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JESSA ZIEKENHUIS MEDISCH PROTOCOL 06.07.01.20.02 Severe sepsis Datum opmaak: 07/11/2013 Pagina’s protocol: 4 Datum laatste herziening: 01/2016 Pagina’s bijlagen: 50 Sleutelwoorden: Sepsis, hemodynamische bewaking, shock, septische shock Toepassingsgebied/doelgroep: Urgentieartsen en anesthesisten _______________________________________________________________________________________ 1. Doel Sepsis treft jaarlijks 19 miljoen mensen wereldwijd (=onderschatting) en omvat tot 25% van de opnames op IZ. Sepsis is een medische urgentie met een hoge en toenemende (+1,5%/jaar) incidentie door de vergrijzing, meer co-morbiditeit, HIV, meer immuun-gecompromitteerde patiënten, toename beademde patiënten, hogere overleving na heelkunde en meer invasieve diagnostiek en therapie met devices. (Brun-Buisson and Matot) Gelijktijdig gaat sepsis gepaard met een zeer hoge kost (€7,6 biljoen/j) en een hoge mortaliteit van 28 tot 50% en septische shock tot 80%. Oorzaken voor deze hoge mortaliteit zijn te laat met starten van antibiotica, ongepast antibioticagebruik, een te te trage en incorrecte vochttoediening, vaak ernstige co-morbiditeit en meer acuut orgaanfalen. (Intensive Care National Audit Research Centre, 2005) Onderstaande richtlijnen en bijbehorende care bundle (bijlage 1) helpen een correcte sepsis-diagnose te stellen en een adequate therapie op te starten. 2. Indicaties Volgende stadia volgen elkaar op: infectie – SIRS (systemic inflammatory response syndrome) – sepsis – severe sepsis – septische shock 1. Infectie: a. WBC aanwezig in lichaamsvocht dat normaal steriel is OF b. Positieve kweek (urine, bloed, sputum, …) OF c. Geperforeerd hol orgaan OF d. Op RX thorax pneumonie met klinisch productie van purulent sputum 2. SIRS = systemic inflammatory response syndrome: minstens 2 van de volgende: a. Temp >38.2°C of <36°C b. Hartfrequentie >90/min (cave: ptn onder beta-blockers zijn vaak niet tachycard) c. Ademhalingsfrequentie >20/min of PaCO2 <32mmHg d. WBC >12000 cellen/mm² of <4000 cellen/mm² Severe sepsis care bundle 06.07.01.20.02 3. Sepsis = SIRS tgv infectie 4. Severe sepsis = sepsis met >1 acuut falen van een orgaan 5. Septische shock = severe sepsis met blijvende MAP <65 ondanks 30ml/kg crystalloïden IV 3. Contra-indicaties nvt 4. Benodigdheden MetaVision: plan zorg –sets – sepsis: sepsisformulier als hulpmiddel om te bepalen of patiënt voldoet aan criteria voor sepsis of severe sepsis 5. Werkwijze - Parameters en klinisch onderzoek o o o - Centraal zenuwstelsel: bewustzijnsverandering, (perifere neuropathie) Klinisch nazicht van perfusie: Bloeddruk: syst BD <90mmHg of mean BD = MAP <65mmHg Capillaire refill >3sec Verminderde doorbloeding van de huid (gemarbreerd, “bloemetjes”), Koude of juist warme extremiteiten Aanwezigheid paralytische ileus Onderzoeken: o Bloedafname met klinische en biochemische tekens van orgaanfalen o o - Nierfunctie: creatinine >2mg% of stijging creatinine > 0.5mg% - Urine-output Stollingstesten: INR >1.5, aPTT >60sec, bloedplaatjes < 100.000/µL Bilirubine >4mg% Arterieel bloedgas Lactaat >2, pH<7.33 BE Bicarbonaat<22 Centraal veneuze zuurstofsaturatie, mixed veneuze pCO2, weefsel pCO2, oxygenatie skeletspieren Behandeling: betrek vroegtijdig de intensivist van wacht a. Vochtbolus: cristalloïden (NaCl 0.9% of Plasmalyte of Ringer lactaat) i. max 30ml/kg binnen 1 uur zo MAP <65mmHg b. Antibiotica snel opstarten (idealiter binnen het uur na aankomst) i. Eerst afname hemoculturen!!! ii. Indien mogelijk ook andere culturen ifv kliniek iii. Welke antibioticum? Kies op Zorgnet: Antibioticumrichtlijnen - empirische therapie – volwassenen - sepsis bij niet-neutropene volwassenen OF sepsis bij neutropene volwassenen. 29-4-2017 9:56:03 Pagina 2 van 54 Severe sepsis care bundle 06.07.01.20.02 c. Monitoring: i. Arteriële lijn o Bloeddruk opvolgen Streefwaarden: mean BD >65mmHg of systolische BD >90mmHg (ifv kliniek: hoger bij patiënten die gekend zijn met art. hypertensie of lager bij jonge patiënten die gekend zijn met normale of lage drukken) o Lactaat serieël lactaatclearance >10%/uur tot normalisatie <2 ii. Saturatie iii. Pols, ademhalingsfrequentie iv. Blaassonde o Opvolgen van de diurese Streefwaarde urine-output >0.5ml/kg/h o Opvolgen vochtbalans v. DVC o CVD Streefwaarde: CVD 8-12mmHg (bij beademde ptn: gecorrigeerd voor PEEP = van gemeten CVD-waarde PEEP aftrekken) d. Indien onvoldoende effect van vochtbolus: opstarten vasopressie IV (noradrenaline 0.1gamma) en verder titreren minstens om de 10 minuten tot MPA >65mmHg e. Verdere vochttoediening ifv CVD, urine-output en bloeddruk f. Centraal veneuze zuurstofsaturatie (ScvO2) = streefwaarde > 70% i. < 70% EN hemoglobingehalte < 7g% = transfusie ii. < 70% EN hemoglobingehalte > 7g% = dobutamine IV (5 gamma 15 gamma) g. Bij onvoldoende respons: indicatie voor invasieve monitoring (picco of swan-ganzmonitoring: op Intensieve zorgen) 6. Complicaties 7. Aandachtspunten (Concrete formulering van de aanbevelingen in het protocol) 8. Observatie 9. Sleutelinterventies/indicatoren (Indicatoren zijn meetbare elementen van zorg voor de continue bewaking en verbetering van de klinische en organisatorische kwaliteit van de zorg in het ziekenhuis) 10. Verwijzingen (Andere bestaande, gerelateerde protocols) 29-4-2017 9:56:03 Pagina 3 van 54 Severe sepsis care bundle 06.07.01.20.02 11. Referenties (Wetgeving,…) 12. Bijlagen _______________________________________________________________________________ Geldigheidsduur: De geldigheidsduur van een protocol bedraagt maximaal 3 jaar, tenzij anders bepaald. Deze termijn vangt aan op de datum van de laatste herziening door de inhoudsdeskundige. We streven er naar dat van al de protocols die gelden binnen het Jessa Ziekenhuis de laatste versie beschikbaar is op JessaZorgnet. Een uitgeprinte versie blijft slechts 24u geldig (zie datum onderaan). Herziening voorzien voor: 01/2019 Opgesteld en goedgekeurd door: Dr. Hubert De Baetselier Dr Ph . Jamaer Riet Minnekeer Spoedarts Dr. Barbara Vantroyen Medisch diensthoofd Spoedgevallen Dinesthoofd ITE Verpleegkundige IZ Datum: Datum: Datum: Datum: Ter kennisname: Dr. Patrik Peene Louis Verpoorten Dr. Jos Vandekerkhof Els Nelissen Medisch manager Zorgmanager Medisch manager Zorgmanager Datum: Datum: Datum: Datum: Goedgekeurd door: Els Volders Dr. Dirk Ramaekers Ludo Meyers Dienst kwaliteit Medisch Directeur Directeur patiëntenzorg Datum: Datum: Datum: 29-4-2017 9:56:03 Pagina 4 van 54 Bijlage 1: Care bundle severe sepsis 1. Background 2. Definitions 3. Pathogenesis of sepsis 4. Inclusion – criteria. 5. Goal: early recognition of patients in severe sepsis and providing prompt goal directed therapy. Sepsis Clinical Pathway: a. Definition Care Bundle (CB) b. Protocol Sepsis CB c. What is the evidence and support for the Sepsis Care Bundle? d. Two bundles i. The 3 hours Resuscitationbundle 1. Treatment algorithms used by clinicians and nurses to recognize, treat and ensure quality of care for severe sepsis, beginning in the emergency department a. Monitor for Lactate clearance b. Blood cultures before antibiotics c. Broad spectrum antibiotics d. Fluids: 30ml/kg crystalloids for MAP < 65mmHg or lactate >4mmol/L ii. 6 hr septic shock bundle 1. Vasopressors : goal MAP > 65mmHg 2. If hypotension persists despite fluids (=septic shock) or initial lactate > 4mmol/L: a. Measurement of CVP: goal 8-12mmHg b. Measurement of ScvO2: goal > 70% 3. Lactate measurement iii. The 24 hrs Sepsis Management Bundle — part of the previous version of the Severe Sepsis Bundles — has been eliminated, and Other Supportive Therapies have been added Screening and Registration – Orders in Metavision : i. Orders including laboratories, hemodynamic monitoring, antibiotics, fluid resuscitation, vasopressors, inotropes, transfusion, corticosteroids. APACHE II score will be assessed. ii. APACHE II, SOFA en SAPS II data for prospective store. f. Checklist : Are the 5 Quality Indicators completed? i. Checked weekly a posteriori Evidence based medicine and references about the important therapeutic issues: a. Lactate and lactate clearance b. SvO2 and ScvO2 User’s Guide c. Appropriate Empiric Antibiotics d. Fluids : which? How much? When to stop? e. 6. 7. Risk Stratification : who is the most severe patient? 8. Goals a. Quality indicators (QI) i. Definitions of evidence-based quality indicators ii. These indicators are modelled after ongoing efforts by the Surviving Sepsis Campaign, Institute for Healthcare Improvement and JCAHO. They serve the basis for the individual components in the Bundle. iii. Monitoring the compliance b. Prospective Data measurement c. Education and feedback d. Achieving uniformity in the process of care: Continuous Quality Improvement Program. 9. Implementation a. Baseline (2011: retrospective data) b. Education; transmural. c. Operational (trial) d. 5 QI cfr 2007;35(4):1 10. Quality Measurement Tool a. Metavision : input of data to help the clinicians and nurses in early recognizing of these patients b. A list of patients with severe sepsis or septic shock is obtained from Metavision and reviewed each week. Each patient’s chart is carefully reviewed to determine the completion of each component of the Bundle. c. Quality is improved as the numerator for each component increases over time. 11. Addendum *Fulbrook, P and Mooney, S. Care bundles in Critical Care: a practical approach to evidence based practice. Nursing in Critical Care 2003;8(6). Severe sepsis care bundle 06.07.01.20.02 The theory behind care bundles is that when several evidence-based interventions/guidelines are grouped together and applied in a single ‘protocol’, it will improve patient outcome* 1. Background Why Focus on SEPSIS? Sepsis is a complex syndrome with its wide spectrum of severity. - Sepsis is a leading cause of mortality; at 30-50%, the mortality rate associated with sepsis is markedly high (SSC 2008). Severe sepsis ( 1)is one of the most common causes of death in Critical Care Units. Casefatality rate depends on the setting and severity of disease (sepsis, severe sepsis and septic shock resp 30%, 50% up to 80%). (2). Husak et al reported a mortality for patients with sepsis of 20.9% and for patients with severe sepsis 45.2%. (3). - Some patients with sepsis were more likely to die than others: older age, presence of co-morbidities (Charlson-index). Severe sepsis and hospital-acquired sepsis were associated with higher odds of dying. - Severe sepsis and septic shock account for approximately 571000 annual US Emergency Department visits and 215000 deaths. ( 4-6). Most recently, the Sepsis Occurrence in Acutely ill Patients (SOAP) study in Europe observed an overall hospital mortality of 36%. Data from the Surviving Sepsis Campaign (SSC) showed a mortality of 34.8% among 15022 patients. There are few disease processes with such a high mortality. (7,8) Figure 1: mortality of sepsis. - The incidence of sepsis is high. Issrah Jawad et al (2) reported in their study a population sepsis incidence ranged from 22 to 240/100 000; of severe sepsis from 13 to 300/100 000 and of septic shock 11/100 000. This incidence is growing over the past years (+1.5%/year) as also the hospitalization rate. This doubled from 2000 through 2008, increasing from 11.6 to 24.0 per 10,000 population in the USA. Reasons for these increases may include an aging population with more chronic illnesses, greater use of invasive procedures, immunosuppressive drugs, chemotherapy and transplantation; and increasing microbial resistance to antibiotics. (8,9) 29-4-2017 9:56:03 Pagina 6 van 54 Severe sepsis care bundle - 06.07.01.20.02 Sepsis is a complex syndrome that is difficult to define. Because the signs and symptoms are highly variable, there is no “typical presentation”. That’s why it is difficult to recognize and diagnose. Early recognition and implementation of evidence-based bundles of care have been shown to improve outcomes for patients with sepsis (8). Sepsis is categorized as a ‘time critical illness’. The sepsis management should mirror acute myocardial infarction, stroke and trauma in order to realize the best outcomes.(6). In 2002 was the Surviving Sepsis Campaign developed as a collaboration between the European Society of Critical Care Medicine, the international Sepsis Forum and the Society of Critical Care Medicine. Care bundles were created in collaboration with the Institute for Healthcare Improvement (IHI). These bundles reduce the mortality. Compliance with the 6-hour sepsis bundle is very important: non-compliance was associated with a more than twofold increase in hospital mortality. (3). The most current guidelines for management of severe sepsis and septic shock written by the Surviving Sepsis Campaign (SSC) date from 2012.(10). To have a continuous increase in outcome for these patients, it is important to have a continuous quality improvement process (CQI). An educational program for the clinicians and nurses is crucial. Implementing an educational program based on the SSC guidelines reduces mortality in patients with severe sepsis and septic shock. A CQI process provides feedback to the clinician to make sure all of those goals are being completed.(2). This CQI is very important because there is evidence that the majority of patients with sepsis did not receive a sepsis diagnosis in the emergency department, only 26.4% ! (Ref 11). References 1. 2. 3. 4. 5. 6. 7. 8. 9. Vincent JL, Martinez EO, Silva E. Evolving concepts in sepsis definitions. Crit Care Clin 2009;25:665-75 Issrah Jawad, Ivana Luksic, Snorri Bjorn Rafnsson. Assessing avaliable information on the burden of sepsis: global estimates of incience, prevalence and mortality. J of global health 2012;2(1):010404 National Intstitue of General Medical Sciences. National Institutes of Health. Sepsis fact sheet 2009 Strehlow MC, Emond SD, Shapiro NI, et al. National study of ermergency department visits for sepsis, 1992to 2001. Ann Emerg Med 2006;48(3):326-331 Dellinger RP, Carlet JM, Masur H et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-72. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77. Vincent JL, Sakr Y, Sprung CL et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006;34:344-53. Levy MM, Dellinger RP, Townsend SR et al. The SSC: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010;38:1-8. Angus DC, Linde-Zwirble WT, Lidicker J et al. Epdemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated costs of care. Crit Car Med 2001;29(7):1303-10 29-4-2017 9:56:03 Pagina 7 van 54 Severe sepsis care bundle 06.07.01.20.02 10. R.Phillip Dellinger, Mitchell M.Levy, Andrew Rhodes, MB, et al. SSC : international guidelines for management of SS and SS: 2012. Crit Care Med 2013;41(2):580-637. 11. Husak, Marcuzze A, Herring J et al. National analysis of sepsis hospitalizations and factors contributing to sepsis in hospital mortality in Canada. Health care Quaterly 2010;13:35-41 29-4-2017 9:56:03 Pagina 8 van 54 Severe sepsis care bundle 06.07.01.20.02 2. Definitions (ref 4,5,6) These definitions are an adaptation of the definitions used by literature (4,5,6). Infection: A microbial phenomenon characterized by an inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms. An infection can be recognized as: 1. 2. 3. 4. Presence of white cells in a normally sterile body fluid OR Positive culture (urine, blood, sputum) OR Perforated viscous OR Radiographic evidence of pneumonia in association with the production of purulent sputum. Signs of inflammation: A systemic response to inflammation (SIRS) and is manifested by two or more of the following: 1. 2. 3. 4. Temp > 38.2°C or < 36°C Heart rate > 90/min Respiratory rate > 20 breaths/min or PaCO2 < 32mmHg WBC > 12000 cells/mm² , < 4000 cells/mm² or >10% immature bands Sepsis: The systemic response to an infection and can be recognnized by the presence of suspected or confirmed infection AND the systemic inflammatory response. Severe sepsis : Sepsis associated with more than one acute organ dysfunction or hypoperfusion. Hypoperfusion: not limited to: lactate > 2mmol/L, oliguria, or an acute alteration in mental status, slow capillary refill (mottled skin). Clinical AND biochemical indices of the adequacy of tissue/organ perfusion: MAP Urine output Mentation Capillary refill Skin perfusion/mottling Cold extremities Blood lactate Arterial pH, BE and bicarbonate ScvO2 Mixed venous pCO2 Tissue pCO2 Skeletal mucle tissue oxygenation Organ dysfunction can be defined as : respiratory failure, acute renal failure (RIFLE), acute liver failure, coagulopathy or trombopenia; signs of myocardial dysfunction. Laboratories that will suggest organ dysfunction include: 1. paO2(mmHg)/FiO2 < 300 - ARDS 29-4-2017 9:56:03 Pagina 9 van 54 Severe sepsis care bundle 2. Creatinine > 2mg% OR creatinine increase > 0.5mg% 3. INR > 1.5 4. aPTT > 60 s 5. platelets < 100 000/µl 6. total bilirubin > 4mg% 06.07.01.20.02 Septic shock = sepsis with: - hypotension, despite adequate fluid resuscitation of maximum 30 ml/kg crystalloid, along with - the presence of perfusion abnormalities that may include, - but are not limited to lactic acidosis, oliguria, or an actue alteration in mental status. - Patients who are on inotropic or vasopressor agents may not be hypotensive at the time that perfusion abnormalities are measured. Cryptic shock: sepsis with severe lactic acidosis (lactate >4mmol/L) irrespective of blood pressure, and is considered to be equivalent to traditional septic shock ! Refractory septic shock : MAP > 65mmHg needing Levophed (NA) in a dose of more than 0.25µg/kg/min despite fluid resuscitation. Fluid resuscitation with an initial maximum of 30ml/kg crystalloids. Hypotension: SAP < 90mmHg or MAP < 65mmHg or a reduction in SAP of > 40mmHg from baseline; in the absence of other causes for hypotension. Figure 2: from infection to septic shock. The transition from sepsis tot septic shock occurs most often during the first 24 hours of hospitalization, with increasing morbidity and mortality. 3. Pathogenesis of sepsis We do not fully understand the pathogenesis of sepsis and there is no specific treatment. Therefore, it is important to recognize it early, so that supportive measures may be implemented as soon as possible. 29-4-2017 9:56:03 Pagina 10 van 54 Severe sepsis care bundle 06.07.01.20.02 Infection+SIRS = sepsis SIRS can be caused by other pathologies: trauma, pancreatitis, … Cfr Figure 3 Figure 3 The cause of the organ failure in severe sepsis is unknown, but is resembles the multiple organ dysfunction syncrome (MODS) seen in patients who survive serious traumatic injury. (1) There is an interaction between microbial agents and host factors. The immune system initially generates a pro-inflammatory state (by TNF alfa, IL-1 en 6) in response to molecular patterns that are derived from damaged host cells. In most patients, this pro-inflammatory response is self-limited, even in the absence of effective treatment. But, in patients who develop sepsis, the response is exaggerated (or hyper-inflammatory) and leads to a compensatory downregulation of the immune system. Bone (2) helped to stress the importance of a ‘compensatory anti-inflammatory response syndrome’, which he called CARS (mediated by IL-4 en 10) , especially in patients who developed severe sepsis. (Figure 4 and 5). A major risk factor appears to be some degree of pre-existing immune dysfunction, for instance, elderly and immunosuppressed patients who have a higher mortality rate. A genetic predisposition may also be involved. (3). Fig. Adapted from Figure 4. 29-4-2017 9:56:03 Pagina 11 van 54 Severe sepsis care bundle 06.07.01.20.02 Crit Rev Clin Lab Sci, 2013;50(1):23-36. Biomarkers of sepsis. James D.Faix. In overwhelming sepsis there is a dysregulation in the complex balance between pro-inflammatory mediators or the SIRS, and the anti-inflammatory mediators, or the CARS, resulting in processes that directly damage endothelial, cardiovascular, hemodynamic and coagulation mechanisms. Figure 5. Pro-inflammatory cytokines: TNF, IL-1bèta and IL-6 are cytokines that mediate the initial response. Inflammatory mediator release becomes a self-stimulating process and release of other such mediators, including IL-2,8 en 10, and nitric oxide (NO), further increases cytokine levels. This leads to continued activation of polymorphonuclear leukocytes, macrophages and lymphocytes. They causing fever and other systemic symptoms. IL-6 has received the most attention. It’s measurable and appears to be prognostic, not diagnostic. Elevated levels of IL-6 in septic patients are associated with an increase in mortality. (4). PAMP: from invading organisms: endotoxin is an excellent example of a pathogen-associated molecular pattern. Macrophages have receptors (TLR) that recognize different types of PAMPS. 29-4-2017 9:56:03 Pagina 12 van 54 Severe sepsis care bundle 06.07.01.20.02 DAMP: from tissue injury: damage-associated molecular patterns that are derived from damaged host cells Sepsis begins with eiter infection or tissue injury. Figure 6. Hemodynamic: There is an impairment in oxygen delivery and utilization at the tissue level. This pathogenic mechanism leads to global tissue hypoxemia. Oxygen delivery: CO * oxygen content = (HR * stroke volume) * (Hb oxygen saturation * Hb *1.34) + pO2 * 0.003. Oxygen consumption: The tissue extracts a percentage of the delivered oxygen; the remaining oxygenation returns to the venous circulation: ScvO2. Development of SHOCK = inadequate tissue perfusion with a inbalance between DO2 and VO2 (consumption of oxygen). Hypoxemia and oxygen depth occur. Lactate is a consequence of this anaerobe metabolism. It’s important to measure lactate ! Pathophysiology of the organ dysfunctions: - tissue hypoxemia. direct cytotoxicity: endotoxin, TNF-alpha, and NO may cause damage to mitochondrial electron transport. Apoptosis Immunosuppression: an imbalance between SIRS and CARS Coagulopathy; overt DIC is rare; caused by deficiencies of proteins, like protein C, antithrombin III and TF inhibitors. 29-4-2017 9:56:03 Pagina 13 van 54 Severe sepsis care bundle 06.07.01.20.02 The organ dysfunctions 1. Circulatory derangement: = dysfunction in autoregulation of circulation (distributive shock). NO plays a central role in the vasodilatation of septic shock. Cardiac output is often increased to maintain blood pressure. a. Microcirculation is the key target organ for injury in sepsis: increased endothelial permeability leads to tissue edema involving protein-rich fluid. b. Mitochondrial depression causes regional tissue distress and regional hypoxia therefore persists. There is a disturbance in oxygen delivery and consumption. The figure shows all the elements which have an influence and therapeutic use. 2. Septic shock and SIRS are characterized by reversible myocardial depression, which can prove resistant to catecholamine and fluid administration. 29-4-2017 9:56:03 Pagina 14 van 54 Severe sepsis care bundle 06.07.01.20.02 Ref: Circulation 2007;116:793-802. M.W.Merx et al. Sepsis and the heart. 3. - Pulmonary dysfunction: endothelial injury in the pulmonary vasculature leads to disturbed capillary blood flow resulting in interstitial and alveolar edema. a. Acute lung injury: up to 40% of patients with severe sepsis b. ARDS: acute respiratory distress syndrome: severe injury to the alveolo-capillary unit. ARDS 2005: Delphi consensus 2010: Berlin definition: o Mild: PaO2/FiO2 <300 o Moderate: < 200 o Severe: < 100 o The term “ALI” has been removed o Timing: respiratory insufficiency within 1 week 29-4-2017 9:56:03 Pagina 15 van 54 Severe sepsis care bundle - - 06.07.01.20.02 o PaO2/FiO2 is influenced by ventilation settings Protective ventilation protocol: o TV < 6ml/kg of predicted body weight o Delta P : Pplat – P PEEP: if > 16: worse outcome ! Respiratory infection is the most common cause or trigger of ARDS Using EVLWI and PVPI at bedside to define ARDS (5) 4. Gastrointestinal dysfunction: overgrowth of bacteria in the upper GI tract may be aspirated into the lungs. There is translocation of bacteria and endotoxins into the systemic circulation. a. Septic shock can cause paralytic ileus. b. Be carefull with the use of narcotics and muscle relaxants. 5. Liver dysfunction: shock liver can be manifested by elevations in liver enzymes and bilirubin, coagulation defects and failure to excrete toxins such as ammonia, wich lead to worsening encephalopathy. 6. Renal dysfunction: acute tubular necrosis, resulting from systemic hypotension, direct renal vasoconstriction, release of cytokines. 7. Central nervous system dysfunction: encephalopathy and peripheral neuropathy, due to systemic hypotension. Causative microorganisms: - Gram + and Gram – bacteria - anaerobic pathogens are becoming less important as a cause of sepsis. - Fungal infections are the cause of sepsis in 0.8-10.2% of patients with sepsis, and their incidence appears to be increasing. Site of infection: - respiratory tract infection and urinary tract infection are the most frequent causes, followed by - abdominal and - soft tissue infections. - The highest mortality is due to respiratory tract infections (higher severity of illness). Figure: pathophysiology: phases and monitoring. 6 hrs FIRST HIT MONITORING Infection + SIRS MAP Microcirculatory dysfunction: Lactate - Vasodilatation - Capillary leak Diuresis ScvO2 Fluid balance Distributive shock = EBB PHASE 48-72 hrs SECOND HIT EVLWI MOF: ALI, intra-abdominal hypertension, acute renal failure, liverfailure THIRD HIT Vocht = biomarker for critical illness FLUID = TOXIC ! 1.SHOCK REVERSAL = FLOW PHASE: 29-4-2017 9:56:03 Pagina 16 van 54 Severe sepsis care bundle 06.07.01.20.02 - diuresis - less edema - EVLWI : wheening 2.IRREVERSIBLE SHOCK Pro > anti-inflammatory cytokines: more MOF Edema: cerebral, peripheral, gastro-intestinal, renal, pulmonary: ARDS FLUID REMOVAL ! PAL: PEEP+albumin and hemodialysis or furosemide Ref: Malbrain et al. References 1. Choileain NN, Redmond HP. The immunological consequences of injury. Surgeon 2006;4:23-31 2. 2 Bone RC, Grodzin CJ, Balk RA. Sepsis: a new hypothesis for pathogenensis of the disease process. Chest 1997;112:235-43 3. Chung LP, Waterer GW. Genetic predisposition to respiratory infectio and sepsis. Crit Rev Clin Lab Sci 2011;48:250-68 4. Petilla V, Hynninen M, Takkunen O et al. Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis. Intensive Care Med 2002;28:1220-5 5. Kushimoto et al. Crit Care 2013;17:418. A bedside definition of ARDS. 4. Inclusion - Criteria Patients who will benefit from Early Goal Directed Therapy (EGDT): 1. 2. 3. Two or more signs of inflammation (SIRS) AND Suspected OR confirmed infection AND Systolic blood pressure < 90mmHg after a 30ml/kg fluid bolus OR lactate > 4mmol/L Exclusion criteria: age < 18 years, pregnancy, stroke, acute coronary syndrome, acute pulmonary edema, status astmaticus, active GI hemorrhage, seizure, drug overdose, burn, trauma, emergent surgery, uncured cancer with do-not-resuscitate order, do-not-resuscitate orderII 5. Sepsis Clinical Pathway a. Definition of “Care Bundles” A bundle is not a collection of guidelines, but a method to implement the guidelines. Bundles are a group of “therapies/elements of a therapy” built around the best evidence-based guidelines, which, when implemented TOGETHER, produce greater benefit in terms of outcome than the individual therapeutic interventions. The bundles reduce the now existing variation in therapy of sepsis patients. b. What is the evidence and support? There are many studies proving the benefit of sepsis care bundles and protocols on the outcome of these patients. (1). An integrated sepsis protocol appears also to be cost effective.(2). MUST protocol is a prospectively studied integrated sepsis protocol that showed a relative risk reduction for mortality reduction of 31%. This is consistent with the expected benefit of adoption of the SSC bundles and with several other studies. (3, 4, 5)I refer to table 1. 29-4-2017 9:56:03 Pagina 17 van 54 Severe sepsis care bundle 06.07.01.20.02 Gao et al (6) carried out the first study to demonstrate the impact of compliance to the bundles on hospital mortality in patients with severe sepsis. Noncompliance with the 6-hour bundle was associated with a more than twofold increase in hospital mortality. The NNT to save one life was determined to be approximately 4! The compliance to the sepsis guidelines is low. An educational program and effort to promote bundles of care for sepsis is associated with improved guideline compliance and lower hospital mortality (7) However there is a gap between evidence (guidelines) and practice. Rubenfeld categorized the possible reasons into three major groups: knowledge barriers, attitude barriers and behavioral barriers. A clinical pathway or protocol with an educational program will overcome knowledge barriers and probably have some impact on attitude and behavioral barriers. These changes need time of course. (8, 9). Table 1 Study design and bundle care treatment and mortality end points. Adapted from Barochia et al. (10). Study Rivers et al(4) Trzeciak et al(11) Kortgen et al Shapiro et al Micek et al Nguyen et al (12) (3) (13) (14) Jones et al (15) El Solh et al (16) Year 2001 2006 2006 2006 2006 20007 2007 2008 Design Prospect Beforeafter Beforeafter Beforeafter Beforeafter Before- Beforeafter Before- Randomized after after Setting ED ED/ICU ICU ED/ICU ED/ICU ED/ICU ED ED/ICU Initial treatment time 0-6h Time in ED 0-6h 0-6h Time in ED Time in ED 0-6h 0-6h Antibiotics No No Yes Yes Yes Yes Yes Yes EGDT Yes Yes Yes Yes Yes Yes Yes Yes Cortico’s No No Yes Yes Yes Yes No Yes Mortality end point In hospital In hospital 28 days 28 days 28 days In hospital In hospital 28 days Protocol R/ References: 1. 2. 3. 4. 5. 6. 7. 8. Levy MM, Pronovost PJ, Dellinger RP, et al. Sepsis change bundles: Converting guidelines into meaningful change in behavior and clinical outcome. Crit Care Med 2004;32:S595-7 Daniel Talmor, Dan Greenberg, Michael D.Howell, et al. The costs and cost-effectiveness of an integrated sepsis treatment protocol. Crit Care Med 2008;36(4):1168-1174 Shapiro NI, Howell MD, Talmor D et al. Implemetation and outcomes of the Multiple Urgent Sepsis Therapies (MUST)protocol. Crit Care Med 2006;34(4):1025-32 Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe spsis and septic shock. N Engl J Med 2001;345:1368-77. Lin SM, Huang CD, Lin HC et al. A modified goas-directed protocol improves clinical outcomes in tensive care unit patients with septic shock: A randomized controlled trial. Shock 2006;26:551-7 Gao F, Melody T, Daniels DF, et al. The impact of compliance with 6-hour and 24-hour sepsis bundles on hospital mortality in patients with severe sepsis: A prospective observational study. Crit Care Med 2005;9:764-70 Ricard Ferrer, Antonia Artigas, Mitchell M.Levy, et al. Improvement in Process of Care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 2008;299(19):2294-2303 Rubenfeld GD. Translating clinical research into clinical practice in the intensive care unit: the central role of respiratory care. Respir Care 2004;49(7):837-843 29-4-2017 9:56:03 Pagina 18 van 54 Severe sepsis care bundle 9. 10. 11. 12. 13. 14. 15. 16. 06.07.01.20.02 Carlbom DJ, Rubenfeld GD. BGarriers to implementing protocol-based sepsis resucitation in the emergency department: results of a national survey. Crit Care Med 2007;35(11):2525-32) Barochia AV, CuiX, Vitber D, et al. Bundled care for septic shock: An analysis of clinical trials. Crit Care Med 2010;38:668-78 Treciak S, Dellinger RP, Abate NL, et al. Tranlating research to clinical practice: A 1-year experience with implementing EGDT for septic shock in the ED. Chest 2006;129:225-32. Kortgen A, Niederprum P, Bauer M. Implementation of an evidence-based “standard operating procedure” and oucome in septic shock. Crit Care Med 2006;34:943-9. Micek ST, Roubinian N, Heuring T, et al. Before-after sutdy of a standardized hospital order set for the management of severe sepsis and septic shock is assoicated with decreased mortality. Crit Care Med 2006;34:2707-13. Nguyen HB, Corbett SW, Steele R, et al . Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007;35:1105-12. Jones AE, Focht A, Horton JM, et al. Prospective external validation of the clinical effectiveness of an emergency department-base early goal-directed therapy protocol for severe sepsis and septic shock. Chest 2007;132:425-32. El Solh AA, Akinnusi ME, Alswalha LN, et al. Outocme of septic shock in older adults after implementation of the sepsis “bundle”. J Am Geriatr Soc 2008;56:272-8. c. Protocol Sepsis CB (prospective observational study in patients with sepsis) i. Early recognition with the help of METAVISION ii. Starting diagnostic tests and therapy as soon as possible 1. Metavision: SET sepsis 2. Early therapy: the 3 and 6 hr resuscitation bundle with EGDT d. Two bundles 1. 3 hr Resuscitationbundle 3 hr - RESUSCITATIONBUNDLE ASAP after clinical investigation GOALS PRIOR TO ICU ADMISSION: 1. Measurement lactate 2. Blood cultures before antibiotics 3. Broad spectrum antibiotics 4. Fluids: 30ml/kg crystalloids for MAP < 65mmHg or lactate >4mmol/L 1.Monitoring for LACTATE and lactate CLEARANCE 29-4-2017 9:56:03 Pagina 19 van 54 Severe sepsis care bundle 06.07.01.20.02 Lactate concentration is a complex result of an anaerobic production, via the Na-K ATPase channel, and a decrease in lactate utilization. High lactate levels have been found to be of prognostic value in septic patients: lactate using for risk stratification (informative for severity of illness). The global prevalence of severe sepsis patients initially presenting with either hypotension with lactate > 4mmol/L or lactate >4mmol/L alone, is reported as 16.6% and 5.4% respectively. (1) The mortality of patients with only a high lactate (>4mmol/L) is 30%! During severe sepsis and septic shock blood lactate concentration and lactate clearance are both predictive for 28-day mortality. (2) Mortality is high in septic patients with both hypotension and lactate ≥4 mmol/L (46.1%).(3) Goal of resuscitation in the first 6 hours: lactate clearance > 10%. (4,5) If ScvO2 is not available, lactate normalization may be a feasible option in the patient with severe sepsis-induced tissue hypoperfusion. (6,7) However, lactate clearance indicates the success of resuscitation in improving tissue perfusion and repayment of the oxygen debt. But the decrease in lactate depends on the rate of production and metabolism in the muscle, kidney and liver. Normal lactate with persistent microcirculatory blood flow alterations can still suggest an unpaid oxygen debt! (8). Achieving a decrease greater than or equal to 20% in lactate levels per 2 hours of the first 8 hrs in addition to ScvO2 target achievement, resulted in a 9.6% absolute reduction in mortality. (9) It’s important that results of lactate measurement can be known within minutes of testing where possible. Measurement of the standard base excess (SBE) is important. It can reflect a great amount of disturbances secondary to sepsis and its resuscitation.(10) Low values are associated with higher mortality in the ICU. The evolutive behaviour of SBE has not been clinically studied following EGDT (Cfr PiCCO trial). (11). Limitations A number of studies have suggested that elevated lactate levels may result from cellular metabolic failure in sepsis rather than from global hypoperfusion. Elevated lactate levels can also result from decreased clearance by the liver; associated with diabetic ketoacidosis, hyperventilation, other reasons of shock, … References 1. Levy MM, Dellinger RP, Townsend SR, et al. SSC: Results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med 2010;38:367-74 2. Philippe Marty, Antoine Roquilly, Fabrice Vallée, et al. Lactate clearance for death prediction in severe sepsis or septic hsock patients during the first 24 hours in ICU: an observational study. Annals of Intensive Care 2013;3:3 3. Focht A, Jones AE, Lowe TJ. Early goal-directed therapy: improving mortality and morbidity of sepsis in the emergency department. Jt Comm J Qual Patient Saf. 2009;35:186-91. 4. Nguyen HB, Rivers EP, Knoblich BP et al. Early lactate clearance is associated with impoved outcome in severe sepsis and septic shock. Crit Care Med 2004;32(8):1637-42 5. Tian HH, Han SS, Lv DJ et al. The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia. Zhongguo Wei Zhong Bing Ji Jiu Xue 2012;24(1):42-5 29-4-2017 9:56:03 Pagina 20 van 54 Severe sepsis care bundle 06.07.01.20.02 6. Jones AE, Shapiro NI, Treciak S et al. Emergency Medicine Shock Research Network investigators: lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: A randomized clinical trial. JAMA 2010;303:739-46 7. Arnold RC, Shapiro NI, Jones AE et al. Multi center study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2009;32(1):35-9 8. Sakr Y, Dubois MF, De Backer D et al. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care med 2004;33:113-122. 9. Jansen TC, Van Mommel J, Schoonderbeek FJ, et al. LACTATE study group: early lactate-guided therapy in intensive care unit patients: A multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010;182:752-61 10. Singer M et al. Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation. Lancet 2004;364:545-8. 11. Marcelo Park, et al. Evolutive standard base excess and serum lactate level in severe sepsis and septic shock patients resuscitated with early goal-directed therapy: still outcome markers? Clinics 2006;61(1):47-52. 2. BLOOD CULTURES PRIOR TO ANTIBIOTIC ADMINISTRATION 30-50% of patients representing with a clinical picture of severer sepsis have positive blood cultures. Blood cultures should therefore be taken from all patients presenting with clinical signs of sepsis if such cultures do not cause significant delay (>45 minutes). Failure to collect blood cultures prior to AB administration may affect the growth of bacteria and therefore the further selection of appropriate AB (IHI 2005). Indications Fever, chills, hypothermia, leukocytosis, left shift of neutrophils, neutropenia, and the development of otherwise unexplained organ dysfunction (e.g., renal failure or signs of hemodynamic compromise) are specific indications for obtaining blood for culture. Blood cultures should be taken as soon as possible after the onset of fever or chills. To optimize identification of causative organisms, we recommend obtaining at least two sets of blood cultures (both aerobic and anaerobic bottles), with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (<48 hours) inserted. ( 1 , 2) The volume of blood drawn with the culture tube should be equal to or more than 10 ml. (3) Cultures of other sites should also be obtained before AB if doing so does not cause significant delay in AB administration. References 1. Blot F, Schmidt E, Nitenberg G, et al. Earlier positivity of central venous versus perpheral blood cultures is highly predictive of catheter-related sepsis. J of Clinical Microbiology. 1998;36:105-9 2. Weinstein MP, Reller LB, Murphy JR, et al. The clinical significante of positieve blood cultures: A comprehensive analysis of 500 episodes of bactgeriam and fungemia in adults. Loboratory and epidemiologic observations. Rev Infect Dis 1983;5:35-53. 3. Mermel LA, Maki DG. Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood. Ann Intern Med 1993;119:270-2. 3.EARLY ADMINISTRATION OF ANTIBIOTICS (AB) - The administration of AB: o appropriate 29-4-2017 9:56:03 Pagina 21 van 54 Severe sepsis care bundle o within the first hour of recognition of severe sepsis and septic shock o should be the goal of therapy! (1) 06.07.01.20.02 - Every hour of delay in the administration of appropriate antibiotic therapy has been associated with a cumulative increase in the risk of death.(2,3) - Definition of appropriate antibiotic (AB) use depends on: Ref: systematic review : inappropriate antibiotic use and outcome. (not yet published) These are the elements of appropriate AB therapy: - Timing of starting AB (>24 <72u) Indication of AB correct? Choice – druginteractions – allergy – other contra-indications – according Sanford or other guidelines? Combination therapy in indicated patients Route Adequate dosage (according infection severity – renal function – age); monitoring drug level Frequention of administration Duration of therapy Intervaltiming Clinical affect? One study : including de-escalation therapie (broadspectrum to smaller spectrum; from IV to po). The choice of empirical antimicrobial therapy depends om complex issues related to: The patient’s history Drug intolerances Recent receipt of AB (< 3 months) Underlying disease – comorbidities The clinical syndrome Susceptibility patterns of pathogens in the community and hospital Prevalence of drug-resistant organisms is significant Previously have been documented to colonize or infect the patient It’s important to make a difference between empiric and definitive AB therapy and prophylactic AB use prior major surgery. Inappropriate AB use in patients with sepsis is an enormous problem (up to 50% of the patients !) - Antimicrobial resistance is a major cause of inappropriate AB. Antimicrobial stewardship, meaning a multidisciplinary cooperation with an infectiologe and microbiologist, can help reducing inappropriate AB because of the knowledge about microbial resistance. Recommendations : ° The initial selection should be broad to cover all likely pathogens. 29-4-2017 9:56:03 Pagina 22 van 54 Severe sepsis care bundle 06.07.01.20.02 Failure to initiate appropriate therapy correlates with increased morbidity and mortality in patients with severe sepsis or septic shock. (4) Collaboration with antimicrobial stewardship programs is encouraged to ensure appropriate choices. Recently used anti-infective agents should generally be avoided. ° The importance of dose adjustment. Patients with sepsis often have abnormal renal or hepatic function or may have abnormally high volumes of distribution due to aggressive fluid resuscitation. ° Empiric combination therapy for neutropenic patients with severe sepsis and for patients with pathogens such as Acinetobacter and Pseudomonas. (5,6). - Not for longer than 3 to 5 days. - De-escalation to the most appropriate single-agent therapy should be performed as soon as the susceptibility profile is known. ° Daily reassessment for potential de-escalation to prevent the development of resistance, to reduce toxicity and to reduce costs. - Duration of therapy typically 7-10days - Longer courses in patients with clinical need, undrainable foci of infection, bacteremia with S.Aureus; neutropenia. ° Viral origin has to taken in the different diagnosis. Active CMV viremia is common (15-35%) in critically ill patients. In patients with severe primary or generalized varicella-zoster virus infection and disseminated herpes simplex infections, acyclovir can be highly effective when initiated early in the course of infection. ° Risk factors for candidemia: immunosuppressed or neutropenic state, prior AB therapy, or colonization in multiple sites. Mannan and anti-mannan antibody assays when invasive candidiasis is in the differential diagnosis of infection. ° Infection control also means control of the potential source of infection and sepsis. Intervention be undertaken for source control within the first 12 hours after the diagnosis is made. References: 1. 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;34:1589-96. 2. Kumar A. Early antimicrobial therapy in severe sepsis and septic shock. Curr Infect Dis Resp 2010;12:336-44 3. Kumar A et . Initiation of appropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009;136:1237-48. 4. Kumar cfr supra, Ref. Ibrahim EH, Sherman G, Ward S, et al. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000;118:146-55 5. Kumar A, Safdar N, Kethireddy S, et al. A survival benefit of combination AB therapy for serious infections associated with sepsis and septic shock is contingent only on the risk of death: A metaAnalytic/meta-regression study. Crit Care Med 2010;38:1651-64 6. Kumar et al. Early combination therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med 2010;38:1773-85. 4. FLUIDS : crystalloids 29-4-2017 9:56:03 Pagina 23 van 54 Severe sepsis care bundle 06.07.01.20.02 = this recommendation is an expert opinion As soon as sepsis-induced tissue hypoperfusion is recognised and should not be delayed pending Critical Care admission ! The aim is to ensure an initial fluid challenge of 30ml/kg of crystalloid - Goals: CVD 8-12 mmHg (<15mmHg if ventilated) ScvO2 > 70% MAP > 65mmHg OR SAP > 90mmHg (individualised !: younger vs old people, hypertension in history!) Urine output > 0.5ml/kg/hr Lactate < 2mmol/L NOT WAITING FOR PLACEMENT OF CENTRAL ACCESS !! Type of fluid: - - - Crystalloids: which? o Large volumes of normal saline can precipitate hyperchloraemic metabolic acidosis (1) o It is not been convincingly demonstrated in vivo that hyperchloraemic acidosis is harmful. o Balanced solutions: Hartmanns or Ringer’s lactate solution probably be safer. NO colloids ! This recommendation of the SSC 2012 is based on the results of the VISEP, Crystmas, 6S and CHEST trial (increased mortality and higher need for renal replacement therapy in the HES group!) o The question, whether or not HES may be harmfulm when it is limited to immediate haemodynamic stabilisation, cannot be answered yet. o Critical care 2013;17: R166 Albumin: when patients require substantial amounts of crystalloids ! The SAFE study indicated that albumin administration is safe and equally as effective as 0.9% saline ! Rate of infusion: 1000 ml / 20 minutes (more rapid administration may be needed in some patients!) Safety limits i.e. observe for pulmonary oedema; heart failure patients ! Evidence: This recommendation of resuscitation was associated with a 15.9% absolute reduction in 28-day mortality rate (Rivers study 2001). 29-4-2017 9:56:03 Pagina 24 van 54 Severe sepsis care bundle 06.07.01.20.02 “the real challenge” When to stop fluid resuscitation? When the goals are achieved or clinical signs of fluid overload. PiCCO trial: stop fluids when EVLWI > 10 !!! = safety !!! - EVLWI = extra vascular lung water index = safety parameter to point out WHEN to stop fluids ! Measured by PiCCO - Increased EVLWI is the central pathophysiologic element of ARDS (is not yet included in the most recent Berlin definition of ARDS) - Is associated with severity of lung injury; response to therapy and clinical outcome. - Associated with positive fluid balance - = a good independent predictor of mortality with an odds ratio of 8.8. - BUT there is no good consensus for definition of the normal or cut off values and which index the most correct one is. (actual or predicted body weight?) - In morbid obese patient is the EVLW lower - Predicts the progression to ARDS in an early phase (2.6 days before the diagnose of ALI according the AECC criteria) - = use as risk stratification GEDVI : reflecting central bloodvolume = preload : a guiding parameter for fluid therapy Fluid responsiveness - Passive leg raising test for all patients (no consensus): you have to measure the cardiac output ! 29-4-2017 9:56:03 Pagina 25 van 54 Severe sepsis care bundle 06.07.01.20.02 - Sensitivity = 89.4% and specificity = 91.4% - Ventilated, sedated patients in a sinus rhythm: dynamic tests based on monitoring changes in stroke volume, pulse pressure variation. (2,3) o PiCCO monitoring: SVV and PPV > 10%: fluid responsive patient. o SVV and PPV allow the prediction of fluid responsiveness and thus the determination of the actual position on an individual Frank-Starling curve” or in other words the assessment of an individual preload reserve. (4) cfr infra. DO NOT USE CVP !! - CVP has a low predictive value in estimating fluid responsiveness during mechanical ventilation ! (5) - Using the CVP to direct fluid resuscitation of patients with elevated intra-abdominal or intrathoracic pressure may place the patient at risk for under-resuscitation with organ dysfunction and increased mortality. (6) - Even a CVP of less than 5mmHg in patients on the ventilator had a positive predictive value of 47% !!! Frank Starling curve 29-4-2017 9:56:03 Pagina 26 van 54 Severe sepsis care bundle 06.07.01.20.02 Once the ventricle is functioning on the steep part of the FS curve, there is a preload reserve. Volume expansion induces a significant increase in stroke volume. The pulse pressure (PPV) and stroke volume (SVV) variations are marked and the passive leg raising (PLR) are positive. By contrast, once the ventricle is operating near the flat part of the curve, there is no preload reserve and fluid infusion has little effect on the stroke volume. The PPV is a reliable predictor of fluid responsiveness only when the tidal volume is at least 8ml/kg. The patient is full sedated and the rhythm is sinusal. - * with inspiration : pleural pressure decreases and transmural pressure increases: left shifting of the FStarling curve: increase in CO - * with mechanical ventilation and PEEP: shifting to the right of the F-S curve: decrease in CO. Mechanical insufflation decreases preload and increases afterload of the right ventricle. This leads to a decrease in RV stroke volume, which is at a minimum at the end of the inspiratory period. The LV preload is reduced and that may induce a decrease in LV stroke volume, which is at its minimum during the expiratory period. It’ s very important to know that your patient is fluid responsive!! - Fluid challenge is used very frequently in the ICU: however there is not much hemodynamic response. More than 50% of the fluid challenges are even harmfull! - Fluid overload leads to worse outcome !! Risk of fluid overload Pulmonary edema, cerebral edema, abdominal compartment syndrome with renal failure, right ventricular overload, … Keep a negative fluid balance ! (literature: on day 3-7) A positive fluidbalance increases mortality ! The impact of EGDT (Rivers) is due to the first hours !!! If the goals are reached: NO fluids to maintain ! 29-4-2017 9:56:03 Pagina 27 van 54 Severe sepsis care bundle 06.07.01.20.02 Repeating clinical evaluation ! References 1. Kellum JA. Saline-induced hyperchloremic metabolic acidosis. Crit Care Med 2002;30:259-61. 2. Marik PE, Monnet X, Teboul JL: hemodynamic parameters to guide fluid therapy. Ann Intensive Care 2011;1:1. 3. Marik PE, Cavallazzi R, Vasu T et al. Dynmic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: A systematic review of the literature. Crit Care Med 2009;37:2642-47 4. Hofer et al. Acta Anaesthesiol Taiwan 2011;49(2):59-65. Monitoring fluid responsiveness. 5. Bendjelid K, Romand JA. Fluid responsiveness in mechanically ventilated patients: a review of indices used in itnesive care. Intensive Care Med 2003;29:352-60) 6. Cheatham ML. Ti is time to pay attention – now more than ever! Crit Care Med 2007;35:1629-30 6hr – SEPTIC SHOCK BUNDLE A. Vasopressor When ? if the MAP stays below threshold of 65mmHg despite fluid resuscitation of 30ml/kg crystalloid. Goal: maintaining perfusion Which? Norepinephrine (Levophed) is the first choice vasopressor. - Increases MAP due to its vasoconstrictive effects - Little change in heart rate - More potent than dopamine - More effective at reversing hypotension Epinephrine when an additional agent is needed to maintain adequate blood pressure. NOT Dopamine: more tachycardia, more arrythmogenic and influences the endocrine response via the hypothalamic pituitary axis and have immunosuppressive effects. Low-dose dopamine should not be used for renal protection. The titration of norepinephrine to as low as MAP of 65 mm Hg has been shown to preserve tissue perfusion. In addition, pre-existing comorbidities should be considered as to most appropriate MAP target. For example, a MAP of 65 mm Hg might be too low in a patient with severe uncontrolled hypertension, and in a young previously normotensive patient, a lower MAP might be adequate. 29-4-2017 9:56:03 Pagina 28 van 54 Severe sepsis care bundle 06.07.01.20.02 Additional end points such as blood pressure with assessment of regional and global perfusion, such as blood lactate concentrations and urine output, is important. Other vasopressors? The Surviving Sepsis Campaign suggests that epinephrine, phenylephrine, or vasopressin should not be administered as the initial vasopressor in septic shock (Grade 2C). Vasopressin 0.03 units/minute may be subsequently added to norepinephrine with anticipation of an effect equivalent to norepinephrine alone. The Surviving Sepsis Campaign suggests that epinephrine be the first chosen alternative agent in septic shock that is poorly responsive to norepinephrine (Grade 2B). B. SEPTIC SHOCK OR LACTATE > 4 mmol/L: CVP AND ScvO2 MONITORING within 2 hours A. Maintain adequate CVP Goal: CVP 8-12 mmHg if ventilation: 12-15mmHg (1) In circumstances of increased abdominal pressure we have to take this in account ! (2) CVP is not for use in patients with preexisting clinically significant pulmonary artery hypertension Fluid responsiveness: ° awake patients: passive leg raising test You have to measure CO ! ° ventilated and full sedated, sinus rhythm: o SVV and PPV (PiCCO measurement) o Cut off value : 13% Limitation of CVP: Central venous pressure is a controversial measurement in critical care management (Michard and Teboul cfr Figure). CVP measures pressure and not volume and depends on both fluid and compliance of the heart. As the compliance of the heart varies, so will pressure measurement but not volume measurement (Shapiro et al). This is a fundamental issue of the value of PiCCO guiding. Marik et al (3) reviewed 24 studies examining the accuracy of CVP measurement. CVP is a very poor measurement of blood volume or of volume responsiveness. 29-4-2017 9:56:03 Pagina 29 van 54 Severe sepsis care bundle 06.07.01.20.02 Boyed et al (4) found that the CVP measurements in the early phase of resuscitation correlated modestly with fluid balance at 12 hours, but had no significant correlation on days 1-4. What is the normal or ideal CVP ? We don’t know. Figure: Michard and Teboul: review of 12 studies. Some studies showed CVP(=static parameter) discriminate between responders and nonresponders, but other studies did not! Dynamic parameters (PPV, SSV) predicted fluid responsiveness with high positive and negative predictive values. - A higher CVP and positive fluid balance are independently associated with mortality in septic shock ! (5) References 1. Bendjelid K, Romand JA: fluid responsiveness in mechanically ventilated patients: A review of indices used in intensive care. Intensive Care Med 2003;29:352-60 2. Malbrain ML, Deeren D, De Potter Tj. Intra-abdominal hypertensio in the critically ill: it is time to pay attention. Curr Opin Crit Care 2005;11:156-71 3. Marik PE, Monnet X, Teboul JL: Hemodynamic paramters to guide fluid therapy. Ann Intensive Care 2011;1:1 4. Boyd JH, Forbes J, Nakada T et al. Fluid resuscitaion in septic shokc: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011;39(2):259-65 5. Varpula M, Tallgren M, Saukkonene K, et al. Hemodynamic variables related to outcome in septic shock. Intensive Care Med 2005;31(8):1066-71 B. Maintain adequate ScvO2 Definition: = a measurement of the amount of oxygen remaining in the venous circulation after oxygen for cellular metabolism has been extracted systemically. Upon reaching the microcirculation, about 20-30% of the oxygen is removed and oxygen saturation is 70-80% in blood that is returning to the heart through the venous system. ScvO2 is an approximation of the SvO2 (if an PAC is in situ). Literature has shown that there is a good correlation between the two. 29-4-2017 9:56:03 Pagina 30 van 54 Severe sepsis care bundle 06.07.01.20.02 The difference between these two parameters is influenced by the sampling site of central venous blood, the presence of left-to-right shunts, oxygen extraction in the renal and the splanchnic beds, redistribution of blood flow through the upper and lower body and myocardial VO2. The reliability of ScvO2 is also dependent on the position of the tip of the catheter. DO2 = CO X ((1.34 * Hb * SaO2) + (0.0031 * PaO2)) DO2 results in 100% oxygen delivered to the tissue. The tissue will consume (VO2) with an oxygen extraction ratio of 25-35%. The remainder in the venous side is 65-75%. 29-4-2017 9:56:03 Pagina 31 van 54 Severe sepsis care bundle 29-4-2017 9:56:03 Pagina 32 van 54 06.07.01.20.02 Severe sepsis care bundle 06.07.01.20.02 Low ScvO2 due to low DO2 and / or high VO2: Low DO2: hypoxia (low SaO2), anemia, haemorrhage (low Hb), cardiac dysfunction, hypovolemia, shock, arrhythmia (low CO). High VO2: exercise, pain, hyperthermia, shivering, seizure. High ScvO2 due to high DO2 and / or low VO2: High DO2: hyperoxia (high FiO2), erythrocytosis (high Hb), hyperdynamic state (high CO). Low VO2: hypothermia, anesthesia, pharmacologic paralysis, arterio-venous shunting, mitochondria defect, terminal shock. How to measure? Via a CVC (distal port) with the tip placed at the atriocaval junction. ScvO2 or SvO2? SvO2 is not readily measurable without a Swan-Ganz catheter: indicates the level of venous oxygenation throughout the body. It generally reflects venous oxygenation from the head and upper extremities. ScvO2 measurements will read higher: 5-6% but correlate well with SvO2.(1) Goal: ScvO2 > 70% During the first 6 hours of resuscitation of severe sepsis or septic shock, if ScvO2 of 70% is not achieved with fluid challenges to a CVP pressure of 8-12mmHg, then transfuse packed red blood cells to achieve a Hb >7g%. If the Hb is above 7g%, then administer a dobutamine infusion (start 4µg/kg/min with a maximum of 15µg/kg/min) to achieve this goal. The transfusion threshold of 7g/dl contrasts with early goal-directed resuscitation protocols that use a target hematocrite of 30% in patients with low ScvO2. (Rivers 2001). An initial hyperoxia (defined as an ScvO2>90%) was associates with a higher mortality rate compared with a ScvO2 between 70 and 90%. 29-4-2017 9:56:03 Pagina 33 van 54 Severe sepsis care bundle 06.07.01.20.02 Dobutamine has to administered in the presence of: myocardial dysfunction (echocardiography, clinical suggested by elevated cardiac filling pressures and low cardiac output) or ongoing signs of hypoperfusion, despite adequate intravascular volume and MAP. Resuscitation guided by ScvO2 has a greater benefit on survival than guided by lactate clearance. (2) TIP During the first 6 hours of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as one part of a treatment protocol (Grade 1C): o Central venous pressure (CVP) 8‒12 mm Hg o Mean arterial pressure (MAP) ≥65 mm Hg o Urine output ≥0.5 mL.kg-1 .hr-1 o Central venous (superior vena cava) ≥70 percent References 1. Intensive Care Med 2004;30:1572-8. Reinhart K et al. Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. 2. Acad Emerg Med 2012;19(3):252-58. MA Puskarich et al. Prognostic value and agreement of achieving lactate clearance or central venous oxygen saturation goals during early sepsis resuscitation. SUPPORTIVE THERAPIES ON THE ICU 1. Blood Product Administration 2. Maintain Adequate Glycemic Control 3. Mechanical Ventilation of Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS) 4. Sedation, Analgesia, and Neuromuscular Blockade 5. Deep Vein Thrombosis (DVT) and Peptic Ulcer Disease (PUD) Prophylaxis 6. Nutrition 7. Setting Goals of Care 1. BLOOD PRODUCTS administration Goal: a hemoglobin concentration of 7.0 to 9.0 g/dL in adults The 2012 Surviving Sepsis Campaign guidelines suggest not using: Erythropoietin as a specific treatment of anemia associated with severe sepsis (Grade 1B) Fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (Grade 2D) Administer Platelets Prophylactically 29-4-2017 9:56:03 Pagina 34 van 54 Severe sepsis care bundle 06.07.01.20.02 *In patients with severe sepsis, administer platelets prophylactically when counts are <10,000/mm3 (10 x 109/L) in the absence of apparent bleeding. *The 2012 Surviving Sepsis Campaign guidelines suggest prophylactic platelet transfusion when counts are <20,000/mm3 (20 x 109/L) if the patient has a significant risk of bleeding. *Higher platelet counts of ≥50,000/mm3 (50 x 109/L) are advised for active bleeding, surgery, or invasive procedures. 2. Glucose control < 180mg%: protocol starting when two consecutive blood glucose levels are more than 180mg%. a. Prevent hypoglycemia b. Monitor the levels every 1-2 hrs until stable and then every 4 hrs. c. Ref. 5 NICE-SUGAR Study: Intensive versus convetnional glucose controle in critically ill patients. N Engl J Med 2009;360:1283-1297). There is insufficient information from randomized controlled trials to determine the optimal target range of blood glucose in the severely septic patient. The NICE-SUGAR trial is the largest most compelling study to date on glucose control in ICU patients given its inclusion of multiple ICUs and hospitals, and a more general patient population. Based on the results of this trial, we recommend against intravenous insulin therapy titrated to keep blood glucose in the normal range (80‒110 mg/dL) in patients with severe sepsis. It is clear that attempts to normalize blood glucose with IV insulin during critical illness results in higher rates of hypoglycemia. Until additional information is available, teams seeking to implement glucose control should consider initiating insulin therapy when blood glucose levels exceed 180 mg/dL with a goal blood glucose approximating 150 mg/dL as was observed in the beneficial arm of the NICESUGAR trial. 3. Mechanical ventilation of sepsis induced ARDS a. Plateau pressures : upper limit goal < 30cmH20 b. Tidal Volume of 6ml/kg predicted body weight c. Max inspiratoire plateaudruk < 30cmH2O d. PEEP to avoid alveolar collapse at end expiration e. Prone postioning can be used with a PaO2/FiO2 < 100mmHg f. Head of the bed elevated to 30-45 degrees to limit aspiration risk and to prevent VAP g. Weening protocol: indications: i. Arousable ii. Hemdynamically stable without vasopressor agents iii. No new serious conditions iv. Low ventilatory requirements v. Low FiO2 vi. Spontaneous breathing trial succesful h. 4. Sedation, Analgesia, and Neuromuscular Blockade a. 5. ‘no safe upper limit for CO2, but pH levels > 7.25 has been recommended. Daily review and interruption of sedation infusion Deep Vein Thrombosis (DVT) and Peptic Ulcer Disease (PUD) Prophylaxis 29-4-2017 9:56:03 Pagina 35 van 54 Severe sepsis care bundle 6. 7. 06.07.01.20.02 Nutrition a. 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 b. Avoid mandatory full caloric feeding in the first week, but rather provide low-dose feeding (e.g., up to 500 kcal per day), advancing only as tolerated. c. 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. d. Use nutrition with no specific immunomodulating supplementation in patients with severe sepsis. e. Early enteral nutrition has theoretical advantages in the integrity of gut mucosa and prevention of bacterial translocation and organ dysfunction, but the risk of ischemia, mainly in hemodynamically unstable patients, is also a concern. (Use of Recombinant Activated protein C (aPC)) a. Approved for use in adult patients in 2001 follwing the PROWESS trial (6) b. Ineffective in less severely ill patients with severe sepsis as well as in children: 2008 SSC recommendation was downgraded: for patients with an APACHE II > 25 or MODS c. Not in low-risk patients, APACHE II < 20 d. PROWESS shock trial (released in late 2011): no benefit of rAPC. The drug was withdrawn from the market. (7) 8. °Low dose corticosteroids in patients with resistant septic shock. ( Ref 1 study of Greet van den Berghe!) °The SSC guidelines update of 2012 suggest intravenous hydrocortisone alone at a dose of 200mg per day. °Use of the ACTH test is not recommended. °In ‘low risk’ patients: hydrocortisone failed to show any benefit on outcome (2,3). a. = hypotension for more than two hours with the support of norepinephrine. b. Hydrocortisone 100mg 3/day IV (nieuwe richtlijnen?) (Ref 4 Marik 2008 = consensus; Annane 2002 en Sprung 2008) c. In patients with acute adrenal insufficiencie (prim or secundair) d. Chronic steroid use e. COPD patients References 1. study of Greet van den Berghe 2013 2. Patel GP, Balk RA: systemic steroids in severe sepsis and septic shock. Am J Resp Crit Care Med 2012;185:133-9 3. Sprung CL, Annane D, Keh D, et al. CORTICUS study group: hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111-24 4. Marik 2008 = consensus; Annane 2002 en Sprung 2008 5. NICE-SUGAR Study: Intensive versus convetnional glucose controle in critically ill patients. N Engl J Med 2009;360:1283-1297 29-4-2017 9:56:03 Pagina 36 van 54 Severe sepsis care bundle 06.07.01.20.02 6. Bernard GR, Vincent JL, Laterre PF, et al. Recombinant human protein C Worldwide evaluation in Severe Sepsis (PROWESS) Study group: efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699-709. 7. Dellinger, Levy, Rhodes et al. Surviving sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41(2):580 e. A. Screening and Registration - Metavision : Laboratory data obtained within ONE HOUR after physician evaluation: 1. baseline WBC with formule, metabolic panel, PT/aPTT, D-dimer, troponin, Brain Natriuretic peptide, thyroid function, lipid profile, liver set, renal function and elektrolytes, albumin, platelets, hemoglobine, … capillary leak incidence: CRP(mg%)/albumin(g/L)*100 Lactate Urine analysis Blood culture Urine culture Sputum culture if possible ScvO2 on admission ScvO2 Lactate 2.Baseline and every two hours: B. Hemodynamic monitoring within 2 hours after physician evaluation: 1. 2. 3. 4. C. Cardiac monitoring and ECG Pulse oximetry CVP monitoring with intermittent ScvO2 measurements Intra-arterial catheterization APACHE II data, SAPS data. f. Checklist The data in Metavision will be controlled each week. The compliance of each bundle element will be documented in excel files. ResuscitationBundle 1 Blood cultures 2 Antibiotics 3 Lactate clearance Variables Min 2 blood cultures prior to AB < 1 hr: broad spectrum, combination therapy; cfr guidelines < 2 hr? 4 A. Fluids If SAP<90mmHg and/or lactate >4mmol/L: Crystalloids 1000ml over 15-30 min < 6 hr? B. Norepinefrine 29-4-2017 9:56:03 Pagina 37 van 54 If SAP<90mmHg and/or lactate >4mmol/L AND Y N Severe sepsis care bundle 06.07.01.20.02 persistant SAP<90 despite 2 l crystalloid: Vasopressors < 6 hr? 5 Venous saturation ManagementBundle Taken from DVC < 6 hr? Variables 1 Protective ventilation < 24 uur? 2 Normoglycemia Goal < 180mg% without hypo? 3 Glucocorticoïds The right indication and are they started in the correct dose? Y N 6. Evidence based medicine and references about the important therapeutic issues: Reference: Dellinger, Levy, Rhodes et al. Surviving Sepsis Campaign: International Guidelines for management of severe sepsis and septic shock: 2012. Critical Care Med 2012;41(2):580-635. 7. Risk stratification Early identification of the high-risk patients is very important ! Significant global tissue hypoxia can coexist with vital signs within normal ranges !(1) Vital sign like SAP can be normal! Respiratory rate is an important predictor of risk. Shock Index = HR / SAP. Shock index of more than 0.7 is a good sensitive screening test for hyperlactatemia and 28-day mortality. SI >1 : a specific predictor of mortality. (2) Modified Shock Index = HR/MAP ((MAP= (DAP*2 + SAP)/3)) The MSI is an important predictor of mortality in patients presenting to the emergency department. Lactate help to identify high – risk patients. Serum bicarbonate measurements and arterial base deficits correlate and remain indicators of tissue hypoperfusion. However, serum bicarbonate may be depressed when large volumes of chloride-rich crystalloid resuscitation fluids are administered. (3) 29-4-2017 9:56:03 Pagina 38 van 54 Severe sepsis care bundle 06.07.01.20.02 Biomarkers: CRP , brain natriuretic peptide (an indicator of myocardial dysfunction), procalcitonin (PCT) and interleukin-6. The use of PCT shortens the antibiotic therapy duration in septic patients. It correlates also with severity, better than CRP does. (4) Role of natriuretic peptides: = a tool in management of heart failure (diagnosis, risk stratification d treatment) = might be help in guiding fluid therapy = is associated with prognosis and clinical outcome. N-Terminal pro-B-type natriuretic peptide levels elevation imply the poor prognosis in patients with sepsis. (5,6) This association may be attributable to sepsis related cardiac depression that is characterized by myocardial stiffness and mechanical insufficiency. Our study: prospective : correlation between GEDVI, BNP, diastolic cardiac function (E/E’) and outcomes? Changes in BNP concentration was correlated with changes in GEDVI and serial measurement of BNP might be a useful tool for monitoring volume status. The Delta BNP is significantly correlated to the amount of fluid balance. (6) Further studies are important. Hyponatremia and low albumin are correlated with poor outcome. Risk factors for severe sepsis and septic shock Extremes of age (<10y and >65y) Comorbidity: liver cirrhosis, alcoholism, diabetes mellitus, cardiopulmonary diseases, solid malignancy, hematologic malignancy Immunosuprression: neutropenia, immunosuppressive therapy, corticosteroid therapy, IV drug abuse, complement deficiencies, asplenia, HIV Major sugery, trauma and burns Invasive procedures: intravascular devices, hemodialysis and peritoneal dialysis catheters, endotracheal tubes) Previous antibiotic treatment Prolonged hospitalization Several scoring systems have been developed to determine severity of illness in the ICU and predict the risk of death in populations of critically ill patients. These include: Risk scores APACHE II (and III) SAPS (Simplified acute physiology score) SOFA score (Sepsis related Organ Failure Assessment Score) MODS (multiple organ dysfunction score) 29-4-2017 9:56:03 Pagina 39 van 54 Severe sepsis care bundle 06.07.01.20.02 References 1. Domino M, Nguyen H, Jacobsen G et al. Cryptic septic shock: a sub-analysis of arly, goal-directed therapy. Chest 2003;124:90S. 2. Berger, Green, Horeczko et al. Shock Index and early recognition of sepsis in the ED: pilot study. West J Emerg Med 2013;14(2):168-174. 3. Skellet S, Mayer A, Durward A, et al. Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation. Arch Dis Child 2000;83:514-6. 4. Nobre V et al. Am J Resp Crit Care Med 2008;3:498-505. 5. Liu J, Wang HX, Men K. The relationship between the level of NTproBNP and prognosis in patients with sepsis. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2012;24(11):662-4. 6. Zhongheng Zhang, et al. Prognostic value of BNP and its potential role in guiding fluid therapy in critically ill septic patients. Scandinavian J of Trauma, resuscitation and emergency medicine 2012;20:86. 8. Goals - Increasing awareness - early recognition of patients with severe sepsis and septic shock - as soon as possible starting diagnostics and therapy by using all elements of the bundles - collaboration between clinicians and nurses; emergency physicians and intensivists, microbiologist and infectiologe. - no waiting time for admission to ICU - reducing the mortality rate and costs. 1. 2. 3. 4. 5. 6. g. Quality indicators: which? Blood cultures < 1 hr Antibiotics < 4 hr in patients with sepsis; < 1 hr in patients with severe sepsis and septic shock EGDT < 6 hr; goals: CVD 8-12mmHg; MAP >65mmHg; ScvO2 > 70% CVP and ScvO2 measurement < 2 hr Lactate on admission and lactate clearance ! Corticoids in patients depending on vasopressors and still MAP < 65mmHg. References: 1. Nguyen HB, Corbett SW, Steele R, et al. Implementation of a bundle of quality indicatiors for the early management of severe sepsis and septic shock is associatesd with decreased mortality. Crit Care Med 2007 2. Jones, Focht, Horton, et al. Prospective External validation of the clinical effectiveness of an Emergency departmens-Based Early Goal-Directed Therapy protocol for severe sepsis and septic shock. Chest 2007;132:425-432. h. Data measurement i. Observation of the bundle ends 24 hours after admission and starting the bundle ii. Follow-up of in hospital mortality and other outcomes like: number of ventilation days, number of ARDS, fluid balance iii. APACHE II score : important to compare groups (severity of illness is a confounder). Cfr table. i. Education and feedback of the compliance The patient mortality improves by just accomplishing each bundle element. The bundle has to be started as soon as possible after making the diagnosis of severe sepsis or septic shock. That’s the reason why education “What is sepsis and how to recognize it early” about the bundle is very important. 29-4-2017 9:56:03 Pagina 40 van 54 Severe sepsis care bundle 06.07.01.20.02 Education of health-care personnel and process changes improves the adherence to guidelines and the survival rate of patients with severe sepsis and septic shock admitted to the ICU.(1) The bundles are often unreliably performed. Barriers include lack of awareness and supporting controlled trials, and complex diagnostic criteria leading to recognition delays. Reliable, timely delivery of more complex lifesaving tasks, such as EGDT, demands greater awareness, faster recognition and initiation of basic care and more effective collaboration between clinicans and nrurses, and specialists in microbiology and infectious diseases. The bundles are a crucial peace of the clinical pathway ‘sepsis’ and make part of a continuous quality improvement process (CQI). This CQI process provides feedback to the clinician and nurses to make sure all of those goals are being completed. Sepsis is a “time critical illness” ! j. Achieving UNIFORMITY in the process of care by CQIP. References: 1. Massimo Girardis, Laura Rinaldi, Lara Donno, et al. Effects on management and outcome of sever s and septic shock patiens admitted to the ICU after implementation of a sepsis program: a pilot study. Critical Care 2009;13:R143 9. Implementation Implementation of a bundle of Quality Indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. (1). Important issues: 1. Create a feeling of urgency: all healthcare professionals must know why these changes are important and they have to know that sepsis is a ‘TIME critical illness’. a. In Jessa there is an ongoing retrospective trial (zero-measurement): adherence of quality indicators and in-hospital mortality. 2. Multidisciplinair team. 3. Quality-indicators in METAVISION. 4. Need of a leading team with a doctor and nurse who are more responsible for the working of this clinical pathway. This team consists maximum six members. 5. Make clear that the future therapy of these patients will be different and better than the therapy of the past. The strategy of treatment lays in a plan with concrete activities and education moments. a. Giving feedback where the bundles stand; what the results are. 6. Good and clear communication: everybody has to understand the meaning, the purpose of the clinical pathway. 7. Create successes on short term. Give feedback of these results. 8. The team must be able to function independently. They have the right to deliver criticisme. 9. The team must be encouraged and get awards for the delivered activities. 10. We have to hold on with this new culture. 1. Baseline - Gathering data on the current level of care - Using a checklist to gather bundle compliance data 29-4-2017 9:56:03 Pagina 41 van 54 Severe sepsis care bundle 06.07.01.20.02 - A three monthly review of the medical charts - Checking if the patients meet the inclusion criteria - Data: demographics, date and time of arrival in the ED, time for initirating of the CB, sepsis category, completion of the CB, ED LOS, hospital and ICU LoS, in hospital mortality; vital signs, biochemistry and therapies in the ED and ICU; severity scores: APACHE II, SAPS II, SOFA score, Charlson score and Pitt Bacteremia. 2. Education phase - - Who? o Physician, nurse and staff training o Transmural education: paramedics, the “911”, and general practitioners o Public awareness What? o Sepsis definition and recognition o Hemodynamic monitoring o Inclusion criteria o Quality indicators of de Sepsis Care Bundle 3. Operational phase = bundle delivery in the ED = METVISION with an alert system = pocket cards = trial period 4. QI phase - Feedback by physician and nurses : used to increase the bundle compliance - A report including: - o Number of included patients o Therapy in the ED o % compliance with QI o Outcome Discussing individual cases during staff meeting (multidisciplinary) An example of implemented bundle: The Sepsis Six (of SSC) Implementation of these six elements improved outcomes. (2) 29-4-2017 9:56:03 Pagina 42 van 54 Severe sepsis care bundle 1. Delivery high-flow oxygen 2. Blood cultures and other cultures, source control 3. Empirical IV antibiotics 4. Serum lactate 5. IV fluid resuscitation using Hartmann’s of equivalent 6. Accurate urine output measurement 06.07.01.20.02 All these orders we put in METAVISION under SET SEPSIS (prospective observational study) References 1. Nguyen HB, Corbett SW, Steele R, et al. Crit Care Med 2007;35(4):1105-12. 2. Daniels R et al. The sepsis six and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J 2010;doi:10.1136/emj.2010.095067. 10. Quality Measurement Tool a. b. c. Metavision : input of data to help the clinicians and nurses in early recognizing these patients A list of patients with severe sepsis or septic shock is obtained from Metavision and reviewed each week. Each patient’s chart is carefully reviewed to determine the completion of each component of the Bundle. Quality is improved as the numerator for each component increases over time. 11. Addendum INCLUSION 1. SUSPECTED SEPTIC PATIENT Suspected or proven infection? Pneumonia Urinary tract infection Acute abdominal infection (Cholecystitis, pancreatitis, colitis, diverticulitis, …) Meningitis Skin/soft tissue infection: cellulitis, erysipelas Bone/joint infection Bloodstream catheter infection Endocarditis Implantable device infection Other ° YES: labo, RX thorax, urine; who are the high risk patients? Cfr supra 29-4-2017 9:56:03 Pagina 43 van 54 Severe sepsis care bundle 2. 06.07.01.20.02 SIRS : 2 or more? a. Hyperthermia > 38°C b. Hypothermia < 36°C c. Tachycardia > 90 bpm d. Tachypnoe > 20 bpm e. Acutely altered mental status prior to sedation (GCS < 15) f. Leukocytosis WBC > 12 000) g. > 5% immature bands ° Yes: lactate measurement ! 3. Evidence of any new end organ dysfunction? a. O2 sat < 90% b. SAP < 90 or MAP < 65 c. Oliguria < 0.5ml/kg/hr d. Mottled e. Creat > 0.5mg% from baseline or > 2mg% f. INR > 1.5 g. Platelets < 100 000 h. Bilirubinemia > 4mg% i. Hyperlactatemia > 4mmol / L °Yes: monitored bed !!!! What actions do we do : nurses and physicians? 1. Oxygen to pO2 > 90% (attention in patients with COPD !) 2. Apply cardiac monitor leads and perform a 12 lead ECG; pulse oxymetry (RR) 3. 2 IV’s with as large a bore annula as possible. 4. Infuse Normal Saline 1000 ml over 15-30 minutes. 5. Blood: cfr metavision protocol set and bloodgas with lactate ! 6. Blood cultures: 2 sets (aerobic and anaerobic bottle); from two different sites ! prior AB 7. AB < 1 hr 8. Urine test 29-4-2017 9:56:03 Pagina 44 van 54 Severe sepsis care bundle 9. 06.07.01.20.02 Central venous catheterization : CDP monitoring and ScvO2 measurements 10. Document all vital signs and control them each 10 minutes; in patients with shock: arterial line ! EGDT 29-4-2017 9:56:03 Pagina 45 van 54 Severe sepsis care bundle 06.07.01.20.02 De grote aanpassing van deze tabel: GEEN colloid Hct > 30% wordt Hb > 7g% Risk factor for mortality Age APACHE II Organ dysfunction > 2 Lactate level Inappropriate AB Presence of shock Bacteremia as source Site of infection: respiratory origin (uro: lowest mortality) Risk factors for severe sepsis and septic shock Extremes of age (<10y and >65y) Comorbidity: liver cirrhosis, alcoholism, diabetes mellitus, cardiopulmonary diseases, solid malignancy, hematologic malignancy 29-4-2017 9:56:03 Pagina 46 van 54 Severe sepsis care bundle 06.07.01.20.02 Immunosuppression: neutropenia, immunosuppressive therapy, corticosteroid therapy, IV drug abuse, complement deficiencies, asplenia, HIV Major surgery, trauma and burns Invasive procedures: intravascular devices, hemodialysis and peritoneal dialysis catheters, endotracheal tubes) Previous antibiotic treatment Prolonged hospitalization Risk scores APACHE II score = used as a clinical scoring system to classify the severity of illness. = the worst last values in the last 24 hours APACHE II score consists the following parameters: 1. Temperature 2. MAP 3. HR 4. RR 5. Oxygenation with: a. A-a gradiënt als FiO2 meer dan 50% is b. PaO2 als FiO2 kleiner dan 50% is 6. Arterial pH 7. Serum Na 8. Serum potassium 9. S creatinin in mg/dl 10. Hematocrite in % 11. WBC 12. GCS APACHE II score = APS + age + chronic health points 29-4-2017 9:56:03 Pagina 47 van 54 Severe sepsis care bundle 29-4-2017 9:56:03 Pagina 48 van 54 06.07.01.20.02 Severe sepsis care bundle 06.07.01.20.02 Charlson comorbidity Index = method for classifying comorbid conditions that might alter the risk of mortality (for use in longitudinal studies). 1 point: myocardial infarct, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chornic pulmonary disease, connective tissue disease, ulcer disease, mild liver disease and diabetes. 2 points: hemiplegia, moderate or severe renal disease, diabetes with end-organ damage, any tumor, leukemia, lymphoma 3 points: moderate or severe liver disease 6 points: metastatic solid tumor and AIDS Points 1-Y mortality rate Points Predicted risk of death from comorbid disease at 10-Y followup 0 12% 0 8% 3-4 52% 1 25% 5 or more 85% 2 48% 3 or more 59% References : 1. Charlson, ME et al. J Chronic Dis 1987;40:373-383. 29-4-2017 9:56:03 Pagina 49 van 54 Severe sepsis care bundle SOFA score: sequential organ failure assessment = score designed to describe the degree of organ dysfunction in critically ill patients. 29-4-2017 9:56:03 Pagina 50 van 54 06.07.01.20.02 Severe sepsis care bundle Ref: Vincent JL et al. Int Care Med 1996;22:707-710. 29-4-2017 9:56:03 Pagina 51 van 54 06.07.01.20.02 Severe sepsis care bundle 06.07.01.20.02 MODS score = score designed to describe the degree of organ dysfunction in critically ill patients. = it correlates with intensive care and hospital mortality and intensive care unit length of stay SAPS II score = score to calculate the probability of hospital mortality = revised in 2005 = uses the worst value (the one that gives the most points) in the last 24 hours Variables: Age, HR, SAP, body temperature °C, if on mechanical ventilation: PaO2/FiO2, diuresis in L/day, urea nitrogen, WBC, Potassium, Sodium, Bicarbonate, bilirubin and Glasgow Coma Score. Chronic diseases: metastatic cancer: 9 points; hematological malignancy 10 points, AIDS 17 points Type of admission: medical 6 points; surgical 8 points. 29-4-2017 9:56:03 Pagina 52 van 54 Severe sepsis care bundle To calculate the predicted mortality : formule or a calculator (cfr Google). References: 1. Ref. Le Gall, JR et al . JAMA 1993;270:2957-63. 2. Ref. Le Gall, J.R. et al. Critical care 2005; R645-652. The bundles BUNDLE 1: 3-hr RESUSCITATIONBUNDLE Measurement lactate and clearance Blood cultures before antibiotics Broad spectrum antibiotics Fluids: 30ml/kg crystalloids for MAP < 65mmHg or lactate >4mmol/L BUNDEL 2: 6-hr SEPTIC SHOCK BUNDLE Vasopressor after 30ml/kg crystalloids if MAP < 65mmHg OR lactate > 4mmol/L CVP and ScvO2 measurement 29-4-2017 9:56:03 Pagina 53 van 54 06.07.01.20.02 Severe sepsis care bundle 29-4-2017 9:56:03 Pagina 54 van 54 06.07.01.20.02