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Reprint from MCIF 3. /4-2011 Reprint from MCIF 3./4 -2011

E. C. T. H. TAN, C. P. BLEEKER (NETHERLANDS) Field experience with a chitosan-based haemostatic dressing B Uncontrolled hemorrhage is the leading cause of death among combat casualties A and is the second major cause of death in civilian trauma patients. Major impro- vements have been made in the deve- lopment of novel dressings with D haemostatic properties to control heavy bleeding in non-compressible areas. We describe the use of chitosan gauze (Celox GauzeTM), a chitosan-based hae- mostatic agent for the control of massive traumatic bleeding in 7 patients. C Introduction Fig. 9: A CeloxTM Gauze; B ChitoGauzeTM; C HemCon®; D QuikClot® Gauze (previously Combat Gauze). Bleeding remains a leading cause of death in trauma patients, both in civilian Table 2: Overview of a number of haemostatic dressings (prices October 2010 in the Netherlands). and military settings. Military experience in Vietnam, Iraq and Afghanistan has led Fig. 1: Lifeliner 3’s mobile medical team in action during an operation. Product Material Cost in € Effective- Shelf Side Use Weight Regis- Website to the introduction of the Combat Appli- (excl. VAT) ness life effects tration International importer cation Tourniquet (CAT-T®)(1) to treat haemostatic dressing in the field based on tracted from shrimp, cross react with red Dutch distributor severe bleeding from the extremities and BATLS 2006 JSP (57). Many comparative blood cells and form a solid clot, regard- Celox Chitosan 43,50 + 3 yr None USA, Singapore, 57 gram FDA + http://www.celoxmedical.com/ haemostatic dressings for severe bleeding animal studies 1-8 and case series 9-12 less of the natural clotting mechanism of Gauze Germany, Poland, CE+ index.htm from extremities, head, neck and torso. have been written on the use of haemosta- the body. In addition, chitosan absorbs Czech Republic, http://www.innoventa.nl/medisch- Meanwhile, several NATO countries have tic dressings. water, one of the main components of Malaysia, Italy, Mex- eerste-hulp/celox.html equipped their troops with haemostatic Chitosan gauze is a new haemostat blood, allowing the natural clotting fac- ico, Chile. dressings and included the use of different based on the polysaccharide chitosan. It is tors to become more concentrated, pro- QuickClot Kaolin 32,50 + 3 yr Does not USA, Canada, 30 gram FDA + http://www.z-medica.com/ protocols, such as the TCCC (Tactical derived from chitin, a complex carbohy- moting activation of the body's clotting Gauze resorb, Poland, Germany, CE+ http://www.specialmedics.com/nl/ Combat Casualty Care) guidelines of drate which occurs in the exoskeleton of mechanism. The function of chitosan is (Combat must be Slovakia, Italy, products.php?group=2&product=8 November 2009 and the BATLS (Battlefield crustaceans such as shrimps. Among other not affected by external factors such as Gauze) removed Turkey, Denmark, Advanced Trauma Life Support) guide- factors that promote the reaction with the body temperature (hypothermia or heat) Netherlands (DSI lines. Since 2009 the Royal Netherlands blood, chitosan contains small positively and works in heparinised patients and and special forces) Army have used HemCon® as their charged particles. These particles, ex- patients using aspirin. Chitosan causes no (TCCC guideline)

Hemcon Chitosan 179,00 + 3 yr None USA, Canada, Aus- 14 gram FDA + http://www.hemcon.com/ Les hémorragies non contrôlées sont La hemorragia no controlada es la Also antimi- tralia, Israel, UK, CE+ la cause principale de décès parmi principal causa de muerte entre http://www.renesmit.com/ les blessés de guerre et constituent los heridos en combate, y la crobial effect Netherlands, Ger- la deuxième cause principale de segunda causa de muerte en los many, Austria, Italy, décès chez les patients traumatisés pacientes civiles con trauma. Se civils. Des améliorations considérab- han realizado importantes mejo- Poland, South les ont été effectuées dans le déve- ras en el desarrollo de novedosos Africa. (in BATLS loppement de nouveaux équipe- apósitos con propiedades hemos- ments ayant des propriétés táticas para controlar sangrados guideline). hémostatiques pour contrôler les importantes en áreas no compre- Do not fold. saignements importants dans les sibles. Describimos el uso de + zones non compressibles. Nous la gasa de chitosan (Celox Chito- Chitosan 44,55 also antimi- 3 yr None USA, Israel, UK, 32 gram FDA + décrivons l’utilisation de la gaze au GauzeTM), un agente hemostático http://www.hemcon.com/ chitosane (Celox GauzeTM), un agent con base de chitosan para el con- Gauze crobial effect Netherlands http://www.renesmit.com/ hémostatique à base de chitosane trol de la hemorragia traumática pour le contrôle des saignements masiva en 7 pacientes. massifs traumatiques chez 7 patients.

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Reprint from MCIF 3./4 -2011 Reprint from MCIF 3./4 -2011

exothermic reaction and is not toxic. After and partly stopped bleeding in the nose a gauze bandage. The haemostatic band- be brought near to the source of bleeding. The ideal haemostatic dressing needs no use the wound is easily rinsed with saline. and ears. Although the haemorrhage ages with chitosan are CeloxTM Gauze (Fig. One option could be an applicator with training to use, does not decay, is flexible Chitosan is available in granular form and seemed to reduce, leaking continued in 9A), currently on the market and Chito- chitosan beads. In patient 6, it remains and cheap, attaches only to the bleeding impregnated in gauze. We describe our the hospital. Additional studies using a CT GauzeTM(2) (Fig. 9B), the successor to Hem- debatable whether the tamponade effect wound, has no side effects, has no risk of experience in seven patients using the scan showed a fractured skull. Con® (HemCon is a kind of thick parch- came from the abdominal gauze pads. We infection has no effect on wound healing new chitosan gauze (CeloxTM Gauze(3)). The last four patients were treated dur- ment, which is difficult to conform mould advice to use a haemostat in a dressing and effectively stops arterial, venous and ing our deployment in the Dutch Role 2E into wounds) (Fig. 9C). An antibacterial format, given the “natural” and “known” soft tissue bleeding. In our view, chitosan- TM Materials and methods in Uruzgan,the Uruzgan Medical Center, effect is claimed for ChitoGauze . It is use (as opposed to an applicator or bag of based haemostatic dressings fulfil these Afghanistan (Fig. 2). slightly more expensive than CeloxTM loose beads or the thicker parchment criteria. We conclude that chitosan-based For the past six months we have imple- Patient 4 was an Afghan wounded by a Gauze (see Table 2). There are case series HemCon®) for stopping bleeding. haemostatic dressings are a safe and useful mented chitosan gauze, pre-hospital, dur- roadside bomb. He had several blast describing the use of Celox in The working group for military surgery tool in stopping or controlling external ing our work on Lifeliner 3 (one of the injuries including a tear wound in his left Fig. 3: Care for patient 4 with shrapnel Fig. 4: Groin wound by patient 4 from Afghanistan, also use in surgery. In addi- of the Royal Netherlands Army was asked blood loss in our series of patients. Future four Dutch trauma helicopters, stationed groin (Fig. 3). An emergency bandage was injury from a roadside bomb. shrapnel injury treated with chitosan tion there is QuikClot® Combat Gauze(2) to give an advice on the use of haemosta- clinical studies should be conducted to at Volkel Airbase, falling within the applied in the field. On arrival at the bandages. (Fig. 9D), with the active ingredient tic dressings within the military. A small identify the ideal haemostatic dressing. ■ Regional Emergency Healthcare Network, emergency room there was fresh blood kaolin, the successor to QuikClot ACS + ™ subgroup of the military surgery working and the Radboud University Nijmegen leaking through the dressing. At the emer- (zeolite). This is now available without group, consisting of physician Colonel References with the autor Medical Centre), and during our deploy- gency room we applied chitosan gauze to exothermic reaction (see Table 2 for Teun van Egmond, MD, Major Oscar van ment in August and September 2010 to the wound, with pressure for a few min- review). The authors intend to carry out Waes, MD and the first author, formulated This article has been published previously the Dutch Role 2E at Camp Holland in the utes, after which the injury stopped bleed- further clinical testing on all of the above an advisory opinion to the Emergency in the Netherlands Military Medical Review provence of Uruzgan, Afghanistan. Indica- ing. Also in the operating room, about ten dressings. Medical Advisory Group at the end of 2011, 64, p 45-49, and has been reproduced tions were bleedings that could not be minutes later, the wound was still not The authors are aware that these cases 2009. This opinion is based on literature with consent of the Netherlands Military controlled with an “ordinary” compressive bleeding (Fig. 4). In the operating room, are purely observational and descriptive review, interviews with representatives Medical Review bandage. In total, seven patients were the various injuries were cleaned and a and there are many confounding vari- and their own experience with haemosta- treated with chitosan gauze: three patients small arterial bleed in the groin was iden- ables, as well as lack of long-term follow- tic bandages and was approved by the Notes: pre-hospital on the Lifeliner 3 and four tified (lesser tributary of the superficial up. Although no adverse reactions were above military surgeons. The opinion is (1) Combat Application Tourniquet patients during our deployment in femoral artery, superficial circumflex iliac reported, it is possible that later re-bleed- supported by the military anesthesiologist. (CAT-T®), QuikClot (Combat) Gauze®: Afghanistan (two patients in the emer- artery). Fig. 5: Patient 5 with a bleeding gunshot Fig. 6: Patient 6 with a pelvic fracture. ing has occurred (particularly in the three The authors of this article stand behind Special Medics, Utrecht. gency department, one patient during sur- Patient 5, also an Afghan, had several wound in the thigh. pre-hospital cases), or other possible com- these recommendations, namely: (2) HemCon®, ChitoGauzeTM: HemCon Fig. 2: Specialist Team 25 in front of the Uruzgan Medical Center. gery and one postoperative patient (see gunshot wounds to an arm, leg and but- plications that have occurred, such as ■ The use of haemostatic dressings has a Benelux, Rene Smit International BV, Table 1). The average age of patients was tock. Bleeding was most persistent from infection, delayed wound healing and clear added value for the military. The Hague. 37 years (20-76 years), three patients were vital functions of a patient are threatened. Patient 2 was a high energy trauma, the buttock wound (Fig. 5). Packing with increased scarring. Yet the authors found ■ Haemostatic dressings must be present (3) CeloxTM Gauze, Emergency (Israeli) Band- Dutch and four were Afghan. No patient The Lifeliner 3 carries a Mobile Medical cyclist against car, with venous bleeding sterile gauze had an insufficient haemosta- that the haemostatic dressings in patient at every military nurse, Medic and age: Innoventa, De Bilt. had significant comorbidity or use of med- Team, consisting of a nurse and a physi- from the left side of the neck. A normal tic effect. On packing with chitosan gauze 1, 2, 4, 5 and 7 have been successful, after corpsman in the chain of care (Role 1 ications. The indication in six patients was cian (anesthesiologist or trauma surgeon). pressure bandage did not help, then chi- the bleeding was stopped (as observed for having first tried conventional dressings. and Role 2 and Role 3). traumatic bleeding, while the last patient The first author was, as member of the tosan gauze was introduced, which 15 minutes with no more leaks). On In patient 3 chitosan gauze did not work, ■ We suggest that every soldier who goes in- suffered post-surgical bleeding. After team (trauma surgeon) involved in the res- stopped the bleeding. The dressing was inspection after 12 and 24 hours there was probably because the dressing could not to combat carries a haemostatic dressing. applying the chitosan gauze, manual cue of the three patients (Fig. 1). In the observed for 15 minutes (during both no further bleeding. After 24 hours chi- pressure was applied for about five minutes case of patient 1 there was a large wound transport to hospital and care in the tosan gauze was easily removed. and then covered with an occlusive in the left thigh muscle. This was treated hospital) and did not leak during this Patient 6 had become buried under AUTHORS bandage. initially with a compressive bandage, but time. rocks and suffered a fracture of the right Fig. 7: Patient 7 with an infected fracture Fig. 8: Postoperative bleeding after following leakage this was changed en Patient 3 was a patient with a clinically iliac crest (Fig. 6). The operative plan was on the left upper leg (after previous left guillotine amputation in patient 7. Lieutenant Colonel (reservist) E. C. T. H. Tan, MD, PhD Patients route to the hospital for chitosan gauze fractured skull who had fallen from a to stabilise the pelvic ring using plates and lower leg amputation). Royal Netherlands Army covered with an Emergency (Israeli) Band- height. There was considerable bleeding screws through an ilio-inguinal approach. Army reserve Lieutenant-Colonel Edward Tan was born on the 21th October 1971 in Nijmegen, the Netherlands. In 1997 he graduated in (3) The first three patients were treated pre- age , also known as the Israeli emergency from the ears and nose. The several During the operation, on repositioning ture and a femur fracture, three years ago. Discussion Medicine with honours (cum laude); he started his residency in General Surgery in 1999 at the Radboud University Nijmegen Medical hospital during our work at the Lifeliner 3. dressing, (a type of compression bandage). attempts to stop the bleeding by binding the fracture, there was an uncontrollable The femoral fracture was treated at the Centre.In 2005 he started his fellowship in Trauma surgery at the Radboud University Nijmegen Medical Centre and worked as a HEMS- The Helicopter Emergency Service is used Upon arrival at the hospital (approxi- the head with gauze and a compression venous bleeding (probably from the time with plate and screws. Now, three These seven cases provide a broad use of physician (Helicopter Emergency Medical System) at the Lifeliner 3 (Nijmegen). Since 2007 he works as a military trauma surgeon at the on strict indication alongside the ambu- mately eight minutes later), this combina- bandage were unsuccessful. As this leaked, sacral venous plexus) adjacent to the years later, the patient fell again (a few chitosan gauze as one of the many avail- Radboud University Nijmegen Medical Centre. He is involved in the training of medical students, nurses and surgical residents and is an in- lance service at large accidents or when tion had not leaked through. chitosan gauze was tied around the head inner pelvic ring near the right sacro-iliac weeks ago) and had a grade 3 open femur able haemostatic dressings. In our opin- structor at various advanced life support courses (ATLS®, APLS®, ALS) and is course director of the Definitive Surgical Trauma Care® course joint. fracture (just below the plate) with a piece ion, it is easy to use and simple to apply (www.dstc-datc.nl). As active reservist of the Royal Dutch Army, he has been deployed several times to Uruzgan and Kandahar Given the acute blood loss (three litres of bone protruding through the skin and and the dressing format is preferred. (Afghanistan). Table 1: Patients in total during the operation) and brief pus everywhere (Fig. 7). We decided to Haemostatic materials can be used in the Sex Age (yr) Ethnicity Accident Cause Location Successful period of cardiopulmonary resuscitation , carry out a guillotine above knee amputa- field, certainly have a place in Emergency Address for the authors: 1 M 40 Caucasian Car collision Soft tissue bleeding Upper leg Yes it was decided to treat the bleeding with tion. Postoperatively, a conical pressure Room and postoperatively on the ward. Radboud University Nijmegen Medical Centre 2 F 20 Caucasian Cycle collision Neck wound Lateral side of neck Yes tamponade of chitosan gauze and large bandage was applied, but after six hours They have the potential to be applied as a Department of General Surgery - Traumasurgery Internal postal code 690 with car abdominal pads, stabilising the patient in the wound was still leaking (Fig. 8). Chi- haemostatic agent during surgery. Ulti- P.O. Box 9101, 6500 HB Nijmegen, The Netherlands intensive care. After 24 hours the patient tosan gauze was placed on the open mately we chose to use haemostatic dress- 3 F 47 Caucasian Fall from height Fractured skull base. Ears and nose No Phone: +31 24 36 13871, Fax: +31 24 354 0501, E-mail: [email protected] was haemodynamically normal. At re- wound and pressure applied for five min- ings with the active agent chitosan, 4 M 26 Pashtun IED blast Arterial bleeding Left groin Yes (First and Corresponding Author) operation, the chitosan gauze and abdom- utes and again a conical pressure bandage because (so far) no significant side effects fragments from the groin inal pads were easily removed and the area applied. Over the next 12 hours, the have been described, although of course 5 M 25 Pashtun Gunshot wound Muscular bleed Buttock Yes was dry. At this operation the pelvis was wound no longer leaked. After five days, there may be side effects in patients aller- CO-AUTHOR 6 M 23 Hazara Rock crushing Pelvic girdle . pelvis Yes stabilised with plates and screws. the wound was no longer leaking, there gic to shrimp. In addition, chitosan is Captain (Nav) C. P. Bleeker, MD pelvis fracture, venous Finally, the last patient, an Afghan male were no signs of infection and the defini- absorbed by the body if it is accidentally Royal Netherlands Army 7 M 76 Pashtun Sharp amputation Muscular bleed Thigh stump Yes who had undergone a below knee amputa- tive above knee amputation was carried left in the patient. The chitosan dressing is Radboud University Nijmegen Medical Centre, department of Anaesthesiology tion because of an grade 3 open talus frac- out. flexible and easy to use in the same way as

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