1、广州市妇女儿童医疗中心 广州市儿童医院PICU 杨镒宇,解读2008年脓毒血症与感染性休克 管理国际指南（儿科部分） 广州，2009.12.18,Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008,广州市妇女儿童医疗中心,Surviving Sepsis Campaign历史, Society of Critical Care Medicine 2007 The article will also be published in Cr
2、iticalCare Medicine. Sponsor of 2004 guidelines; Sponsor of 2008 guidelines but did not participateformally in revision process; Members of the 2007 SSC Guidelines Committee are listed in Appendix I.; Please see Appendix J for author disclosure information.,广州市妇女儿童医疗中心,跨洲、跨国的多中心联合,Sponsoring Organiz
3、ations: 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 Respirat
4、ory 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 Care,广州市妇女儿童医疗中心,Ta
5、ble 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 availa
6、ble 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 inc
7、rease 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 gradientRCT, randomized controlled trial; RR, relative risk,广州市妇女儿
8、童医疗中心,Table 2 Factors Determining Strong vs. Weak Recommendation,What should be considered Recommended ProcessQuality 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 recommendati
9、on 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 strongrecommendation more or less likely re
10、spectively 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
11、 treatment, the less likely a strong recommendation,广州市妇女儿童医疗中心,Table 3 Initial Resuscitation and Infection Issues,Initial 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 adde
12、d 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 press
13、ure (CVP) 812 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),广州市妇女儿童医疗中心,Table 3 Initial Resuscitation and Infection Issues （续一）, If venous O2 saturat
14、ion target not achieved: (2C) consider further fluid transfuse packed red blood cells if required to hematocrit of 30% and/or dobutamine infusion max 20 g.kg1.min1 A higher target CVP of 1215 mmHg is recommended in the presence of mechanical ventilation or pre-existing decreased ventricular complian
15、ce. 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
16、 as clinically indicated Perform imaging studies promptly in order to confirm and sample any source of infection; if safe to do so. (1C) .,广州市妇女儿童医疗中心,Table 3 Initial Resuscitation and Infection Issues （续二）,Antibiotic therapy Begin intravenous antibiotics as early as possible, and always within the
17、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 penetrationinto presumed source.(1B) Reassess antimicrobial regimen daily to optimise efficacy, prevent resistance, avoid toxicity long
18、er if response slow, undrainable foci of infection,or immunologic deficiencies. (1D) Stop antimicrobial therapy if cause is found to be non-infectious. (1D),广州市妇女儿童医疗中心,Table 3 Initial Resuscitation and Infection Issues （续三）,Source identification and control A specific anatomic site of infection sho
19、uld 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 successf
20、ul 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),广州市妇女儿童医疗中心,I. Management o
21、f 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 initi
22、ated 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: EGDT,广州市妇女儿童医疗中心,include a
23、ll of the following as one part of a treatment protocol:,EGDT Central venous pressure (CVP): 812mm HgMean arterial pressure (MAP) 65mm HgUrine output 0.5mL.kg1.hr 1Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively(Grade 1C),广州市妇女儿童医疗中心,Limitations OF CVP,
24、There are recognized limitations to ventricular filling pressure estimates as surrogates for fluid resuscitation28, 29. CVP is the most obtainable target for fluid resuscitation. Other technologies advantages to flow, volumetric indices and microcirculation changes at the ICU bedside 3033,34,35,but
25、inaccessible during the critical early resuscitation period and research to validate utility.,广州市妇女儿童医疗中心,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
26、blood cells to achieve a hematocrit of 30% And/or dobutamine infusion (up to a maximum of 20 g.kg1.min1) be utilized to achieve this goal (Grade 2C).,广州市妇女儿童医疗中心,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 ）
27、 Post-load regitine （Early,mid- and late）BPVascular Resistance,广州市妇女儿童医疗中心,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 wi
28、th a haemodynamic improvement. (1D) Give fluid challenges of 1000 ml of crystalloids or 300500 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 wi
29、thout concurrent hemodynamic improvement. (1D) Vasopressors,广州市妇女儿童医疗中心,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 vasopressi
30、n 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
31、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,广州市妇女儿童医疗中心,Table 4 Hemodynamic Support and Adjunctive Therapy(3),Inotropic therap
32、y 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 remain
33、s 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 (50g orally once a day) ma
34、y be included if an alternative to hydrocortisone is being used which lacks significant mineralocorticoid activity. Fludrocortisone is optional if hydrocortisone is used. (2C),广州市妇女儿童医疗中心,Table 4 Hemodynamic Support and Adjunctive Therapy(4),Steroids Steroid therapy may be weaned once vasopressors a
35、re 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 patients endocrine or corticosteroid history warrants it. (1D) Recombinant human activated protein C (rhAPC) Consider rhAPC in adult patients with
36、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 II20 or one organ failure) s
37、hould not receive rhAPC. (1A),广州市妇女儿童医疗中心,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 7.09.0 g/dL (7090 g/L) (Grade 1B),in the absence of extenuating circumstances, myocardial ischemia,
38、 severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis,广州市妇女儿童医疗中心,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 pa
39、tients with severe sepsis, we suggest that platelets should be administered when counts are (Grade 2D). 5000/mm3 (5 109/L) regardless of apparent bleeding. 5,00030,000/mm3 (530 109/L) WITH significant risk of bleeding 50,000/mm3 (50 109/L) for surgery or invasive procedures,广州市妇女儿童医疗中心,Lung Protecte
40、d 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 8895% Anticipated PEEP
41、settings at various FIO2 requirementsFiO2 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 1.0PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 2024* 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 (
42、height (cm) 152.4) TV, tidal volume; SaO2, arterial oxygen saturation; PEEP, positive end-expiratory pressure,广州市妇女儿童医疗中心,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 tha
43、t 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
44、 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 hypoper
45、fusion) or ARDS or 2 or more other organ dysfunctions299. 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 15.,广州市妇女儿童医疗中心,A
46、. 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.,广州市妇女儿童医疗中心,B. Mechanical Ventilati
47、on,No graded recommendations. Due to low functional residual capacity, young infants and neonates with severe sepsis may require early intubation300. 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
48、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.,广州市妇女儿童医疗中心,C. Fluid Resuscitation,1. We suggest initial resuscitation begin with infusion of crystalloids with boluses of 2
49、0 mL/kg over 510 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,
50、 but its encouraged early in PALS302. 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 303308. 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.,
