SIRS and SEPSIS_2.pptx Dr Nannika Pradhan

Dr.Nannika Pradhan

1. SIRS and SEPSIS Presenter : Srijana Pradhan Chairperson : Dr Sandip Saha

2. Definition SIRS (Systemic inflammatory Response Syndrome) 2 of the following Temperature >38⁰C or <36⁰C Heart >90 beats/min Respiratory rate >20 breaths/min WBC count >12000/ cumm or <4000/ cumm

3. Prior to Sepsis 3 Sepsis Severe sepsis Septic shock After sepsis 3 Sepsis Septic shock Changes in Sepsis 3 update

4. Sepsis Life threatening organ dysfunction caused by a dysregulated host response to infection Septic shock Subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities lead to substantially increased mortality risk Definition

5. Criteria in 2016 (Sepsis-3) Sepsis Suspected (or documented) infection Acute increase in ≥2 sepsis related organ failure assessment (SOFA) points Septic shock Suspected (or documented) infection Vasopressor therapy needed to maintain MAP≥65mmHg serum lactate >2 mmol /L despite adequate fluid resusitation

6. SOFA

7. qSOFA Respiratory rate ≥22/min Altered mentation Systolic blood pressure ≤100 mmHg ≥2 variables - qSOFA positive

8. qSOFA no longer recommended as screening tool for sepsis Consider non infectious causes and delay antimicrobials administration in patients at low risk of sepsis Use procalcitonin only for antibiotic de-escalation Changes in the 2021 update

9. Pathogenesis

10. Lactic acidosis in Sepsis impaired regional microvascular blood flow mitochondrial dysfunction with impaired pyruvate oxidation excess catecholamines may impair hepatic lactate extraction lactate clearance is decreased because pyruvate dehydrogenase activity is reduced in both skeletal muscle and liver

11. Main goals of management Early recognition, prompt disease stratification and rapid treatment initiation Prevention and support of organ dysfunction Rapid infection source control Adequate antimicrobial therapy Surgical/ instrumental intervention

12. Elements of Care Resuscitation Infection control Respiratory support General supportive care

13. Surviving Sepsis Campaign

14. Initial Resustitation Sepsis and septic shock –medical emergencies Recommendation: treatment to be started immediately IV crystalloid fluid 30 mL /kg of should be given within the first 3 hr of resuscitation Crystalloids as first-line fluid for resuscitation. Strong recommendation, moderate quality of evidence.

15. Fluid therapy Albumin in patients who received large volumes of crystalloids over using crystalloids alone. Weak recommendation, moderate quality of evidence. Recommends against using starches for resuscitation. Strong recommendation, high quality of evidence. Suggests against using gelatin for resuscitation . Weak recommendation, moderate quality. Dynamic measures to guide fluid resuscitation, over physical examination, or static parameters alone.

16. Vasoactive medications Norepinephrine as the first-line agent over other vasopressors . Strong recommendation Septic shock on norepinephrine with inadequate MAP levels- suggests adding vasopressin instead of escalating the dose of norepinephrine . Weak recommendation, moderate-quality evidence. Inadequate MAP levels despite norepinephrine and vasopressin - suggests adding epinephrine

17. Ionotropes Cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure – suggests either adding dobutamine to norepinephrine or using epinephrine alone . Weak recommendation, low quality of evidence.

18. Summary of vasoactive agents recommendation

19. Elevated serum lactate levels - resuscitation should be guided towards normalizing these levels when possible Capillary refill time to guide resuscitation as an adjunct to other measures of perfusion. Weak, low quality of evidence Initial Resustitation

20. Andromeda Shock Study 2015 Evaluated whether a resuscitation strategy targeting CRT normalization was more effective than a resuscitation strategy aiming at normalization or decreasing lactate levels by 20 % At day 3, the CRT group had significantly less organ dysfunction as assessed by SOFA score U sing CRT during resuscitation has physiologic plausibility and is easily performed, noninvasive, and no cost .

21. Early Goal-Directed Therapy

22. Early Goal-Directed Therapy

23. Newer Trials deemphasized EGDT ProCESS (2014) 3 arms Bundle of care described by Rivers trial Similar arm without the use of ionotropes or blood transfusions Usual care No mortality benifit ARISE (2014) No mortality benefit ProMIse (2015) No mortality benifit

24. CLOVERS trial Restrictive fluid vs liberal fluid strategy Less intravenous fluids in restructive group than in liberal group No difference in 90 day mortality between the two strategies

25. Infection Control Early administration of appropriate antimicrobials - most effective intervention to reduce mortality in patients with sepsis. Delivering antimicrobials to patients with sepsis or septic shock - treated as an emergency Suggests against using procalcitonin to decide when to start antimicrobials. Weak recommendation, very low quality of evidence

26. Timing of antibiotic administration

27. Choice of Antimicrobial therapy 2016 Empirical broad-spectrum therapy with one or more antimicrobials for patients presenting with sepsis or septic shock to cover all likely pathogens (including bacterial and potentially fungal or viral coverage).

28. 2021 low risk of MRSA- suggests against using empiric antimicrobials with MRSA coverage Suggests against using double gram-negative coverage once the causative pathogen and the susceptibilities are known. High risk of fungal infection - suggests using empiric antifungal therapy over no antifungal therapy no recommendation on the use of antiviral agents. Choice of Antimicrobial therapy

29. Antimicrobial therapy Unconfirmed infection - recommends continuously re-evaluating and searching for alternative diagnoses and discontinuing empiric antimicrobials. High likelihood for sepsis - administering antimicrobials immediately, ideally within 1 hr of recognition. Suggests using prolonged infusion of beta- lactams for maintenance (after an initial bolus) over conventional bolus infusion. Weak recommendation, moderate quality of evidence

30. Source control should be undertaken as soon as is medically and logistically possible. Best practice statement Prompt removal of intravascular access devices that are a possible source of sepsis or septic shock after other vascular access has been established. Best practice statement Suggests using shorter over longer duration of antimicrobial therapy. Weak recommendation, very low quality of evidence. Daily assessment for de-escalation of antimicrobial therapy should be conducted Antimicrobial therapy

31. Antimicrobial therapy

32. Respiratory Support A target tidal volume of 6ml/kg is recommended in sepsis induced ARDS In severe ARDS, prone positioning is recommended Suggests the use of high flow nasal oxygen over noninvasive ventilation. Weak recommendation, low quality of evidence.

33. Corticosteroids O ngoing requirement for vasopressor therapy - suggests using IV corticosteroids. Weak recommendation; moderate quality of evidence. Indication dose of norepinephrine or epinephrine ≥ 0.25 mcg/kg/min at least 4 hours after initiation. Dose IV hydrocortisone at a dose of 200 mg/d given as 50 mg every 6 hours or as a continuous infusion.

34. 200mg of hydrocortisone administed by infusion or by matched placebo No statistically significant difference in 90 day mortality between the two groups Secondary outcomes in hydrocortisone group Earlier shock reversal Faster liberation from mechanical ventilation Earlier discharge from ICU ADRENAL study (2018)

35. APROCCHSS study Hydrocortisone combined with fludricortisone vs placebo Mortality was significantly lower in the group that received steroids

36. Blood products Recommends using a restrictive (over liberal) transfusion strategy. Strong recommendation; moderate quality of evidence . Red blood cell transfusion is recommended only when the Hb <7g/dl in the absence of myocardial infraction , severe hypoxemia or acute hemorrhage Suggests against using IV immunoglobulins . Weak, low quality of evidence

37. Stress Ulcer Prophylaxis For adults with sepsis or septic shock, and who have risk factors for gastrointestinal (GI) bleeding - suggests using stress ulcer prophylaxis. Weak recommendation, moderate quality of evidence.

38. Venous Thromboembolism Recommends using pharmacologic VTE prophylaxis unless a contraindication to such therapy exists. Strong recommendation, moderate quality of evidence. Recommends using low molecular weight heparin(LMWH) over unfractionated heparin (UFH) for VTE prophylaxis. Strong recommendation, moderate quality of evidence. Suggests against using mechanical VTE prophylaxis in addition to pharmacological prophylaxis, over pharmacologic prophylaxis alone. Weak recommendation, low quality of evidence.

39. Renal Replacement Therapy In adults with sepsis or septic shock and AKI who require renal replacement therapy, we suggest using either continuous or intermittent renal replacement therapy. Weak recommendation, low quality of evidence. no definitive indications for renal replacement therapy, we suggest against using renal replacement therapy . Weak recommendation, moderate quality of evidence

40. Additional therapies Glucose Control recommends initiating insulin therapy at a glucose level of ≥ 180 mg/ dL (10 mmol /L). Strong recommendation; moderate quality of evidence. Following initiation of an insulin therapy, a typical target blood glucose range is 144−180 mg/ dL (8−10 mmol /L). Recommendation to commence insulin when two consecutive blood glucose levels are > 180 mg/ dL derived from the NICE-SUGAR trial

41. Suggests against using IV vitamin C. Weak recommendation, low quality of evidence Suggest early (within 72 hours) initiation of enteral nutrition. Weak recommendation; very low quality of evidence. Advantages maintenance of gut integrity prevention of intestinal permeability dampening of the inflammatory response modulation of metabolic responses that may reduce insulin resistance Additional therapies

42. Additional therapies Sodium bicarbonate therapy Hypoperfusion induced lactic acidemia - suggests against using sodium bicarbonate therapy to improve hemodynamics or to reduce vasopressor requirements. Weak recommendation, low quality of evidence. For severe metabolic acidemia (pH ≤ 7.2) and AKI - suggest using sodium bicarbonate therapy . Weak recommendation, low quality of evidence.

43. Acetaminophen reduces temperature in non-critically ill patients but does not change mortality or other outcomes should not be considered one of the main pillars of sepsis treatment Additional therapies

44. Goals of Care For adults with sepsis or septic shock - recommends discussing goals of care and prognosis with patients and families over no such discussion . Addressing goals of care early (within 72 hours) Weak recommendation, low-quality evidence.

45. Take Home Message qSOFA no longer recommended as screening tool for sepsis Consider non infectious causes and delay antimicrobials administration in patients at low risk of sepsis Elements of Care Resuscitation Infection control Respiratory support General supportive care 5 steps of the 1hr Bundle according to the Surviving Sepsis Campaign

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