1、感染性休克的液体复苏,感染性休克的液体复苏,补什么? 补多少? 补多快?,Fluid resuscitation of septic shock,2001 EGDT 2004 initial guidelines 2008 updated version guidelines 2010 severe sepsis bundles,Fluid resuscitation of septic shock,2001 EGDT 2004 initial guidelines 2008 updated version guidelines 2010 severe sepsis bundles 2012
2、updated Guidelines,Emanuel Rivers et al.N Engl J Med 2001;345:1368-77,In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P=0.009).,Emanuel Rivers et al.N Engl J Med 2001;345:1368-77,Ema
3、nuel Rivers et al.N Engl J Med 2001;345:1368-77,Emanuel Rivers et al.N Engl J Med 2001;345:1368-77,R. Phillip Dellinger et al. Crit Care Med. 2008;36(1):296-327.,R. Phillip Dellinger et al. Crit Care Med. 2008;36(1):296-327.,Fluid therapy,Fluid-resuscitate using crystalloids or colloids. （1B ） Targe
4、t a CVP of 8mmHg （ 12mmHg if mechanically ventilated ）. （ 1C ） Use a fluid challenge technique while associated with a haemodynamic improvement. （ 1D ）,R. Phillip Dellinger et al. Crit Care Med. 2008;36(1):296-327.,Fluid therapy,Give fluid challenges of 1000 ml of crystalloids or 300500 ml of colloi
5、ds 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 ）,R. Phillip Dellinger et al. Crit Care Med. 2008;36(1):29
6、6-327.,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,Sepsis Resuscitation Bundle（first 6hrs）,1. Serum lactate measured. 2. Blood cultures obtained prior to antibiotic administration. 3. From the time of presentation, broad-spectrum antibiotics administered within 3 hours for ED admissions an
7、d 1 hour for non-ED ICU admissions.,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,Sepsis Resuscitation Bundle（first 6hrs）,4. In the event of hypotension and/or lactate 4 mmol/L (36 mg/dl): a) Deliver an initial minimum of 20 ml/kg of crystalloid (or colloid equivalent). b) Apply vasopressors
8、 for hypotension not responding to initial fluid resuscitation to maintain mean arterial pressure (MAP) 65 mm Hg.,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,Sepsis Resuscitation Bundle（first 6hrs）,5. In the event of persistent hypotension despite fluid resuscitation (septic shock) and/or
9、lactate 4 mmol/L (36 mg/dl): a) Achieve central venous pressure (CVP) of 8 mm Hg. b) Achieve central venous oxygen saturation (ScvO2) of 70%.*,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,1. Low-dose steroids administered for septic shock in accordance with a standardized hospital policy. 2
10、. Drotrecogin alfa (activated) administered in accordance with a standardized hospital policy.,Sepsis Management Bundle（first 24hrs）,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,3. Glucose control maintained lower limit of normal, but 150 mg/dl (8.3 mmol/L). 4. Inspiratory plateau pressures
11、 maintained 30 cm H2O for mechanically ventilated patients.,Sepsis Management Bundle（first 24hrs）,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,Main results,Data from 15,022 subjects at 165 sites were analyzed to determine the compliance with bundle targets and association with hospital mort
12、ality.,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,Main results,Compliance with the entire resuscitation bundle increased linearly from 10.9% in the first site quarter to 31.3% by the end of 2 years (P 0.0001). Compliance with the entire management bundle started at 18.4% in the first quar
13、ter and increased to 36.1% by the end of 2 years (P = 0.008).,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,Main results,Unadjusted hospital mortality decreased from 37 to 30.8% over 2 years (P = 0.001). The adjusted odds ratio for mortality improved the longer a site was in the Campaign, re
14、sulting in an adjusted absolute drop of 0.8% per quarter and 5.4% over 2 years (95% CI, 2.58.4%).,Levy MM et al. Intensive Care Med. 2010;36(2):222-31.,补什么：晶体 or 胶体？,R. Phillip Dellinger et al. Crit Care Med. 2008;36(1):296-327.,We recommend fluid resuscitation with either natural/artificial colloid
15、s or crystalloids. There is no evidence-based support for one type of fluid over another (Grade 1B).,R. Phillip Dellinger et al. Crit Care Med. 2008;36(1):296-327.,液体复苏-2004年SAFE研究,随机对照多中心研究 共6997例需要液体复苏的ICU病人 观察28天的结果 组别： 干预组：3497 4%人血白蛋白 对照组：3500 生理盐水,N Engl J Med 2004;350:2247-56.,结论 在液体复苏时，应用4%白
16、蛋白与生理盐水在28天内效果相当；,N Engl J Med 2004;350:2247-56.,亚组分析 脓毒性休克：死亡率有减少趋势 （30.7% vs 35.3%，P=0.09） 创伤病人，特别是脑外伤病人：死亡率有增加趋势 （13.6% vs 10.0%，P=0.06）,N Engl J Med 2004;350:2247-56.,Surviving Sepsis Campaign Previews Updated Guidelines for 2012,Additions to Fluid Therapy Recommendations（2012）,With regard to fl
17、uid therapy, the use of crystalloids in the initial fluid resuscitation in severe sepsis is recommended (strong recommendation; Grade 1A).,Additions to Fluid Therapy Recommendations（2012）,We recommend that initial fluid challenge in patients with sepsis-induced tissue perfusion with suspicion of hyp
18、ovolemnic be 1,000 mL of crystalloids or more to achieve a minimum of 30 mL/kg of crystalloids in the first four to six hours.,Additions to Fluid Therapy Recommendations（2012）,The researchers also suggest adding albumin to the initial fluid resuscitation for severe sepsis and septic shock (weak reco
19、mmendation; Grade 2B).,Delaney AP et al. Crit Care Med. 2011;39(2):386-91.,Delaney AP et al. Crit Care Med. 2011;39(2):386-91.,Delaney AP et al. Crit Care Med. 2011;39(2):386-91.,Conclusions: In this meta-analysis, the use of albumin-containing solutions for the resuscitation of patients with sepsis
20、 was associated with lower mortality compared with other fluid resuscitation regimens. Until the results of ongoing randomized controlled trials are known, clinicians should consider the use of albumin-containing solutions for the resuscitation of patients with sepsis.,Delaney AP et al. Crit Care Me
21、d. 2011;39(2):386-91.,Additions to Fluid Therapy Recommendations（2012）,They recommend against the use of hydroxyethyl starches (hetastarches) with molecular weight greater than 200 dalton or a degree of substitution of more than 0.4 (strong recommendation; Grade 1B). “We are silent on the use of het
22、astarches of lower molecular weight pending the results of ongoing trials and we are also silent on the use of gelatins,” Dellinger noted.,CONCLUSIONSPatients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require
23、renal-replacement therapy, as compared with those receiving Ringers acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.),Reinhart K et al. Intensive Care Med. 2012;38(3):368-83.,Recommendations and conclusions,We recommend not to use HES with molecu
24、lar weight 200 kDa and/or degree of substitution 0.4 in patients with severe sepsis or risk of acute kidney injury and suggest not to use 6% HES 130/0.4 or gelatin in these populations.,Reinhart K et al. Intensive Care Med. 2012;38(3):368-83.,Recommendations and conclusions,We recommend not to use c
25、olloids in patients with head injury and not to administer gelatins and HES in organ donors.,Reinhart K et al. Intensive Care Med. 2012;38(3):368-83.,Recommendations and conclusions,We suggest not to use hyperoncotic solutions for fluid resuscitation. Until the results of the ongoing studies (ESM) b
26、ecome available and in the absence of other RCTs comparing the use of hyperoncotic albumin with other fluid for shock resuscitation, the safety of hyperoncotic albumin remains unclear for the correction of hypoalbuminaemia and for resuscitation in shock.,Reinhart K et al. Intensive Care Med. 2012;38
27、(3):368-83.,Recommendations and conclusions,We conclude and recommend that any new colloid should be introduced into clinical practice only after its patient-important safety parameters are established,Reinhart K et al. Intensive Care Med. 2012;38(3):368-83.,Brochard L et al. Am J Respir Crit Care M
28、ed.2010 ;181(10):1128-55.,Panel recommendations,We consider fluid resuscitation with crystalloids to be as effective and safe as fluid resuscitation with hypooncotic colloids (gelatins and 4% albumin). Based on current knowledge, we recommend that hyperoncotic solutions (dextrans, hydroxyethylstarch
29、es, or 20-25% albumin) not be used for routine fluid resuscitation because they carry a risk for renal dysfunction.,Brochard L et al. Am J Respir Crit Care Med.2010 ;181(10):1128-55.,Decreased glomerular filtration pressure due to increased intracapillary oncotic pressure and (direct) colloid nephro
30、toxicity (osmotic nephrosis) are the two purported mechanisms responsible for the higher incidence of renal dysfunction with hyperoncotic colloids than with crystalloids or hypooncotic colloids .,Brochard L et al. Am J Respir Crit Care Med.2010 ;181(10):1128-55.,In addition, many adverse effects hav
31、e been described using synthetic colloids . These include anaphylactic and anaphylactoid reactions, blood coagulation disorders, and, in the case of starches, also liver failure and pruritus.,Brochard L et al. Am J Respir Crit Care Med.2010 ;181(10):1128-55.,补多少？& 补多快？,Resuscitation goals: (1C),CVP
32、8-12 mmHg(A higher target CVP of 12-15 mmHg is recommended in the presence of mechanical ventilation or pre-existing decreased ventricular compliance.) MAP65 mm Hg Urine output 0.5 mL.kg-1.hr-1 Central venous (superior vena cava) oxygen saturation 70%, or mixed venous 65%,R. Phillip Dellinger et al.
33、 Crit Care Med. 2008;36(1):296-327.,CVP 8-12mmHg?,Frank-Starling Curve,心室P-V曲线,Marik PE et al.Ann Intensive Care. 2011;1(1):1.,Marik PE et al.Ann Intensive Care. 2011;1(1):1.,Does Central Venous Pressure Predict Fluid Responsiveness?,Marik PE et al.Chest. 2008;134(1):172-8.,Conclusions: This systema
34、tic review demonstrated a very poor relationship between CVP and blood volume as well as the inability of CVP/CVP to predict the hemodynamic response to a fluid challenge. CVP should not be used to make clinical decisions regarding fluid management.,Marik PE et al.Chest. 2008;134(1):172-8.,Discussio
35、n,In other words, our results suggest that at any CVP the likelihood that CVP can accurately predict fluid responsiveness is only 56% (no better than flipping a coin). Furthermore, an AUC of 0.56 suggests that there is no clear cutoff point that helps the physician to determine if the patient is “we
36、t” or “dry”.,Marik PE et al.Chest. 2008;134(1):172-8.,Discussion,It is important to emphasize that a patient is equally likely to be fluid responsive with a low or a high CVP. The results from this study therefore confirm that neither a high CVP, a normal CVP, a low CVP, nor the response of the CVP
37、to fluid loading should be used in the fluid management strategy of any patient.,Marik PE et al.Chest. 2008;134(1):172-8.,Discussion,It should also be recognized that CVP was a component of early goal-directed therapy in the landmark article by Rivers and colleagues. However, both the control and in
38、tervention groups had CVP targeted to 8 to 12mm Hg.,Marik PE et al.Chest. 2008;134(1):172-8.,Discussion,Based largely on the results of the early goal-directed therapy study, the Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock recommend a CVP of 8 to 12mmHg as t
39、he “goal of the initial resuscitation of sepsis-induced hypoperfusion” and “a higher targeted central venous pressure of 1215 mmHg” in patients receiving mechanical ventilation.,Marik PE et al.Chest. 2008;134(1):172-8.,Discussion,The results of our study suggest that these recommendations should be
40、revisited.,Marik PE et al.Chest. 2008;134(1):172-8.,MAP65 mmHg?,Emanuel Rivers et al.N Engl J Med 2001;345:1368-77,LeDoux D et al.Crit Care Med. 2000;28(8):2729-32.,Mean arterial pressure,Organ Blood flow,mmHg,65,Mean arterial pressure,Organ Blood flow,mmHg,no prior hypertension,65,Strandgaard S et
41、al.Br Med J.1973;1(5852):507-10,Urine output 0.5 mL.kg-1.hr-1?,ScvO2 70%?,Variable and Treatment group,Base Line 0 hr,CVP mmHgStandard therapy 6 8EGDT 5 9,6 hrs after the start of therapy,Total fluids (mL),Any vasopressor (%),12 7 14 4,3499 2438 4981 2984,81 18 95 19,66 16 77 10,30.3 27.4,Emanuel Ri
42、vers et al.N Engl J Med 2001;345:1368-77,其他指标?,Lactate clearance Passive leg raising PPV Dynamic measures of echocardiographic function ,Lactate clearance?,the researchers suggest that in the initial resuscitation phase of severe sepsis and septic shock, patients with elevated lactate levelsa marker
43、 of tissue hypoperfusionshould be normalized as quickly as possible in facilities that do not have the capability to target central venous oxygen saturation (weak recommendation; Grade 2C).,Surviving Sepsis Campaign Previews Updated Guidelines for 2012,Passive leg raising?,Marik PE et al.Ann Intensi
44、ve Care. 2011;1(1):1.,Marik PE et al.Ann Intensive Care. 2011;1(1):1.,Prau S et al.Crit Care Med. 2010;38(3):819-25.,Conclusions: Changes in stroke volume, radial pulse pressure, and peak velocity of femoral artery flow induced by passive leg raising are accurate and interchangeable indices for pred
45、icting fluid responsiveness in nonintubated patients with severe sepsis or acute pancreatitis.,Prau S et al.Crit Care Med. 2010;38(3):819-25.,Study name sample size AUC,Monnet CCM 2006 71 0.96 Lafanchre CC 2006 22 0.95 Lamia ICM 2007 24 0.96 Maizel ICM 2007 34 0.89 Monnet CCM 2009 34 0.94 Thiel CC 2
46、009 102 0.89 Biais CC 2009 30 0.96 Preau CCM 2010 34 0.94351 0.95,Cavallaro F et al. Intensive Care Med.2010;36(9):1475-83.,Conclusions: Passive leg raising-induced changes in cardiac output can reliably predict fluid responsiveness regardless of ventilation mode and cardiac rhythm. PLR-cCO has a si
47、gnificantly higher predictive value than PLR-cPP.,Cavallaro F et al. Intensive Care Med.2010;36(9):1475-83.,PPV?,Ventricular preload,Stroke volume,preload responsiveness,preload unresponsiveness,Sensitivity,PPV,CVP,PAOP,1 - Specificity,Michard F et al. Am J Respir Crit Care Med.2000;162(1):134-8,Add
48、itions to Fluid Therapy Recommendations（2012）,The committee also recommends that a fluid challenge technique using incremental fluid boluses be continued for as long as patients improve hemodynamically based on dynamic (eg, delta pulse pressure) or static (eg, arterial pressure) variables (strong recommendation; Grade 1C).,
