Posted August 16, 2016
Andriy Batchinsky, M.D., U.S. Army Institute of Surgical Research
Combat explosions rose significantly, from 18% to 69%, between 2003 and 2005, resulting in an increased number of combat-related burn injuries1 . Acute lung Injury (ALI), and its most severe form, Acute Respiratory Distress Syndrome (ARDS), often result from smoke inhalation, which is especially detrimental to those who suffer burn injuries. Patients who acquire ALI and ARDS from combat-related burns are characterized by the sudden onset of edema in the lungs, leading to decreased exchange of oxygen and carbon dioxide. Approximately 33% of mechanically ventilated Warfighters with burn injuries develop ARDS, and this often prevents them from returning to duty1,2 . Recent studies also indicate mortality rates significantly increase for burn victims whom develop ARDS2. Additionally, mortality rates were found to increase with ARDS severity with mild, moderate, and severe ARDS diagnoses accounting for mortality rates of 11.1%, 36.1% and 43.8%, respectively2 . The mortality rate for burn victims who do not develop ARDS was 8.7%2 . Current treatment options for ALI and ARDS are limited to supportive care such as use of a mechanical ventilator, which exacerbates ALI and leads to multiorgan failure. Developing guidelines for the use of new, minimally invasive therapeutic interventions for ALI and ARDS will enable both early treatment and standardization, while decreasing the need for mechanical ventilation.
Dr. Andriy Batchinsky, Research Scientist at the U.S. Army Institute of Surgical Research, studies and develops both noninvasive and invasive techniques to treat ARDS due to smoke inhalation, burns and combined models of trauma. With FY12 funding from the Military Burn Research Program (MBRP), Dr. Batchinsky is carrying out a comprehensive benchmarking study of three minimally invasive extracorporeal gas exchange (ECGE) devices: the Hemolung® (Alung Technologies, USA), the MiniLung® Petite System (Novalung, Xenios, Germany), and the Cardiohelp (Maquet Cardiopulmonary, USA). These miniaturized, self-operating, and portable ECGE devices are evaluated for therapeutic feasibility and improved outcomes in combat-burn patients. Using an animal model, the therapeutic efficacy of the ECGE devices is evaluated for their ability to lower injurious ventilator settings during transport and to reduce inflammatory responses, thereby preventing the onset of ARDS. Preliminary data obtained in the first two years showed that all the devices enabled removal of nearly 50% of metabolically produced CO2 and significant (from 25%–50%) reduction in minute ventilation settings at blood flow rates ranging from only 500–800 milliliters/min using 15F-18F catheters. This alone is an improvement over traditional methods of extracorporeal life support utilizing large catheters (27F-32F) that require blood flow rates of 2 to 5 liters/min. Decreasing the high mechanical ventilator settings has a crucial effect on reducing ventilator-induced lung injury. Recently acquired benchmarking data suggests that the NovaLung Mini Lung Petite device is the most versatile and therapeutically efficient because it can be connected to oxygenators of various sizes (pediatric to large size) – all within the same system which can address ARDS of varying severity.
The clinical practice guidelines on minimally invasive extracorporeal life support as adjunct to mechanical ventilation were recently published with respect to the Pump-Assisted Lung Protection (PALP) device6 . Similar publications will follow for the Hemolung® and NovaLung (Xenios) devices. Cytokine profiles for inflammatory expression as well as coagulation data for ECGE circuits and membrane oxygenators are currently being collected and analyzed. This work was recently published in the American Society of Artificial Organs (ASAO)3 and Critical Care Medicine (CCM)4,5 .
Through another FY12 MBRP award, Dr. Batchinsky is identifying ways to treat ARDS using freshly harvested autologous concentrated bone marrow aspirate (cBMA) and cultured allogeneic mesenchymal stem cells (MSCs). The goal is to show that use of point-of-care cell therapies improves oxygenation and reduces the production of inflammatory mediators (e.g., MIP-2, IL-8, and TNF-alpha) in ARDS. Dr. Batchinsky’s team is conducting experiments to compare the therapeutic effectiveness of cBMA and cultured MSCs to treat ARDS in swine. As a result of this work, a new cell-based approach to management of patients with lung failure is being developed, thereby providing life-sustaining respiratory support and possible early lung epithelial and endothelial cellular regeneration during evacuation of mechanically ventilated combat-burn casualties. To date, a novel clinical protocol which demonstrates that repeat point-of-care treatment with cBMA and MSCs improves oxygenation and delays ARDS by approximately 45-60 hours has been developed. A standard operating procedure of standard harvesting, culturing, and therapeutic administration that will form the basis for a clinical practice guideline on bedside utilization of MSCs in ARDS and multi-organ failure has also been created. Parameters for in vivo stem cell administration have also been standardized to yield a consistent high dose of 9-10x106 cells per kilogram per day on average. The preclinical efficacy of the stem cell therapies was vigorously tested and the therapeutic properties of the cells were investigated in detail. Results obtained in severely injured animals suggest that early interventions with stem cells staved off severe ARDS and prolonged life. In addition, the stem cells from these animals were more actively recruited from bone marrow during critical illness. In light of these results, Dr. Batchinsky recently filed a patent for the treatment of lung injury with aerosolized and extremely cooled stem cells.
Management of ALI and ARDS is a major step for advancing care of critically injured burn patients. Dr. Batchinsky’s work from these two awards offers modern solutions for Soldiers and civilian patients with severe lung injuries, as well as those patients receiving mechanical ventilation for any reason.
1 Kauvar DS, Wolf SE, Wade CE, Cancio LC, Renz EM, and Holcomb JB. 2006. Burns sustained in combat explosions in Operations Iraqi and Enduring Freedom (OIF/OEF explosion burns). Burns 32(7):853-857.
2 Belenkiy SM, Buel AR, Cannon JW, Sine CR, Aden JK, Henderson JL, Liu NT, Lundy JB, Renz EM, Batchinsky AI, Cancio LC, and Chung KK. 2014. Acute respiratory distress syndrome in wartime military burns: application of the Berlin criteria. J Trauma Acute Care Surg 76(3):821-827.
3 Scaravilli V, Kreyer S, Linden K, Belenkiy SM, Pesenti A, Zanella A, Cancio LC, and Batchinsky AI. 2015. Enhanced extracorporeal CO2 removal by regional blood acidification: effect of infusion of three metabolizable acids. ASAIO, doi: 10.1097/MAT.0000000000000238
4 Kreyer S, Scaravilli V, Linden K, Belenkiy S, Necsoiu C, Putensen C, Chung KK, Cannon J, Cancio LC, and Batchinsky AI. 2015. Early utilization of extracorporeal CO2 removal for treatment of acute respiratory distress syndrome due to smoke inhalation and burns in sheep. CCM, doi: 10.1097/SHK.0000000000000471
5 Scaravilli V, Kreyer S, Belenkiy S, Linden K, Zanella A, Cancio LC, Pesenti A, and Batchinsky AI. 2015. Extracorporeal CO2 removal enhanced by lactic acid infusion: effect on spontaneous breathing in conscious sheep. CCM, doi: 10.1097/ALN.0000000000000995
6 Morimont P, Batchinsky A, Lambermont B. Update on the role of extracorporeal CO2 removal as an adjunct to mechanical ventilation in ARDS. Crit Care 2015;19:117.