Choc septique. Frédéric Pène

Transcription

1 Choc septique Frédéric Pène Réanimation Médicale, Hôpital Cochin, AP-HP Université Paris Descartes Institut Cochin, Inserm U1016, CNRS UMR-8104, Département 3i

2 No conflict of interest

3 A 54 y.o. male patient Diffuse B-cell NHL with bone marrow involvement Complete remission after 2 lines of chemotherapy High-dose chemotherapy intensification Conditioning regimen BEAM Bendamustine Etoposide Cytosine arabinoside Melphalan Autologous hematopoietic stem cell transplantation Antifungal prophylaxis by fluconazole

4 A 54 y.o. male patient Day 5 post-hsct : fever of unknown origin (Pip-Taz) Day 9 Fever 39.5 C with chills Hemodynamic instability: HR 125/min, BP 70/45 mmhg Acute respiratory failure: RR 28/min, SpO 2 88% in room air Grade 3 mucositis Catheter: no signs of inflammation Abdomen: painful, tender, diarrhea WBC 0.2 G/L, Hb 7,1 g/dl, PLT 9 G/L Arterial lactate level 4.5 mmol/l Rectal swab: positive for ESBL Enterobacter cloacae

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7 24/25 infections Neutropenic enterocolitis (n=9) Severe oral mucositis (n=3) Pneumonia (n=9) Catheter-related (n=3)

8 Patchy necrotic ulcerations Necrosis and hemorrhage Mucosal infiltration by Gram-negative rods

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10 Complicated febrile neutropenia: The de-escalation antimicrobial approach D1 D3-5 Fever + organ involvement Initiate or change betalactam + aminoglycosides ± glycopeptides ± antifungals De-escalation? More likely to achieve appropriate coverage in the first 48h, before microbiology data become available Unnecessary use of broad-spectrum antibiotics in many patients Consequent risk of selecting for resistance

11 Haematologica 2013; 98 (12)

12 Combination of β-lactam + aminosides increases empirical coverage of multiresistant bacteria 4,863 Gram-negative bacteremias 710 (15%) patients with haematological malignancy or post-hsct Multivariate analysis for 30-day mortality: Inappropriate empirical therapy 0R 1.8 [ ] Martinez, Antimicrob Agents Chemother 2010

13 Impact of antibiotic combination on Gram negative bacteremia in neutropenic patients Klastersky, Am J Med 1986

14 Combination therapy adjusted OR 0.16; 95%CI [ ], p=0.002 Crit Care Med 2012

15 Early steps of management Broad-spectrum antimicrobial treatment Imipenem + Amikacine Vancomycin Echinocandin Acute circulatory failure requiring RBC transfusion and vasopressor support Endotracheal intubation and mechanical ventilation 2 sets of blood cultures positive in 8h ESBL Enterobacter cloacae

16 Complicated febrile neutropenia: The de-escalation antimicrobial approach D1 D3-5 Fever + organ involvement Initiate or change betalactam + aminoglycosides ± glycopeptides ± antifungals De-escalation? Pathogen identified: No definite documentation: Consider narrowing the spectrum Consider streamlining ECIL4 guidelines, Haematologica 2013; 98 (12)

17 Consider de-escalation and simplification of empirical antibiotic therapy at 48-72h Step-down to β-lactam with narrower spectrum Prefer penicillins ± β-lactamase inhibitor over cephalosporins or carbapenems Stop aminosides if no Gram-neg bacteria isolated Stop glycopeptides if no resistant Gram-positive coccus isolated

18 Definitions of de-escalation Deleting one antibiotic of a combination regimen Using a betalactam with narrower spectrum 101 neutropenic patients with severe sepsis Pts with microbiological documentation De-escalation 32/63 (51%) In-ICU death 18% Pts without documentation De-escalation 12/38 (32%) In-ICU death 23%

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20 Management of neutropenic enterocolitis: the dilemna of surgery Basic rules Neutropenic enterocolitis is a contra-indication to lower digestive endoscopy Neutropenia (w/wo thrombocytopenia) is not a contraindication to surgery The treatment is neutropenia recovery, and not surgery Proposed indications for surgery Perforation Bowel necrosis Major colon dilation Uncontrolled digestive bleeding New-onset or worsening organ failures

21 A 67 y.o. male patient Acute myeloid leukemia Induction course (idarubicine + aracytine) Day 8: fever Emprical antimicrobial treatment Piperacillin + tazobactam 6 days Vancomycine 2 days Imipenem 3 days Persistence of fever Acute respiratory failure requiring endotracheal intubation Septic shock Tracheal sample: Gram- neg bacteria Antigen galactomannan neg 3 days before

22 Which pathogens should be suspected? Which treatment should be implemented?

23 Araoka, Transplant Infect Dis 2012

24 A 72 y.o. male patient Diffuse large B-cell lymphoma diagnosed 15 days ago (biopsy of cervical lymph nodes) Ann Harbor staging: stage IIIAa HIV serology: negative Clinical deterioration Acute respiratory failure Lower limb oedema Confusion Fever > 39 C

25 Biology WBC 14 G/L, Hb 11.2 g/dl, PLT 122 G/L Prothrombin time 82%, TCA 29/34 s, Factor II 79%, Factor V 143%, Fg 1.5 g/l, D-dimers 15 µg/ml, Na 137 mm, K 4.4 mm, Ca mm, Ph 1.1 mm, uric acid 1267 µmol/l Arterial lactate 5.6 mm Creatinine 124 µm, urea 16.6 mm LDH 496 (2 x normal value) Ferritin 712 µg/l PCT 0.42 µg/l

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27 Which diagnosis should be suspected?

28 What looks like sepsis is not always sepsis Sepsis Infection Severe sepsis Septic shock Systemic Inflammatory Response Syndrome (SIRS)

29 DLBCL-related sepsis-like MODS Shock Liver infiltration HLH Cytokine storm Release of DAMPs Hyperphosphatemia Hypercalcemia Hyperuricemia Shock Pleural effusion Pulmonary infiltration Compression Acute lung injury Intra-alveolar hemorrhage Shock Hypercalcemia Lymphomatous meningitis Bone marrow involvement DIC Fibrinolysis

30 Treatment Empirical antibitic treatment (Pip-Taz) Draining pleural effusion (pleural lymphomatous involvement) Organ failure support Vasopressors Mechanical ventilation Renal replacement therapy Biphosphonates Rasburicase Urgent chemotherapy

31 COP R-CHOP

32 COP R-CHOP

33 Septic shock: what have we been learning in the past 10 years? Still a frequent and dreaded complication in cancer patients Early recognition and management are key to the prognosis Adequate antimicrobial treatment Appropriate source control The increased prevalence of MDR and XDR bacteria raises new challenges Some malignancy-related complications can mimick sepsis Sepsis may have an impact on the own prognosis of the underlying malignancy Cancer patients with septic shock are liable to specific interventional studies