Surviving Sepsis: A CRASH Course. Justin Jones, PharmD Sanford Medical Center, Fargo Staff Education 2015

Transcription

1 Surviving Sepsis: A CRASH Course Justin Jones, PharmD Sanford Medical Center, Fargo Staff Education 2015

2 Disclosures No financial conflicts of interest

3 Abbreviations ULN Upper limit of normal SVCO2 Central venous oxygen saturation SVO2 Mixed venous oxygen saturation MV Mechanical Ventilation SBO Small bowel obstruction LA Lactic acid T2DM Type 2 diabetes mellitus Px Prophylaxis SUP Stress ulcer prophylaxis TV Tidal volume FiO2 Fraction inspired oxygen SpO2 Oxygen saturation PEEP Positive end-expiratory pressure F/U Follow-up BC Blood culture RASS Richmond agitation-sedation scale

4 Patient Case History of Present Illness JL presents to the ED on 4/28 with low-grade fever (37.8 o C), N/V x 3-4 weeks, decreased appetite and diffuse abdominal pain. She appears weak and in moderate distress. After initial examination, a decision is made to admit her to perform a workup for intra-abdominal infection. While waiting for a bed on the general medical floor she developed hypotension refractory to 3 L of NS, altered mental status, respiratory failure and anuria. She was intubated, rushed to the ICU and placed on MV.

5 Patient Case NKDA Past Medical History Past Surgical History Asthma 6/13/1960 SBO/hernia repair 1/30/2014 T2DM 4/5/1998 Cholecystectomy Unknown HTN 10/30/1993 Depression 7/6/2004 Social History Morbid Obesity 8/20/ cigarettes every other day smoker (stopped in 1980 s) Home Medications Albuterol MDI Metformin 850 mg Fluticasone 110 mcg inhaler Lisinopril 10 mg Mirtazapine 15 mg Promethazine 25 mg 2 puffs every 4-6 hours PRN SOB One tablet by mouth twice daily 2 puffs twice daily One tablet daily One tablet at bedtime Every 6 hours PRN N/V

6 Patient Case VS: BP 87/43; P ; RR 14-33; T 37.8 o C; SpO2: 91% on MV; UOP (24h) 25 ml; Wt kg; Ht 5 2 Labs: Lab Value Unit Na 133 meq/l K 2.9 meq/l Cl 98 meq/l CO 2 12 meq/l BUN 13 Mg/dL scr 1.1 mg/dl Glu 230 mg/dl Ca 6.9 mg/dl Mg 2.5 mg/dl Lab Value Unit Phos 2.5 mg/dl Alb 2.1 g/dl Alk Phos 127 IU/L T. Bili 0.2 mg/dl AST 11 IU/L ALT 7 IU/L Hgb 13.6 g/dl Hct 42 % Plt 261 x10 3 /mm 3 Lab Value Unit WBC 25.5 x103 /mm 3 Bands 15 % ph 7.14 pco2 26 mmhg po2 189 mmhg HCO3 8.9 mmol/l Base def -9.3 mmol/l Lactate 9.8 mmol/l Assessment J.L. is a 74 year-old Caucasian woman admitted with septic shock secondary to suspected intra-abdominal infection.

7 Objectives 1. Quantify the impact of early antibiotic administration on patient outcomes in severe sepsis 2. Identify four clinical endpoints of early goaldirected therapy 3. Recommend therapeutic interventions to achieve these clinical endpoints

8 Definitions Sepsis Severe Sepsis Suspected infection + some of the following Sepsis + tissue hypoperfusion Septic Shock Fever ( >38.3 o C) or hypothermia (<36 o C) Tachycardia Lactate (> > 90 ULN BPM) Severe sepsis + persistent Tachypnea UOP (RR < 0.5 > 20) ml/kg/h x 2 hrs hypotension despite Leukocytosis SCr > 2.0 (WBC mg/dl > 12000/uL) adequate fluid bolus Leukopenia Bilirubin (WBC > 2 < mg/dl 4000/uL) Altered Coagulopathy mental status ( INR > 1.5) Thrombocytopenia Sepsis-induced (PLT hypotension < /uL) Hyperglycemia (in the absence of DM)

9 Early Goal-Directed Therapy Parameter Endpoint (goal) Marker for: Correction: Central Venous Pressure Mean Arterial Pressure 8-12 mmhg Intravascular fluid status >/= 65 mmhg Global organ perfusion Fluid bolus Fluid, pressors Central Venous Oxygen Sat > 70% Cardiac Output Inotropes Urine Output > 0.5 ml/kg/h Renal perfusion Fluids, pressors Within 6 hours

10 Surviving Sepsis Campaign Bundles Within 3 hours Within 6 hours Additional Therapies Measure lactate Obtain blood Cx Administer Abx Fluid Bolus Apply Vasopressors Measure CVP* Measure SCVO 2 * Re-measure Lactate* Corticosteroids Inotropes

11 Surviving Sepsis Campaign Bundles Within 3 hours Measure lactate Obtain blood Cx Administer Abx Fluid Bolus Guideline Recommendations: 1. BROAD SPECTRUM IV antibiotics which will cover ALL SUSPECTED PATHOGENS administered within ONE HOUR of diagnosis and INFUSED as RAPIDLY as allowable (grade 1B/1C) 2. Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial(s) (grade 1C) 1. Empiric combination therapy should not be administered for more than 3 5 days. Deescalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2B)

12 Fraction of Patients Surviving Sepsis Campaign Bundles Within 3 hours Survival Fraction Cumulative effective antimicrobial initiation Measure lactate Obtain blood Cx Administer Abx Fluid Bolus 1 0 ~7% mortality/hr Time from hypotension onset (hrs)

13 Surviving Sepsis Campaign Bundles Common Empiric Regimens for Severe Sepsis GPC + GNR MRSA Pseudomonas Anaerobes Atypicals Ceftriaxone + Azithromycin Ceftriaxone + Azithromycin Ceftriaxone + metronidazole Ceftriaxone + metronidazole Cefepime Cefepine Cefepime pip-tazo pip-tazo pip-tazo pip-tazo pip-tazo + Levofloxacin pip-tazo + Levofloxacin pip-tazo + Levofloxacin pip-tazo + Levofloxacin pip-tazo + Levofloxacin Meropenem + Levofloxacin Meropenem + Levofloxacin Meropenem + Levofloxacin Meropenem + Levofloxacin Meropenem + Levofloxacin * Addition of ESBL activity

14 Surviving Sepsis Campaign Bundles Sequence Matters Carbapenems Cefepime Ceftriaxone Vancomycin Piperacillin/ Tazobactam Levofloxacin Ceftazidime Metronidazole Broadest Narrowest

15 Surviving Sepsis Campaign Bundles Within 3 hours Measure lactate Obtain blood Cx Administer Abx Fluid Bolus Place in therapy Recommended Challenge (dose) (Theoretical) Intravascular equivalent Crystalloids Lactated Ringers FIRST Line Normal Saline FIRST Line Albumin* 25% Unknown Colloids 30 ml/kg 30 ml/kg N/A N/A Albumin* 5% Unknown 25 ml 25 ml 500 ml 100 ml *May administer as rapidly as necessary to improve clinical condition. After volume replacement: 5%: DNE 5-10 ml/minute in patients with hypoproteinemia 25%: DNE 2-3 ml/minute in patients with hypoproteinemia

16 Surviving Sepsis Campaign Bundles Within 3 hours Within 6 hours Additional Therapies Measure lactate Obtain blood Cx Administer Abx Fluid Bolus Apply Vasopressors Measure CVP* Measure SCVO 2 * Re-measure Lactate* Inotropes Corticosteroids

17 Surviving Sepsis Campaign Bundles Within 6 hours Apply Vasopressors Measure CVP* Measure SCVO 2 * Re-measure Lactate* Vasopressor α 1 β 1 β 2 Place in therapy Norepinephrine First line for septic shock Epi mcg/kg/min Epi > 0.05 mcg/kg/min Second line/adjunct for septic shock Phenylephrine Salvage therapy for shock, sedationinduced HOTN Dopamine 3-10 uc/kg/min Dopamine > 10 ug/kg/min Convenience, adjunct for septic shock in low CO states Tips and Tricks: Multiple pressors may be used concomitantly to achieve adequate perfusion All pressor orders should have a titration target (MAP, SBP, etc)

18 Surviving Sepsis Campaign Bundles Within 6 hours Apply Vasopressors Measure CVP* Measure SCVO 2 * Re-measure Lactate* Outcome Illustrative Comparative Risk Assumed Risk Dopamine Corresponding Risk Norepinephrine Effect Mortality 530/ /1000 RR 0.91 ( ) Supraventricular arrhythmias Ventricular arrhythmia 229/ /1000 RR 0.47 ( ) 39/ /1000 RR 0.35 ( ) N Takeaway - Pooled evidence demonstrates greater risk for arrhythmia and mortality with dopamine use vs NE as the initial vasopressor in septic shock.

19 Surviving Sepsis Campaign Bundles Within 3 hours Within 6 hours Additional Therapies Measure lactate Obtain blood Cx Administer Abx Fluid Bolus Apply Vasopressors Measure CVP* Measure SCVO 2 * Re-measure Lactate* Corticosteroids Inotropes

20 Surviving Sepsis Campaign Bundles Additional Therapies Corticosteroids Inotropes Hydrocortisone 50 mg q6h IV push 50 mg q6h x 7 days then stop 50 mg Q6H x 5 days, then 50 mg BID x 3 days, then 50 mg QD x 3 days Wean/discontinue when vasopressors off

21 Surviving Sepsis Campaign Bundles Additional Therapies Corticosteroids Inotropes Are inotropes indicated??? Low central/mixed venous oxygen saturation Signs of hypoperfusion despite adequate MAP Elevated cardiac filling pressures Low cardiac output Inotrope α 1 β 1 β 2 Range Parameters Dobutamine mcg/kg/min Heart rate or MAP

22 Early Goal-Directed Therapy Parameter Endpoint (goal) Marker for: Correction: Central Venous Pressure Mean Arterial Pressure 8-12 mmhg Intravascular fluid status >/= 65 mmhg Global organ perfusion Fluid bolus Fluid, pressors Central Venous Oxygen Sat > 70% Cardiac Output Inotropes Urine Output > 0.5 ml/kg/h Renal perfusion Fluids, pressors Within 6 hours

23 Surviving Sepsis Campaign Bundles Within 3 hours Within 6 hours Additional Therapies Measure lactate Obtain blood Cx Administer Abx Fluid Bolus Apply Vasopressors Measure CVP* Measure SCVO 2 * Re-measure Lactate* Corticosteroids Inotropes

24 Patient Case History of Present Illness JL, 74 yo female, presents to the ED on 4/28 with low-grade fever (37.8 o C), N/V x 3-4 weeks, decreased appetite and diffuse abdominal pain. She appears weak and in moderate distress. After initial examination, a decision is made to admit her to perform a workup for intra-abdominal infection. While waiting for a bed on the general medical floor she developed hypotension refractory to 3 L of NS, altered mental status, respiratory failure and anuria. She was intubated, rushed to the ICU and placed on MV.

25 Patient Case NKDA Past Medical History Past Surgical History Asthma 6/13/1960 SBO/hernia repair 1/30/2014 T2DM 4/5/1998 Cholecystectomy Unknown HTN 10/30/1993 Depression 7/6/2004 Social History Morbid Obesity 8/20/ cigarettes every other day smoker (stopped in 1980 s) Home Medications Albuterol MDI Metformin 850 mg Fluticasone 110 mcg inhaler Lisinopril 10 mg Mirtazapine 15 mg Promethazine 25 mg 2 puffs every 4-6 hours PRN SOB One tablet by mouth twice daily 2 puffs twice daily One tablet daily One tablet at bedtime Every 6 hours PRN N/V

26 Patient Case VS: BP 87/43; P ; RR 14-33; T 37.8 o C; SpO2: 91% on MV; UOP (24h) 25 ml; Wt kg; Ht 5 2 Labs: Lab Value Unit Na 133 meq/l K 2.9 meq/l Cl 98 meq/l CO 2 12 meq/l BUN 13 Mg/dL scr 1.1 mg/dl Glu 230 mg/dl Ca 6.9 mg/dl Mg 2.5 mg/dl Lab Value Unit Phos 2.5 mg/dl Alb 2.1 g/dl Alk Phos 127 IU/L T. Bili 0.2 mg/dl AST 11 IU/L ALT 7 IU/L Hgb 13.6 g/dl Hct 42 % Plt 261 x10 3 /mm 3 Lab Value Unit WBC 25.5 x103 /mm 3 Bands 15 % ph 7.14 pco2 26 mmhg po2 189 mmhg HCO3 8.9 mmol/l Base def -9.3 mmol/l Lactate 9.8 mmol/l Assessment J.L. is a 74 year-old Caucasian woman admitted with septic shock secondary to suspected intra-abdominal infection.

27 Patient Case Question #1: What interventions and/or therapies should be accomplished within the first 6 hours of all septic shock or severe sepsis patients? Parameter Goal Management Strategy Central Venous Pressure (CVP) Mean Arterial Pressure (MAP) 8-12 mmhg Crystalloids >65 mmhg Crystalloids, Pressors UOP >0.5 ml/kg/hr Crystalloids, Pressors SVCO 2 /SVO 2 >70%/65% As above, inotropes, PRBs

28 Patient Case Within 3 Hours Treatment Bundles Measure Lactate Obtain BCs Fluid Bolus Antibiotics Within 6 Hours Vasopressors Measure CVP Measure SVCO 2 To resolution Fluids to target CVP Pressors to target MAP Deescalate Antibiotics as appropriate Dellinger 2012

29 Patient Case Question #2: What type of fluid should be recommended to appropriately resuscitate patients with septic shock/severe sepsis Agent Volume Rate Goal Crystalloid (NS,LR) Colloid (Albumin) ml/kg 1000 ml bolus CVP 8-12 mmhg ml bolus CVP 8-12 mmhg DO NOT USE: Hetastarch (Renal dysfunction) D5W (Does not stay intravascular)

30 Patient Case Question #3: When should vasopressor agents be considered in the treatment of hypotension related to sepsis, and which agents are appropriate? Receptor Norepinephrine* Epinephrine ( mcg/kg/min) Dopamine Alpha Variable ++++ Beta Variable + Beta Variable Dopamine Add on option: Vasopressin 0.03 units/min Phenylephrine

31 Surviving Sepsis: A CRASH Course Justin Jones, PharmD Sanford Medical Center, Fargo Staff Education 2015

32 References and further reading Delinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock. Crit Care Med 2013;41: Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6): The SAFE Study Investigators. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit N Engl J Med 2004; 350: Annane D, Véronique Sébille, Claire Charpentier et al. Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock. JAMA. 2002;288(7): Sprung CL, et al. "Hydrocortisone therapy for patients with septic shock". New England Journal of Medicine (2):