|Year : 2014 | Volume
| Issue : 1 | Page : 43-50
Topical heparin versus conventional treatment in acute burns: A comparative study
Muhsin Masoud, Adil Hafeez Wani, Mohammad Ashraf Darzi
Department of Plastic Surgery, Burns and Reconstructive Microsurgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, Jammu and Kashmir, India
|Date of Web Publication||15-Dec-2014|
Department of Plastic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Background: In order to alleviate pain, reduce scarring, and to improve the overall outcome in burn patients multitude of novel agents are being utilized. In this regard, heparin has been introduced because of its research proven role in burn wound management. Objective: The objective was to evaluate, whether the addition of heparin, administered only topically, could improve burn treatment. Materials and Methods: The subjects in this study were 40 consecutive burn patients with 10-20% burns, randomly allocated to heparin group (H-group) (20) and control group (C-group) (20). Results: All patients in the H-group were receiving analgesics on demand only from the 2 nd week onwards. This was in contrast to the C-group wherein 35% patients received twice daily dosage of analgesics in the 2 nd week of their treatment. When compared to the average hospital stay of 18.3 days in the C-group, patients belonging to the H-group had an average hospital stay of 12.3 days (P < 0.05). Conclusions: The current comparative study demonstrates that heparin significantly decreases the requirement of analgesics and the time required to prepare a burn wound for grafting. Besides as compared to silver sulfadiazine dressings, heparin appears to be cost-effective.
Keywords: Burn, conventional burn treatment, topical heparin
|How to cite this article:|
Masoud M, Wani AH, Darzi MA. Topical heparin versus conventional treatment in acute burns: A comparative study. Indian J Burns 2014;22:43-50
|How to cite this URL:|
Masoud M, Wani AH, Darzi MA. Topical heparin versus conventional treatment in acute burns: A comparative study. Indian J Burns [serial online] 2014 [cited 2019 Aug 24];22:43-50. Available from: http://www.ijburns.com/text.asp?2014/22/1/43/147002
| Introduction|| |
Burn is a complex disease process, a trauma to physique as well as psyche. Visible disFigurement caused by burns translates into an altered pattern of socialization which in turn can have serious psychological ramifications. Pain, prolonged hospital stay, loss of working days, draining of financial resources-all these factors are of pivotal importance, which a health care provider should bear in mind, while managing these patients. Many of these aspects hold true in the context of burn care in developing countries. Patients with burns require immediate specialized care in order to minimize morbidity and mortality. 
The breached skin barrier is the hallmark of thermal injury. Because of the importance of the skin as a barrier to microbial host invasion, it is not surprising that the risk of subsequent burn wound infection and systemic infection correlates with the size of the burn injury. ,, Causative factors, which are implicated in pathological scar formation are a prolonged and subsequently dysregulated inflammatory phase, a misbalance between pro- and anti-fibrogenic factors, and the involvement of specific cell subpopulations. 
In order to alleviate pain, reduce scarring, and to improve the overall outcome in burn patients multitude of novel agents are being utilized. This in itself reflects the suboptimal response to conventional treatment modalities. In this regard, heparin has been introduced because of its research proven role in burn wound management. Heparin can be divided into two types: Unfractionated heparin (UFH) and low-molecular-weight heparin UFH is a mixture of saccharide polymers, with molecular weights ranging from about 5000 to 30,000 kDa, whereas LWMH is a mixture of smaller polymers with weights ranging from 2000 to 15,000 kDa.  Multiple mechanisms explain the role of heparin in burns when used topically. Firstly, heparin may work partially because of antiinflammatory activity. The effects may directly or indirectly mediate on many factors producing inflammation.  The mechanism of action may also include influencing monocyte, T-cell and neutrophil activity, nitric oxide production, chemokine and cytokine activity, complement activity, platelet activation and aggregation, and smooth muscle cell proliferation.  Second, heparin can restore blood flow in a shorter time and revascularize ischemic tissue, through enhanced vascular growth.  Possible mechanisms of this action are the inhibition of selectin-mediated cell-cell interactions, heparinase inhibition, binding of proangiogenic growth factors and stimulation of tissue factor pathway inhibitor release.  Third, wound healing is affected by enzymes such as elastase, cathepsin G, and proteinases, which degrade the extracellular matrix, growth factors and further recruit neutrophils to the wound area. Heparin and related molecules could inhibit the function of these cells through electrostatic interactions and enhance the healing. ,
| Materials and methods|| |
This randomized control study was conducted between February 2012 and January 2014 in the Department of Plastic Surgery, Burns and Reconstructive Microsurgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India. The subjects in this study were 40 consecutive burn patients involving 10-20% total body surface area (TBSA). This study comprised of two groups and patients were randomly allocated to each group, with alternate patients being included in a particular group.
- Study group: Which was termed as heparin group (H-group) - 20 patients
- Control group: C-group - 20 patients.
- A total of 40 consecutive acute burn patients involving 10-20% TBSA.
Burn patients with a contraindication to the use of heparin:
- Patients with liver disease, renal disorders, blood coagulating diathesis
- An allergy to heparin
- Active peptic ulcer
- Active or potential bleeding due to trauma.
- Patients on drugs having a negative impact on wound healing
- Acute and chronic disease processes, which adversely affect wound healing
- Electric burn patients
- Burns reporting 48 h after the accident.
Analgesia and pain scores
All patients in this study received injection tramadol as analgesic. Visual analog pain scores were calculated for all patients.
In both groups, scar parameters such as vascularity, thickness, pliability, and pigmentation were recorded as part of Vancouver scar scale.
Data analysis was carried out using Student's t-test and Fisher's exact test.
After being discharged from the unit patients were followed-up as per the following schedule:
- Weekly in the 1 st month
- After every 2 weeks in the 2 nd month
- Every 6 months thereafter
- Yearly follow-up until 2 years.
Twenty of these randomly selected patients were designated to be the C-group. C-group patients received the traditional routine treatment without the addition of heparin. C-group treatment included pain medications on demand, intravenous resuscitation fluids, antibiotics, topical antimicrobial-silver sulfadiazine cream 1%. In C-group patients, silver sulfadiazine was applied topically as an even, thick coating after cleaning of wounds on the day of admission. Daily application of silver sulfadiazine (SSD) followed. SSD treatment was standardized.
The other 20 randomly selected patients were assigned to the heparin-treated group (H group). H-group patients received the same treatment, but without the use of topical antimicrobial creams, so that sodium aqueous heparin solution was applied topically in diminishing doses until final healing. Between heparin applications, patients were treated with dressings soaked in normal saline.
A total 20 ml of 5000 IU/ml of heparin solution was added to 500 ml of normal saline solution to make a total 520 ml of 200 IU/ml concentration heparin sodium solution (heparin) [Figure 1]. The solution was prepared a fresh every time. This diluted heparin solution was evenly dripped or sprayed onto the open burn surfaces a total of 2-3 times a day, starting from day 1. Topical heparin in diminishing doses was continued until final healing. The total day 1 topically administered heparin dose was 100,000 IU of heparin per each 15% of burn surface size. Approximately, 50% or more of day 1 dose was initially dripped on the burn surfaces repeatedly in the first 10-15 min of heparin treatment, until the patient reported that the burn pain was relieved, and the initial burn erythema, if present, was blanched. Then the burn blisters were treated. A hypodermic needle on a syringe filled with 200 IU/ml heparin was introduced into a blister, and a small hole was thus made, of which the blister fluid was allowed to spontaneously drain by gravity. The blister was then slowly rinsed with heparin 2-3 times, and then the needle withdrawn, leaving a residual volume of heparin within the blister [Figure 2]. The blister cover was permitted to settle onto the blister's inner surface. Blisters were not debrided or removed. Heparin treatment was also standardized.
|Figure 1: A dilute heparin solution-25,000 IU/500 ml of normal saline being used (heparin group)|
Click here to view
|Figure 2: Intra-blister heparin injection in a case of second-degree superficial hand burn (heparin group)|
Click here to view
Majority of the patients in our study had second and third degree burns. 95% of our patients in both the groups had second degree burns while only 5% in either group had third degree burns [Table 1]. All the patients in Heparin group were on "on-demand analgesics only" from the beginning of second week [Table 2]. Control group analgesia requirement involved OD analgesics from second week in 20% cases and on demand analgesia in 55% cases [Table 3]. Out of the 30% patients who needed skin grafting 10% were from the Heparin group and 20% from the control group [Table 4]. The average time period required to prepare a wound for skin grafting after eschar separation was 7 days in the Heparin group where as it was 11 days in the control group [Table 5]. The maximum duration of hospital stay was 5 weeks in the Heparin group and 7 weeks in the control group [Table 6]. In comparison to an average hospital stay of 18.3 days in the control group, we observed an 12.3 days average hospital stay in the Heparin group [Table 7]. Hypertrophic scarring occurred in 10% of patients in Heparin group and 20% in control group [Table 8]. Prolonged antibiotic adminstration for over 3 weeks was required in 5% of patients in Heparin group and 10% of patients in control group [Table 9]. An average cost difference of rupees 1995 per day per patient was observed between heparin and control groups [Table 10]. Analysis of average cost for whole duration of treatment reveals a cost difference of Rupees 172 between the groups, with heparin dressings appearing cheaper [Table 11]. Serial photographs of Heparin group patients [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8] and Control group [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16] revealed early healing and less scar related complications in the heparin group.
|Figure 5: Day 14 - Regression of facial edema and healed burn wounds (heparin group)|
Click here to view
|Figure 6: Day 1 - Case of kerosene flame burn injury face, chest wall and arms (heparin group)|
Click here to view
|Figure 7: Day 5 - Residual blisters necessitating heparin injections (heparin group)|
Click here to view
|Figure 11: Day 7 - Status of burn wounds while on conventional treatment (control group)|
Click here to view
|Figure 12: Day 30 - Healed hand burn wounds on conventional treatment (control group)|
Click here to view
|Figure 14: On admission - Silver sulfadiazine cream application (control group)|
Click here to view
|Figure 15: Day 35 - Healed left-shoulder region burn wound (control group)|
Click here to view
| Discussion|| |
This randomized case-control study was commenced after acquiring an Ethics Committee approval (Institute Ethical Committee 01-2012) and was conducted at the Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India. The only tertiary referral centers for burn patients for the entire state of Jammu and Kashmir, India.
Requirement of analgesia
A striking observation made in our series was that all patients in the H-group were receiving analgesics on demand only from the 2 nd week onwards. This was in contrast to the C-group, wherein 35% patients received B.D dosage of analgesics and 45% received O.D analgesics in the 2 nd week of their treatment (P < 0.05).
These findings are consistent with observation made in recent burn studies as exemplified by the results of Agbenorku et al.,  who found heparin to be effective in the alleviation of pain. Ferreira Chacon et al.,  similarly, concluded that the topical application of heparin spray in patients with superficial second-degree burns reduced pain.
In addition to alleviation of pain, subjective findings like reduction of erythema and edema were observed in our study. The above-mentioned findings demonstrate the antiinflammatory effects of heparin as reported in several other studies. The reduction in analgesic requirements had an additional benefit of less analgesic complications in the H-group.
In our entire series, of the 30% patients who needed skin grafting 10% belonged to the H-group and 20% to the C-group (P < 0.05).
Srivastava et al.,  have reported that superficial and deep burns healed in a record time in patients treated with heparin. There is literature evidence to support these findings as the skin adnexal elements present in the deeper layers of skin were made to survive by the vasodilatory and antithrombin effects of heparin. Epithelization by proliferation of these surviving de-epithelized island cells is induced with heparin thus making superficial and deep burns to heal in shorter periods of time.
Duration of hospital stay
Majority of patients in the H-group-35% had a hospital stay of 1 week, whereas in the C-group the same percentage of patients stayed for around 2 weeks (P < 0.05). Agbenorku et al.,  have reported that the time spent by patients during admission was reduced in the H-group.
Improved outcome in H-group patients as compared to the C-group, in the form of reduced pain, reduced antibiotic requirement, reduced requirement of skin grafts, reduced graft loss, translates into a reduced hospital stay.
In our part of the country with most of our patients belonging to low socioeconomic labor class, a reduced hospital stay in turn means quick return to work. Not only does it quickly rehabilitate the patient in the society, but it also has advantages for hospital administration in the form of reduced bed occupancy thus making available the beds for other patients.
Wound healing complications
Around 10% of patients from the H-group and 20% from the C-group experienced wound healing complications in the form of hypertrophic scarring (P < 0.05). Our observations correlate well with literature as Venakatachalapathy et al.,  in a comparative study noticed that the appearance of new skin was generally better in the H-group patients. Heparin initially accelerates collagen production and deposition, and in the second phase decelerates and reabsorbs collagen, which would tend to inhibit fibrin accumulation and scar formation.
Requirement of antibiotics
We analyzed the use of antibiotics in our study and C-groups and found that 2-3 weeks antibiotic requirement was needed in 45% patients in the H-group, whereas the antibiotic requirement for the same duration was seen in 60% of C-group patients (P > 0.05). Blood and wound swab culture reports were not significantly different in the two groups. There was also no significant disparity vis-a-vis the organisms isolated and their drug sensitivity. Antibiotic administration continued till clinical parameters showed improvement.
Venakatachalapathy et al.,  have reported that patients treated with topical heparin required fewer antibiotics. One explanation may be that heparin by its neo angiogenic effects mediates an enhanced blood flow to ischemic areas, which in turn leads to delivery of antibiotics more effectively to the burnt areas.
In our research project, we did not encounter any case of adverse effect to topical heparin. H-group patients were observed subjectively for excessive bleeding from burn wounds, epistaxis, hemoptysis, and hematuria. In addition, objective assessment included regular lab assessment of coagulation profile, urine examination, and stool for occult blood. Patients allergic to heparin were excluded from the study. Use of dilute solution of heparin, lack of significant absorption seems to be the factors responsible.
As a corollary to above-mentioned observation, in our series, we calculated the average expenditure on intravenous antibiotics and made a comparison between the two groups. The average number of days of intravenous antibiotic usage was 9 days in H-group, and it was 14 days in the C-group. We further observed that whereas Rs. 3591 was the average expenditure on intravenous antibiotics in the H-group, it was Rs. 5586 in the C-group.
We also calculated the daily cost of treatment for an average 15% TBSA burn for comparative purpose and noticed that the total expenditure on heparin dressings/silver sulfadiazine dressings and intravenous antibiotics was Rs. 987/day in H-group and was Rs. 1159 in the C-group.
Similar cost benefits were reported by Venakatachalapathy et al.  The above-mentioned cost benefit observed in the H-group may have far reaching implications, especially in the context of burn management in developing countries. Jammu and Kashmir constitutes an economically underprivileged state of the nation and the majority of the patients who reach tertiary care burn centers face financial constraints. Hence a treatment option, which in addition to providing medical benefits to this patient subgroup, if cost-effective, will be readily acceptable to health care providers and the patients both.
We studied 40 patients over 3 years and would recommend a larger sample size in future studies on this topic. Besides being a novel study at our center, we restricted burn percentage to 20% burn only; study of higher burn percentage patients is also needed. In addition, the effect of topical heparin on intravenous fluid requirement, as reported in literature, needs in depth study.
| Conclusion|| |
The current comparative study demonstrates that heparin decreases the requirement of analgesics and time required to prepare a burn wound for grafting after eschar separation. In addition, it also seems to positively impact the quality of life parameters by decreasing hospital stay and wound complications like hypertrophic scarring.
| References|| |
Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev 2006;19:403-34.
Gibran NS, Heimbach DM. Current status of burn wound pathophysiology. Clin Plast Surg 2000;27:11-22.
Heimbach D, Mann R, Engrav L. Evaluation of the burn wound management decisions. In: Herndon D, editor. Total Burn Care. London, England: Saunders; 2002. p. 101-8.
Roth JJ, Hughes WB. The Essential Burn Unit Handbook. St. Louis, MO: Quality Medical Publishing; 2004.
Teot L, Otman S. Burn scar treatment. Handbook of Burns. Vienna: Springer. 2012;2:55-67.
Lu J, Xu T. Heparin for the Treatment of Burns. [Intervention Protocol] The Cochrane Collaboration; 2011. p. 2.
Saliba MJ Jr. The effects and uses of heparin in the care of burns that improves treatment and enhances the quality of life. Acta Chir Plast 1997;39:13-6.
Tyrrell DJ, Horne AP, Holme KR, Preuss JM, Page CP. Heparin in inflammation: potential therapeutic applications beyond anticoagulation. Adv Pharmacol 1999;46:151-208.
Saliba MJ Jr. The effects of heparin in the treatment of burns. International Meeting, San Diego, CA; 1994.
Elsayed E, Becker RC. The impact of heparin compounds on cellular inflammatory responses: A construct for future investigation and pharmaceutical development. J Thromb Thrombolysis 2003;15:11-8.
Peplow PV. Glycosaminoglycan: a candidate to stimulate the repair of chronic wounds. Thromb Haemost 2005;94:4-16.
Wang J, Zheng H, Qiu X, Kulkarni A, Fink LM, Hauer-Jensen M. Modulation of the intestinal response to ionizing radiation by anticoagulant and non-anticoagulant heparins. Thromb Haemost 2005;94:1054-9.
Agbenorku P, Fugar S, Akpaloo J, Hoyte-Williams PE, Alhassan Z, Agyei F. Management of severe burn injuries with topical heparin: The first evidence-based study in Ghana. Int J Burns Trauma 2013;3:30-6.
Ferreira Chacon JM, Mello de Andrea ML, Blanes L, Ferreira LM. Effects of topical application of 10,000 IU heparin on patients with perineal dermatitis and second-degree burns treated in a public pediatric hospital. J Tissue Viability 2010;19:150-8.
Srivastava JL, Babu KR, Tewari VK, Narayan RP. Heparin in the management of extensive burns. Indian J Plast Surg 1988;21:7-12.
Venakatachalapathy TS, Mohan Kumar S, Saliba MJ. A comparative study of burns treated with topical heparin and without heparin. Ann Burns Fire Disasters 2007;20:189-98.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]