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Level of evidence I 比較重要 其他參考

Management of Severe Sepsis

  1. Initial Resuscitation
    1. The guideline committee recommends the protocolized resuscitation of a patient with sepsis-induced shock, defined as tissue hypoperfusion (hypotension persisting after initial fluid challenge or blood lactate concentration equal to or greater than 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending intensive care unit (ICU) admission. 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:
      • Central venous pressure (CVP): 8–12 mm Hg
      • Mean arterial pressure (MAP) >65 mm Hg
      • Urine output >0.5 mL/kg/hour
      • Central venous (superior vena cava) or mixed venous oxygen saturation >70% or >65%, respectively

      上面是hemodynamic最重要的目標

      (Grade 1C)

    2. The guideline committee suggests that during the first 6 hours of resuscitation of severe sepsis or septic shock, if central venous oxygen saturation (SCVO2) or mixed venous saturation (SvO2) of 70% or 65% respectively is not achieved with fluid resuscitation to the CVP target, then transfusion of packed red blood cells to achieve a hematocrit of >30% and/or administration of a dobutamine infusion (up to a maximum of 20 micrograms/kg/min) be utilized to achieve this goal. (Grade 2C)

Diagnosis

    1.  
      1. The guideline committee recommends obtaining appropriate cultures before antimicrobial therapy is initiated if such cultures do not cause significant delay in antibiotic administration. To optimize identification of causative organisms, the committee recommends at least two blood cultures be obtained prior to antibiotics with at least one drawn percutaneously and one drawn through each vascular access device, unless the device was recently (less than 48 hours) inserted. Cultures of other sites (preferably quantitative where appropriate) such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of infection should also be obtained before antibiotic therapy if not associated with significant delay in antibiotic administration. (Grade 1C)再給抗生素前先做血液培養 但不能拖延到給抗生素的時間 血液培養至少要抽兩套 從不同的地方抽 
      2. 2.The guideline committee recommends that imaging studies be performed promptly in attempts to confirm a potential source of infection. Sampling of potential sources of infection should occur as they are identified; however, some patients may be too unstable to warrant certain invasive procedures or transport outside of the ICU. Bedside studies, such as ultrasound, are useful in these circumstances. (Grade 1C)
  1. Antibiotic Therapy

    1. The guideline committee recommends that intravenous antibiotic therapy be started as early as possible and within the first hour of recognition of septic shock (Grade 1B) and severe sepsis without septic shock (Grade 1D). Appropriate cultures should be obtained before initiating antibiotic therapy, but should not prevent prompt administration of antimicrobial therapy. (Grade 1D)抗生素趕快給

    2a. The guideline committee recommends that initial empirical anti-infective therapy include one or more drugs that have activity against all likely pathogens (bacterial and/or fungal) and that penetrate in adequate concentrations into the presumed source of sepsis. (Grade 1B)

    2b. The guideline committee recommends that the antimicrobial regimen be reassessed daily to optimize activity, to prevent the development of resistance, to reduce toxicity, and to reduce costs. (Grade 1C)

    2c. The guideline committee suggests combination therapy for patients with known or suspected Pseudomonas infections as a cause of severe sepsis. (Grade 2D)如果是severe sepsis or septic shock 經驗性抗生素最好給可以cover綠膿桿菌的

  2. 2d. The guideline committee suggests combination empiric therapy for neutropenic patients with severe sepsis. (Grade 2D)

    2e. When used empirically in patients with severe sepsis, the guideline committee suggests that combination therapy should not be administered for more than 3 to 5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known. (Grade 2D)

    3. The guideline committee recommends that the duration of therapy typically be 7 to 10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, or who have immunologic deficiencies including neutropenia. (Grade 1D) 一般抗生素治療至少需7到10天

    4. If the presenting clinical syndrome is determined to be due to a noninfectious cause, the guideline committee recommends antimicrobial therapy be stopped promptly to minimize the likelihood that the patient will become infected with an antibiotic resistant pathogen or will develop a drug related adverse effect. (Grade 1D)

    Source Control

    1a. The guideline committee recommends that a specific anatomic diagnosis of infection requiring consideration for emergent source control- for example necrotizing fasciitis, diffuse peritonitis, cholangitis, intestinal infarction – be sought and diagnosed or excluded as rapidly as possible (Grade 1C) and within the first 6 hours following presentation (Grade 1D).須排除上述臨床病程較快的病

    1b. The guideline committee further recommends that all patients presenting with severe sepsis be evaluated for the presence of a focus of infection amenable to source control measures, specifically the drainage of an abscess or local focus of infection, the debridement of infected necrotic tissue, the removal of a potentially infected device, or the definitive control of a source of ongoing microbial contamination (Grade 1C) (see Appendix A in the original guideline document for examples of potential sites needing source control).需要外科介入或是引流的病 要辨認出來 光是打抗生素是不夠的 孩子!!

    2. The guideline committee suggests that when infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and non-viable tissues has occurred. (Grade 2B)

    3. The guideline committee recommends that when source control is required, the effective intervention associated with the least physiologic insult be employed, for example, percutaneous rather than surgical drainage of an abscess. (Grade 1D)

    4. The guideline committee recommends that when intravascular access devices are a possible source of severe sepsis or septic shock, they be promptly removed after establishing other vascular access. (Grade 1C)若是懷疑是catheter related infection 最好的治療是移除 不過需要在有其他管路建立之下

  3. Fluid Therapy

    1. The guideline committee recommends fluid resuscitation with either natural/artificial colloids or crystalloids. There is no evidence-based support for one type of fluid over another. (Grade 1B)

    2. The guideline committee recommends fluid resuscitation initially target a CVP of at least 8 mm Hg (12 mm Hg in mechanically ventilated patients). Further fluid therapy is often required. (Grade 1C)

    3a. The guideline committee recommends that a fluid challenge technique be applied, wherein fluid administration is continued as long as the hemodynamic improvement (for example, arterial pressure, heart rate, urine output) continues. (Grade 1D)

    3b. The guideline committee recommends fluid challenge in patients with suspected hypovolemia be started with at least 1000 mL of crystalloids or 300 to 500 mL of colloids over 30 minutes. More rapid administration and greater amounts of fluid may be needed in patients with sepsis induced tissue hypoperfusion (see initial resuscitation recommendations). (Grade 1D)所以若是輸N/S 大約半小時輸1000ml 而若是輸Haes 半小時可輸約300到500ml

    3c. The guideline committee recommends the rate of fluid administration be reduced substantially when cardiac filling pressures (CVP or pulmonary artery balloon-occluded pressure) increase without concurrent hemodynamic improvement. (Grade 1D)

  4. Vasopressors

    1. The guideline committee recommends mean arterial pressure (MAP) be maintained >65 mm Hg. (Grade 1C)

    The guideline committee recommends either norepinephrine or dopamine as the first choice vasopressor agent to correct hypotension in septic shock (administered through a central catheter as soon as one is available). (Grade 1C) dopamine 跟levophed最推薦

    3a. The guideline committee suggests that epinephrine, phenylephrine, or vasopressin should not be administered as the initial vasopressor in septic shock. (Grade 2C) Vasopressin .03 units/min may be subsequently added to norepinephrine with anticipation of an effect equivalent to norepinephrine alone.若是levophed沒效的話 也可以打vasopressin 0.3U/min 不過並不推薦bosmin phebylephrine

    3b. The guideline committee suggests that epinephrine be the first chosen alternative agent in septic shock that is poorly responsive to norepinephrine or dopamine. (Grade 2B)

    5. The guideline committee recommends that low dose dopamine not be used for renal protection. (Grade 1A)

    6. The guideline committee recommends that all patients requiring vasopressors have an arterial line placed as soon as practical if resources are available. (Grade 1D)

  5. Inotropic Therapy
    1. The guideline committee recommends a dobutamine infusion be administered in the presence of myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output. (Grade 1C) 若是心臟沒力 可以考慮使用dobutamine
    2. The guideline committee recommends against the use of a strategy to increase cardiac index to predetermined supranormal levels. (Grade 1B)
  6. Corticosteroids
    1. The guideline committee suggests intravenous hydrocortisone be given only to adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy. (Grade 2C)
    2. The guideline committee suggests the adrenocorticotropic hormone (ACTH) stimulation test not be used to identify the subset of adults with septic shock who should receive hydrocortisone. (Grade 2B)
    3. The guideline committee suggests that patients with septic shock should not receive dexamethasone if hydrocortisone is available. (Grade 2B)
    4. The guideline committee suggests the daily addition of oral fludrocortisone (50 micrograms) if hydrocortisone is not available and the steroid that is substituted has no significant mineralocorticoid activity. Fludrocortisone is considered optional if hydrocortisone is used. (Grade 2C)
    5. The guideline committee suggests clinicians wean the patient from steroid therapy when vasopressors are no longer required. (Grade 2D)
    6. The guideline committee recommends doses of corticosteroids comparable to >300 mg hydrocortisone daily not be used in severe sepsis or septic shock for the purpose of treating septic shock. (Grade 1A) 不建議使用劑量大於300毫克的hydrocortisone治療septic shock
    7. The guideline committee recommends corticosteroids not be administered for the treatment of sepsis in the absence of shock. There is, however, no contraindication to continuing maintenance steroid therapy or to using stress-dose steroids if the patient's endocrine or corticosteroid administration history warrants. (Grade 1D)
  7. Recombinant Human Activated Protein C (rhAPC)
    1. The guideline committee suggests that adult patients with sepsis induced organ dysfunction associated with a clinical assessment of high risk of death, most of whom will have Acute Physiology and Chronic Health Evaluation II (APACHE II) >25 or multiple organ failure, receive recombinant human activated protein C (rhAPC) if there are no contraindications (Grade 2B except for patients within 30 days of surgery where it is Grade 2C). Relative contraindications should also be considered in decision making.
    2. The guideline committee recommends that adult patients with severe sepsis and low risk of death, most of whom will have APACHE II <20 or one organ failure, do not receive rhAPC. (Grade 1A)若是apache score小於20 或是預期死亡風險較小 不接受APC治療
  8. Blood Product Administration
    1. Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis (see recommendations for initial resuscitation), the guideline committee recommends that red blood cell transfusion occur when hemoglobin decreases to <7.0 g/dL (<70 g/L) to target a hemoglobin of 7.0 to 9.0 g/dL (70 to 90 g/L) in adults. (Grade 1B) 若是沒有出血 嚴重心肌缺血 低血氧 那基本上Hb維持大約7即可
    2. The guideline committee recommends that erythropoietin not be used as a specific treatment of anemia associated with severe sepsis, but may be used when septic patients have other accepted reasons for administration of erythropoietin such as renal failure-induced compromise of red blood cell production. (Grade 1B) EPO通常不用在sepsis造成的貧血
    3. The guideline committee suggests that fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures. (Grade 2D)
    4. The guideline committee recommends against antithrombin administration for the treatment of severe sepsis and septic shock. (Grade 1B) Antithrombin不用在治療septic shock
    5. In patients with severe sepsis, the guideline committee suggests that platelets should be administered when counts are <5000/mm3 (5 × 109/L) regardless of apparent bleeding. Platelet transfusion may be considered when counts are 5,000 to 30,000/mm3 (5 to 30 × 109/L) and there is a significant risk of bleeding. Higher platelet counts (>50,000/mm3 (50 × 109/L) are typically required for surgery or invasive procedures. (Grade 2D)

Supportive Therapy of Severe Sepsis

  1. Mechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)

    1. The guideline committee recommends that clinicians target a tidal volume of 6 mL/kg (predicted) body weight in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). (Grade 1B)ARDS的MV tidal volume設定的目標值為6ml/kg 重要@!!

    2. The guideline committee recommends that plateau pressures be measured in patients with ALI/ARDS and that the initial upper limit goal for plateau pressures in a passively inflated patient be <30 cm H2O. Chest wall compliance should be considered in the assessment of plateau pressure. (Grade 1C)

    3. The guideline committee recommends that hypercapnia (allowing partial pressure of arterial carbon dioxide [PaCO2] to increase above its pre-morbid baseline, so-called permissive hypercapnia) be allowed in patients with ALI/ARDS if needed to minimize plateau pressures and tidal volumes. (Grade 1C)在為了達成TV跟plateau pressure在一定範圍內 可以允許hypercapnia 稱為permissive hypercapnia

    4. The guideline committee recommends that positive end-expiratory pressure (PEEP) be set so as to avoid extensive lung collapse at end-expiration. (Grade 1C)最好設定PEEP 防止吐氣末期肺泡坍陷

    5. The guideline committee suggests prone positioning in ARDS patients requiring potentially injurious levels of fraction of inspired oxygen (FIO2) or plateau pressure who are not at high risk for adverse consequences of positional changes in those facilities who have experience with such practices. (Grade 2C)

    6a. Unless contraindicated, the guideline committee recommends mechanically ventilated patients be maintained with the head of the bed elevated to limit aspiration risk and to prevent the development of ventilator-associated pneumonia. (Grade 1B)最好維持頭高的姿勢 避免吸入性肺炎

    6b. The guideline committee suggests that the head of bed is elevated approximately 30 to 45 degrees. (Grade 2C)

    7. The guideline committee suggests that noninvasive mask ventilation (NIV) only be considered in that minority of ALI/ARDS patients with mild-moderate hypoxemic respiratory failure (responsive to relatively low levels of pressure support and PEEP) with stable hemodynamics who can be made comfortable and easily arousable, who are able to protect the airway, spontaneously clear the airway of secretions, and are anticipated to recover rapidly from the precipitating insult. A low threshold for airway intubation should be maintained. (Grade 2B)

    8. The guideline committee recommends that a weaning protocol be in place, and mechanically ventilated patients with severe sepsis undergo spontaneous breathing trials on a regular basis to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria: a) arousable; b) hemodynamically stable (without vasopressor agents); c) no new potentially serious conditions; d) low ventilatory and end-expiratory pressure requirements; and e) FIO2 requirements that could be safely delivered with a face mask or nasal cannula. If the spontaneous breathing trial is successful, consideration should be given for extubation (see Appendix E in the original guideline document). Spontaneous breathing trial options include a low level of pressure support, continuous positive airway pressure (approximately 5 cm H2O) or a T-piece. (Grade 1A)插管後的病人須評估可否拔管使用的方法為 SBT 若是滿足上述五項條件 則可嘗試拔管

    9. The guideline committee recommends against the routine use of the pulmonary artery catheter for patients with ALI/ARDS. (Grade 1A)PA catheter不要routine使用在ARDS的病人

    10. To decrease days of mechanical ventilation and ICU length of stay the guideline committee recommends a conservative fluid strategy for patients with established acute lung injury who do not have evidence of tissue hypoperfusion. (Grade 1C)

  1. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
    1. The guideline committee recommends sedation protocols with a sedation goal when sedation of critically ill mechanically ventilated patients with sepsis is required. (Grade 1B)
    2. The guideline committee recommends intermittent bolus sedation or continuous infusion sedation to predetermined end points (e.g., sedation scales) with daily interruption/lightening of continuous infusion sedation with awakening and retitration if necessary for sedation administration to septic mechanically ventilated patients. (Grade 1B)
    3. The guideline committee recommends that neuromuscular blocking agents (NMBAs) be avoided if possible in the septic patient due to the risk of prolonged neuromuscular blockade following discontinuation. If NMBAs must be maintained, either intermittent bolus as required or continuous infusion with monitoring the depth of blockade with train-of-four monitoring should be used. (Grade 1B)盡量避免使用神經肌肉阻斷劑 因為病人常會有長期阻斷的現象
  1. Glucose Control
    1. The guideline committee recommends that, following initial stabilization, patients with severe sepsis and hyperglycemia who are admitted to the ICU receive intravenous (IV) insulin therapy to reduce blood glucose levels. (Grade 1B)
    2. The guideline committee suggests use of a validated protocol for insulin dose adjustments and targeting glucose levels to the <150 mg/dL range. (Grade 2C)
    3. The guideline committee recommends that all patients receiving intravenous insulin receive a glucose calorie source and that blood glucose values be monitored every 1 to 2 hours until glucose values and insulin infusion rates are stable and then every 4 hours thereafter. (Grade 1C)
    4. The guideline committee recommends that low glucose levels obtained with point-of-care testing of capillary blood be interpreted with caution, as such measurements may overestimate arterial blood or plasma glucose values. (Grade 1B)
  1. Renal Replacement
    1. The guideline committee suggests that continuous renal replacement therapies and intermittent hemodialysis are equivalent in patients with severe sepsis and acute renal failure. (Grade 2B)
    2. The guideline committee suggests the use of continuous therapies to facilitate management of fluid balance in hemodynamically unstable septic patients. (Grade 2D)
  1. Bicarbonate Therapy
    1. The guideline committee recommends against the use of 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 1B) 當乳酸中毒 但ph>7.15 不建議使用Jusomin來治療病人
  1. Deep Vein Thrombosis Prophylaxis
    1. The guideline committee recommends that severe sepsis patients receive deep vein thrombosis (DVT) prophylaxis with either (a) low-dose unfractionated heparin (UFH) administered twice daily or three times daily or (b) daily low-molecular weight heparin (LMWH) unless there are contraindications (i.e., thrombocytopenia, severe coagulopathy, active bleeding, recent intracerebral hemorrhage). (Grade 1A) 除非有禁忌症 不然都需要DVT預防
    2. The guideline committee recommends that septic patients who have a contraindication for heparin use receive mechanical prophylactic device such as graduated compression stockings (GCS) or intermittent compression devices (ICD) unless contraindicated. (Grade 1A) 如果對heparin有禁忌症 可以使用GCS或ICD
    3. The guideline committee suggests that in very high-risk patients such as those who have severe sepsis and history of DVT, trauma, or orthopedic surgery, a combination of pharmacologic and mechanical therapy be used unless contraindicated or not practical. (Grade 2C)
    4. The guideline committee suggests that in patients at very high risk, LMWH be used rather than UFH as LMWH is proven superior in other high-risk patients. (Grade 2C)
  1. Stress Ulcer Prophylaxis (SUP)
    1. The guideline committee recommends that stress ulcer prophylaxis (SUP) using H2 blocker (Grade 1A) or proton pump inhibitor (Grade 1B) be given to patients with severe sepsis to prevent upper gastrointestinal (GI) bleed. Benefit of prevention of upper GI bleed must be weighed against potential effect of an increased stomach pH on development of ventilator-associated pneumonia.在ICU book上有談到這個問題 可以使用PPI或H2blocker來防止敗血症病人的上消化道出血 然而也因為上升了胃部的PH值 導致更容易產生VAP
  1. Selective Digestive Tract Decontamination (SDD)
    1. The guideline committee was evenly split on the issue of selective digestive tract decontamination (SDD), with equal numbers weakly in favor and against recommending the use of SDD (see Appendix H of the original guideline document). The committee therefore chose not to make a recommendation for the use of SDD specifically in severe sepsis at this time. The final consensus on use of SDD in severe sepsis was achieved at the last nominal committee meeting and subsequently approved by the entire committee.還需要臨床試驗做評估
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