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British Journal of Oral and Maxillofacial Surgery xxx (2013) xxxxxx

Impairment of wound healing after operative treatment of mandibular fractures, and the inuence of dexamethasone
Johanna Snll a, , Kormi Eeva a , Lindqvist Christian a , Suominen Anna Liisa b,c,d , Mesimki Karri a , Trnwall Jyrki a , Thorn Hanna a
Department of Oral and Maxillofacial Surgery, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland University of Eastern Finland, Institute of Dentistry, Kuopio, Finland c Department of Oral and Maxillofacial Surgery, Kuopio University Hospital, Kuopio, Finland d Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland
b a

Accepted 29 August 2013

Abstract Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to nd out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benets of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and xation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ signicantly. Only age over 25 was signicantly associated with delayed healing (p = 0.02). The use of dexamethasone 30 mg perioperatively did not signicantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures xed with titanium miniplates through an intraoral approach. Older age is a signicant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation. 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Keywords: Mandibular; Fracture; Glucocorticoid; Dexamethasone; Wound; Healing

Introduction Glucocorticoids have proved to be effective in reducing postoperative nausea, pain, and oedema after various procedures.13 Their perioperative use in association with facial operations in general, and operations for maxillofacial fractures in particular, is therefore common and widespread. However, glucocorticoids suppress the immune

Corresponding author. Tel.: +358 053621191. E-mail address: johanna.snall@helsinki. (J. Snll).

system through various mechanisms,4 including processes that are essential in wound healing.5 It can therefore be assumed that the use of perioperative dexamethasone may increase the risk of different types of impaired wound healing. A study of the adverse effects of glucocorticoids on wound healing in patients who had open reduction and osteosynthesis of facial fractures showed no signicant difference in wound healing between patients who had been given perioperative glucocorticoids and those who had not.6 An intraoral approach remained the only signicant predictor. The study mentioned was retrospective, however, and comprised patients with various types of fractures having different

0266-4356/$ see front matter 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.bjoms.2013.08.015

Please cite this article in press as: Snll J, et al. Impairment of wound healing after operative treatment of mandibular fractures, and the inuence of dexamethasone. Br J Oral Maxillofac Surg (2013), http://dx.doi.org/10.1016/j.bjoms.2013.08.015

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J. Snll et al. / British Journal of Oral and Maxillofacial Surgery xxx (2013) xxxxxx

procedures and being given various regimens of glucocorticoids. The question of whether steroids had an adverse effect on wound healing in patients treated for facial fractures, therefore, requires further evaluation. The aims of the present study were to clarify the incidence of impaired healing after open reduction and ostheosynthesis of a mandibular fracture through an intraoral approach, and to nd out whether the operative use of dexamethasone increases the risk.

miniplates, and fractures in the mandibular body and angle were xed with one miniplate according to the technique described by Champy and Lodde.7 A postoperative follow-up period of 30 days was required for the patient to be included in the analysis. Study variables The outcome variable was impaired wound healing, the presence of which was established when any aberrant wound healing, or signs of infection of the wound, developed. The primary predictive variable was the perioperative use of dexamethasone. Other predictive variables included in the analysis were age, sex, smoking habit, type of fracture, delay of treatment, and duration of operation. Statistical analysis The statistical signicance of associations between the impairment of wound healing and the perioperative use of dexamethasone, sex, smoking habit, and fracture type were evaluated using the chi square test. Because of the skewed distributions for age, delay in treatment, and duration of operation, we used Wilcoxon two sample tests to evaluate the signicance between these variables and the impairment of wound healing. Ethical approval The Ethics Committee of the Department of Surgery and the Internal Review Board of the Division of Musculoskeletal Surgery, Helsinki University Central Hospital, Finland, approved the study (Dno 33/E6/06).

Patients and methods Design of the study Patients were drawn from a larger group of healthy dentate patients aged 18 years or more who had participated in a single-blind, randomised study that aimed to clarify the effects of dexamethasone on pain, oedema, and nausea after open reduction and xation of facial fractures. We excluded patients with infected fractures; histories of liver or kidney dysfunction, peptic ulcer, or psychosis from the use of steroids; pregnancy; breastfeeding; or allergy to any constituent of the dexamethasone preparation used. For each type of facial fracture, patients were randomly assigned to one of two groups. The patients in the study group were given dexamethasone (Oradexon ) 10 mg intravenously during induction of anaesthesia and an additional 10 mg intramuscularly every 8 h for 16 h, making a total dose of 30 mg. The control patients were given no steroids. All patients were given antibiotics until the 7th10th postoperative day, starting with 3 doses of cefuroxime 1.5 g intravenously in the ward during the rst 24 h postoperatively. This was followed by 3 doses of cephalexin 500 mg orally. Patients with allergies were given 4 doses of clindamycin by corresponding routes. One examiner (JS or EK) followed patients up one day, 2 days, one week, one month, 3 months, and 6 months postoperatively. Patients were followed up for surgical reasons as needed. In addition, all patients had routine radiological investigation with panoramic imaging immediately, and one month, 3 months, and 6 months postoperatively. Inclusion criteria Patients included in the analysis had one or 2 fractures in dentate areas of the mandible and had had open reduction and xation with titanium miniplates. Types of fracture included: one single fracture in the angle, one single fracture in the body, one single fracture of the symphysis/parasymphysis, or a double mandibular fracture (for example, angle + body, angle + symphyseal/parasymphyseal fracture). All fractures were xed through an intraoral approach with the aid of 2.0 mm miniplates and non-locking monocortical screws. We did not use a transbuccal approach. Symphyseal/parasymphyseal fractures were xed with 2

Results Of the patients recruited into the initial study, 49 fullled the inclusion criteria for the present analysis; of these, 4 refused to participate. Of the remaining 45 patients, 4 were excluded: one because he attended no follow-up appointments, one because he required an additional operation as the reduction of the fracture was unsatisfactory, and 2 because they failed to complete all the doses. Forty-one patients were therefore followed up for at least a month. The mean follow-up period was 9 months (range 123). The patients descriptive statistics are shown in Table 1. In 2 patients the wound broke down sufciently to necessitate removal of the osteosynthesis material (Fig. 1). In 2 patients pus was seen in the gingival pocket of the tooth in the fracture line on the 41st and 86th postoperative days, respectively. One of these wounds healed with antibiotics taken orally and root canal treatment. The other patient required removal of the osteosynthesis material and extraction of the lower third molar 15 weeks postoperatively. In 2 other patients secretion of pus and a stula in the surgical

Please cite this article in press as: Snll J, et al. Impairment of wound healing after operative treatment of mandibular fractures, and the inuence of dexamethasone. Br J Oral Maxillofac Surg (2013), http://dx.doi.org/10.1016/j.bjoms.2013.08.015

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Table 1 Details of the patients (n = 41). Data are number (%) unless otherwise stated. Variable Sex Male Mean (range) age (years) Smokers Site of fracture Angle Body Symphysis/parasymphysis Angle + body Angle + symphysis/parasymphysis Mean (range) delay in treatment (days) Delay (days) <2 22.9 35 Mean duration of operation (minutes) (range) Given dexamethasone Median (range) follow-up (days) No of patients 40 (98) 28 (1851) 27 (66) 15 (37) 2 (5) 12 (29) 2 (5) 10 (24) 2 (05) 18 (44) 15 (37) 8 (20) 54 (23129) 20 (49) 255 (30680) Fig. 2. Swelling, redness, and pain after repair of an angle fracture 22 days postoperatively.

area were noted one and 3 months postoperatively. Local infections healed after removal of the osteosynthesis material. Seven patients developed swelling, redness, and pain with or without pus 276 days (median 32 days) after the operation (Fig. 2). Three of these patients were successfully treated with antibiotics taken orally, and 4 required removal of the Plate 103268 days postoperatively. In summary 9/13 patients required removal of the osteosynthesis material as a result of impaired wound healing. One healed with antibiotics and root canal treatment, and 3 with antibiotics taken orally. Table 2 shows the relations between impaired wound healing and possible risk factors. Healing was impaired in 7 of the 20 patients given dexamethasone and in 6 of the 21 controls (p = 0.66). Wound healing was more likely to be impaired in association with angle fractures (p = 0.13) than with those of

the body (p = 0.98) and symphysis/parasymphysis (p = 0.12), but the differences were not signicant. Age over 25 years was signicantly associated with impairment of healing (p = 0.02), but smoking (p = 0.27), delay in treatment (p = 0.43), and duration of operation (p = 0.64) were not.

Table 2 Association between impairment of wound healing and possible predictors (n = 41). Data are number or number (%) unless otherwise stated. Variable Sex Male Female Age (years) 25 and under Over 25 Smoking Yes No Site of infection Angle Body Symphysis/parasymphysis Delay in treatment (days) <2 2.93 35 Dexamethasone given operatively Yes No Total number of patients 40 1 20 21 27 14 27 4 22 18 15 8 20 21 13 Affected wounds 12 (30) 1 4 9 7 (26) 6 9 (33) 1 3 4 6 3 7 6 31 (293)

Fig. 1. Wound dehiscence in the region of an angle fracture 4 months postoperatively just before the plate was removed.

Wound healing impaired (median (range) days postoperatively)

Please cite this article in press as: Snll J, et al. Impairment of wound healing after operative treatment of mandibular fractures, and the inuence of dexamethasone. Br J Oral Maxillofac Surg (2013), http://dx.doi.org/10.1016/j.bjoms.2013.08.015

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Discussion We aimed to clarify the incidence of impaired wound healing after open reduction and osteosynthesis of mandibular fractures through an intraoral approach, and nd out whether the perioperative use of dexamethasone increased it. Wound healing was impaired in 13/41 (32%) of patients and in 13/53 (25%) of fractures. We found no signicant difference in the incidence between patients given dexamethasone and those who were not. Only age was signicantly associated with impaired wound healing in that the older the patient was the more likely were they to have impaired healing (p = 0.02). Published papers have shown conicting results about the inuence of perioperative glucocorticoids on postoperative complications. A study by Percival et al. showed that patients with postoperative infections (including local infections at the operative sites as well as generalised infections) were more likely to have been given dexamethasone intraoperatively and less likely to have been given perioperative antibiotic prophylaxis than those who had no infections.8 The authors concluded that the intraoperative administration of dexamethasone for anti-emetic purposes may confer an increased risk for postoperative infection. The operations in the analysis included orthopaedic, thoracic, neurosurgical, ENT, vascular, plastic, breast, urology, colonic, and gastroenterological procedures. Another study that focussed on gynaecological surgery showed contradictory results, in that there was no evidence of increased risk of surgical infections after a single dose of dexamethasone 48 mg.9 The oral area in general and the intraoral surgical approach in particular offer advantageous circumstances for bacterial infections. The meta-analysis by Dan et al., however, showed that giving glucocorticoids during oral surgery did not signicantly increase the risk of infection.3 Previously we arrived at the same result when we claried retrospectively whether perioperative glucocorticoids are associated with impaired wound healing in patients being treated for facial fractures: we found no signicant difference in the incidence of impaired wound healing between patients who were given perioperative glucocorticoids and those who were not.6 The results of the present study conrm these ndings. The perioperative use of dexamethasone 30 mg does not signicantly increase the risk of impaired wound healing in clinically uninfected mandibular fractures being treated surgically through an intraoral approach. One should note, however, that all the patients in this study were healthy and had no medical predisposition for infections such as autoimmune disease or taking immunosuppressive drugs. The potential effects of glucocorticoids on the immune system call for careful selection of patients, and a thorough history is essential to identify possible contraindications to their use.

Our only signicant correlation was between impairment of healing and age. Previous studies have shown that older patients are more likely to have postoperative infections in association with a mandibular fracture.10,11 Pre-existing medical conditions and drugs that potentially increase the risk of postoperative inammatory complications are more common among people over the age of 25 and may explain the results. The present study, however, included no patients with chronic conditions or taking long-term drugs, and conrms that increasing age is an independent predictor of infections. Wound healing was impaired in 13/53 (25%) of all fractures. There was more of an association with angle fractures (33%) than those of the body (25%) or symphysis/parasymphysis (14%), but not a signicant one. These rates are clearly higher than those previously reported in the USA. Ellis and Walker reported 25% in 69 angle fractures that were treated with two non-compression miniplates, with a wound dehiscence in one fracture and postoperative infections in 16.12 Ellis also reported 9% in 265 fractures of the body/symphysis that were treated with two miniplates, 16 wounds dehisced and 7 developed postoperative infections.13 In the present study the corresponding rate of infection in fractures of the symphysis, parasymphysis, or body 15%. Obviously several local and patient-related factors inuence the rate of impairment and explain the differences in the results. Nevertheless, the results of the present study as well of those of the above-mentioned studies indicate that fractures of the mandibular angle are particularly susceptible to postoperative complications. Because in the present study impairment of healing was established by 93 days or fewer, a follow-up period of 3 months seems sufcient to identify impaired wound healing and infection at the surgical site. One should note, however, that 3 of the patients not diagnosed with impaired healing were followed-up for fewer than 3 months (30, 40, and 42 days, respectively); one of these had been given dexamethasone. Although the wounds healed uneventfully in all 3 patients by the time of the nal examination, some patients with impairments may have been overlooked. A further multicentre study with a larger sample would provide more reliable conclusions about the drawbacks and benets of dexamethasone in the treatment of facial injuries. In summary, the use of dexamethasone 30 mg perioperatively was not signicantly associated with an increased risk of impaired healing in healthy patients with clinically uninfected mandibular fractures xed with titanium miniplates through an intraoral approach. Age over 25 was the only signicant predictor of impairment, which emphasises the importance of thorough anti-infective care in these patients during and after operation.

Conict of interest statement The authors declare that they have no conict of interest.

Please cite this article in press as: Snll J, et al. Impairment of wound healing after operative treatment of mandibular fractures, and the inuence of dexamethasone. Br J Oral Maxillofac Surg (2013), http://dx.doi.org/10.1016/j.bjoms.2013.08.015

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J. Snll et al. / British Journal of Oral and Maxillofacial Surgery xxx (2013) xxxxxx 5 6. Thoren H, Snall J, Kormi E, et al. Does perioperative glucocorticosteroid treatment correlate with disturbance in surgical wound healing after treatment of facial fractures? A retrospective study. J Oral Maxillofac Surg 2009;67:18848. 7. Champy M, Lodde JP. Mandibular synthesis. Placement of the synthesis as a function of mandibular stress (in French). Rev Stomatol Chir Maxillofac 1976;77:9716. 8. Percival VG, Riddell J, Corcoran TB. Single dose dexamethasone for postoperative nausea and vomitinga matched casecontrol study of postoperative infection risk. Anaesth Intensive Care 2010;38: 6616. 9. Eberhart LH, Holdorf S, Albert US, et al. Impact of a single perioperative dose of dexamethasone on the incidence of surgical site infections: a casecontrol study. J Obstet Gynaecol Res 2011;37:180712. 10. Hindawi YH, Oakley GM, Kinsella Jr CR, et al. Antibiotic duration and postoperative infection rates in mandibular fractures. J Craniofac Surg 2011;22:13757. 11. Malanchuk VO, Kopchak AV. Risk factors for development of infection in patients with mandibular fractures located in the tooth-bearing area. J Craniomaxillofac Surg 2007;35:5762. 12. Ellis III E, Walker L. Treatment of mandibular angle fractures using two noncompression miniplates. J Oral Maxillofac Surg 1994;52: 10327. 13. Ellis III E. A study of 2 bone plating methods for fractures of the mandibular symphysis/body. J Oral Maxillofac Surg 2011;69:197887.

Ethical approval The Ethics Committee of the Department of Surgery and the Internal Review Board of the Division of Musculoskeletal Surgery, Helsinki University Central Hospital, Finland, approved the study (Dno 33/E6/06).

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Please cite this article in press as: Snll J, et al. Impairment of wound healing after operative treatment of mandibular fractures, and the inuence of dexamethasone. Br J Oral Maxillofac Surg (2013), http://dx.doi.org/10.1016/j.bjoms.2013.08.015