The Efficacy of Cutanplast Nasal Packing After Endoscopic Sinus Surgery: A Prospective, Randomized, Controlled Trial

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1 The Laryngoscope VC 2012 The American Laryngological, Rhinological and Otological Society, Inc. The Efficacy of Cutanplast Nasal Packing After Endoscopic Sinus Surgery: A Prospective, Randomized, Controlled Trial Kyu-Sup Cho, MD, PhD; Seung-Kuk Shin, MD; Jung-Hoon Lee, MD; Joo-Yeon Kim, MD; Soo-Kweon Koo, MD, PhD; Yong-Wan Kim, MD; Min-Jung Kim, MD; Hwan-Jung Roh, MD, PhD Objectives/Hypothesis: Absorbable packing materials are commonly used after endoscopic sinus surgery (ESS). Cutanplast is a novel gelatin sponge with a powerful hemostatic effect that is rapidly absorbed. The purpose of this study was to investigate the efficacy of Cutanplast in patients following ESS. Study Design: A multicenter, prospective, randomized, double-blind, paired, controlled trial. Methods: One hundred adult patients with chronic sinusitis requiring the same extent of ESS were included. Patients were excluded if they were undergoing septoplasty, turbinate surgery, revision surgery, and taking anticoagulants. Following surgery, one nasal cavity was packed with Cutanplast and the other one with Merocel. Hemostatic properties, patient discomfort while the packing was in situ, patient pain on removal, degree of bleeding on removal, time required to control bleeding after removal, the cost of the pack, and postoperative wound healing were evaluated. Results: Both packs were effective at preventing postoperative hemorrhage. However, Cutanplast was significantly more comfortable while in situ (mean difference, 0.90; 95% confidence interval [CI], ) and less painful on removal of the pack (mean difference, 1.36; 95% CI, ). The Merocel pack was associated with significantly more bleeding on removal (mean difference, 1.23; 95% CI, ), therefore much time was needed to control hemorrhage (mean difference, 1.05; 95% CI, ). There was no significant difference in the cost of the pack used and outcome measure of wound healing. Conclusions: Cutanplast nasal pack results in significantly less pain and less bleeding compared to Merocel pack. Key Words: Gelatin sponge, absorbable gelatin sponge, biocompatible materials, nose, endoscopic sinus surgery, postoperative care. Level of Evidence: 1b. Laryngoscope, 123: , 2013 INTRODUCTION Postoperative care of patients undergoing endoscopic sinus surgery (ESS) is important both to minimize discomfort for the patients and to obtain the best outcome. The first step in this care is the decision as to whether to pack the nose and if so with what. Although some authors advise against nasal packing, 1,2 From the Department of Otorhinolaryngology and Biomedical Research Institute (K.-S.C., S.-K.S., J.-H.L.), Pusan National University School of Medicine, Busan; Department of Otolaryngology (J.-Y.K.), Kosin University College of Medicine, Busan; Department of Otorhinolaryngology (S.-K.K.), Busan St. Mary s Medical Center, Busan; Department of Otolaryngology (Y.-W.K.), Inje University Haeundae Paik Hospital, Busan; Department of Otorhinolaryngology (M.-J.K.), Wallace Memorial Baptist Hospital, Busan; and Department of Otorhinolaryngology and Research Institute for Convergence of Biomedical Science and Technology (H.-J.R.), Pusan National University Yangsan Hospital, Yangsan, South Korea. Editor s Note: This Manuscript was accepted for publication July 12, Presented at the 85th Annual Congress of the Korean Society of Otorhinolaryngology Head and Neck Surgery, Seoul, South Korea, May 1 3, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Hwan-Jung Roh, MD, Department of Otorhinolaryngology, Pusan National University Yangsan Hospital, Beom-eo li, Mul-geum eup, Yang-san si, Gyeongsangnam-do , South Korea. rohhj@pusan.ac.kr DOI: /lary others advocate its use. 3,4 The purpose of postoperative nasal packing lies in the prevention of adhesions, improved and accelerated wound healing, and most importantly to control possible postoperative bleeding. 5 8 The use of removable nasal packing for the patients is highly uncomfortable and induces local pain and pressure The removal of nasal packing has been described as the most painful part of the whole treatment. 6,12,13 Therefore, there has been an increasing tendency to move away from removable nasal packing due to the discomfort and bleeding experienced on removal. The use of an absorbable packing material following ESS obviates some of the drawbacks of removable nasal packing. Due to their excellent hemostatic properties and superior patient comfort, a number of absorbable materials have been developed and are now routinely used after ESS. 4 These materials differ substantially in their mechanisms of action, composition, method of delivery, clearance profile, and cost. 14 The hemostatic gelatin sponge (Cutanplast; Mascia Brunelli S.p.A., Milan, Italy) is a novel sterile reabsorbable gelatin sponge with a powerful hemostatic effect. 15,16 It was developed in 1998 and approved as a hemostat by the Korea Food and Drug Administration in The porous surface of the gelatin induces the rapid rupture of the blood plaques with consequent activation

2 Fig. 1. Endoscopic findings of right middle meatus after packing of the hemostatic gelatin sponge (asterisk) at the conclusion of surgery (A) and postoperative day 1 (B). The hemostatic gelatin sponge is almost liquefied 24 to 48 hours after application and can be gently removed by a suction device. NS ¼ nasal septum; MT ¼ middle turbinate; S ¼ suction device. of the enzymatic cascade such as platelet factor 4, which leads to natural coagulation. A hemostatic gelatin sponge is applicable dry or moistened, with sterile physiological saline squeezed out before application. It dissolves and can be suctioned at 24 to 48 hours after application. However, as yet there are no currently available studies in regard to its efficacy for packing material after ESS. The purpose of this study was to review our initial experience with the hemostatic gelatin sponge and to investigate the efficacy of the hemostatic gelatin sponge on patient s comfort, reduced bleeding, and wound healing following ESS. MATERIALS AND METHODS Subjects Six institutions were included in this prospective, randomized, controlled study involving 100 patients from a total of 105 enrolled patients for a 6-month enrollment period from June 2010 to November The institutional review board (IRB) approved this study before patient enrollment at each location. Each patient signed an IRB-approved consent form to participate in the study before each operation. Patients included in the study were 18 years or older and undergoing elective primary ESS for chronic rhinosinusitis (CRS), in whom nasal packing was deemed to be medically appropriate. Patients were required to have a diagnosis of CRS, defined as symptomatic inflammation of the sinuses for at least 12 consecutive weeks duration. The diagnosis, presence of bilateral ethmoid disease, and candidacy for ESS were confirmed by computed tomography scan examination. After the extent of disease evaluation was recorded based on the Lund-Mackay staging system, 17 patients with the same Lund-Mackay score in both sides were included. Exclusion criteria included a simultaneous performed septoplasty, turbinate surgery, other nasal surgery that would make a comparison of different sides impossible, and the additional use of a different nasal packing material. Additional exclusion criteria were patents with massive nasal polyposis, a history of previous ESS, bleeding disorders or anticoagulant therapy, pregnancy, and the presence of a severe medical or neuropsychiatric disorder. Surgical Procedure and Intervention Surgical procedures were performed under general anesthesia for all patients. Cotton pledgets soaked with 1:5,000 epinephrine and submucosal injection of 1% lidocaine with 1:100,000 epinephrine were used for hemostasis. ESS was then performed bilaterally with the same sinuses addressed on each side using conventional techniques. At the conclusion of the procedure, one ethmoid cavity was packed with a Cutanplast standard hemostatic sponge and the other with a Merocel (Medtronic Xomed, Jacksonville, FL) according to a randomized assignment, and therefore patients acted as their own controls. A hemostatic gelatin sponge was prepared by dividing it into four pieces. Each piece was soaked with normal saline and inserted into the middle meatus and ethmoid sinus (Fig. 1A). The 10-cm-sized and nonlaminated Merocel was divided into two pieces and tied with 3-0 white silk so that it could be removed easily. Only one piece of Merocel was then placed between the middle turbinate and lateral nasal wall. Once in position, the Merocel was activated by 10 ml of normal saline. All patients received postoperative antibiotics (either a second generation cephalosporin or clarithromycin) as selected by the surgeon for 10 days, analgesic medications as required, and a systemic corticosteroid taper (prednisone 20 mg daily starting at 0 day after surgery, which was tapered off postoperatively over 7 days). All nasal packs were removed the day after without prior anesthesia or analgesia. When Merocel was removed, a dissolving hemostatic gelatin sponge could be gently removed by a suction device (Fig. 1B). The order of removal was also randomized. The patients were not informed of which nasal packing was placed on each side. Furthermore, the surgeon carrying out the operation did not know until the time came to insert the pack. The resident who removed the packs the following morning and who collected the data were also unaware as to which side the patient had been assigned to. All patients were discharged 1 day after surgery without acute complications. As part of the postoperative care, patients were instructed to perform a nasal irrigation using normal saline twice a day by 565

3 TABLE I. Analysis of Postoperative Outcomes Between Cutanplast and Merocel. VAS Parameter Type Mean 6 SD P Value Discomfort during insertion Cutanplast <.001 Merocel Pain on removal Cutanplast <.001 Merocel Bleeding on removal Cutanplast Merocel Time for hemostasis Cutanplast Merocel Data are expressed as numbers. SD ¼ standard deviation; VAS ¼ visual analogue scale. themselves. All patients applied one spray of a mometasone nasal spray (Nasonex; Merck, Whitehouse Station, NJ) in each nostril twice daily following the nasal irrigation. Postoperative Assessment Clinical assessment was performed at 0, 1, 7, 14 28, 60, and 90 days after surgery. The difference in outcomes for patients treated with the two different types of packing are mentioned below. 1. Patients discomfort while in situ, where while the packing was in situ, the patients were asked to record their level of discomfort in each side of the nose on a visual analogue scale with a range of 0 to 4, 0 being no discomfort and 4 being worst possible discomfort. 2. Patients pain on removal, where the patients were asked to record their pain on removal of the packs on a separate fivepoint scale, 0 being no pain and 4 being worst possible pain. 3. The degree of bleeding on removal of the packing, where the treating clinician recorded their perception by grading bleeding as no bleeding ¼ 0, staining of dressing ¼ 1, oozing ¼ 2, moderate bleeding ¼ 3, severe bleeding ¼ Time required to control bleeding after removal of the packing on scoring system with a range of 0 to 3, 0 ¼ under 5 minutes, 1 ¼ 5 to 10 minutes, 2 ¼ 10 to 20 minutes, 3 ¼ over 20 minutes. 5. The cost of the pack used. 6. Postoperative healing assessment of edema, crusting, secretions, and scarring were done at postoperative days 7, 14, 28, 60, and 90 using validated Lund-Kennedy scores. Statistical Analysis Data were presented as mean 6 standard error of mean. The data were analyzed using SPSS for Windows version 16.0 (SPSS Inc., Chicago, IL). Categorical variables were analyzed by a v 2 test. Differences between the groups were analyzed by a paired t test. A value of P <.05 was considered to be significant. RESULTS A total of 105 patients were enrolled in the study, including 67 males and 38 females from 20 to 76 years of age, with mean age of 35.7 years. Of these, 100 patients successfully completed all follow-up visits according to the clinical protocol, whereas five patients were not evaluated in all follow-up visits because of protocol violations and patient s early discontinuation of the study. There was no difference in the grade of nasal polyp. The mean Lund-Mackay score for the side of the hemostatic gelatin sponge packing was 5.8, and that for the side of Merocel packing was 5.7 (P ¼.654). Complete bilateral ethmoidectomy was performed in all cases. Middle meatal antrostomy was created in 96% of cases. Concurrent sphenoidotomy and frontal sinusotomy were performed in 50% and 45% of patients, respectively. There were no differences of extent of surgery performed on each side. In hemostatic properties, the hemostatic gelatin sponge and Merocel were equally effective in the control of postoperative bleeding while the packs were in place. There were no intraoperative complications, and all patients were discharged one day after surgery. Patients Discomfort While In Situ and Pain on Removal The discomfort scores while the packs were in situ were for the hemostatic gelatin sponge and for Merocel. The hemostatic gelatin sponge packing was more comfortable than Merocel while in situ (P <.001). The pain scores on removal of the hemostatic gelatin sponge pack was and for the Merocel The hemostatic gelatin sponge pack was statistically significantly less painful than the Merocel pack on removal (P <.001) (Table I). Degree of Bleeding on Removal The scores for degree of bleeding while the packs were removed were for the hemostatic gelatin sponge and for Merocel. There was significant difference in the degree of bleeding on removal of packing between the hemostatic gelatin sponge and Merocel pack (P ¼.007) (Table I). Time for Hemostasis After Removal Bleeding on removal of packing did not necessitate any further treatment other than application of 566

4 epinephrine-soaked gauze. The time score on hemostasis of the hemostatic gelatin sponge was and for the Merocel Compared to Merocel, the hemostatic gelatin sponge showed significantly shorter time to control. bleeding after removal of packing (P ¼.001) (Table I). Cost of the Pack The hemostatic gelatin sponge costs 8,000 won ($7.1 US dollars) per pack, and 12,000 won ($10.7 US dollars) for Merocel. The mean total cost of the hemostatic gelatin sponge in each procedure was 13,200 won ($11.7 US dollars), 13,500 won ($12.0 US dollars) for Merocel. There was no significant difference in the cost of the pack used between the hemostatic gelatin sponge and Merocel. Lund-Kennedy Endoscopic Score Both groups received a postoperative endoscopic examination at 1 week, 2 weeks, 1 month, 2 months, and 3 months. When comparing postoperative endoscopic scores between the hemostatic gelatin sponge and Merocel, there was no statistically significant difference (Table II). Adverse Reactions and Complications No packs inadvertently fell out, no patients had postoperative bleeding necessitating change of pack, and no patients had any significant bleeding after the packs were removed. Therefore, both packs were deemed equally effective in their stability and hemostatic effect. DISCUSSION The choice of packing materials, or whether packing is used at all after ESS, is dependent on the preference and experience of the surgeon and the particular details of the case. Although no packing is physiologic and can avoid the rare complication associated with packing, 1,2 there may be inevitably some bleeding following surgery even with meticulous nasal preparation and surgical technique. Ongoing bleeding may risk airway embarrassment due to inhalation of blood, although most postoperative bleeding is fairly small. This can also be a source of significant anxiety and may negatively impact the patient s sense of overall recovery. 18 Various absorbable materials have been introduced to overcome the disadvantages of removable nasal packing or no packing. The ideal materials should be effective in immediate and prolonged hemostasis, have no detrimental effect on wound healing, and be absorbable and comfortable for patients. 6,9,14 Although many studies have evaluated the absolute effect of absorbable packing materials on patient s comfort, hemostasis, and wound healing, there was a relative paucity of literature comparing these materials to removable packing materials. Therefore, this study was designed to examine the efficacy of the hemostatic gelatin sponge compared to Merocel, which is one of the Period (POD) TABLE II. Lund-Kennedy Scores Between Cutanplast and Merocel. Cutanplast Merocel Mean 6 SD Range Mean 6 SD Range P Value POD ¼ postoperative day; SD ¼ standard deviation. most common removable packing material used after ESS. The hemostatic gelatin sponge is made from 99.7% pig gelatin, and is resorbable, insoluble in water, and digestible by trypsin. 15 The sponges had no additives, contaminants, or residues that could affect biocompatibility, except sodium lauryl sulfate in minimal amounts. 15 The hemostatic gelatin sponge was neither cytotoxic nor genotoxic in any test. 15 Although Gelfoam is also an absorbable gelatin sponge that is obtained from pig skin gelatin, the hemostatic gelatin sponge is different from Gelfoam in density of gelatin and porosity. According to the manufacturer, the hemostatic gelatin sponge has higher gelatin by volume and more porosity than Gelfoam. These characteristics make the packs soft and less adhesive, allowing them to be liquefied earlier and removed easily. 16 Small changes in the chemical composition lead to significant changes in their biochemical and biological effect. Patient s comfort plays an increasingly important role and must be considered when choosing a packing material, even if functional effectiveness remains the primary concern. Discomfort is mainly caused by pain, reduction in nasal air flow, impaired sense of smell, and increased nasal secretion. 19 Pain is mainly associated with removal of packing but may also develop while placed. This study showed that the hemostatic gelatin sponge and Merocel were equally effective in their hemostatic abilities for the duration of the pack being in situ. However, the hemostatic gelatin sponge was significantly more comfortable during insertion and less painful on removal of the pack. Moreover, its capacity for programmed dissolution in the early postoperative period eliminates the need for removal of packing, leading to a significant improvement in patient comfort. The diminished discomfort and pain scores during insertion and on removal of the hemostatic gelatin sponge may be explained by its lack of adhesion to the nasal mucosa when compared with Merocel, which tends to stick to the mucosa. In this study, removal of Merocel pack was associated with significantly more bleeding, therefore much time was needed to control hemorrhage. Because Merocel has large pores, it allows granulation tissue to grow into the pack. 7,19 Therefore, foam packs such as Merocel may cause difficult removal and significant bleeding, 9,10,20,21 although laminated Merocel with small 567

5 pores is less likely to carry the same risk of in-growth or shearing force on removal. 19 Economic factors, including cost-effectiveness ratio, must also be considered when using nasal packs. The cost of materials for performing nasal packing should be weighed against their potential advantages. The greatest advantage of the hemostatic gelatin sponge in comparison to other absorbable hemostatic materials is its low cost (approximately $10/procedure). Therefore, a hemostatic gelatin sponge can be used as much as necessary for hemostasis during surgery. When evaluating the suitability of the various biomaterials following ESS, their influence on wound healing should be given particular attention. Wound healing may be related to the retention time of the biomaterials and the biomaterial itself. 22 The longer the duration of packing, the more it increases the influence on wound healing. 6,7 Prolonged exposure of regenerating mucosa to foreign material during the early phases of wound healing can be detrimental. 23 In this study, we found no significant difference between the hemostatic gelatin sponge and Merocel with regard to endoscopically observed parameters of wound healing in any of the follow-up examinations. The formation of postoperative scarring is considered to be a leading cause of surgical failure and poor outcomes after ESS. 23,24 Furthermore, because scarring is the most relevant of the elements of the Lund-Kennedy score, a separate evaluation of the scarring data was performed. Scarring was rare in both the hemostatic gelatin sponge and Merocel groups. Although there was a trend to less scarring formation in the hemostatic gelatin sponge, the data lacked statistical significance (P ¼.25). Although some human studies suggest that gelatin may predispose toward the formation of granulation tissue, the hemostatic gelatin sponge was not found to have an appreciable effect on wound healing. The hemostatic gelatin sponge is liquefied and can be cleared from the wound site within only 24 to 48 hours. It is conceivable that the hemostatic gelatin sponge had little or no effect on the mucosa because the duration of contact was too short. The limitation of our study was the inability to mask the physicians and all investigators to the assigned packing material. This had the potential to introduce significant observer bias. We attempted to minimize any resulting bias by not informing patients which packing material was inserted in each side of the nose. Furthermore, the pain scores were collected by an investigator, who also was unaware of treatment assignment, after packing material had already been removed. CONCLUSION A newer gelatin-based hemostat, Cutanplast, offers distinct advantages because of its unique composition and rapid clearance profile. Based on this initial study, the hemostatic gelatin sponge appears to be an effective hemostat that works in sinus cavities. The use of the hemostatic gelatin sponge after ESS results in significantly less discomfort and greater patient satisfaction without an apparent adverse effect on wound healing when compared with Merocel packing. Therefore, the hemostatic gelatin sponge may be a safe and useful packing material in terms of efficacy and cost-benefit after ESS. BIBLIOGRAPHY 1. Eliashar R, Gross M, Wohlgelernter J, Sichel JY. Packing in endoscopic sinus surgery: is it really required? Otolaryngol Head Neck Surg 2006; 134: Orlandi RR, Lanza DC. 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