History

Fact Explanation
Sudden onset, severe pain Gas gangrene is rare, and develops & spreads rapidly. It is caused by toxins produced by Clostridium spp.Patients become toxic, develops shock & eventually multi organ failure.[6].The well known causative organism of post traumatic gas gangrene is Clostridium perfringens. Non traumatic/ spontaneous gas gangrenes are very rare & caused by Clostridium septicum[3]. This anaerobic,gram positive, spore forming bacteria is encountered in soil, sewage & gastrointestinal tract of humans & many animals. It secretes an extracellular enzyme named "Clostridium perfringens phospholipase". At lytic concentrations it results in membrane disruption & at lower concentrations by inducing oxidative stress it activates MEK/ERK path & results in cytotoxic, myotoxic effects[1]. This disease typically starts with very severe pain, pain doesn't response to pain killers[2]. Though the mechanism of this severe pain is not understood clearly, it is proposed that microvascular thrombosis resulting in insufficient tissue perfusion causing hypoxia is responsible[4].
Extensive local swelling Gas gangrene can be caused by: Clostridial myonecrosis, Clostridial cellulitis, non Clostridial causes. The term " true gas gangrenes" is refers to clostridial myonecrosis[2]. Toxins affect the function of the vascular endothelium and microvascular damage causes leakage of the albumin, electrolytes & water causing edema[7].
Fever Systemic infection causes sweating, tachycardia & delirium other than fever[8].
Skin color change from pale to bronze, then becomes purplish red & eventually hemorrhagic bullae develop. [2] Initially skin is tense & pale. The color change is rapidly progressing[5]. First skin appears normal. Then as the swelling takes place it becomes pale. That is because the pressure drives away the blood from the site. As the gangrene established it shows the dirty cream tint. The next changes are rapidly spreading. Skin becomes purple & bullae develops filled with altered blood. The last color change is to dark yellow- green. This is identical to post mortem changes happens following bacterial action on dead tissue[10].
Presence of predisposing factors such as underlying malignancies, diabetes mellitus, atherosclerotic disease and severe peripheral vascular disease.[2] Clostridium perfringens myonecrosis usually occurs in patients with underlying predisposing causes. [2] These happen in a contaminated traumatic wound with soil, surgeries in bowel or biliary tract, secondary to septic abortions, occlusive arterial disease, improper technique of injections (i.e.illicit drugs). [9]
References
  1. MONTURIOL-GROSS L, FLORES-DíAZ M, PINEDA-PADILLA MJ, CASTRO-CASTRO AC, ALAPE-GIRON A. Clostridium perfringens phospholipase C induced ROS production and cytotoxicity require PKC, MEK1 and NFκB activation. PLoS One [online] 2014, 9(1):e86475 [viewed 06 June 2014] Available from: doi:10.1371/journal.pone.0086475
  2. YING ZHIMIN, ZHANG MIN, YAN SHIGUI, ZHU ZHONG. Gas Gangrene in Orthopaedic Patients. Case Reports in Orthopedics [online] 2013 December, 2013:1-9 [viewed 06 June 2014] Available from: doi:10.1155/2013/942076
  3. JANSSEN E, DEN OUDEN H, VAN HERWAARDEN J, BOLLEN T, GEERS T, WILLE J, DE VRIES JP. Gas gangrene spreading to the bone marrow. Neth J Med [online] 2006 Jul-Aug, 64(7):256-7 [viewed 06 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16929090
  4. BRYANT AE. Biology and pathogenesis of thrombosis and procoagulant activity in invasive infections caused by group A streptococci and Clostridium perfringens. Clin Microbiol Rev [online] 2003 Jul, 16(3):451-62 [viewed 06 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12857777
  5. MINUTTI CZ, IMMERGLUCK LC, SCHMIDT ML. Spontaneous gas gangrene due to Clostridium perfringens. Clin Infect Dis [online] 1999 Jan, 28(1):159-60 [viewed 07 June 2014] Available from: doi:10.1086/517192
  6. SATHYANARAYANA HEMAVATHI, RANI LEELA, RAJENDRAN R, SARMAH POOJA. Iatrogenic infection of Clostridium welchii following intramuscular injection of sodium diclofenac. J Lab Physicians [online] 2013 December [viewed 07 June 2014] Available from: doi:10.4103/0974-2727.115924
  7. BRYANT AE, STEVENS DL. Phospholipase C and perfringolysin O from Clostridium perfringens upregulate endothelial cell-leukocyte adherence molecule 1 and intercellular leukocyte adherence molecule 1 expression and induce interleukin-8 synthesis in cultured human umbilical vein endothelial cells. Infect Immun [online] 1996 Jan, 64(1):358-62 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8557365
  8. HEADLEY AJ. Necrotizing soft tissue infections: a primary care review. Am Fam Physician [online] 2003 Jul 15, 68(2):323-8 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12892352
  9. CRUM-CIANFLONE N. F.. Bacterial, Fungal, Parasitic, and Viral Myositis. Clinical Microbiology Reviews [online] December, 21(3):473-494 [viewed 10 June 2014] Available from: doi:10.1128/CMR.00001-08
  10. WALLACE C. THE COLOUR CHANGES SEEN IN SKIN AND MUSCLE IN GAS GANGRENE. Br Med J [online] 1917 Jun 2, 1(2944):725-726.3 [viewed 13 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20768608

Examination

Fact Explanation
Febrile Systemic infection causes increased body temperature & also result in sweating[7].
Tachycardia Systemic infection causes increased heart rate[7].
Hypotension Gas gangrenes are known to cause multi organ failure & shock. Hypotension is a sign of severe sepsis,1) sepsis induced hypotension-" infection induced decrease in blood pressure( SBP< 90 mmHg, mean arterial pressure < 70mmHg)[2].
Extensive local odema Toxins affect the function of vascular endothelium. Microvascular damage cause leakage of the albumin, electrolytes & water causing edema[8].
exudate & odor This is thin & brownish in color. It has a 'mousey' odor[3].
Crepitus Sign is caused by gas in the tissue.This can / can not be there. Though absence of crepitus , can't exclude gas gangrene[3].
Skin color changes at the site of infection.. initially it is pale to bronze, then becomes purplish red & eventually hemorrhagic bullae develops[5]. initially skin is tense & pale. The color change is rapidly progressing[6]. First skin appears normal. Then as the swelling takes place it becomes pale. That is because the pressure drives away the blood from the site. As the gangrene established it shows the dirty cream tint. The next changes are rapidly spreading. Skin becomes purple & bullae develops filled with altered blood. The last color change is to dark yellow- green. This is identical to post mortem changes happens following bacterial action on dead tissue[9].
Bullae with purplish liquid[3]. By this time patient becomes anuric resulting from irreversible vascular collapse[3].
lack of bleeding[4] Muscle is pale to grey & it doesn't bleed when cut during surgical exploration[1].
muscle fail to contract when stimulated[4] dead muscles doesn't react to stimulus.
References
  1. URSCHEL JD. Necrotizing soft tissue infections. Postgrad Med J [online] 1999 Nov, 75(889):645-9 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10621873
  2. SCHORR CHRISTA A, ZANOTTI SERGIO, DELLINGER R PHILLIP. Severe sepsis and septic shock: Management and performance improvement. virulence [online] 2014 January, 5(1):190-199 [viewed 07 June 2014] Available from: doi:10.4161/viru.27409
  3. OILL PA, MONTGOMERIE JZ, CRYAN WS, EDWARDS JE. Specialty conference. Infectious disease emergencies. Part V: patients presenting with localized infections. West J Med [online] 1977 Mar, 126(3):196-208 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/349885
  4. CRUM-CIANFLONE N. F.. Bacterial, Fungal, Parasitic, and Viral Myositis. Clinical Microbiology Reviews [online] December, 21(3):473-494 [viewed 07 June 2014] Available from: doi:10.1128/CMR.00001-08
  5. YING ZHIMIN, ZHANG MIN, YAN SHIGUI, ZHU ZHONG. Gas Gangrene in Orthopaedic Patients. Case Reports in Orthopedics [online] 2013 December, 2013:1-9 [viewed 06 June 2014] Available from: doi:10.1155/2013/942076
  6. MINUTTI CZ, IMMERGLUCK LC, SCHMIDT ML. Spontaneous gas gangrene due to Clostridium perfringens. Clin Infect Dis [online] 1999 Jan, 28(1):159-60 [viewed 07 June 2014] Available from: doi:10.1086/517192
  7. HEADLEY AJ. Necrotizing soft tissue infections: a primary care review. Am Fam Physician [online] 2003 Jul 15, 68(2):323-8 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12892352
  8. BRYANT AE, STEVENS DL. Phospholipase C and perfringolysin O from Clostridium perfringens upregulate endothelial cell-leukocyte adherence molecule 1 and intercellular leukocyte adherence molecule 1 expression and induce interleukin-8 synthesis in cultured human umbilical vein endothelial cells. Infect Immun [online] 1996 Jan, 64(1):358-62 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8557365
  9. WALLACE C. THE COLOUR CHANGES SEEN IN SKIN AND MUSCLE IN GAS GANGRENE. Br Med J [online] 1917 Jun 2, 1(2944):725-726.3 [viewed 13 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20768608

Differential Diagnoses

Fact Explanation
Steptococcal myositis This also has odema, necrosis & gaseous lesions. This is rather localized disease. But eventually it shows systemic toxicity like of gas gangrenes[1]. This is caused by group A streptococcus, commonly occur in penetrating wounds or in immunocompromised patients. NSAID thought to be a risk factor. The rout of entry is not very clear[2].
necrotizing fasciitis Necrotizing soft tissue infections are fatal, so need early interventions[4].Causative organism group A beta hemolytic streptococcus, can be poly microbial as well. It is progressing rapidly & has a significant systemic toxicity[3].
crepitant cellulitis -caused by Clostridium species. - but minor changes are seen in skin, less pain & less systemic toxicity[3]. As this is a superficial infection surgical exploration shows live fascia & muscles. Skin & soft tissue debridement is the treatment, extensive surgical interventions are not necessary[4].
References
  1. WELLS CL, WILKINS TD, BARON S. Clostridia: Sporeforming Anaerobic Bacilli [online] 1996 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/21413315
  2. CRUM-CIANFLONE N. F.. Bacterial, Fungal, Parasitic, and Viral Myositis. Clinical Microbiology Reviews [online] December, 21(3):473-494 [viewed 10 June 2014] Available from: doi:10.1128/CMR.00001-08
  3. LANGHAN M, ARNOLD L. Clostridial myonecrosis in an adolescent male. Pediatrics [online] 2005 Nov, 116(5):e735-7 [viewed 13 June 2014] Available from: doi:10.1542/peds.2004-2876
  4. URSCHEL JD. Necrotizing soft tissue infections. Postgrad Med J [online] 1999 Nov, 75(889):645-9 [viewed 13 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10621873

Investigations - for Diagnosis

Fact Explanation
radiology - Xray, CT scan -Presence of free gas in the tissue. - in clostridial myonecrosis feather like pattern of gas is observed in the muscle. -CT scans are better to identify infected psoas & iliacus muscles[1].
Gram stain of wound exudate -gram positive rod shaped bacilli -less neutrophills[3].This infection is less inflammatory compared to others. this establish the causative organism, so allow selecting most suitable antibiotics, though initial therapy is empiric[2].
References
  1. BROOK I. Microbiology and management of myositis. Int Orthop [online] 2004 Oct, 28(5):257-60 [viewed 07 June 2014] Available from: doi:10.1007/s00264-004-0578-6
  2. BROOK I. Microbiology and management of myositis. Int Orthop [online] 2004 Oct, 28(5):257-60 [viewed 07 June 2014] Available from: doi:10.1007/s00264-004-0578-6
  3. CRUM-CIANFLONE N. F.. Bacterial, Fungal, Parasitic, and Viral Myositis. Clinical Microbiology Reviews [online] December, 21(3):473-494 [viewed 07 June 2014] Available from: doi:10.1128/CMR.00001-08

Investigations - Fitness for Management

Fact Explanation
Leukocytosis This is caused by effects of alpha toxin[2].
Low hemoglobin Hemolytic anaemia caused by alpha toxin result in low hemoglobin[2].Alpha toxin damage the red cell membrane, leading to spherocytosis. This results in hemolysis. Intravascular hemolysis also occur in Clostridial septicemia[1].
Acidosis pH less than 7.35 [3]
hypocalcemia serum calcium less than 8.4mg/dL {2.1 mmol/L} [3]
References
  1. VAN BUNDEREN CC, BOMERS MK, WESDORP E, PEERBOOMS P, VEENSTRA J. Clostridium perfringens septicaemia with massive intravascular haemolysis: a case report and review of the literature. Neth J Med [online] 2010 Sep, 68(9):343-6 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20876913
  2. CRUM-CIANFLONE N. F.. Bacterial, Fungal, Parasitic, and Viral Myositis. Clinical Microbiology Reviews [online] December, 21(3):473-494 [viewed 07 June 2014] Available from: doi:10.1128/CMR.00001-08
  3. HEADLEY AJ. Necrotizing soft tissue infections: a primary care review. Am Fam Physician [online] 2003 Jul 15, 68(2):323-8 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12892352

Investigations - Screening/Staging

Fact Explanation
Colonoscopy Patients who survives from Clostridium septicum should be investigated for carcinoma of the colon[1].
References
  1. URSCHEL JD. Necrotizing soft tissue infections. Postgrad Med J [online] 1999 Nov, 75(889):645-9 [viewed 07 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/10621873

Management - General Measures

Fact Explanation
resuscitation -fluid When the patient is diagnosed in septic shock resuscitation should be started within first 6 hours. Crystalloid is given in fluid resuscitation.Albumin is also considered. But hetastarch shouldn't be used. Fluid challenge is started in patients who have tissue hypoperfusion & who have features of hypovolumia. Crystolloids are given 30ml/kg, till hemodynamic improvement[1].
vasopressors & inotropes 1) norepinephrine- Maintain mean arterial pressure >65mmHg 2) epinephrine- this is additionally used to maintain BP 3)vasopressin- 0.03units/min, this is used at the weaning of norepinephrine. As there is a risk of arrhythmia dopamine is avoided. Dobutamine infusion is started if signs of myocardial dysfunction[1].
antibiotic therapy This is to control infections. Before giving antibiotics take blood for culture. Within first hour of diagnosis give broad spectrum antibiotic. Review culture reports when available & change antibiotic accordingly[1].
Respiratory support Patients who are having sepsis induced ARDS give high positive end expiratory pressure. It is necessary to use recruitment methods when patients are having severe respiratory hypoxemia. Elevate head end of the bed[1].
CNS support Use sedatives, Administer short term neuro muscular blocker in early severe ARDS[1].
supportive care 1.Blood glucose management- target level <180mg/dL 2. intermittent hemodialysis- renal failure / fluid overloaded patients. 3. DVT prophylaxis 4. stress ulcer prophylaxis 5. oral/ enteral feedings [1]
References
  1. ANGUS DEREK C., VAN DER POLL TOM. Severe Sepsis and Septic Shock. N Engl J Med [online] 2013 August, 369(9):840-851 [viewed 12 June 2014] Available from: doi:10.1056/NEJMra1208623

Management - Specific Treatments

Fact Explanation
Emergency surgical exploration -helps to identify nature of the infective process -allow the direct examination of the infected muscles[3]
Immediate surgical intervention Appropriate debriment should be done. It is known to increase survival rates[4]. affected muscles should be removed. complete amputations may necessary[3].
Antibiotic coverage Medicine like high dose penicillin G, Clindamicin is used. But initially broad spectrum coverage is used as gas gangrenes are dirty wounds that has many organisms other than Clostridium sp. Antibiotic use must follow the culture reports[2]
Hyperbaric oxygen This inhibits the crostridial alpha toxin production. in high concentrations this oxidative free radicles kill the bacteria by activating polymorphonuclear leukocytes[1]. this remains controversial [3].
References
  1. VISHWANATH GURUSWAMY, BHUTANI SOURABH. Hyperbaric oxygen and wound healing. Indian J Plast Surg [online] 2012 December [viewed 07 June 2014] Available from: doi:10.4103/0970-0358.101309
  2. CRUM-CIANFLONE N. F.. Bacterial, Fungal, Parasitic, and Viral Myositis. Clinical Microbiology Reviews [online] December, 21(3):473-494 [viewed 07 June 2014] Available from: doi:10.1128/CMR.00001-08
  3. BROOK I. Microbiology and management of myositis. Int Orthop [online] 2004 Oct, 28(5):257-60 [viewed 07 June 2014] Available from: doi:10.1007/s00264-004-0578-6
  4. HEADLEY AJ. Necrotizing soft tissue infections: a primary care review. Am Fam Physician [online] 2003 Jul 15, 68(2):323-8 [viewed 12 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12892352