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Original Article

Nutritional Therapy & Metabolism / Vol. 26 no. 4, pp. 177-183 Wichtig Editore, 2008

Successful treatment of surgical abdominal woundscomplicated by multiple bowel fistulas with a combinationof total parenteral nutrition, hyaluronan-iodine complexand delayed surgery: results of a monocentric experience

L. SOBOTKA1, J. MANAK1, P. VYROUBAL1, R. MOTTL1, V. BLAHA1, M. SLEMROVA1, M. CHOBOLA2

1Department of Metabolic Care and Gerontology, Medical Faculty, Charles University, Hradec Kralove - Czech Republic 2Department of Surgery, Medical Faculty, Charles University, Hradec Kralove - Czech Republic

© SINPE-GASAPE

ABSTRACT: Background: Abdominal catastrophe, suture leakage and wound dehiscence are seri-ous complications of surgical procedures. Wound infection is a frequent complication and the mor-tality is high due to long and difficult treatment procedures. Treatment is often difficult as a resultof fistula formation, presence of necrotic and infected tissue, and complex surgical management.Long-term nutritional support is necessary between treatment periods. We have developed a newhealing system which is based on the combination of hyaluronan and iodine. This system has beensuccessfully used in our department for more than 4 years. The aim of this observational study wasto assess the effect of this complex in subjects with abdominal catastrophe. Methods: Seven patients with multiple fistulas and extensive wound dehiscence were admitted toour metabolic care unit. Total parenteral nutrition (TPN) providing full coverage of nutritionalneeds was used in all cases until full recovery of oral nutrition. After removal of necrotic tissue thewounds were dressed once daily with sterile gauze soaked in hyaluronate-iodine complex (Hyio-dine®). Intestinal fistula secretions were drained using negative pressure. After wound granulationand improvement of patient condition (no sooner than after 2 months) the intestinal fistulas wereresected and intestinal continuity established. Then, when primary suture was impossible, thehyaluronan-iodine complex was again used for healing of the open abdominal wound. Results: TPN and hyaluronan-iodine treatment led to significant wound healing in all patients.Within 14 days all wounds were dirt free and covered with granulation tissue. After 3.3±0.9months, patients were operated on (fistula resection and anastomosis). The abdominal wall was notclosed surgically in 4 patients during fistula resection. However, local treatment with hyaluronan-iodine complex led to complete wound healing in all patients within 4-10 weeks. Conclusions: We obtained excellent results with the sodium hyaluronate-iodine complex in combi-nation with TPN in the treatment of complicated abdominal wounds. We presume this effect is relat-ed to the combination of immune cell activation, angiogenic properties, and a strong affinity ofhyaluronate to water together with the antimicrobial effect of iodine. (Nutritional Therapy & Me-tabolism 2008; 26: 177-83)

KEY WORDS: Intestinal fistula, Postoperative care, Total parenteral nutrition, Wound dehiscence,Wound healing, Hyaluronate

INTRODUCTION

Multiple intestinal perforations with fistula forma-tion and open abdomen are frequent causes of the so-called abdominal catastrophe. The treatment of abdomi-nal catastrophe is complex and time consuming. It in-cludes treatment of infection complications, drainage of

potential abscesses and intestinal fistulas, nutrition sup-port and treatment of possible metabolic complications.In spite of this complex treatment, the open abdomenwith multiple fistulas is a common result. Moreover,massive visceral swelling, abdominal wall defect and in-traabdominal infection (abscess or peritonitis) may posean extreme surgical challenge. Dynamic-retention su-

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tures were used in similar patients after trauma, vascularreconstruction, tumor extirpation, and intraabdominalinfection (1). However, the presence of intestinal fistulaslimits their use. Additional surgical procedures such asskin grafting or plastic surgical reconstruction of the ab-dominal wall are also difficult in patients with intestinalfistulas (2). As the wound is often infected, a modifica-tion of the surgical treatment combined with a medicalapproach might improve the outcome of patients. Non-surgical treatment of complicated abdominal catastropheconsists mainly of systemic antibiotic therapy and localmanagement based on frequent wound dressing. Vacu-um-assisted therapy has also been successfully used inrecent years (3). Final abdominal wall reconstruction ispossible only after treatment of all infectious foci andintestinal fistulas; however, a simple, safe and universalmethod for local treatment is neither widely used norknown.

Hyaluronic acid (HA) is a nonsulfated glycosamino-glycan, which is an integral part of the extracellular ma-trix. It is a linear polysaccharide with repeating disac-charide units composed of glucuronic acid and N-acetylglucosamine. In particular, it forms the backbone for theorganization of proteoglycans (4). Early response to tis-sue injury includes the formation of a temporary matrixrich in hyaluronan and fibrin, which aids the influx of fi-broblasts and endothelial cells to the wound site, and thesubsequent formation of granulation tissue (5).

A unique characteristic of HA, related to its variablefunctions, is its hydration capacity. It contains approxi-mately 1000-fold more water than polymer saccharidewhen hydrated. In this respect HA is the most hy-drophilic molecule occurring in the human body. Thehydrophilic nature of HA creates an environment suit-able for the migration of cells to new tissue sites and of-fers protection to cells and extracellular matrix mole-cules, which can have a beneficial effect on the healingof both acute and chronic wounds (5). HA also facili-tates morphogenesis in the neonatal period and is proba-bly an important molecule for organ-regenerativeprocesses. A rapid increase in the concentration of HAsets the stage for reorientation and differentiation ofcells to allow regrowth of the forelimbs of newts. An in-crease in HA in the microenvironment promotes the or-ganization of connective tissue at the wound site (6).Many cell surface receptors for HA have been detectedon various types of cells and tissues. This structural rela-tionship could explain the effect of HA on cellular activ-ities such as migration and phagocytosis (7).

Because of the ubiquitous nature of HA, its solu-tions would appear to be useful in bandaging difficultwounds. HA was tested as an aid in wound healing, butthe results were not convincing. We therefore use a mix-

ture of iodine with hyaluronate (Hyiodine®, CPN, DolniDobrouc, Czech Republic) to inhibit its bacterial degra-dation and improve its healing capacity. We found thiscomplex very effective in the bandaging of infected anddifficult wounds (8). Currently, we are unaware of anyother studies that have assessed the results of this typeof therapy in patients with complicated abdominalwounds. Therefore we decided to study its effect in pa-tients with abdominal catastrophe.

MATERIAL AND METHODS

Seven patients with multiple intestinal fistulas andlarge abdominal wound dehiscences were treated at theMetabolic Unit of the Department of Metabolic Careand Gerontology, Medical Faculty, Charles University,Hradec Kralove, Czech Republic. The characteristics ofthe patients are shown in Table I. Informed consent wasobtained from each patient according to the HelsinkiDeclaration of 1975.

All patients were operated on several times at vari-ous regional hospitals in the Czech Republic. However,all surgical procedures (often repeated) were complicat-ed by the development of multiple intestinal fistulas,open abdomen and systemic inflammation. Intestinalfluid leakage to the peritoneal cavity was apparent in allpatients at the time of admission to our department.

After admission, all patients received total parenteralnutrition (TPN) by central venous catheter. According tothe protocol defined for these patients at our departmentthey received 34 Kcal, 4.5 g glucose, 0.8 g lipid emul-sion and 2 g amino acid solution per kg of body weightper day. Electrolytes, vitamins and trace elements werean integral part of TPN.

Secretions from fistulas were drained using negativepressure. Necrotic tissue was partially removed; entiredebridement was not possible due to the risk of multipleintestinal injury and perforations. Therefore the only lo-cal treatment of infected abdominal dehiscence wasbased on daily dressing with hyaluronan-iodine complexgauze and careful intestinal drainage. Patients receivedTPN and intravenous fluid replacement. Intravenous an-tibiotic therapy was administered during the first 2-3weeks. This treatment was continued for 2-5 months un-til improvement of local status and patient’s generalcondition. Then reconstruction of intestinal continuitywas performed in all patients. All intestinal fistulas wereresected and subsequent multiple intestinal anastomoseswere completed during one surgical procedure. Howev-er, the abdominal cavity could not be closed in 4 pa-tients because the tension was too great to physicallypermit fascia and skin reapproximation.

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Wound dressing protocolThe dressing of each abdominal wound was

changed daily. The sterile gauze was immersed inhyaluronan-iodine complex (Hyiodine®) and this satu-rated gauze was wrapped round the entire wound sur-face including the intestine. Several layers of steriledry gauze covered the gauze layers saturated inhyaluronan-iodine. This dressing was held in place us-ing tape. When the surface cover of the dressing waswet, the outer layers of gauze were replaced with newlayers of sterile dry gauze. However, the gauze thatwas immersed in hyaluronan-iodine and was in directcontact with the wound surface stayed in place for 24hours. The process of wound healing was monitored byone observer (LS) and pictures of the wounds wereregularly taken until healing was complete (Camedia –Olympus). The results included time to operation, timeto complete wound closure, and reported complica-tions associated with the use of the dressing.

RESULTS

Combination of TPN, fistula suction and local treat-ment led to significant clinical improvement before thefinal reconstructive procedure. Hyaluronan-iodine wasused as the only dressing in all patients. Its moisture-re-tentive and antiadhesive properties were very efficient.The dressing was usually changed every 24 hours. Theupper gauze layers were changed 2-3 times daily be-cause of wound secretion during the first 2 weeks oftreatment. Then the whole bandage was changed once aday only. No adherence of gauze to the wound bed wasevident in our group of patients.

During 2 weeks of careful intestinal suction, localtherapy and TPN all wounds were dirt free and showedgrowth of new granulation tissue. Throughout the next2-5 months the nutritional and metabolic status of thepatients improved; muscle force and mental activity alsoimproved considerably. Then final surgery was per-formed in all patients (Tab. II). Intestinal fistulas were

TABLE I - STUDY GROUP

Patient Age (years) Sex Disease Intestinal complications

1 66 M Perforated gastric ulcer 8 intestinal fistulas Wound dehiscence, stercoral peritonitis2 72 F Perforated sigmoid diverticulitis 4 intestinal fistulas Wound dehiscence, stercoral peritonitis,

necrotizing fasciitis 3 48 F Complication of gynecological operation 4 intestinal fistulas, short Wound dehiscence, sepsis, peritonitis

bowel 4 75 M Mesenteric embolization 2 intestinal fistulas, short Wound dehiscence and peritonitis

bowel5 69 M Sigmoid cancer resection 6 intestinal fistulas Wound dehiscence, diffuse peritonitis

6 62 M Acute pancreatitis 2 intestinal fistulas Wound dehiscence, retroperitoneal phlegmon7 64 F Sigmoid cancer resection 4 intestinal fistulas Wound dehiscence, severe bleeding

M, male; F, female

TABLE II - RESULTS OF TREATMENT

Patient Time to surgical treatment Time to complete wound Commentof intestinal fistulas (months) healing after surgery (weeks)

1 5 10 Open abdomen after second operation 2 2 3 Abdominal wall closure during fistula surgery3 3 2 Abdominal wall closure during fistula surgery4 3 4 Open abdomen after second operation5 3 4 Open abdomen after second operation

Plastic surgery6 4 3 Abdominal wall closure during fistula surgery7 3 5 Open abdomen after second operation

Mean 3.3 4.9Standard deviation 0.9 2.2Median 3.0 4.0

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resected and bowel continuity (single or multiple anas-tomosis) was reconstructed successfully in all patientsduring this surgical procedure. In 4 subjects final clo-sure of the abdominal cavity was possible (Tab. II). Theabdominal wound could not be closed in 4 patients dueto abdominal wall defects and because there was too

much tension to permit fascia and skin reapproximation(Figs. 1-8). In these 4 patients, the open abdomen andintestinal loops were again covered with hyaluronan–io-dine-impregnated gauze. In spite of multiple sutures nodehiscence developed in any patient. The wound healedspontaneously in 3 patients, while the granulation tissue

Fig. 1 - A 66-year-old man with a large abdominal wound after com-plicated gastric resection and subsequent reoperations in a local ho-spital. Result: complete wound dehiscence and 8 intestinal fistulas (4jejunal, 2 ileal and 2 fistulas of the transverse colon).

Fig. 2 - Situation before operation after 5 months of conservativetreatment (parenteral nutrition, drainage of fistulas and local admi-nistration of hyaluronan-iodine). The abdominal cavity is obliteratedby apparent intestinal fistulas.

Fig. 3 - Situation 3 days after surgery consisting of jejunojejunalanastomosis and hemicolectomy with ileotransverse anastomosis.The open abdominal cavity was treated again with hyaluronan-iodi-ne complex.

Fig. 4 - Granulation tissue covering a small part of the wound 2weeks after operation.

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on the exposed abdominal cavity was covered by skinautograft in 1 patient (Fig. 8). In spite of difficult, largeand complicated abdominal wounds all patients weresuccessfully discharged from the hospital. No adverse orallergic side effects were apparent in any patient treatedwith hyaluronan-iodine complex.

DISCUSSION

Abdominal wound dehiscence complicated by mul-tiple fistulas is still associated with a high rate of com-plications (new fistula formation) and even mortality.Combination of severe malnutrition and abdominal sep-

Fig. 5 - A 69-year-old man with a large abdominal wound after com-plicated sigmoid cancer resection and subsequent reoperations in alocal hospital. Result: complete wound dehiscence and 6 intestinalfistulas (4 jejunal and 2 fistulas of the transverse colon).

Fig. 6 - Situation after 2 months of conservative treatment (parente-ral nutrition, drainage of fistulas and local administration of hyalu-ronan-iodine). The abdominal cavity is obliterated by apparent inte-stinal fistulas

Fig. 7 - Situation 3 days after surgery consisting of jejunojejunalanastomosis and resection of the transverse colon with anastomosis.The open abdominal cavity was treated again with hyaluronan-iodi-ne complex.

Fig. 8 - Complete wound healing 5 weeks after operation and 1 weekafter skin transplantation.

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sis greatly limits the spontaneous or surgically-obtainedhealing rate.

The results of our study imply that treatment ofthese patients must be complex. Careful drainage of in-testinal fistulas by negative pressure is an important partof complex treatment. It reduces wound maceration butalso decreases systemic inflammation. Routine use ofTPN and careful monitoring of nutritional parameters isof paramount importance in these hard-to-treat compli-cated patients. TPN is essential for improvement of gen-eral catabolic condition, nutrition status, proteosynthesisand wound healing. It also enhances the patient’s mus-cle function and physical activity, which is essential forthe final (usually delayed) surgical procedure.

According to our results, topical treatment with ahyaluronan-iodine complex is a useful adjunct to com-plicated abdominal wound care. This complex improvedthe rate of granulation tissue formation and enhancedthe rate of wound healing in comparison with our previ-ous experience. Despite the presence of intestinal perfo-rations and fascia necrosis, the wound condition im-proved and subsequent delayed surgical procedureswere completed in all 7 patients. After resection of in-testinal fistulas all intestinal anastomoses healed withoutany fistula formation including cases where abdominalclosure was not possible (Fig. 1-8).

Hyaluronan is a major structural molecule in the ex-tracellular matrix. It provides structural support for tis-sue regeneration and is crucial for developmental regu-lation, especially in the fetal period (9). In the extracel-lular matrix, hyaluronan creates an hydrophilic environ-ment, regulates water retention, ionic and molecular dif-fusion, and forms 3-dimensional structures (7). Hyaluro-nan also assists in receptor-mediated gene expression(7). In children its concentration in wound fluid peaksearly after injury and decreases significantly within 3 to24 hours (10). As a major molecule, it affects inflamma-tion regulation, regulation of oxidative stress (11), an-giogenesis, granulation formation (12), and re-epithe-lialization; it therefore appears to be a very versatileagent. Hyaluronan may increase the rate of granulationtissue formation, decrease the formation of fibrotic tis-sue, and improve the rate of healing. Several studiesshowed that hyaluronan increases bone regeneration(13). Hyaluronate is also important for healing duringthe fetal period (9).

Several studies reported varying levels of success indifferent wound categories both in human and animalmodels. It was shown that sodium hyaluronate was ef-fective in vesical mucosa healing in rabbits (14).Hyaluronan improved the healing process in injuredmenisci of New Zealand white rabbits up to 12 weeksafter injury (15). The therapeutic effect of hyaluronic

acid in mucosal wound healing was confirmed in humanstudies (16). In a multicenter controlled study, 50 pa-tients with venous ulceration were treated daily withdextranomer cream or hyaluronan-impregnated gauze.Faster closure of ulceration was observed in the grouptreated with hyaluronan (17).

Pure hyaluronate, however, is not normally used forwound dressing. The problem is that hyaluronate can besplit by hyaluronidase bacteria present on the woundsurface. According to our previous results the combina-tion of hyaluronate with iodine prevents hyaluronatesplitting. The hydrophilic properties of high-molecular-weight hyaluronan attracted water from the patient’s tis-sue, which concentrated moisture under the dressing andpossibly led to the concentration of endogenous growthregulators in the wound area.

In spite of the increasing resistance to various antibi-otics used to treat surgical wound infections, no signifi-cant variation in the susceptibility to iodine antisepticswas demonstrated during this 6-year study (18). More-over, povidone-iodine dramatically increased the healingrate of chronic leg ulcers in comparison with silver sul-fadiazine or chlorhexidine digluconate, although typicalantimicrobial activity was similar (19). No changes in fi-broblast viability, morphology, cellular proliferation, orability to produce collagen in vitro were found in iodineconcentrations of up to 0.45% in cadexomer-iodinecomplex (20).

We conclude that a combined approach to compli-cated abdominal wounds is necessary. This approachmust be based on TPN, suction of intestinal secretionsand local treatment. In our study the use of hyaluronan-iodine complex proved highly effective in the localtreatment of complicated abdominal wounds. Our studywas only an observational one and prospective studiesare needed to substantiate our observations. However, asall our patients healed remarkably well, we can presumethat the hyaluronan-iodine complex method is an effec-tive method for the local dressing of difficult-to-heal ab-dominal wounds.

ACKNOWLEDGMENT

This study was supported by grant MSM Czech RepublicNo. 0021620820.

Conflict of interest: None declared.Financial Support: This study was supported by grant MSM CzechRepublic No 0021620820.

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Address for correspondence:Lubos Sobotka, MD, PhDDepartment of Metabolic Care and GerontologyMedical Faculty, Charles University50005 Hradec Kralove, Czech Republic e-mail: pustik@lfhk.cuni.cz

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Received: October 2, 2008Accepted: October 29, 2008