Nabil Abouchala, MD, FCCP, FACP Consultant, Pulmonary and Critical Care Medicine

1. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012A Guide To The Guidelines … Nabil Abouchala, MD, FCCP, FACP Consultant, Pulmonary and Critical Care Medicine Medical Director, Med-Sug ICU-C King Faisal Hospital & Research Center Riyadh, Saudi Arabia

2. Surviving Sepsis Campaign: History of the guidelines… 2001 2004 2008 2012

3. Crit Care Med 2013; 41:580–637

4. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 1. Initial Resuscitation and Infection Issues 2. Hemodynamic Support and Adjunctive Therapy​ 3. Other Supportive Therapy of Severe Sepsis 4. Special Considerations in Pediatrics​​

5. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012

8. Sepsis Bundle A. Initial Resuscitation Serum Lactate Measured Resuscitation Bundle Blood Culture Obtained Prior to Antibiotic Administration Broad-Spectrum Antibiotics Administered within 1 Hour of ED Admission Fluid Resuscitation (30 ML/Kg) for Hypotension or Lactate >4mmol/L Vasopressors for Ongoing Hypotension Maintain Adequate Central Venous Pressure (CVP ≥ 8) Maintain Adequate Central Venous Oxygen Saturation (ScvO2 ≥ 70%) Re-measure Serum Lactate

9. Early Goal-directed Therapy in the Treatment of Severe Sepsis and Septic Shock To Examine whether Early Goal Directed Therapy (EGDT) before admission to the ICU is superior to standard hemodynamic therapy in patients with sever sepsis and septic shock #Citing articles 2469 N Engl J Med, 2001;345:1368-77

10. 10-20% Sudden Death! MOrtality

11. Results 37 Observational studies showing improved outcomes with early quantitative resuscitation between 2001 and 2011 • Mortality • EGT : 30.5 % • Standard: 46.5 % • Absolute Risk Reduction • NNT = 16% 7 Multicenter trial of 314 patients with severe sepsis in eight Chinese centers (2010). This trial reported a 17.7% absolute reduction N Engl J Med, 2001;345:1368-77

12. fluid in septic shock, How much ?

13. 2012: IVF recommendation • Initial fluid challenge ≥ 1000 mL of crystalloids or minimum of 30 mL/kg of crystalloids in the 1st 4-6 hours • (Strong recommendation; Grade 1C). • Crystalloids is the initial fluid for resuscitation • (Strong recommendation; Grade 1A). • Adding albumin to the initial fluid resuscitation • (Weak recommendation; Grade 2B). • Against hydroxyethyl starches (hetastarches) with MW >200 dalton • (Strong recommendation; Grade 1B).

14. Timing of Antibiotic Administration

15. % Survival % Total receiving antibiotics Only 50% of patients in Septic Shock received antibiotics w/in 6 hrs. Septic Shock: Timing of Antibiotics Percent 1.00 14 ICUs; n = 2,731 .80 .60 .40 .20 0.0 .5 – 1.0 1 - 2 2 - 3 3-4 4 - 5 5 - 6 6 - 9 9 - 12 12 - 24 24 - 36 > 36 0 - .5 Time, hrs Kumar Crit Care Med 2006

16. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012

18. Which Inotropes to use? Norepinephrine as the first choice ( Grade 1B) Adding or substituting epinephrine when an additional drug is needed (Strong recommendation; Grade 1B). Vasopressin 0.03 units/min may be added (Weak recommendation; Grade 2A) Dopamine only in highly selected patients at very low risk of arrhythmias or low heart rate (Weak recommendation; Grade 2C). Dobutamine infusion be started or added with low cardiac output) or ongoing signs of hypoperfusion, even after adequate intravascular volume (Strong recommendation; Grade 1C)

19. Norepinephrine Compared With Dopamine in Severe Sepsis Summary of Evidence

20. Crit Care Med 2012; 40:725–730

21. Sepsis induced vasodilatation Lower amount of fluid required to fill the tank NE

22. Crit Care Med 2007; 35:1736–1740 Early NE + Fluids Late NE + Fluids Fluids NE LPS

23. Adequate fluid resuscitation …

24. Early administration of norepinephrine aimed at rapidly achieving a sufficient perfusion pressure in severely hypotensive septic-shock (DBP < 40) patients is able to increase cardiac output through an increase in cardiac preload and cardiac contractility

25. Crit Care Med 2007; 35:64–68

26. Crit Care Med 2007; 35:64–68

27. Passive Leg raising

29. Stroke volume variation SVV = SV max – SV min / SV mean

30. Pleth Variability index (PVI) to Help Clinicians Optimize Preload / Cardiac Output Stroke Volume Lower PVI = Less likely to respond to fluid administration 10 % 24 % Higher PVI = More likely to respond to fluid administration 0 0 Preload Maxime Cannesson, MD, PhD

31. Target MAP ≥ 65 …

32. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012

34. K. Blood Product Administration Target Hemoglobin (7-9 g/dl) unless … L. Immunoglobulins: Not recommended M. Selenium: Not recommended N. History of Recommendations Regarding Use of Recombinant Activated Protein C R. Renal Replacement Therapy S. Bicarbonate Therapy

35. The Rise and Fall of xigris! -6.5% +1.2%

36. K. Blood Product Administration Target Hemoglobin (7-9 g/dl) unless … L. Immunoglobulins: Not recommended M. Selenium: Not recommended N. History of Recommendations Regarding Use of Recombinant Activated Protein C O. Mechanical Ventilation of Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS) P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis Q. Glucose Control R. Renal Replacement Therapy S. Bicarbonate Therapy T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer V. Nutrition W. Setting Goals of Care

37. O. Mechanical Ventilation of Sepsis-Induced (ARDS) 1. Target a TV of 6 mL/kg predicted body weight (grade 1A vs. 12 mL/kg) 2. Plateau pressures be measured in patients with ARDS be ≤30 cm H2O (grade 1B) 3. (PEEP) be applied (grade 1B) 4. Higher rather than lower levels of PEEP for moderate or severe ARDS (grade 2C) 5. Recruitment maneuvers be used with severe refractory hypoxemia (grade 2C) 6. Prone positioning be used Pao2/Fio2 ratio ≤ 100 mm (grade 2B) 7. HOB elevated to 30-45 (grade 1B) 8. (NIV) be used in minority of patients in whom the benefits of NIV (grade 2B) 9. Weaning protocol be in place 10. Against the routine use of the pulmonary artery catheter (grade 1A) 11. A conservative rather than liberal fluid strategy (grade 1C) 12. not using beta 2-agonists for treatment of sepsis-induced ARDS (grade 1B)

38. ARMA Trial Reducing from 12 to 6 ml/kg VT saved lives NNT 12 14000 Lives Saved/Year

41. Wet First –Dry later CHEST 2009; 136:102–109 Approach that combines both adequate initial fluid resuscitation followed by conservative late-fluid management was associated with improved survival

42. Wet First –Dry later CHEST 2009; 136:102–109

43. JAMA. 2010;303(9):865-873

44. Higher PEEP is betterin Moderate to Severe ARDS (PO2/FiO2 ≤ 200 mmHg) JAMA. 2010;303(9):865-873

45. Higher PEEP is betterin Moderate to Severe ARDS (PO2/FiO2 ≤ 200 mmHg) Death in ICU  6.3 % NNT 16 Days off the MV -5 days JAMA. 2010;303(9):865-873

48. Glucose control in ICU -10% +1.5% ITT- 2001 NICE-SUGAR- 2009

49. P. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis • (NMBAs) be avoided if possible without ARDS • Short course of NMBA (<48 hours) for early ARDS + Pao2/Fio2<150 mm Hg Q. Glucose Control T & U. Prophylaxis: Deep Vein Thrombosis and Stress Ulcer • PPIs rather than H2RA (grade 2D) V. Nutrition

50. Omega/EDEN* studies • Objective: dietary supplementation of Omega-3 FA increase ventilator –free days in patients with ALI/ARDS • Intervention: BID bolus supplementation of omega-3 FA vs isocaloric control Rice at al. for the NHLBI ARDS Clinical Trials Network JAMA. 2011;306(14):1574-1581