Sprayable Foam: Limiting Blood Loss on the Battlefield

Sprayable Foam: Limiting Blood Loss on the Battlefield

Posted: April 12, 2016 | By: Matthew Dowling

Combat survivability is at an all-time high, however caring for the wounded on the battlefield is an ongoing challenge for military forces. The ability to quickly stabilize the injured on-site increases
the likelihood of successful treatment and transport to a medical facility. Between 2001 and 2011, hemorrhage, or uncontrolled blood loss, represented more than 80 percent of potentially
survivable battlefield deaths. [1] With improved medical technologies and techniques, hemorrhage control and survivability could significantly increase.

Non-compressible injuries are difficult for field medics to control, and therefore, the majority of deaths occur before transporting the patient to a hospital. [2,3] The current protocol for field treatment of hemorrhage, according to Tactical Combat Casualty Care guidelines, is to apply tourniquets and other topical agents, such as Combat Gauze, to the affected area. [4] Topical hemostatic sealants may be used as adjuncts in cases where conventional measures for bleeding control fail, but the majority of these products are bandages or powders that require compression and wound visibility. [5] These attributes make the protocol products ineffective in treating non-compressible wounds, such as those in the groin or neck. [6]

The capability gap is evident. The Defense Health Agency is currently assessing technologies to address the unmet medical need of hemorrhage control. [7] The lack of a readily available capability for non-compressible hemorrhage is a high research priority for the Department of Defense. [8]

When wounded, the body naturally begins the healing process by clotting the blood. A network of proteins comes together to form an insoluble barrier, preventing further blood loss. [9]

Many experiments on alternate clotting technologies, such as fibrinogen- coated albumin microparticles, thrombin-based hemostatic agents, lyophilized platelets and conjugated red blood cells, show insignificant outcomes on both compressible and non-compressible hemorrhage wounds. [10,11] These experimental hemostatic agents were not only ineffective, but expensive, required refrigeration and, in some cases, caused septicemia. [12]

Currently available products, such as proteins and aluminosilicates, contain significant challenges for use in military environments. Protein formulations are expensive and degrade in hot climates, making them impractical for use in current theaters of operation, such as Iraq and Afghanistan. [13] Aluminosilicates are inexpensive, but may be toxic and cause permanent tissue damage when administered. [14] Scientists created an artificial clotting process that mimics natural clotting principles. The research resulted in the development of a hemostatic bandage that will stop the flow of blood. This development, if implemented in both military and civilian trauma centers, will increase survivability. [15]

Additionally, scientists developed a hemostatic foam, which uses a compound of widely available and cost effective naturally occurring biopolymers. [16] The foam uses chitosan, the second most abundant biopolymer on earth, which functions similarly to the natural healing process. [17] Chitosan is a polysaccharide, obtained by modifying chitin, a naturally occurring compound found in crustaceans. [18] Scientists add hydrophobic tails, creating a hydrophobically modified chitosan, which allows the biopolymer to self-assemble into gellike physical seals upon contact with blood. [15]

The blood cells integrate into a matrix connected by the hm-chitosan, creating a gel network to stop the blood flow. The gelation activates only at the contacting interface of the wound site; therefore, the hm-chitosan will not cause clotting in undesirable areas of the body. [15] The blood cells agglutinate rapidly into a large 3-dimensional network, creating a gel that forms a strong bond and inhibits bleeding. [19]

Once at the hospital, medical personnel remove the hemostatic patch by adding α-cyclodextrin, which reverses the hemostatic gel and neutralizes the foam, rendering the hydrophobic properties of the hm-chitosan ineffective. [19]

Hm-chitosan is used commercially as a compressible hemostatic agent, but aerosolized hemostatic foam has not been utilized. [20] The hm-chitosan- modified aerosol produces a foam dispensed from a standard, lightweight, pressurized aluminum canister, making it a practical tool for field medics. The compact canister does not require refrigeration and does not expire. [20] Soldiers would be able to carry the products and treat wounds onsite, speeding response time and improving survivability. In addition, the foam could potentially be self-administered. [21]

Because of its self-expanding properties, the hemostatic foam fills the cavities of non-compressible wounds rapidly, reducing blood loss and improving survival. The foam uses the same principles of hm-chitosan by converting the liquid blood into a self-supporting gel.

In pre-trial tests, the foam lessened blood loss from a non-compressible bleed in a pig liver. In the experiment, scientists allowed the liver to bleed for one minute. After one minute, they applied the foam to the injury site, monitored the site for hemostasis and recorded the total blood loss. Different concentrations (5 percent, 2.5 percent and 1 percent of available amines along the chitosan backbone) of hydrophobic modifications to the chitosan foam were tested. [22]

Hemostasis was achieved immediately and sustained over the duration of the experiment with hm-chitosan foams. The experiments’ results showed the 5 percent hydrophobically-modified
chitosan foam was the most effective, decreasing blood loss by 90 percent. [23] The hydrophobes increase stability and promote interaction between the hm-chitosan foam and the blood cells at the injury site, while showing no significant toxicity to the cells. [20]

The ability to control blood loss on the battlefield will be a significant factor in increasing survivability of wounded soldiers. The use of an aerosolized hemostatic foam agent will, additionally,meet the DoD’s requirements for a cost-effective, easy to use and resilient technology.

References

  1. Kime, P. (2013, March 29). Study: 25 % of war deaths medically preventable. Army Times, 21-22. http://archive.armytimes.com/article/20120628/NEWS/206280315/Study-25-war-deaths-medically-preventable (accessed January 28, 2016).
  2. Kelly, J. F., Ritenour, A. E., Mclaughlin, D. F., Bagg, K. A., Apodaca, A. N., Mallak, C. T., . . . Holcomb, J. B. (2008). Injury Severity and Causes of Death From Operation Iraqi Freedom
    and Operation Enduring Freedom: 2003-2004 Versus 2006. The Journal of Trauma: Injury, Infection, and Critical Care, 64(Supplement).
  3. Kotwal, R. S. (2011). Eliminating Preventable Death on the Battlefield. Arch Surg Archives of Surgery, 146(12), 1350.
  4.  Kotwal, R.S. et al. (2014). The Tactical Combat Casualty Care Casualty Card. TCCC Guidelines. http://www.chinookmed.com/TCCC-Change-Prop-1301-TCCC-Card.pdf (accessed January 28, 2016).
  5.  Glick, J.B. et al. (2013). Achieving Hemostasis in Dermatology—Part II: Topical Hemostatic Agents. Indian Dermatology Online Journal, 4(3): 172-176. Doi: 10.4103/2229-5178.115509
  6. Cobden, R.H. et al. (1976). Topical Hemostatic Agents to Reduce Bleeding from Cancellous Bone. A Comparison of Microcrystalline Collagen, Thrombin, and Thrombin-soaked Gelatin Foam. Journal of Bone and Joint Surgery American Volume, 58(1): 70-73.
  7. Pusateri, A.E. (2014). Unmet Medical needs in Prehospital Hemorrhage Control: DoD Perspective. Defense Health Agency. http://www.fda.gov/downloads/MedicalDevices/NewsEvents/WorkshopsConferences/UCM415997.pdf (accessed January 28, 2016).
  8. Eastridge, BJ, et al. (2011). Died of Wounds on the Battlefield: Causation and implications for Improving Combat Casualty Care. J Trauma, 71(1 Supplement): S4-8.
  9. Saito, H., Matsushita, T., & Kojima, T. (2011). Historical perspective and future direction of coagulation research. Journal of Thrombosis and Haemostasis, 9(1), 352-363. doi:10. 1111/j.1538-7836.2011.04362
  10. Beekley AC, Sebesta JA, Blackbourne LH, et al. Prehospital tourniquet use in operation Iraqi Freedom: effect on hemorrhage control and outcomes. J Trauma 2008;64:S28.
  11. Hawksworth JS, Elster EA, Fryer D, et al. Evaluation of lyophilized platelets as an infusible hemostatic agent in experimental non-compressible hemorrhage in swine. Journal of
    Thrombosis and Haemostasis 2009; 7, 1663-1671
  12. Wilsonson, W.C., Grande, C.M., and Hoyt, D.B. (2007). Trauma: Resuscitation, Perioperative Management and Critical Care. Taylor and Francis Group: New York.
  13. Camp, M.A. (2014). Hemostatic Agents: A Guide to Safe Practice for Perioperative Nurses. AORN Journal, 100(2): 131-147. DOI: http://dx.doi.org/10.1016/j.aorn.2014.01.024
  14. Savitsky, E., ed. Combat Casualty Care: Lessons Learned from OEF and OIF. Office of the Surgeon General, Department of the Army. 2012.
  15. Dowling, M., Kumar, R., Keibler, M., Hess, J., Bochicchio, G., & Raghavan, S. (2011). A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action. Biomaterials, 32(13), 3351- 3357. doi:10.1016/j.biomaterials. 2010.12.033
  16. Ige, O.O. et al. (2012). Natural Products: A Minefield of Biomaterials. International Scholarly Research Notices, Materials Science, Article ID 983062, 20 pages. doi: 10.5402/2012/983062
  17. Bochicchio, G. et al. (2009). Use of a Modification Chitosan dressing in a Hypothermic Coagulaopathic Grade V Liver Injury Model. The American Journal of Surgery, 198(5): 617-622.
    doi: 10.1016/j.amjsurg.2009.07.028
  18. Lewandowska, K. (2015). Characterization of chitosan composites with synthetic polymers and inorganic additives. International Journal of Biological Macromolecules, 81, 159-164. doi: 10.1016/j.ijbiomac. 2015.08.003
  19. Philippova, O.E. and Korchagina,E.V. (2012). Chitosan and Its Hydrophobic Derivatives: Preparation and Aggregation in Dilute Aqueous Solutions. Polymer Science, Ser.A, 54(7): 552-572. doi: 10.1134/ S0965545X12060107
  20. Dowling, M.B. et al. (2015). Hydrophobically- modified Chitosan Foam: Description and Hemostatic Efficacy. Journal of Surgical Research, 193(1): 316-323. doi: 10.1016/j. jss.2014.06.019’
  21. Rago, A.P., Duggan, M.J., Hannett, P., et al. (2015). Chronic Safety Assessment of Hemostatic Self-expanding Foam: 90-day Survival Study and Intramuscular Biocompatibility. Journal of Trauma Acute Care Surgery, 79(4 Supplement 2): S78-8. doi: 10.1097/TA.0000000000000571
  22. Peng, Tao. (2010). Biomaterials for Hemorrhage Control. Trends in Biomaterials and Artificial Organs, 24(1): 27-68. http://medind.nic.in/ taa/t10/i1/taat10i1p27.pdf (accessed January 28, 2016).
  23. Department of Health and Human Services. Hemogrip Patch Premarket Notification. http://www.accessdata.fda.gov/cdrh_docs/pdf14/K143466.pdf (accessed January 28, 2016).

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