Necrotising Soft Tissue Infection (NSTI): State of the Old Art

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Short Course in Critical Infection (SCCI) 2017 Necrotising Soft Tissue Infection (NSTI): State of the Old Art Nai An Lai Director, Surgical Critical Care, Anaesthesia and Perioperative Support Services (SCAPPS), Mater Health, Brisbane Director of Clinical Governance, Surgical and Acute Care Services, Mater Health, Brisbane Senior Intensivist, Mater, QEII Jubilee and Sunnybank Private Hospitals Associate Professor, School of Medicine, Griffith University

Declaration Research Grant from Edwards Life Sciences Honorarium from Gambro Acknowledgement Dr Geoff Muduioa, A/Director of Surgery, QEII Dr Jason Paterdis, Director of Urology, QEII Dr Chris Bell, Director of Orthopaedics, QEII Dr Sanjeev Naidu, Director of Surgical and Acute Care Stream, Mater health Prof Praga Pillay, Senior Surgeon, QEII No patients, health administrators, HREC members or animals were harmed in the preparation of this lecture

Outline Case vignettes Historical Perspective Definition, Classification and Nomenclature Epidemiology Diagnosis Management Prognosis Challenges and Controversies Case Presentation and Panel Discussion Take Home Message

Case Vignettes Case 1: 43 year-old lady, POD2 elective left salphingo-oophorectomy. C/o increasing wound and abdominal pain, increasing PCA use, spreading purpura around surgical wound, hypotensive with acute kidney injury.

Case 2: 41 year-old lady, h/o IVDU. P/w 2-day history of severe left arm and elbow pain, fever, agitated delirium and acute kidney injury. U/S left UL showed no evidence of thrombophlebitis or collection.

Case 3: 72 year-old male, frequent user of NSAID for low back pain. P/w septic shock and an infected left lower limb laceration sustained during a recent flood. Crepitus felt on palpation of left lower limb.

Quotes from the Vignettes It is just some bruising, check her haemoglobin and ask the pain service to see her. She is possibly drug-seeking We do not think necrotising fasciitis is likely because the ultrasound was negative for a collection The patient has some leukocytes in her urine and some CXR changes. It must either be pneumonia or urosepsis. Cellulitis cannot account for her septic shock. Surgical exploration is not warranted Septic shock, source unknown. Cellulitis with blisters left arm Please organise an MRI. We will review the patient after the MRI

NSTI in Popular Media https://www.explainxkcd.com/wiki/index.php/1242:_scary_names

NSTI in Popular Media

Historical Perspective Hippocrates (500 BC) many were attacked by erysipelas all over the body when the inciting cause was a trivial accident. Flesh, sinews and bones fell away in large quantities there were many deaths. Wilhelm Friedrich von Ludwig (1836) described an often necrotising infection of the submandibular, sublingual and submental spaces now known as Ludwig s angina. It was also known as Morbus Strangularis Joseph Jones (1871) described 2642 cases of hospital gangrene during the American Civil War with mortality of 46% Jean-Alfred Fournier (1883) reported cases of necrotising infection of the perineum and scrotum

Historical Perspective William H. Welch (1891) described Bacillus aerogenes capsulatus as the cause of gas gangrene. The bacterium was later renamed numerous times as Bacillus welchii, Clostridium welchii and finally Clostridium perfringens W. Pfanner (1918) described cases of necrotising erysipelas during World War I and implicated Streptococcus as the cause Frank Meleney (1924) Postoperative gangrene Meleney s Ulcer, Meleney s synergistic gangrene B. Wilson (1952) First to use the term necrotising fasciitis Misiakos EP, et al. Frontiers in Surgery. 2014, 00036 Leiblein M., et al. Eur J Trauma Emerg Surg DOI 10.1007/s00068-017-0792-8

Definition and Nomenclature Necrotising Soft Tissue Infection (NSTI) Life or limb threatening infection of any of the layers within the soft tissue compartment (dermis, subcutaneous tissue, superficial fascia, deep fascia or muscle) that is associated with severe systemic toxicity and fulminant tissue destruction necessitating emergent surgical management Misiakos EP, et al. Frontiers in Surgery. 2014, 00036 Anaya DA, Dellinger EP. Clin Inf Diseases. 2007; 44:705-10 Sartelli M, et al. World J of Emergency Surgery. WSES 2014, 9:57

Terms used to describe NSTI based on clinical, anatomical, microbiological or pathological features Hospital gangrene Haemolytic Streptococcal gangrene Necrotising erysipelas Phagedena Meleney s synergistic gangrene Crepitant cellulitis Necrotising cellulitis Fournier s gangrene Streptococcal myositis Necrotising fasciitis Type I to IV Necrotising myositis Galloping gangrene Gas gangrene Clostridial myonecrosis Clostridial cellulitis Ballesteros JR., et al. Int J of Adv Joint Recon 2016; 3(1):1 9 Leiblein M., et al. Eur J Trauma Emerg Surg DOI 10.1007/s00068-017-0792-8

NSTI and Associated Conditions Anatomical Classification Rhinocerebral mucormycosis Non-necrotising SSTI: Impetigo, ecthyma, folliculitis, furunculosis, carbunculosis, erysipelas, cellulitis, Necrotising Cellulitis Ludwig s Angina Vincent s Angina Lemiere s Syndrome Meleney s Synergistic Gangrene Fournier s Gangrene Necrotising Fasciitis Necrotising Myositis Clostridial Myonecrosis Pyomyositis Devised and Modified by N. Lai 2017, based on WSES classification 2014

NSTI Microbiological Classification Group A Strep or Staph infection can be associated with Toxic Shock Syndrome (TSS) Misiokos EP, et al. Frontiers in Surgery. 2014, 00036

Epidemiology a.k.a Epimythology of NSTI Widely misquoted incidence of 0.4 per 100,000 persons thus misperceived to be rare. Some authors suggested that an average physician would see only 1 or 2 in his/her entire career (Wong, CH, et al. The Am J of Surg 2008. 196, e19 e24) The sources of these figures are Ontario Group A Streptococcal Study: Canadian data between 1991 to 1995 (McGeer KR, et al. Am J Med. 1997 103: 18-24) An epidemiological study based on insurance database (Simonsen, ESM, et al. Epidemiol Infect 2006; 134: 293-9) No modern data available since the new and less confusing terminology to track the incidence and outcomes of NSTI Reported mortality figures vary from 8% to 76% (Anaya DA, Dellinger EP. Clin Inf Diseases. 2007; 44:705-10)

QEII NSTI Data 2009 to 2017 43 episodes of NSTI over 9 years involving 35 patients Average age of 50 (range 22 to 86) 20 males (57.1%) and 15 females (42.9%) 48.6% had diabetes mellitus, 22.9% were IVDU Mortality - 8% (3/35) Microbiological data Monomicrobial 48.8%, polymicrobial 37.2%, no positive micro in 16% Positive blood culture in 16.3% Organisms: Staph aureus - 13 (10 MSSA, 3 MRSA) Mixed enteric bacteria - 7 Strep milleri group 6 Pseudomonas 3 Group A Strep - 2 N. Lai 2009-2017 unpublished QA data

Diagnosis

High index of suspicion NSTI Diagnosis - Clinical Initial symptoms and signs are non-specific: pain, swelling, erythema, tachycardia (up to 71% not recognised as NSTI in ED in one case series) Useful symptoms and signs (often later in the course): Pain out of proportion to physical findings Tenderness beyond overt area of inflammation Tense oedema beyond area of inflammation Skin discolouration/purpura/ecchymoses Blisters/bullae Crepitus indication subcutaneous gas Obvious area of necrosis Systemic compromise in the absence of other causes should raise the possibility of NSTI Wall et al. J Am Coll Surg 2000; 191-227 Anaya DA, Dellinger EP. Clin Inf Diseases. 2007; 44:705-10 Goh T, et al. Br J Surg. 2014 101:119-25

NSTI Diagnosis LRINEC Score Laboratory Risk Indicator for Necrotising Fasciitis Retrospective cohort study n=314 in the development cohort, n=140 in the validation cohort LRINEC 6 has a PPV of 92% and NPV of 96% Subsequent validation studies yielded mixed results Wong CH, et al. Critical Care Med 2004; 32:1535-41

NSTI Diagnosis - Imaging Sensitivity in picking up soft tissue changes MRI >> CT > US ~ X Rays Logistic/ease of access X Rays > US~CT >> MRI Most studies (except MRI) have insufficient sensitivities to rule out NSTI in the setting of high clinical suspicion Potentially delaying surgical assessment and management Hayeri MR, et al. RadioGraphics 2016; 36:1888-1910 Sartelli M, et al. World J of Emergency Surgery. 2014, 9:57

NSTI Diagnosis Surgical & Histopathological Macroscopic findings Greyish or blackish necrotic tissue Lack of bleeding during dissection Positive finger test Foul smelling dishwater pus Microscopic findings Liquefactive necrosis PMNL infiltration Fibrinoid thrombosis of vessels Presence of large quantities of micro-organisms Wong, CH, et al. The Am J of Surg 2008. 196, e19 e24 www.dermnetnz.org

Management of NSTI Cornerstones of NSTI management Early diagnosis Resuscitation and organ support Early broad spectrum antimicrobial therapy Early and aggressive source control

Empirical Antimicrobial Therapy for NSTI etg recommendations: Meropenem 1 g (Child 25 mg/kg up to 1 g) IV 8-hourly, and Vancomycin IV, loading dose 25 to 30 mg/kg, maintenance dose 15 to 20 mg/kg 12-hourly Clindamycin/Lincomycin IV 600 mg (Child 15 mg/kg up to 600 mg) IV 8-hourly Consider adding IVIG if Strep pyogenes suspected

Surgical Management of NSTI General principles: Early surgical exploration is mandatory 9 fold increase in mortality when primary surgery was delayed for more than 24 hours (Roje Z, et al. 2011) 2 fold increase in mortality when patients are transferred for initial debridement (Holena DN, et al. 2011) Aggressive debridement of necrotic and at risk tissue is mandatory 7.5 fold increase in mortality in restricted primary debridement (Mok MY, et al. 2006) No consideration should be given to subsequent cosmetic outcome or reconstruction (Rogers AD, et al. UptoDate 2017) Routine reassessments under anaesthesia at regular intervals (usually 12 to 48 hrs) are strongly advisable at least initially

Surgical Management of NSTI Other aspects: Tissue samples for microbiology and histology Intraoperative antiseptic irrigation Hydrosurgery water jet based debridement system Amputation Faecal diversion Antimicrobial dressings Negative pressure wound therapy Images courtesy of Dr Alan D Rogers

Prognosis Reported mortality varies widely: 8% to 76% Factors associated with worse prognosis: Patient factors Pathogen/disease factors Treatment factors Advanced age Group A Strep Delay in primary debridement Female gender Clostridium sp. Inadequate primary debridement Number of co-morbidities Toxic shock syndrome Delay in administering appropriate antimicrobial therapy Diabetes mellitus Fournier s gangrene Interhospital transfer prior to primary debridement PVD Organ failure especially kidneys Myonecrosis Bacteraemia +/- septic embolisation Immunosuppression Nordqvist G, et al. Inf Dis, 2015; Acidosis 47: 319-325 Anaya DA, et al. Surg Inf, 2009; Hypotension 10(6): 517-22

Controversies and Challenges Molecular diagnostics Transcutaneous oxygen saturation IVIG Hyperbaric O2 therapy Intraoperative perfusion imaging (eg. SPY Elite fluorescence imaging system) Intermittent wound irrigation using negative pressure wound therapy Drotrecogin alfa

Case Presentation Dr Tasnim Hassan Panel Discussion and questions from the audience Pierre Janin Monica Slavin Jon Iredell Nai An Lai

Take Home Message NSTI (necrotising soft tissue infection) is a group of life threatening infection affecting the soft tissue compartment High index of suspicion facilitates early diagnosis Emergent and aggressive surgical intervention is paramount All elements of sepsis and septic shock management apply A NSTI database would better characterise the incidence, microbiology, clinical course and prognosis of this devastating condition

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