1. Resuscitation in SepsisDEEPAK CHANDRAPGY3 IM

2. Significance ? All age grps, 2001 Avg costs per case = $22,100 Annual total costs = $16.7 billionnationallyEpidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. Angus D et al.And Sepsis.com 3. SEPSISALLIANCE.orgSept 13 World Sepsis Day 4. Definitions Sepsis : presence (probable or documented) of infection + SIRS (Temp, HR, RR, WCC ; 2) Severe sepsis : Sepsis + sepsis-induced organ dysfn / tissue hypoperfusion. Septic shock : Sepsis-induced HoTN not responding despite adequate fluid resuscitationSepsis-induced hypotension : SBP4UOP < 0.5 mL/kg/hr >2 hrs(despite adequate fluid challenge) Sepsis induced organ dysfunction- Acute lung injury : Pao2/Fio2 < 250 in absence of pneumoniaAcute lung injury : Pao2/Fio2 < 200 in the presence of pneumonia- Creatinine > 2.0 mg/dL- Bilirubin > 2 mg/dL- Platelet count < 100,000 L- Coagulopathy (INR > 1.5) 6. Infection/Trauma SIRS SEPSIS Severe Sepsis 7. MICU CALL DAY ED wants admission for a 75 yo lady brought in by family for fever, dysuriafor 2 days and AMS for 1 day. Vitals at presentation significant for T-102 F, HR-130, BP-Systolic in 50s withonly minimal improvement with 2L NS. Labs reveal a WCC-25k, Cr 1.7. Dirty UA. 8. INITIAL MANAGEMENT A=Airway ; ? ETT - MV B=breathing. O2, MV C=perfusion D=Abx 9. 1st 3 hours = ED Correct hypoxemia Fluid challenge : 30ml/kg crystalloid Get lactate level Draw appropriate Cx Start broad spectrum abx Imaging : identify a source of infection that requires removal/drainage.SURVIVING SEPSIS CAMPAIGN, 2012 10. http://survivesepsis.org/the-sepsis-six/ 11. Goals in the first 6 hours = ICU MAP 65 mm Hg UOP 0.5 ml/kg/hr CVP 812 mm Hg Scvo2>70% or MVO2 >65%SURVIVING SEPSIS CAMPAIGN, 2012 = EGDT 12. Venous access Peripheral CVC = Fluids, medications (eg. vasopressors), blood products,freq lab studies, hemodynamic monitoring(CVP, ScvO2) Pulmonary artery catheters (PACs) not in the routine management. 13. Choice of fluid ? Crystalloid versus albumin Albumin = anti oxidant (ROS); Buffer for acid ; NO scavenger Multiple studies : showed a/e albumin = coagulopathy, fluid overload SAFE Study(2004) ALBIOS study (2014) 14. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit The SAFE StudyInvestigators* N Engl J Med 2004;350:2247-56. 15. Choice of fluid ? Crystalloid versushydroxyethyl starch Scandinavian Starch for SevereSepsis and Septic Shock (6S) trial HES vs Ringers acetate at ~33mL/kg of ideal weightPerner A et al. N Engl J Med 2012; 367:124-134. 16. Choice of fluid ? Crystalloid vs Pentastarch The Efficacy of Volume Substitution and Insulintherapy in Severe Sepsis (VISEP) trial Pentastarch vs modified Ringer's lactate inpatients with severe sepsis no difference in 28-day mortality Trial was stopped early as trend of increased 90-day mortality in pts with pentastarchBrunkhorst FM et al. N Engl J Med 2008;358:125-139. 17. Final verdict ? Crystalloid (NS, RL) fluid challenges : Repeat till BP/perfusion improvedOR pulmonary edema ensuesOR Fluid fails to augment perfusion Albumin not preferred as : no significant benefithigh cost Volume status ; ?pulm edemaBP must be assessed before and after each bolus. Early administration of fluid -> more important than volume or type of fluidin reducing mortality associated with sepsis. 18. Vasopressors 2nd line : hypotensive despite adequate fluid resuscitationcardiogenic pulmonary edema. 1st line nor epi. Phenylephrine (pure agonist) if tachycardia or arrhythmias preclude theuse of agents with activity (norepinephrine). 19. Additional therapies Targeted at increasing CO to improve tissue perfusion and thereby raise theScvO2 70 percent Indicated in pts with refractory shock in whom the ScvO2 remains 7.Except if concurrent hemorrhage or active MI 20. Goals in the first 6 hours = ICU MAP 65 mm Hg UOP 0.5 ml/kg/hr CVP 812 mm Hg Scvo2>70% or MVO2 >65%SURVIVING SEPSIS CAMPAIGN, 2012 = EGDT 21. MAP SSC : MAP 65 Compared MAP 65 to 70mmHg (low target MAP) VS80 to 85 mmHg (high targetMAP) 22. Lactate clearance Trend lactate till clearly falling Studies sugges that lactate clearance may be an acceptable alternativeto ScvO2 criteria. Lactate not useful after restoration of perfusion but a rising lactate levelshould prompt reevaluation of perfusion 23. Dynamic indices Respiratory changes in the vena caval diameter,Radial artery pulse pressureAortic blood flow peak velocityBrachial artery blood flow velocity. Some evidence that dynamic measures are more accurate predictors offluid responsiveness than static measures, as long as the patients are in sinusrhythm and passively ventilated with a sufficient tidal volume.Not a lot of data to support. 24. Vena caval collapse = Fluid responsiveVideo courtesy: Scott Weingart, youtube.com 25. Treat Cause Source control : Drain foci, removed potentially infected foreign bodies, debridement/amputation. IV abx within first hour of diagnosis (per IDSA) ; obtain appropriate cultures. Empiric broad spectrum + t/s penetration in adequate concentrations. Combination empiric preferred if : Neutropenic or MDR pathogens(Pseudo, Acinteobacter) If candidemia likely: (immunosuppressed or neutropenic/ Prior intense abx / colonization in multiplesites)Empiric antifungal =fluconazole or AMB or echinocandinEmpiric echinocandin preferred : Severe illness, esp if recent antifungal Rx or Candida glabrata) Descalate after ID ; Duration : 7-10 days 26. If Pseudomonas unlikely : Combine Vancomycin with :Ceftriaxone/cefotaximeorPiperacillin-tazobactam, ticarcillin-clavulanateorImipenem or meropenem 27. Suspect Pseudomonas Vancomycin with 2 of the following, from different class :Antipseudomonal cephalo = Ceftaz / CefepimeAntipseudomonal carbapenem = Imipenem or meropenemAntipseudomonal beta-lactam = Zosyn / TicarcillinAnti-pseudomonal FQ = CiproAminoglycoside = Gent, amikacinMonobactam = aztreonam 28. ADDITIONAL THERAPIES 29. Steroids If Hemodynamic instability inspite of fluids and pressors IV hydrocortisone No indication ACTH or random cortisol levels If iInappropriately low random cortisol level : start steroid therapy Hydrocortisone taper after need ends 30. Blood Products PRBC transfusion if Hb7.15 34. JOURNAL CLUB 35. Albumin Italian Outcome Sepsis Study Multicenter : 100 ICUs in Italy RCT ; Open Label Investigate effect of administering albumin and crystalloids vs crystalloidsalone in pts with severe sepsis 36. STUDY METHODS Patient : 18yrs or older who met criteria for severe sepsis in the last 24hrs inICU Intervention :Receive either 20% albumin (targeting albumin>30g/l) and crystalloid(Albumin group)or crystalloids solution alone (Crystalloid group)Until day 28 or discharge from ICU, whichever came first. 37. Patient : 18yrs or older who met criteria for severe sepsis in the last 24hrs inICU Intervention :Receive either 20% albumin (targeting albumin>30g/l) and crystalloid(Albumin group)or crystalloids solution alone (Crystalloid group)Until day 28 or discharge from ICU, whichever came first. Comparison : Hemodynamic parameters, SOFA score, Mortality 38. Outcomes measured Primary : Any cause death at 28 days SecondaryMain Any cause death at 90 daysOther number and degree of Organ dysfunctionLOS ICU, hospital Tertiary (post-hoc)RRT, Duration of MV, Time to suspension of pressors 39. Inclusion Criteria1. Proved or suspected infection in at least one site: lung, abdomen, genito-urinarytract, other2. Two or more of the following: a) core temperature 38 C o 36 C; b) HR 90 beats/min; c) RR 20 breaths/min or PaCO2 32 mmHg or use of MV for an acuteprocess; d) WBC 12000/ml or 4000/ml or immature neutrophils > 10%.3. Presence of at least a severe and acute sepsis-related organ dysfunctionbased on SOFA score. 40. Exclusion Criteria1. Age 6hrs after meeting criteriafor sepsis. Open label 45. Conclusion No survival benefit in adding albumin to crystalloid solution in Rx of pt withsevere sepsis. Statistically significant improvement in hemodynamic variables in albumingroup but no clinical benefit Results are applicable in daily practice Dont use albumin for resuscitation in severe sepsis unless Nephrology orHepatology recommends ! 46. Relative Risk(Risk Ratio) 47. Outline What is Relative Risk? How can it be interpreted? How is the relative risk different from the odds ratio? 48. DefinitionRelative Risk is the ratio of the probability of an event occurring in thetreatment group to the probability of an event occurring in the control group. = 28 ( 28 ) 49. CalculationRisk Death No Death TotalAlbumin a b a+bNo Albumin c d c+dTotal a+c b+d a+b+c+d =/( + )/( + ) 50. Interpretation RR = 1 No difference in risk. (risk = the probability of an event occurring) RR < 1 Event of interest (death) is less likely to occur in the treatment group. RR > 1 Event of interest is more likely to occur in the treatment group. 51. Interpretation Cont. To find the decrease in risk for a RR