Table 1.

Clinical and Biochemical Summary of Events.

Day	Events	Investigations	Management
0	Presentation to ED via ambulance for worsening left leg swelling from a recent cactus plant prick (see supplementaryfig 1A). Blood Pressure (BP): 71/41mmHg, Mean Arterial Pressure (MAP): 48mmHg, Respiratory Rate: 36 breaths per minute, Heart Rate (HR): 125 beats per minute, sinus tachycardia, Temperature: 39°C, Oxygen Saturation: 86% with 0.21 FiO2. Admitted to the intensive care unit (ICU).	pH 7.15 (7.35-7.45), PO2 84 (83-108 mmHg), HCO3 15 (21-27 mmol/L), Lactate 7.6 (0.5-1.6 mmol/L), Sodium (Na) 134 (135-145 mmol/L), Urea 7.6 (3.3-7.6 mmol/L), Creatinine (sCr) 173 (44-80 μmol/L), eGFR 27 (>60 ml/min/1.73m2), White Cell Count (WCC) 13.8 (3.6-9.2 x109/L), C-reactive protein (CRP) 22, Hemoglobin (Hb) 114 (120-152 g/L), Platelet (Plt) 81 (140-380 x109/L), Liver Function Test (LFT)- Total Bilirubin (Bili) 99 (<17 μmol/L), Alanine transaminase (ALT) 61 (4-31 U/L), Aspartate aminotransferase (AST) 83 (4-31 U/L), Alkaline Phosphatase (ALP) 96 (30-110) U/L)	Triple vasopressor support initiated: Noradrenaline 20mcg/min, Adrenaline 20mcg/min, Vasopressin 0.04units/min. Antibiotics: Piperacillin-Tazobactam IV 4.5g stat and then ceased. Meropenem IV 2g, Lincomycin IV 600mg, Vancomycin IV 2g. Source control: Emergency left lower limb fasciotomy, debridement and below knee amputation for high suspicion of necrotizing fasciitis with an LRINEC Score of 5. Intraoperatively, he had an extensive left foot and below knee tissue necrosis (see supplementaryfig.1B) with “dishwasher fluid” in appearance along with liquefied fat. There were large areas of unviable skin and muscle. Histopathology was undertaken to confirm diagnosis (see supplementaryfig.1C)
1	Post operatively, patient was transferred to ICU intubated for possible re-exploration in 24-48hrs. Patient developed oliguria 10-14ml/hour and his blood gas showed severe acidosis requiring left internal jugular vascath insertion in preparation for continuous renal replacement therapy (CRRT).	pH 7.28, Lactate 4.7, Na 130, sCr 206, Hb 89, Plt 105, WCC 17, CRP 78, International normalized ratio (INR) 2.2 (0.8-1.2), Activated Partial Thromboplastin Time (APTT) 150 (26 - 36 secs), Initial blood cultures (BCs) isolated Group B Streptococcus pneumoniae (GBSPn)	Ventilation sedation: Propofol 170mg/hr, Fentanyl 40mcg/hr. CRRT (Day 1) on heparin circuit commenced. Renal dose - 30ml/kg/hr. Triple vasopressor support continued: Noradrenaline 23mcg/min, Adrenaline 18mcg/min, Vasopressin 0.04units/min. Antibiotics (MLV): Meropenem IV 2g TDS, Lincomycin IV 600mg TDS, Vancomycin IV 2g BD. Intravenous Immunoglobin G (IVIgG) therapy 100g was initiated. He was taken back to theatre to confirm source control and the viability of the left stump noting no evidence of necrotic tissue.
2	Remained intubated but developed new onset of Rapid Atrial Fibrillation (RAF) with HR 110bpm. Patient remained oliguric 7-25ml/hour despite ongoing hemofiltration.	pH 7.40, Lactate 3.9, Na 131, sCr 116, WCC 26, CRP 105, Procalcitonin (PCT) 21.18 μg/L, Hb 83, Plt 63, INR 3.1, Fibrinogen 2.4 (2.0-4.0 g/L). Echocardiography: Moderate segmental left ventricular dysfunction, Ejection Fraction 40-45%, Dilated atria bilaterally, Raised Right Atrial Pressure.	Amiodarone loading dose 300mg over 1 hour followed by maintenance dose 900mg over 24 hours. Antibiotics remained unchanged (MLV). CRRT (Day 2) – AN69 anti-inflammatory heparin laden adsorbing filter applied (Oxiris Filter) to dampen the inflammatory surge. Citrate based anticoagulation circuit applied.
3	Patient developed features consistent with Sepsis Induced Coagulopathy (ISTH -SIC criteria). Bedside surgical debridement was performed by surgical team.	pH 7.31, Lactate 2.4, Na 135, sCr 79, WCC 27, CRP 127, Hb 78, Plt 50, INR 2.0. Histopathology consistent with NF. Wound culture for microscopy culture and sensitivity (MCS) had medium growth of GBSPn. Tissue culture (intraoperatively) had medium growth of GBSPn.	Vasopressor support - weaning: Noradrenaline 20mcg/min, Adrenaline weaned off, Vasopressin 2.4units/min. Antibiotics remained unchanged (MLV). CRRT (Day 3) - ongoing.
4	Patient remained oliguric (6-20ml/hr) despite being challenged with a single dose Furosemide IV 250mg stat to assess renal response to which he did not respond. Citrated based CRRT was continued. New onset purpura over the right forearm along with multiple weeping skin tears on right upper thigh. Ongoing RAF HR 130.	pH 7.36, Lactate 1.5, Na 130, sCr 116, WCC 33, CRP 103, PCT 15.37, Hb 91, Plt 53, INR 1.7, LFT - Bili 131, AST 127, ALP 121	Double inotropic support: Noradrenaline 20mcg/min, Vasopressin 2.4units/min. Antibiotics remained unchanged (MLV). CRRT (Day 4). Amiodarone infusion.
5	Patient developed fulminant hepatic failure/ encephalopathy. Refractory oliguria 0-5ml/hr was noted.	pH 7.39, Lactate 1.2, Na 134, sCr 124, WCC 39.5, CRP 74, Hb 116, Plt 49, INR 1.5, LFT- Bili 139, AST 69, ALT 97, ALP 140	Dual inotropic support: Noradrenaline 20mcg/min, Vasopressin weaned off. Antibiotics remained unchanged (MLV). CRRT (Day 5).
6	Patient was severely deconditioned and developed ICU acquired weakness. He was unarousable and had no response to noxious stimuli. Remained intubated and ventilated on Pressure Support Ventilation. Refractory oliguria at 5ml/hr.	PH 7.44, Lactate 1.1, WCC 43.5, CRP 109, Hb 90, Plt 57, INR 1.5, LFT - Bili 150, AST 95, ALP 154	Sedation weaned off. Off vasopressor, Noradrenaline weaned off. Antibiotic de-escalation: Lincomycin and Vancomycin ceased, Meropenem IV 2g TDS continued. CRRT (Day 6). Hyper-Ammonium Therapy initiated -Rifaximin NGT 550mg BD, Lactulose NGT 20ml TDS. 2 units of PRBCs transfusion.
7	Patient developed jaundice. Hypoactive delirium, remained deeply sedated despite being off sedation with a RASS -5. New onset lateralizing signs to the left upon painful stimuli compared to the right side. Refractory oliguria.	CT Brain: No acute intracranial pathology. Ultrasound abdomen: Acute Calculous Cholecystitis noted. pH 7.44, Lactate 1.1, WCC 44.3, CRP 109, Hb 129, Plt 66, INR 1.3, LFT - Bili 235, AST 75, ALP 175, Conjugated Bilirubin 142 (<5.1 µmol/L)	Meropenem IV 2g TDS. CRRT (Day 7) on a Heparin circuit.
8	Anuria was established by this stage. Hypotensive BP 71/33, MAP 51mmHg, Febrile 39°C, RAF HR 160. Significant deterioration despite ongoing medical therapy. Patient was commenced on palliative care pathway, deceased shortly post treatment withdrawal. Family was involved in this decision and consent for critical care supportive therapy was withdrawn. The patient was not deemed to be a coroner's case.	Troponin 616, Ammonia 158 (11-32 umol/L), LFT - Bili 352, AST 100, ALP 299	CRRT (Day 8) Renal recovery assessment -challenged with combination of Furosemide IV 250mg and Acetazolamide IV 500mg. Recommenced Vasopressor support; Noradrenaline 2.5mcg/min. Antibiotic regimen: Lincomycin IV 600mg TDS – recommenced as antitoxin. Meropenem IV 2g TDS – continued. Digoxin IV 500mcg, Metoprolol IV 15mg.

Description: Table outlining daily case summary

CRRT, Continuous Renal Replacement Therapy; ED, Emergency Department; ISTH-SIC, International Society on Thrombosis and Hemostasis – Sepsis Induced Coagulopathy; GBSPn, Group B Streptococcus pneumonia; LRINEC, Laboratory Risk Indicator for Necrotising Fasciitis scoring system; MLV, Meropenem Lincomicin Vancomycin; PRBCs, Packed Red Blood Cells; RAF, Rapid Atrial Fibrillation