Factors influencing the development of wound infection following free-flap reconstruction for intra-oral cancer q

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1 The British Association of Plastic Surgeons (2004) 57, Factors influencing the development of wound infection following free-flap reconstruction for intra-oral cancer q D.J. Cloke*, J.E. Green, A.L. Khan, P.D. Hodgkinson, N.R. McLean Department of Plastic and Reconstructive Surgery, Royal Victoria Infirmary, Newcastle-Upon-Tyne NE1 4LP, UK Received 14 October 2003; accepted 20 April 2004 KEYWORDS Head and neck cancer; Free flap reconstruction; Wound infection Summary Wound infection following tissue transfer in head and neck oncology is common. Factors known to be associated with infective complications include blood transfusion, pre-operative radiotherapy, duration of surgery, duration of preoperative stay and a history of smoking. The present study specifically examined 100 consecutive patients on a standard antibiotic protocol undergoing free flap reconstruction following resection of cancers of the oral cavity or oropharynx. Despite prophylactic antibiotics, 21 patients developed a head and neck wound infection. No statistically significant association was found between infective wound complications and a history of smoking, pre-operative radiotherapy or chemotherapy, length of pre-operative hospital stay, duration of surgery, or number of units of blood transfused. We conclude that, in this group of patients, wound infection is a common and difficult problem, but with no statistically significant association with any of the variables studied. Q 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. q Presented to the British Association of Plastic Surgeons, Summer Meeting, July 2000, Birmingham *Corresponding author. Address: 17 Windsor Terrace, South Gosforth, Newcastle-Upon-Tyne NE3 1YL, UK. Tel./fax: þ address: d.rcloke@lineone.net Infective complications following major head and neck surgery, which breaches the upper aerodigestive tract are commonplace. Such procedures are, by definition, clean-contaminated, 1 but infection rates are often higher than would be expected, being quoted as up to 68% without antimicrobial prophylaxis, 2 infection commonly being due to Gram negative organisms and Stapylococcus aureus. 2 Antibiotic prophylaxis is now routine, and suitable cover can be provided by cefuroxime and metronidazole, co-amoxiclav, clindamycin plus gentamicin or cefazolin. 3,4 Free-flap reconstruction after resection of intraoral cancer is now standard practice; however, this has been associated with increased risk of wound infections (rates of between 26 and 48% have been quoted for flap reconstruction in the upper aero-digestive tract, with prophylactic antibiotics. 5,6 The wound complication rate may also be higher if bone is transferred as part of a composite flap. 7 Previous studies of infection rates in head and S /$ - see front matter Q 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. doi: /j.bjps

2 The development of wound infection following free-flap reconstruction for intra-oral cancer 557 neck cancer surgery have identified several possible association with wound infection, including blood transfusion, pre-operative chemo- or radiotherapy, duration of surgery, length of hospital stay, tracheostomy and smoking. 2,5,6,8,9,10 However, no studies to our knowledge have specifically addressed infection rates in oral and oropharyngeal flap reconstructive surgery following cancer resection. To define those variables that might be associated with an increased risk of wound infection could be advantageous in terms of wound healing and surgical outcome. The present study investigated post-operative wound infection, following specified criteria, 1,11 for resection of head and neck cancer with free flap reconstruction in which the aerodigestive mucosa of the mouth or oropharynx was breached, and the neck dissected. Materials and methods The clinical records of 100 consecutive patients undergoing free flap reconstruction following resection of intraoral and oro-pharyngeal cancers in a single team between 1992 and 2000 were collected prospectively, and then the records reviewed. In all cases, the resection communicated between the neck and the oral cavity or oropharynx; hence all wounds were, by definition, classified as clean-contaminated. Data recorded included demographic factors, indication for surgery, the method of reconstruction, a history of smoking, pre-operative radiotherapy or chemotherapy, length of pre- and post-operative hospital stay, duration of surgery, number of units of blood transfused, antibiotic prophylaxis used, presence of a tracheostomy, and any evidence of head and neck wound infection, its treatment and outcome. As per unit protocol, the standard antimicrobial prophylaxis was intravenous cefuroxime 1.5 g and metronidazole 500 mg on induction of anaesthesia, followed by a further 5 days by NG tube. 4 Any deviation from this protocol was recorded. The diagnosis of wound infection was made when there was pus (or a serous discharge with positive culture) in, or exuding from, the wound, or painful a spreading erythema indicative of cellulitis around the wound. 11 Evidence of post-operative wound infection was recorded up to a maximum of sixmonths after surgery. Treatment of the infection (including surgery), any isolated causative organism, its duration and outcome were recorded. Analysis of categorical data was performed using Fisher s exact test, with a two-tailed p-value of less than or equal to 0.05 considered significant. Unpaired Student s t-tests were used to analyse continuous variables, with the same level of significance. Results A total of 100 patients with a mean age of 60.4 years (range 20 89) were studied, 25 of whom were female, and 75 male. The indications for operation are shown in Table 1, the commonest reason being intraoral squamous cell carcinoma. Surgery was performed for recurrent disease in 30 cases, of whom 18 had received previous radiotherapy. Thirteen patients had received neo-adjuvant radiotherapy of their primary lesion, giving a total of 33 patients who had irradiation prior to surgery. Reconstruction was by free radial forearm free flap in 94 cases, pedicled pectoralis major flap with radial forearm free flap in two cases, DCIA flap in two cases, a combined pectoralis major flap and vascularised fibular graft in one case, and combined radial forearm free flap and DCIA in one case. The most common disease site was floor of mouth (38 cases), followed by tongue (32), retromolar trigone (12), buccal (8), tonsillar (6), submandibular (2), and one case each of skin basal cell carcinoma and parotid disease necessitating full thickness resection into the oral cavity. Nine patients received antibiotic prophylaxis outwith the protocol due to a known pre-existing drug reaction: seven received flucloxacillin and metronidazole, one flucloxacillin, amoxycillin and metronidazole, and one erythromycin and metronidazole (who suffered an infective wound complication from which a haemolytic Streptococcus was grown). There was no significant increase in infection rate in those who received antibiotic prophylaxis other than the protocol. Ninety-eight patients underwent tracheostomy at the time of surgery for airway control; neither of Table 1 Diagnosis Indications for surgery Squamous cell carcinoma 93 Adenocarcinoma 3 Basal cell carcinoma a 1 Mucoepidermoid carcinoma 1 Small cell carcinoma 1 Osteosarcoma of mandible 1 Number of cases a BCC of chin requiring resection into floor of mouth.

3 558 D.J. Cloke et al. Table 2 Organism Organisms isolated from infected cases S. aureus 11 Haemolytic Streptococci spp 6 Methicillin-resistant S. aureus (MRSA) 5 Nonhaemolytic Streptococci spp 5 Pseudomonas spp 2 Anaerobes 1 Proteus spp 1 E. coli 1 Number of cases the two patients without tracheostomy developed a wound infection. Twenty-one patients developed a post-operative head and neck wound infection, of whom seven patients were readmitted. Infection was diagnosed between five and 168 days post operatively (mean 30.1 days). Seventeen infections were in the neck, two in the cheek, one in the mouth, and one concurrently in the mouth and neck. Six patients required surgical management of their infection; three abcesses were drained, one sinus curetted, one mandibular plate was removed, and one flap required debridement. In 11 of the infected cases, a mixed growth of organisms was isolated, and in seven cases only one organism was grown; Staphylococcus aureus (including methicillin-resistant S. aureus: MRSA) was the organism in all such cases. In three cases no organism was isolated, but there were clinical signs of infection. The organisms isolated are listed in Table 2. Antibiotic treatment of the infection consisted of a cephalosporin with metronidazole in seven cases with mixed growth, trimethoprim and fusidic acid for four cases of MRSA, flucloxacillin alone for four patients with S. aureus, flucloxacillin with penicillin for three mixed growths of Staph. and Strep., and one case each received teicoplanin (MRSA), clindamycin (S. aureus; penicillin allergic) and amoxycillin (Strep. infection). When the variables known to be associated with the potential for post-operative infection were analysed, the only one that achieved statistical significance was the length of post-operative stay in hospital ðp ¼ 0:002Þ: As well as the seven patients re-admitted with wound infections, those who acquired an infection whilst in hospital had a significantly longer post-operative hospital stay (mean 44.9 days, range 6 126) compared with those who did not (mean 24.7 days, range 5 75). Table 3 summarises the results. There were no significant differences between the infected and noninfected groups in terms of age, sex, preoperative stay, blood transfusion, duration of surgery, pre-operative radiotherapy or a history of smoking. Discussion Post-operative infection in head and neck oncological surgery is common, Bartzokas and colleagues 2 reporting a wound infection rate of 68% in a group of 32 patients undergoing a variety of clean-contaminated major head and neck procedures. The infection rate is somewhat lower with appropriate antibiotic prophylaxis, however. Coskun et al. 8 reported a wound infection rate of 30% in a series of clean-contaminated head and neck resections without reconstruction using antibiotic prophylaxis (clindamycin, or cefazolin plus tobramycin). Similarly, a wound infection rate of 33% has been reported by Sturgis et al. 9 in a study of resections from various head and neck sites without reconstruction. Murdoch et al. 4 noted an infection rate of only 3% in 100 patients with a variety of clean and clean contaminated procedures in the head and neck region; however, only eight of these were clean-contaminated resections of cancer with reconstruction. Girod et al. 6 quoted an infection rate of 26.2% in those patients in their series who had undergone flap reconstruction, but these were a combination of oral and laryngeal procedures. Penel et al. 5 found a total wound infection rate of 42% in their series of patients with resection of cancer from the upper aero-digestive tract. Of these, the rate was 48% for those undergoing flap reconstruction at all sites, and 32% for those undergoing oral/oropharyngeal resection, with or without reconstruction. The infection rate for hypopharynx/laryngeal resection was 55% in their series, compared with only 8.8% for laryngectomy by Rodrigo and Suarez. 2 Grandis and co-workers 12 found a local infection rate of 22% in their series of 134 cases of head and neck cancer resection without reconstruction. Eighty-three percent of their cases were oral cavity or oropharyngeal resections, but it is unclear how many infections occurred in this subgroup. More specifically, Rodrigo et al. 3 quoted rates of infection of four of 16 patients (25%) undergoing pedicled flap reconstruction in the head and neck, and 10 of 54 patients (18.5%) having resections from the oral cavity or oropharynx. There is little specific data on reconstruction within the oral cavity or oropharynx following resection of cancer in these cases. The local infection rate of 21% in our series, all of whom underwent free flap reconstruction within

4 The development of wound infection following free-flap reconstruction for intra-oral cancer 559 Table 3 Results Infected cases Noninfected cases Statistical test p-value N ¼ Mean age T-test NS Mean pre-op stay (days) T-test NS Mean duration of surgery (hours) T-test NS Mean number of units transfused T-test NS Post-operative stay (days) a T-test Significant Sex 8F/13M 17F/62M Fisher s NS Pre-op radiotherapy 7 24 Fisher s NS No. of patients transfused Fisher s NS No. of smokers Fisher s NS No. with surgery.8 h 9 33 Fisher s NS No. transfused. 4 units 6 16 Fisher s NS No. with pre-op stay. 4 days Fisher s NS NS, nonsignificant. a Patients re-admitted with infection excluded. the mouth or oropharynx, compares favourably with other, less specific, data. In our series, seven out of 100 cases required re-admission due to wound infection, and there was a significantly longer hospital stay in the remainder of patients with infection. Apart from the increased morbidity and hospital stay associated with wound infection, it has been hypothesised that tumour recurrence rates may be affected, possibly by immunological mechanisms. Rodrigo and Suarez 13 noted a higher rate of recurrence in laryngectomy patients who had suffered wound infections, and Grandis et al. 12 suggested this association may be due to lowered host immunity. However, Sturgis et al. 9 found no association between infection and recurrence rate in their series of 61 cases of head and neck cancer resection. Previously reported associations with post-operative wound infection include blood transfusion, pre-operative chemo- or radiotherapy, duration of surgery, length of hospital stay, tracheostomy and smoking. 2,5,6,8,9,10 Penel et al. 5 studied a series of 165 resections of head and neck cancer from various sites, and found a higher wound infection rate associated with chemotherapy, longer preoperative stay and tracheostomy. However, flap reconstruction was carried out in only 82 of this series. Coskun et al. 8 studied a large series of head and neck procedures, of which 207 were clean contaminated, but none underwent flap reconstruction. They did not find any association between radiotherapy and infection. Similarly, in a smaller group of 32 patients undergoing clean-contaminated procedures, Bartzokas et al. 2 found no link with radiotherapy in their 22 cases of wound sepsis. Sturgis et al. 9 described a significantly higher wound infection rate in patients with a history of smoking, blood transfusion (a linear trend), longer operative time, higher blood loss, and increased pre- and post-operative stay. It is not clear, however, whether these were patients who underwent reconstructive surgery. However, Hoffmann et al. 10 have described complications in their series of 227 microsurgical free tissue transfers in the head and neck region, of which 70% were for malignancy. Seven percent of cases showed delayed wound healing at the recipient site. They used a variety of flaps, of which 46 were radial forearm free flaps. They described a variety of complications, including donor site problems, but noted a higher incidence of recipient site problems after radio- or chemotherapy. However, the authors did not specifically analyse neck wound infection rates. In another series of patients undergoing procedures within the oral or pharyngeal cavity, with a wound communicating with the neck, 6 a higher overall complication rate was correlated with radiotherapy, blood transfusion, operative time and flap reconstruction (52% of their series). However, wound infections were only more frequent in association with pre-operative radiotherapy, and only infections occurring up to 30 days postoperatively were recorded. These reports on the factors associated with wound infection in head and neck reconstructive procedures are clouded in several aspects. In many series, there are a variety of surgical indications, resection sites, and reconstructive procedures, and some studies have also included wound complications from the tissue transfer donor site. We believe our study has several significant advantages. We have selected only patients undergoing microvascular free flap reconstruction for malignancy within the oral and oropharyngeal cavities, have specifically addressed recipient site wound infections, and have recorded these at any

5 560 D.J. Cloke et al. point following surgery, up to 6 months postoperatively. Our wound infection rate of 21% compares well with previous, less specific, studies. The microorganisms isolated justify our use of cefuroxime and metronidazole as prophylaxis. We have demonstrated no statistical association in this series between wound infection and blood transfusion, length of pre-operative stay, smoking or duration of surgery. This appears to be in contrast to previous studies, but may be due to the specificity of our sample population. What is clear, however, is that wound infection following free tissue transfer to the oral and oropharyngeal cavities is a common problem, often necessitating readmission following hospital discharge, further surgery, and prolonged hospital stay. We cannot identify any factors in our series that may be useful to address this, but further study is required to enable us to reduce the rate of this cause of increased morbidity in this group. References 1. Cruse PJE. Classification of operations and audit of infection. In: Taylor EW, editor. Infection in surgical practice. Oxford: Oxford University Press; p Bartzokas CA, Raine CH, Stell PM, Corkhill JE, Withana N, Trafford-Jones GM. Bacteriological assessment of patients undergoing major head and neck surgery. Clin Otolaryngol 1984;9: Rodrigo JP, Alvarez JC, Gomez JR, Suarez C, Fernandez JA, Martinez JA. Comparison of three prophylactic antibioltic regimens in clean-contaminated head and neck surgery. Head Neck 1997; Murdoch DA, Telfer MR, Irvine GH. Audit of antibiotic policy and wound infection in neck surgery. J R Coll Surg Edinb 1993;38: Penel N, Lefebvre D, Fournier C, Sarini J, Kara A, Lefebvre J- L. Risk factors for wound infection in head and neck cancer surgery. Head Neck 2001; Girod DA, McCulloch TM, Tsue TT, Weymuller EA. Risk factors for complications in clean-contaminated head and neck surgical procedures. Head Neck 1995;17: Kroll SS, Schusterman MA, Reece GP, Miller MJ, Evans GRD, Robb GL, Baldwin BJ. Choice of flap and incidence of free flap success. Plast Reconstr Surg 1996;98: Coskun H, Erisen L, Basut O. Factors affecting wound infection rates in head and neck surgery. Otolarngol Head Neck Surg 2000;123: Sturgis EM, Congdon DJ, Mather FJ, Miller RH. Peroperative transfusion, postoperative infection, and recurrence of head and neck cancer. South Med J 1997;90: Hoffmann J, Eherenfeld M, Hwang S, Schwenzer N. Complications after microsurgical transfer in the head and neck region. J Cranio-Max Surg 1998;26: Peel ALG. Definition of infection. In: Taylor EW, editor. Infection in surgical practice. Oxford: Oxford University Press; p Grandis JR, Snyderman CH, Johnson JT, Yu VL, D Amico F. Postoperative wound infection a poor prognostic sign for patients with head and neck cancer. Cancer 1992;70: Rodrigo JP, Suarez C. Prognostic significance of postoperative wound infection on head and neck cancer. Otolarngol Head Neck Surg 1998;118:272 5.