Tissue-Sparing Surgical Debridement versus Radical ...

Tissue-Sparing Surgical Debridement versus Radical Surgical Debridement in a Patient Presenting with Necrotizing Fasciitis Department of Surgery Leiden University Medical Centre (LUMC), Leiden, the Netherlands

Course Supervisor Second Reader Student Student Number

Academic Scientific Writing K.A.A. Kwa Dr. A. de Vries J. Dahmen 1915339

TABLE OF CONTENTS Chapter I [I.I] [I.II]

General Introduction Clinical Scenario and Question Introduction

Chapter II [II.I] [II.II] [II.II.I] [II.II.II] [II.II.III] [II.III] [II.IV] [II.V]

Critical Appraisal of a Topic Literature Search Critical Evaluation: Validity Proud et al. (2016) Eggerstedt et al. (2016) Tom et al. (2016) Summary of Results Applicability, Evidence and Commentary Bottom line

Chapter III [III.I]

General Discussion Discussion

References Appendix [I] [II] [III] [IV]

Search Strategy Inclusion and Exclusion Criteria Criteria used for Critical Evaluation of the Articles Evidence Tables

Chapter I

General Introduction

I.I

Clinical Scenario and Clinical Question

A 34-year old woman was admitted to the emergency department of the Leiden University Medical Centre (LUMC) with a sepsis. Her symptoms included: a tachycardia of 132 beats per minute, a respiratory rate of 34 per minute, a blood pressure of 90/45 mmHg and a temperature of 39.5°Celsius. Her symptoms were a localized swelling, pain and erythema around her left mamma. The emergency doctor confirmed a septic shock and a mastitis on the left side of her thorax and immediately started intravenous antibiotic treatment. She was taken to the operating theatre with the diagnosis of a necrotizing fasciitis, which was confirmed perioperatively. Positive swabs showed a group A hemolytic streptococcal infection. During the first operation, a stepwise debridement was performed until healthy looking tissue was reached. The left mamma, the skin, subcutis and fascia of the left thoracic wall were all resected. A re-exploration was conducted several hours later in which more fascia of the shoulder was resected due to progression of infection. This time, the subcutis and skin were spared. The progression of infection was halted and the patient was left with a substantial soft tissue defect of approximately 7% of her body surface area. The defect of the first operation was treated with negative pressure therapy and a subsequent grafting procedure took place in order to achieve wound closure. The wounds in which the subcutis and skin were spared were closed primarily. The wound that was grafted left a large adherent scar. The primarily closed wound left only a small line. The outcome of scar quality and possible accompanying decrement in quality of life leaves us and the patient with the clinical question whether it would be possible to perform a skinsparing or tissue-sparing debridement technique for patients with necrotizing in the acute phase, rather than a radial debridement. I.I

Introduction

Necrotizing fasciitis is a rapidly advancing infection of the fascia that has a mortality rate of around 1-3 20% worldwide . An alternative term used to describe a large collective of infections of both the subcutaneous tissues and the fascia is a necrotizing soft-tissue infection (NSTI). In the United States 4 of America alone, the incidence has been assessed to range from 3800 to 5800 . The majority of the cases are secondary infections due to traumatic events, such as skin lesions, surgical wounds, insect bites and traumatic lacerations. Other causes of the disease include varicella zoster infections, 5-7 consumption of raw or undercooked seafood, pressure sores and skin abscess drainages . Patients with necrotizing fasciitis generally present with the classical triad of symptoms: erythema, pain and 8 swelling . Most commonly occurring signs are tachycardia, fever, hypotension and less frequently tachypnea. Moreover, the affected site might display skin necrosis, hemorrhagic bullae, tenderness 9 and sclerosis . When analyzing co-morbidities and risk factors, one should note that generally there are two types of bacteriologic infectious entities to be considered. The first one is the polymicrobial infection in immunocompromised patients, such as patients suffering from diabetes mellitus (DM) and immunosuppressed patients, for instance patients with liver cirrhosis, chronic heart failure, systemic 10-13 cardiovascular diseases and other chronic illnesses . The second entity is the group A 8, 14, 15 streptococcal infections (GAS) in otherwise healthy patients . Early diagnosis is of paramount importance in the course of treatment. The golden standard for the diagnosis is a combination of surgical exploration and microbiological and histopathological analysis in the form of biopsy of the 5, 16 involved fascia, after which gram staining is executed . Subsequent acute care with appropriate antibiotics and wide radical surgical debridement is essential and is considered as traditional primary 17-19 preferred management being closely correlated with clinically favorable outcomes . A combination of quick diagnosis and surgery is vital, as delay in both diagnosis and prompt aggressive surgical debridement is not solely associated with rapid tissue destruction and severe sepsis, but also with 5, 6, 20, 21 higher rates of mortality and amputation . Due to the adequate and quick management by means of radical surgical debridement, the mortality related to necrotizing fasciitis has been 4, 17-19, 22 decreasing considerably for the past 15 years from nearly 40% to 10% to 5% . However, after performing aggressive surgical debridement the quality of life in patients with necrotizing fasciitis will

be severely depressed, because the majority of the survivors are left with extensive surface-area 23 wounds comparable to full-thickness burns . This indicates that the increasing survivorship demands that the focus of current optimal treatment expands from solely preserving life to optimizing quality of life. In order to address this important issue, a different surgical debridement technique in the form of 24-26 skin- or tissue-sparing strategy has been developed . Due to this, it is desirable to consider tissuesparing surgical debridement as a possible acute management option for patients presenting with necrotizing fasciitis. The accompanying critical question and objective arising and belonging to the present Critical Appraisal of a Topic (CAT) project is therefore as follows: is tissue-sparing or skinsparing surgical debridement a possible management option for treating the (our) acute patient presenting with necrotizing fasciitis (in terms of mortality and morbidity), and might it be clinically preferred over aggressive and radical surgical debridement with reference to (long-term) clinical outcomes such as scar quality, quality of life and amputation rates.

Chapter II: Critical Appraisal of a Topic II.I

Literature Search

The literature search was performed via the PubMed National Library of Medicine, and the full literature search is included in Appendix I. The components containing the full strategy were: “necrotizing fasciitis”[Mesh], “debridement”[Mesh], “skin-sparing”[tw], “tissue-sparing”[tw]. We also included a specific filter in order to solely identify clinical studies. We aimed at identifying primary research articles describing the clinical results after aggressive (wide) surgical debridement in patients suffering from a necrotizing soft-tissue infection in any part of the body. We wished to compare this to a control group treated with a tissue-sparing or skin-sparing surgical debridement technique. The inclusion criteria included patients suffering from a necrotizing fasciitis infection to a nonparticular body part treated by either radical surgical debridement or by tissue- or skin-sparing surgical debridement. The other relevant inclusion criteria as well as the specific exclusion criteria are presented in Appendix II. As can be deduced from the flowchart in Appendix III, 1317 articles were identified from the literature and after excluding duplicate articles in combination with applying our inclusion and exclusion criteria to the screening of the titles and abstracts, 1183 articles were excluded. Then,134 articles were included for full-text reading, and again, after adhering to our inclusion and exclusion criteria, we were able to include three studies in the analysis of the present CAT manuscript. The following three 27, 28 articles matched our inclusion criteria, and were evaluated using the JAMA guidelines : 1. Proud D, Bruscino Raiola F, Holden D, Paul E, Capstick R, Khoo A (2014) Are we getting 29 necrotizing soft tissue infections right? A 10-year review. ANZ J Surg 84:468-472 2. Eggerstedt M, Gamelli RL, Mosier MJ (2015) The care of necrotizing soft-tissue infections: 30 patterns of definitive intervention at a large referral center. J Burn Care Res 36:105-110 3. Tom LK, Wright TJ, Horn DL, Bulger EM, Pham TN, Keys KA (2016) A Skin-Sparing Approach to the Treatment of Necrotizing Soft-Tissue Infections: Thinking Reconstruction at 24 Initial Debridement. J Am Coll Surg 222:e47-60 [II.II]

Critical Evaluation: Validity

This section on critical evaluation will give an evaluation of the validity, results and applicability of the selected articles. The research goal of the specific article in question will be presented after which it 27, 28 will be assessed according to the JAMA-guidelines on therapy . We will shortly summarize this section by means of a outline of the validity, results and applicability section. 29

[II.II.I] Proud et al. (2014) 29 Proud et al. (2014) conducted a retrospective cohort study in Australia including 219 patients that were admitted to the Alfred Hospital in Australia between 1 January 2001 and 31 December 2010 with 29 a necrotizing soft-tissue infection . The author of the present CAT thesis sought contact with dr. Proud and by these means it was assessed that all patients underwent a radical surgical debridement procedure. There was a two-fold aim of the study in question:1) to compare the current practice in the Alfred Hospital in Australia and the outcomes against published data, and 2) to examine management at referring hospitals in order to determine whether adjustments to current practice were required. As this is a retrospective cohort study assessing the clinical outcomes of radical debridement for one group of patients without a comparative nature of study, there was no randomization performed making it therefore methodologically impossible to assess whether certain groups were similar at baseline and whether – aside from the experimental intervention – the groups were treated equally. Patients were included if they adhered to the inclusion criteria which described that the patient needed to have a necrosis of muscle, fat or fascia or the patient in question had undergone a histopathology report confirming necrosis at the level of muscle, fat or fascia. Patients were excluded if they did not have a necrotizing soft-tissue infection described in their medical report. For this

reason, 32 patients were excluded. Information about lost to follow-up and whether all patients completed the study protocol is lacking. Additionally, it was not described whether the patients excluded from the review nor the potential patients lost-to-follow-up were included in the statistical analysis. Therefore, it is unclear whether the authors adhered to an intention-to-treat analysis protocol. Patients, health workers, and study personnel were not blinded to treatment. There were three primary outcome measures reported. The first one was acute mortality rate in percentages, the second one morbidity rate measured as number of amputations performed and the third one health status as assessed by percentages of patients undergoing inotropic support and mechanical ventilation. Secondary outcome measures included were median length of hospital stay, diversity of microbiology, number of debridement and reconstructive procedures performed and the discharge dispositions. Although the number of patients included in this retrospective cohort study is relatively high, the 29 methodological quality and thus the validity of the manuscript of Proud et al. can be considered low. 30

[II.II.II] Eggerstedt et al. (2014) 30 Eggerstedt et al. also conducted a retrospective cohort study, but included a smaller number of patients (n = 81) that were diagnosed with necrotizing soft-tissue infections. A retrospective chart review was performed including patients that were treated by the burn center in the University Medical Centre in Illinois from January 1, 2007 to December 31, 2012. The objective of this particular study was three-fold. Firstly, the author group wished to assess the methods employed in treating NSTIs by an experienced referral center. Secondly, it was their aim to characterize the patient population at risk for the development of an NSTI and subsequently determine predictors of mortality within this population. Lastly, the objective was to directly compare outcomes between those who are transferred to a burn center after diagnosis and those who present directly to such a center. Concerning the grading of the internal validity of this specific study, there was no randomization performed. Rather, the two groups were analyzed retrospectively, without any type of blinding. Therefore, patients, health workers, and study personnel were not blinded to treatment nor nature of transfer of the patients. Four patients were excluded from the study protocol as they were diagnosed with an NSTI of such an extent that it was deemed inappropriate to perform radical debridement. These patients were treated with comfort care, and were not included in the statistical analysis. Furthermore, there was no information on lost-to follow-up rates. Concerning the similarity of both patient populations at baseline, it must be noted that there was no difference in surgical technique but solely in the transfer nature.That is, direct admits to the hospital or those patients that were transferred to a burn center after diagnosis. Apart from this, the group of transferred patients versus the group of direct admits were similar at baseline concerning age, gender, BMI, Charlson score (numerical judgement of prior health), acute kidney failure on admission and multiple organ failure on admission. Later in the process, it became clear that other clinically important characteristics, such as median days of mechanical ventilation, median duration of admission till initial debridement, number of operations and hospital mortality rates were also similar, as the p-values were assessed to be equal to or lager than 0.05. Solely the characteristic of median duration of initial debridement until grafting was different (p < 0.05): the median duration in the transfer group was 25 days with interquartiles (IQRs) ranging from 13 to 39 days, and in the direct admits group this was calculated to be 16 days, with IQRs ranging from 10 to 23 days. The primary outcomes reported were acute mortality rate,1-year post-operatively mortality rate, and the morbidity rate concerning health status with reference to acute kidney injury and multiple organ failure on admission. The secondary outcome measurements were median length of hospital stay, diversity of microbiology, number of debridement procedures performed and the different discharge positions the patients were sent to. Despite the high number of patients (n = 81) with NSTIs included and the comparative nature of the 30 study, the retrospective cohort study by Eggerstedt et al. is of low methodological quality.

24

[II.II.III] Tom et al. (2016) By means of reviewing the medical records of 11 patients with necrotizing soft-tissue infections, Tom 24 et al. (2016) conducted a retrospective case series study. These patients were not treated by the radical surgical debridement technique, but rather were surgically debrided in a skin-sparing debridement approach with the use of an incision diagram protocol. The objective of the study was to evaluate and describe the rationale and implementation of the surgical skin-sparing debridement technique, and to present a case series of patients with necrotizing soft-tissue infections presenting at the Seattle University Hospital (United States of America) having undergone this surgical technique. As this is a retrospective case series assessing the clinical outcomes of skin-sparing debridement for one group of patients without a comparative nature of study, there was no randomization performed. Therefore, it was not possible to assess whether specific patient populations were similar at baseline and whether – aside from the experimental intervention – the groups were treated equally. Patients were included if they adhered to the sole inclusion criterion of being diagnosed with a NSTI and being treated at the Harborview Medical Center (Seattle) by means of a skin-sparing debridement approach. There were no exclusion criteria described. Information about lost-to-follow-up and whether all patients completed the study protocol is lacking. Additionally, it was not described whether the patients excluded from the review nor the potential patients lost to follow-up were included in the statistical analysis. It is therefore unclear whether the authors adhered to an intention-to-treat analysis protocol. Additionally, it was not clear after full-text reading whether patients, health workers, and study personnel were blinded to treatment. Concerning outcome measures, there were two primary outcome measures reported, being acute 29 mortality rate and morbidity rate. Different from the study by Proud et al. , the morbidity rate was presented as number of major amputations performed rather than number of total amputations. Secondary outcome measures included in the particular study were diversity of microbiology and the number of debridement and reconstructive procedures performed. All in all, the methodological quality and thus the validity of the manuscript of Tom et al. considered low.

24

can be

[II.III] Summary of Results Only a brief discussion on the relevant results will be presented below. For a detailed overview of the results per separate study, see the evidence tables (Table I, II and III) included. Concerning the 29 30 primary outcomes, in both the studies by Proud et al. and by Eggerstedt et al. , acute mortality rates were 16%. However, at one-year follow-up the mortality raised slightly to 23% in the study by 30 24 Eggerstedt et al. . The study by Tom et al. reported that none of the included participants had died 29 in the acute phase. When analyzing morbidity, Proud et al. reported an overall amputation rate of 24 11%, while the overall rate of major amputations in the study by Tom et al. was calculated to be 0%. No data was available with reference to the patients included in the retrospective cohort of Eggerstedt 30 et al. The morbidity concerning health status was evaluated in two studies as we were not able to 24 24 extract data on health status from the study by Tom et al. The study of Proud et al. showed that 50% of the patients included had to undergo inotropic support and 54% of the same cohort eventually 30 underwent mechanical ventilation. It was assessed by the study of Eggerstedt et al. that on admission, respectively, 40% and 24% of the patients had acute kidney injury and multiple organ failure. Initially, it was sought to determine the quality of life and the scar quality of the patients having undergone an extensive surgical debridement or a skin-sparing approach. However, we were not able to extract any data at all on these parameters. Proceeding to the secondary outcomes: the median 29 length of hospital stay in the study by Proud et al. was comparable (21 days, range: 0 – 473 days) to 30 the one by Eggerstedt et al. (28 days, range: 1 – 231 days). There was no median length of hospital 24 stay reported in the study by Tom et al. All studies reported on the different organism cultured. In 30 24 both studies of Eggerstedt et al. and Tom et al. , it was observed that more than one organism was cultured (i.e. polymicrobial). Apart from that, in all studies we observed that the organisms cultured most frequently were the Staphylococcus Aureus, the group A streptococci and the Escherichia Coli.

29

30

The number of debridement procedures in the studies by Proud et al. , Eggerstedt et al. , and Tom 24 et al. , were 3, 3.5 and 6, respectively, whereas the number of reconstructive procedures were not 29 30 reported in the studies by Proud et al. and Eggerstedt et al. . Tom et al. reported that there were two reconstructive procedures performed by the senior author. Lastly, we see that in the publication of 29 Proud et al. , 31%, 30% and 24% of the patients were discharged respectively to their home, to an acute hospital and to a rehabilitation facility. This was comparable to the patients included in the 30 retrospective cohort of Eggerstedt et al. , as 56% were discharged home and respectively 15%, 15% and 4% were discharged to a skilled nursing facility, rehabilitation facility and hospice care. Summarized, we state that the two studies on radical surgical debridement give comparable shortterm outcomes concerning acute mortality rate, namely approximately 16%. Skin-sparing surgical debridement yielded a mortality rate of 0%. Although we were able retrieve data on some of the morbidity parameters, such as percentage of amputations and health status, no definite conclusions can be drawn from this data. We were not able to extract any data on the other morbidity parameters, such as quality of life and scar quality . [II.IV] Applicability and Commentary When thinking about the question whether the results of the three studies presented above can be applied and extrapolated to our patient, a few aspects need to be taken into account. Firstly, one observes in Table IV that our patient, to some extent, fits the demographic numbers. When evaluating this more deeply, one notices that the age the female patient presented in the LUMC is relatively lower than the means presented in the three studies as the patient population was calculated to be 29 approximately 50 years old. However, as the study by Proud et al. concludes that advancing age was observed to be a significant predictor of mortality (OR = 1.06, 95% CI = 1.03 – 1.09) one could expect that the treatment benefits would rather be overestimated than underestimated. In most studies, a predominance of men is reported. Although our patient is of the female gender, no reports have been found by the authors that gender significantly tends to clinically influence primary nor secondary outcomes in patients with necrotizing fasciitis. Additionally, one can appreciate that our patient was suffering from a Group A hemolytic streptococcal infection causing the mastitis and the subsequent sepsis and necrotizing fasciitis. In the three studies, this was a relatively frequently 29 30 occurring microbiological organism. Besides this, Proud et al. and Eggerstedt et al. reported the 29 existing co-morbidities in the patient groups. Diabetes mellitus (Proud et al. : 34%, Eggerstedt et 30 30 30 al .: 42%), vascular disease (Eggerstedt et al. : 42%) and obesity (Eggerstedt et al. : 59%) seemed to be the most frequently present, whereas immunosuppression was not found to be present in the 30 29 study by Eggerstedt et al. and was 13% in the publication of Proud et al. . The risk factor of 29 smoking was found to be occurring in 23% of the cases in the study by Proud et al. . Furthermore, it must be stated that the incidence of the specific involved location being the trunk or thorax was calculated to range from 5% to 29%, meaning that this correspond to a certain extent to our patient. All in all, one could state that the results of the three selected studies are to a limited extent applicable to the patient presented in our clinical scenario. For an extended overview of the evidence and results see the tables IV, V and VI included in the Appendix V. [II.V] Bottom line Despite the fact that we were not able to gather data on most of the desired morbidity parameters and that we based our conclusion on low-quality methodological evidence, we conclude that we advise the patient and treating physicians that it would have been possible to have undergone a skin-sparing debridement surgery technique for the necrotizing fasciitis on the thorax, as this technique was proven to be safe and effective concerning mortality.

Chapter III: Discussion III.I

Discussion

The most important finding of the present CAT thesis is that, although based on low methodological quality of the included articles, a tissue-sparing or skin-sparing surgical debridement for the treatment of necrotizing fasciitis is a possible, safe and promising alternative surgical surgical management option. Compared to the numbers on mortality rates derived from the articles included on radical 29 30 surgical debridement by Proud et al. and Eggerstedt et al. , the mortality rate was more favourable when performing a skin-sparing surgical debridement approach as opposed to a radical surgical 24 debridement approach . An important clinical aspect when it comes to treating patients with necrotizing fasciitis by radical surgical debridement is that the majority of the patients are left with large open wounds postoperatively, urging the need for a skin graft or transplantation. The quality of life of a patient can thus be severely depressed postoperatively. A potential surgical clinical solution to reach an objective of optimizing quality of life are the skin-sparing or tissue-sparing debridement procedure approaches in which a maximal amount of native tissue is maintained. Unfortunately, in the present CAT, we were not able to investigate the clinical effects of this skin-sparing debridement approach on outcomes, such as scar quality, quality of life, health status and discharge positions. 3 Moreover, the most recent meta-analysis by Angoules et al. did mention any clinical parameters such as quality of life or scar quality after radical surgical debridement. It should also be noted that – a finding in line with our methodological findings – this systematic review concluded that 10 out of the 12 studies had a retrospective nature and thus were of low methodological value. Strengths of the present research are the thorough selection process of the articles and the grading of 27, 28 the methodological quality of the articles in a systematic manner by the JAMA criteria . The senior author of one of the included articles was contacted to elaborate on the type of surgical debridement performed. Limitations of the CAT are the low level of evidence of the included articles, the fact that solely a maximum of three articles could be included, and the low number of patients on which conclusion were based. To conclude, although quick radical surgical debridement is a clinically effective management option, a tissue-sparing debridement approach seems a possible alternative for patients with necrotizing softtissue infections concerning mortality and rates of major amputations. Future research should focus on investigating skin-sparing or tissue-sparing debridement surgery techniques with regards to mortality, quality of life and other morbidity parameters.

References 1. Rajput A, Waseem, Samad A, Khanzada TW, Shaikh GM, Channa GA. Mortality in necrotizing fasciitis. J Ayub Med Coll Abbottabad. 2008;20(2):96-8. 2. Khamnuan P, Chongruksut W, Jearwattanakanok K, Patumanond J, Yodluangfun S, Tantraworasin A. Necrotizing fasciitis: risk factors of mortality. Risk Manag Healthc Policy. 2015;8:17. 3. Angoules AG, Kontakis G, Drakoulakis E, Vrentzos G, Granick MS, Giannoudis PV. Necrotising fasciitis of upper and lower limb: a systematic review. Injury. 2007;38 Suppl 5:S19-26. 4. Psoinos CM, Flahive JM, Shaw JJ, Li Y, Ng SC, Tseng JF, et al. Contemporary trends in necrotizing soft-tissue infections in the United States. Surgery. 2013;153(6):819-27. 5. Misiakos EP, Bagias G, Patapis P, Sotiropoulos D, Kanavidis P, Machairas A. Current concepts in the management of necrotizing fasciitis. Front Surg. 2014;1:36. 6. Goh T, Goh LG, Ang CH, Wong CH. Early diagnosis of necrotizing fasciitis. Br J Surg. 2014;101(1):e119-25. 7. Park KH, Jung SI, Jung YS, Shin JH, Hwang JH. Marine bacteria as a leading cause of necrotizing fasciitis in coastal areas of South Korea. Am J Trop Med Hyg. 2009;80(4):646-50. 8. Anaya DA, Dellinger EP. Necrotizing soft-tissue infection: diagnosis and management. Clin Infect Dis. 2007;44(5):705-10. 9. Frazee BW, Fee C, Lynn J, Wang R, Bostrom A, Hargis C, et al. Community-acquired necrotizing soft tissue infections: a review of 122 cases presenting to a single emergency department over 12 years. J Emerg Med. 2008;34(2):139-46. 10. Roje Z, Roje Z, Matic D, Librenjak D, Dokuzovic S, Varvodic J. Necrotizing fasciitis: literature review of contemporary strategies for diagnosing and management with three case reports: torso, abdominal wall, upper and lower limbs. World J Emerg Surg. 2011;6(1):46. 11. Yeung YK, Ho ST, Yen CH, Ho PC, Tse WL, Lau YK, et al. Factors affecting mortality in Hong Kong patients with upper limb necrotising fasciitis. Hong Kong Med J. 2011;17(2):96-104. 12. Martinschek A, Evers B, Lampl L, Gerngross H, Schmidt R, Sparwasser C. Prognostic aspects, survival rate, and predisposing risk factors in patients with Fournier's gangrene and necrotizing soft tissue infections: evaluation of clinical outcome of 55 patients. Urol Int. 2012;89(2):173-9. 13. Das DK, Baker MG, Venugopal K. Risk factors, microbiological findings and outcomes of necrotizing fasciitis in New Zealand: a retrospective chart review. BMC Infect Dis. 2012;12:348. 14. Wong CH, Chang HC, Pasupathy S, Khin LW, Tan JL, Low CO. Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am. 2003;85(8):145460. 15. Brook I, Frazier EH. Clinical and microbiological features of necrotizing fasciitis. J Clin Microbiol. 1995;33(9):2382-7. 16. Garssen FP, Goslings JC, Bouman CS, Beenen LF, Visser CE, de Jong VM. [Necrotising softtissue infections: diagnostics and treatment]. Ned Tijdschr Geneeskd. 2013;157(31):A6031. 17. Bilton BD, Zibari GB, McMillan RW, Aultman DF, Dunn G, McDonald JC. Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study. Am Surg. 1998;64(5):397-400; discussion -1. 18. Lille ST, Sato TT, Engrav LH, Foy H, Jurkovich GJ. Necrotizing soft tissue infections: obstacles in diagnosis. J Am Coll Surg. 1996;182(1):7-11. 19. McHenry CR, Piotrowski JJ, Petrinic D, Malangoni MA. Determinants of mortality for necrotizing soft-tissue infections. Ann Surg. 1995;221(5):558-63; discussion 63-5. 20. Morgan MS. Diagnosis and management of necrotising fasciitis: a multiparametric approach. J Hosp Infect. 2010;75(4):249-57. 21. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52.

22. Mills MK, Faraklas I, Davis C, Stoddard GJ, Saffle J. Outcomes from treatment of necrotizing soft-tissue infections: results from the National Surgical Quality Improvement Program database. Am J Surg. 2010;200(6):790-6; discussion 6-7. 23. Brengard-Bresler T, De Runz A, Bourhis F, Mezzine H, Khairallah G, Younes M, et al. [Postoperative quality of life of patients with a bacterial necrotizing dermis-hypodermitis or necrotizing fasciitis, a ten-year study]. Ann Chir Plast Esthet. 2016. 24. Tom LK, Wright TJ, Horn DL, Bulger EM, Pham TN, Keys KA. A Skin-Sparing Approach to the Treatment of Necrotizing Soft-Tissue Infections: Thinking Reconstruction at Initial Debridement. J Am Coll Surg. 2016;222(5):e47-60. 25. Rufenacht MS, Montaruli E, Chappuis E, Posfay-Barbe KM, La Scala GC. Skin-Sparing Debridement for Necrotizing Fasciitis in Children. Plast Reconstr Surg. 2016;138(3):489e-97e. 26. ten Voorde PC, Breiting B, Ebbesen LS. [Skin-sparing surgical revision in a woman with necrotizing fasciitis in her face]. Ugeskr Laeger. 2015;177(26). 27. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. Jama. 1993;270(21):2598-601. 28. Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature. II. How to use an article about therapy or prevention. B. What were the results and will they help me in caring for my patients? Evidence-Based Medicine Working Group. Jama. 1994;271(1):59-63. 29. Proud D, Bruscino Raiola F, Holden D, Paul E, Capstick R, Khoo A. Are we getting necrotizing soft tissue infections right? A 10-year review. ANZ J Surg. 2014;84(6):468-72. 30. Eggerstedt M, Gamelli RL, Mosier MJ. The care of necrotizing soft-tissue infections: patterns of definitive intervention at a large referral center. J Burn Care Res. 2015;36(1):105-10.

Appendix [I]

Table I: Search Strategy

Search Strategy #1 (“Fasciitis, Necrotizing”[MeSH] OR “necrotizing fascitis”[tw] OR “necrotising fascitis”[tw] OR “Necrotizing fasciitis”[tw] OR “Necrotising Fasciitis”[tw] OR “Flesh-eating disease”[tw] OR “Flesh-eating disease”[tw] OR “Necrotizing soft-tissue infections”[tw] OR “Necrotising soft-tissue infections”[tw] OR “Necrotising fasciitis”[tiab] OR “Necrotising fasciitis”[tiab] OR “necrotising fascitis”[tw] OR “necrotizing fascitis”[tw]) AND (“Skin-sparing”[tw] OR “Tissue-sparing”[tw] OR “Sparing”[tw] OR “saving”[tw] OR “tissue”[tw] OR “skin”[tw]) AND (“Debridement”[Mesh] OR “Debridement”[tw] OR “surgery”[tw] OR “surgical technique”[tw] OR “debridement technique”[tw] OR “technique”[tw]) AND ("clinical trial"[pt] OR "clinical trial"[tiab] OR "clinical trials as topic"[mesh] OR "clinical trials"[tiab] OR "control groups"[mesh] OR "control group"[tiab] OR "control groups"[tiab] OR "controlled clinical trial"[pt] "controlled clinical trials as topic"[mesh] OR "cross-over studies"[mesh] OR "cross over study"[tiab] OR "cross over studies"[tiab] OR "double-blind method"[mesh] OR "double blind"[tiab] OR "evaluation studies as topic"[mesh] OR "follow-up studies"[mesh] OR "follow up study"[tiab] OR "follow up studies"[tiab] OR "placebos"[mesh] OR placebo*[tiab] OR placebos*[tiab] OR "pragmatic clinical trial"[pt] OR "prospective studies"[mesh] OR "prospective study"[tiab] OR "prospective studies"[tiab] OR "RaCT"[tiab] OR "RaCTs"[tiab] OR "random allocation"[mesh] OR "randomised "[tiab] OR "randomized controlled trial"[pt] OR "randomized controlled trials as topic"[mesh] OR "randomized"[tiab] OR random*[tiab] OR "RCT"[tiab] OR "RCTs"[tiab] OR "Research Design"[MeSH:noexp] OR "Research design"[tiab] OR "Research designs"[tiab] OR "single blind"[tiab] OR "single-blind method"[mesh] OR ((single*[tiab] OR double*[tiab] OR triple*[tiab]) AND (blind*[tiab] OR mask*[tiab])) OR volunteer*[tiab] OR "trial"[ti] OR "trials"[ti]) AND (“1990/01/01”[PDAT] ; “2017/12/31”[PDAT])

Results 113

#2

(“Fasciitis, Necrotizing”[MeSH] OR “necrotizing fascitis”[tw] OR “necrotising fascitis”[tw] OR “Necrotizing fasciitis”[tw] OR “Necrotising Fasciitis”[tw] OR “Flesh-eating disease”[tw] OR “Flesh-eating disease”[tw] OR “Necrotizing soft-tissue infections”[tw] OR “Necrotising soft-tissue infections”[tw] OR “Necrotising fasciitis”[tiab] OR “Necrotising fasciitis”[tiab] OR “necrotising fascitis”[tw] OR “necrotizing fascitis”[tw]) AND (“Skin-sparing”[tw] OR “Tissue-sparing”[tw] OR “Sparing”[tw] OR “saving”[tw] OR “tissue”[tw] OR “skin”[tw]) AND (“Debridement”[Mesh] OR “Debridement”[tw] OR “surgery”[tw] OR “surgical technique”[tw] OR “debridement technique”[tw] OR “technique”[tw]) AND (“1990/01/01”[PDAT] : “2017/12/31”[PDAT])

1203

#1 AND #2

#1 AND #2

1317

[II]

Table II: Inclusion and Exclusion Criteria

Inclusion criteria Population with a necrotizing soft-tissue infection/necrotizing fasciitis treated by either radical surgical debridement or tissue-/skin-sparing surgical debridement English, Dutch or German articles Randomized controlled trials (RCTs), randomized clinical trials, prospective (randomized and/or nonrandomized) cohort studies, retrospective (nonrandomized or randomized) cohort study, (randomized and/or non-randomized) case control studies, (randomized and/or non-randomized) case series Interpretable clinical data: mortality, morbidity, +/quality of life ≥10 patients Studies published in the year of and after 1990

Exclusion criteria Population with a necrotizing soft-tissue infection/necrotizing fasciitis treated by other surgical treatment options than radical surgical debridement or tissue-/skin-sparing surgical debridement Non-surgically managed patients Articles written in another language than stated in the inclusion criteria section (Systematic) review and/or meta-analysis, single case reports describing surgical techniques and outcomes on sole patients, editorials/opinions, current concepts manuscripts, animal research, in vitro research

Data not interpretable: no data on mortality, morbidity, and/or quality of life