1. Surviving Sepsis 2008 Guidelines Early Goal Directed Therapy MAZEN KHERALLAH, MD, FCCP INFECTIOUS DISEASE AND CRITICAL CARE MEDICINE

2. Sepsis SIRSSevere SepsisSeptic ShockInfection Chest 1992;101:1644 Therapy Across the Sepsis Continuum  A clinical response arising from a nonspecific insult, with  2 of the following:  T >38 o C or <36 o C  HR >90 beats/min  RR >20/min  WBC >12,000/mm 3 or 10% bands Microorganism invading sterile tissue SIRS with a presumed or confirmed infectious process Sepsis with organ failure  Vascular collapse  Renal  Hemostasis  Lung  LA Refractory hypotension

3. Burns Trauma Sepsis Syndromes 1992: SCCM/ACCP Parasite Virus Fungus Bacteria BSI Severe Sepsis Shock Severe SIRS Infection SIRS Sepsis

4. Surviving Sepsis Campaign Launched in Fall 2002 as a collaborative effort of European Society of Intensive Care Medicine, the International Sepsis Forum, and the Society of Critical Care Medicine Goal: reduce sepsis mortality by 25% in the next 5 years Guidelines revealed at SCCM in Feb 2004  Critical Care Medicine March 2004 32(3):858-87.  Website: survivingsepsis. org

5. THE SEVERE SEPSIS BUNDLES: SSC/IHI 6 Hour Bundle Measure serum lactate Blood Cultures prior to antibiotics Broad spectrum antibiotics within 3 hours of presentation, 1 hour in hospital Initial fluid resuscitation with 20-40 mL/kg crystalloid (or equivalent colloid) if hypotensive (SBP 4 mmol/L Vasopressors If septic shock or lactate > 4 mmol/L: CVP and ScvO 2 or SvO 2 measured CVP maintained 8-12 mm Hg Inotropes (and/or PRBCs if Hct 8 mmHg 24 Hour Bundle Glucose control maintained < 150 mg/dL Drotrecogin alfa (activated) administered in accordance with hospital guidelines Steroids given for septic shock requiring continued use of vasopressors for > 6 hours Lung protective strategy with plateau pressures < 30 cm H 2 O for mechanically ventilated patients http://www.ihi.org

6. SCCM 2009: Sepsis Management "Bundles" Boost Guideline Implementation, Reduce Mortality 15,022 Patients 7% Absolute Risk Reduction 19% Relative Risk Reduction Society of Critical Care Medicine (SCCM) 38th Critical Care Congress. Late breaker. Presented February 2, 2009

7. SUMMARY: SEPSIS GUIDELINES 2008 Strong Recommendation (1): Recommended DVT Prophylaxis H2 Blocker PUD Prophylaxis No Routine Use of SGC ADCB Glycemic Control Consider Limiting Support BC prior to Abx Antibiotics within 1 hr for Septic Shock EGDT and Protocolized Resuscitation Antibiotics within 1 hr in No septic Shock Patients De-escalation Antibiotic Therapy 7-10 day Antibiotic Duration Source Control Fluid Challenge Dopamine or Norepinephrine Limit P plateau <30 cm H2O PEEP Conservative Fluid in ALI with no Shock No Renal Dose Dopamine No High Dose Steroids Weaning Protocol/SBT Avoid NMB PPI PUD Prophylaxis Crystalloid = Colloid Limited Transfusion Low VT for ALI HOB >45 Intermittent = Continuous sedation No Antithrombin II No Erythropoietin

8. SUMMARY: SEPSIS GUIDELINES 2008 Weak Recommendation (2): Suggested APC in high risk and non-surgical ADCB equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis Wean Steroids Low dose steroids for septic shock B/S < 150 APC for high risk and surgical PRBCs or Dobutamine ACTH test not to be done Prone Position in ARDS NIV for ALI/ARDS mild/moderate hypoxemia

9. Sepsis SIRSSevere SepsisSeptic ShockInfection Insulin and Tight Glucose Control Early Goal Directed Therapy Steroids Antibiotics and Source Control Chest 1992;101:1644 Therapy Across the Sepsis Continuum * Drotrecogin Alpha

10. Sepsis SIRSSevere SepsisSeptic ShockInfection Early Goal Directed Therapy Therapy Across the Sepsis Continuum Early Goal-Directed Therapy (EGDT): involves adjustments of cardiac preload, afterload, and contractility to balance O 2 delivery with O 2 demand: Fluids, Blood, and Inotropes Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001;345:1368.  CVP > 8-12 mm Hg  MAP > 65 mm Hg  Urine Output > 0.5 ml/kg/hr  ScvO 2 > 70%  SaO 2 > 93%  Hct > 30% *

11. Rivers E, Nguyen B, Havstad S, et al 2001;345:1368-1377.

13. 49.2% 33.3% 0 10 20 30 40 50 60 Standard Therapy N=133 EGDT N=130 P = 0.01* *Key difference was in sudden CV collapse, not MODS Early Goal-Directed Therapy Results: 28 Day Mortality Vascular Collapse 21% vs 10% p=0.02 MODS 22% vs 16% P=0.27 NEJM 2001;345:1368-77. Mortality %

14. Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377. In-hospital mortality (all patients) 0 10 20 30 40 50 60 Standard therapy EGDT 28-day mortality 60-day mortality NNT to prevent 1 event (death) = 6 - 8 Mortality (%) The Importance of Early Goal-Directed Therapy for Sepsis-induced Hypoperfusion

16. ◦ If venous O2 saturation target not achieved: (2C) Consider further fluid Tansfuse packed red blood cells if required to hematocrit of ≥30% and/or Dobutamine infusion max 20 µg.kg −1.min −1 Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

17. First section screens for SIRS  SIRS includes objective vital signs data:  Temperature ≥ 100.4 or ≤ 96.8 F  Heart Rate ≥ 90  Respiratory Rate ≥ 20  WBC count ≥ 12,000 or ≤ 4,000, or greater than 0.5K/uL bands  If the patient has 2 or more of the above, they screen positive for SIRS SIRS Screen

18. Second section screens for infection  The patient is screened for infection if they have SIRS  Does the patient have suspected or documented infection?  Has the patient received antibiotics (not prophylaxis)?  If one of the above is confirmed, the patient is screened for organ dysfunction Infection Screen

19. Third section screens for Organ Dysfunction  Respiratory: SaO2 < 90 %  Cardiovascular: SBP < 90  Renal: urine output 0.5mg/dl from baseline  CNS: altered LOC, Glascow coma scale ≤ 5 Any one of the above, in addition to positive results from sections 1 and 2, indicates severe sepsis. Severe Sepsis Screen

20. The RN should approache the MD, informing him using SBAR technique, that the patient has screened positive for severe sepsis. SBAR

21. SBAR Communication Technique Situation:  RN caring for John Smith  Screened positive for severe sepsis Background:  Positive for SIRS (describe)  Known or suspected infection  Organ dysfunction (describe) Assessment:  Share complete VS and SaO2

22. Recommendation:  I need you to come and evaluate the patient to confirm if they have severe sepsis.  It is recommended that I get an ABG, lactate, and CBC, Can I proceed and get these?  Any other labs you would like me to obtain?  If the pt is hypotensive: Can I start an IV and give a bolus of NS – 20 ml/kg? SBAR Communication Technique

24. Resuscitation Goals (Grade 1C) Central venous pressure (CVP): 8–12mm Hg Mean arterial pressure (MAP) ≥ 65mm Hg Urine output ≥ 0.5mL.kg–1.hr –1 Central venous (superior vena cava) or mixed Venous oxygen saturation ≥ 70% or ≥ 65%, respectively Hemoglobin >10 mg/dL Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

25. Initiation of Resuscitation (1C) Begin resuscitation immediately in patients with CVP 4mmol/l; Do not delay pending ICU admission. Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

26. CVP <8 mmHg Central line placement and CVP monitoring 500 mL 0.9% NaCl bolus every 15 minutes to maintain a CVP goal Colloids if CVP <4 Transfuse 1 unit of PRBC’s if Hg <10

27. A higher target CVP of 12–15 mmHg is recommended in the presence of Mechanical ventilation Pre-existing decreased ventricular compliance Increased intra-abdominal pressure

28. MAP <65 mmHg Arterial line placement Norepinephrine 2-20 mcg/min Vasopressin 0.04 Unit/min Phenylephrine 40-200 mcg/min Hydrocortisone 50 mg IV every 6 hours

29. ScvO2 <70% Arterial line placement Transfuse 1 PRBC’s if Hg level <10 mg/dL Start Dobutamine 2.5-20 mcg/kg/min IV infusion Intubation and ventilation

31. Critical Care is A Promise ان الله يحب العبد اذا عمل عملا أن يتقنه

32. If you are admitted to our ICU with severe sepsis we will:  Obtain blood cultures and lactic acid level  Start antibiotics within one hour  Target a central venous pressure target to ≥8 mmHg  Target a mean arterial blood pressure target of ≥65 mmHg  Target a central venous O2 saturation of ≥ 70%  Target your urine output to >0.5 mL/Kg/Hour

33. Thank You