Treatment of superficial second degree burn of face and neck with topical heparin : a comparative , prospective and randomized study

Background: New treatment options for thermal injuries are very desirable, especially if they reduce healing time and pain without increase of infection rates. Recent studies suggest that heparin topical use can achieve those goals. This study has the objective to evaluate healing time, pain and infection rate comparing topical use of heparin and collagenase in the treatment of superficial second degree burns of face and neck. Methods: Twenty patients were randomized into 2 groups: group treated with topical heparin and group treated with collagenase (control group). The exclusion criteria were: history of bleeding, blood discrasia, allergies to the product, active peptic ulcer and burns with more than 24 hours. Mann-Whitney test was applied to evaluate the results. The pain was measured by the use of opioid analgesics. Results: The heparin was not effective in decrease of healing time nor the use of opioids, and the infection rate didn’t present significant difference between the groups. Conclusions: The heparin can be used safely in treatment of superficial second degree burn of face and neck, but its beneficial effects need to be proven.

Vendramin FS et al.

INTRODUCTION
Two main events summarize the physiopathology of burns: edema and an increase in capillary hydrostatic pressure.Thermal injury induces a cascade of systemic inflammatory reactions by the exposure of the subendothelial collagen.This cascade results in tissue edema and hypovolemia.Ac tivation of the calicrein system produces cy tokinins that aggravate both the edema and hypovole mia.Cytokinin and collagen exposure activate the arachnoid acid-phospholipase system, liberating prostaglandins and, thus, elevating capillary permeability.Locally, substance P, serotonin, nitric oxide, bradykinin and leukotrienes play a role in increased local capillary permeability.
One of the first authors to study the effect of heparin in thermal injuries was McCleery et al. 1 .He verified a favorable alteration in animals with the use of parenterally administered heparin sodium.Saliba Jr. [2][3][4] , the current author who most studies this subject, also demonstrated favorable effects on humans.
Second degree burns cause great pain to the patient, be cause the nerve endings are exposed.Superficial partial thickness burns heal in, at most, two weeks.Blistering is very common.
Multiple studies [1][2][3][4][5][6] suggest that treating burns with topi cal heparin is of beneficial effect in various ways such as: healing time shortened by several days, reduced burn edema, reduced pain, anti-inflammatory effect, limited cell destruction, and better scar quality, without change in rates of infection.However, there is no strong evidence of those effects because of the poor quality of those articles.
This study aims to evaluate epithelialization time, pain and infection rate, comparing the use of heparin and the use of topical collagenase (control group) in the treatment of superficial second-degree burn of face and neck.

METHODS
After institutional review board approval, 20 patients were evaluated during a period July, 2006 through August, 2007.
Patients with superficial second degree burns of face and neck of less than 24 hours were candidates for our study.
Patients with a history of bleeding, blood dyscrasia, burns of more than 24 hours, allergies to one of the products, or active peptic ulcer were excluded from our study.
After initial evaluation, the treatment was randomized by raffle of 20 envelopes (10 for each group) kept in a safe.
The patients were informed of the study and after this, signed a consent term of their participation, with possible com plications, ethical and legal implications.
On the heparin group, we performed rupture of the burn blisters, cleaned the burn wound with chlorexidine and applied topical heparin (10.000UI/ml) with 3 "puffs" of spray three times a day until the formation of the crusts (Figures 1   to 3).The heparin was then applied two times a day at a 20 cm distance totalizing 1% of the burn.
On the collagenase group, we performed rupture of the burn blisters, cleaned the burn wound with chlorexidine and applied a thin layer of collagenase one time a day (Figures 4 and 5).
Both groups were evaluated as to need for hospitalization, time elapsed between burn and treatment, total body surface area, need for analgesics (evaluation of pain), healing time, and rate of infection.
The Mann-Whitney test was used with a significance le vel of 5%.

RESULTS
A total of 20 patients with burns of face and neck were enrolled prospectively, ten treated with collagenase (control group) and 10 treated with topical heparin.

A B Figure 1 -In A, formation of crusts after heparin administration.
In B, complete healing.

Figure 2 -In A, formation of crusts after heparin administration.
In B, complete healing.
Treatment of superficial second degree burn of face and neck with topical heparin Average age was 22.85 years, ranging from 1 to 58 years.The main cause of burns was flames (40%).There was no bleeding or allergies to the product.
The percentage of total body surface area (TBSA) varied from 0.5% to 47%.
The time elapsed between burn and treatment was on average 11 hours and 1 minute (variation = 30 minutes to 24 hours).Seven patients required hospitalization.
Time of epithelization varied from 5 to 17 days with healing, on average, in 10.5 days for the topical heparin group and 6.2 days for the collagenase group (P=0,010).
Patients of the heparin group needed less non-opioid me dicine than those of the collagenase group (P=0.029).Ho wever, there was no significant difference between the use of opioids in both groups (P=0.648).
Only one of the patients enrolled had wound infection in the heparin group; nevertheless, there was no statistical relevance (P=0.317).One patient had hyperpigmentation and another, hypertrophic scarring.
The results of analysis of the parametric and non-parametric variables are presented respectively in Tables 1 and 2.

DISCUSSION
The treatment of burns with topical heparin is another choice in burn therapy.Heparin is a glycosaminoglycan, are highly acidic long chain compounds and with a negative charge.Heparin is the most sulfated and acidic 2 .The treatment of burns with heparin has been advocated by some authors because of its supposed anti-inflammatory and neoangiogenic effects 3 .
Superficial second-degree burns of face and neck have, in most cases, been treated, with open topical ointments.Open topical collagenase is the standard treatment for burns of the face and neck at our institution.Burns on the face and neck need special care because of possible damage to upper airway, ear cartilage and eye; likewise, of cicatri cial microstomy and cervical contracture.
A number of non-comparative studies suggest that heparin reduces the healing time of burns leading to better quality scaring.
The results of our study comparing time of epithelization between both groups showed that the collagenase had a faster healing time as compared to the heparin group (P<0.05).This means that heparin does not exert a significant influence on healing time.
Results comparing pain showed us that the heparin group used less non-opioids analgesics than the collagenase group (P<0.05).This may have been so because the burn on the heparin group is not manipulated causing less pain or, because the heparin itself really exerts an analgesic effect.There was no significant difference between both groups in the use of opiods (P>0.05);hence, we can say that heparin  was not effective in reducing use of opioids.This could have occurred due to the heterogeneity of the population studied with regard to the extent of surface burnt area, because the patients that used opioids had more extensive burnt areas.
The ideal topical agent should have the following characteristics: promote healing, control infection, be easy to apply and store, relieve pain and not soil the bed and clothing.Heparin does not have all of these characteristics.

CONCLUSIONS
Heparin can be applied safely in the treatment of second degree burns of face and neck, however its beneficial effects need to be proven.

Figure 3 -Figure 4 -Figure 5 -
Figure 3 -In A, formation of crusts after heparin administration.In B, complete healing.
Hospital dos Defeitos da Face, associate physician of the Hospital Municipal Infantil Menino Jesus, São Paulo, SP, Brazil.2. Full member of the SBCP, associate physician of the Hospital Santa Cruz, São Paulo, SP, Brazil.3. Full member of the SBCP, associate physician of the Hospital dos Defeitos da Face, São Paulo, SP, Brazil.4. Associate member of the SBCP, associate physician of the Hospital dos Defeitos da Face, São Paulo, SP, Brazil. 5. Associate member of the SBCP, plastic surgeon, São Paulo, SP, Brazil.
1. Full member of the Sociedade Brasileira de Cirurgia Plástica/ Brazilian Society of Plastic Surgery (SBCP), associate physician of the