Management of Severe Sepsis:

Transcription

1 Management of Severe Sepsis: Update from the Surviving Sepsis Campaign Barbara Birriel, MSN, ACNP-BC, FCCM The Pennsylvania State University NONE Disclosures Review evidence-based international sepsis guidelines Identify criteria and systems for early diagnosis of sepsis Discuss initial management of sepsis Discuss hemodynamic support in severe sepsis Discuss supportive therapy in severe sepsis Objectives WHY DO WE CARE ABOUT SEPSIS? Incidence Cost Prevalence 1

2 Overall mortality from sepsis in the U.S. approximately 20% Linear relationship to the number of organ failures each additional organ failure raises the mortality rate by 15%. Hypothermia is one of the worst prognostic signs. Patients presenting with sepsis and hypothermia have an overall mortality of ~80%. Mortality Mortality WHAT IS SEPSIS? Organ failure in sepsis Vincent, J.-L., Sakr, Y., Sprung, C. L., Ranieri, V. M., Reinhart, K., Gerlach, H., Moreno, R., et al. (2006). Sepsis in European intensive care units: results of the SOAP study. Critical Care Medicine, 34(2), /3 of cases no organism is identified Sepsis: The 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 Any microbe may cause, but gram negative most common historically Higher incidence recently of gram positive due to Hospitalized patients Immunocompromised Indwelling catheters Increasing drug resistance Surviving Sepsis Campaign 2012 Sepsis -?organism 2

3 Epidemiology : Causative organism Relationship Between Sepsis, Infection, and Bacteremia OTHE R BACTEREMIA TRAUMA INFECTION SEPSIS SEPSIS SIRS BURNS PANCREATITIS Vasodilation Infection or Insult Inflammatory Mediators Endothelial Dysfunction permeability Hypotension Microvascular Plugging Vasoconstriction Edema Maldistribution of Microvascular Blood Flow Ischemia / Tissue Hypoxia Bacterial Endotoxin TNF-α Interleukin-1 Interleukin-6 Interleukin-8 Platelet Activating Factor (PAF) Interferon-Gamma Prostaglandins Leukotrienes Nitric Oxide Cell Death Organ Dysfunction Pro-inflammatory Mediators Infection or Insult Interleukin-10 PGE2 Protein C Interleukin-6 Interleukin-4 Interleukin-12 Lipoxins GM-CSF TGF IL-1RA Anti-inflammatory Mediators Vasodilation Inflammatory Mediators Endothelial Dysfunction permeability Hypotension Microvascular Plugging Vasoconstriction Edema Maldistribution of Microvascular Blood Flow Ischemia / Tissue Hypoxia Cell Death Organ Dysfunction 3

4 DIAGNOSTIC CRITERIA Infection inflammatory response to microorganism Systemic Inflammatory Response Syndrome (SIRS) Sepsis infection + SIRS Severe Sepsis sepsis + organ dysfunction Septic Shock sepsis + hypotension despite fluid resuscitation Multiple Organ Dysfunction Syndrome organ failure in acutely ill patient Trajectory of Sepsis Two or more of the following Temperature > 38 C or <36 C Heart rate > 90 Respiratory rate > 20 resp/min or PaCO2 <32 WBC > 12,000, < 4,000, or >10% bands SIRS Systemic Inflammatory Response Syndrome Infection (documented or suspected) and some of: General Fever (> 38.3 C) Hypothermia (core temperature < 36 C) Heart rate > 90/min or more than two sd above the normal value for age Tachypnea Altered mental status Significant edema or positive fluid balance (> 20 ml/kg over 24 hr) Hyperglycemia (plasma glucose > 140 mg/dl or 7.7 mmol/l) in the absence of diabetes Sepsis Infection (documented or suspected) and some of: Inflammatory variables Leukocytosis (WBC count > 12,000 μl 1) Leukopenia (WBC count < 4000 μl 1) Normal WBC count with greater than 10% immature forms Plasma C-reactive protein more than two sd above the normal value Plasma procalcitonin more than two sd above the normal value Sepsis Infection (documented or suspected) and some of: Hemodynamic variables Arterial hypotension (SBP < 90 mm Hg, MAP < 70 mm Hg, or an SBP decrease > 40 mm Hg in adults or less than two sd below normal for age) Sepsis 4

5 Infection (documented or suspected) and some of: Organ dysfunction variables Arterial hypoxemia (Pao2/Fio2 < 300) Acute oliguria (urine output < 0.5 ml/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase > 0.5 mg/dl or 44.2 μmol/l Coagulation abnormalities (INR > 1.5 or aptt > 60 s) Ileus (absent bowel sounds) Thrombocytopenia (platelet count < 100,000 μl 1) Hyperbilirubinemia (plasma total bilirubin > 4 mg/dl or 70 μmol/l) Sepsis Infection (documented or suspected) and some of: Hypoperfusion variables Hyperlactatemia (> 1 mmol/l) Decreased capillary refill or mottling Sepsis Sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following thought to be due to the infection): Sepsis-induced hypotension Lactate above upper limits laboratory normal Urine output < 0.5 ml/kg/hr for more than 2 hrs despite adequate fluid resuscitation Acute lung injury with Pao2/Fio2 < 250 in the absence of pneumonia as infection source Acute lung injury with Pao2/Fio2 < 200 in the presence of pneumonia as infection source Creatinine > 2.0 mg/dl (176.8 μmol/l) Bilirubin > 2 mg/dl (34.2 μmol/l) Platelet count < 100,000 μl Coagulopathy (international normalized ratio > 1.5) Severe Sepsis Same criteria as sepsis Persistent hypotension (MAP < 70) AFTER fluid resuscitation Septic Shock A- high quality B- intermediate C- low D- very low Grading Quality of Evidence GRADE System Case series or expert opinion Upgrade capability Ungraded (UG) recommendation 5

6 Grading Strength of Recommendation GRADE System 1- strong recommendation We recommend 2- weak recommendation We suggest Screening for Sepsis and Performance Improvement 1. Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy (grade 1C). 2. Hospital based performance improvement efforts in severe sepsis (UG). Therapeutic Strategies in Sepsis Time Zero = time of presentation ED, Medical Floors, ICU Two time based bundles Most important time based elements: Antibiotic timing Resuscitation timing (EGDT) After Before Time Zero Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis Thiel, S. W., Asghar, M. F., Micek, S. T., Reichley, R. M., Doherty, J. A., & Kollef, M. H. (2009). Hospital-wide impact of a standardized order set for the management of bacteremic severe sepsis*. Critical Care Medicine, 37(3), doi: /ccm.0b013e b Why measure lactate? Diagnose severe sepsis with elevated lactate as a diagnosis of tissue hypoperfusion Trigger for quantitative resuscitation if lactate is 4 mg/dl or more 6

7 Blood Cultures Diagnosis 1. To optimize identification of causative organisms, we recommend at least two blood cultures be obtained before antimicrobial therapy is administered as long as such cultures do not cause significant delay (>45 minutes) in antimicrobial administration, with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hr.) inserted (Grade 1C). Time to Antibiotics Following Onset Septic Shock Antibiotic Therapy We recommend that intravenous antibiotic therapy be started as early as possible and within the first hour of recognition of septic shock (1B) and severe sepsis without septic shock (1C). Remark: Although the weight of evidence supports prompt administration of antibiotics following the recognition of severe sepsis and septic shock, the feasibility with which clinicians may achieve this ideal state has not been scientifically validated. Kumar A, et al. Crit Care Med 2006; 34:

8 Antibiotic Therapy Initial empiric anti-infective therapy activity against all likely pathogens and adequate concentrations into suspected or potential sources of infection (1B) Reassess antibiotic regimen daily for deescalation (1B) Fluid therapy 4. We recommend that initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemic be started with 1000 ml of crystalloids (to achieve a minimum of 30ml/kg of crystalloids in the first 4 to 6 hours). (Grade 1B). Fluid therapy Fluid therapy 1. Crystalloids (1B) 2. Albumin (2C) 3. Avoid HES (1B) 4. Initial fluid challenge in sepsis-induced tissue hypoperfusion (hypotension or elevated lactate) with suspicion of hypovolemia to be a minimum of 30ml/kg of crystalloids(a portion of this may be albumin equivalent). More rapid administration and greater amounts of fluid, may be needed in some patients ( 1B) 8

9 Resuscitation of Sepsis Induced Tissue Hypoperfusion Recommend MAP 65 mm Hg Grade 1C Sepsis Induced Tissue Hypoperfusion Requirement for vasopressors after fluid challenge Vasopressors Lactate 4 mg/dl 28-day Survival Meta-analysis NE versus dopamine De Backer D, et al. N Engl J Med 2010, 362;9: Crit Care Med Mar;40(3):

10 Vasopressors Vasopressors Front line: (1) Norepinephrine (1B). (2) Epinephrine (2B) Vasopressin.03 units/min (UG) In general avoid Dopamine, unless Relative or absolute bradycardia and low risk of tachyarrhythmias (2C) Phenylephrine, unless Norepinephrine associated with serious arrhythmias Cardiac output is known to be high and blood pressure target difficult to achieve As salvage therapy (1C) Protocolized Care Initial Resuscitation of Sepsis Induced Tissue Hypoperfusion Recommend Insertion central venous catheter Recommended goals : Central venous pressure: 8 12 mm Hg Higher with altered ventricular compliance or increased intrathoracic pressure ScvO2 saturation (SVC) 70% Grade 1C Limitation of pressure measurement to predict fluid responsiveness 10

11 Lactate Clearance In patients with elevated lactate levels as a marker of tissue hypoperfusion we suggest targeting resuscitation to normalize lactate as rapidly as possible (grade 2C). Diagnosis Cultures (grade 1C). Imaging studies to confirm source of infection (UG). Therapeutic Strategies in Sepsis Antimicrobial Therapy Effective intravenous antimicrobials within the first hour (1B/1C) Empiric anti-infective therapy of one or more drugs activity against all likely pathogens and penetrate suspected source tissue (1B) Combination therapy if neutropenic, MDRO, resp failure + septic shock (2B) Reassessed daily for potential de-escalation (1B) Procalcitonin or similar biomarkers to assess for discontinuation in those without evidence of infection(2c) Therapeutic Strategies in Sepsis Source Control Diagnosis and intervention in first 12 hours (1C) In severe sepsis Choose the effective intervention associated with the least physiologic insult (UG) Remove vascular access devices if suspected source (UG). Therapeutic Strategies in Sepsis Infection Prevention Selective oral decontamination Selective digestive decontamination Oropharyngeal decontamination Oral chlorhexidine gluconate To reduce the risk of ventilatorassociated pneumonia (2B) Therapeutic Strategies in Sepsis 11

12 Fluid Therapy in Severe Sepsis Crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock (1B) Against the use of hydroxyethyl starches for fluid resuscitation of severe sepsis and septic shock (1B) Albumin in the fluid resuscitation of severe sepsis and septic shock when patients require substantial amounts of crystalloids (2C) Continue as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (UG) Hemodynamic Support Effect on Cardiac Filling Vasopressors Target a mean arterial pressure (MAP) of 65 mm Hg (1C) Norepinephrine as the first choice vasopressor (1B) Add next or to decrease the norepi dose: Epinephrine (2B) Vasopressin 0.03 units/min (UG) Dopamine as an alternative rarely (2C) Phenylephrine is not recommended unless complications from norepi or salvage therapy (1C) Low-dose dopamine should not be used for renal protection (1A) Place an arterial catheter (UG) Hemodynamic Support Crit Care Med Mar;40(3): Meta-analysis NE versus dopamine Inotropic Therapy Dobutamine infusion up to 20 micrograms/kg/min be administered or added to vasopressor (if in use) in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP (1C) Not using a strategy to increase cardiac index to predetermined supranormal levels (1B) During Septic Shock Diastole Systole 10 Days Post Shock Diastole Systole Hemodynamic Support 12

13 Corticosteroids NO Unless hemodynamic stability not achievable in septic shock (2C) No ACTH stimulation test (2B) Blood Products Hgb 7.0 (1B) IV immunoglobulins no (2B) Recombinant Activated Protein C - NO Mechanical Ventilation ARDSNET Sedation and Analgesia Glucose Control Renal Replacement Therapy DVT Prophylaxis Stress Ulcer Prophylaxis Nutrition within 48 hrs (2C), low dose (2B) Setting Goals of Care Adjunctive Therapy Other Supportive Therapy Goals Rivers 2001 RCT CVP >8 MAP > 65 ScVO2 >70% HCT >30 Sebat 2005 Before-After MAP > 70 SaO2 > 92 UOP > 30ml/h SvO2 > 60 CI > 2.5 Nguyen 2007 Thiel 2009 Levy 2011 Complete or Not Before-After Before-After ABX in 4 h Early ABX, Blood CVP > 8, MAP > Appropriate ABX Cultures, 65, ScVO2 > in 4 h, CVP > 8, Appropriate 70%, HCT > 30 MAP > 65, ABX, CVP > 8, Check Lactate ScVO2 > 70% MAP > 65, Steroids SvO2 > 70% A Where Do The Gains Live? B Specific Interventions Fluids, Blood, Pressors ABX, Fluids Pressors ABX, Fluids, Blood, Pressors ABX, Fluids, Pressors, Steroids, Xigris, Other Supportive Care ABX, Fluids, Pressors, Steroids, Xigris, Other Supportive Care System Interventions ED-based Sepsis Team Screening, Education, Shock Team, Protocols Education, Inservices, Protocols Education, Inservices, Order Education, Order Screening, Set, Protocols Sets Lead Time to Diagnosis Delivery of Proper Treatment Absolute Change in Mortality -16% -12% -19% -16% -7% Summary of Trials Lead time to Diagnosis & Treatment 13