Toward achieving reliable sepsis care

1. Toward achieving reliable sepsis care Dr Ron Daniels FFICM FRCA FRCPEd Chair, UK Sepsis Trust CEO, Global Sepsis Alliance @SepsisUK

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8. Bowel cancer Breast cancer Annual UK sepsis deaths

9. What is sepsis?

10. What is sepsis? Sepsis, Septic Shock, SIRS (systemic inflammatory response syndrome), SSI (signs and symptoms of infection), Septicaemia, Bacteraemia, Toxic Shock Syndrome, Bloodstream infection etc, etc….

11. ACCP/SCCM defs • Severe Sepsis • Sepsis • Organ dysfunction • Septic shock • Sepsis • Hypotension despite fluid resuscitation • Infection • Inflammatory response to microorganisms, or • Invasion of normally sterile tissues • Systemic Inflammatory Response Syndrome (SIRS) • Systemic response to a variety of processes • Sepsis • Infection plus • 2 SIRS criteria Bone RC et al. Chest. 1992;101:1644-55.

12. Pancreatitis Bacteria Trauma SEVERE SEPSIS SIRS Infection Virus Burns Burns Fungi Sepsis Other Parasite

13. Screening tool Are any 2 of the following SIRS criteria present and new to your patient? Obs: Temperature >38.3 or <36 0C Respiratory rate >20 min-1 Heart rate >90 bpmAcutely altered mental state Bloods: White cells <4x109/l or >12x109/l Glucose>7.7mmol/l (if patient is not diabetic) If yes, patient has SIRS

14. Is this likely to be due to an infection? • For example Cough/ sputum/ chest pain Dysuria Abdo pain/ diarrhoea/ distension Headache with neck stiffness Line infection Cellulitis/wound infection/septic arthritis Endocarditis If yes, patient has SEPSIS Start SEPSIS SIX

15. What is shock?

16. Septic Shock Shock secondary to systemic inflammatory response to a new infection What is shock? Tissue perfusion is not adequate for the tissues’ metabolic requirements • Types of Shock • Cardiogenic • Neurogenic • Hypovolaemic • Anaphylactic and…

17. What is shock? Tissue perfusion is not adequate for the tissues’ metabolic requirements For sepsis, shock is one of: SBP < 90 mmHg MBP < 65 mmHg after IV fluids Drop of < 40 mmHg Lactate > 4 mmol/l

18. BPSyst< 90 / Mean < 65 (after initial fluid challenge) Lactate > 2 mmol/l Urine output < 0.5 ml/kg/hr for 2 hrs Clotting INR > 1.5 oraPTT > 60 s Bilirubin> 34 μmol/l O2Nec. to keep SpO2 > 90% Platelets < 100 x 109/l Creatinine> 177 μmol/l UO < 0.5 ml/kg/hr Severe Sepsis: Ensure Outreach and Senior Doctor attend NOW!

21. Merinoff definition • Sepsis is a life-threatening condition that arises when the body's response to an infection injures its own tissues and organs. • Sepsis leads to shock, multiple organ failure and death especially if not recognized early and treated promptly. • Sepsis remains the primary cause of death from infection despite advances in modern medicine, including vaccines, antibiotics and acute care. • Millions of people die of sepsis every year worldwide

22. Why do we need to change??

24. SSC Bundle 2008 Serum lactate measured Blood cultures obtained prior to antibiotic administration From the time of presentation, broad-spectrum antibiotics to be given within 1 hour Control infective source In the event of hypotension and/or lactate >4mmol/L (36mg/dl): Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent) Give vasopressors for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) > 65 mm Hg. In the event of persistent arterial hypotension despite volume resuscitation (septic shock) and/or initial lactate >4 mmol/l (36 mg/dl): Achieve central venous pressure (CVP) of >8 mm Hg Achieve central venous oxygen saturation (ScvO2) >70%

26. SSC Bundle 2012 To be completed within 3?? hours: 1) Measure lactate level 2) Obtain blood cultures prior to administration of antibiotics 3) Administer broad spectrum antibiotics 4) Administer 30 mL/kg crystalloid for hypotension or lactate 4mmol/L To be completed within 6 hours: 5) Apply vasopressors for hypotension that does not respond to initial fluid resuscitation to maintain a mean arterial pressure [MAP] 65 mm Hg) 6) In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/L (36 mg/dL): - Measure central venous pressure (CVP)* - Measure central venous oxygen saturation (ScvO2)* 7) Remeasure lactate if initial lactate was elevated*

27. Perspective

28. Perspective

30. Available at sepsistrust.org

33. The Sepsis Six

34. The Sepsis Six • Give high-flow oxygen via non-rebreathe bag • Take blood cultures and consider source control • Give IV antibiotics according to local protocol • Start IV fluid resuscitation Hartmann’s or equivalent • Check lactate • Monitor hourly urine output consider catheterisation within one hour ..plus Critical Care support to complete EGDT

35. Step 1: Oxygen Aim to give 100% initially In practice you can’t! NRB with reservoir: 60-98% Needs regular review After initial resusc target SpO2 > 94% Septic patients exempt from BTS guidelines May still be appropriate in COPD!! Monitor carefully

36. Step 2: Cultures Beforestarting antibiotics, at least one blood culture: Percutaneously AND at least one from each vascular access device (if > 48 hrs) Other cultures urine, CSF, wounds, sputum, other fluids Consider NOW diagnostic support such as imaging • Weinstein, MP Rev Infect Dis 1983; 5: 35 – 53 • Blot F. J Clinical Microbiol 1999; 36; 105 -109

37. Step 2: Cultures Reassess antimicrobial regimen daily to optimise efficacy, prevent resistance, avoid toxicity & minimise costs. (1C) Do we practice de-escalation? As few as 23% of opportunities Alvarez-Lerma F, Alvarez B, Ruiz F et al for the ADANN Study Group. Crit Care 2006; 10: R 78

38. Step 3: Antibiotics Start therapy as soon as possible and certainly in the first hour... ...preferably aftertaking blood cultures!! Choice should include one or more with activity against likely pathogen Penetration of presumed source Guided by local pathogens Give broad spectrum until defined

39. Early, appropriate antibiotics are the key to improved outcomes

42. First hour antibiotics in 27%...

43. Effective Antimicrobial Therapy &Survival in Septic Shock 1.0 survival fraction cumulative antibiotic initiation 0.8 0.6 fraction of total patients 0.4 0.2 0.0 12-24 24-36 0-0.5 0.5-1 9-12 36+ 3-4 6-9 1-2 2-3 4-5 5-6 time from hypotension onset (hrs) Kumar et al. CCM. 2006:34:1589-96.

44. Running average survival in septic shock based on antibiotic delay (n=2154) For each hour’s delay in administering antibiotics in septic shock, mortality increases by 7.6% Funk and Kumar Critical Care Clinics 2011 (in press)

45. Begin IV antibiotics as early as possible, and always within the first hour of recognising severe sepsis (1D) and septic shock. (1B) Citation: Kumar A et al. Crit Care Med 2006: 34(6) Retrospective, 15 years, 14 sites n = 2,154 median 6 h, 50% administered in 6h Only 5% first 30 minutes- survival 87% 12% first hour- survival 84%

46. Early abx are good.

47. Survival in septic shock based on antibiotic delay (n=4195) Funk and Kumar Critical Care Clinics 2012

48. Retrospective, 22 hospitals, n= 4532 Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81

49. Retrospective, 22 hospitals, n= 4532 64.4% septic shock patients developed early AKI Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81

50. 64.4% septic shock patients developed early AKI Retrospective, 22 hospitals, n= 4532 Median time shock to antibiotic = 5.5 h Bagshaw SM et al Intensive Care Med. 2009;35(5):871-81