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Necrotizing soft tissue infections of the head and neck: Case reports and literature review
Necrotizing soft tissue infections of the head and neck: Case reports and literature review Jeremy McMahon, BDS, MBChB, FDS, FRCS,a Terrence Lowe, BDS, MBChB, FDSRCPS, FRCS,b and David A. Koppel, BDS, MBBS, FDS, FRCS,c Glasgow, Scotland WEST OF SCOTLAND MAXILLOFACIAL SERVICE
A small but nevertheless important part of a surgeon’s experience comprises necrotizing soft tissue infections of the head and neck. The purpose of this report is to heighten awareness of necrotizing soft tissue infections in any patient with an infection of the head and neck. The article also outlines an appropriate management strategy for use in the treatment of patients with this potentially fatal condition. Prompt diagnosis and early radical surgical debridement are significant factors in avoiding a fatal outcome in these patients. This article reviews the literature on necrotizing soft tissue infections of the head and neck and presents cases from our recent experience. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:30-7)
Necrotizing soft tissue infections constitute a small but nevertheless important part of a surgeon’s experience. The importance rests with the fact that advancing tissue necrosis signifies a life-threatening condition that demands prompt surgical intervention if a fatal outcome is to be averted. These infections respect no anatomic boundaries and present to surgeons of all specialties, maxillofacial surgery being no exception. To distinguish these from less serious infections requires a high level of awareness because their initial presentation may be deceptive. Delay in diagnosis has been demonstrated to be associated with an increased mortality in several studies.1-4 This infection is neither common nor rare, so that every surgeon is highly likely to encounter the condition but not with sufficient frequency to produce familiarity.5 The taxonomy applied to these infections is varied (Table), confusing, and not always conceptually useful. Dellinger3 states that much of this terminology may be dispensed with or simplified, and the separate syndromes cited in the medical literature may be considered different manifestations of the same pathologic process. The exception to this is the particular case of histotoxic clostridial myonecrosis (gas gangrene). This condition differs in important respects. Histologically, toxin-induced muscle necrosis proceeds rapidly in advance of actual bacterial invasion. Furthermore, this a
Consultant Maxillofacial Surgeon, West of Scotland Maxillofacial Service. b Specialist Registrar, West of Scotland Maxillofacial Service. c Consultant Craniofacial/Maxillofacial Surgeon, West of Scotland Maxillofacial Service. Received for publication May 29, 2002; returned for revision Sep 5, 2002; accepted for publication Oct 1, 2002. © 2003, Mosby, Inc. 1079-2104/2003/$30.00 ⫹ 0 doi:10.1067/moe.2003.15
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Table. Terms applied to necrotizing soft tissue infections Nonclostridial gas gangrene Hemolytic streptococcal gangrene Necrotizing erysipelas Synergistic necrotizing cellulitis Meleney’s bacterial gangrene Necrotizing cellulitis Fournier’s gangrene Necrotizing fasciitis
infection is more rapidly progressive and has a higher mortality than its nonclostridial myonecrosis counterpart.4,6 Thus, the taxonomy can be reduced to 2 clinical entities: histotoxic clostridial myonecrosis and all other necrotizing soft tissue infections, both clostridial and nonclostridial. This classification has utility because the treatment is the same for all the described anatomic sites. We prefer the term necrotizing soft tissue infection to the commonly applied term necrotizing fasciitis because the former provides a better conceptual framework for the radical surgical debridement required. The problem with the term necrotizing fasciitis is that it implies the process involves only subcutaneous fascial layers. Although this is not infrequently the case, it is by no means necessarily so. The necrotizing infective process may involve any adjacent tissue, including muscle. The management principles have been clearly defined; the crucial step lies with the prompt recognition of the presence of necrotic tissue and its radical surgical debridement, irrespective of composition, immediately after resuscitative measures, combined with antimicrobials in high dosage. These measures must be accompanied by careful physiologic monitoring to identify
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Fig 2. Initial resection of necrotic tissue.
Fig 1. Head shaved to reveal necrotizing soft tissue infection.
any organ dysfunction with early institution of appropriate supportive therapy. A brief survey of the literature yields many reports of necrotizing soft tissue infections in the head and neck region.4,7-18 CASE REPORTS Case 1 A 49-year-old woman was referred to the emergency service by her general medical practitioner with an infected scalp wound. The history given was that of a fall 3 to 4 weeks previously causing a scalp laceration. At the time the patient thought the injury was trivial and did not require any medical attention. However, during the 24 hours before admission the patient had become increasingly ill with anorexia, nausea, and vomiting. The medical history was significant for epilepsy controlled with sodium valproate, previous abdominal surgery, and alcohol dependency. She was noted to be a heavy smoker. On examination she appeared generally ill with a fluctuant swelling behind the right ear. She was afebrile, and vital signs were heart rate 120 bpm, blood pressure 100/60 mm Hg, and respiratory rate 22/min. Full blood count and routine biochemistry showed white blood count 19.3 ⫻ 109/L, hemoglobin 114 g/L, and a urea of 27.3 mmol/L. The remaining hematologic and biochemical investigations were within normal limits. Intravenous fluids were administered, and cefuroxime 1.5 g plus metronidazole 500 mg every 8 hours were commenced intravenously. A provisional diagnosis of cellulitis was made. Twelve hours later there had been no improvement in her general condition. She was transferred to the operating suite for an examination under general anesthesia and wound debridement. At surgery, hair was shaved to reveal a necrotizing soft tissue infection (Fig 1). The area of necrotic tissue was resected to include pericranium, and the peripheral margins were taken back to the bleeding scalp (Fig 2). Intraoperatively, the estimated blood loss was 3 L. Cardiovascular instability required inotropic support as well as transfusion of
packed red cells to maintain blood pressure and urine output. Central venous pressure was maintained above 24 mm H2O. The wound was dressed; microbiologic samples were sent to the laboratory; and the patient was transferred to the intensive care unit, intubated, and ventilated. During the next 24 hours hemodynamic instability required maximal inotropic support, and signs of acute respiratory distress syndrome developed. Computed tomography (CT) scanning to exclude intracranial pathologic condition was precluded by hypotension induced by movement. Initial antimicrobial therapy comprised benzyl penicillin 2.4 g every 4 hours, clindamycin 1.2 g every 6 hours, and continuation of metronidazole 500 mg every 8 hours. On the fourth day after presentation the patient’s condition had stabilized enough to allow a CT scan. This showed no evidence of brain abscess or skull fracture but did reveal small infarctions in both cerebral hemispheres and left temporal lobe calcification. A further debridement of necrotic scalp tissue was performed (Fig 3). Throughout this period she remained intubated and on ventilation support. On day 8, purpura of the flanks developed (Fig 4), and spontaneous bleeding occurred from the mouth, nose, and vagina. The platelet count had decreased to 27 ⫻ 109/L. A diagnosis of heparin-induced thrombocytopenia was made, and subcutaneous heparin was discontinued. Although the platelet count improved, the patient remained inotropic and ventilator dependent. On day 14, a deterioration in the neurologic state became obvious with the development of hemiparesis. A further CT scan showed a large brain stem infarct, and on day 20 she died without regaining consciousness.
Case 2 Forty-eight hours before admission a 40-year-old woman had tripped and fallen while jogging, striking the left forehead and orbital region on the curb. This produced an apparently superficial laceration of the forehead approximately 2 cm long as well as swelling and bruising about the left eye. The following morning, 36 hours before admission, she came to the emergency department at the treating hospital. Vital signs were normal; there was no visual impairment or injury to the
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Fig 3. Further debridement of necrotic scalp.
globe. A full range of eye movements was noted, and neurologic examination was normal. No evidence of skull or facial bone fractures was found on physical or radiographic examinations. The facial wound was assessed as minor in nature, and, after ensuring adequate tetanus immunity, the patient was discharged with arrangements made for ophthalmology follow-up at the next available clinic, 48 hours from the time of presentation. Twelve hours before admission the patient revisited the emergency department complaining of a yellow purulent discharge from the left eye that had developed overnight. The left periorbital swelling was now very marked, with crusting evident on the lid margins (Fig 5). She was now unable to open her left eye. Mild right periorbital edema was also noted. The emergency department medical officer was under the impression that this was a severe bacterial conjunctivitis. Antibiotic ophthalmic drops were prescribed, and she was advised to keep her ophthalmology clinic appointment the following day. She reappeared with her family 12 hours later at which time a referral was made to the maxillofacial surgical service. During that time period there had been progressive pain and swelling in the left periorbital and temporal region with anorexia, malaise, and rigors. In addition, the left upper eyelid skin had clearly undergone necrosis. On examination she was febrile with a peripheral temperature of 39°C and tachycardic at 112 bpm, and the peripheral circulation was assessed as being hyperdynamic. Tachypnea (30 breaths per minute) was also present. A full blood count showed a marked neutrophil leukocytosis (total white blood count 41.0 ⫻ l09/L, neutrophils 37.3 ⫻ l09/L). All other hematologic parameters were normal, and the serum urea, creatinine, and electrolytes were all within the normal range. She was well oxygenated on supplemental oxygen (PaO2 20.3 kPa on fraction of inspired oxygen of 40%) and exhibited no metabolic acidosis (base excess ⫹2 and arterial bicarbonate of 22 mmol/L). No significant medical or surgical history was elicited in this patient, who was a nonsmoker and drank no ethanol. The ischemic skin on the upper eyelid was incised, and a swab was taken. Similar specimens were taken after incision through the superficial lateral forehead laceration and sent for
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Fig 4. Purpura on flanks.
immediate Gram stain. After blood culture samples were obtained, high-dose antibiotic therapy was commenced, comprising benzyl penicillin 2.4 g every 4 hours, cefotaxime 2.0 g every 8 hours, and metronidazole 500 mg every 8 hours. Arrangements were made to transfer her to the operating suite with the diagnosis of a necrotizing soft tissue infection. At operation the necrotic eyelid skin and orbicularis muscle were excised, leaving an intact and apparently viable tarsal plate and levator muscle. The skin around the lateral forehead laceration was assessed as only marginally viable and therefore excised over an area of 3 ⫻ 1.5 cm. Underlying fascia was clearly necrotic and excised back to clearly bleeding tissue in the temporal fossa. The wounds were dressed, and the patient was transferred to the intensive care unit with a plan for second-look surgery during the ensuing 12 to 24 hours. The Gram stain on swabs taken from the wound had identified gram-positive cocci compatible with streptococci. On the advice of the clinical microbiology service the cefotaxime was discontinued and gentamicin 120 mg every 12 hours was commenced. Benzyl penicillin and metronidazole were continued according to the dose regimen described above for a total of 6 days. The patient remained intubated and sedated on the intensive care unit overnight. The following morning the wounds were examined on the intensive care unit, and no further areas of tissue necrosis were seen. She was weaned from the ventilator and discharged from the intensive care unit to a regular unit in stable condition. On admission to the regular unit this patient was found to be well oxygenated with a saturation of 99% on a fraction of inspired oxygen of 40%. A satisfactory urine output was maintained. Urea and electrolytes were normal, as were coagulation indexes. However, a persistent neutrophil leukocytosis (white blood count 26.8 ⫻ 109/L) was noted, and hemoglobin estimation had fallen to 9.0 g/dL and albumin to 25 g/L. In view of persistent pyrexia and tachycardia, a further inspection of the wound was performed at 8 PM. At this time a clear deterioration had occurred, with a seropurulent discharge from the wound and further necrotic tissue visible in the temporal fossa on retrac-
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Fig 6. Resection of necrotic tissue. Fig 5. Left periorbital swelling and crusting of lid margins.
tion of the skin edge. Arrangements were made for prompt transfer to the operating suite. A coronal flap was raised to gain wide exposure of the tissues of scalp and left temporal fossa. The left temporoparietal fascia and in-continuity galea from the zygomatic arch to a point approximately 3 cm above the superior temporal line and extending from above and behind the pinna to the lateral orbit were found to be necrotic. In addition, the entire left deep temporal fascia was necrotic. All necrotic tissue in this region was debrided. The skin overlying this region was resected. Edematous pericranium was found in the region of the vertex and in continuity with areas of necrosis described. This abnormal-appearing tissue was also removed (Fig 6). A small area of necrotic orbital fat was removed from the vicinity of the lateral canthus. The temporalis muscle underlying the necrotic fascia was viable, ie, bleeding freely and contracting on stimulation. At this point there was no residual nonviable or marginally viable tissue present, and the wound was dressed. The patient remained normotensive throughout. During the procedure, 2 units of concentrated red cells were transfused as well as 1500 mL of a crystalloid solution, and the patient was transferred to the intensive care unit. A further return to the operating suite was scheduled for the following morning. Overnight, erythema and swelling extending from the parotid region to clavicle were noted in the ipsilateral neck. The patient was, however, afebrile and remained so for the rest of her stay, the tachycardia was no longer present, and all other vital signs remained normal and stable. At operation the following day, the ipsilateral neck was explored with no abnormality found other than mild edema anterior to the carotid sheath. A small amount of pericranium and orbital fat of doubtful viability was resected, and the wound was dressed. Postoperatively she was begun on nasogastric tube
feeding and was able to resume oral intake 2 days later. Two further dressing changes were performed during the ensuing 3 days without further debridement being necessary. She was transferred to another hospital for reconstruction 7 days after her admission in a stable condition with normal vital signs as well as normal hematologic and serum biochemical parameters.
Case 3 An 86-year-old woman was referred to the emergency department by her general medical practitioner after having fallen 2 days previously. Since this minor fall, which did not result in loss of consciousness, her face had become increasingly painful and swollen. Her medical history was significant for controlled hypertension, vertebrobasilar insufficiency, and peptic ulcer disease. Regular medications included ranitidine and a loop diuretic. She lived in sheltered accommodation, and her mobility was limited by osteoarthritis. On examination she was found to be alert with a Glasgow Coma Score of 14, her heart rate was 94 bpm, and her blood pressure was recorded as 97/70 mm Hg. The left side of her face was swollen and erythematous; the left eye was shut with a serous discharge from the lateral aspect of the left infraorbital region. Visual acuity, assessed by counting fingers, was intact in both eyes. The remainder of the examination was unremarkable. Skull radiography showed no vault fracture; however, an infraorbital rim fracture was suspected on facial views. A diagnosis of orbital cellulitis was made, and referral to the ophthalmology service was made. After review by the duty ophthalmologist 1.5 hours later, referral to the maxillofacial surgical service for further management was initiated. On examination the patient was obviously confused, tachy-
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Fig 7. Left periorbital edema and soft tissue necrosis.
pneic and tachycardic at 120 bpm, and clinically dehydrated. Other significant findings were pyrexia (38.9°C) and hypoxemia (oxygen saturation in arterial blood of 81%). Immediate resuscitation measures comprised intravenous crystalloid fluids and supplemental oxygen via a mask. Benzyl penicillin 1.2 g and metronidazole 500 mg were administered intravenously. Hematologic and biochemical investigations were within normal range apart from an increased urea level of 14.9 mmol/L and creatinine of l97 mol/L. A clotting screen was also within normal limits. Arterial blood gases on oxygen 4 L/min via mask were consistent with a metabolic acidosis. Blood cultures were taken, a urinary catheter was passed, and a provisional diagnosis of a necrotizing soft tissue infection was made (Fig 7). She was promptly transferred to the operating suite. At operation nonviable infraorbital skin and underlying muscle were excised to bleeding, grossly healthy tissue. The wound was copiously irrigated and dressed; the excised tissue was sent for immediate microbiologic investigation. During the procedure the patient became cardiovascularly unstable, requiring intravenous fluids and dopamine plus adrenaline to maintain her blood pressure above 100/50 mm Hg. Urine output was minimal, and several episodes of atrial fibrillation occurred that spontaneously reverted to sinus tachycardia. She was transferred to intensive care following this procedure, where she remained intubated and on ventilation. Maximal inotropic support (adrenaline, noradrenaline, and dopamine) was required. Eight hours postoperatively the wound was inspected, and there was a progressing erythema down the left side of the neck and anterior chest wall, across the bridge of the nose to involve the contralateral eyelids, and extending posteriorly to the mastoid region. The urine output remained negligible, and she died with no further surgical intervention 56 hours after presentation. All the microbiologic investigations showed heavy growth of Streptococcus pyogenes (group A).
DISCUSSION Necrotizing soft tissue infections caused by S pyogenes alone have been called hemolytic streptococcal
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gangrene.19 However, the clinical course is indistinguishable from that caused by a polymicrobial flora of aerobic and anaerobic, gram-positive and gram-negative bacteria.3,4,20 Furthermore, management is identical irrespective of what subsequently proves to be the microbiologic basis. When only a single organism is isolated, this is most often reported as being S pyogenes3,4,20; however, this is not uniformly the case.4 Taken as a whole, necrotizing soft tissue infections (excluding histotoxic clostridial myonecrosis) usually show multiple species,3,4,20 with up to 11 organisms being isolated from a single case.20 In the head and neck region, the majority of reports indicate that the origin is most often the mouth or oropharynx, and odontogenic sepsis predominates.4,8,9,13,15,16,21 Although this has not been our recent experience, senior clinicians in our unit can certainly recount cases in which this was the case. Streptococcal species are frequently seen, but a highly variable polymicrobial flora is most often reported in this region as elsewhere, including Enterobacter, Pseudomonas, Proteus, Enterococcus,21 Fusobacterium, Bacteroides, staphylococci,15 and diptheroids,13 to name but a few. The clinical relevance of this is that initial empiric antibiotic therapy must be of broad spectrum as well as high dosage to be certain of adequate treatment of these serious infections. Clostridium species may be found as copathogens or even the predominant pathogen in cases that are not histotoxic clostridial myonecrosis (gas gangrene).1,3,4,13 It should be noted therefore that the diagnosis of this latter clinical entity must be made on clinical features, operative findings, and the patient’s progress. It does not rest solely on the recovery of clostridium in culture.6 It is our practice to begin all patients with necrotizing soft tissue infections on high-dose intravenous benzyl penicillin (2.4 g every 4 hours in adult patients), flucloxacillin (1 g every 6 hours), and metronidazole (500 mg every 8 hours). Otherwise, our initial antibiotic selection is in accordance with that of Dellinger,6 who suggests that all patients receive cefotaxime (2 g every 8 hours in adult patients) or another third-generation cephalosporin, and metronidazole (500 mg every 8 hours). Clindamycin 900 mg every 8 hours can be given as a substitute for metronidazole and will also cover streptococci. Imipenem/cilastatin alone, 500 mg intravenously every 6 hours, also provides adequate empiric therapy. If a Gram stain shows the presence of gram-positive cocci, then penicillin 20 million units during a 24-hour period is the treatment of choice. However, it is prudent to continue the cefotaxime and metronidazole until the details of culture become available because polymicrobial sepsis is a feature of many necrotizing soft tissue infections as already stated. Dos-
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age and dosing interval adjustments are frequently necessary in these patients because of preexisting renal disease or acute renal failure. On presentation, every effort must be made to obtain appropriate bacteriologic specimens. These should comprise a minimum of 2 sets of blood cultures taken 20 minutes apart as well as specimens from the wound. Care must be exercised with respect to the interpretation of culture results of specimens obtained from open wounds because contamination is frequent. The most reliable specimens are those obtained at operation at a point remote from any open wound, and such specimens must be obtained. However, it is our practice to defer commencement of empiric antibiotic therapy only while initial blood cultures and wound swabs are taken and not to await operative samples. There is clearly a requirement for an early and ongoing close consultation with the clinical microbiology/ infectious disease service. It was previously mentioned that recognition of necrotizing soft tissue infection may be problematic. The significance of this cannot be overemphasized because delay to diagnosis has been demonstrated to have a clear adverse effect on the patient’s likelihood of survival in numerous studies.1-4,22-24 That the local features may belie a more extensive subcutaneous process is a characteristic of necrotizing soft tissue infections and is a significant factor leading to delay in diagnosis. A simple subcutaneous abscess has a central necrotic portion but differs from the conditions being considered here in that it is localized to the area of discernible abnormality.6 The necrotizing soft tissue infections, on the other hand, are poorly localized and are characterized by inflammation and necrosis extending deep to what is normal-appearing skin. Skin changes are characterized by the signs of acute inflammation, in particular erythema, edema, and hyperesthesia. Pain, however, may not be an especially prominent feature in the nonclostridial myonecrosis6 type. This has certainly been our experience. What is prominent are fever and the other features of systemic inflammatory response syndrome (SIRS).26 Thus, a necrotizing soft tissue infection should be suspected whenever a trivial or clean wound is followed, in 12 to 36 hours, by prominent systemic signs of sepsis. Crepitus and blistering are generally late features, the former representing the presence of gas in the tissues. It is recognized that most necrotizing soft tissue infections with the presence of gas are not of the histotoxic clostridial myonecrosis (gas gangrene) type but rather of the more common nonclostridial necrotizing soft tissue infection6 forming the focus of this report. In the presence of infection, the identification of gas within the tissues is always significant unless there
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is an alternative explanation such as pulmonary barotrauma, pneumothorax, or upper airway injury. Most facultative bacteria produce insoluble gas during anaerobic, but not aerobic, metabolism. The presence of gas in the tissues with infection implies an anaerobic tissue environment incompatible with viable living tissue.6 In other words, tissue necrosis has occurred, and prompt operative intervention with radical debridement is mandated. Radiology, especially CT, is much more sensitive than palpation in detecting gas in the tissues.10,13 This may be useful in distinguishing a necrotizing soft tissue infection from a cellulitis. We do, however, have reservations about its accuracy in guiding clinical decision making. The defining and clinically important feature is that of tissue necrosis rather than gas production. Furthermore, it is not clear from the literature how frequently necrotizing soft tissue infections are accompanied by the production of gas in the tissues. Certainly, in the presence of rapidly progressive infection and a marked systemic response, we would not omit prompt surgical exploration on the basis of a negative CT scan. Necrotizing soft tissue infections often result in the sequestration of a significant amount of fluid and a marked hemodynamic response. This response is highly variable, from minimal to profound septic shock. In every case, the potential for profound cardiovascular and respiratory failure exists. In addition, renal failure is a frequently associated complication.4,6 Careful evaluation, resuscitation, and appropriate monitoring are therefore mandatory. An intensive unit level of care is the minimum requirement, with continuous pulse oximetry, hourly monitoring of urine output, and frequent recording of hemodynamic values and respiratory rate. In 1984 Stamenkovic and Lew3 reported the use of frozen section biopsy to make an early diagnosis in necrotizing soft tissue infections. In a retrospective analysis of an institution’s experience with this condition, they were able to demonstrate a significant improvement in survival associated with a much reduced delay to diagnosis where this investigation was used. This diagnostic test appears both sensitive and specific. However, it is plausible that the most important step was considering the diagnosis early, rather than actually performing the test, in producing the markedly reduced mortality in the group who underwent frozen section biopsy. These patients are widely held to be susceptible hosts; ie, systemic illness renders them more susceptible to infection. This perception is borne out by the largest series of patients reported to date.4 In this series, comprising 198 patients at the University of Maryland Shock Trauma Center, the large majority could be considered to have a preexisting medical condition
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rendering them susceptible; the most common of these was diabetes mellitus, present in more than half of the patients. However, one of our patients (case 2) demonstrates this not to be universally the case, and clinicians should be aware that increased host susceptibility is not necessarily a precondition for necrotizing soft tissue infection. With a logistic regression analysis applied to the broad range of potentially interdependent variables, Elliott et al4 in their large series of patients were able to demonstrate a number of factors significantly associated with an increased likelihood of a fatal outcome. Mortality among those older than 60 years was 5 times that of younger patients. Female gender was also associated with a worse prognosis. Other factors shown to be independently associated with mortality were renal impairment and a shift in peripheral energy utilization from aerobic to anaerobic metabolism as evidenced by elevated serum lactate level. A delay to first debridement was a significant factor associated with increased mortality in this as well as other studies. The extent of infection as a percentage of body surface area and the degree of organ system dysfunction at admission also correlated with an excess risk of death. These latter findings are hardly surprising because, in critical illness due to other causes, admission lactic acidosis and multiple organ dysfunction had a significant impact on a patient’s survival expectation.26,27 In the 2 patients who died in this case report, multiple organ dysfunction was an admission feature as was premorbid systemic illness. In the surviving patient, on the other hand, a base deficit was not seen, and significant dysfunction did not occur in any organ system. The absence of a preexisting systemic disease in a patient who was young and healthy, ie, good physiologic reserve, was undoubtedly a highly significant factor in the favorable outcome. The findings that extent of infection and delay to initial surgery adversely affect outcome emphasize the importance of prompt recognition and surgical intervention to halt the spread of the necrotizing process and to prevent the development of systemic complications produced by inflammatory mediators. The mortality rate in the series reported by Elliott et al was 25.3%. This, however, rose to more than 40% when 3 organ systems were failing and 80% when 5 organ systems demonstrated dysfunction. With the high mortality of this condition and the frequent development of organ failure, the early involvement of an intensivist is indicated in all cases. The extent of surgical excision and debridement is determined by the gross findings at operation. Careful consideration should be given to the placement of incisions so that wide access is accomplished to all extensions of the necrotizing processes without compromising the perfusion of the surrounding
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tissues. Excision of all tissue that is nonviable continues until normal-appearing tissue is encountered that bleeds freely on incision. Potentially involved muscle should contract normally on stimulation, and it is important to inspect muscle lying beneath deep fascia at the initial procedure. Extensions of the process may be connected by narrow bridges of necrosis that must be carefully sought. In all cases, a minimum of 2 operations is considered advisable.4,6 Extension is easily overlooked at the first procedure, and what was marginally viable at the first procedure may be necrotic in 24 hours. The second procedure is therefore scheduled for the following day at completion of the first. If significant infection is discovered at this second procedure, a third must be scheduled and so on. When no further infection is found, the surgical phase of the treatment is completed pending commencement of reconstruction of the resultant defect, after the patient has been stable for a number of days. The management of skin overlying areas of subcutaneous and fascial necrosis is controversial. Some authors20 advocate excision to the margins of such areas of necrosis, whereas others favor a more conservative approach.4 The latter leave the wound open until it is clear that the process has been arrested and the patient has stable physiology. This was the dilemma in case 2 in which necrosis of temporoparietal fascia had exposed hair follicles in the deep dermis. In reconstructive surgery this is the superficial plane of dissection in raising the temporoparietal fascial flap, a procedure not usually associated with healing problems in the overlying skin. At the second procedure there appeared to be a rapidly progressive necrotizing soft tissue infection, and it was elected to remove this skin. This may not have been necessary and certainly significantly increased the resulting disfigurement. Hyperbaric oxygen therapy has been used as an adjunct in the treatment of necrotizing soft tissue infections.6,28,29 No randomized clinical trials have been conducted to validate the role of hyperbaric oxygen, and given the infrequency with which this condition is encountered, it seems unlikely that such a study will take place.28 Subexperimental studies have not consistently demonstrated a significant survival advantage, but all have been conducted in small numbers of patients with an apparent trend toward improved outcome. Therefore, if hyperbaric oxygen treatment is available, it seems prudent to add this treatment. However, it is emphasized that such adjunctive treatment should take place only after adequate resuscitation, appropriate empiric antimicrobial administration, and operative treatment have been instituted. Delay in any of these 3 aspects of therapy in patients with necrotiz-
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ing soft tissue infections is contraindicated for any reason, including transfer to a unit with a hyperbaric oxygen facility. To summarize, the treatment of necrotizing soft tissue infections should consist of hemodynamic and respiratory evaluation, resuscitation, and monitoring; obtaining appropriate bacteriologic specimens; instituting high dose broad spectrum intravenous antimicrobial therapy; surgical excision and debridement; planned second look surgery; nutritional support; and possibly hyperbaric oxygen therapy. CONCLUSIONS Every surgeon during a practicing career is likely to encounter the devastating and fortunately uncommon condition of necrotizing soft tissue infection. Delay to diagnosis and treatment is a significant factor in the high mortality of necrotizing soft tissue infections. Preventable deaths can be avoided only by a high level of awareness by clinicians at all levels and particularly in those who are at the first point of patient contact.
12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23.
We would like to thank all our colleagues who were involved in the care of the patients presented in this article, particularly Mr A. W. Baker, Mr N. Hammersley, Mr S. Hislop, Mr D. I. Russell, and Mr S. Watson.
24. 25.
REFERENCES 1. Kaiser RE, Cerra FB. Progressive necrotizing surgical infections: a unified approach. J Trauma 1981;21:349-55. 2. Pessa ME, Howard RJ. Necrotizing fasciitis. Surg Gynecol Obstet 1985;161:357-61. 3. Dellinger EP. Severe necrotizing soft tissue infections: multiple disease entities requiring a common approach. JAMA 1981;246: 1717-21. 4. Elliott DC, Kufera JA, Myers RAM. Necrotizing soft tissue infections: risk factors for mortality and strategies for management. Ann Surg 1996;224:672-83. 5. Burton TS, Watson JD. Necrotizing fasciitis. BMJ 1994;308: 1453-4. 6. Dellinger EP. Necrotizing soft-tissue infections. In: Davis JM, Shires GT, editors. Principles and Management of Surgical Infections. Philadelphia: Lippincott; 1991. p. 23-39. 7. Maisel RH, Karlen R. Cervical necrotizing fasciitis. Laryngosope 1994;104:795-8. 8. Kaddour HS, Smelt GJ. Necrotizing fasciitis of the neck. Laryngol Otol 1992;106:1008-10. 9. Scott PMJ, Dhillon RS, McDonald PJ. Cervical necrotizing fasciitis and tonsillitis. J Laryngol Otol 1994;108:435-7. 10. Kaplan DM, Fliss DM, Shulman H, Leiberman A. Computed tomographic detection of necrotizing soft tissue infection of dental origin. Ann Otol Rhinol Laryngol 1995;104:164-6. 11. Levine TM, Wurster CF, Krespi YP. Mediastinitis occurring as a
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27. 28.
29.
complication of odontogenic infections. Laryngoscope 1986;96: 747-50. Chelsom E, Halstensen A, Haga T, Hoiby EA. Necrotizing fasciitis due to group A streptococci in western Norway: incidence and clinical features. Lancet 1994;344:1111-5. Falender LG, Barbieri D, Leban SG. Gas-producing necrotizing fasciitis following mandibular fracture. J Oral Maxillofac Surg 1989;47:856-9. Margolis RD, Cohen KR, Loftus MJ, Weiss WW. Non-odontogenic -hemolytic necrotizing fasciitis of the face. J Oral Maxillofac Surg 1989;47:1098-102. Balcerak RJ, Sisto JM, Bosack RC. Cervico facial necrotizing fasciitis: report of three cases and literature review. J Oral Maxillofac Surg 1988;46:450-9. Lloyd RE. Necrotizing fasciitis of the orbit. Br J Oral Maxillofac Surg 1987;25:323-5. Einarsson OJ, Pers M. Streptococcal gangrene of the eyelids. Scand J Plast Surg 1986;20:331-5. Yii NW, Quinn SJ, Andersson LC, Niranjan NS, Kenyon GS. Cervical necrotizing fasciitis with pharyngeal perforation: treatment and reconstruction. Br J Plast Surg 1996;49:237-41. Aitken DR, Mackett MC, Smith LL. The changing pattern of hemolytic streptococcal gangrene. Arch Surg 1982;117:561-7. Giuliano A, Lewis F, Hadley K, Blaisdell FW. Bacteriology of necrotizing fasciitis. Am J Surg 1977;134:52-6. Fliss DM, Tovi F, Zirkin HJ. Necrotizing soft-tissue infections of dental origin. J Oral Maxillofac Surg 1990;48:1104-8. Ward RG, Walsh MS. Necrotizing fasciitis: 10 years’ experience in a district general hospital. Br J Surg 1991;78:488-9. Stamenkovic I, Lew PD. Early recognition of potentially fatal necrotizing fasciitis: the use of frozen section biopsy. New Engl J Med 1984;310:1689-3. Janevicius RV, Hann S-E, Batt MD. Necrotizing fasciitis. Surg Gynecol Obstet 1982;154:97-102. Bone RC, Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864-72. Rixen D, Siegel JH, Friedman HP. “Sepsis/sirs,” physiologic classification, severity stratification, relation to cytokine elaboration and outcome prediction in post trauma critical illness. Trauma 1996;41:581-98. Hirshberg A, Mattox KL. “Damage control” in trauma surgery. Br J Surg 1993;80:1501-2. Brown DR, Davis NL, Lepawsky M, Cunningham J, Kortbeek J. A multi-center review of the treatment of major truncal necrotizing infections with and without hyperbaric oxygen therapy. Am J Surg 1994;167:485-9. Gozal D, Ziser A, Shupak A, Ariel A, Melamed Y. Necrotizing fasciitis. Arch Surg 1986;121:233-5.
Reprint requests: David A. Koppel Consultant Craniofacial/Maxillofacial Surgeon Regional Maxillofacial Unit Southern General Hospital 1345 Govan Road Glasgow G51 4TF Scotland, United Kingdom [email protected]
A small but nevertheless important part of a surgeon’s experience comprises necrotizing soft tissue infections of the head and neck. The purpose of this report is to heighten awareness of necrotizing soft tissue infections in any patient with an infection of the head and neck. The article also outlines an appropriate management strategy for use in the treatment of patients with this potentially fatal condition. Prompt diagnosis and early radical surgical debridement are significant factors in avoiding a fatal outcome in these patients. This article reviews the literature on necrotizing soft tissue infections of the head and neck and presents cases from our recent experience. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:30-7)
Necrotizing soft tissue infections constitute a small but nevertheless important part of a surgeon’s experience. The importance rests with the fact that advancing tissue necrosis signifies a life-threatening condition that demands prompt surgical intervention if a fatal outcome is to be averted. These infections respect no anatomic boundaries and present to surgeons of all specialties, maxillofacial surgery being no exception. To distinguish these from less serious infections requires a high level of awareness because their initial presentation may be deceptive. Delay in diagnosis has been demonstrated to be associated with an increased mortality in several studies.1-4 This infection is neither common nor rare, so that every surgeon is highly likely to encounter the condition but not with sufficient frequency to produce familiarity.5 The taxonomy applied to these infections is varied (Table), confusing, and not always conceptually useful. Dellinger3 states that much of this terminology may be dispensed with or simplified, and the separate syndromes cited in the medical literature may be considered different manifestations of the same pathologic process. The exception to this is the particular case of histotoxic clostridial myonecrosis (gas gangrene). This condition differs in important respects. Histologically, toxin-induced muscle necrosis proceeds rapidly in advance of actual bacterial invasion. Furthermore, this a
Consultant Maxillofacial Surgeon, West of Scotland Maxillofacial Service. b Specialist Registrar, West of Scotland Maxillofacial Service. c Consultant Craniofacial/Maxillofacial Surgeon, West of Scotland Maxillofacial Service. Received for publication May 29, 2002; returned for revision Sep 5, 2002; accepted for publication Oct 1, 2002. © 2003, Mosby, Inc. 1079-2104/2003/$30.00 ⫹ 0 doi:10.1067/moe.2003.15
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Table. Terms applied to necrotizing soft tissue infections Nonclostridial gas gangrene Hemolytic streptococcal gangrene Necrotizing erysipelas Synergistic necrotizing cellulitis Meleney’s bacterial gangrene Necrotizing cellulitis Fournier’s gangrene Necrotizing fasciitis
infection is more rapidly progressive and has a higher mortality than its nonclostridial myonecrosis counterpart.4,6 Thus, the taxonomy can be reduced to 2 clinical entities: histotoxic clostridial myonecrosis and all other necrotizing soft tissue infections, both clostridial and nonclostridial. This classification has utility because the treatment is the same for all the described anatomic sites. We prefer the term necrotizing soft tissue infection to the commonly applied term necrotizing fasciitis because the former provides a better conceptual framework for the radical surgical debridement required. The problem with the term necrotizing fasciitis is that it implies the process involves only subcutaneous fascial layers. Although this is not infrequently the case, it is by no means necessarily so. The necrotizing infective process may involve any adjacent tissue, including muscle. The management principles have been clearly defined; the crucial step lies with the prompt recognition of the presence of necrotic tissue and its radical surgical debridement, irrespective of composition, immediately after resuscitative measures, combined with antimicrobials in high dosage. These measures must be accompanied by careful physiologic monitoring to identify
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Fig 2. Initial resection of necrotic tissue.
Fig 1. Head shaved to reveal necrotizing soft tissue infection.
any organ dysfunction with early institution of appropriate supportive therapy. A brief survey of the literature yields many reports of necrotizing soft tissue infections in the head and neck region.4,7-18 CASE REPORTS Case 1 A 49-year-old woman was referred to the emergency service by her general medical practitioner with an infected scalp wound. The history given was that of a fall 3 to 4 weeks previously causing a scalp laceration. At the time the patient thought the injury was trivial and did not require any medical attention. However, during the 24 hours before admission the patient had become increasingly ill with anorexia, nausea, and vomiting. The medical history was significant for epilepsy controlled with sodium valproate, previous abdominal surgery, and alcohol dependency. She was noted to be a heavy smoker. On examination she appeared generally ill with a fluctuant swelling behind the right ear. She was afebrile, and vital signs were heart rate 120 bpm, blood pressure 100/60 mm Hg, and respiratory rate 22/min. Full blood count and routine biochemistry showed white blood count 19.3 ⫻ 109/L, hemoglobin 114 g/L, and a urea of 27.3 mmol/L. The remaining hematologic and biochemical investigations were within normal limits. Intravenous fluids were administered, and cefuroxime 1.5 g plus metronidazole 500 mg every 8 hours were commenced intravenously. A provisional diagnosis of cellulitis was made. Twelve hours later there had been no improvement in her general condition. She was transferred to the operating suite for an examination under general anesthesia and wound debridement. At surgery, hair was shaved to reveal a necrotizing soft tissue infection (Fig 1). The area of necrotic tissue was resected to include pericranium, and the peripheral margins were taken back to the bleeding scalp (Fig 2). Intraoperatively, the estimated blood loss was 3 L. Cardiovascular instability required inotropic support as well as transfusion of
packed red cells to maintain blood pressure and urine output. Central venous pressure was maintained above 24 mm H2O. The wound was dressed; microbiologic samples were sent to the laboratory; and the patient was transferred to the intensive care unit, intubated, and ventilated. During the next 24 hours hemodynamic instability required maximal inotropic support, and signs of acute respiratory distress syndrome developed. Computed tomography (CT) scanning to exclude intracranial pathologic condition was precluded by hypotension induced by movement. Initial antimicrobial therapy comprised benzyl penicillin 2.4 g every 4 hours, clindamycin 1.2 g every 6 hours, and continuation of metronidazole 500 mg every 8 hours. On the fourth day after presentation the patient’s condition had stabilized enough to allow a CT scan. This showed no evidence of brain abscess or skull fracture but did reveal small infarctions in both cerebral hemispheres and left temporal lobe calcification. A further debridement of necrotic scalp tissue was performed (Fig 3). Throughout this period she remained intubated and on ventilation support. On day 8, purpura of the flanks developed (Fig 4), and spontaneous bleeding occurred from the mouth, nose, and vagina. The platelet count had decreased to 27 ⫻ 109/L. A diagnosis of heparin-induced thrombocytopenia was made, and subcutaneous heparin was discontinued. Although the platelet count improved, the patient remained inotropic and ventilator dependent. On day 14, a deterioration in the neurologic state became obvious with the development of hemiparesis. A further CT scan showed a large brain stem infarct, and on day 20 she died without regaining consciousness.
Case 2 Forty-eight hours before admission a 40-year-old woman had tripped and fallen while jogging, striking the left forehead and orbital region on the curb. This produced an apparently superficial laceration of the forehead approximately 2 cm long as well as swelling and bruising about the left eye. The following morning, 36 hours before admission, she came to the emergency department at the treating hospital. Vital signs were normal; there was no visual impairment or injury to the
32 McMahon, Lowe, and Koppel
Fig 3. Further debridement of necrotic scalp.
globe. A full range of eye movements was noted, and neurologic examination was normal. No evidence of skull or facial bone fractures was found on physical or radiographic examinations. The facial wound was assessed as minor in nature, and, after ensuring adequate tetanus immunity, the patient was discharged with arrangements made for ophthalmology follow-up at the next available clinic, 48 hours from the time of presentation. Twelve hours before admission the patient revisited the emergency department complaining of a yellow purulent discharge from the left eye that had developed overnight. The left periorbital swelling was now very marked, with crusting evident on the lid margins (Fig 5). She was now unable to open her left eye. Mild right periorbital edema was also noted. The emergency department medical officer was under the impression that this was a severe bacterial conjunctivitis. Antibiotic ophthalmic drops were prescribed, and she was advised to keep her ophthalmology clinic appointment the following day. She reappeared with her family 12 hours later at which time a referral was made to the maxillofacial surgical service. During that time period there had been progressive pain and swelling in the left periorbital and temporal region with anorexia, malaise, and rigors. In addition, the left upper eyelid skin had clearly undergone necrosis. On examination she was febrile with a peripheral temperature of 39°C and tachycardic at 112 bpm, and the peripheral circulation was assessed as being hyperdynamic. Tachypnea (30 breaths per minute) was also present. A full blood count showed a marked neutrophil leukocytosis (total white blood count 41.0 ⫻ l09/L, neutrophils 37.3 ⫻ l09/L). All other hematologic parameters were normal, and the serum urea, creatinine, and electrolytes were all within the normal range. She was well oxygenated on supplemental oxygen (PaO2 20.3 kPa on fraction of inspired oxygen of 40%) and exhibited no metabolic acidosis (base excess ⫹2 and arterial bicarbonate of 22 mmol/L). No significant medical or surgical history was elicited in this patient, who was a nonsmoker and drank no ethanol. The ischemic skin on the upper eyelid was incised, and a swab was taken. Similar specimens were taken after incision through the superficial lateral forehead laceration and sent for
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Fig 4. Purpura on flanks.
immediate Gram stain. After blood culture samples were obtained, high-dose antibiotic therapy was commenced, comprising benzyl penicillin 2.4 g every 4 hours, cefotaxime 2.0 g every 8 hours, and metronidazole 500 mg every 8 hours. Arrangements were made to transfer her to the operating suite with the diagnosis of a necrotizing soft tissue infection. At operation the necrotic eyelid skin and orbicularis muscle were excised, leaving an intact and apparently viable tarsal plate and levator muscle. The skin around the lateral forehead laceration was assessed as only marginally viable and therefore excised over an area of 3 ⫻ 1.5 cm. Underlying fascia was clearly necrotic and excised back to clearly bleeding tissue in the temporal fossa. The wounds were dressed, and the patient was transferred to the intensive care unit with a plan for second-look surgery during the ensuing 12 to 24 hours. The Gram stain on swabs taken from the wound had identified gram-positive cocci compatible with streptococci. On the advice of the clinical microbiology service the cefotaxime was discontinued and gentamicin 120 mg every 12 hours was commenced. Benzyl penicillin and metronidazole were continued according to the dose regimen described above for a total of 6 days. The patient remained intubated and sedated on the intensive care unit overnight. The following morning the wounds were examined on the intensive care unit, and no further areas of tissue necrosis were seen. She was weaned from the ventilator and discharged from the intensive care unit to a regular unit in stable condition. On admission to the regular unit this patient was found to be well oxygenated with a saturation of 99% on a fraction of inspired oxygen of 40%. A satisfactory urine output was maintained. Urea and electrolytes were normal, as were coagulation indexes. However, a persistent neutrophil leukocytosis (white blood count 26.8 ⫻ 109/L) was noted, and hemoglobin estimation had fallen to 9.0 g/dL and albumin to 25 g/L. In view of persistent pyrexia and tachycardia, a further inspection of the wound was performed at 8 PM. At this time a clear deterioration had occurred, with a seropurulent discharge from the wound and further necrotic tissue visible in the temporal fossa on retrac-
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Fig 6. Resection of necrotic tissue. Fig 5. Left periorbital swelling and crusting of lid margins.
tion of the skin edge. Arrangements were made for prompt transfer to the operating suite. A coronal flap was raised to gain wide exposure of the tissues of scalp and left temporal fossa. The left temporoparietal fascia and in-continuity galea from the zygomatic arch to a point approximately 3 cm above the superior temporal line and extending from above and behind the pinna to the lateral orbit were found to be necrotic. In addition, the entire left deep temporal fascia was necrotic. All necrotic tissue in this region was debrided. The skin overlying this region was resected. Edematous pericranium was found in the region of the vertex and in continuity with areas of necrosis described. This abnormal-appearing tissue was also removed (Fig 6). A small area of necrotic orbital fat was removed from the vicinity of the lateral canthus. The temporalis muscle underlying the necrotic fascia was viable, ie, bleeding freely and contracting on stimulation. At this point there was no residual nonviable or marginally viable tissue present, and the wound was dressed. The patient remained normotensive throughout. During the procedure, 2 units of concentrated red cells were transfused as well as 1500 mL of a crystalloid solution, and the patient was transferred to the intensive care unit. A further return to the operating suite was scheduled for the following morning. Overnight, erythema and swelling extending from the parotid region to clavicle were noted in the ipsilateral neck. The patient was, however, afebrile and remained so for the rest of her stay, the tachycardia was no longer present, and all other vital signs remained normal and stable. At operation the following day, the ipsilateral neck was explored with no abnormality found other than mild edema anterior to the carotid sheath. A small amount of pericranium and orbital fat of doubtful viability was resected, and the wound was dressed. Postoperatively she was begun on nasogastric tube
feeding and was able to resume oral intake 2 days later. Two further dressing changes were performed during the ensuing 3 days without further debridement being necessary. She was transferred to another hospital for reconstruction 7 days after her admission in a stable condition with normal vital signs as well as normal hematologic and serum biochemical parameters.
Case 3 An 86-year-old woman was referred to the emergency department by her general medical practitioner after having fallen 2 days previously. Since this minor fall, which did not result in loss of consciousness, her face had become increasingly painful and swollen. Her medical history was significant for controlled hypertension, vertebrobasilar insufficiency, and peptic ulcer disease. Regular medications included ranitidine and a loop diuretic. She lived in sheltered accommodation, and her mobility was limited by osteoarthritis. On examination she was found to be alert with a Glasgow Coma Score of 14, her heart rate was 94 bpm, and her blood pressure was recorded as 97/70 mm Hg. The left side of her face was swollen and erythematous; the left eye was shut with a serous discharge from the lateral aspect of the left infraorbital region. Visual acuity, assessed by counting fingers, was intact in both eyes. The remainder of the examination was unremarkable. Skull radiography showed no vault fracture; however, an infraorbital rim fracture was suspected on facial views. A diagnosis of orbital cellulitis was made, and referral to the ophthalmology service was made. After review by the duty ophthalmologist 1.5 hours later, referral to the maxillofacial surgical service for further management was initiated. On examination the patient was obviously confused, tachy-
34 McMahon, Lowe, and Koppel
Fig 7. Left periorbital edema and soft tissue necrosis.
pneic and tachycardic at 120 bpm, and clinically dehydrated. Other significant findings were pyrexia (38.9°C) and hypoxemia (oxygen saturation in arterial blood of 81%). Immediate resuscitation measures comprised intravenous crystalloid fluids and supplemental oxygen via a mask. Benzyl penicillin 1.2 g and metronidazole 500 mg were administered intravenously. Hematologic and biochemical investigations were within normal range apart from an increased urea level of 14.9 mmol/L and creatinine of l97 mol/L. A clotting screen was also within normal limits. Arterial blood gases on oxygen 4 L/min via mask were consistent with a metabolic acidosis. Blood cultures were taken, a urinary catheter was passed, and a provisional diagnosis of a necrotizing soft tissue infection was made (Fig 7). She was promptly transferred to the operating suite. At operation nonviable infraorbital skin and underlying muscle were excised to bleeding, grossly healthy tissue. The wound was copiously irrigated and dressed; the excised tissue was sent for immediate microbiologic investigation. During the procedure the patient became cardiovascularly unstable, requiring intravenous fluids and dopamine plus adrenaline to maintain her blood pressure above 100/50 mm Hg. Urine output was minimal, and several episodes of atrial fibrillation occurred that spontaneously reverted to sinus tachycardia. She was transferred to intensive care following this procedure, where she remained intubated and on ventilation. Maximal inotropic support (adrenaline, noradrenaline, and dopamine) was required. Eight hours postoperatively the wound was inspected, and there was a progressing erythema down the left side of the neck and anterior chest wall, across the bridge of the nose to involve the contralateral eyelids, and extending posteriorly to the mastoid region. The urine output remained negligible, and she died with no further surgical intervention 56 hours after presentation. All the microbiologic investigations showed heavy growth of Streptococcus pyogenes (group A).
DISCUSSION Necrotizing soft tissue infections caused by S pyogenes alone have been called hemolytic streptococcal
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gangrene.19 However, the clinical course is indistinguishable from that caused by a polymicrobial flora of aerobic and anaerobic, gram-positive and gram-negative bacteria.3,4,20 Furthermore, management is identical irrespective of what subsequently proves to be the microbiologic basis. When only a single organism is isolated, this is most often reported as being S pyogenes3,4,20; however, this is not uniformly the case.4 Taken as a whole, necrotizing soft tissue infections (excluding histotoxic clostridial myonecrosis) usually show multiple species,3,4,20 with up to 11 organisms being isolated from a single case.20 In the head and neck region, the majority of reports indicate that the origin is most often the mouth or oropharynx, and odontogenic sepsis predominates.4,8,9,13,15,16,21 Although this has not been our recent experience, senior clinicians in our unit can certainly recount cases in which this was the case. Streptococcal species are frequently seen, but a highly variable polymicrobial flora is most often reported in this region as elsewhere, including Enterobacter, Pseudomonas, Proteus, Enterococcus,21 Fusobacterium, Bacteroides, staphylococci,15 and diptheroids,13 to name but a few. The clinical relevance of this is that initial empiric antibiotic therapy must be of broad spectrum as well as high dosage to be certain of adequate treatment of these serious infections. Clostridium species may be found as copathogens or even the predominant pathogen in cases that are not histotoxic clostridial myonecrosis (gas gangrene).1,3,4,13 It should be noted therefore that the diagnosis of this latter clinical entity must be made on clinical features, operative findings, and the patient’s progress. It does not rest solely on the recovery of clostridium in culture.6 It is our practice to begin all patients with necrotizing soft tissue infections on high-dose intravenous benzyl penicillin (2.4 g every 4 hours in adult patients), flucloxacillin (1 g every 6 hours), and metronidazole (500 mg every 8 hours). Otherwise, our initial antibiotic selection is in accordance with that of Dellinger,6 who suggests that all patients receive cefotaxime (2 g every 8 hours in adult patients) or another third-generation cephalosporin, and metronidazole (500 mg every 8 hours). Clindamycin 900 mg every 8 hours can be given as a substitute for metronidazole and will also cover streptococci. Imipenem/cilastatin alone, 500 mg intravenously every 6 hours, also provides adequate empiric therapy. If a Gram stain shows the presence of gram-positive cocci, then penicillin 20 million units during a 24-hour period is the treatment of choice. However, it is prudent to continue the cefotaxime and metronidazole until the details of culture become available because polymicrobial sepsis is a feature of many necrotizing soft tissue infections as already stated. Dos-
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age and dosing interval adjustments are frequently necessary in these patients because of preexisting renal disease or acute renal failure. On presentation, every effort must be made to obtain appropriate bacteriologic specimens. These should comprise a minimum of 2 sets of blood cultures taken 20 minutes apart as well as specimens from the wound. Care must be exercised with respect to the interpretation of culture results of specimens obtained from open wounds because contamination is frequent. The most reliable specimens are those obtained at operation at a point remote from any open wound, and such specimens must be obtained. However, it is our practice to defer commencement of empiric antibiotic therapy only while initial blood cultures and wound swabs are taken and not to await operative samples. There is clearly a requirement for an early and ongoing close consultation with the clinical microbiology/ infectious disease service. It was previously mentioned that recognition of necrotizing soft tissue infection may be problematic. The significance of this cannot be overemphasized because delay to diagnosis has been demonstrated to have a clear adverse effect on the patient’s likelihood of survival in numerous studies.1-4,22-24 That the local features may belie a more extensive subcutaneous process is a characteristic of necrotizing soft tissue infections and is a significant factor leading to delay in diagnosis. A simple subcutaneous abscess has a central necrotic portion but differs from the conditions being considered here in that it is localized to the area of discernible abnormality.6 The necrotizing soft tissue infections, on the other hand, are poorly localized and are characterized by inflammation and necrosis extending deep to what is normal-appearing skin. Skin changes are characterized by the signs of acute inflammation, in particular erythema, edema, and hyperesthesia. Pain, however, may not be an especially prominent feature in the nonclostridial myonecrosis6 type. This has certainly been our experience. What is prominent are fever and the other features of systemic inflammatory response syndrome (SIRS).26 Thus, a necrotizing soft tissue infection should be suspected whenever a trivial or clean wound is followed, in 12 to 36 hours, by prominent systemic signs of sepsis. Crepitus and blistering are generally late features, the former representing the presence of gas in the tissues. It is recognized that most necrotizing soft tissue infections with the presence of gas are not of the histotoxic clostridial myonecrosis (gas gangrene) type but rather of the more common nonclostridial necrotizing soft tissue infection6 forming the focus of this report. In the presence of infection, the identification of gas within the tissues is always significant unless there
McMahon, Lowe, and Koppel 35
is an alternative explanation such as pulmonary barotrauma, pneumothorax, or upper airway injury. Most facultative bacteria produce insoluble gas during anaerobic, but not aerobic, metabolism. The presence of gas in the tissues with infection implies an anaerobic tissue environment incompatible with viable living tissue.6 In other words, tissue necrosis has occurred, and prompt operative intervention with radical debridement is mandated. Radiology, especially CT, is much more sensitive than palpation in detecting gas in the tissues.10,13 This may be useful in distinguishing a necrotizing soft tissue infection from a cellulitis. We do, however, have reservations about its accuracy in guiding clinical decision making. The defining and clinically important feature is that of tissue necrosis rather than gas production. Furthermore, it is not clear from the literature how frequently necrotizing soft tissue infections are accompanied by the production of gas in the tissues. Certainly, in the presence of rapidly progressive infection and a marked systemic response, we would not omit prompt surgical exploration on the basis of a negative CT scan. Necrotizing soft tissue infections often result in the sequestration of a significant amount of fluid and a marked hemodynamic response. This response is highly variable, from minimal to profound septic shock. In every case, the potential for profound cardiovascular and respiratory failure exists. In addition, renal failure is a frequently associated complication.4,6 Careful evaluation, resuscitation, and appropriate monitoring are therefore mandatory. An intensive unit level of care is the minimum requirement, with continuous pulse oximetry, hourly monitoring of urine output, and frequent recording of hemodynamic values and respiratory rate. In 1984 Stamenkovic and Lew3 reported the use of frozen section biopsy to make an early diagnosis in necrotizing soft tissue infections. In a retrospective analysis of an institution’s experience with this condition, they were able to demonstrate a significant improvement in survival associated with a much reduced delay to diagnosis where this investigation was used. This diagnostic test appears both sensitive and specific. However, it is plausible that the most important step was considering the diagnosis early, rather than actually performing the test, in producing the markedly reduced mortality in the group who underwent frozen section biopsy. These patients are widely held to be susceptible hosts; ie, systemic illness renders them more susceptible to infection. This perception is borne out by the largest series of patients reported to date.4 In this series, comprising 198 patients at the University of Maryland Shock Trauma Center, the large majority could be considered to have a preexisting medical condition
36 McMahon, Lowe, and Koppel
rendering them susceptible; the most common of these was diabetes mellitus, present in more than half of the patients. However, one of our patients (case 2) demonstrates this not to be universally the case, and clinicians should be aware that increased host susceptibility is not necessarily a precondition for necrotizing soft tissue infection. With a logistic regression analysis applied to the broad range of potentially interdependent variables, Elliott et al4 in their large series of patients were able to demonstrate a number of factors significantly associated with an increased likelihood of a fatal outcome. Mortality among those older than 60 years was 5 times that of younger patients. Female gender was also associated with a worse prognosis. Other factors shown to be independently associated with mortality were renal impairment and a shift in peripheral energy utilization from aerobic to anaerobic metabolism as evidenced by elevated serum lactate level. A delay to first debridement was a significant factor associated with increased mortality in this as well as other studies. The extent of infection as a percentage of body surface area and the degree of organ system dysfunction at admission also correlated with an excess risk of death. These latter findings are hardly surprising because, in critical illness due to other causes, admission lactic acidosis and multiple organ dysfunction had a significant impact on a patient’s survival expectation.26,27 In the 2 patients who died in this case report, multiple organ dysfunction was an admission feature as was premorbid systemic illness. In the surviving patient, on the other hand, a base deficit was not seen, and significant dysfunction did not occur in any organ system. The absence of a preexisting systemic disease in a patient who was young and healthy, ie, good physiologic reserve, was undoubtedly a highly significant factor in the favorable outcome. The findings that extent of infection and delay to initial surgery adversely affect outcome emphasize the importance of prompt recognition and surgical intervention to halt the spread of the necrotizing process and to prevent the development of systemic complications produced by inflammatory mediators. The mortality rate in the series reported by Elliott et al was 25.3%. This, however, rose to more than 40% when 3 organ systems were failing and 80% when 5 organ systems demonstrated dysfunction. With the high mortality of this condition and the frequent development of organ failure, the early involvement of an intensivist is indicated in all cases. The extent of surgical excision and debridement is determined by the gross findings at operation. Careful consideration should be given to the placement of incisions so that wide access is accomplished to all extensions of the necrotizing processes without compromising the perfusion of the surrounding
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tissues. Excision of all tissue that is nonviable continues until normal-appearing tissue is encountered that bleeds freely on incision. Potentially involved muscle should contract normally on stimulation, and it is important to inspect muscle lying beneath deep fascia at the initial procedure. Extensions of the process may be connected by narrow bridges of necrosis that must be carefully sought. In all cases, a minimum of 2 operations is considered advisable.4,6 Extension is easily overlooked at the first procedure, and what was marginally viable at the first procedure may be necrotic in 24 hours. The second procedure is therefore scheduled for the following day at completion of the first. If significant infection is discovered at this second procedure, a third must be scheduled and so on. When no further infection is found, the surgical phase of the treatment is completed pending commencement of reconstruction of the resultant defect, after the patient has been stable for a number of days. The management of skin overlying areas of subcutaneous and fascial necrosis is controversial. Some authors20 advocate excision to the margins of such areas of necrosis, whereas others favor a more conservative approach.4 The latter leave the wound open until it is clear that the process has been arrested and the patient has stable physiology. This was the dilemma in case 2 in which necrosis of temporoparietal fascia had exposed hair follicles in the deep dermis. In reconstructive surgery this is the superficial plane of dissection in raising the temporoparietal fascial flap, a procedure not usually associated with healing problems in the overlying skin. At the second procedure there appeared to be a rapidly progressive necrotizing soft tissue infection, and it was elected to remove this skin. This may not have been necessary and certainly significantly increased the resulting disfigurement. Hyperbaric oxygen therapy has been used as an adjunct in the treatment of necrotizing soft tissue infections.6,28,29 No randomized clinical trials have been conducted to validate the role of hyperbaric oxygen, and given the infrequency with which this condition is encountered, it seems unlikely that such a study will take place.28 Subexperimental studies have not consistently demonstrated a significant survival advantage, but all have been conducted in small numbers of patients with an apparent trend toward improved outcome. Therefore, if hyperbaric oxygen treatment is available, it seems prudent to add this treatment. However, it is emphasized that such adjunctive treatment should take place only after adequate resuscitation, appropriate empiric antimicrobial administration, and operative treatment have been instituted. Delay in any of these 3 aspects of therapy in patients with necrotiz-
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ing soft tissue infections is contraindicated for any reason, including transfer to a unit with a hyperbaric oxygen facility. To summarize, the treatment of necrotizing soft tissue infections should consist of hemodynamic and respiratory evaluation, resuscitation, and monitoring; obtaining appropriate bacteriologic specimens; instituting high dose broad spectrum intravenous antimicrobial therapy; surgical excision and debridement; planned second look surgery; nutritional support; and possibly hyperbaric oxygen therapy. CONCLUSIONS Every surgeon during a practicing career is likely to encounter the devastating and fortunately uncommon condition of necrotizing soft tissue infection. Delay to diagnosis and treatment is a significant factor in the high mortality of necrotizing soft tissue infections. Preventable deaths can be avoided only by a high level of awareness by clinicians at all levels and particularly in those who are at the first point of patient contact.
12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23.
We would like to thank all our colleagues who were involved in the care of the patients presented in this article, particularly Mr A. W. Baker, Mr N. Hammersley, Mr S. Hislop, Mr D. I. Russell, and Mr S. Watson.
24. 25.
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Reprint requests: David A. Koppel Consultant Craniofacial/Maxillofacial Surgeon Regional Maxillofacial Unit Southern General Hospital 1345 Govan Road Glasgow G51 4TF Scotland, United Kingdom [email protected]