0099-2399/93/1904-0174/$03.00/0 JOURNAL OF ENDODONTICS Printed in U.S.A. Copyright © 1993 by The American Association of Endodontists VOL. 19, No. 4, APRIL 1993 Ferric Sulfate Hemostasis: Effect on Osseous Wound Healing, II, With Curettage and Irrigation Billie G. Jeansonne, DDS, PhD, William S. Boggs, DDS, MS, and Ronald R. Lemon, DMD Hemorrhage control is often a problem for the clini- MATERIALS AND METHODS cian during osseous surgery. Ferric sulfate is an effective hemostatic agent, but with prolonged ap- The experiments were performed in 12 New Zealand White plication to an osseous defect can cause persistent rabbits (2.3 to 3.7 kg). Anesthesia was obtained by the intra- inflammation and delayed healing. The purpose of muscular injection of a combination of xylazine (7 mg/kg), ketamine (30 mg/kg), and atropine (0.3 mg/kg). On both this investigation was to evaluate the effectiveness sides of the mandible, an incision was made along the alveolar of ferric sulfate as a hemostatic agent and to deter- crest in the naturally edentulous space between the incisor mine its effect on healing after thorough curettage and premolar teeth. An envelope flap was reflected to expose and irrigation from osseous surgical wounds. Stand- the alveolar cortical bone. An osseous defect (3 mm in di- ard size osseous defects were created bilaterally in ameter, 2 mm into cancellous bone) was created on each side the mandibles of rabbits. Ferric sulfate was placed with a #8 round bur. All defects were curetted and irrigated in one defect until hemostasis was obtained; the with saline. contralateral defect was allowed to fill with blood Drops of the 15.5% ferric sulfate solution were placed in and clot. After 5 min both defects were curetted and the osseous defect on the experimental (fight) site until com- irrigated. The repair of the defects was evaluated plete hemostasis was obtained. Blood was allowed to fill the histologically at 18 and 46 days. There were no control (left) site which did not receive ferric sulfate. After 5 significant differences between the ferric sulfate- min the sites were gently curetted with a small bone curette treated defects and the untreated controls. When and irrigated with sterile saline until all visible ferric sulfate adequately curetted and irrigated from the surgical coagulum (right) or the blood clot (left) was removed and site prior to closure, ferric sulfate did not cause hemorrhage reestablished. The flaps were repositioned and persistent inflammation or delay osseous repair in closed with resorbable sutures. The rabbits received a combination of penicillin (100,000 comparison to controls. units of procaine-G) and streptomycin (base equipment of 125 mg) for 3 days for infection control, and meperidine (5 mg/kg) for pain control. The rabbits were fed a soft diet of crushed rabbit pellets for 1 wk to minimize trauma to the surgical sites. The rabbits were killed in groups of six at 18 and 46 days Commercial preparations of ferric sulfate have been adver- postoperatively. After obtaining anesthesia, the animals were tised for use in periapical surgery (1). However, only two cases killed and perfused with Poly-LEM (Polysciences, Warring- using ferric sulfate as a hemostatic agent (2) have been re- ton, PA) via the carotid arteries. Specimens were sectioned ported in available literature. The authors did not comment from the mandibles to include the osseous defects and adja- on removal of the hemostatic agent prior to wound closure cent bone and fixed in Poly-LEM. The specimens were de- or assessment of wound healing. calcified in a 10% sodium formate-formic acid solution and In a previous study, we found that ferric sulfate left in situ processed for routine paraffin embedding. Seven-micrometer in surgical osseous defects had adverse effects (3). An intense sections were cut in a coronal plane through the center of the foreign body reaction and abscess formation was found in defect and stained with hematoxylin and eosin. some of the experimental specimens after 46 days. The pur- The sections were examined for inflammation and evidence pose of this study was to determine if the foreign body of healing and were scored based upon the following scale: 0 response and delayed healing caused by the ferric sulfate -- complete healing with surgical site filled with healthy can- (Astringident; Ultradent Products, Inc., Salt Lake City, UT) cellous bone; I = fibrosis with dense collagen, with or without could be reduced or eliminated by curettage and irrigation of early bone formation; 2 = granulation tissue filling the surgical the osseous defect prior to wound closure. site, with or without chronic inflammation; 3 = acute inflam- 174 Vol. 19, No. 4, April 1993 Ferric Sulfate Curettage 175 TABLE 1. Histological scores 18-Day Specimens 46-Day Specimens 1 2 3 4 5 6 7 8 9 10 11 12 Control 0 1 1 -- 0 1 1 1 0 0 0 0 Experimental 0 1 -- 1 0 1 1 0 0 0 0 0 FIG 2. Photomicrograph of an 18-day experimental specimen. A, Active bone formation with new trabeculae fills the defect. Original cortical bone is to the left. B, Enlarged area of upper left of A: isolated foreign body giant cell (arrow) adjacent to an area of new bone formation (hematoxylin and eosin; original magnifications ×12 and ×25; respectively). FIG 1. Photomicrograph of an 18-day control specimen. A, New bone trabeculae almost fill the defect. Original bone surface is on the left was maintained without additional applications for 5 min. side. B, Enlarged area of box in A: very active bone formation with The ferric sulfate coagulum was removed by gentle curettage plump osteoblasts is seen on all surfaces of the trabeculae (hematox- and irrigation with saline. ylin and eosin; original magnifications x12 and ×25, respectively). One set of poor quality histological sections in the l 8-day experimental group and one set in the 18-day control group were eliminated from grading. All scores for the 22 graded mation, with or without granulation tissue; and 4 = abscess specimens were either "0" (complete healing with the surgical formation. site filled with healthy cancellous bone) or "l" (fibrosis with The scores were analyzed by nonparametric t tests (Wil- dense collagen with bone formation (Table 1). Both the coxon rank sum test and Wilcoxon signed rank test) to experimental and control sites demonstrated active cancellous determine whether significant differences exist between the bony trabeculae with numerous plump osteoblasts. Inter- experimental and control groups or specimens. spersed were focal areas of loose to dense fibrous connective tissue (Figs. I and 2). RESULTS All 46-day specimens demonstrated either complete healing or fibrosis with bone formation. Although the general healing Hemostasis was achieved in less than 1 min with the ferric of the 18-day and 46-day experimental and control groups sulfate. The dark color of the coagulum contrasted with any were scored equally, there were histological findings in the red areas of residual hemorrhage. Spot application of addi- 18-day experimental group not found in the controls. Aggre- tional ferric sulfate provided complete hemostasis. Hemostasis gates of ferric sulfate residue were found in association with 176 Jeansonne et al. Journal of Endodontics foreign body giant cells (Fig. 2). Inflammatory infiltrates were Further studies comparing the biocompatibility of curetted limited to a few focal collections of lymphocytes, but no ferric sulfate with resorbable hemostatic agents are being significant collection of granulation tissue was seen. None of conducted. the 46-day experimental group demonstrated ferric sulfate This project was supported in whote/in part by BRSG S07RR05704, Division aggregates or foreign body giant cells. of Research Resources, National Institutes of Health. Statistical analysis of the scores showed no significant dif- Dr. Jeansonne is associate professor and coordinator, Postgraduate En- ference (p > 0.05) between any of the specimens or groups dodontics, Louisiana State University School of Dentistry, New Orleans, LA. (experimental versus control and 18-day versus 46-day). Dr. Boggs was a postgraduate student in endodontics at Louisiana State University School of Dentistry; he is currently in private practice in Coeur d'Alene, Idaho. Dr. Lemon is associate professor and chairman, Department of Endodontics, Louisiana State University School of Dentistry. Address requests DISCUSSION for reprints to Dr. Billie G. Jeansonne, Department of Endodontics, School of Dentistry, Louisiana State University, 1100 Flodda Ave., New Orleans, LA 70119. In studies of dermatological use, ferric sulfate solution was not removed from the soft tissue surgical site and considerable acute inflammation, foreign body reaction, and delayed heal- References ing was reported (4-7). The same response was found in our previous study when ferric sulfate was not removed from 1. Advertisement for Cut-Trol (Ichthys Enterprises, Mobile, AL). J Endodon 1991 ;17:inside back cover. osseous defects (3). 2. GaJlini G, Merlini C, Fischer D. II solfata ferrico nelta piccola chirurgia In this investigation, intraosseous hemostasis with a ferric orale. Dent Cadmos 1986;54:81-2, 85-91. 3. Lemon RR, Steele PJ, Jeansonne BG Ferric sulfate hemostasis: I. Left sulfate solution followed by curettage and irrigation with in situ. J Endodon (in press). sterile saline produced a transient, mild foreign body reaction 4. Larson PO. Topical hemostatic agents for dermatologic surgery. J Der- but did not delay osseous wound healing. The foreign body matol Surg Onco11988;14:623-32. 5. Epstein E. Topical hemostatic agents for dermatologic surgery [Letter]. reaction found in the 18-day specimens was minimal and was J Dermatol Surg Onco11989;15:342-3. not observed in any of the 46-day specimens. 6. Armstrong RB, Nichols J, Pachanca J. Punch biopsy wounds treated The long-lasting foreign body reactions and delayed wound with Monsel's solution or a collagen matrix.