- Email: [email protected]
Modern Concepts of the Diagnosis and Treatment of Necrotizing Fasciitis
The Journal of Emergency Medicine, Vol. 39, No. 2, pp. 261–265, 2010 Copyright © 2010 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$–see front matter
doi:10.1016/j.jemermed.2008.06.024
Clinical Reviews
MODERN CONCEPTS OF THE DIAGNOSIS AND TREATMENT OF NECROTIZING FASCIITIS Richard F. Edlich,
MD, PHD,*
Catherine L. Cross,† Jill J. Dahlstrom,† and William B. Long III,
MD‡
*Director of Trauma Prevention, Education and Research, Legacy Verified Level I Shock Trauma Center at Legacy Emanuel Hospital, Portland, Oregon, †Research Assistant, Legacy Emanuel Hospital, Portland, Oregon, and ‡President and Medical Director of Trauma Specialists, LLP, Legacy Emanuel Hospital, Portland, Oregon Reprint Address: Richard F. Edlich, MD, PHD, Legacy Emanuel Hospital, 22500 NE 128th Circle, Brush Prairie, WA 98606
baric oxygen therapy, for necrotizing fasciitis infection continues to receive much attention. © 2010 Elsevier Inc.
e Abstract—Background: Necrotizing fasciitis is a potentially fatal infection involving rapidly progressive, widespread necrosis of the superficial fascia. Objectives: The purpose of this collective review is to review modern concepts of the treatment and diagnosis of necrotizing fasciitis. Discussion: Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis. During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is usually polymicrobial, rather than monomicrobial. Although there has been no published well-controlled, clinical trial comparing the efficacies of various diagnostic imaging modalities in the diagnosis of necrotizing infections, magnetic resonance imaging (MRI) is the preferred technique to detect soft tissue infection. MRI provides unsurpassed soft tissue contrast and spatial resolution, has high sensitivity in detecting soft tissue fluid, and has multiplanar capabilities. Percutaneous needle aspiration followed by prompt Gram’s staining and culture for a rapid bacteriologic diagnosis in soft tissue infections is recommended. Surgery complemented by antibiotics is the primary treatment of necrotizing fasciitis. Conclusion: Wide, extensive debridement of all tissues that can be easily elevated off the fascia with gentle pressure should be undertaken. Successful use of intravenous immunoglobulin has been reported in the treatment of streptococcal toxic shock syndrome. The use of adjunctive therapies, such as hyper-
RECEIVED: 20 February 2008; FINAL ACCEPTED: 11 June 2008
SUBMISSION RECEIVED:
e Keywords—necrotizing fasciitis; MRI; percutaneous needle aspiration; debridement; antibiotics
INTRODUCTION Necrotizing fasciitis is a destructive infection that involves both skin and soft tissues. In this collective review we will outline its pathophysiology as well as the diagnostic studies that are needed for rapid, accurate diagnosis of this life-threatening infectious disease. Second, we will review the bacteriology of necrotizing fasciitis. Finally, we will review the treatment strategies for managing this massive infectious soft tissue disease.
PATHOPHYSIOLOGY Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. It was once considered an uncommon clinical entity. In the 1990s, the media popularized this infection as being caused by “flesh-eating bacteria.” Although the pathogenesis of necrotizing fasciitis is still open to specula-
8 May 2008; 261
262
tion, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis (1). Historically, group A -hemolytic streptococcus (GABS) has been identified as a major cause of this infection. This monomicrobial infection is usually associated with an underlying cause such as diabetes, atherosclerotic vascular disease, or venous insufficiency with edema. GABS usually affects the extremities, with approximately two-thirds of cases being located in the lower extremities (2). During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is usually polymicrobial, rather than monomicrobial. In 1982, Rouse et al. reported 28 cases of necrotizing fasciitis (3). They pointed out that all but four infections were polymicrobial. The overall mortality rate was 74% (20 of 27). They indicated that prompt recognition and treatment of necrotizing fasciitis is essential. Eleven of 12 patients who had a delay in treatment for more than 12 h died. In 1995, McHenry et al. found very similar findings to that of Rouse et al. (4). McHenry et al. reported on the determinants of mortality for recognizing soft tissue infections. Necrotizing soft tissue infections were polymicrobial in 45 patients (69%). The average time from admission to operation was 90 h in nonsurvivors vs. 20 h in survivors. Early debridement of the infection was obviously associated with a significant decrease in mortality. In a series of 163 consecutive patients reported by Andreasen et al., it was noted that 71% of their patients with necrotizing fasciitis had a polymicrobial infection (5). In many cases of necrotizing fasciitis, an identifiable antecedent trauma was evident. Surprisingly, the initial lesion was often trivial, such as an insect bite, minor abrasion, boil, or injection site. Other indicative findings included edema extending beyond the area of erythema, skin vesicles, and crepitus. They noted that the subcutaneous tissue will demonstrate a wooden, hardened feel. The fascial planes and muscle groups cannot be detected by palpation. Laboratory evaluation should include complete blood counts, blood chemistries, arterial blood gases, and tissue and blood cultures. Radiographic studies must be undertaken to detect air in soft tissues. When the patient is seriously ill, Fugitt et al. pointed out, necrotizing fasciitis is a surgical emergency with high mortality; therefore, imaging studies should not delay surgical intervention (6). On the west coast of the United States, necrotizing fasciitis has been associated with the injection use of black tar heroin, a dense, gummy, coal-colored substance that is produced from opium grown in the mountainous region of northern Mexico (7). Crude processing techniques lead to the production of compounds that are commonly laced with organic resins and other contaminants. Injection of this drug into the skin can predispose to the development of necrotizing fasciitis.
R. F. Edlich et al.
DIAGNOSTIC STUDIES We have reported appropriate radiological studies that allow an early diagnosis of necrotizing infections (8). In addition, they permit visualization of the location of the rapidly spreading infection. Plain radiographs, often obtained to detect soft tissue gas that is sometimes present in polymicrobial or clostridial necrotizing fasciitis, are of no value in the diagnosis of necrotizing infections (8,9). In their study of 29 patients with necrotizing soft tissue infections, Lille et al. reported that non-diagnostic radiographs correlate with a delay in operative intervention and consequent increased morbidity and mortality (9). The majority of fluid collections in the tissue, especially the musculoskeletal system, can be localized and aspirated under ultrasound guidance. Whether or not fluid is infected cannot be determined from ultrasound appearances; laboratory analysis is required. In complicated infections, particularly septic arthritis and osteomyelitis, combined use of magnetic resonance imaging (MRI) and aspiration under ultrasound is very useful. Its role in the diagnosis of necrotizing fasciitis should be considered (10). Early muscle necrosis may be apparent. Parenti et al. retrospectively reviewed the ultrasound appearances of 32 pathologically proven cases of necrotizing fasciitis (11). Ultrasound revealed changes in the subcutaneous fat (28 of 32), investing fascia (18 of 32), and muscle (15 of 32) that correlated well with histological findings. However, in some cases, ultrasound did not reveal histologically apparent inflammation in the subcutaneous tissues (3 of 32) or muscle (8 of 32). Ultrasoundguided aspiration of perifascial fluid can help isolate the pathogen (12). Successful treatment requires early recognition, aggressive antibiotic therapy, and adequate surgical debridement. Although there has been no published, well-controlled, clinical trial comparing the efficacies of various diagnostic imaging modalities in the diagnosis of necrotizing infections, MRI is the preferred technique to detect soft tissue infection. MRI provides unsurpassed soft tissue contrast and spatial resolution, has high sensitivity in detecting soft tissue fluid, and has multiplanar capabilities (13,14). In a study of 13 patients with thoracic and abdominal wall infections, Sharif et al. reported that computed tomography (CT) and MRI were superior to sonography, scintigraphy, and plain radiography in providing useful information about the nature and extent of infections (15). Furthermore, they suggested that although CT compares favorably with MRI in the accurate diagnosis of soft tissue infection, multiplanar magnetic resonance images can be obtained without ionizing radiation and the use of i.v. contrast agents. The usefulness of MRI in the diagnosis of necrotizing fasciitis has been supported in a study by Rahmouni et al., who in 36 patients
Necrotizing Fasciitis
263
were able to differentiate between non-necrotizing cellulitis that would respond to medical treatment and severe, necrotizing infections that required rapid, life-saving surgery (16). In a reported case of necrotizing fasciitis, MRI provided dramatic evidence of an inflammatory process infiltrating the fascial planes (8). Uman and Kunin recommended percutaneous needle aspiration followed by prompt Gram’s stain and culture for a rapid bacteriologic diagnosis in soft tissue infections (17). A needle aspirate should be taken on the advancing edge of the infection where GABS are plentiful (18). A Gram’s stain of the tissue aspirate can be used to differentiate erysipelas from necrotizing infections. Cocci are plentiful in the aspirate from necrotizing infection, whereas they are rarely identified in the aspirate in patients with erysipelas (18). The results of the microbiological aspirate should be complemented by blood cultures. The “finger-test” and rapid-frozen section biopsy examinations also should be used in the diagnosis of patients presenting with suspected necrotizing fasciitis (19,20). The area of suspected involvement is first infiltrated with local anesthesia. A 2-cm incision is made in the skin down to the deep fascia. Lack of bleeding is a sign of necrotizing fasciitis. On some occasions, a dishwater-colored fluid is noticed seeping from the wound. A gentle, probing maneuver with the index finger covered by a sterile powder-free surgical double glove is then performed at the level of the deep fascia. If the tissues dissect with minimal resistance, the “finger test” is positive. Tissue biopsies are then sent for frozen-section analysis. The characteristic histologic findings are obliterative vasculitis of the subcutaneous vessels and acute inflammation, as well as subcutaneous tissue necrosis. If either the “finger-test” or rapid frozen-section analysis is positive, or if the patient has progressive clinical findings consistent with necrotizing fascia, immediate operative treatment must be initiated.
TREATMENT Whenever possible, aggressive resuscitation must be initiated immediately to maintain hemodynamic stability. A polymicrobial, symbiotic infection recently has been found to be the most common cause of necrotizing fasciitis (4). Polymicrobial infections are often associated with previous surgical procedures, pressure ulcers, penetrating trauma, and perianal abscesses, as well as intravenous drug use. In the study by Andreasen et al., 71% of their patients had polymicrobial infections (5). Antibiotic therapy is a key consideration for these polymicrobial infections. The physician may use a com-
bination of penicillin G, an aminoglycoside, if renal function permits, as well as clindamycin to treat necrotizing fasciitis caused by streptococci, staphylococci, and Gram-negative bacilli, as well as anaerobes. Clindamycin remains the antibiotic of choice for necrotizing infections (21). Unlike penicillin, the efficacy of clindamycin is not affected by the inoculum size or stage of bacterial growth (22,23). Second, clindamycin is a potent suppressor of bacterial toxin synthesis (24,25). Third, subinhibitory concentrations of clindamycin facilitate the phagocytosis of GABS (8). Fourth, clindamycin reduces the synthesis of penicillin-binding protein, which, in addition to being a target for penicillin, is also an enzyme involved in cell wall synthesis and degradation (22). Fifth, clindamycin has a longer post-antibiotic effect than lactins such as penicillin (25). Finally, Stevens et al. demonstrated that clindamycin causes suppression of lipopolysaccharide-induced mononuclear synthesis of tumor necrosis factor-␣ (26). Consequently, the success of clindamycin also may be related to its ability to modulate the immune response (27). Initial antimicrobial therapy should be broad-based to cover aerobic Gram-positive and Gram-negative organisms and anaerobes. We recommend penicillin G, 24 million units per day i.v., divided into q 4 – 6-h doses; clindamycin, 900 mg i.v. q 8 h; and gentamicin, 1 mg/kg i.v. q 8 h. A more specifically targeted antibiotic regimen may be begun after initial Gram’s stain smear, culture, and sensitivities are available. Although some necrotizing infections still may be susceptible to penicillin, clindamycin is the treatment of choice for necrotizing infections because it is a potent suppressor of bacterial toxin synthesis and because the inoculum size or stage of bacterial growth does not affect its efficacy. If staphylococci are involved, nafcillin or vancomycin should be used in place of penicillin. Surgery is the primary treatment for necrotizing fasciitis. During surgery, all operating room personnel should be wearing a powder-free double-glove hole indication system that protects the staff as well as the patient from gaining access to deadly blood-borne infections (27). The Food and Drug Administration requires that the glove manufacturer produce sterile surgical gloves whose leakage rate does not exceed 2.5%. This high frequency of glove holes is an invitation to the spread of deadly blood-borne infections between operating room personnel and the patient. The double-glove system is also powder-free, thereby reducing the potentially serious complications of cornstarch. It has been well documented that cornstarch in wounds potentiates the development of infection. In addition, the cornstarch on latex gloves can carry the latex antigen and precipitate anaphylactic reactions in individuals allergic to latex (28). It is essential that surgeons be consulted early in the
264
care of these challenging patients. Early surgical debridement of necrotic tissue is a life-saving treatment. The importance of early diagnosis is underscored by many studies that document the significant benefit to prognosis and outcome associated with early and aggressive debridement of necrotizing soft tissue infections (9,21–32). In addition, early surgical treatment may minimize tissue loss, eliminating the need for amputation of the infected extremity (33,34). The literature recommends wide, extensive debridement of all tissues that can be easily elevated off the fascia with gentle pressure. Wide debridement of all necrotic and poorly perfused tissues is associated with more rapid clinical improvement. There has been controversy regarding how much tissue should be initially excised because the skin may often appear normal. Andreasen et al. examined the normal-appearing tissues microscopically and reported that they had extensive early vascular thrombosis as well as vasculitis (5). Their findings indicate that these normal-appearing tissues have a high potential for full-thickness loss. After debridement, the wound must be carefully examined, especially after the initial procedure. Because hemodynamic instability is usually present after surgery, it may cause progressive skin necrosis. After debridement, the patient may be returned to the operating room as often as necessary for further surgical debridements. The anesthesiologist is an important member of the operative team because continued resuscitative efforts will be undertaken during the operative procedure. Once all of the affected tissues have been debrided, soft tissue reconstruction can be considered. In our experience, this may take at least two debridements. When the debridement involves relatively small body surface areas (⬍ 25%), skin grafts and flaps can provide coverage. When there is limited donor-site availability, alternatives to standard skin graft construction must be considered, to include either Integra artificial skin (Integra Life Sciences, Plainsboro, NJ) or AlloDerm (Lifecell Corporation, Blanchburg, NJ) (34,35). Due to persistent hypotension and diffuse capillary leak, massive amounts of intravenous fluids may be necessary after admission to the hospital. Nutritional support is also an integral part of treatment for patients with necrotizing fasciitis. This supplementation should be initiated as soon as hemodynamic stability is achieved. Enteral feeding should be established as soon as possible to offset the catabolism associated with large open wounds. Unfortunately, appropriate antitoxins are not available in this country. Successful use of intravenous immunoglobulin has been reported in the treatment of streptococcal toxic shock syndrome (36,37). A 5-day course of immunoglobulin was used in our reported patient (8). Recently, the efficacy and safety of high-dose
R. F. Edlich et al.
intravenous polyspecific immunoglobulin (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome were evaluated in a multicenter, randomized, doubleblind, placebo-control trial (38). The trial was prematurely stopped due to slow patient recruitment. The results were determined from 21 enrolled patients, 10 IVIG recipients and 11 placebo recipients. The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was noted in the placebo group. The use of adjunctive therapies, such as hyperbaric oxygen (HBO) therapy, for necrotizing fasciitis infection continues to receive much attention (8). Well-controlled, randomized clinical trials demonstrating a statistically significant benefit of HBO are lacking. Consequently, HBO as an adjunctive therapy for necrotizing fasciitis infections continues to be controversial (39 – 41). However, in hospitals where it is available, HBO therapy is recognized for its potential benefit in patients with these severe life-threatening infections (21,42). The beneficial effects of HBO were recently confirmed by another nonrandomized study reported in 2004 (43).
CONCLUSION Necrotizing fasciitis is a potentially fatal infection involving rapidly progressive, widespread necrosis of the superficial fascia. Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis. During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is usually polymicrobial, rather than monomicrobial. Although there has been no published well-controlled clinical trial comparing the efficacies of various diagnostic imaging modalities in the diagnosis of necrotizing infections, MRI is the preferred technique to detect soft tissue infection Percutaneous needle aspiration followed by prompt Gram’s stain and culture for a rapid bacteriologic diagnosis in soft tissue infections is recommended. Surgery, complemented by antibiotics, is the primary treatment of necrotizing fasciitis. On the basis of the review of the surgical literature, wide, extensive debridement of all tissues that can be easily elevated off the fascia with gentle pressure is recommended. Successful use of intravenous immunoglobulin has been reported in the treatment of streptococcal toxic shock syndrome. The use of adjunctive therapies, such as HBO therapy, for necrotizing fasciitis infection continues to receive much attention.
Necrotizing Fasciitis
265
REFERENCES 1. Quirk WF Jr, Sternbach G. Joseph Jones: infection with flesh eating bacteria. J Emerg Med 1996;14:747–53. 2. Stone DR, Gorbach S. Necrotizing fasciitis. The changing spectrum. Dermatol Clin 1997;15:213–20. 3. Rouse TM, Malangoni MA, Schulte WJ. Necrotizing fasciitis: a preventable disaster. Surgery 1982;92:765–70. 4. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg 1995;221:558 – 63. 5. Andreasen TJ, Green SD, Childers BJ. Massive infectious softtissue injury: diagnosis and management of necrotizing fasciitis and purpura fulminans. Plast Reconstr Surg 2001;107:1025–34. 6. Fugitt JB, Puckett ML, Quigley MM, Kerr SM. Necrotizing fasciitis. Radiographics 2004;24:1472– 6. 7. Lonergan S, Rodriguez RM, Schaulis M, Navaran P. A case series of patients with black tar heroin-associated necrotizing fasciitis. J Emerg Med 2004;26:47–50. 8. Drake DB, Woods JA, Bill TJ, et al. Magnetic resonance imaging in the early diagnosis of group A  streptococcal necrotizing fasciitis: a case report. J Emerg Med 1998;16:403–7. 9. Lille ST, Sato TT, Engrav LH, Foy H, Jurkovich GJ. Necrotizing soft tissue infections: obstacles in diagnosis. J Am Coll Surg 1996;182:7–11. 10. Craig JG. Infection: ultrasound-guided procedures. Radiol Clin North Am 1999;37:669 –78. 11. Parenti GC, Marri C, Calandra G, Morisi C, Zabberoni W. Necrotizing fasciitis of soft tissues: role of diagnostic imaging and review of the literature. Radiol Med 2000;99:334 –9. 12. Chao HC, Kong MS, Lin TY. Diagnosis of necrotizing fasciitis in children. J Ultrasound Med 1999;18:277– 81. 13. Beltran J, McGhee RB, Shaffer PB, et al. Experimental infections of the musculoskeletal system: evaluation with MR imaging and Tc-99m MDP and Ga-67 scintigraphy. Radiology 1988;167:167– 72. 14. Tang JHS, Gold RH, Bassett LW, Seeger LL. Musculoskeletal infection of the extremities. Radiology 1988;166:205–9. 15. Sharif HS, Clark DC, Aabed MY, Aideyan OA, Haddad MC, Mattsson TA. MR imaging of thoracic and abdominal wall infections: comparison with other imaging procedures. AJR Am J Roentgenol 1990;154:989 –95. 16. Rahmouni A, Chosidow O, Mathieu D, et al. MR imaging in acute infectious cellulitis. Radiology 1994;192:493– 6. 17. Uman SJ, Kunin CM. Needle aspiration in the diagnosis of soft tissue infections. Arch Intern Med 1975;135:959 – 61. 18. Francis J, Warren RE. Streptococcus pyogenes bacteria in Cambridge: a review of 67 episodes. Q J Med 1988;256:603–13. 19. Stamenkovic I, Lew PD. Early recognition of potentially fatal necrotizing fasciitis. The use of frozen-section biopsy. N Engl J Med 1984;310:1689 –93. 20. Childers BJ, Potyondy LD, Nachreiner R, et al. Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive patients. Am Surg 2002;68:109 –16. 21. Namias N, Martin L, Matos L, Sleeman D, Snowdon B. Symposium: necrotizing fasciitis. Contemp Surg 1996;49:167–78. 22. Yan S, Bohach GA, Stevens DL. Persistent acylation of highmolecular weight penicillin binding proteins by penicillin induces the post antibiotic effect in Streptococcus pyogenes. J Infect Dis 1994;170:609 –14.
23. Stevens DL, Maier KA, Mitten JE. Effect of antibiotics on toxin production and viability of Clostidium perfringens. Antimicrob Agents Chemother 1987;31:213– 8. 24. Stevens DL, Bryant AE, Yan S. Invasive group A streptococcal infection: new concepts in antibiotic treatment. Int J Antimicrob Agent 1994;4:297–301. 25. Gemmell CG, Peterson PK, Schmelling D, et al. Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin. J Clin Invest 1981;6: 1249 –56. 26. Stevens DL, Bryant AE, Hackett SP. Antibiotic effect on bacterial viability, toxin production, and host response. Clin Infect Dis 1995;20:S154 –7. 27. Edlich RF, Wind TC, Heather CL, Thacker JG. Reliability and performance of innovative surgical double-glove hole puncture indication systems. J Long Term Eff Med Implants 2003;13:69 – 83. 28. Edlich RF, Woodard CR, Pine SA, Lin KY. Hazards of power on surgical and examination gloves: a collective review. J Long Term Eff Med Implants 2001;11:15–27. 29. Chelsom J, 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. 30. Sudarsky LA, Laschinger JC, Coppa GF, Spencer FC. Improved results form standardized approach in treating patients with necrotizing fasciitis. Ann Surg 1987;206:661–5. 31. Wang KC, Shih CH. Necrotizing fasciitis of the extremities. J Trauma 1992;32:179 – 82. 32. Kaufman JL. Clinical problem-solving: necrotizing fasciitis (letter). N Engl J Med 1994;331:279 – 80. 33. Adams EM, Gudmundsson S, Yocum DE, Haselby RC, Craig WA, Sundstrom WR. Streptococcal myositis. Arch Intern Med 1985; 145:1020 –3. 34. Frame JD, Still J, Lakhel-LeCoadou A, et al. Use of dermal regeneration template in contracture release procedures: a multicenter evaluation. Plast Reconstr Surg 2004;113:1330 – 8. 35. Wainwright DJ. Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns 1995;21:243– 8. 36. Barry W, Hudgins L, Donta S, Pesanti E. I.V. immunoglobulin therapy for toxic shock syndrome. JAMA 1992;267:3315– 6. 37. Yong JM. Necrotizing fasciitis (letter). Lancet 1994;343:1427. 38. Darenberg J, Ihendyane N, Sjölin J, et al.; the Streptig Study Group. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003;37:333– 40. 39. Riseman JA, Zamboni WA, Curtis A, Graham DR, Konrad HR, Ross DS. Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements. Surgery 1990;108: 847–50. 40. Brown DR, Davis NL, Lepawsky M, Cunningham J, Kortbeek J. A multicenter review of the treatment of major truncal necrotizing infection with and without hyperbaric oxygen therapy. Am J Surg 1994;167:485–9. 41. Monestersky JH, Myers RAM. Hyperbaric oxygen treatment of necrotizing fasciitis. Am J Surg 1995;169:187– 8. 42. Green RJ, Dafoe DC, Raffin TA. Necrotizing fasciitis. Chest 1996;110:219 –29. 43. Sugihara A, Watanabe H, Oohashi M, et al. The effect of hyperbaric oxygen on the bout of treatment for soft tissue infections. J Infect 2004;48:330 –3.
doi:10.1016/j.jemermed.2008.06.024
Clinical Reviews
MODERN CONCEPTS OF THE DIAGNOSIS AND TREATMENT OF NECROTIZING FASCIITIS Richard F. Edlich,
MD, PHD,*
Catherine L. Cross,† Jill J. Dahlstrom,† and William B. Long III,
MD‡
*Director of Trauma Prevention, Education and Research, Legacy Verified Level I Shock Trauma Center at Legacy Emanuel Hospital, Portland, Oregon, †Research Assistant, Legacy Emanuel Hospital, Portland, Oregon, and ‡President and Medical Director of Trauma Specialists, LLP, Legacy Emanuel Hospital, Portland, Oregon Reprint Address: Richard F. Edlich, MD, PHD, Legacy Emanuel Hospital, 22500 NE 128th Circle, Brush Prairie, WA 98606
baric oxygen therapy, for necrotizing fasciitis infection continues to receive much attention. © 2010 Elsevier Inc.
e Abstract—Background: Necrotizing fasciitis is a potentially fatal infection involving rapidly progressive, widespread necrosis of the superficial fascia. Objectives: The purpose of this collective review is to review modern concepts of the treatment and diagnosis of necrotizing fasciitis. Discussion: Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis. During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is usually polymicrobial, rather than monomicrobial. Although there has been no published well-controlled, clinical trial comparing the efficacies of various diagnostic imaging modalities in the diagnosis of necrotizing infections, magnetic resonance imaging (MRI) is the preferred technique to detect soft tissue infection. MRI provides unsurpassed soft tissue contrast and spatial resolution, has high sensitivity in detecting soft tissue fluid, and has multiplanar capabilities. Percutaneous needle aspiration followed by prompt Gram’s staining and culture for a rapid bacteriologic diagnosis in soft tissue infections is recommended. Surgery complemented by antibiotics is the primary treatment of necrotizing fasciitis. Conclusion: Wide, extensive debridement of all tissues that can be easily elevated off the fascia with gentle pressure should be undertaken. Successful use of intravenous immunoglobulin has been reported in the treatment of streptococcal toxic shock syndrome. The use of adjunctive therapies, such as hyper-
RECEIVED: 20 February 2008; FINAL ACCEPTED: 11 June 2008
SUBMISSION RECEIVED:
e Keywords—necrotizing fasciitis; MRI; percutaneous needle aspiration; debridement; antibiotics
INTRODUCTION Necrotizing fasciitis is a destructive infection that involves both skin and soft tissues. In this collective review we will outline its pathophysiology as well as the diagnostic studies that are needed for rapid, accurate diagnosis of this life-threatening infectious disease. Second, we will review the bacteriology of necrotizing fasciitis. Finally, we will review the treatment strategies for managing this massive infectious soft tissue disease.
PATHOPHYSIOLOGY Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. It was once considered an uncommon clinical entity. In the 1990s, the media popularized this infection as being caused by “flesh-eating bacteria.” Although the pathogenesis of necrotizing fasciitis is still open to specula-
8 May 2008; 261
262
tion, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis (1). Historically, group A -hemolytic streptococcus (GABS) has been identified as a major cause of this infection. This monomicrobial infection is usually associated with an underlying cause such as diabetes, atherosclerotic vascular disease, or venous insufficiency with edema. GABS usually affects the extremities, with approximately two-thirds of cases being located in the lower extremities (2). During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is usually polymicrobial, rather than monomicrobial. In 1982, Rouse et al. reported 28 cases of necrotizing fasciitis (3). They pointed out that all but four infections were polymicrobial. The overall mortality rate was 74% (20 of 27). They indicated that prompt recognition and treatment of necrotizing fasciitis is essential. Eleven of 12 patients who had a delay in treatment for more than 12 h died. In 1995, McHenry et al. found very similar findings to that of Rouse et al. (4). McHenry et al. reported on the determinants of mortality for recognizing soft tissue infections. Necrotizing soft tissue infections were polymicrobial in 45 patients (69%). The average time from admission to operation was 90 h in nonsurvivors vs. 20 h in survivors. Early debridement of the infection was obviously associated with a significant decrease in mortality. In a series of 163 consecutive patients reported by Andreasen et al., it was noted that 71% of their patients with necrotizing fasciitis had a polymicrobial infection (5). In many cases of necrotizing fasciitis, an identifiable antecedent trauma was evident. Surprisingly, the initial lesion was often trivial, such as an insect bite, minor abrasion, boil, or injection site. Other indicative findings included edema extending beyond the area of erythema, skin vesicles, and crepitus. They noted that the subcutaneous tissue will demonstrate a wooden, hardened feel. The fascial planes and muscle groups cannot be detected by palpation. Laboratory evaluation should include complete blood counts, blood chemistries, arterial blood gases, and tissue and blood cultures. Radiographic studies must be undertaken to detect air in soft tissues. When the patient is seriously ill, Fugitt et al. pointed out, necrotizing fasciitis is a surgical emergency with high mortality; therefore, imaging studies should not delay surgical intervention (6). On the west coast of the United States, necrotizing fasciitis has been associated with the injection use of black tar heroin, a dense, gummy, coal-colored substance that is produced from opium grown in the mountainous region of northern Mexico (7). Crude processing techniques lead to the production of compounds that are commonly laced with organic resins and other contaminants. Injection of this drug into the skin can predispose to the development of necrotizing fasciitis.
R. F. Edlich et al.
DIAGNOSTIC STUDIES We have reported appropriate radiological studies that allow an early diagnosis of necrotizing infections (8). In addition, they permit visualization of the location of the rapidly spreading infection. Plain radiographs, often obtained to detect soft tissue gas that is sometimes present in polymicrobial or clostridial necrotizing fasciitis, are of no value in the diagnosis of necrotizing infections (8,9). In their study of 29 patients with necrotizing soft tissue infections, Lille et al. reported that non-diagnostic radiographs correlate with a delay in operative intervention and consequent increased morbidity and mortality (9). The majority of fluid collections in the tissue, especially the musculoskeletal system, can be localized and aspirated under ultrasound guidance. Whether or not fluid is infected cannot be determined from ultrasound appearances; laboratory analysis is required. In complicated infections, particularly septic arthritis and osteomyelitis, combined use of magnetic resonance imaging (MRI) and aspiration under ultrasound is very useful. Its role in the diagnosis of necrotizing fasciitis should be considered (10). Early muscle necrosis may be apparent. Parenti et al. retrospectively reviewed the ultrasound appearances of 32 pathologically proven cases of necrotizing fasciitis (11). Ultrasound revealed changes in the subcutaneous fat (28 of 32), investing fascia (18 of 32), and muscle (15 of 32) that correlated well with histological findings. However, in some cases, ultrasound did not reveal histologically apparent inflammation in the subcutaneous tissues (3 of 32) or muscle (8 of 32). Ultrasoundguided aspiration of perifascial fluid can help isolate the pathogen (12). Successful treatment requires early recognition, aggressive antibiotic therapy, and adequate surgical debridement. Although there has been no published, well-controlled, clinical trial comparing the efficacies of various diagnostic imaging modalities in the diagnosis of necrotizing infections, MRI is the preferred technique to detect soft tissue infection. MRI provides unsurpassed soft tissue contrast and spatial resolution, has high sensitivity in detecting soft tissue fluid, and has multiplanar capabilities (13,14). In a study of 13 patients with thoracic and abdominal wall infections, Sharif et al. reported that computed tomography (CT) and MRI were superior to sonography, scintigraphy, and plain radiography in providing useful information about the nature and extent of infections (15). Furthermore, they suggested that although CT compares favorably with MRI in the accurate diagnosis of soft tissue infection, multiplanar magnetic resonance images can be obtained without ionizing radiation and the use of i.v. contrast agents. The usefulness of MRI in the diagnosis of necrotizing fasciitis has been supported in a study by Rahmouni et al., who in 36 patients
Necrotizing Fasciitis
263
were able to differentiate between non-necrotizing cellulitis that would respond to medical treatment and severe, necrotizing infections that required rapid, life-saving surgery (16). In a reported case of necrotizing fasciitis, MRI provided dramatic evidence of an inflammatory process infiltrating the fascial planes (8). Uman and Kunin recommended percutaneous needle aspiration followed by prompt Gram’s stain and culture for a rapid bacteriologic diagnosis in soft tissue infections (17). A needle aspirate should be taken on the advancing edge of the infection where GABS are plentiful (18). A Gram’s stain of the tissue aspirate can be used to differentiate erysipelas from necrotizing infections. Cocci are plentiful in the aspirate from necrotizing infection, whereas they are rarely identified in the aspirate in patients with erysipelas (18). The results of the microbiological aspirate should be complemented by blood cultures. The “finger-test” and rapid-frozen section biopsy examinations also should be used in the diagnosis of patients presenting with suspected necrotizing fasciitis (19,20). The area of suspected involvement is first infiltrated with local anesthesia. A 2-cm incision is made in the skin down to the deep fascia. Lack of bleeding is a sign of necrotizing fasciitis. On some occasions, a dishwater-colored fluid is noticed seeping from the wound. A gentle, probing maneuver with the index finger covered by a sterile powder-free surgical double glove is then performed at the level of the deep fascia. If the tissues dissect with minimal resistance, the “finger test” is positive. Tissue biopsies are then sent for frozen-section analysis. The characteristic histologic findings are obliterative vasculitis of the subcutaneous vessels and acute inflammation, as well as subcutaneous tissue necrosis. If either the “finger-test” or rapid frozen-section analysis is positive, or if the patient has progressive clinical findings consistent with necrotizing fascia, immediate operative treatment must be initiated.
TREATMENT Whenever possible, aggressive resuscitation must be initiated immediately to maintain hemodynamic stability. A polymicrobial, symbiotic infection recently has been found to be the most common cause of necrotizing fasciitis (4). Polymicrobial infections are often associated with previous surgical procedures, pressure ulcers, penetrating trauma, and perianal abscesses, as well as intravenous drug use. In the study by Andreasen et al., 71% of their patients had polymicrobial infections (5). Antibiotic therapy is a key consideration for these polymicrobial infections. The physician may use a com-
bination of penicillin G, an aminoglycoside, if renal function permits, as well as clindamycin to treat necrotizing fasciitis caused by streptococci, staphylococci, and Gram-negative bacilli, as well as anaerobes. Clindamycin remains the antibiotic of choice for necrotizing infections (21). Unlike penicillin, the efficacy of clindamycin is not affected by the inoculum size or stage of bacterial growth (22,23). Second, clindamycin is a potent suppressor of bacterial toxin synthesis (24,25). Third, subinhibitory concentrations of clindamycin facilitate the phagocytosis of GABS (8). Fourth, clindamycin reduces the synthesis of penicillin-binding protein, which, in addition to being a target for penicillin, is also an enzyme involved in cell wall synthesis and degradation (22). Fifth, clindamycin has a longer post-antibiotic effect than lactins such as penicillin (25). Finally, Stevens et al. demonstrated that clindamycin causes suppression of lipopolysaccharide-induced mononuclear synthesis of tumor necrosis factor-␣ (26). Consequently, the success of clindamycin also may be related to its ability to modulate the immune response (27). Initial antimicrobial therapy should be broad-based to cover aerobic Gram-positive and Gram-negative organisms and anaerobes. We recommend penicillin G, 24 million units per day i.v., divided into q 4 – 6-h doses; clindamycin, 900 mg i.v. q 8 h; and gentamicin, 1 mg/kg i.v. q 8 h. A more specifically targeted antibiotic regimen may be begun after initial Gram’s stain smear, culture, and sensitivities are available. Although some necrotizing infections still may be susceptible to penicillin, clindamycin is the treatment of choice for necrotizing infections because it is a potent suppressor of bacterial toxin synthesis and because the inoculum size or stage of bacterial growth does not affect its efficacy. If staphylococci are involved, nafcillin or vancomycin should be used in place of penicillin. Surgery is the primary treatment for necrotizing fasciitis. During surgery, all operating room personnel should be wearing a powder-free double-glove hole indication system that protects the staff as well as the patient from gaining access to deadly blood-borne infections (27). The Food and Drug Administration requires that the glove manufacturer produce sterile surgical gloves whose leakage rate does not exceed 2.5%. This high frequency of glove holes is an invitation to the spread of deadly blood-borne infections between operating room personnel and the patient. The double-glove system is also powder-free, thereby reducing the potentially serious complications of cornstarch. It has been well documented that cornstarch in wounds potentiates the development of infection. In addition, the cornstarch on latex gloves can carry the latex antigen and precipitate anaphylactic reactions in individuals allergic to latex (28). It is essential that surgeons be consulted early in the
264
care of these challenging patients. Early surgical debridement of necrotic tissue is a life-saving treatment. The importance of early diagnosis is underscored by many studies that document the significant benefit to prognosis and outcome associated with early and aggressive debridement of necrotizing soft tissue infections (9,21–32). In addition, early surgical treatment may minimize tissue loss, eliminating the need for amputation of the infected extremity (33,34). The literature recommends wide, extensive debridement of all tissues that can be easily elevated off the fascia with gentle pressure. Wide debridement of all necrotic and poorly perfused tissues is associated with more rapid clinical improvement. There has been controversy regarding how much tissue should be initially excised because the skin may often appear normal. Andreasen et al. examined the normal-appearing tissues microscopically and reported that they had extensive early vascular thrombosis as well as vasculitis (5). Their findings indicate that these normal-appearing tissues have a high potential for full-thickness loss. After debridement, the wound must be carefully examined, especially after the initial procedure. Because hemodynamic instability is usually present after surgery, it may cause progressive skin necrosis. After debridement, the patient may be returned to the operating room as often as necessary for further surgical debridements. The anesthesiologist is an important member of the operative team because continued resuscitative efforts will be undertaken during the operative procedure. Once all of the affected tissues have been debrided, soft tissue reconstruction can be considered. In our experience, this may take at least two debridements. When the debridement involves relatively small body surface areas (⬍ 25%), skin grafts and flaps can provide coverage. When there is limited donor-site availability, alternatives to standard skin graft construction must be considered, to include either Integra artificial skin (Integra Life Sciences, Plainsboro, NJ) or AlloDerm (Lifecell Corporation, Blanchburg, NJ) (34,35). Due to persistent hypotension and diffuse capillary leak, massive amounts of intravenous fluids may be necessary after admission to the hospital. Nutritional support is also an integral part of treatment for patients with necrotizing fasciitis. This supplementation should be initiated as soon as hemodynamic stability is achieved. Enteral feeding should be established as soon as possible to offset the catabolism associated with large open wounds. Unfortunately, appropriate antitoxins are not available in this country. Successful use of intravenous immunoglobulin has been reported in the treatment of streptococcal toxic shock syndrome (36,37). A 5-day course of immunoglobulin was used in our reported patient (8). Recently, the efficacy and safety of high-dose
R. F. Edlich et al.
intravenous polyspecific immunoglobulin (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome were evaluated in a multicenter, randomized, doubleblind, placebo-control trial (38). The trial was prematurely stopped due to slow patient recruitment. The results were determined from 21 enrolled patients, 10 IVIG recipients and 11 placebo recipients. The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was noted in the placebo group. The use of adjunctive therapies, such as hyperbaric oxygen (HBO) therapy, for necrotizing fasciitis infection continues to receive much attention (8). Well-controlled, randomized clinical trials demonstrating a statistically significant benefit of HBO are lacking. Consequently, HBO as an adjunctive therapy for necrotizing fasciitis infections continues to be controversial (39 – 41). However, in hospitals where it is available, HBO therapy is recognized for its potential benefit in patients with these severe life-threatening infections (21,42). The beneficial effects of HBO were recently confirmed by another nonrandomized study reported in 2004 (43).
CONCLUSION Necrotizing fasciitis is a potentially fatal infection involving rapidly progressive, widespread necrosis of the superficial fascia. Necrotizing fasciitis is characterized by widespread necrosis of the subcutaneous tissue and the fascia. Although the pathogenesis of necrotizing fasciitis is still open to speculation, the rapid and destructive clinical course of necrotizing fasciitis is thought to be due to multibacterial symbiosis. During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is usually polymicrobial, rather than monomicrobial. Although there has been no published well-controlled clinical trial comparing the efficacies of various diagnostic imaging modalities in the diagnosis of necrotizing infections, MRI is the preferred technique to detect soft tissue infection Percutaneous needle aspiration followed by prompt Gram’s stain and culture for a rapid bacteriologic diagnosis in soft tissue infections is recommended. Surgery, complemented by antibiotics, is the primary treatment of necrotizing fasciitis. On the basis of the review of the surgical literature, wide, extensive debridement of all tissues that can be easily elevated off the fascia with gentle pressure is recommended. Successful use of intravenous immunoglobulin has been reported in the treatment of streptococcal toxic shock syndrome. The use of adjunctive therapies, such as HBO therapy, for necrotizing fasciitis infection continues to receive much attention.
Necrotizing Fasciitis
265
REFERENCES 1. Quirk WF Jr, Sternbach G. Joseph Jones: infection with flesh eating bacteria. J Emerg Med 1996;14:747–53. 2. Stone DR, Gorbach S. Necrotizing fasciitis. The changing spectrum. Dermatol Clin 1997;15:213–20. 3. Rouse TM, Malangoni MA, Schulte WJ. Necrotizing fasciitis: a preventable disaster. Surgery 1982;92:765–70. 4. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg 1995;221:558 – 63. 5. Andreasen TJ, Green SD, Childers BJ. Massive infectious softtissue injury: diagnosis and management of necrotizing fasciitis and purpura fulminans. Plast Reconstr Surg 2001;107:1025–34. 6. Fugitt JB, Puckett ML, Quigley MM, Kerr SM. Necrotizing fasciitis. Radiographics 2004;24:1472– 6. 7. Lonergan S, Rodriguez RM, Schaulis M, Navaran P. A case series of patients with black tar heroin-associated necrotizing fasciitis. J Emerg Med 2004;26:47–50. 8. Drake DB, Woods JA, Bill TJ, et al. Magnetic resonance imaging in the early diagnosis of group A  streptococcal necrotizing fasciitis: a case report. J Emerg Med 1998;16:403–7. 9. Lille ST, Sato TT, Engrav LH, Foy H, Jurkovich GJ. Necrotizing soft tissue infections: obstacles in diagnosis. J Am Coll Surg 1996;182:7–11. 10. Craig JG. Infection: ultrasound-guided procedures. Radiol Clin North Am 1999;37:669 –78. 11. Parenti GC, Marri C, Calandra G, Morisi C, Zabberoni W. Necrotizing fasciitis of soft tissues: role of diagnostic imaging and review of the literature. Radiol Med 2000;99:334 –9. 12. Chao HC, Kong MS, Lin TY. Diagnosis of necrotizing fasciitis in children. J Ultrasound Med 1999;18:277– 81. 13. Beltran J, McGhee RB, Shaffer PB, et al. Experimental infections of the musculoskeletal system: evaluation with MR imaging and Tc-99m MDP and Ga-67 scintigraphy. Radiology 1988;167:167– 72. 14. Tang JHS, Gold RH, Bassett LW, Seeger LL. Musculoskeletal infection of the extremities. Radiology 1988;166:205–9. 15. Sharif HS, Clark DC, Aabed MY, Aideyan OA, Haddad MC, Mattsson TA. MR imaging of thoracic and abdominal wall infections: comparison with other imaging procedures. AJR Am J Roentgenol 1990;154:989 –95. 16. Rahmouni A, Chosidow O, Mathieu D, et al. MR imaging in acute infectious cellulitis. Radiology 1994;192:493– 6. 17. Uman SJ, Kunin CM. Needle aspiration in the diagnosis of soft tissue infections. Arch Intern Med 1975;135:959 – 61. 18. Francis J, Warren RE. Streptococcus pyogenes bacteria in Cambridge: a review of 67 episodes. Q J Med 1988;256:603–13. 19. Stamenkovic I, Lew PD. Early recognition of potentially fatal necrotizing fasciitis. The use of frozen-section biopsy. N Engl J Med 1984;310:1689 –93. 20. Childers BJ, Potyondy LD, Nachreiner R, et al. Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive patients. Am Surg 2002;68:109 –16. 21. Namias N, Martin L, Matos L, Sleeman D, Snowdon B. Symposium: necrotizing fasciitis. Contemp Surg 1996;49:167–78. 22. Yan S, Bohach GA, Stevens DL. Persistent acylation of highmolecular weight penicillin binding proteins by penicillin induces the post antibiotic effect in Streptococcus pyogenes. J Infect Dis 1994;170:609 –14.
23. Stevens DL, Maier KA, Mitten JE. Effect of antibiotics on toxin production and viability of Clostidium perfringens. Antimicrob Agents Chemother 1987;31:213– 8. 24. Stevens DL, Bryant AE, Yan S. Invasive group A streptococcal infection: new concepts in antibiotic treatment. Int J Antimicrob Agent 1994;4:297–301. 25. Gemmell CG, Peterson PK, Schmelling D, et al. Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin. J Clin Invest 1981;6: 1249 –56. 26. Stevens DL, Bryant AE, Hackett SP. Antibiotic effect on bacterial viability, toxin production, and host response. Clin Infect Dis 1995;20:S154 –7. 27. Edlich RF, Wind TC, Heather CL, Thacker JG. Reliability and performance of innovative surgical double-glove hole puncture indication systems. J Long Term Eff Med Implants 2003;13:69 – 83. 28. Edlich RF, Woodard CR, Pine SA, Lin KY. Hazards of power on surgical and examination gloves: a collective review. J Long Term Eff Med Implants 2001;11:15–27. 29. Chelsom J, 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. 30. Sudarsky LA, Laschinger JC, Coppa GF, Spencer FC. Improved results form standardized approach in treating patients with necrotizing fasciitis. Ann Surg 1987;206:661–5. 31. Wang KC, Shih CH. Necrotizing fasciitis of the extremities. J Trauma 1992;32:179 – 82. 32. Kaufman JL. Clinical problem-solving: necrotizing fasciitis (letter). N Engl J Med 1994;331:279 – 80. 33. Adams EM, Gudmundsson S, Yocum DE, Haselby RC, Craig WA, Sundstrom WR. Streptococcal myositis. Arch Intern Med 1985; 145:1020 –3. 34. Frame JD, Still J, Lakhel-LeCoadou A, et al. Use of dermal regeneration template in contracture release procedures: a multicenter evaluation. Plast Reconstr Surg 2004;113:1330 – 8. 35. Wainwright DJ. Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns 1995;21:243– 8. 36. Barry W, Hudgins L, Donta S, Pesanti E. I.V. immunoglobulin therapy for toxic shock syndrome. JAMA 1992;267:3315– 6. 37. Yong JM. Necrotizing fasciitis (letter). Lancet 1994;343:1427. 38. Darenberg J, Ihendyane N, Sjölin J, et al.; the Streptig Study Group. Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2003;37:333– 40. 39. Riseman JA, Zamboni WA, Curtis A, Graham DR, Konrad HR, Ross DS. Hyperbaric oxygen therapy for necrotizing fasciitis reduces mortality and the need for debridements. Surgery 1990;108: 847–50. 40. Brown DR, Davis NL, Lepawsky M, Cunningham J, Kortbeek J. A multicenter review of the treatment of major truncal necrotizing infection with and without hyperbaric oxygen therapy. Am J Surg 1994;167:485–9. 41. Monestersky JH, Myers RAM. Hyperbaric oxygen treatment of necrotizing fasciitis. Am J Surg 1995;169:187– 8. 42. Green RJ, Dafoe DC, Raffin TA. Necrotizing fasciitis. Chest 1996;110:219 –29. 43. Sugihara A, Watanabe H, Oohashi M, et al. The effect of hyperbaric oxygen on the bout of treatment for soft tissue infections. J Infect 2004;48:330 –3.