Maturing Capability for Enabled Care

COL Jerome Buller
Commander
U.S. Army Institute of Surgical Research

From Combat & Casualty Care, Q3 Summer 2019 Issue

A Louisiana native, Colonel Buller began his military career in the enlisted ranks in 1982 as a Medical Laboratory Specialist. In 1985, he left active duty and entered the Louisiana Army National Guard while completing his undergraduate studies. During his undergraduate training, he concurrently attended Officer Candidate School at the Louisiana State Military Academy, where he was the distinguished honor graduate, followed by completion of the Infantry Officer Basic Course at Ft. Benning, Georgia. His first assignment as a military officer was as a platoon leader with C Co., 3rd Battalion, 156th Infantry Regiment.

After earning his medical degree, Colonel Buller completed his residency training in Obstetrics and Gynecology at Madigan Army Medical Center in Tacoma, Washington, followed by a three-year fellowship in Urogynecology and Reconstructive Pelvic Surgery at the Johns Hopkins Hospital in Baltimore, Maryland. He then served as the Chief of Urogynecology at Walter Reed Army Medical Center. In 2003, he deployed with the 801st Combat Support Hospital in support of Operation Iraqi Freedom. While serving as the Division Surgeon for the 1st Armored Division from 2006 to 2009, Colonel Buller again deployed in support of Operation Iraqi Freedom as the Multi-National Division-North Surgeon.

Colonel Buller, as an associate professor, served as the Director of the Telerobotics and Advanced Minimally Invasive Surgery Program and the OB/GYN Director of Simulation Education at Uniformed Services University, until June 2011. At USU, he was the Program Director for the National Capital Consortiums Fellowship in Female Pelvic Medicine and Reconstructive Surgery and also later served as Assistant Chief, Department of Obstetrics and Gynecology at Walter Reed Army Medical Center. After a one-year tour as the Command Surgeon for the National Defense University, Colonel Buller completed senior service college at the Dwight D. Eisenhower School for National Security and Resource Strategy. He subsequently was assigned as the Director, Directorate of Communications, Office of The Surgeon General and the U.S. Army Medical Command from July 2013 to May 2015 and as the Executive Officer to the Army Surgeon General from May 2015 to February 2016. From March 2016 to June 2018 he served as Brigade Commander, Uniformed Services University (USU) in Bethesda, Maryland, a DoD organization with over 1,500 Army, Navy, Marine, Air Force, and Public Health Service personnel. As Brigade Commander he was the senior active duty military officer and principal military advisor to the President of the University and the Deans of the School of Medicine, Graduate School of Nursing and Post-Graduate Dental College. He partnered with academic faculty on all matters of military affairs to ensure optimal development of U.S. and international students as military medical leaders.

Combat & Casualty Care spoke recently with COL Jerome Buller, Commander, U.S. Army Institute of Surgical Research (USAISR), regarding various capabilities in surgical trauma care that USAISR is working to advance to a fieldable state of readiness.

C&CC: Provide some background into trends in field surgical care that USAISR is focused on to the present.

COL Buller: Since the inception of this Institute in the 1940’s, we have focused on providing novel products and information that drive evidence-based, best clinical practice solutions and deliver advanced technologies to the Warfighter. The medical and medical research activities that we perform are focused on saving lives on todays’ and tomorrow’s battlefield. We are the home of the only Burn Center in the Department of Defense and the synergy between our laboratory scientists and clinical researchers makes us the U.S. Government’s premier translational research center focusing on trauma, burns, and critical care of the combat wounded because we are able to take clinical problems to the laboratory and translate laboratory advances to the clinic, operating room, or the battlefield.

For example, in the early and mid-2000s we helped launch the modern tourniquet era. We validated several tourniquets, most notably the Combat Action Tourniquet (CAT) and conducted clinical studies on combat casualties that documented the life-saving effects of tourniquet application in casualties at risk of exsanguination from extremity injuries. We also performed a number of validation studies on junctional tourniquets, as well as studies on user training designed to reduce the incidence of tourniquet failure due to user error. Ongoing and future work will focus on development of “smart” tourniquets that can detect loss of hemorrhage control and potentially self-adjust to reduce risk of failure. In addition, studies are ongoing to help develop strategies for conversion from tourniquet to pressure dressing, thus reducing the risk of prolonged limb ischemia and amputation or poor functional outcome. One potential solution being explored is isolated limb perfusion in which blood or other resuscitation fluids could be perfused distal to the tourniquet to maintain viability of the limb without risking exsanguination of the patient.

We also helped launch the age of the modern hemostatic dressing. Prior to the Iraq conflict, the primary option for wound dressing was the venerable cotton gauze bandage. That’s the same bandage used in similar format since the dawn of medicine in Ancient Egypt. Our research explored dressings incorporating fibrinogen as clot substrate, kaolin as a clot accelerator, chitosan for its muco-adhesive properties, and other substances to enhance hemostasis. Ultimately, kaolin-impregnated gauze, known as “Combat Gauze” was chosen for use by our Warfighters based on performance and cost. We are continuing to evaluate potentially improved dressings.

For non-compressible hemorrhage, intravascular approaches to hemorrhage control prior to the availability of surgical management have shown great promise, in particular, Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). This approach dates from enterprising work of Army surgeons in the Korean War and was made practical through the pioneering work of Air Force surgeons, Todd Rasmussen and Jonathan Eliason, who developed devices that could safely be placed without the use of fluoroscopic guidance, thus making them practical for battlefield use. We continue to advance hemorrhage control by exploring how REBOA can used with other technologies to sustain patients at risk for or in hemorrhagic shock. A limitation of REBOA is that it occludes blood flow distal to the occlusion site, limiting blood loss from damaged tissue but also starving healthy tissue of oxygen-carrying blood. We are studying ways to improve perfusion of healthy tissue distal to the REBOA occlusion.

Another approach to controlling hemorrhage in the abdomen, where it cannot be readily controlled by external pressure, is to introduce a space-filling substance like a polymer foam into the abdominal cavity to provide pressure on bleeding vessels in a manner similar to the urethane foam used to re-inflate a flat tire (“fix a flat”). We have worked with industry partners to test this approach and work continues in this area.

Also, the concept of Damage Control Resuscitation (DCR) was developed from the U.S. military experience in Iraq, and we play a central role. DCR was the natural extension of the Damage Control Surgery (DCS) concept proposed by surgeons at the University of Pennsylvania in the mid-90s. DCS prioritizes hemorrhage control surgery and defers staged, definitive repair of injury-induced anatomic defects until after physiologic stabilization. DCR incorporates a modern understanding of the role of blood products in restoring hemostatic function and oxygen delivery while preventing the physiologic disturbances such as acidosis, dilution and hypothermia associated with the administration of intravenous fluids such as normal saline or lactated ringer’s solution, which were the mainstays of resuscitation prior to the wars in Iraq and Afghanistan. Recent improvements to DCR based on our research and in collaborating research groups funded by the DoD includes the adoption of 1:1:1 transfusion ratios of red blood cells, plasma and platelets, in an approximation of whole blood, for patients requiring resuscitation from hemorrhagic shock.

More recently whole blood, particularly blood from group O donors with low titers of anti-A and anti-B antibodies (low titer O whole blood or LTOWB), has been widely adopted in military and civilian trauma programs for urgent resuscitation of exsanguinating patients. Finally, analysis of data from the DoD Trauma Registry (DoDTR) revealed that early (within the first 30-40 minutes post-injury) blood transfusion was the single most important factor in decreasing combat casualty mortality. Therefore, our research and development efforts have been focused on improving the delivery of blood to the point of injury on the battlefield through shelf life extension, improved storage and delivery systems and the development of products that extend the therapeutic effects of blood in shocked trauma patients.

Additionally, the Blood Far Forward (BFF) concept grew from the observation that delaying resuscitation in hemorrhaging patients would essentially increase shock depth and duration or shock dose, and that doing so would worsen outcomes. In Basic Life Support (BLS), CPR is started as soon as cardiac arrest is diagnosed to minimize duration of tissue hypoperfusion; so it is with hemorrhage: the heart does not need to be compressed, it needs to be filled with blood. Anecdotal observations from WWI suggested that the common sense remedy to blood loss might be replacement of lost blood. A century of experimentation with every conceivable alternative to blood for hemorrhage resuscitation has not yielded a better alternative. U.S. and United Kingdom forces in Afghanistan fielded blood products in the pre-hospital setting and the outcomes of these interventions were captured in the DoDTR. The results are clear by looking at the data: early resuscitation of hemorrhaging patients with blood resulted in decreased mortality. These results have also been confirmed in randomized trials conducted at several locations in the U.S. So some of our current research efforts are focused on delivering blood products with both oxygen carrying capacity and hemostatic function in the pre-hospital setting.

Something else that we have done is to realign some of our research efforts to better support multi-domain operations (MDO). Swift medical evacuation may not be an option; ensuring that Warfighters remain mission capable even while injured is crucial. Previously, some of our research efforts focused on decreasing complications of open fractures (primarily preventing infection and nonunion) and improving long term outcomes by restoring function by regenerating missing skeletal muscle. With the anticipated inability to quickly evacuate casualties, infections will go from becoming a complication to limb and life-threatening. Fractures and soft tissue injuries will take able bodied Warriors out of the fight in order to care for those who have been injured until they get medevacked. Tourniquets, which saved lives and caused little to no morbidity in recent wars, will likely cause loss of limb and even life when left on too long. So, we are focusing on getting solutions into the hands of medics and Warfighters like local antimicrobial irrigants and other treatments to prevent infection; an exoskeleton or brace that will allow wounded Warriors with lower extremity wounds to remain mobile and stay in the fight; and strategies to allow tourniquets to remain on limbs safely for longer periods of time.

C&CC: With a growing focus on prolonged field care (PFC), talk about some focus areas of field surgical care that USAISR is working to promote.

COL Buller: We are working on delivering hemorrhage control products and blood products for far forward resuscitation, without which there will be no prolonged field care (bleeding, non-resuscitated patients simply die). We are also working on pharmaceutical interventions that increase the body’s ability to handle the metabolic stress of shock so that blood-based resuscitation will be even more effective. Furthermore, we are developing diagnostic technologies and decision support systems that will enhance the ability of the combat medic to diagnose life-threatening bleeding and intervene with the right products at the right time to the right patient.

One of our research departments, funded by Telemedicine and Advanced Technology Research Center or TATRC, is working to provide an overall life support system, parts of which initially can be placed on the ground or a stretcher with a wounded Warrior. Then, given availability transport, these components would be attached to the stretcher in compact form and managed by an autonomous master controller maximizing the stabilization and maintenance of a casualty, to include transfusion control, continued aspiration, respiration support, REBOA catheter balloon control, and potentially extracorporeal membrane oxygenation (ECMO) and many other life support systems. Ideally, our goals for this system will be compactness, ruggedness, and simplicity, so components can be quickly attached to a stretcher and loaded onto an unmanned aerial vehicle, unmanned ground vehicle, or manned transport.

Additionally, we now have the capability to support research protocols designed to address field surgical care concerns. This capability allows us to perform long-term intensive care research studies to address prolonged field surgical care in the same focus areas that I’ve described above.

C&CC: From a damage control surgery (DCS) perspective, what are some challenge areas USAISR is shedding light on to better point of injury surgical care?

COL Buller: Autonomous systems that aid in intelligent tourniquet deployment and vascular access will greatly improve care at the point of injury. We hope to show that autonomous systems will help the clinician accurately assess patient’s condition, deliver clinical care guidance and potentially improve outcomes when timely medevac is not available and/or when operating in resource constrained environments.

We are developing software and evaluating use cases for usage in the field by clinicians trained at different levels of care. We expect augmented reality to have several roles to fulfill: bidirectional communication tool to facilitate the skills of the trained physician at the location of the untrained medic or first responder; a convenient deployment platform for decision support apps; a light-weight display tool to provide displays of medical devices without the traditional size and weight of conventional medical devices; niche rolls in dark or noisy environments where sight or sound cannot be effectively utilized, such as transport on an aircraft; and an enabler for hand-free operation.

Also, as mentioned before, tourniquet use has proven to be an extremely effective tool in controlling bleeding; however, extended use of tourniquets can be detrimental to limbs due to the lack of tissue perfusion. This can lead to limb dysfunction and/or amputation. Finding novel approaches to extend tourniquet time is absolutely essential due to the decrease in evacuation time.

Additionally, traumatic eye injuries are a common occurrence and a leading cause of blindness in military Warfighters. Unlike civilian corneal trauma, battlefield ocular trauma involves high morbidity with complex multiple full thickness lacerations, severe ocular hypotony, or intraocular pressure and iris prolapse, which happens when the iris tissue is outside of the wound. Another issue is the loss of intraocular fluids due to gaping corneal wounds, which results in damage to the posterior segment, including retinal detachment and choroidal hemorrhage. So we’re looking for interventions that can temporarily stabilize the eye and seal corneal wounds to protect it until the appropriate clinical treatments or operative procedures can be performed.

C&CC: As capabilities advance what’s possible in field surgical care, such as telemedicine and even robotics, speak to some areas USAISR sees as most promising.

COL Buller: We are developing capabilities such as miniaturized extracorporeal life-support (ECLS) that will make it possible to provide care that has previously been available only in the hospital setting. Our goals is to provide this capability for our troops in the field and during transport. ECLS is a life-saving therapy that involves taking part of the patient’s blood out of the body through a system of small tubes, similar to dialysis, and then returning it back after adding oxygen and removing carbon dioxide (replacement of lung function); removing waste products (replacing kidney function). ECLS can also be connected to the patient in a way that permits replacing the patient’s heart function, thus making ECLS useful for returning circulation to patients who suffer cardiac arrest, myocardial infarction or severe trauma with stoppage of the heart. Various iterations and efforts on ECLS are ongoing within the DoD from miniaturized wearable system testing to development of new prototypes, to making the plastic catheters of ECLS circuits friendly to blood.

Also, the evolving theme in trauma and critical care medicine generally is that earlier intervention prevents problems and improves outcomes compared to reactive strategies that attempt to reverse established patterns of organ failure. Overall, we are teaming up with our collaborators to seek technologies that enable a shift from in-hospital care to delivery of advanced care at the point of injury and during patient transport. ECLS, REBOA and semi-autonomous/autonomous surgical intervention technologies represent a suite of technologies that would move the most advanced life support systems available in Level One trauma centers and move them to far forward environments. ECLS, as currently implemented, generally depends on heparin anticoagulation to prevent circuit thrombosis. This is not compatible with the care of trauma patients who have not had definitive surgery to repair all injury-induced anatomic defects. A major goal of our research is to design ECLS systems that do not require anticoagulation medicine.

Also, REBOA is effective in controlling hemorrhage but results in ischemia in large vascular beds, often involving uninjured tissue, which thus suffers an iatrogenic insult. Some or our research aims to develop strategies to use REBOA to prevent exsanguination while maximizing perfusion of uninjured tissues. Eventually, these efforts will contribute to development of semi/autonomous systems that may be able to carry out life-saving interventions on combat casualties.

On telemedicine, we are looking at how to improve clinical performance and decision making when taking care of a critically ill patient in a prolonged field care environment. We are also investigating how local decision support systems can correspondingly improve clinical performance and workload when communications are down and telemedicine is not available. Additionally, we are researching how multiple medical algorithms can be combined to eventually be used in a semi-autonomous medical evacuation system.

We are also conducting research in novel technologies such as augmented reality; it has immense capabilities, such as line of sight visualization and holographic imagery that overlays on top of the real environment. This helps to provide additional information to help guide medics through complex procedures such as mapping a body and providing context for incisions. For example, we are developing holographic overlays on where incisions must be done for an escharotomy in order to properly release the compression for adequate perfusion and movement. Additionally, augmented reality devices can bring in a remote expert who can see in “first-person view” what the medic is undertaking to provide additional support when performing complex surgical procedures.

Similarly, we are working with TATRC and Stanford University for semi-autonomous surgical intervention using medical robotics. Through a collaborative effort, we are implementing virtual reality systems to remotely control a medical robotic system while also implementing artificial intelligence to complete surgical procedures when connectivity is lost.

Lastly, we want to develop an external fixation device (exoskeleton) that can help a Warfighter ambulate which would decrease the number of personnel required to care for that individual to free up more resources on the battlefield.

C&CC: Feel free to speak to other goals/challenges moving forward.

COL Buller: We are working with our colleagues at our headquarters, U.S. Army Medical Research and Development Command, U.S. Special Operations Command (SOCOM) and the Armed Services Blood Program (ASBP) to expand the program that supplies freeze-dried plasma (FDP) produced by the French Military to SOCOM. Specifically, plasma collected by ASBP will be sent to France for freeze-drying and then returned to the U.S. for distribution to U.S. forces. We have played a central role in the development and maintenance, and recently, in the expansion of this program. We continue to conduct stability studies on the FDP product and to inform our leaders and the Food and Drug Administration on product function and viability.

The DoD is funding a randomized clinical trial comparing the safety and efficacy of hemoglobin-based oxygen carriers (HBOCs) with or without FDP in the resuscitation of bleeding trauma patients compared to crystalloid fluids. The study will be performed in South Africa where these products are licensed. Ultimately, this study will assess the viability of HBOCs with/without FDP as a bridge therapy to blood transfusion in hospital. If successful, the combination of HBOC with/without FDP would be a much more logistically sustainable point of injury care bundle than labile blood products and would significantly increase resuscitation capability far forward.

At present, ECLS, or extracorporeal life support, is the flagship product within DoD as the next most promising life-saving technology. Various iterations and efforts on ECLS are ongoing within the DoD from miniaturized wearable system testing to development of new prototypes, to making the plastic catheters of ECLS circuits friendly to blood. We have formed a new department to lead these efforts.

For our burn casualties, we know that there’s a need for a temporizing burn treatment. Burns sustained in Iraq and Afghanistan constitute five to 10 percent of injuries. Burns to a small surface area can be incapacitating for the Warfighter and strain the resources available for deployed military medical units. Burn patietns are particularly vulnerable to infections with more than 75 percent of all burn deaths (after initial resuscitation) result from infection.

For military burn injuries, the standard of care is described in the chapter “Burns” in the Emergency War Surgery Handbook. After burn casualties are stabilized, including fluid resuscitation, early burn wound care should be provided in a clean warm environment. The wound should be thoroughly cleansed with a surgical detergent such as chlorhexidine gluconate, followed by the application of topical antimicrobials. The topical antimicrobials include: 5 percent Sulfamylon solution applied to the dressings to maintain their moisture about every eight hours; and, the creams, Silvadene or Sulfamylon, applied as often as needed to keep the burns covered. Cream to cover a 20 percent total burn surface area burn weighs about 400 grams, just under a pound, which is not ideal for point of injury and for prolonged field care. While Silverlon has advantages during casualty transport because it can be kept in place for 72 hours, its effectiveness depends on continuous moistening with water that may be in short in supply, which over longer periods risks oversaturation and possible hypothermia and maceration. Moreover, the existing standard of care is not designed to temporize burn wounds to limit deterioration and allow delayed excision and grafting.

In recent conflicts, burn casualties have been evacuated to our Burn Center in San Antonio, Texas, where they arrive on average about four days after injury for definitive care, including skin grafting. However, in future conflicts the time until definitive care may be delayed a week, or longer. We are developing the temporizing wound dressing to stabilize burn wounds for better outcomes.

For battlefield pain control, we are investigating and developing solutions that will close multiple critical knowledge gaps for pain management which includes inadequate alternatives to current opioid analgesics for severe pain management by the medic/corpsman on the battlefield; inadequate acute pain management in deployed locations, including battlefield and resource-limited environments; and inadequate strategies for management of acute pain under the care of a clinician in non-deployed settings. This research into novel compounds for analgesic efficacy will provide the valuable preliminary data required for eventual FDA submission and use in human trials. It is expected that the novel compounds tested will provide analgesic efficacy as evidenced by a reduction in pain related behavioral responses in a thermal injury research. It is also expected that the novel compounds, when paired with opioids, will provide analgesic synergy, thus reducing opioid requirements and their side effects. We expect that if a novel compound shows analgesic efficacy equal to opioids then the novel compound would be a candidate to replace opioids for combat medics. This could potentially completely eliminate physiological and cognitive deficits experienced when taking opioids; as well as, negate the possibility for abuse and diversion. If the novel compound is not as efficacious as opioids but does show analgesic synergy then it may be possible to reduce opioid amounts while providing the same level of analgesia. Combat medics could then carry less opioid analgesics and therefore reduce the potential for physiological and cognitive side effects as well as abuse and diversion.

As you can see, we have done a lot of work for our combat wounded, but we still have a lot of work to do. We’re excited about the direction in which our research is taking us. It’s all about our Warfighters who deserve the best care from point of injury to definitive care. We strive every day to fulfill our mission of “optimizing combat casualty care” on today’s and future battlefields.