1. Surviving Sepsis Campaign: Guidelines for the Management of Severe Sepsis and Septic Shock (2012)

2. Background Surviving Sepsis Campaign (2002): Original guidelines 2004
Barcelona
Original guidelines 2004
Revised 2008
Third edition printed in the February 2013 edition of Critical Care Medicine and Intensive Care Medicine

3. Aims Provide guidance for ICU and non-ICU settings
Greatest outcome improvement from non-ICU setting and across the spectrum of acute care
Recommendations aimed to be best practice and not created to represent standard of care

4. “The surviving sepsis campaign guidelines committee hopes that over time, particularly through education programs and formal audit and feedback performance improvement initiatives, the guidelines will influence bedside healthcare practitoner behaviour that will reduce the burden of sepsis worldwide”

5. Development of the Guidelines
Committee members
Grading of recommendations: GRADE system
Determines the:
Quality of evidence (A-D)
Strength of recommendations as strong (grade 1) or weak (grade 2)

6. Severe Sepsis and Septic Shock
Systemic, deleterious host response to infection leading to severe sepsis (acute organ dysfunction secondarily to documented or suspected infection)
Septic Shock:
Severe sepsis plus hypotension not reversed with fluid resuscitation
Major health-care problems affecting millions of people around the world each year, killing often >1 in 4 people and increasing in incidence
Speech and appropriateness of therapy in the initial hours after severe sepsis develops significantly influences the outcome.

7. Definitions Sepsis: Severe Sepsis: Septic Shock:
Presence (probable or documented) of infection together with systemic manifestations of infection
Severe Sepsis:
Sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion
Septic Shock:
Sepsis-induced hypotension persisting despite adequate fluid resuscitation
Sepsis-induced tissue hypoperfusion = infection-induced hypotension, elevated lactate or oliguria

10. MANAGEMENT OF SEVERE SEPSIS

11. Initial Resuscitation
and
Infection Issues

12. a) Initial Resuscitation – Early Goal Directed Therapy
Initiated as soon as hypoperfusion is recognized
Should not be delayed awaiting ICU admission
Goals during the first 6 hours:
CVP 8-12mmHg
MAP >65mmHg
Urine output >0.5 ml/kg/hr
SVCO2 or SVO2 70% or 65% respecitvely
Normalise lactate levels
 15.9% absolute reduction in 28-day mortality

13. b) Screening for Sepsis and Performance Improvement
Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy
Hospital-based performance improvement efforts in severe sepsis

14. c) Diagnosis
Cultures as clinically appropriate prior to anti-microbials if no significant delay (>45min)
At least 2 sets of blood cultures with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently inserted (<48hrs)
Use of 1,3 b-D-glucan assay, mannan and anti-mannan antibody assay in invasive candidiasis
Imaging studies performed promptly to confirm a potential source of infection

15. d) Anti-Microbial Therapy
IV antibiotics within 1hr of recognition of septic shock (1b) and severe sepsis without shock (1c) as the goal of therapy
Initial empiric anti-effective therapy of one or more drugs that have activity against all likely pathogens (bacterial +/- fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis
Failure to initiate appropriate therapy correlates with increased morbidity and mortality in patients with severe sepsis or septic shock

16. d) Anti-Microbial Therapy cont…
Antimicrobial regimen should be reassessed daily for potential de-escalation to prevent the development of resistance, to reduce toxicity and to reduce costs (1b)
Use of low procalcitonin levels or similar biomarkers to assist in the discontinuation of empiric antibiotics in patients who appeared septic, but have no subsequent evidence of infection (2c)

17. d) Anti-Microbial Therapy cont…
Antibiotic choice:
Neutropenic: combination empiric therapy
Respiratory failure: combination therapy with extended spectrum beta-lactam and either aminoglycoside or a fluroquinolone (for pseudomonas bacteraemia)
Strep pneumoniae: complex combination of beta-lactam and macrolide
Combination therapy when used empirically should not be administered for longer than 3-5 days. De-escalation to the most appropriate single agent should be performed as soon as susceptibility profile
Duration of therapy typically be 7-10 days if clinically indicated; longer courses in patients who have a slow clinical response, undrainable foci of infection, bacteremia with s.aureus, immunological deficiency (incl neutropenia)

18. d) Anti-Microbial Therapy cont…
Use of ant-viral therapy be initiated as early as possible in patients with severe sepsis or septic shock of viral origin (2c)
Anti-microbial agents not be used in patients with severe inflammatory states determined to be of non- infectious cause

19. e) Source Control
A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12hr after the diagnosis is made, if feasible (1c)
In Infected peri-pancreatic necrosis, definitive intervention is best delayed until adequate demarcation of viable and non- viable tissues has occurred (2b)
The intervention with the least physiological insult should be used
If intravascular access devices are a possible source they should be removed promptly after other vascular access has been established

20. f) Infection Prevention
Selective oral decontamination (SOD) and selective digestive decontamination (SDD) should be introduced and investigated as a method to reduce the incidence of VAP (2b)
Oral chlorhexidine be used as a form of oropharyngeal decontamination to reduce the risk of VAP in patients with severe sepsis (2b)

21. Haemodynamic Support And Adjunctive Therapy

22. g) Fluid Therapy of Severe Sepsis
Crystalloids be used as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (1b)
Against the use of HES for fluid resuscitation (1b)
Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (2c)

23. g) Fluid Therapy of Severe Sepsis cont….
Initial fluid challenge: 30ml/kg
Fluid challenge continued as long as there is haemodynamic improvement either based on dynamic or static variables

24. h) Vasopressors
Vasopressor therapy initially target a MAP of 65mmHg (1c) (Individualise)
Noradrenaline as the first-choice vasopressure (1b)
Adrenaline when an additional agent is needed (2b)
Vasopressin (up to 0.03U/min) can be added to norad with the intent of raising MAP to target or decreasing noradrenaline

25. h) Vasopressors cont…..
Low-dose vasopressin not recommended as the single initial vasopressor, and doses higher than U/min should be reserved for salvage therapy
Dopamine as an alternative vasopressor agent to noradrenaline only in highly selected patients (2c)
Low dose dopamine not be used for renal protection (1a)
All patients have an arterial line

26. i) Inotropic Therapy
Trial of dobutamine infusion up to 20ug/kg/min in the presence of (1c):
Myocardial dysfunction (elevated cardiac filling pressures and low cardiac output)
Ongoing signs of hypoperfusion, despite adequate intravascular volume and adequate MAP
Against the use of a strategy to increase cardiac index to predetermined supranormal levels (1b)

27. j) Corticosteroids
Against using intravenous hydrocortisone as a treatment of adult septic shock in patients if adequate fluid resuscitation and vasopressor therapy are able to restore haemodynamic stability. If this is not achievable, suggest IV hydrocortisone of 200mg/day (2c)
Against the use of ACTH stimulation test to identify the subset of adults who should receive hydrocortisone (2b)

28. i) Corticosteroids cont…..
Clinician taper the treated patient from steroid therapy when vasopressors are no longer required (2d)
Recommend corticosteroids not be administered for the treatment of sepsis in the absence of shock (1d)
When low-dose hydrocortisone is given, suggest using continuous infusion rather than repetitive bolus injections (2d)

29. Supportive therapy of Severe Sepsis

30. k) Blood product administration
Once tissue hypoperfusion has resolved, and in the absence of extenuating circumstances, recommend that red blood cell transfusion occur when the target Hb <7.0 g/dL to target a level of g/dL (1b)
Against using erythropoietin as a specific treatment of anaemia associated with severe sepsis (1b)
FFP not be used to correct clotting abnormalities in the absence of bleeding or planned invasive procedures

31. k) Blood product administration cont….
Against the use of Anti-thrombin administration for the treatment of severe sepsis and septic shock (1b)
Platelets be administered prophylactically when counts <10 x109/L in the absence of apparent bleeding, as well as when counts <20 if the patient has a significant risk of bleeding. Higher platelet counts >50 are advised for active bleeding, surgery or invasive procedures (2d)

32. l) Immunoglobulins m) Selenium
Against using IV immunoglobulins in adult patients with severe sepsis and septic shock (2b)
m) Selenium
Against using IV selenium to treat severe sepsis (2c) (excluding standard use in TPN)

33. n) Recombinant Activated Protein C
PROWESS  recommendations of its use in the guidelines
PROWESS-SHOCK 2011:
1, 696 pts showing no benefit
Mortality 26.4% cf 24.2% placebo with a relative risk of 1.09
Drug has been withdrawn for the market and is no longer available, so there is no need for an SCC recommendation regarding its use

34. o) Mechanical Ventilation in sepsis-induced ARDS
Recommend target a tidal volume of 6ml/kg predicted body weight in patients with sepsis-induced acute respiratory distress syndrome (cf 12ml/kg) (1a)
Recommend plateau pressures be measured in patients with ARDS and that the initial upper limit goal for pressures in a passively inflated lung be <30cmH20 (1b)
 9% decrease in all cause mortality

35. o) Mechanical ventilation cont……
Recommend PEEP be applied to avoid alveolar collapse at end expiration (atelectotrauma) (1b)
Strategies based on higher rather than lower levels of PEEP for patients with severe sepsis-induced moderate to severe ARDS (2c)
Recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2c)
Prone positioning in severe ARDS in hospitals with experience (2b)

38. o) Mechanical ventilation cont……
Mechanically ventilated sepsis patients be maintained with the head of the bed between degrees to limit aspiration risk and to prevent development of VAP (1b)
NIV be used in the minority of sepsis-induced ARDS patients in whom the benefits of NIV have been carefully considered and are thought to outweigh the risks (2b)

39. o) Mechanical ventilation cont……
Ventilation weaning protocol be in place and ventilated patients undergo spontaneous breathing regularly to evaluate the ability to discontinue mechanical ventilation when:
Arousable
Haemodynamically stable (off vasopressors)
No new potentially serious conditions
Low ventilatory and end-expiratory pressure requiredment
Low FiO2 requirements (face mask or NP)
If spontaneous breathing trial is successful, extubation should be considered (1a)

40. o) Mechanical ventilation cont……
Against the routine use of a pulmonary artery catheter for patients with sepsis-induced ARDS (1a)
Recommend a conservative fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion (1c)
In the absence of specific indication such as bronchospasm, recommend against the use of b- agonists for treatment of patients with sepsis-induced ARDS (1b)

41. p) Sedation, Analgesia, and Neuromuscular Blockade
Recommend either continuous or intermittent sedation be minimised in mechanically ventilated sepsis patients, targeting specific titration endpoints (1b)
Recommend that NMBAs be avoided if possible in patients without ARDS due to the risk of prolonged blockade following discontinuation. If NMBAs must be maintained, either intermittent bolus as required or continusous infusion with train- of-four monitoring of depth of blockade should be used (1c)
Suggest a short course of NMBA (<48hrs) for patients with early sepsis-induced ARDS and PaO2/FiO2 <150mmHg (2c)

42. q) Glucose control
Recommend a protocolised approach to blood glucose management, commencing insulin dosing when two consecutive readings are >180mg/dL (10mmol/L). This approach should target an upper BSL <180mg/dL rather than an upper target of <110mg/dL (7.8mmol/L) (1a)
BSL monitoring every 1-2 hours until glucose values and insulin infusion rates are stable, then every 4hrs thereafter (1c)
BSL obtained from point of care testing be interpreted with caution as may not accurately estimate arterial blood or plasma glucose levels

43. r) Renal Replacement Therapy
Recommend continuous renal replacement therapies and intermittent haemodialysis are equivalent in patients with severe sepsis and acute renal failure because they achieve similar short-term survival rates (2b)
Recommend the use of continuous therapies to facilitate the management of fluid balance in haemodynamically unstable patients (2d)

44. s) Bicarbonate therapy
Recommend against the use of sodium bicarbonate for the purpose of improving haemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidaemia with pH>7.15 (2b)

45. t) DVT prophylaxis
Recommend daily pharmacoprophylaxis against VTE (1b). Via LMWH. If CL <30ml/min recommend dalteparin or another form of LMWH with low renal metabolism.
Recommend treatment with a combination of pharmacologic therapy and intermittent pneumatic compression devices when possible (2c)
Patients with a contra-indication to heparin use not receive pharmacoprophylaxis (1b) but mechanical treatment (2c) unless contraindicated. When the risk decreases, recommend starting pharmacoprophylaxis (2c)

46. u) Stress Ulcer Prophylaxis
Recommend stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to those who have bleeding risk factors (1b)
When SUP used, suggest PPI rather and H2 antagonists (2c)
Suggest patients without risk factors should not receive prophylaxis (2b)

47. v) Nutrition
Recommend administering oral or enteral feedings, as tolerated, rather than complete fasting or IV glucose within the first 48hrs after a diagnosis of severe sepsis/septic shock (2c)
Recommend avoiding mandatory full caloric feeding in the first week, but recommend low-dose feeding and advancing only as tolerated (2b)
Recommend IV glucose and enteral nutrition rather than TPN alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock (2b)
Recomment using nutrition with no specific immunomodulating supplementation (2c)

48. w) Setting goals of care
Recommend goals of care and prognosis be discussed with patients and families (1b)
Recommend that goals of care be incorporated into treatment and end-of-life care planning, utilising palliative care principles where appropriate (1b)
Suggest that goals of care be addressed as early as feasible, but no later than within 72hrs of ICU admission (2c)

49. SPECIAL CONSIDERATIONs IN PAEDIATRICS

50. Overall mortality from severe sepsis is much lower cf adults (2-10%)
Hospital mortality for severe sepsis in previously healthy children = 2%
Hospital mortality for severe sepsis in chronically ill children = 8% (USA)

51. Definitions of sepsis, severe sepsis, septic shock and multi-organ dysfunction/failure syndromes are similar to adult definitions but depend on age-specific heart rate, respiratory rate and WCC.
The SSC guidelines provide recommendations only for term newborns and children in the industrialized resource-rich setting with full access to mechanical ventilation ICUs.

52. Initial Resuscitation
Venous access:
Peripheral IV or intra-osseous access for fluid resuscitation and inotrope infusion when a CVC is not available
Endpoints of Resus:
Capillary refill <2 seconds
Normal BP for age
Normal pulses with no differential between peripheral and ventral pulses
Warm extremities
Urine output >1ml/kg/hr
Normal mental status
Recommend following paediatric advanced life support guidelines (figure on handout)

53. Antibiotics
Empiric drug choice should be changed as epidemic and endemic ecologies dictate
Clindamicin and anti-toxin therapies for toxic shock

54. Fluid Resuscitation/ Inotropes and vasopressors
Boluses of up to 20ml/kg of crystalloids over 5-10 minutes
Fluids should be titrated to reversing hypotension, increasing urine output and attaining normal capillary refill, peripheral pulses and level of consciousness without inducing hepatomegaly or auscultatory chest changes
Peripheral inotropic support until central access can be attained in children who are not responsive to fluids
Patients with low cardiac output and increased systemic vascular resistance with normal blood pressure be given vasodilator therapies

55. Adjunctive/Supportive Therapies
ECMO should be used with refractory septic shock
Hydrocortisone therapy in children with fluid-refractory, catecholamine-resistance shock and suspected or proven absolute (classic) adrenal insufficiency
Use of diuretics to reverse fluid overload (or haemofiltration if unsuccessful) to prevent greater than 10% total body weight fluid overload
No recommendation of use of DVT or stress ulcer prophylaxis

56. Future Directions
Optimum treatment of severe sepsis and septic shock is a dynamic and evolving process
Additional evidence has appeared since the guidelines
New interventions will be proven and established interventions may need modification