|Year : 2012 | Volume
| Issue : 6 | Page : 784-787
Comparison of safety and efficacy of papaya dressing with hydrogen peroxide solution on wound bed preparation in patients with wound gape
Mangala B Murthy1, Bhasker K Murthy2, Sanjay Bhave3
1 Department of Pharmacology, GMC, Miraj, India
2 Department of Obstetrics and Gynecology, GMC, Miraj, India
3 PVPGH Sangli, Maharashtra, India
|Date of Submission||12-Jan-2012|
|Date of Decision||30-Jun-2012|
|Date of Acceptance||31-Aug-2012|
|Date of Web Publication||8-Nov-2012|
Mangala B Murthy
Department of Pharmacology, GMC, Miraj
Source of Support: None, Conflict of Interest: None
Objective: Indian papaya or Carica papaya is known to have de-sloughing and wound-healing properties due to the presence of protease enzymes. The present study was done to compare the efficacy and safety of papaya dressing with hydrogen peroxide solution for preparation of wound bed in patients of postoperative wound gape.
Materials and Methods: A randomized, open-labeled interventional study was carried out over a period of 8 months at a tertiary care hospital on post-caesarean section patients with wound gape. The efficacy parameters studied were duration of time required to induce development of healthy granulation tissue and total duration of hospitalization. Safety parameters studied were adverse effects reported by patients and development of hypersensitivity reaction.
Results: A total of 64 patients were enrolled, of which 32 patients received hydrogen peroxide dressing and 31 patients received papaya dressing (one patient withdrew after randomization). Time required to induce the development of healthy granulation tissue and total duration of hospitalization were 6.2 ± 1.6 days vs 2.5 ± 0.5 days and 19.2 ± 5.8 days vs 12.92 ± 4.6 days in papaya and hydrogen peroxide dressing groups, respectively. Both primary efficacy parameters were significantly shorter in papaya dressing group. The incidence of adverse effects like local irritation and itching were comparable in both groups and the difference was not statistically significant.
Conclusion: Papaya dressing is more efficacious and equally safe as compared to hydrogen peroxide dressing when used for wound bed preparation in patients with postoperative wound gape.
Keywords: Hydrogen peroxide, papaya, wound debridement, wound gape
|How to cite this article:|
Murthy MB, Murthy BK, Bhave S. Comparison of safety and efficacy of papaya dressing with hydrogen peroxide solution on wound bed preparation in patients with wound gape. Indian J Pharmacol 2012;44:784-7
|How to cite this URL:|
Murthy MB, Murthy BK, Bhave S. Comparison of safety and efficacy of papaya dressing with hydrogen peroxide solution on wound bed preparation in patients with wound gape. Indian J Pharmacol [serial online] 2012 [cited 2021 Aug 5];44:784-7. Available from: https://www.ijp-online.com/text.asp?2012/44/6/784/103302
| » Introduction|| |
Superficial wound dehiscence or wound gape is a common post-surgical complication with an incidence of 0.5 to 20%. , Wound gape does not contribute directly to mortality but causes significant morbidity , in the patient due to prolonged hospitalization  and requirement of re-suturing of the gaped wound.  One of the commonest causes of wound gape is infection of the surgical wound , which results in accumulation of necrotic debris, poor oxygenation, wound discharge, and scanty blood supply. This is clinically seen as slough on the wound bed. Unhealthy granulation tissue or slough prevents angiogenesis and re-epithelization of the surgical wound leading to wound gape.  Preparation of wound bed (by a process known as wound debridement) before re-suturing is meant to clear debris  and induce a healthy granulation tissue to assist the healing process. ,,
Hydrogen peroxide solution is routinely used for dressing of gaped wounds in our hospital. Release of nascent oxygen from hydrogen peroxide oxidizes the debris and the effervescence pushes it from the depth of the wound. It takes around one week for hydrogen peroxide to prepare a healthy wound bed suitable for re-suturing. Indian papaya or Carica papaya is known to have rapid de-sloughing and wound-healing properties since ancient times due to the presence of protease enzymes. Apart from anecdotal reports and few studies on chronic ulcers and burns, no planned or controlled studies have been done to support its action in patients with postoperative wounds. The present study was planned to compare the efficacy and safety of papaya dressing with hydrogen peroxide solution for preparation of wound bed in patients of wound gape before re-suturing.
| » Materials and Methods|| |
This was a randomized, open-labeled interventional study carried out over a period of 8 months in the inpatient department of Obstetrics and Gynaecology at a tertiary care hospital. The study was approved by the Institutional Ethics Committee and was carried out according to the Declaration of Helsinki. It was known from previous experience that wound preparation requires around 7 days with hydrogen peroxide and around 4 days with papaya. Assuming a standard deviation of 2 days for wound bed preparation in the population, power of the study at 80% and level of significance to be 5%, approximately 31 patients per group were required to detect any statistically significant difference between the study groups.
Post-caesarean section patients with wound gape, defined as absence of continuity between edges of the surgical wound after removal of sutures on the seventh post-operative day, and those willing to participate in the study by giving an informed consent were enrolled in the study. Patients suffering from severe systemic illnesses which impair wound healing (diabetes, hypothyroidism), immunodeficiency states including HIV infection and steroid therapy, severe anemia (Hb<6 g%), and complete burst abdomen involving separation of peritoneum and rectus with evisceration were excluded from the study. Patients with a history of allergy to any of the study medications and body mass index >30 were also excluded.
Details of the enrolled patients like age, parity, gravidity, history of allergies and atopic nature, and any significant medical history were noted. General examination of various organ systems and vital parameters were also noted. Local examination of the wound was done to observe the presence of slough, type of discharge, and nature of granulation tissue at the base of the wound. A swab taken from the wound was sent for culture sensitivity test and empirical antibiotic therapy was started to cover the common infecting organisms which was then modified based on result of the test. Patients were randomized to two groups, group A and group B. Patients randomized to group A (control) received daily dressing with hydrogen peroxide solution. Patients randomized to group B received papaya dressing. This consisted of placing autoclaved dressing gauze containing 200 g of well-cleaned, peeled, and grated partially ripe papaya between the edges of gaped wound which remained in situ for 48 hours. The dressing was removed on the third day to note the condition of the wound and re-dressing was done, if required.
The end point in both groups was presence of healthy granulation tissue, defined as pink tissue with beaded or granular appearance; serous non-foul smelling discharge; and complete absence of slough at the center of the wound. Dressing in both groups was continued till the end point was achieved after which the patients were posted for re-suturing. Number of days for which dressing was required before achieving the end point was noted. The patients were followed up until surgical wound healing was adequately achieved and total duration of hospitalization was noted. The number of patients requiring partial surgical debridement and repeat re-suturing were also noted. Those who failed to achieve the desired end point in 10 days were classified as treatment failure and posted for surgical wound debridement. Safety and tolerability of study medications was assessed by questioning the patient regarding any adverse effects he/she could recall. They were also closely monitored for any hypersensitivity reactions.
Statistical analysis was done by Z test for the difference between mean and proportion for quantitative and qualitative data, respectively. P<0.05 was considered statistically significant.
| » Results|| |
A total of 64 patients were enrolled into the study. On randomization, 32 patients were allocated to group A and received daily dressing with hydrogen peroxide as a control medication while 31 patients allocated to group B received papaya dressing. One patient allocated to group B opted to receive treatment in a private hospital after randomization. Patient accounting is represented as a CONSORT flow diagram [Figure 1].  Both the groups were comparable with respect to baseline parameters like age, weight, parity, and condition of the wound.
The duration of time required to induce development of healthy granulation tissue was 6.2 ± 1.6 days in hydrogen peroxide group and 2.5 ± 0.5 days in the papaya dressing group [Figure 1]. The total duration of hospitalization was 19.2 ± 5.8 days in group A and 12.92 ± 4.6 days in patients of group B [Figure 2]. Both these intervals were significantly shorter in papaya dressing group as compared to the group receiving hydrogen peroxide dressing.
|Figure 2: Comparison of time required to achieve specified end point and total duration of hospitalization in group A and group B|
Click here to view
The proportion of patients requiring additional partial surgical wound debridement was significantly less in the papaya dressing group as compared to hydrogen peroxide-treated group as shown in [Figure 3] (3.2% vs 56%, respectively). However, there were no treatment failure cases in both groups as per the predefined criteria. Only one patient in the hydrogen peroxide group was posted for repeat re-suturing. There were no such cases in papaya dressing group [Figure 3].
|Figure 3: Comparison of group A and group B with respect to the number of patients requiring partial surgical wound debridement and repeat re-suturing|
Click here to view
Adverse effects like local irritation and itching were reported by patients receiving both medications, but the difference was not statistically significant. There were no cases of severe hypersensitivity reactions observed during the trial [Figure 4].
| » Discussion|| |
Enzymatic wound debridement is an emerging concept in hastening the wound-healing process.  Till date, many enzymatic debriding agents like collagenase, pure papain, and papain-urea have been tried for preparation of the wound bed.  A detailed literature search revealed abundant anecdotal reports, some review articles, and a few planned studies which have analyzed the action of papaya fruit on wound debridement. Based on these reports, it was decided to study the effects of papaya on wound bed preparation in postoperative wound gape. The results showed higher efficacy of papaya dressing as compared to hydrogen peroxide dressing which is the current method of dressing used for postoperative wound gape in our hospital. Animal studies have demonstrated efficacy of papaya extract in induction of healthy granulation tissue on excision wounds in diabetic rats.  Human studies have been mostly conducted in burn patients  or patients suffering from chronic non-healing ulcers like pressure, diabetic, or venous ulcers. , Despite good efficacy and tolerability, papaya dressing had to be used for a longer duration in these studies as compared to our study as they were chronic ulcers and not incised wounds. The action of papaya as a wound-debriding agent is attributed to its enzymatic content and antibacterial activity. , Enzymes such as papain and chymopapain present in papaya assist removal of necrotic debris and induce development of healthy granulation tissue.  In the study conducted on diabetic rats, papaya extract also increased the hydroxyproline content of the wound. Increased amounts of vitamin C in papaya fruit helps in the conversion of proline to hydroxyproline which is an indicator of collagen content of granulation tissue laid down during healing.  Papaya fruit has been found to be active against some common organisms involved in wound infection like Staphylococcus aureus and Pseudomonas. , Constituents of papaya extract exert their antibacterial effects by breaking the biofilm defenses under the cover of which bacteria protect themselves against environmental factors like ultraviolet light and host immune mechanisms.  The healing action of papaya in pediatric burn wounds can be attributed partially to its antibacterial action. Although hydrogen peroxide is an agent routinely employed for wound dressing, its inhibitory action on healthy keratinocytes and fibroblasts might be responsible for unsatisfactory wound bed preparation with this chemical agent. Thus, in terms of efficacy, papaya dressing can be a good alternative to hydrogen peroxide. Safety and tolerability of papaya dressing was comparable to hydrogen peroxide dressing in our study. Previous studies have also upheld the safety of papaya fruit, , although an increase in severe hypersensitivity reactions with purified papain preparations was observed to the extent that some of them had to be withdrawn from the market. Despite concerns of hypersensitivity, no such reactions have been noted with papaya fruit so far. However, it would be prudent to use papaya fruit under close supervision, at least for the first time when dressing is performed. Additional advantages of papaya fruit include its availability in plenty in all seasons and its low cost. Papaya fruit for the purpose of dressing, as used in the present study, can be easily prepared even by unskilled personnel provided aseptic precautions are taken.
Limitations of the present study are related to lack of standardized methods for papaya preparation. There are no guidelines regarding selection of the fruit, (some studies have used ripe  while others have used unripe  or partially ripe papaya), preparation of dressing (studies have used either mashed fruit  or extract  ), and method of application. The enzymatic content of papaya is said to decrease as the fruit ripens  suggesting a better efficacy of raw papaya. However, most studies have used mashed ripe papaya for dressing due to ease of preparation and have obtained satisfactory induction of granulation tissue. In spite of differences in enzyme content, studies confirm that there are no differences between ripe and unripe papaya in terms of their antibacterial activity.  Thus, there is a need for development of standardized methods of papaya dressing which could be adopted for further studies. Extraction of the active principle and studying its role in wound healing should be targeted. Despite the limitations, a sincere attempt was made to assess the efficacy and safety of a time-honored traditional medication for its applicability in day-to-day practice.
In conclusion, papaya dressing is more efficacious than hydrogen peroxide dressing when used for wound bed preparation in patients with postoperative wound gape. Both dressings are well tolerated. Due to easy availability in the tropical countries, duration of hospitalization and hence the total cost of therapy can be significantly reduced by using papaya in those settings where this option can be made available.
| » References|| |
|1.||Pavlidis TE, Galatianos IN, Papaziogas BT, Lazaridis CN, Atmatzidis KS, Makris JG, et al. Complete dehiscence of the abdominal wound and incriminating factors. Eur J Surg 2001;167:351-4. |
|2.||Waqar SH, Malik ZI, Razzaq A, Abdullah MT, Shaima A, Zahid MA. Frequency and risk factors for wound dehiscence/burst abdomen in midline laparotomies. J Ayub Med Coll Abbottabad 2005;17:70-3. |
|3.||Mazilu O, Grigoraº D, Cnejevici S, Dabelea CT, Prundeanu H, Stef D, et al . Postoperative complete abdominal dehiscence: Risk factors and clinical correlations. Chirurgia (Bucur) 2009;104:419-23. |
|4.||Fleischer GM, Rennert A, Rühmer M. Infected abdominal wall and burst abdomen. Chirurg 2000;71:754-62. |
|5.||Ousey K, McIntosh C. Understanding wound bed preparation and wound debridement. Br J Community Nurs 2010;15:S22, S24, S26. |
|6.||Singer AJ, Taira BR, Anderson R, McClain SA, Rosenberg L. The effects of rapid enzymatic debridement of deep partial-thickness burns with Debrase on wound reepithelialization in swine. J Burn Care Res 2010;31:795-802. |
|7.||Falabella AF. Debridement and wound bed preparation. Dermatol Ther 2006;19:317-25. |
|8.||Stephen-Haynes J, Thompson G. The different methods of wound debridement. Br J Community Nurs 2007;12:S6, S8-10, S12-14, S16. |
|9.||Beitz JM. Wound debridement: Therapeutic options and care considerations. Nurs Clin North Am 2005;40:233-49. |
|10.||Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomised trials. Ann Intern Med 2010;152:726-32. |
|11.||Collier M. Wound-bed preparation. Nursingtimes.net; 2002;98:55. Available from: http://www.nursingtimes.net/nursing-practice-clinical-research/wound-bed-preparation/200408.article [Last accessed on 2012 Feb 24]. |
|12.||Ramundo J, Gray M. Enzymatic wound debridement. J Wound Ostomy Continence Nurs 2008;35:273-80. |
|13.||Nayak BS, Pereira LP, Maharaj D. Wound healing activity of Carica papaya L. in experimentally induced diabetic rats. Indian J Exp Biol 2007;45:739-43. |
|14.||Starley IF, Mohammed P, Schneider G, Bickler SW. The treatment of paediatric burns using topical papaya. Burns 1999;25:636-9. |
|15.||Ahmad F, Haq A, Askari H, Khan SA. Diabetic foot management; role of topical application of "papaya" in wound-healing. Pak Postgrad Med J 2001;12:138-42. |
|16.||Hewitt H, Whittle S, Lopez S, Bailey E, Weaver S. Topical use of papaya in chronic skin ulcer therapy in Jamaica. West Indian Med J 2000;49:32-3. |
|17.||Pieper B, Caliri MH. Nontraditional wound care: A review of the evidence for the use of sugar, papaya/papain, and fatty acids. J Wound Ostomy Continence Nurs 2003;30:175-83. |
|18.||Emeruwa AC. Antibacterial substance from Carica papaya fruit extract. J Nat Prod 1982;45:123-7. |
|19.||Dawkins G, Hewitt H, Wint Y, Obiefuna PC, Wint B. Antibacterial effects of Carica papaya fruit on common wound organisms. West Indian Med J 2003;52:290-2. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]