Lisa Johnson DrNP, CRNP, ACNP BC Director, AG ACNP Program, DeSales University ACNP with Eastern Pennsylvania Infectious Disease Associates SURVIVING SEPSIS: FROM THE OFFICE TO THE ICU TERMINOLOGY Infection Bacteremia SIRS Sepsis Severe sepsis Septic shock or refractory (septic) shock SIRS Systemic Inflammatory Response Syndrome Occurs as a result of a wide variety of severe clinical insults manifested by 2 or more of the following: Temperature > 38.0c or < 36.0c Heart rate > 90 beats /min RR > 20 breaths per min or PaCO2 < 32mm Hg WBC > 12,000, <4,000 or > 10% immature band forms 1
WHAT IS SEPSIS? The systemic inflammatory response to infection. In association with infection plus SIRS. A broad term that describes the body trying to fight a potentially serious infection. SEVERE SEPSIS defined as sepsis with either hypotension or manifestations of hypoperfusion or organ dysfunction SEPTIC SHOCK severe sepsis with hypotension and hypoperfusion despite adequate fluid resuscitation Sepsis Definition & Diagnostic Criteria ACCP/SCCM Consensus Conference 1992 Sepsis is the Systemic Inflammatory response caused by an infection SIRS Criteria Temperature > 38 C or < 36 C Heart Rate > 90/min Tachypnea > 20/min Infection Toxins Sepsis SIRS Mediators Leukocytes > 12,000 or < 4,000/mm 3 or > 10% immature PMNs Sepsis = SIRS + Infection Severe Sepsis = Sepsis + Organ Dysfxn Septic Shock = Severe Sepsis + Hypotension inspite of fluid resuscitation 2
SEPSIS BARRIERS: Young definition. Limited funding. Sepsis can be confused with other disease states. Not well understood by providers. Sepsis is unpredictable. Symptoms are generic. Treatment is complex. FUNDING DOLLARS University of Florida Health has been awarded a $12 million, five year grant from the National Institutes of Health to create a one of a kind center to help generate treatments and prevention strategies for sepsis. In 2012, UF researchers identified a condition they call persistent inflammation, immunosuppression and catabolism syndrome (PICS), after decades of research involving critically ill patients. Sepsis is Common & Lethal Incidence 750,000 severe sepsis and septic shock/year 215,000 deaths/year #1 cause of non-cardiac ICU death #10 cause of overall death Mortality in Severe Sepsis Deaths per Year Martin GS et al. New Engl J Med. 2003;348:1546-54. SEER Cancer Statistics Review. National Cancer Institute. www.cancer.gov. 2007. HIV/AIDS Surveillance Report. Centers for Disease Control. 2001;11. Incidence & Prevalence: 2006 Chart Book on Cardiovascular and Lung Diseases. NHLBI, NIH. 2006. 3
Severe Sepsis vs Other Major Diseases Cases/100,000 Annual Deaths (000) Severe sepsis is more common than other major diseases and comparable in mortality to AMI. National Center for Health Statistics, 2001. American Cancer Society, 2001. *American Heart Association. 2000. Angus DC et al. Crit Care Med. 2001. Length of Stay Impact SEVERE SEPSIS PROLONGS PATIENT LENGTH OF STAY IN THE ICU AND HOSPITAL BY MORE THAN HALF* All analyses were performed utilizing the 2004 through 2005 MEDPAR Hospital Discharge Databases; sepsis.com Mortality Impact HOSPITAL MORTALITY OF SEVERE SEPSIS PATIENTS WITH AN ICU STAY IS 4 TIMES THAT OF OTHER ICU PATIENTS. Mortality of ICU Patients (%) 28% 7% All analyses were performed utilizing the 2004 through 2005 MEDPAR Hospital Discharge Databases; sepsis.com 4
WE CANDOBETTER DIAGNOSIS AND MANAGEMENT # 1 # 2 # 3 http://www.youtube.com/watch?v=eljthkdk6u4 Until a cure for sepsis is found, early detection is the surest hope for survival. -The Sepsis Alliance SEVERE SEPSIS IS A COMPLEX AND UNPREDICTABLE CLINICAL SYNDROME High mortality rate Heterogeneous patient population Unpredictable disease progression Studies indicate that severe sepsis has inflammatory, prothrombotic, and impaired fibrinolytic components Systemic Inflammation Impaired Fibrinolysis Coagulation Angus DC, et al. Crit Care Med. 2001;29:1303-1310. Wheeler AP, et al. N Engl J Med. 1999;340:207-214. 5
IDENTIFYING ACUTE ORGAN DYSFUNCTION AS A MARKER OF SEVERE SEPSIS Altered Consciousness Reduced GCS Tachypnea PaO 2 /FiO 2 250 Mechanical Ventilation PEEP >7.5 Liver Enzymes >2x ULN Low ph with high lactate (eg, ph, 7.3 & lactate>uln) Tachycardia Systolic BP 90, or MAP 70 despite fluids Vasopressors Urine Output <0.5 ml/kg/hr despite fluids Creatinine >50% from baseline Acute dialysis Platelets <100,000/mm 3 PT/aPTT D-dimer Balk RA. Crit Care Clin. 2000;16:179-192. SEPSIS BUNDLES WITHIN 3 HOURS Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics Administer 30 ml/kg crystalloid for hypotension or lactate 4mmol/L SEPSIS BUNDLES WITHIN 6 HOURS Apply vasopressors to maintain a mean arterial pressure (MAP) 65 mm Hg In the event of persistent arterial hypotension despite volume resuscitation (septic shock) or initial lactate 4 mmol/l (36 mg/dl): Measure central venous pressure (CVP) Measure central venous oxygen saturation Remeasure lactate if initial lactate was elevated 6
INITIAL RESUSCITATION Goals during the first 6 hrs of resuscitation: a) Central venous pressure 8 12 mm Hg b) Mean arterial pressure (MAP) 65 mm Hg c) Urine output 0.5 ml/kg/hr d) Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively (grade 1C). Also, in patients with elevated lactate levels targeting resuscitation to normalize lactate (grade 2C). Reprinted from Dellinger RP, Levy MM, Rhodes A, et al: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013; 41:580 637 DIAGNOSIS Cultures before antimicrobial therapy if no significant delay (> 45 mins.) in the start of antimicrobial(s) (grade 1C). At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy (grade 1C). Imaging studies performed promptly to confirm a potential source of infection. ANTIMICROBIAL THERAPY Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock or severe sepsis (grade 1B) Choose smart initial empiric anti infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis (grade 1B). Reassess daily for potential de escalation (grade 1B). Use of low Procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection (grade 2C). 7
Procalcitonin Healthy individuals: PCT concentrations < 0.05ng/ml Elevated PCT levels indicate bacterial infection accompanied by a systemic inflammatory reaction PCT levels increase with progression of disease from sepsis to severe sepsis and septic shock PCT could potentially impact therapeutic decisions and healthcare costs PCT increase reflects the continuous development from a healthy condition to the most severe states of disease (severe sepsis and septic shock). Interpretation of PCT Values Interpretation of PCT values in critically ill ICU patients SIRS, sepsis, severe sepsis, and septic shock are categorized according to the criteria of the consensus conference of the American College of Chest Physicians/Society of Critical Care Medicine. The reference ranges below are provided for orientation purposes only. PCT Concentration Interpretations Risk or options for further action PCT 0.5 ng/ml PCT>0.5 and 2 ng/ml Systemic infection (sepsis) is not likely. Local bacterial infection is possible. Systemic infection (sepsis) is possible, but other conditions are known to elevate PCT as well. Low risk for progression to severe systemic infection (severe sepsis/ septic shock). Caution: PCT levels below 0.5 ng/ml do not exclude an infection, because localized. Moderate risk for progression to severe systemic infection (severe sepsis/ septic shock). The patient should closely monitored both clinically and by re-assessing PCT within 6-24 hours. PCT> 2ng/mL Systemic infection (sepsis) is likely, unless other causes are known. High risk for progression to severe systemic infection (severe sepsis/ septic shock). PCT 10 ng/ml Important systemic inflammatory response, almost exclusively due to severe bacterial sepsis or septic shock. High likelihood of severe sepsis or septic shock. ANTIMICROBIAL THERAPY Combination empirical therapy for neutropenic patients with severe sepsis (grade 2B). For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia (grade 2B). A combination of beta lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B). 8
ANTIMICROBIAL THERAPY Duration of therapy typically 7 10 days. Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause. Empiric combination to the most appropriate single therapy should be performed as soon as the susceptibility profile is known therapy should not be administered for more than 3 5 days. De escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known (grade 2b). BLOODPRODUCT ADMINISTRATION Red blood cell transfusion occur only when hemoglobin concentration decreases to <7.0 g/dl to target a hemoglobin concentration of 7.0 9.0 g/dl in adults (grade 1B). Not using erythropoietin as a specific treatment of anemia associated with severe sepsis (grade 1B). Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (grade 2D). Not using antithrombin for the treatment of severe sepsis and septic shock (grade 1B). In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding. MECHANICAL VENTILATION OFSEPSIS INDUCED ARDS Target a tidal volume of 6 ml/kg. Plateau pressures be measured in patients with ARDS and initial upper limit goal for plateau pressures in a passively inflated lung be 30 cm H2O (grade 1B). PEEP be applied to avoid alveolar collapse at end expiration (grade 1B). Strategies based on higher rather than lower levels of PEEP be used for patients with sepsis induced moderate or severe ARDS (grade 2C). Recruitment maneuvers be used in sepsis patients with severe refractory hypoxemia (grade 2C). Prone positioning be used in sepsis induced ARDS patients with a Pao2/Fio2 ratio 100 mm Hg in facilities that have experience with such practices (grade 2B). 9
MECHANICAL VENTILATION OFSEPSIS INDUCED ARDS HOB elevated to 30 45 degrees to limit aspiration risk and to prevent the development of ventilator associated pneumonia (grade 1B). Noninvasive mask ventilation (NIV) be used in that minority of sepsis induced ARDS patients in whom the benefits of NIV have been carefully considered and are thought to outweigh the risks (grade 2B). That a weaning protocol be in place and spontaneous breathing trials occur regularly (grade 1A). Against the routine use of the pulmonary artery catheter for patients with sepsis induced ARDS (grade 1A). In the absence of specific indications such as bronchospasm, not using beta 2 agonists for treatment of sepsis induced ARDS (grade 1B). CRITERIA FOR VENT DISCONTINUATION: Arousable Hemodynamically stable (without vasopressor agents) No new potentially serious conditions Low ventilatory and end expiratory pressure requirements Low Fio2 requirements which can be met safely delivered with a face mask or nasal cannula SEDATION, ANALGESIA, AND NEUROMUSCULAR BLOCKADE IN SEPSIS Continuous or intermittent sedation be minimized in mechanically ventilated sepsis patients (grade 1B). Neuromuscular blocking agents (NMBAs) be avoided if possible in the septic patient without ARDS (grade 1C). 10
GLUCOSE CONTROL Commence insulin dosing when 2 consecutive blood glucose levels are >180 mg/dl. (grade 1A). Blood glucose values be monitored every 1 2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter (grade 1C). Glucose levels obtained with point of care testing of capillary blood be interpreted with caution. Renal Replacement Therapy Continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure (grade 2B). Use continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients (grade 2D). Bicarbonate Therapy Not using sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion induced lactic acidemia with ph 7.15 (grade 2B) DVT PROPHYLAXIS Patients with severe sepsis receive daily pharmacoprophylaxis against venous thromboembolism (VTE) (grade 1B). Patients with severe sepsis be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible (grade 2C). Septic patients who have a contraindication for heparin use not receive pharmacoprophylaxis (grade 1B) but receive mechanical prophylactic treatment. 11
STRESS ULCER PROPHYLAXIS Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor be given to patients with severe sepsis/septic shock who have bleeding risk factors (grade 1B). When stress ulcer prophylaxis is used, proton pump inhibitors rather than H2RA (grade 2D). Patients without risk factors do not receive prophylaxis (grade 2B). NUTRITION Administer oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock (grade 2C). Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (eg, up to 500 calories per day), advancing only as tolerated (grade 2B). Use intravenous glucose and enteral nutrition rather than total parenteral nutrition (TPN) alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock (grade 2B). CASE STUDY PHYLLIS 85 year old female who has a history of RAF who underwent a pacemaker insertion. 5 days after pacer placement she presents to her PCP stating chest pain and fatigue. PCP states she is sluggish from the pacemaker placement. No further workup in the office. Temp 99.8 and HR is 100 but in sinus. 12
CASE STUDY PHYLLIS Patient presents 10 days post pacer insertion to the local ER with her family. Family stating she is now confused, not eating or drinking much for past 3 4 days complaining of pain at pacer pocket site. ER physician states she is old and they should consider hospice care. Hospice care initiated. CASE STUDY PHYLLIS Family decides to reach out for second opinion as patient was quite independent just 2 weeks ago. Proceed to second ER 20 hours later. UA noted to be positive for UTI. Patient admitted with UTI related SIRS with leukocytosis and metabolic encephalopathy. So why after 2 days of antibiotics does she not improve but rather get admitted to the ICU with severe sepsis? CASE STUDY PHYLLIS ICU and ID consult Cultures drawn and imaging for abscess Broad spectrum abx Pacer pocket opened MRSA bacteremia and septicemia 6 weeks of IV Vanco 13
1 YEAR LATER PICS is evident Independent to living with family and requiring visiting nurses 3 4 x s per week Confusion most profound chronic element In A fib KNOW THE SIGNS, KNOW SEPSIS THANK YOU! Lisa.Johnson@desales.edu www.desales.edu 14