of the transplanted eye achieved in this study may serve as a step toward the goal of globe transplant for restoration of vision,” wrote the authors.
The complexity of the combined transplant required a deep understanding of facial and ocular anatomy, as well as tissue preservation techniques. The surgical team reported significant challenges, including the need to align delicate anatomical structures and ensure immunological compatibility between the donor and recipient. Meticulous planning from donor selection to postoperative follow-up was considered essential to maximize the likelihood of success and minimize the risk for allograft rejection.
The patient will now be continuously monitored and receive treatment with immunosuppressants such as tacrolimus and prednisone, adjusted according to his response to the transplant. According to the researchers, further studies will be needed to assess the long-term functionality of the transplanted eye and its integration with the central nervous system.
Despite being the fifth facial transplant surgery performed under Dr. Rodriguez’s leadership, this is the first record of a whole-eye transplant. “The mere fact that we have successfully performed the first whole-eye transplant along with a face transplant is a tremendous achievement that many believed to be impossible,” the doctor said in a statement. “We have taken a giant step forward and paved the way for the next chapter in vision restoration.”
This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Vacationing Doctors Intervene After Shark Attack
Ryan Forbess, MD: I live at the beach in Orange Beach, Alabama. I’ve lived in Hawaii, the Caymans, and other beach areas for years. I’ve seen a lot of sharks but never a shark attack. Not until now.
Mohammad Ali, MD: Ryan and I have been friends for 20 years. Every year, my family goes to 30A in Florida (a popular resort stretch of highway) to celebrate my wife’s birthday, and the Forbesses always meet us there. This year we had a group of about 18 people.
On Friday, it was beautiful, and we decided to make it a beach day. We had nine kids with us. So by the time we rounded them up and got there, it was noon, and there was nowhere to sit. We almost turned around and went to the pool. But my wife finally found a spot for an umbrella.
Dr. Forbess: We were in the water boogie boarding. I was with my 8-year-old son, and Mo was with his daughter who is the same age. Suddenly, we noticed a lot of commotion just to the left of us. My first thought was: Someone saw a shark, not an attack. They’re so rare. But seeing one would scare people.
We grabbed our kids and started running out of the water. As we got closer to the shore,
Dr. Ali: It was mass panic. People were screaming and running out of the water. Other people were running in and grabbing their kids. Everyone just looked frantic.
We saw two men dragging this poor girl out of the water. It was surreal. The majority of her right leg was severed, her femur bone visible and stark white; it didn’t look real. I kept telling myself I was in a dream and now I’d wake up.
A young EMT who was there had put an informal tourniquet on her leg, but she was still bleeding. So I compressed the femoral artery as hard as I could, something I’m very familiar with doing.
Dr. Forbess: People asked me later what we used for a tourniquet. I said, “Mo’s big hands.” I tease him because most doctors play golf or go fishing; Mo lives in the gym. He was just holding pressure.
The girl’s left hand was also severed off at the wrist. There were two nurses there, and they helped with holding tourniquets on her arm.
Lulu (the girl’s name) was 15 years old. She was in and out of consciousness. At one point, her face started getting really pale, so we tried to lift her extremities up to keep the blood flow to the heart. With such severe blood loss, I thought she might go into cardiovascular shock, and we would have to start compressions. But she had a pulse, and she was breathing.
Dr. Ali: The beach was very crowded, and a lot of people had gathered around. Everyone was emotional, shocked, really shaken up. But they gave us space to work.
Dr. Forbess: People were handing us things — towels, a ratchet strap to use as a tourniquet. There was even an anesthesiologist there who said, “If you need an airway, let me know.” It was like we had a trauma team.
Dr. Ali: Lulu’s mom had been having lunch with friends. When she saw all the commotion, she ran down to the beach to look for her daughter. It was heartbreaking to hear her screams when she saw Lulu. But I was able to tune it out because we had to just concentrate on decreasing the loss of blood.
Dr. Forbess: Another girl came over and said, “That’s my sister.” Lulu has a twin. So she sat there holding Lulu’s hand and being with her the whole time.
Waiting for the EMTs to get there, the seconds were like hours. It seemed like it took forever. Finally, they came, and we were able to get the real tourniquets on, get her boarded and off the beach.
After that, they closed the beach. We got all our stuff and got on the little trolley that would take us back to the house. The lady who was driving asked us, “Did y’all hear about the shark attack?” My wife said, “Yeah, we were there.” And she said, “No, there was one an hour and a half ago.”
Dr. Ali: What we didn’t know was there had been two other attacks that day. Around the same time, one of Lulu’s friends was bitten and got a flesh wound on her heel. And before that, about 4 miles away, there was a serious injury: A lady in her 40s lost her hand and forearm and was bitten in the pelvis.
Dr. Forbess: At that point, my wife leaned back to me and said, “You know we’re never going to the beach again, right? We’re never ever going to the beach.”
If we had known about those attacks, we definitely wouldn’t have been in the water.
Dr. Ali: My wife has never liked going in the water. The evening before, we had debated about taking our daughters in the ocean because she was worried about sharks. I had given her this condescending speech about waist-deep water and the statistical probabilities of ever witnessing a shark attack. I was in trouble.
Dr. Forbess: We didn’t know if Lulu would make it. I’ve done rural family medicine in Oklahoma, so I’ve seen my fair share of injuries — guys on oil rigs, this and that. But I had never seen anything like this kind of trauma and blood loss.
Later that day, I called my office manager to catch up with her and told her what happened. She was actually in Pensacola having dinner across the street from Sacred Heart Hospital where they had taken Lulu. She went over to the emergency room to try to find out Lulu’s status — she was alive.
My office manager was able to go upstairs and talk to Lulu’s mom. Then she called, and we talked to her mom on the phone. She just said, “Thank you for helping my daughter.” It was an emotional moment.
Dr. Ali: It was such a relief. We had no idea how things would turn out. Even if Lulu did survive, was she going to be neurologically sound? But thank God she was. We were so relieved to hear her mom say that it was looking good. We still didn’t know for sure. But at least she was alive and seemed to be functioning.
Dr. Forbess: A few days later, my wife and I went to go visit her at the hospital. Her mom and her grandma were there. They were giving us hugs. We FaceTimed Mo because he was back in Jackson. It was really amazing.
What are the odds? The chances of a shark attack are about one in 12 million. And to have two physicians trained in trauma, a trauma nurse, another nurse, and an anesthesiologist less than 20 yards away when it happened? It’s crazy to think about.
Dr. Ali: And we almost weren’t there. We could have turned away.
Dr. Forbess: Humans are on top of the food chain. Or we think we are. But water really isn’t our element. Against a 12-foot bull shark, we don’t stand a chance. Lulu is here though. It’s unbelievable.
Her mom told me that when Lulu woke up, she just said, “I made it!” That girl is meant to be here. She is a tough girl with a great personality. She has these new prosthetics now that she can move with her mind; it’s like Star Wars. She says she wants to be a physician someday. So she’ll probably cure cancer.
Dr. Forbess is a family medicine physician at Orange Beach Family Medicine in Orange Beach, Alabama. Dr. Ali is an interventional radiologist with Baptist Memorial Health in Jackson, Mississippi.
A version of this article first appeared on Medscape.com.
Ryan Forbess, MD: I live at the beach in Orange Beach, Alabama. I’ve lived in Hawaii, the Caymans, and other beach areas for years. I’ve seen a lot of sharks but never a shark attack. Not until now.
Mohammad Ali, MD: Ryan and I have been friends for 20 years. Every year, my family goes to 30A in Florida (a popular resort stretch of highway) to celebrate my wife’s birthday, and the Forbesses always meet us there. This year we had a group of about 18 people.
On Friday, it was beautiful, and we decided to make it a beach day. We had nine kids with us. So by the time we rounded them up and got there, it was noon, and there was nowhere to sit. We almost turned around and went to the pool. But my wife finally found a spot for an umbrella.
Dr. Forbess: We were in the water boogie boarding. I was with my 8-year-old son, and Mo was with his daughter who is the same age. Suddenly, we noticed a lot of commotion just to the left of us. My first thought was: Someone saw a shark, not an attack. They’re so rare. But seeing one would scare people.
We grabbed our kids and started running out of the water. As we got closer to the shore,
Dr. Ali: It was mass panic. People were screaming and running out of the water. Other people were running in and grabbing their kids. Everyone just looked frantic.
We saw two men dragging this poor girl out of the water. It was surreal. The majority of her right leg was severed, her femur bone visible and stark white; it didn’t look real. I kept telling myself I was in a dream and now I’d wake up.
A young EMT who was there had put an informal tourniquet on her leg, but she was still bleeding. So I compressed the femoral artery as hard as I could, something I’m very familiar with doing.
Dr. Forbess: People asked me later what we used for a tourniquet. I said, “Mo’s big hands.” I tease him because most doctors play golf or go fishing; Mo lives in the gym. He was just holding pressure.
The girl’s left hand was also severed off at the wrist. There were two nurses there, and they helped with holding tourniquets on her arm.
Lulu (the girl’s name) was 15 years old. She was in and out of consciousness. At one point, her face started getting really pale, so we tried to lift her extremities up to keep the blood flow to the heart. With such severe blood loss, I thought she might go into cardiovascular shock, and we would have to start compressions. But she had a pulse, and she was breathing.
Dr. Ali: The beach was very crowded, and a lot of people had gathered around. Everyone was emotional, shocked, really shaken up. But they gave us space to work.
Dr. Forbess: People were handing us things — towels, a ratchet strap to use as a tourniquet. There was even an anesthesiologist there who said, “If you need an airway, let me know.” It was like we had a trauma team.
Dr. Ali: Lulu’s mom had been having lunch with friends. When she saw all the commotion, she ran down to the beach to look for her daughter. It was heartbreaking to hear her screams when she saw Lulu. But I was able to tune it out because we had to just concentrate on decreasing the loss of blood.
Dr. Forbess: Another girl came over and said, “That’s my sister.” Lulu has a twin. So she sat there holding Lulu’s hand and being with her the whole time.
Waiting for the EMTs to get there, the seconds were like hours. It seemed like it took forever. Finally, they came, and we were able to get the real tourniquets on, get her boarded and off the beach.
After that, they closed the beach. We got all our stuff and got on the little trolley that would take us back to the house. The lady who was driving asked us, “Did y’all hear about the shark attack?” My wife said, “Yeah, we were there.” And she said, “No, there was one an hour and a half ago.”
Dr. Ali: What we didn’t know was there had been two other attacks that day. Around the same time, one of Lulu’s friends was bitten and got a flesh wound on her heel. And before that, about 4 miles away, there was a serious injury: A lady in her 40s lost her hand and forearm and was bitten in the pelvis.
Dr. Forbess: At that point, my wife leaned back to me and said, “You know we’re never going to the beach again, right? We’re never ever going to the beach.”
If we had known about those attacks, we definitely wouldn’t have been in the water.
Dr. Ali: My wife has never liked going in the water. The evening before, we had debated about taking our daughters in the ocean because she was worried about sharks. I had given her this condescending speech about waist-deep water and the statistical probabilities of ever witnessing a shark attack. I was in trouble.
Dr. Forbess: We didn’t know if Lulu would make it. I’ve done rural family medicine in Oklahoma, so I’ve seen my fair share of injuries — guys on oil rigs, this and that. But I had never seen anything like this kind of trauma and blood loss.
Later that day, I called my office manager to catch up with her and told her what happened. She was actually in Pensacola having dinner across the street from Sacred Heart Hospital where they had taken Lulu. She went over to the emergency room to try to find out Lulu’s status — she was alive.
My office manager was able to go upstairs and talk to Lulu’s mom. Then she called, and we talked to her mom on the phone. She just said, “Thank you for helping my daughter.” It was an emotional moment.
Dr. Ali: It was such a relief. We had no idea how things would turn out. Even if Lulu did survive, was she going to be neurologically sound? But thank God she was. We were so relieved to hear her mom say that it was looking good. We still didn’t know for sure. But at least she was alive and seemed to be functioning.
Dr. Forbess: A few days later, my wife and I went to go visit her at the hospital. Her mom and her grandma were there. They were giving us hugs. We FaceTimed Mo because he was back in Jackson. It was really amazing.
What are the odds? The chances of a shark attack are about one in 12 million. And to have two physicians trained in trauma, a trauma nurse, another nurse, and an anesthesiologist less than 20 yards away when it happened? It’s crazy to think about.
Dr. Ali: And we almost weren’t there. We could have turned away.
Dr. Forbess: Humans are on top of the food chain. Or we think we are. But water really isn’t our element. Against a 12-foot bull shark, we don’t stand a chance. Lulu is here though. It’s unbelievable.
Her mom told me that when Lulu woke up, she just said, “I made it!” That girl is meant to be here. She is a tough girl with a great personality. She has these new prosthetics now that she can move with her mind; it’s like Star Wars. She says she wants to be a physician someday. So she’ll probably cure cancer.
Dr. Forbess is a family medicine physician at Orange Beach Family Medicine in Orange Beach, Alabama. Dr. Ali is an interventional radiologist with Baptist Memorial Health in Jackson, Mississippi.
A version of this article first appeared on Medscape.com.
Ryan Forbess, MD: I live at the beach in Orange Beach, Alabama. I’ve lived in Hawaii, the Caymans, and other beach areas for years. I’ve seen a lot of sharks but never a shark attack. Not until now.
Mohammad Ali, MD: Ryan and I have been friends for 20 years. Every year, my family goes to 30A in Florida (a popular resort stretch of highway) to celebrate my wife’s birthday, and the Forbesses always meet us there. This year we had a group of about 18 people.
On Friday, it was beautiful, and we decided to make it a beach day. We had nine kids with us. So by the time we rounded them up and got there, it was noon, and there was nowhere to sit. We almost turned around and went to the pool. But my wife finally found a spot for an umbrella.
Dr. Forbess: We were in the water boogie boarding. I was with my 8-year-old son, and Mo was with his daughter who is the same age. Suddenly, we noticed a lot of commotion just to the left of us. My first thought was: Someone saw a shark, not an attack. They’re so rare. But seeing one would scare people.
We grabbed our kids and started running out of the water. As we got closer to the shore,
Dr. Ali: It was mass panic. People were screaming and running out of the water. Other people were running in and grabbing their kids. Everyone just looked frantic.
We saw two men dragging this poor girl out of the water. It was surreal. The majority of her right leg was severed, her femur bone visible and stark white; it didn’t look real. I kept telling myself I was in a dream and now I’d wake up.
A young EMT who was there had put an informal tourniquet on her leg, but she was still bleeding. So I compressed the femoral artery as hard as I could, something I’m very familiar with doing.
Dr. Forbess: People asked me later what we used for a tourniquet. I said, “Mo’s big hands.” I tease him because most doctors play golf or go fishing; Mo lives in the gym. He was just holding pressure.
The girl’s left hand was also severed off at the wrist. There were two nurses there, and they helped with holding tourniquets on her arm.
Lulu (the girl’s name) was 15 years old. She was in and out of consciousness. At one point, her face started getting really pale, so we tried to lift her extremities up to keep the blood flow to the heart. With such severe blood loss, I thought she might go into cardiovascular shock, and we would have to start compressions. But she had a pulse, and she was breathing.
Dr. Ali: The beach was very crowded, and a lot of people had gathered around. Everyone was emotional, shocked, really shaken up. But they gave us space to work.
Dr. Forbess: People were handing us things — towels, a ratchet strap to use as a tourniquet. There was even an anesthesiologist there who said, “If you need an airway, let me know.” It was like we had a trauma team.
Dr. Ali: Lulu’s mom had been having lunch with friends. When she saw all the commotion, she ran down to the beach to look for her daughter. It was heartbreaking to hear her screams when she saw Lulu. But I was able to tune it out because we had to just concentrate on decreasing the loss of blood.
Dr. Forbess: Another girl came over and said, “That’s my sister.” Lulu has a twin. So she sat there holding Lulu’s hand and being with her the whole time.
Waiting for the EMTs to get there, the seconds were like hours. It seemed like it took forever. Finally, they came, and we were able to get the real tourniquets on, get her boarded and off the beach.
After that, they closed the beach. We got all our stuff and got on the little trolley that would take us back to the house. The lady who was driving asked us, “Did y’all hear about the shark attack?” My wife said, “Yeah, we were there.” And she said, “No, there was one an hour and a half ago.”
Dr. Ali: What we didn’t know was there had been two other attacks that day. Around the same time, one of Lulu’s friends was bitten and got a flesh wound on her heel. And before that, about 4 miles away, there was a serious injury: A lady in her 40s lost her hand and forearm and was bitten in the pelvis.
Dr. Forbess: At that point, my wife leaned back to me and said, “You know we’re never going to the beach again, right? We’re never ever going to the beach.”
If we had known about those attacks, we definitely wouldn’t have been in the water.
Dr. Ali: My wife has never liked going in the water. The evening before, we had debated about taking our daughters in the ocean because she was worried about sharks. I had given her this condescending speech about waist-deep water and the statistical probabilities of ever witnessing a shark attack. I was in trouble.
Dr. Forbess: We didn’t know if Lulu would make it. I’ve done rural family medicine in Oklahoma, so I’ve seen my fair share of injuries — guys on oil rigs, this and that. But I had never seen anything like this kind of trauma and blood loss.
Later that day, I called my office manager to catch up with her and told her what happened. She was actually in Pensacola having dinner across the street from Sacred Heart Hospital where they had taken Lulu. She went over to the emergency room to try to find out Lulu’s status — she was alive.
My office manager was able to go upstairs and talk to Lulu’s mom. Then she called, and we talked to her mom on the phone. She just said, “Thank you for helping my daughter.” It was an emotional moment.
Dr. Ali: It was such a relief. We had no idea how things would turn out. Even if Lulu did survive, was she going to be neurologically sound? But thank God she was. We were so relieved to hear her mom say that it was looking good. We still didn’t know for sure. But at least she was alive and seemed to be functioning.
Dr. Forbess: A few days later, my wife and I went to go visit her at the hospital. Her mom and her grandma were there. They were giving us hugs. We FaceTimed Mo because he was back in Jackson. It was really amazing.
What are the odds? The chances of a shark attack are about one in 12 million. And to have two physicians trained in trauma, a trauma nurse, another nurse, and an anesthesiologist less than 20 yards away when it happened? It’s crazy to think about.
Dr. Ali: And we almost weren’t there. We could have turned away.
Dr. Forbess: Humans are on top of the food chain. Or we think we are. But water really isn’t our element. Against a 12-foot bull shark, we don’t stand a chance. Lulu is here though. It’s unbelievable.
Her mom told me that when Lulu woke up, she just said, “I made it!” That girl is meant to be here. She is a tough girl with a great personality. She has these new prosthetics now that she can move with her mind; it’s like Star Wars. She says she wants to be a physician someday. So she’ll probably cure cancer.
Dr. Forbess is a family medicine physician at Orange Beach Family Medicine in Orange Beach, Alabama. Dr. Ali is an interventional radiologist with Baptist Memorial Health in Jackson, Mississippi.
A version of this article first appeared on Medscape.com.
Gram Stain Doesn’t Improve UTI Diagnosis in the ED
TOPLINE:
Compared with other urine analysis methods, urine Gram stain has a moderate predictive value for detecting gram-negative bacteria in urine culture but does not significantly improve urinary tract infection (UTI) diagnosis in the emergency department (ED).
METHODOLOGY:
- Researchers conducted an observational cohort study at the University Medical Center Groningen in the Netherlands, encompassing 1358 episodes across 1136 patients suspected of having a UTI.
- The study included the following predefined subgroups: patients using urinary catheters and patients with leukopenia (< 4.0×10⁹ leucocytes/L). Urine dipstick nitrite, automated urinalysis, Gram stain, and urine cultures were performed on urine samples collected from patients presenting at the ED.
- The sensitivity and specificity of Gram stain for “many” bacteria (quantified as > 15/high power field) were compared with those of urine dipstick nitrite and automated bacterial counting in urinalysis.
TAKEAWAY:
- The sensitivity and specificity of Gram stain for “many” bacteria were 51.3% and 91.0%, respectively, with an accuracy of 76.8%.
- Gram stain showed a positive predictive value (PPV) of 84.7% for gram-negative rods in urine culture; however, the PPV was only 38.4% for gram-positive cocci.
- In the catheter subgroup, the presence of monomorphic bacteria quantified as “many” had a higher PPV for diagnosing a UTI than the presence of polymorphic bacteria with the same quantification.
- The overall performance of Gram stain in diagnosing a UTI in the ED was comparable to that of automated bacterial counting in urinalysis but better than that of urine dipstick nitrite.
IN PRACTICE:
“With the exception of a moderate prediction of gram-negative bacteria in the UC [urine culture], urine GS [Gram stain] does not improve UTI diagnosis at the ED compared to other urine parameters,” the authors wrote.
SOURCE:
The study was led by Stephanie J.M. Middelkoop, University of Groningen, University Medical Center Groningen, the Netherlands. It was published online on August 16, 2024, in Infectious Diseases.
LIMITATIONS:
The study’s limitations included a small sample size within the leukopenia subgroup, which may have affected the generalizability of the findings. Additionally, the potential influence of refrigeration of urine samples on bacterial growth could have affected the results. In this study, indwelling catheters were not replaced before urine sample collection, which may have affected the accuracy of UTI diagnosis in patients using catheters.
DISCLOSURES:
No conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Compared with other urine analysis methods, urine Gram stain has a moderate predictive value for detecting gram-negative bacteria in urine culture but does not significantly improve urinary tract infection (UTI) diagnosis in the emergency department (ED).
METHODOLOGY:
- Researchers conducted an observational cohort study at the University Medical Center Groningen in the Netherlands, encompassing 1358 episodes across 1136 patients suspected of having a UTI.
- The study included the following predefined subgroups: patients using urinary catheters and patients with leukopenia (< 4.0×10⁹ leucocytes/L). Urine dipstick nitrite, automated urinalysis, Gram stain, and urine cultures were performed on urine samples collected from patients presenting at the ED.
- The sensitivity and specificity of Gram stain for “many” bacteria (quantified as > 15/high power field) were compared with those of urine dipstick nitrite and automated bacterial counting in urinalysis.
TAKEAWAY:
- The sensitivity and specificity of Gram stain for “many” bacteria were 51.3% and 91.0%, respectively, with an accuracy of 76.8%.
- Gram stain showed a positive predictive value (PPV) of 84.7% for gram-negative rods in urine culture; however, the PPV was only 38.4% for gram-positive cocci.
- In the catheter subgroup, the presence of monomorphic bacteria quantified as “many” had a higher PPV for diagnosing a UTI than the presence of polymorphic bacteria with the same quantification.
- The overall performance of Gram stain in diagnosing a UTI in the ED was comparable to that of automated bacterial counting in urinalysis but better than that of urine dipstick nitrite.
IN PRACTICE:
“With the exception of a moderate prediction of gram-negative bacteria in the UC [urine culture], urine GS [Gram stain] does not improve UTI diagnosis at the ED compared to other urine parameters,” the authors wrote.
SOURCE:
The study was led by Stephanie J.M. Middelkoop, University of Groningen, University Medical Center Groningen, the Netherlands. It was published online on August 16, 2024, in Infectious Diseases.
LIMITATIONS:
The study’s limitations included a small sample size within the leukopenia subgroup, which may have affected the generalizability of the findings. Additionally, the potential influence of refrigeration of urine samples on bacterial growth could have affected the results. In this study, indwelling catheters were not replaced before urine sample collection, which may have affected the accuracy of UTI diagnosis in patients using catheters.
DISCLOSURES:
No conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Compared with other urine analysis methods, urine Gram stain has a moderate predictive value for detecting gram-negative bacteria in urine culture but does not significantly improve urinary tract infection (UTI) diagnosis in the emergency department (ED).
METHODOLOGY:
- Researchers conducted an observational cohort study at the University Medical Center Groningen in the Netherlands, encompassing 1358 episodes across 1136 patients suspected of having a UTI.
- The study included the following predefined subgroups: patients using urinary catheters and patients with leukopenia (< 4.0×10⁹ leucocytes/L). Urine dipstick nitrite, automated urinalysis, Gram stain, and urine cultures were performed on urine samples collected from patients presenting at the ED.
- The sensitivity and specificity of Gram stain for “many” bacteria (quantified as > 15/high power field) were compared with those of urine dipstick nitrite and automated bacterial counting in urinalysis.
TAKEAWAY:
- The sensitivity and specificity of Gram stain for “many” bacteria were 51.3% and 91.0%, respectively, with an accuracy of 76.8%.
- Gram stain showed a positive predictive value (PPV) of 84.7% for gram-negative rods in urine culture; however, the PPV was only 38.4% for gram-positive cocci.
- In the catheter subgroup, the presence of monomorphic bacteria quantified as “many” had a higher PPV for diagnosing a UTI than the presence of polymorphic bacteria with the same quantification.
- The overall performance of Gram stain in diagnosing a UTI in the ED was comparable to that of automated bacterial counting in urinalysis but better than that of urine dipstick nitrite.
IN PRACTICE:
“With the exception of a moderate prediction of gram-negative bacteria in the UC [urine culture], urine GS [Gram stain] does not improve UTI diagnosis at the ED compared to other urine parameters,” the authors wrote.
SOURCE:
The study was led by Stephanie J.M. Middelkoop, University of Groningen, University Medical Center Groningen, the Netherlands. It was published online on August 16, 2024, in Infectious Diseases.
LIMITATIONS:
The study’s limitations included a small sample size within the leukopenia subgroup, which may have affected the generalizability of the findings. Additionally, the potential influence of refrigeration of urine samples on bacterial growth could have affected the results. In this study, indwelling catheters were not replaced before urine sample collection, which may have affected the accuracy of UTI diagnosis in patients using catheters.
DISCLOSURES:
No conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
The Most Misinterpreted Study in Medicine: Don’t be TRICCed
Ah, blood. That sweet nectar of life that quiets angina, abolishes dyspnea, prevents orthostatic syncope, and quells sinus tachycardia. As a cardiologist, I am an unabashed hemophile.
But we liberal transfusionists are challenged on every request for consideration of transfusion. Whereas the polite may resort to whispered skepticism, vehement critics respond with scorn as if we’d asked them to burn aromatic herbs or fetch a bucket of leeches. And to what do we owe this pathological angst? The broad and persistent misinterpretation of the pesky TRICC trial (N Engl J Med. 1999;340:409-417). You know; the one that should have been published with a boxed warning stating: “Misinterpretation of this trial could result in significant harm.”
Point 1: Our Actively Bleeding Patient is Not a TRICC Patient.
They were randomly assigned to either a conservative trigger for transfusion of < 7 g/dL or a liberal threshold of < 10 g/dL. Mortality at 30 days was lower with the conservative approach — 18.7% vs 23.3% — but the difference was not statistically significant (P = .11). The findings were similar for the secondary endpoints of inpatient mortality (22.2% vs 28.1%; P = .05) and ICU mortality (13.9% vs 16.2%; P = .29).
One must admit that these P values are not impressive, and the authors’ conclusion should have warranted caution: “A restrictive strategy ... is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.”
Point 2: Our Critically Ill Cardiac Patient is Unlikely to be a “TRICC” Patient.
Another criticism of TRICC is that only 13% of those assessed and 26% of those eligible were enrolled, mostly owing to physician refusal. Only 26% of enrolled patients had cardiac disease. This makes the TRICC population highly selected and not representative of typical ICU patients.
To prove my point that the edict against higher transfusion thresholds can be dangerous, I’ll describe my most recent interface with TRICC trial misinterpretation
A Case in Point
The patient, Mrs. Kemp,* is 79 years old and has been on aspirin for years following coronary stent placement. One evening, she began spurting bright red blood from her rectum, interrupted only briefly by large clots the consistency of jellied cranberries. When she arrived at the hospital, she was hemodynamically stable, with a hemoglobin level of 10 g/dL, down from her usual 12 g/dL. That level bolstered the confidence of her provider, who insisted that she be managed conservatively.
Mrs. Kemp was transferred to the ward, where she continued to bleed briskly. Over the next 2 hours, her hemoglobin level dropped to 9 g/dL, then 8 g/dL. Her daughter, a healthcare worker, requested a transfusion. The answer was, wait for it — the well-scripted, somewhat patronizing oft-quoted line, “The medical literature states that we need to wait for a hemoglobin level of 7 g/dL before we transfuse.”
Later that evening, Mrs. Kemp’s systolic blood pressure dropped to the upper 80s, despite her usual hypertension. The provider was again comforted by the fact that she was not tachycardic (she had a pacemaker and was on bisoprolol). The next morning, Mrs. Kemp felt the need to defecate and was placed on the bedside commode and left to her privacy. Predictably, she became dizzy and experienced frank syncope. Thankfully, she avoided a hip fracture or worse. A stat hemoglobin returned at 6 g/dL.
Her daughter said she literally heard the hallelujah chorus because her mother’s hemoglobin was finally below that much revered and often misleading threshold of 7 g/dL. Finally, there was an order for platelets and packed red cells. Five units later, Mr. Kemp achieved a hemoglobin of 8 g/dL and survived. Two more units and she was soaring at 9 g/dL!
Lessons for Transfusion Conservatives
There are many lessons here.
The TRICC study found that hemodynamically stable, asymptomatic patients who are not actively bleeding may well tolerate a hemoglobin level of 7 g/dL. But a patient with bright red blood actively pouring from an orifice and a rapidly declining hemoglobin level isn’t one of those people. Additionally, a patient who faints from hypovolemia is not one of those people.
Patients with a history of bleeding presenting with new resting sinus tachycardia (in those who have chronotropic competence) should be presumed to be actively bleeding, and the findings of TRICC do not apply to them. Patients who have bled buckets on anticoagulant or antiplatelet therapies and have dropped their hemoglobin will probably continue to ooze and should be subject to a low threshold for transfusion.
Additionally, anemic people who are hemodynamically stable but can’t walk without new significant shortness of air or new rest angina need blood, and sometimes at hemoglobin levels higher than generally accepted by conservative strategists. Finally, failing to treat or at least monitor patients who are spontaneously bleeding as aggressively as some trauma patients is a failure to provide proper medical care.
The vast majority of my healthcare clinician colleagues are competent, compassionate individuals who can reasonably discuss the nuances of any medical scenario. One important distinction of a good medical team is the willingness to change course based on a change in patient status or the presentation of what may be new information for the provider.
But those proud transfusion conservatives who will not budge until their threshold is met need to make certain their patient is truly subject to their supposed edicts. Our blood banks should not be more difficult to access than Fort Knox, and transfusion should be used appropriately and liberally in the hemodynamically unstable, the symptomatic, and active brisk bleeders.
I beg staunch transfusion conservatives to consider how they might feel if someone stuck a magic spigot in their brachial artery and acutely drained their hemoglobin to that magic threshold of 7 g/dL. When syncope, shortness of air, fatigue, and angina find them, they may generate empathy for those who need transfusion. Might that do the TRICC?
*Some details have been changed to conceal the identity of the patient, but the essence of the case has been preserved.
Dr. Walton-Shirley, a native Kentuckian who retired from full-time invasive cardiology and now does locums work in Montana, is a champion of physician rights and patient safety. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Ah, blood. That sweet nectar of life that quiets angina, abolishes dyspnea, prevents orthostatic syncope, and quells sinus tachycardia. As a cardiologist, I am an unabashed hemophile.
But we liberal transfusionists are challenged on every request for consideration of transfusion. Whereas the polite may resort to whispered skepticism, vehement critics respond with scorn as if we’d asked them to burn aromatic herbs or fetch a bucket of leeches. And to what do we owe this pathological angst? The broad and persistent misinterpretation of the pesky TRICC trial (N Engl J Med. 1999;340:409-417). You know; the one that should have been published with a boxed warning stating: “Misinterpretation of this trial could result in significant harm.”
Point 1: Our Actively Bleeding Patient is Not a TRICC Patient.
They were randomly assigned to either a conservative trigger for transfusion of < 7 g/dL or a liberal threshold of < 10 g/dL. Mortality at 30 days was lower with the conservative approach — 18.7% vs 23.3% — but the difference was not statistically significant (P = .11). The findings were similar for the secondary endpoints of inpatient mortality (22.2% vs 28.1%; P = .05) and ICU mortality (13.9% vs 16.2%; P = .29).
One must admit that these P values are not impressive, and the authors’ conclusion should have warranted caution: “A restrictive strategy ... is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.”
Point 2: Our Critically Ill Cardiac Patient is Unlikely to be a “TRICC” Patient.
Another criticism of TRICC is that only 13% of those assessed and 26% of those eligible were enrolled, mostly owing to physician refusal. Only 26% of enrolled patients had cardiac disease. This makes the TRICC population highly selected and not representative of typical ICU patients.
To prove my point that the edict against higher transfusion thresholds can be dangerous, I’ll describe my most recent interface with TRICC trial misinterpretation
A Case in Point
The patient, Mrs. Kemp,* is 79 years old and has been on aspirin for years following coronary stent placement. One evening, she began spurting bright red blood from her rectum, interrupted only briefly by large clots the consistency of jellied cranberries. When she arrived at the hospital, she was hemodynamically stable, with a hemoglobin level of 10 g/dL, down from her usual 12 g/dL. That level bolstered the confidence of her provider, who insisted that she be managed conservatively.
Mrs. Kemp was transferred to the ward, where she continued to bleed briskly. Over the next 2 hours, her hemoglobin level dropped to 9 g/dL, then 8 g/dL. Her daughter, a healthcare worker, requested a transfusion. The answer was, wait for it — the well-scripted, somewhat patronizing oft-quoted line, “The medical literature states that we need to wait for a hemoglobin level of 7 g/dL before we transfuse.”
Later that evening, Mrs. Kemp’s systolic blood pressure dropped to the upper 80s, despite her usual hypertension. The provider was again comforted by the fact that she was not tachycardic (she had a pacemaker and was on bisoprolol). The next morning, Mrs. Kemp felt the need to defecate and was placed on the bedside commode and left to her privacy. Predictably, she became dizzy and experienced frank syncope. Thankfully, she avoided a hip fracture or worse. A stat hemoglobin returned at 6 g/dL.
Her daughter said she literally heard the hallelujah chorus because her mother’s hemoglobin was finally below that much revered and often misleading threshold of 7 g/dL. Finally, there was an order for platelets and packed red cells. Five units later, Mr. Kemp achieved a hemoglobin of 8 g/dL and survived. Two more units and she was soaring at 9 g/dL!
Lessons for Transfusion Conservatives
There are many lessons here.
The TRICC study found that hemodynamically stable, asymptomatic patients who are not actively bleeding may well tolerate a hemoglobin level of 7 g/dL. But a patient with bright red blood actively pouring from an orifice and a rapidly declining hemoglobin level isn’t one of those people. Additionally, a patient who faints from hypovolemia is not one of those people.
Patients with a history of bleeding presenting with new resting sinus tachycardia (in those who have chronotropic competence) should be presumed to be actively bleeding, and the findings of TRICC do not apply to them. Patients who have bled buckets on anticoagulant or antiplatelet therapies and have dropped their hemoglobin will probably continue to ooze and should be subject to a low threshold for transfusion.
Additionally, anemic people who are hemodynamically stable but can’t walk without new significant shortness of air or new rest angina need blood, and sometimes at hemoglobin levels higher than generally accepted by conservative strategists. Finally, failing to treat or at least monitor patients who are spontaneously bleeding as aggressively as some trauma patients is a failure to provide proper medical care.
The vast majority of my healthcare clinician colleagues are competent, compassionate individuals who can reasonably discuss the nuances of any medical scenario. One important distinction of a good medical team is the willingness to change course based on a change in patient status or the presentation of what may be new information for the provider.
But those proud transfusion conservatives who will not budge until their threshold is met need to make certain their patient is truly subject to their supposed edicts. Our blood banks should not be more difficult to access than Fort Knox, and transfusion should be used appropriately and liberally in the hemodynamically unstable, the symptomatic, and active brisk bleeders.
I beg staunch transfusion conservatives to consider how they might feel if someone stuck a magic spigot in their brachial artery and acutely drained their hemoglobin to that magic threshold of 7 g/dL. When syncope, shortness of air, fatigue, and angina find them, they may generate empathy for those who need transfusion. Might that do the TRICC?
*Some details have been changed to conceal the identity of the patient, but the essence of the case has been preserved.
Dr. Walton-Shirley, a native Kentuckian who retired from full-time invasive cardiology and now does locums work in Montana, is a champion of physician rights and patient safety. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Ah, blood. That sweet nectar of life that quiets angina, abolishes dyspnea, prevents orthostatic syncope, and quells sinus tachycardia. As a cardiologist, I am an unabashed hemophile.
But we liberal transfusionists are challenged on every request for consideration of transfusion. Whereas the polite may resort to whispered skepticism, vehement critics respond with scorn as if we’d asked them to burn aromatic herbs or fetch a bucket of leeches. And to what do we owe this pathological angst? The broad and persistent misinterpretation of the pesky TRICC trial (N Engl J Med. 1999;340:409-417). You know; the one that should have been published with a boxed warning stating: “Misinterpretation of this trial could result in significant harm.”
Point 1: Our Actively Bleeding Patient is Not a TRICC Patient.
They were randomly assigned to either a conservative trigger for transfusion of < 7 g/dL or a liberal threshold of < 10 g/dL. Mortality at 30 days was lower with the conservative approach — 18.7% vs 23.3% — but the difference was not statistically significant (P = .11). The findings were similar for the secondary endpoints of inpatient mortality (22.2% vs 28.1%; P = .05) and ICU mortality (13.9% vs 16.2%; P = .29).
One must admit that these P values are not impressive, and the authors’ conclusion should have warranted caution: “A restrictive strategy ... is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.”
Point 2: Our Critically Ill Cardiac Patient is Unlikely to be a “TRICC” Patient.
Another criticism of TRICC is that only 13% of those assessed and 26% of those eligible were enrolled, mostly owing to physician refusal. Only 26% of enrolled patients had cardiac disease. This makes the TRICC population highly selected and not representative of typical ICU patients.
To prove my point that the edict against higher transfusion thresholds can be dangerous, I’ll describe my most recent interface with TRICC trial misinterpretation
A Case in Point
The patient, Mrs. Kemp,* is 79 years old and has been on aspirin for years following coronary stent placement. One evening, she began spurting bright red blood from her rectum, interrupted only briefly by large clots the consistency of jellied cranberries. When she arrived at the hospital, she was hemodynamically stable, with a hemoglobin level of 10 g/dL, down from her usual 12 g/dL. That level bolstered the confidence of her provider, who insisted that she be managed conservatively.
Mrs. Kemp was transferred to the ward, where she continued to bleed briskly. Over the next 2 hours, her hemoglobin level dropped to 9 g/dL, then 8 g/dL. Her daughter, a healthcare worker, requested a transfusion. The answer was, wait for it — the well-scripted, somewhat patronizing oft-quoted line, “The medical literature states that we need to wait for a hemoglobin level of 7 g/dL before we transfuse.”
Later that evening, Mrs. Kemp’s systolic blood pressure dropped to the upper 80s, despite her usual hypertension. The provider was again comforted by the fact that she was not tachycardic (she had a pacemaker and was on bisoprolol). The next morning, Mrs. Kemp felt the need to defecate and was placed on the bedside commode and left to her privacy. Predictably, she became dizzy and experienced frank syncope. Thankfully, she avoided a hip fracture or worse. A stat hemoglobin returned at 6 g/dL.
Her daughter said she literally heard the hallelujah chorus because her mother’s hemoglobin was finally below that much revered and often misleading threshold of 7 g/dL. Finally, there was an order for platelets and packed red cells. Five units later, Mr. Kemp achieved a hemoglobin of 8 g/dL and survived. Two more units and she was soaring at 9 g/dL!
Lessons for Transfusion Conservatives
There are many lessons here.
The TRICC study found that hemodynamically stable, asymptomatic patients who are not actively bleeding may well tolerate a hemoglobin level of 7 g/dL. But a patient with bright red blood actively pouring from an orifice and a rapidly declining hemoglobin level isn’t one of those people. Additionally, a patient who faints from hypovolemia is not one of those people.
Patients with a history of bleeding presenting with new resting sinus tachycardia (in those who have chronotropic competence) should be presumed to be actively bleeding, and the findings of TRICC do not apply to them. Patients who have bled buckets on anticoagulant or antiplatelet therapies and have dropped their hemoglobin will probably continue to ooze and should be subject to a low threshold for transfusion.
Additionally, anemic people who are hemodynamically stable but can’t walk without new significant shortness of air or new rest angina need blood, and sometimes at hemoglobin levels higher than generally accepted by conservative strategists. Finally, failing to treat or at least monitor patients who are spontaneously bleeding as aggressively as some trauma patients is a failure to provide proper medical care.
The vast majority of my healthcare clinician colleagues are competent, compassionate individuals who can reasonably discuss the nuances of any medical scenario. One important distinction of a good medical team is the willingness to change course based on a change in patient status or the presentation of what may be new information for the provider.
But those proud transfusion conservatives who will not budge until their threshold is met need to make certain their patient is truly subject to their supposed edicts. Our blood banks should not be more difficult to access than Fort Knox, and transfusion should be used appropriately and liberally in the hemodynamically unstable, the symptomatic, and active brisk bleeders.
I beg staunch transfusion conservatives to consider how they might feel if someone stuck a magic spigot in their brachial artery and acutely drained their hemoglobin to that magic threshold of 7 g/dL. When syncope, shortness of air, fatigue, and angina find them, they may generate empathy for those who need transfusion. Might that do the TRICC?
*Some details have been changed to conceal the identity of the patient, but the essence of the case has been preserved.
Dr. Walton-Shirley, a native Kentuckian who retired from full-time invasive cardiology and now does locums work in Montana, is a champion of physician rights and patient safety. She has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
New Tourniquet: The AED for Bleeding?
This discussion was recorded on July 12, 2024. This transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. I recently met an innovative young woman named Hannah Herbst while attending the annual Eagles EMS Conference in Fort Lauderdale, Florida.
Hannah Herbst is a graduate of Florida Atlantic University, selected for Forbes 30 Under 30, and founder of a company called Golden Hour Medical. She has a background in IT and developed an automated pneumatic tourniquet known as AutoTQ, which we’re going to discuss at length here.
Also joining us is Dr. Peter Antevy, a pediatric emergency physician and medical director for Davie Fire Rescue as well as Coral Springs Parkland Fire Rescue. Peter is a member of EMS Eagles Global Alliance and is highly involved in high-quality research in prehospital emergency care and is quite well known in Florida and nationally.
Welcome to both of you.
Hannah Herbst: Thank you very much. Very grateful to be here.
Dr. Glatter: Hannah, I’ll let you start by explaining what AutoTQ is and then compare that to a standard Combat Application Tourniquet (CAT).
Ms. Herbst: Thank you. Unfortunately, blood loss is a leading cause of preventable death and trauma. When there’s blood loss occurring from an arm or a leg, the easiest way to stop it is by applying a tourniquet, which is this compression type of device that you place above the site of bleeding, and it then applies a high amount of pressure to stop blood flow through the limb.
Currently, tourniquets on the market have failure rates as high as 84%. This became very real to me back in 2018, when I became aware of mass casualty incidents when I was a student. I became interested in how we can reimagine the conventional tourniquet and try to make it something that’s very user-friendly, much like an automated external defibrillator (AED).
My team and I developed AutoTQ, which is an automated tourniquet. which is a leading cause of tourniquet failure and being able to effectively administer treatment to a patient that may bleed out.
Tourniquet Failure Rates
Dr. Glatter: In terms of tourniquet failure, how often do standard tourniquets fail, like the CAT combat-type tourniquet?
Ms. Herbst: Unfortunately, they fail very frequently. There are several studies that have been conducted to evaluate this. Many of them occur immediately after training. They found failure rates between 80% and 90% for the current conventional CAT tourniquet immediately after training, which is very concerning.
Dr. Glatter: In terms of failure, was it the windlass aspect of the tourniquet that failed? Or was it something related to the actual strap? Was that in any way detailed?
Ms. Herbst: There are usually a few different failure points that have been found in the literature. One is placement. Many times, when you’re panicked, you don’t remember exactly how to place it. It should be placed high and tight above the bleed and not over a joint.
The second problem is inadequate tightness. For a CAT tourniquet to be effective, you have to get it extremely tight on that first pull before the windlass is activated, and many times people don’t remember that in the stress of the moment.
Dr. Glatter: Peter, in terms of tourniquet application by your medics in the field, certainly the CAT-type device has been in existence for quite a while. Hannah’s proposing a new iteration of how to do this, which is automated and simple. What is your take on such a device? And how did you learn about Hannah’s device?
Peter M. Antevy, MD: We’ve been training on tourniquets ever since the military data showed that there was an extreme benefit in using them. We’ve been doing training for many years, including our police officers. What we’ve noticed is that every time we gather everyone together to show them how to place a tourniquet — and we have to do one-on-one sessions with them — it’s not a device that they can easily put on. These are police officers who had the training last year.
Like Hannah said, most of the time they have a problem unraveling it and understanding how to actually place it. It’s easier on the arm than it is on the leg. You can imagine it would be harder to place it on your own leg, especially if you had an injury. Then, they don’t tighten it well enough, as Hannah just mentioned. In order for a tourniquet to really be placed properly, it’s going to hurt that person. Many people have that tendency not to want to tighten it as much as they can.
Having said that, how I got into all of this is because I’m the medical director for Coral Springs and Parkland, and unfortunately, we had the 2018 Valentine’s Day murders that happened where we lost 17 adults and kids. However, 17 people were saved that day, and the credit goes to our police officers who had tourniquets or chest seals on before those patients were brought out to EMS. Many lives were saved by the tourniquet.
If you look at the Boston Marathon massacre and many other events that have happened, I believe — and I’ve always believed — that tourniquets should be in the glove box of every citizen. It should be in every school room. They should be in buildings along with the AED.
In my town of Davie, we were the first in the country to add an ordinance that required a Stop the Bleed kit in the AED cabinet, and those were required by buildings of certain sizes. In order to get this lifesaving device everywhere, I think it has to be put into local ordinance and supported by states and by the national folks, which they are doing.
Trials Are Underway
Dr. Glatter: In terms of adoption of such a device, it certainly has to go through rigorous testing and maybe some trials. Hannah, where are you at with vetting this in terms of any type of trial? Has it been compared head to head with standard tourniquets?
Ms. Herbst: Yes, we’re currently doing large amounts of field testing. We’re doing testing on emergency vehicles and in the surgical setting with different customers. In addition, we’re running pilot studies at different universities and with different organizations, including the military, to make sure that this device is effective. We’re evaluating cognitive offloading of people. We’re hoping to start that study later this year. We’re excited to be doing this in a variety of settings.
We’re also testing the quality of it in different environmental conditions and under different atmospheric pressure. We’re doing everything we can to ensure the device is safe and effective. We’re excited to scale and fill our preorders and be able to develop this and deliver it to many people.
Dr. Glatter: I was wondering if you could describe the actual device. There’s a brain part of it and then, obviously, the strap aspect of it. I was curious about contamination and reusability issues.
Ms. Herbst: That’s a great question. One of the limitations of conventional tourniquets on the market is that they are single use, and often, it requires two tourniquets to stop a bleed, both of which have to be disposed of.
With AutoTQ, we have a reusable component and a disposable component. I actually have one here that I can show you. We have a cover on it that says: Stop bleed, slide up and power on. You just pull this cover off and then you have a few simple commands. You have powering the device on. I’ll just click this button: Tighten strap above bleeding, then press inflate. It delivers audible instructions telling you exactly how to use the device. Then, you tighten it above your bleed on the limb, and you press the inflate button. Then it administers air into the cuff and stops the patient’s bleed.
Tourniquet Conversion and Limb Salvage
Dr. Glatter: In terms of ischemia time, how can a device like this make it easier for us to know when to let the tourniquet down and allow some blood flow? Certainly, limb salvage is important, and we don’t want to have necrosis and so forth.
Dr. Antevy: That’s a great question. The limb salvage rate when tourniquets have been used is 85%. When used correctly, you can really improve the outcomes for many patients.
On the flip side of that, there’s something called tourniquet conversion. That’s exactly what you mentioned. It’s making sure that the tourniquet doesn’t stay on for too long of a time. If you can imagine a patient going to an outlying hospital where there’s no trauma center, and then that patient then has to be moved a couple hours to the trauma center, could you potentially have a tourniquet on for too long that then ends up causing the patient a bad outcome? The answer is yes.
I just had someone on my webinar recently describing the appropriate conversion techniques of tourniquets. You don’t find too much of that in the literature, but you really have to ensure that as you’re taking the tourniquet down, the bleeding is actually stopped. It’s not really recommended to take a tourniquet down if the patient was just acutely bleeding.
However, imagine a situation where a tourniquet was put on incorrectly. Let’s say a patient got nervous and they just put it on a patient who didn’t really need it. You really have to understand how to evaluate that wound to be sure that, as you’re taking the tourniquet down slowly, the patient doesn’t rebleed again.
There are two sides of the question, Rob. One is making sure it’s not on inappropriately. The second one is making sure it’s not on for too long, which ends up causing ischemia to that limb.
Dr. Glatter: Hannah, does your device collect data on the number of hours or minutes that the tourniquet has been up and then automatically deflate it in some sense to allow for that improvement in limb salvage?
Ms. Herbst: That’s a great question, and I really appreciate your answer as well, Dr Antevy. Ischemia time is a very important and critical component of tourniquet use. This is something, when we were designing AutoTQ, that we took into high consideration.
We found, when we evaluated AutoTQ vs a CAT tourniquet in a mannequin model, that AutoTQ can achieve cessation of hemorrhage at around 400 mm Hg of mercury, whereas CAT requires 700-800 mm Hg. Already our ischemia time is slightly extended just based on existing literature with pneumatic tourniquets because it can stop the bleed at a lower pressure, which causes less complications with the patient’s limb.
There are different features that we build out for different customers, so depending on what people want, it is possible to deflate the tourniquet. However, typically, you’re at the hospital within 30 minutes. It’s quick to get them there, and then the physician can treat and take that tourniquet down in a supervised and controlled setting.
Dr. Glatter: In terms of patients with obesity, do you have adjustable straps that will accommodate for that aspect?
Ms. Herbst: Yes, we have different cuff sizes to accommodate different limbs.
Will AutoTQ Be Available to the Public?
Dr. Glatter: Peter, in terms of usability in the prehospital setting, where do you think this is going in the next 3-5 years?
Dr. Antevy: I’ll start with the public safety sector of the United States, which is the one that is actually first on scene. Whether you’re talking about police officers or EMS, it would behoove us to have tourniquets everywhere. On all of my ambulances, across all of my agencies that I manage, we have quite a number of tourniquets.
Obviously, cost is a factor, and I know that Hannah has done a great job of making that brain reusable. All we have to do is purchase the straps, which are effectively the same cost, I understand, as a typical tourniquet you would purchase.
Moving forward though, however, I think that this has wide scalability to the public market, whether it be schools, office buildings, the glove box, and so on. It’s really impossible to teach somebody how to do this the right way, if you have to teach them how to put the strap on, tighten it correctly, and so on. If there was an easy way, like Hannah developed, of just putting it on and pushing a button, then I think that the outcomes and the scalability are much further beyond what we can do in EMS. I think there’s great value in both markets.
The ‘AED of Bleeding’: Rechargeable and Reusable
Dr. Glatter: This is the AED of bleeding. You have a device here that has wide-scale interest, certainly from the public and private sector.
Hannah, in terms of battery decay, how would that work out if it was in someone’s garage? Let’s just say someone purchased it and they hadn’t used it in 3 or 4 months. What type of decay are we looking at and can they rely on it?
Ms. Herbst: AutoTQ is rechargeable by a USB-C port, and our battery lasts for a year. Once a year, you’ll get an email reminder that says: “Hey, please charge your AutoTQ and make sure it’s up to the battery level.” We do everything in our power to make sure that our consumers are checking their batteries and that they’re ready to go.
Dr. Glatter: Is it heat and fire resistant? What, in terms of durability, does your device have?
Ms. Herbst: Just like any other medical device, we come with manufacturer recommendations for the upper and lower bounds of temperature and different storage recommendations. All of that is in our instructions for use.
Dr. Glatter: Peter, getting back to logistics. In terms of adoption, do you feel that, in the long term, this device will be something that we’re going to be seeing widely adopted just going forward?
Dr. Antevy: I do, and I’ll tell you why. When you look at AED use in this country, the odds of someone actually getting an AED and using it correctly are still very low. Part of that is because it’s complicated for many people to do. Getting tourniquets everywhere is step No. 1, and I think the federal government and the Stop the Bleed program is really making that happen.
We talked about ordinances, but ease of use, I think, is really the key. You have people who oftentimes have their child in cardiac arrest in front of them, and they won’t put two hands on their chest because they just are afraid of doing it.
When you have a device that’s a tourniquet, that’s a single-button turn on and single-button inflate, I think that would make it much more likely that a person will use that device when they’re passing the scene of an accident, as an example.
We’ve had many non–mass casualty incident events that have had tourniquets. We’ve had some media stories on them, where they’re just happening because someone got into a motor vehicle accident. It doesn’t have to be a school shooting. I think the tourniquets should be everywhere and should be easily used by everybody.
Managing Pain
Dr. Glatter: Regarding sedation, is there a need because of the pain involved with the application? How would you sedate a patient, pediatric or adult, who needs a tourniquet?
Dr. Antevy: We always evaluate people’s pain. If the patient is an extremist, we’re just going to be managing and trying to get them back to life. Once somebody is stabilized and is exhibiting pain of any sort, even, for example, after we intubate somebody, we have to sedate them and provide them pain control because they have a piece of plastic in their trachea.
It’s the same thing here for a tourniquet. These are painful, and we do have the appropriate medications on our vehicles to address that pain. Again, just simply the trauma itself is very painful. Yes, we do address that in EMS, and I would say most public agencies across this country would address pain appropriately.
Training on Tourniquet Use
Dr. Glatter: Hannah, can you talk a little bit about public training types of approaches? How would you train a consumer who purchases this type of device?
Ms. Herbst: A huge part of our mission is making blood loss prevention and control training accessible to a wide variety of people. One way that we’re able to do that is through our online training platform. When you purchase an AutoTQ kit, you plug it into your computer, and it walks you through the process of using it. It lets you practice on your own limb and on your buddy’s limb, just to be able to effectively apply it. We think this will have huge impacts in making sure that people are prepared and ready to stop the bleed with AutoTQ.
Dr. Glatter: Do you recommend people training once a month, in general, just to keep their skills up to use this? In the throes of a trauma and very chaotic situation, people sometimes lose their ability to think clearly and straightly.
Ms. Herbst: One of the studies we’re conducting is a learning curve study to try to figure out how quickly these skills degrade over time. We know that with the windlass tourniquet, it degrades within moments of training. With AutoTQ, we think the learning curve will last much longer. That’s something we’re evaluating, but we recommend people train as often as they can.
Dr. Antevy: Rob, if I can mention that there is a concept of just-in-time training. I think that with having the expectation that people are going to be training frequently, unfortunately, as many of us know, even with the AED as a perfect example, people don’t do that.
Yes. I would agree that you have to train at least once a year, is what I would say. At my office, we have a 2-hour training that goes over all these different items once a year.
The device itself should have the ability to allow you to figure out how to use it just in time, whether via video, or like Hannah’s device, by audio. I think that having both those things would make it more likely that the device be used when needed.
People panic, and if they have a device that can talk to them or walk them through it, they will be much more likely to use it at that time.
Final Takeaways
Dr. Glatter: Any other final thoughts or a few pearls for listeners to take away? Hannah, I’ll start with you.
Ms. Herbst: I’m very grateful for your time, and I’m very excited about the potential for AutoTQ. To me, it’s so exciting to see people preordering the device now. We’ve had people from school bus companies and small sports teams. I think, just like Dr Antevy said, tourniquets aren’t limited to mass casualty situations. Blood loss can happen anywhere and to anyone.
Being able to equip people and serve them to better prepare them for this happening to themselves, their friends, or their family is just the honor of a lifetime. Thank you very much for covering the device and for having me today.
Dr. Glatter: Of course, my pleasure. Peter?
Dr. Antevy: The citizens of this country, and everyone who lives across the world, has started to understand that there are things that we expect from our people, from the community. We expect them to do CPR for cardiac arrest. We expect them to know how to use an EpiPen. We expect them to know how to use an AED, and we also expect them to know how to stop bleeding with a tourniquet.
The American public has gotten to understand that these devices are very important. Having a device that’s easily used, that I can teach you in 10 seconds, that speaks to you — these are all things that make this product have great potential. I do look forward to the studies, not just the cadaver studies, but the real human studies.
I know Hannah is really a phenom and has been doing all these things so that this product can be on the shelves of Walmart and CVS one day. I commend you, Hannah, for everything you’re doing and wishing you the best of luck. We’re here for you.
Dr. Glatter: Same here. Congratulations on your innovative capability and what you’ve done to change the outcomes of bleeding related to penetrating trauma. Thank you so much.
Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. Hannah D. Herbst, BS, is a graduate of Florida Atlantic University, was selected for Forbes 30 Under 30, and is the founder/CEO of Golden Hour Medical. Peter M. Antevy, MD, is a pediatric emergency medicine physician and medical director for Davie Fire Rescue and Coral Springs–Parkland Fire Department in Florida. He is also a member of the EMS Eagles Global Alliance.
A version of this article first appeared on Medscape.com.
This discussion was recorded on July 12, 2024. This transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. I recently met an innovative young woman named Hannah Herbst while attending the annual Eagles EMS Conference in Fort Lauderdale, Florida.
Hannah Herbst is a graduate of Florida Atlantic University, selected for Forbes 30 Under 30, and founder of a company called Golden Hour Medical. She has a background in IT and developed an automated pneumatic tourniquet known as AutoTQ, which we’re going to discuss at length here.
Also joining us is Dr. Peter Antevy, a pediatric emergency physician and medical director for Davie Fire Rescue as well as Coral Springs Parkland Fire Rescue. Peter is a member of EMS Eagles Global Alliance and is highly involved in high-quality research in prehospital emergency care and is quite well known in Florida and nationally.
Welcome to both of you.
Hannah Herbst: Thank you very much. Very grateful to be here.
Dr. Glatter: Hannah, I’ll let you start by explaining what AutoTQ is and then compare that to a standard Combat Application Tourniquet (CAT).
Ms. Herbst: Thank you. Unfortunately, blood loss is a leading cause of preventable death and trauma. When there’s blood loss occurring from an arm or a leg, the easiest way to stop it is by applying a tourniquet, which is this compression type of device that you place above the site of bleeding, and it then applies a high amount of pressure to stop blood flow through the limb.
Currently, tourniquets on the market have failure rates as high as 84%. This became very real to me back in 2018, when I became aware of mass casualty incidents when I was a student. I became interested in how we can reimagine the conventional tourniquet and try to make it something that’s very user-friendly, much like an automated external defibrillator (AED).
My team and I developed AutoTQ, which is an automated tourniquet. which is a leading cause of tourniquet failure and being able to effectively administer treatment to a patient that may bleed out.
Tourniquet Failure Rates
Dr. Glatter: In terms of tourniquet failure, how often do standard tourniquets fail, like the CAT combat-type tourniquet?
Ms. Herbst: Unfortunately, they fail very frequently. There are several studies that have been conducted to evaluate this. Many of them occur immediately after training. They found failure rates between 80% and 90% for the current conventional CAT tourniquet immediately after training, which is very concerning.
Dr. Glatter: In terms of failure, was it the windlass aspect of the tourniquet that failed? Or was it something related to the actual strap? Was that in any way detailed?
Ms. Herbst: There are usually a few different failure points that have been found in the literature. One is placement. Many times, when you’re panicked, you don’t remember exactly how to place it. It should be placed high and tight above the bleed and not over a joint.
The second problem is inadequate tightness. For a CAT tourniquet to be effective, you have to get it extremely tight on that first pull before the windlass is activated, and many times people don’t remember that in the stress of the moment.
Dr. Glatter: Peter, in terms of tourniquet application by your medics in the field, certainly the CAT-type device has been in existence for quite a while. Hannah’s proposing a new iteration of how to do this, which is automated and simple. What is your take on such a device? And how did you learn about Hannah’s device?
Peter M. Antevy, MD: We’ve been training on tourniquets ever since the military data showed that there was an extreme benefit in using them. We’ve been doing training for many years, including our police officers. What we’ve noticed is that every time we gather everyone together to show them how to place a tourniquet — and we have to do one-on-one sessions with them — it’s not a device that they can easily put on. These are police officers who had the training last year.
Like Hannah said, most of the time they have a problem unraveling it and understanding how to actually place it. It’s easier on the arm than it is on the leg. You can imagine it would be harder to place it on your own leg, especially if you had an injury. Then, they don’t tighten it well enough, as Hannah just mentioned. In order for a tourniquet to really be placed properly, it’s going to hurt that person. Many people have that tendency not to want to tighten it as much as they can.
Having said that, how I got into all of this is because I’m the medical director for Coral Springs and Parkland, and unfortunately, we had the 2018 Valentine’s Day murders that happened where we lost 17 adults and kids. However, 17 people were saved that day, and the credit goes to our police officers who had tourniquets or chest seals on before those patients were brought out to EMS. Many lives were saved by the tourniquet.
If you look at the Boston Marathon massacre and many other events that have happened, I believe — and I’ve always believed — that tourniquets should be in the glove box of every citizen. It should be in every school room. They should be in buildings along with the AED.
In my town of Davie, we were the first in the country to add an ordinance that required a Stop the Bleed kit in the AED cabinet, and those were required by buildings of certain sizes. In order to get this lifesaving device everywhere, I think it has to be put into local ordinance and supported by states and by the national folks, which they are doing.
Trials Are Underway
Dr. Glatter: In terms of adoption of such a device, it certainly has to go through rigorous testing and maybe some trials. Hannah, where are you at with vetting this in terms of any type of trial? Has it been compared head to head with standard tourniquets?
Ms. Herbst: Yes, we’re currently doing large amounts of field testing. We’re doing testing on emergency vehicles and in the surgical setting with different customers. In addition, we’re running pilot studies at different universities and with different organizations, including the military, to make sure that this device is effective. We’re evaluating cognitive offloading of people. We’re hoping to start that study later this year. We’re excited to be doing this in a variety of settings.
We’re also testing the quality of it in different environmental conditions and under different atmospheric pressure. We’re doing everything we can to ensure the device is safe and effective. We’re excited to scale and fill our preorders and be able to develop this and deliver it to many people.
Dr. Glatter: I was wondering if you could describe the actual device. There’s a brain part of it and then, obviously, the strap aspect of it. I was curious about contamination and reusability issues.
Ms. Herbst: That’s a great question. One of the limitations of conventional tourniquets on the market is that they are single use, and often, it requires two tourniquets to stop a bleed, both of which have to be disposed of.
With AutoTQ, we have a reusable component and a disposable component. I actually have one here that I can show you. We have a cover on it that says: Stop bleed, slide up and power on. You just pull this cover off and then you have a few simple commands. You have powering the device on. I’ll just click this button: Tighten strap above bleeding, then press inflate. It delivers audible instructions telling you exactly how to use the device. Then, you tighten it above your bleed on the limb, and you press the inflate button. Then it administers air into the cuff and stops the patient’s bleed.
Tourniquet Conversion and Limb Salvage
Dr. Glatter: In terms of ischemia time, how can a device like this make it easier for us to know when to let the tourniquet down and allow some blood flow? Certainly, limb salvage is important, and we don’t want to have necrosis and so forth.
Dr. Antevy: That’s a great question. The limb salvage rate when tourniquets have been used is 85%. When used correctly, you can really improve the outcomes for many patients.
On the flip side of that, there’s something called tourniquet conversion. That’s exactly what you mentioned. It’s making sure that the tourniquet doesn’t stay on for too long of a time. If you can imagine a patient going to an outlying hospital where there’s no trauma center, and then that patient then has to be moved a couple hours to the trauma center, could you potentially have a tourniquet on for too long that then ends up causing the patient a bad outcome? The answer is yes.
I just had someone on my webinar recently describing the appropriate conversion techniques of tourniquets. You don’t find too much of that in the literature, but you really have to ensure that as you’re taking the tourniquet down, the bleeding is actually stopped. It’s not really recommended to take a tourniquet down if the patient was just acutely bleeding.
However, imagine a situation where a tourniquet was put on incorrectly. Let’s say a patient got nervous and they just put it on a patient who didn’t really need it. You really have to understand how to evaluate that wound to be sure that, as you’re taking the tourniquet down slowly, the patient doesn’t rebleed again.
There are two sides of the question, Rob. One is making sure it’s not on inappropriately. The second one is making sure it’s not on for too long, which ends up causing ischemia to that limb.
Dr. Glatter: Hannah, does your device collect data on the number of hours or minutes that the tourniquet has been up and then automatically deflate it in some sense to allow for that improvement in limb salvage?
Ms. Herbst: That’s a great question, and I really appreciate your answer as well, Dr Antevy. Ischemia time is a very important and critical component of tourniquet use. This is something, when we were designing AutoTQ, that we took into high consideration.
We found, when we evaluated AutoTQ vs a CAT tourniquet in a mannequin model, that AutoTQ can achieve cessation of hemorrhage at around 400 mm Hg of mercury, whereas CAT requires 700-800 mm Hg. Already our ischemia time is slightly extended just based on existing literature with pneumatic tourniquets because it can stop the bleed at a lower pressure, which causes less complications with the patient’s limb.
There are different features that we build out for different customers, so depending on what people want, it is possible to deflate the tourniquet. However, typically, you’re at the hospital within 30 minutes. It’s quick to get them there, and then the physician can treat and take that tourniquet down in a supervised and controlled setting.
Dr. Glatter: In terms of patients with obesity, do you have adjustable straps that will accommodate for that aspect?
Ms. Herbst: Yes, we have different cuff sizes to accommodate different limbs.
Will AutoTQ Be Available to the Public?
Dr. Glatter: Peter, in terms of usability in the prehospital setting, where do you think this is going in the next 3-5 years?
Dr. Antevy: I’ll start with the public safety sector of the United States, which is the one that is actually first on scene. Whether you’re talking about police officers or EMS, it would behoove us to have tourniquets everywhere. On all of my ambulances, across all of my agencies that I manage, we have quite a number of tourniquets.
Obviously, cost is a factor, and I know that Hannah has done a great job of making that brain reusable. All we have to do is purchase the straps, which are effectively the same cost, I understand, as a typical tourniquet you would purchase.
Moving forward though, however, I think that this has wide scalability to the public market, whether it be schools, office buildings, the glove box, and so on. It’s really impossible to teach somebody how to do this the right way, if you have to teach them how to put the strap on, tighten it correctly, and so on. If there was an easy way, like Hannah developed, of just putting it on and pushing a button, then I think that the outcomes and the scalability are much further beyond what we can do in EMS. I think there’s great value in both markets.
The ‘AED of Bleeding’: Rechargeable and Reusable
Dr. Glatter: This is the AED of bleeding. You have a device here that has wide-scale interest, certainly from the public and private sector.
Hannah, in terms of battery decay, how would that work out if it was in someone’s garage? Let’s just say someone purchased it and they hadn’t used it in 3 or 4 months. What type of decay are we looking at and can they rely on it?
Ms. Herbst: AutoTQ is rechargeable by a USB-C port, and our battery lasts for a year. Once a year, you’ll get an email reminder that says: “Hey, please charge your AutoTQ and make sure it’s up to the battery level.” We do everything in our power to make sure that our consumers are checking their batteries and that they’re ready to go.
Dr. Glatter: Is it heat and fire resistant? What, in terms of durability, does your device have?
Ms. Herbst: Just like any other medical device, we come with manufacturer recommendations for the upper and lower bounds of temperature and different storage recommendations. All of that is in our instructions for use.
Dr. Glatter: Peter, getting back to logistics. In terms of adoption, do you feel that, in the long term, this device will be something that we’re going to be seeing widely adopted just going forward?
Dr. Antevy: I do, and I’ll tell you why. When you look at AED use in this country, the odds of someone actually getting an AED and using it correctly are still very low. Part of that is because it’s complicated for many people to do. Getting tourniquets everywhere is step No. 1, and I think the federal government and the Stop the Bleed program is really making that happen.
We talked about ordinances, but ease of use, I think, is really the key. You have people who oftentimes have their child in cardiac arrest in front of them, and they won’t put two hands on their chest because they just are afraid of doing it.
When you have a device that’s a tourniquet, that’s a single-button turn on and single-button inflate, I think that would make it much more likely that a person will use that device when they’re passing the scene of an accident, as an example.
We’ve had many non–mass casualty incident events that have had tourniquets. We’ve had some media stories on them, where they’re just happening because someone got into a motor vehicle accident. It doesn’t have to be a school shooting. I think the tourniquets should be everywhere and should be easily used by everybody.
Managing Pain
Dr. Glatter: Regarding sedation, is there a need because of the pain involved with the application? How would you sedate a patient, pediatric or adult, who needs a tourniquet?
Dr. Antevy: We always evaluate people’s pain. If the patient is an extremist, we’re just going to be managing and trying to get them back to life. Once somebody is stabilized and is exhibiting pain of any sort, even, for example, after we intubate somebody, we have to sedate them and provide them pain control because they have a piece of plastic in their trachea.
It’s the same thing here for a tourniquet. These are painful, and we do have the appropriate medications on our vehicles to address that pain. Again, just simply the trauma itself is very painful. Yes, we do address that in EMS, and I would say most public agencies across this country would address pain appropriately.
Training on Tourniquet Use
Dr. Glatter: Hannah, can you talk a little bit about public training types of approaches? How would you train a consumer who purchases this type of device?
Ms. Herbst: A huge part of our mission is making blood loss prevention and control training accessible to a wide variety of people. One way that we’re able to do that is through our online training platform. When you purchase an AutoTQ kit, you plug it into your computer, and it walks you through the process of using it. It lets you practice on your own limb and on your buddy’s limb, just to be able to effectively apply it. We think this will have huge impacts in making sure that people are prepared and ready to stop the bleed with AutoTQ.
Dr. Glatter: Do you recommend people training once a month, in general, just to keep their skills up to use this? In the throes of a trauma and very chaotic situation, people sometimes lose their ability to think clearly and straightly.
Ms. Herbst: One of the studies we’re conducting is a learning curve study to try to figure out how quickly these skills degrade over time. We know that with the windlass tourniquet, it degrades within moments of training. With AutoTQ, we think the learning curve will last much longer. That’s something we’re evaluating, but we recommend people train as often as they can.
Dr. Antevy: Rob, if I can mention that there is a concept of just-in-time training. I think that with having the expectation that people are going to be training frequently, unfortunately, as many of us know, even with the AED as a perfect example, people don’t do that.
Yes. I would agree that you have to train at least once a year, is what I would say. At my office, we have a 2-hour training that goes over all these different items once a year.
The device itself should have the ability to allow you to figure out how to use it just in time, whether via video, or like Hannah’s device, by audio. I think that having both those things would make it more likely that the device be used when needed.
People panic, and if they have a device that can talk to them or walk them through it, they will be much more likely to use it at that time.
Final Takeaways
Dr. Glatter: Any other final thoughts or a few pearls for listeners to take away? Hannah, I’ll start with you.
Ms. Herbst: I’m very grateful for your time, and I’m very excited about the potential for AutoTQ. To me, it’s so exciting to see people preordering the device now. We’ve had people from school bus companies and small sports teams. I think, just like Dr Antevy said, tourniquets aren’t limited to mass casualty situations. Blood loss can happen anywhere and to anyone.
Being able to equip people and serve them to better prepare them for this happening to themselves, their friends, or their family is just the honor of a lifetime. Thank you very much for covering the device and for having me today.
Dr. Glatter: Of course, my pleasure. Peter?
Dr. Antevy: The citizens of this country, and everyone who lives across the world, has started to understand that there are things that we expect from our people, from the community. We expect them to do CPR for cardiac arrest. We expect them to know how to use an EpiPen. We expect them to know how to use an AED, and we also expect them to know how to stop bleeding with a tourniquet.
The American public has gotten to understand that these devices are very important. Having a device that’s easily used, that I can teach you in 10 seconds, that speaks to you — these are all things that make this product have great potential. I do look forward to the studies, not just the cadaver studies, but the real human studies.
I know Hannah is really a phenom and has been doing all these things so that this product can be on the shelves of Walmart and CVS one day. I commend you, Hannah, for everything you’re doing and wishing you the best of luck. We’re here for you.
Dr. Glatter: Same here. Congratulations on your innovative capability and what you’ve done to change the outcomes of bleeding related to penetrating trauma. Thank you so much.
Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. Hannah D. Herbst, BS, is a graduate of Florida Atlantic University, was selected for Forbes 30 Under 30, and is the founder/CEO of Golden Hour Medical. Peter M. Antevy, MD, is a pediatric emergency medicine physician and medical director for Davie Fire Rescue and Coral Springs–Parkland Fire Department in Florida. He is also a member of the EMS Eagles Global Alliance.
A version of this article first appeared on Medscape.com.
This discussion was recorded on July 12, 2024. This transcript has been edited for clarity.
Robert D. Glatter, MD: Hi and welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. I recently met an innovative young woman named Hannah Herbst while attending the annual Eagles EMS Conference in Fort Lauderdale, Florida.
Hannah Herbst is a graduate of Florida Atlantic University, selected for Forbes 30 Under 30, and founder of a company called Golden Hour Medical. She has a background in IT and developed an automated pneumatic tourniquet known as AutoTQ, which we’re going to discuss at length here.
Also joining us is Dr. Peter Antevy, a pediatric emergency physician and medical director for Davie Fire Rescue as well as Coral Springs Parkland Fire Rescue. Peter is a member of EMS Eagles Global Alliance and is highly involved in high-quality research in prehospital emergency care and is quite well known in Florida and nationally.
Welcome to both of you.
Hannah Herbst: Thank you very much. Very grateful to be here.
Dr. Glatter: Hannah, I’ll let you start by explaining what AutoTQ is and then compare that to a standard Combat Application Tourniquet (CAT).
Ms. Herbst: Thank you. Unfortunately, blood loss is a leading cause of preventable death and trauma. When there’s blood loss occurring from an arm or a leg, the easiest way to stop it is by applying a tourniquet, which is this compression type of device that you place above the site of bleeding, and it then applies a high amount of pressure to stop blood flow through the limb.
Currently, tourniquets on the market have failure rates as high as 84%. This became very real to me back in 2018, when I became aware of mass casualty incidents when I was a student. I became interested in how we can reimagine the conventional tourniquet and try to make it something that’s very user-friendly, much like an automated external defibrillator (AED).
My team and I developed AutoTQ, which is an automated tourniquet. which is a leading cause of tourniquet failure and being able to effectively administer treatment to a patient that may bleed out.
Tourniquet Failure Rates
Dr. Glatter: In terms of tourniquet failure, how often do standard tourniquets fail, like the CAT combat-type tourniquet?
Ms. Herbst: Unfortunately, they fail very frequently. There are several studies that have been conducted to evaluate this. Many of them occur immediately after training. They found failure rates between 80% and 90% for the current conventional CAT tourniquet immediately after training, which is very concerning.
Dr. Glatter: In terms of failure, was it the windlass aspect of the tourniquet that failed? Or was it something related to the actual strap? Was that in any way detailed?
Ms. Herbst: There are usually a few different failure points that have been found in the literature. One is placement. Many times, when you’re panicked, you don’t remember exactly how to place it. It should be placed high and tight above the bleed and not over a joint.
The second problem is inadequate tightness. For a CAT tourniquet to be effective, you have to get it extremely tight on that first pull before the windlass is activated, and many times people don’t remember that in the stress of the moment.
Dr. Glatter: Peter, in terms of tourniquet application by your medics in the field, certainly the CAT-type device has been in existence for quite a while. Hannah’s proposing a new iteration of how to do this, which is automated and simple. What is your take on such a device? And how did you learn about Hannah’s device?
Peter M. Antevy, MD: We’ve been training on tourniquets ever since the military data showed that there was an extreme benefit in using them. We’ve been doing training for many years, including our police officers. What we’ve noticed is that every time we gather everyone together to show them how to place a tourniquet — and we have to do one-on-one sessions with them — it’s not a device that they can easily put on. These are police officers who had the training last year.
Like Hannah said, most of the time they have a problem unraveling it and understanding how to actually place it. It’s easier on the arm than it is on the leg. You can imagine it would be harder to place it on your own leg, especially if you had an injury. Then, they don’t tighten it well enough, as Hannah just mentioned. In order for a tourniquet to really be placed properly, it’s going to hurt that person. Many people have that tendency not to want to tighten it as much as they can.
Having said that, how I got into all of this is because I’m the medical director for Coral Springs and Parkland, and unfortunately, we had the 2018 Valentine’s Day murders that happened where we lost 17 adults and kids. However, 17 people were saved that day, and the credit goes to our police officers who had tourniquets or chest seals on before those patients were brought out to EMS. Many lives were saved by the tourniquet.
If you look at the Boston Marathon massacre and many other events that have happened, I believe — and I’ve always believed — that tourniquets should be in the glove box of every citizen. It should be in every school room. They should be in buildings along with the AED.
In my town of Davie, we were the first in the country to add an ordinance that required a Stop the Bleed kit in the AED cabinet, and those were required by buildings of certain sizes. In order to get this lifesaving device everywhere, I think it has to be put into local ordinance and supported by states and by the national folks, which they are doing.
Trials Are Underway
Dr. Glatter: In terms of adoption of such a device, it certainly has to go through rigorous testing and maybe some trials. Hannah, where are you at with vetting this in terms of any type of trial? Has it been compared head to head with standard tourniquets?
Ms. Herbst: Yes, we’re currently doing large amounts of field testing. We’re doing testing on emergency vehicles and in the surgical setting with different customers. In addition, we’re running pilot studies at different universities and with different organizations, including the military, to make sure that this device is effective. We’re evaluating cognitive offloading of people. We’re hoping to start that study later this year. We’re excited to be doing this in a variety of settings.
We’re also testing the quality of it in different environmental conditions and under different atmospheric pressure. We’re doing everything we can to ensure the device is safe and effective. We’re excited to scale and fill our preorders and be able to develop this and deliver it to many people.
Dr. Glatter: I was wondering if you could describe the actual device. There’s a brain part of it and then, obviously, the strap aspect of it. I was curious about contamination and reusability issues.
Ms. Herbst: That’s a great question. One of the limitations of conventional tourniquets on the market is that they are single use, and often, it requires two tourniquets to stop a bleed, both of which have to be disposed of.
With AutoTQ, we have a reusable component and a disposable component. I actually have one here that I can show you. We have a cover on it that says: Stop bleed, slide up and power on. You just pull this cover off and then you have a few simple commands. You have powering the device on. I’ll just click this button: Tighten strap above bleeding, then press inflate. It delivers audible instructions telling you exactly how to use the device. Then, you tighten it above your bleed on the limb, and you press the inflate button. Then it administers air into the cuff and stops the patient’s bleed.
Tourniquet Conversion and Limb Salvage
Dr. Glatter: In terms of ischemia time, how can a device like this make it easier for us to know when to let the tourniquet down and allow some blood flow? Certainly, limb salvage is important, and we don’t want to have necrosis and so forth.
Dr. Antevy: That’s a great question. The limb salvage rate when tourniquets have been used is 85%. When used correctly, you can really improve the outcomes for many patients.
On the flip side of that, there’s something called tourniquet conversion. That’s exactly what you mentioned. It’s making sure that the tourniquet doesn’t stay on for too long of a time. If you can imagine a patient going to an outlying hospital where there’s no trauma center, and then that patient then has to be moved a couple hours to the trauma center, could you potentially have a tourniquet on for too long that then ends up causing the patient a bad outcome? The answer is yes.
I just had someone on my webinar recently describing the appropriate conversion techniques of tourniquets. You don’t find too much of that in the literature, but you really have to ensure that as you’re taking the tourniquet down, the bleeding is actually stopped. It’s not really recommended to take a tourniquet down if the patient was just acutely bleeding.
However, imagine a situation where a tourniquet was put on incorrectly. Let’s say a patient got nervous and they just put it on a patient who didn’t really need it. You really have to understand how to evaluate that wound to be sure that, as you’re taking the tourniquet down slowly, the patient doesn’t rebleed again.
There are two sides of the question, Rob. One is making sure it’s not on inappropriately. The second one is making sure it’s not on for too long, which ends up causing ischemia to that limb.
Dr. Glatter: Hannah, does your device collect data on the number of hours or minutes that the tourniquet has been up and then automatically deflate it in some sense to allow for that improvement in limb salvage?
Ms. Herbst: That’s a great question, and I really appreciate your answer as well, Dr Antevy. Ischemia time is a very important and critical component of tourniquet use. This is something, when we were designing AutoTQ, that we took into high consideration.
We found, when we evaluated AutoTQ vs a CAT tourniquet in a mannequin model, that AutoTQ can achieve cessation of hemorrhage at around 400 mm Hg of mercury, whereas CAT requires 700-800 mm Hg. Already our ischemia time is slightly extended just based on existing literature with pneumatic tourniquets because it can stop the bleed at a lower pressure, which causes less complications with the patient’s limb.
There are different features that we build out for different customers, so depending on what people want, it is possible to deflate the tourniquet. However, typically, you’re at the hospital within 30 minutes. It’s quick to get them there, and then the physician can treat and take that tourniquet down in a supervised and controlled setting.
Dr. Glatter: In terms of patients with obesity, do you have adjustable straps that will accommodate for that aspect?
Ms. Herbst: Yes, we have different cuff sizes to accommodate different limbs.
Will AutoTQ Be Available to the Public?
Dr. Glatter: Peter, in terms of usability in the prehospital setting, where do you think this is going in the next 3-5 years?
Dr. Antevy: I’ll start with the public safety sector of the United States, which is the one that is actually first on scene. Whether you’re talking about police officers or EMS, it would behoove us to have tourniquets everywhere. On all of my ambulances, across all of my agencies that I manage, we have quite a number of tourniquets.
Obviously, cost is a factor, and I know that Hannah has done a great job of making that brain reusable. All we have to do is purchase the straps, which are effectively the same cost, I understand, as a typical tourniquet you would purchase.
Moving forward though, however, I think that this has wide scalability to the public market, whether it be schools, office buildings, the glove box, and so on. It’s really impossible to teach somebody how to do this the right way, if you have to teach them how to put the strap on, tighten it correctly, and so on. If there was an easy way, like Hannah developed, of just putting it on and pushing a button, then I think that the outcomes and the scalability are much further beyond what we can do in EMS. I think there’s great value in both markets.
The ‘AED of Bleeding’: Rechargeable and Reusable
Dr. Glatter: This is the AED of bleeding. You have a device here that has wide-scale interest, certainly from the public and private sector.
Hannah, in terms of battery decay, how would that work out if it was in someone’s garage? Let’s just say someone purchased it and they hadn’t used it in 3 or 4 months. What type of decay are we looking at and can they rely on it?
Ms. Herbst: AutoTQ is rechargeable by a USB-C port, and our battery lasts for a year. Once a year, you’ll get an email reminder that says: “Hey, please charge your AutoTQ and make sure it’s up to the battery level.” We do everything in our power to make sure that our consumers are checking their batteries and that they’re ready to go.
Dr. Glatter: Is it heat and fire resistant? What, in terms of durability, does your device have?
Ms. Herbst: Just like any other medical device, we come with manufacturer recommendations for the upper and lower bounds of temperature and different storage recommendations. All of that is in our instructions for use.
Dr. Glatter: Peter, getting back to logistics. In terms of adoption, do you feel that, in the long term, this device will be something that we’re going to be seeing widely adopted just going forward?
Dr. Antevy: I do, and I’ll tell you why. When you look at AED use in this country, the odds of someone actually getting an AED and using it correctly are still very low. Part of that is because it’s complicated for many people to do. Getting tourniquets everywhere is step No. 1, and I think the federal government and the Stop the Bleed program is really making that happen.
We talked about ordinances, but ease of use, I think, is really the key. You have people who oftentimes have their child in cardiac arrest in front of them, and they won’t put two hands on their chest because they just are afraid of doing it.
When you have a device that’s a tourniquet, that’s a single-button turn on and single-button inflate, I think that would make it much more likely that a person will use that device when they’re passing the scene of an accident, as an example.
We’ve had many non–mass casualty incident events that have had tourniquets. We’ve had some media stories on them, where they’re just happening because someone got into a motor vehicle accident. It doesn’t have to be a school shooting. I think the tourniquets should be everywhere and should be easily used by everybody.
Managing Pain
Dr. Glatter: Regarding sedation, is there a need because of the pain involved with the application? How would you sedate a patient, pediatric or adult, who needs a tourniquet?
Dr. Antevy: We always evaluate people’s pain. If the patient is an extremist, we’re just going to be managing and trying to get them back to life. Once somebody is stabilized and is exhibiting pain of any sort, even, for example, after we intubate somebody, we have to sedate them and provide them pain control because they have a piece of plastic in their trachea.
It’s the same thing here for a tourniquet. These are painful, and we do have the appropriate medications on our vehicles to address that pain. Again, just simply the trauma itself is very painful. Yes, we do address that in EMS, and I would say most public agencies across this country would address pain appropriately.
Training on Tourniquet Use
Dr. Glatter: Hannah, can you talk a little bit about public training types of approaches? How would you train a consumer who purchases this type of device?
Ms. Herbst: A huge part of our mission is making blood loss prevention and control training accessible to a wide variety of people. One way that we’re able to do that is through our online training platform. When you purchase an AutoTQ kit, you plug it into your computer, and it walks you through the process of using it. It lets you practice on your own limb and on your buddy’s limb, just to be able to effectively apply it. We think this will have huge impacts in making sure that people are prepared and ready to stop the bleed with AutoTQ.
Dr. Glatter: Do you recommend people training once a month, in general, just to keep their skills up to use this? In the throes of a trauma and very chaotic situation, people sometimes lose their ability to think clearly and straightly.
Ms. Herbst: One of the studies we’re conducting is a learning curve study to try to figure out how quickly these skills degrade over time. We know that with the windlass tourniquet, it degrades within moments of training. With AutoTQ, we think the learning curve will last much longer. That’s something we’re evaluating, but we recommend people train as often as they can.
Dr. Antevy: Rob, if I can mention that there is a concept of just-in-time training. I think that with having the expectation that people are going to be training frequently, unfortunately, as many of us know, even with the AED as a perfect example, people don’t do that.
Yes. I would agree that you have to train at least once a year, is what I would say. At my office, we have a 2-hour training that goes over all these different items once a year.
The device itself should have the ability to allow you to figure out how to use it just in time, whether via video, or like Hannah’s device, by audio. I think that having both those things would make it more likely that the device be used when needed.
People panic, and if they have a device that can talk to them or walk them through it, they will be much more likely to use it at that time.
Final Takeaways
Dr. Glatter: Any other final thoughts or a few pearls for listeners to take away? Hannah, I’ll start with you.
Ms. Herbst: I’m very grateful for your time, and I’m very excited about the potential for AutoTQ. To me, it’s so exciting to see people preordering the device now. We’ve had people from school bus companies and small sports teams. I think, just like Dr Antevy said, tourniquets aren’t limited to mass casualty situations. Blood loss can happen anywhere and to anyone.
Being able to equip people and serve them to better prepare them for this happening to themselves, their friends, or their family is just the honor of a lifetime. Thank you very much for covering the device and for having me today.
Dr. Glatter: Of course, my pleasure. Peter?
Dr. Antevy: The citizens of this country, and everyone who lives across the world, has started to understand that there are things that we expect from our people, from the community. We expect them to do CPR for cardiac arrest. We expect them to know how to use an EpiPen. We expect them to know how to use an AED, and we also expect them to know how to stop bleeding with a tourniquet.
The American public has gotten to understand that these devices are very important. Having a device that’s easily used, that I can teach you in 10 seconds, that speaks to you — these are all things that make this product have great potential. I do look forward to the studies, not just the cadaver studies, but the real human studies.
I know Hannah is really a phenom and has been doing all these things so that this product can be on the shelves of Walmart and CVS one day. I commend you, Hannah, for everything you’re doing and wishing you the best of luck. We’re here for you.
Dr. Glatter: Same here. Congratulations on your innovative capability and what you’ve done to change the outcomes of bleeding related to penetrating trauma. Thank you so much.
Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. Hannah D. Herbst, BS, is a graduate of Florida Atlantic University, was selected for Forbes 30 Under 30, and is the founder/CEO of Golden Hour Medical. Peter M. Antevy, MD, is a pediatric emergency medicine physician and medical director for Davie Fire Rescue and Coral Springs–Parkland Fire Department in Florida. He is also a member of the EMS Eagles Global Alliance.
A version of this article first appeared on Medscape.com.
1 in 4 Unresponsive Coma Patients May Retain Some Awareness
“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.
“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”
The findings were published online in The New England Journal of Medicine.
Clinical Implications?
Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”
Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.
Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.
In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.
Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.
Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
Response to Commands
Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.
To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.
About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.
Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.
Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.
Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.
The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.
Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.
The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear.
The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
Higher Rate of Awareness Than in Previous Research
The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said.
The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).
Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).
Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.
Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.
Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.
Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”
These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”
All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.
Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.
“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote.
Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
Challenging Research
Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.
“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.”
Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.
“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.
Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources.
“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.”
Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal.
The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.
“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”
The findings were published online in The New England Journal of Medicine.
Clinical Implications?
Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”
Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.
Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.
In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.
Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.
Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
Response to Commands
Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.
To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.
About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.
Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.
Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.
Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.
The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.
Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.
The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear.
The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
Higher Rate of Awareness Than in Previous Research
The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said.
The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).
Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).
Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.
Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.
Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.
Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”
These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”
All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.
Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.
“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote.
Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
Challenging Research
Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.
“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.”
Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.
“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.
Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources.
“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.”
Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal.
The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
“We found that at least 1 in 4 patients who are unresponsive to commands might actually be quite present and highly cognitive,” said study investigator Nicholas D. Schiff, MD, Feil Family Brain & Mind Research Institute and Department of Neurology, Weill Cornell Medicine, Rockefeller University Hospital, New York.
“In other words, if you go to the bedside and carefully examine someone with a severe brain injury and find no evidence of responsiveness, no one has been able to give you an a priori number to say how likely you are to be wrong in thinking this person is actually unaware, not processing language, and not capable of high-level cognitive work. And the answer to that now is at least 1 in 4 times.”
The findings were published online in The New England Journal of Medicine.
Clinical Implications?
Cognitive motor dissociation (CMD) is a condition whereby patients with a severe brain injury who are unresponsive to commands at the bedside show brain activity on functional MRI (fMRI) or electroencephalography (EEG) when presented with selective motor imagery commands, such as “imagine playing tennis,” or “ imagine opening and closing your hand.”
Previous research shows that CMD is present in 10%-20% of people with a disorder of consciousness, a rate similar to that in patients with acute or chronic brain injury.
Understanding that a patient who appears unconscious has signs of cognitive processing could change the way clinicians and family interact with such individuals. Unresponsive patients who are aware may eventually be able to harness emerging communication technologies such as brain-computer interfaces.
In addition, knowing an individual’s CMD status could aid in prognosis. “We know from one study that there’s a four times increased likelihood that patients will be independent in a year in their function if they have cognitive motor dissociation,” said Dr. Schiff.
Unlike most previous studies of CMD, which were conducted at single sites and had relatively small cohorts, this new study included 353 adults with a disorder of consciousness (mean age, 37.9 years; 64% male) at six multinational sites.
Participants were recruited using a variety of methods, including consecutive enrollment of critically ill patients in the intensive care unit and enrollment of those with chronic illness or injury who were in the postacute phase of brain injury.
Response to Commands
Study participants were at different stages of recovery from an acute brain injury that had occurred an average of 8 months before the study started.
To determine the presence or absence of an observable response to commands among participants, trained staff used the Coma Recovery Scale–Revised (CRS-R); scores on this instrument range from 0 to 23, and higher scores indicate better neurobehavioral function.
About 40% of individuals were diagnosed with coma or vegetative state, 29% with minimally conscious state–minus, and 22% with minimally conscious state–plus. In all, 10% had emerged from a minimally conscious state.
Researchers assessed response to timed and repeated commands using fMRI or EEG in participants without an observable response to verbal commands, including those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus, and in participants with an observable response to verbal commands.
Of the 353 study participants, 61% underwent at least one fMRI assessment and 74% at least one EEG assessment. Both fMRI and EEG were performed in 35% of participants.
Dr. Schiff explained the two assessment types provide slightly different information, in that they measuring different types of brain signals. He also noted that although “every medical center in the world” has EEG, many do not have fMRI.
The brain imaging assessments captured brain activity within the motor area of the frontal cortex when tasked with motor imagery.
Of the 241 participants deemed to be in a coma or vegetative state or minimally conscious state–minus on the basis of CRS-R score, 60 (25%) had a response to commands on task-based fMRI, task-based EEG, or both.
The percentage of participants with CMD varied across study sites, from 2% to 45%, but Dr. Schiff said the reason for this is unclear.
The proportion of participants with CMD may have been even higher if all individuals had been assessed with both imaging techniques, he said.
Higher Rate of Awareness Than in Previous Research
The investigators noted that the percentage of participants with CMD in their study was up to 10 percentage points higher than in previous studies. This may be due to the multimodal approach that classified participants undergoing assessment with both fMRI and EEG on the basis of responses on either technique, they said.
The median age was lower among participants with CMD than those without CMD (30.5 years vs 45.3 years).
Compared with participants without CMD, a higher percentage of those with such dissociation had brain trauma as an etiologic factor (65% vs 38%) and a diagnosis of minimally conscious state–minus on the CRS-R (53% vs 38%).
Among people with CMD, 18% were assessed with fMRI only, 22% with EEG only, and 60% with both fMRI and EEG.
Dr. Schiff noted that the use of both fMRI and EEG appears to be more sensitive in detecting brain activity during tasks compared with use of one of these techniques alone.
Of the 112 participants with a diagnosis of minimally conscious state–plus or who had emerged from the minimally conscious state, 38% had a response to commands on task-based fMRI, task-based EEG, or both. Among these participants, 23% were assessed with fMRI only, 19% with EEG only, and 58% with both fMRI and EEG.
Research shows “it’s very clear that people with severe brain injury continue to get better over time,” noted Dr. Schiff. “Every month and week matters, and so it probably is the case that a lot of these patients are picking up the level of recovery, and the later we go out to measure them, the more likely we are to find people who are CMD than not.”
These new results should prompt further study to explore whether detection of CMD can lead to improved outcomes, the investigators noted. “In addition, the standardization, validation, and simplification of task-based fMRI and EEG methods that are used to detect cognitive motor dissociation are needed to prompt widespread clinical integration of these techniques and investigation of the bioethical implications of the findings.”
All study participants with chronic brain injury had survived their initial illness or injury and had access to a research facility with advanced fMRI and EEG capabilities. “This survival bias may reflect greater cognitive reserve and resilience over time among the participants. As such, the results of our study may not be generalizable to the overall population of patients with cognitive motor dissociation,” the investigators wrote.
Another study limitation was that participating sites used heterogeneous strategies to acquire, analyze, and interpret data, which led to differences in the number, type, and ordering of the cognitive tasks assessed on fMRI and EEG.
“These differences, along with variations in recruitment strategies and participant characteristics, may have contributed to the unequal percentage of participants with cognitive motor dissociation observed at each site. Our findings may therefore not be generalizable across all centers,” the researchers wrote.
Only a few academic medical centers have the specially trained personnel and techniques needed to assess patients for CMD — which, the researchers noted, limits the feasibility of performing these assessments in general practice.
Challenging Research
Commenting on the research, Aarti Sarwal, MD, professor of neurology and section chief, Neurocritical Care, Virginia Commonwealth University, Richmond, Virginia, noted that this was a “very challenging” study to perform, given that only a few academic centers are equipped to perform both fMRI and quantitative EEG analysis.
“In general, finding patients this far out, who have access to clinical, radiological, and electrophysiological testing and were provided good care enough to receive these, is a mammoth task in itself.”
Dr. Sarwal said the study builds on efforts of the Curing Coma campaign , a clinical, scientific, and public health effort of the Neurocritical Care Society to tackle the concept of coma as a treatable medical entity.
“It continues to highlight the challenges of prognostication in acute brain injured patients by showing a higher presence of cognitive function than previously perceived,” she said.
Dr. Sarwal believes that the study’s largest impact is underscoring the need for more research into understanding the degree and quality of cognitive processing in patients with a disorder of consciousness. But it also underlines the need for a “healthy debate” on the cost/benefit analysis of pursuing such research, given the limited number of patients with access to resources.
“This debate needs to include the caregivers and families outside the traditional realms of stakeholders overseeing the science.”
Although communication with comatose patients is still “a ways away,” this research is “a step in the right direction,” said Dr. Sarwal.
The study was funded by the James S. McDonnell Foundation and others. Dr. Schiff and Dr. Sarwal report no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE