解读2008年脓毒血症与感染性休克管理国际指南（儿科部分）

null解读2008年脓毒血症与感染性休克管理国际指南（儿科部分） 深圳 2010-07-08 解读2008年脓毒血症与感染性休克管理国际指南（儿科部分） 深圳 2010-07-08 公明医院 张文辉Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008Surviving Sepsis Campaign历史Surviving Sepsis Campaign历史© Society of Critical Care Medicine 2007 The article will also be published in Critical Care Medicine. Sponsor of 2004 guidelines; Sponsor of 2008 guidelines but did not participate formally in revision process; Members of the 2007 SSC Guidelines Committee are listed in Appendix I.; Please see Appendix J for author disclosure information. 跨洲、跨国的多中心联合 跨洲、跨国的多中心联合Sponsoring Organizations: American Association of Critical-Care Nurses*, American College of Chest Physicians*, American College of Emergency Physicians*, Canadian Critical Care Society, European Society of Clinical Microbiology and Infectious Diseases*, European Society of Intensive Care Medicine*, European Respiratory Society*, International Sepsis Forum*, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Society of Critical Care Medicine*, Society of Hospital Medicine**, Surgical Infection Society*, World Federation of Societies of Intensive and Critical CareTable 1 Determination of the Quality of EvidenceTable 1 Determination of the Quality of Evidence•Underlying methodology A RCT B Downgraded RCT or upgraded observational studies C Well-done observational studies D Case series or expert opinion • Factors that may decrease the strength of evidence 1. Poor quality of planning and implementation of available RCTs suggesting high likelihood of bias 2. Inconsistency of results (including problems with subgroup analyses) 3. Indirectness of evidence (differing population, intervention, control, outcomes, comparison) 4. Imprecision of results 5. High likelihood of reporting bias • Main factors that may increase the strength of evidence 1. Large magnitude of effect (direct evidence, relative risk (RR) >2 with no plausible confounders) 2. Very large magnitude of effect with RR >5 and no threats to validity (by two levels) 3. Dose response gradient RCT, randomized controlled trial; RR, relative riskTable 2 Factors Determining Strong vs. Weak RecommendationTable 2 Factors Determining Strong vs. Weak RecommendationWhat should be considered Recommended Process Quality of evidence The lower the quality of evidence the less likely a strong recommendation Relative importance of the outcomes If values and preferences vary widely, a strong recommendation becomes less likely Baseline risks of outcomes The higher the risk, the greater the magnitude of benefit Magnitude of relative risk including Larger relative risk reductions or larger benefits, harms, and burden increases in relative risk of harm make a strong recommendation more or less likely respectively Absolute magnitude of the effect The larger the absolute benefits and harms, the greater or lesser likelihood respectively of a strong recommendation Precision of the estimates of the effects The greater the precision the more likely is a strong recommendation Costs The higher the cost of treatment, the less likely a strong recommendationTable 3 Initial Resuscitation and Infection IssuesTable 3 Initial Resuscitation and Infection IssuesInitial resuscitation (first 6 hours) Strength of recommendation and quality of evidence have been assessed using the GRADE criteria, presented in brackets after each guideline.For added clarity: • Indicates a strong recommendation or “we recommend”; ◦ indicates a weak recommendation or “we suggest” • Begin resuscitation immediately in patients with hypotension or elevated serum lactate >4mmol/l; do not delay pending ICU admission. (1C) • Resuscitation goals: (1C)----EGDT – Central venous pressure (CVP) 8–12 mm Hg – Mean arterial pressure ≥65 mm Hg – Urine output ≥0.5 mL.kg-1.hr-1 – Central venous (superior vena cava) oxygen saturation ≥70%, or mixed venous ≥65% ◦ If venous O2 saturation target not achieved: (2C)Table 3 Initial Resuscitation and Infection Issues （续一）Table 3 Initial Resuscitation and Infection Issues （续一）◦ If venous O2 saturation target not achieved: (2C) – consider further fluid – transfuse packed red blood cells if required to hematocrit of ≥30% and/or – dobutamine infusion max 20 μg.kg−1.min−1 ∗ A higher target CVP of 12–15 mmHg is recommended in the presence of mechanical ventilation or pre-existing decreased ventricular compliance. Diagnosis • Obtain appropriate cultures before starting antibiotics provided this does not significantly delay antimicrobial administration. (1C) – Obtain two or more blood cultures (BCs) – One or more BCs should be percutaneous – One BC from each vascular access device in place >48 h – Culture other sites as clinically indicated • Perform imaging studies promptly in order to confirm and sample any source of infection; if safe to do so. (1C) . Table 3 Initial Resuscitation and Infection Issues （续二）Table 3 Initial Resuscitation and Infection Issues （续二）Antibiotic therapy • Begin intravenous antibiotics as early as possible, and always within the first hour of recognizing severe sepsis (1D) and septic shock (1B). • Broad-spectrum: one or more agents active against likely bacterial/fungal pathogens and with good penetration into presumed source.(1B) • Reassess antimicrobial regimen daily to optimise efficacy, prevent resistance, avoid toxicity & minimise costs. (1C) ◦ Consider combination therapy in Pseudomonas infections. (2D) ◦ Consider combination empiric therapy in neutropenic patients. (2D) ◦ Combination therapy no more than 3–5 days and deescalation following susceptibilities. (2D) • Duration of therapy typically limited to 7–10 days; longer if response slow, undrainable foci of infection, or immunologic deficiencies. (1D) • Stop antimicrobial therapy if cause is found to be non-infectious. (1D)Table 3 Initial Resuscitation and Infection Issues （续三）Table 3 Initial Resuscitation and Infection Issues （续三）Source identification and control • A specific anatomic site of infection should be established as rapidly as possible (1C) and within first 6 hrs of presentation (1D). • Formally evaluate patient for a focus of infection amenable to source control measures (eg: abscess drainage, tissue debridement). (1C) • Implement source control measures as soon as possible following successful initial resuscitation. (1C) Exception: infected pancreatic necrosis, where surgical intervention best delayed. (2B) • Choose source control measure with maximum efficacy and minimal physiologic upset. (1D) • Remove intravascular access devices if potentially infected. (1C) I. Management of Severe Sepsis A. Initial Resuscitation I. Management of Severe Sepsis A. Initial Resuscitation I. Management of Severe Sepsis A. Initial Resuscitation 1. We recommend the protocolized resuscitation of a patient with sepsis-induced shock, defined as tissue hypoperfusion. Hypoperfusion (hypotension ， blood lactate ≥4 mmol/L). This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending ICU admission. During the first 6 hrs of resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as one part of a treatment protocol: EGDTinclude all of the following as one part of a treatment protocol: include all of the following as one part of a treatment protocol: EGDT Central venous pressure (CVP): 8–12mm Hg Mean arterial pressure (MAP) ≥ 65mm Hg Urine output ≥ 0.5mL.kg–1.hr –1 Central venous (superior vena cava) or mixed venous oxygen saturation ≥ 70% or ≥ 65%, respectively (Grade 1C) Limitations OF CVP Limitations OF CVPThere are recognized limitations to ventricular filling pressure estimates as surrogates for fluid resuscitation[28, 29]. CVP is the most obtainable target for fluid resuscitation. Other technologies advantages to flow, volumetric indices and microcirculation changes at the ICU bedside [30–33,34,35],but inaccessible during the critical early resuscitation period and research to validate utility. Next step after fluid resuscitation Next step after fluid resuscitation We suggest that during the first 6 hrs the CVP target IS achieved BUT SCVO2 or SvO2 of 70% or 65% respectively is not achieved then transfusion of packed red blood cells to achieve a hematocrit of ≥ 30% And/or dobutamine infusion (up to a maximum of 20 μg.kg–1.min–1) be utilized to achieve this goal (Grade 2C).Rationale: Rationale: DO2= CO * (Hb * SaO2 *1.34 + PaO2 * 0.003) HR （Early stage） X Pre-load CVP（Early,mid- and late） SV Myo dobutamine（ mid- and late ） Post-load regitine （Early,mid- and late） BP Vascular Resistance Table 4 Hemodynamic Support and Adjunctive Therapy(1)Table 4 Hemodynamic Support and Adjunctive Therapy(1)Fluid therapy • Fluid-resuscitate using crystalloids or colloids. (1B) • Target a CVP of ≥8mmHg (≥12mmHg if ventilated). (1C) • Use a fluid challenge technique while associated with a haemodynamic improvement. (1D) • Give fluid challenges of 1000 ml of crystalloids or 300–500 ml of colloids over 30min. More rapid and larger volumes may be required in sepsis-induced tissue hypoperfusion. (1D) • Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement. (1D) VasopressorsTable 4 Hemodynamic Support and Adjunctive Therapy(2)Table 4 Hemodynamic Support and Adjunctive Therapy(2)Vasopressors • Maintain MAP ≥65mmHg. (1C) • Norepinephrine or dopamine centrally administered are the initial vasopressors of choice. (1C) ◦ Epinephrine, phenylephrine or vasopressin should not be administered as the initial vasopressor in septic shock. (2C) – Vasopressin 0.03 units/min maybe subsequently added to norepinephrine with anticipation of an effectequivalent to norepinephrine alone. ◦ Use epinephrine as the first alternative agent in septic shock when blood pressure is poorly responsive to norepinephrine or dopamine. (2B) • Do not use low-dose dopamine for renal protection.(1A) • In patients requiring vasopressors, insert an arterial catheter as soon as practical. (1D) Inotropic therapy Table 4 Hemodynamic Support and Adjunctive Therapy(3)Table 4 Hemodynamic Support and Adjunctive Therapy(3)Inotropic therapy • Use dobutamine in patients with myocardial dysfunction as supported by elevated cardiac filling pressures and low cardiac output. (1C) • Do not increase cardiac index to predetermined supranormal levels. (1B) Steroids ◦ Consider intravenous hydrocortisone for adult septic shock when hypotension remains poorly responsive to adequate fluid resuscitation and vasopressors. (2C) ◦ ACTH stimulation test is not recommended to identify the subset of adults with septic shock who should receive hydrocortisone. (2B) ◦ Hydrocortisone is preferred to dexamethasone. (2B) ◦ Fludrocortisone (50μg orally once a day) may be included if an alternative to hydrocortisone is being used which lacks significant mineralocorticoid activity. Fludrocortisone is optional if hydrocortisone is used. (2C)Table 4 Hemodynamic Support and Adjunctive Therapy(4)Table 4 Hemodynamic Support and Adjunctive Therapy(4)Steroids ◦ Steroid therapy may be weaned once vasopressors are no longer required. (2D) • Hydrocortisone dose should be ≤300 mg/day. (1A) • Do not use corticosteroids to treat sepsis in the absence of shock unless the patient’s endocrine or corticosteroid history warrants it. (1D) Recombinant human activated protein C (rhAPC) ◦ Consider rhAPC in adult patients with sepsis-induced organ dysfunction with clinical assessment of high risk of death (typically APACHE II ≥25 or multiple organ failure) if there are no contraindications. (2B,2Cfor post-operative patients) • Adult patients with severe sepsis and low risk of death (e. g.: APACHE II<20 or one organ failure) should not receive rhAPC. (1A) J. Blood Product Administration J. Blood Product Administration 1. Once tissue hypoperfusion has resolved we recommend that Hb < 7.0 g/dL (< 70 g/L) red blood cell transfusion to target a Hb of 7.0–9.0 g/dL (70–90 g/L) (Grade 1B), in the absence of extenuating circumstances, myocardial ischemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis J. Blood Product Administration(3) J. Blood Product Administration(3)3. We suggest that fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures (Grade 2D). 5. In patients with severe sepsis, we suggest that platelets should be administered when counts are (Grade 2D). < 5000/mm3 (5 × 109/L) regardless of apparent bleeding. 5,000–30,000/mm3 (5–30× 109/L) WITH significant risk of bleeding ≥ 50,000/mm3 (50 × 109/L)) for surgery or invasive procedures Lung Protected Strategy Protocol Lung Protected Strategy Protocol ARDSNET Ventilator Management (96) • Assist control mode – volume ventilation • Reduce tidal volume to 6 mL/kg lean body weight • Keep inspiratory plateau pressure (Pplat) ≤30 cm H2O – Reduce TV as low as 4mL/kg predicted body weight to limit Pplat • Maintain SaO2/SpO2 88–95% • Anticipated PEEP settings at various FIO2 requirements FiO2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0 PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 20–24 * Predicted Body Weight Calculation • Male – 50 + 2.3 (height (inches) – 60) or 50 + 0.91 (height (cm) – 152.4) • Female – 45.5 + 2.3 (height (inches) – 60) or 45.5 + 0.91 (height (cm) – 152.4) TV, tidal volume; SaO2, arterial oxygen saturation; PEEP, positive end-expiratory pressure III. Pediatric Considerations in Severe Sepsis III. Pediatric Considerations in Severe Sepsis While sepsis in children is a major cause of mortality, the overall mortality from severe sepsis in children is much lower that that in adults, estimated at about 10% [298]. The definitions for severe sepsis and septic shock in children are similar but not identical to the definitions in adults [299]. In addition to age-appropriate differences in vital signs, the definition of systemic inflammatory response syndrome (SIRS) requires the presence of either temperature or leukocyte abnormalities. Sepsis is defined as infection plus SIRS [12]. Severe sepsis is defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion. The presence of severe sepsis requires sepsis plus cardiovascular dysfunction (tissue hypoperfusion) or ARDS or 2 or more other organ dysfunctions[299]. Septic shock is defined as severe sepsis plus tissue hypoperfusion, a major healthcare problems, affecting millions of individuals around the world each year, killing one in four (and often more), and increasing in incidence [1–5]. A. Antibiotics A. Antibiotics 1. We recommend antibiotics be administered within one hour of the identification of severe sepsis, after appropriate cultures have been obtained (Grade 1D). Early antibiotic therapy is as critical for children with severe sepsis as it is for adults. B. Mechanical Ventilation B. Mechanical Ventilation No graded recommendations. Due to low functional residual capacity, young infants and neonates with severe sepsis may require early intubation[300]. Drugs used for intubation have important side effects in these patients, for example, concerns have been raised about the safety of using etomidate(依托味酯）in children with meningococcal sepsis because of adrenal suppression effect [301]. The principles of lung-protective strategies are applied to children as they are to adults. C. Fluid Resuscitation C. Fluid Resuscitation 1. We suggest initial resuscitation begin with infusion of crystalloids with boluses of 20 mL/kg over 5–10 minutes, titrated to clinical monitors of cardiac output, including heart rate, urine output, capillary refill, and level of consciousness (Grade 2C). Intravenous access for fluid resuscitation and inotrope/vasopressor infusion is more difficult to attain in children than in adults, but it’s encouraged early in PALS[302]. On the basis of a number of studies, it is accepted that aggressive fluid resuscitation with crystalloids or colloids is of fundamental importance to survival of septic shock in children [303–308]. Three RCTs compare the use of colloid to crystalloid resuscitation in children with dengue shock [303, 307, 308]. No difference in mortality between colloid or crystalloid resuscitation was shown. Blood Pressure & VolumeBlood Pressure & VolumeChildren’s fall in blood pressure can be prevented by vasoconstriction and increasing heart rate. Therefore, blood pressure by itself is not a reliable end point for assessing the adequacy of resuscitation. Once hypotension occurs, cardiovascular collapse may soon follow. Hepatomegaly occurs in children who are fluid overloaded and can be a helpful sign of adequacy of fluid resuscitation. Large fluid deficits typically exist and initial volume resuscitation usually requires 40–60 mL/kg but can be much higher [304–308]. The rate of fluid administration should be reduced substantially when there are (clinical) signs of adequate cardiac filling without hemodynamic improvement. D. Vasopressors/Inotropes D. Vasopressors/InotropesD. Vasopressors/Inotropes (should be used in volume loaded patients with fluid refractory shock) 1. We suggest dopamine as the first choice of support for the pediatric patient with hypotension refractory to fluid resuscitation (Grade 2C). In the initial resuscitation phase, vasopressor therapy may be required to sustain perfusion pressure, even when hypovolemia has not yet been resolved. Children with severe sepsis can present with low cardiac output (CO) and high systemic vascular resistance (SVR), high CO and low SVR, or low CO and low SVR shock. High CO and high SVR (early or mild septic shock?, mixed shock?) At various stages of sepsis or the treatment thereof, a child may move from one hemodynamic state to another, according to which Vasopressor or inotrope therapy should be used selectively and simulatedly. Dopamine-refractory shock may reverse with epinephrine or norepinephrine infusion [309]. Balance between CO and SVR Balance between CO and SVR 2. We suggest that patients with low CO and elevated SVR states (cool extremities, prolonged capillary refill, decreased urine output but normal blood pressure following fluid resuscitation) be given dobutamine (Grade 2C). The choice of vasoactive agent is determined by the clinical examination. For the child w