1、ICUICU中的血液净化指南之我见中的血液净化指南之我见ContentsIntroduction1 Type of therapy2Timing of CRRT3Dose of CRRT4Conclusions56Introductionv Methods of extracorporeal renal replacement therapy (RRT) have been used for the supportive treatment of AKI for over 60 years.v CRRT for the critically ill patient with ARF was i
2、ntroduced in 1977 by Kramer et al. v Since then, many studies have reported on CRRT in the critically ill.Klin Wochenschr 1977;55:1121-1122.Introductionv But for several reasons comparison among studies is difficult: Various treatment modalities have been applied in heterogeneous populations. Differ
3、ences in clinical setting and underlying molecular biological mechanisms that initiate and maintain ARF. Furthermore, more than 35 definitions of ARF.v Practice patterns vary widely between individual centers.v Up to now, there are no standard guidelines for the application of CRRT in critically ill
4、 patients.Curr Opin Crit Care 2002;8:509-514.Introductionv The RIFLE Classification for acute renal failure Crit Care 2004;8:R204-R212.IntroductionvConclusions: More then 200 different definitions of ARF and about 90 RRT start criteria were reported. Oliguria and RIFLE were the most frequent criteri
5、a used to define ARF. RIFLE criteria might show a clinical impact on future daily practice and research. Different RRT techniques are available in most centers, but a general lack of treatment dose standardization is noted by our survey. Non-renal indications to RRT still need to find a definitive r
6、ole in routine practice.Nephrol Dial Transplant (2006) 21: 690696v In the past, the interaction between nephrology and intensive care was minimal.v Today, there is continuous interaction with several moments of high interaction due to common patients and complex syndromes, and much of the treatment
7、of AKI has moved from the renal ward into ICUs. IntroductionContrib Nephrol. Basel, Karger, 2010 (166):13ContentsIntroduction1 Type of therapy2Timing of CRRT3Dose or intensity of CRRT4Conclusions56Type of therapyClassification of blood purification in critical care (BPCC) technologyPMX = polymyxin-B
8、 immobilized fiber; PMMA = polymethylmethacrylate; PAN = polyacrylonitrile; PEPA = polyether polymer alloyContrib Nephrol. Basel, Karger, 2010(166):1120Type of therapyv As a continuous therapy, CRRT can be rapidly tailored to changes in a patients clinical condition during critical illnessBlood puri
9、fication in critical careContrib Nephrol. Basel, Karger, 2010(166):1120HDF = hemodiafiltrationType of therapyv These advantages have contributed to the widespread uptake of CRRT as the first-choice RRT in ICUs throughout Australia, Japan and Europe. In these regions, CRRT is usually initiated and ma
10、naged within the ICU, with RRT being integrated with other aspects of the management of critical illnessNat. Rev. Nephrol. 2010:6:521529.Type of therapyv In north America, however, traditional structures of ICU management favor an open-ICU approach: Within this model, RRT is usually prescribed by a
11、nephrologist in the ICU and is initiated by a dialysis nurse In this environment, IHD has the advantage of requiring only daily or alternate-day attendance by the renal team Conversely, the relative labor costs of providing CRRT are increased, an effect that is compounded by the larger fixed costs a
12、nd higher consumable requirements of CRRTv These logistic factors have led to a preference for IHD over CRRT being maintained in ICUs that use the north American.Nat. Rev. Nephrol. 2010:6:521529.Type of therapyv Clinical studies of CRRT in the ICUv The diversity of clinical approaches to the treatme
13、nt of AKI in the ICU is illustrated by the results of the BEST Kidney study,The multinational epidemiological study of RRT practice in the ICUStudy documented the treatment of AKI in 1,738 patients in 54 ICUs on five continentsNat. Rev. Nephrol. 2010:6:521529.Type of therapyvBEST study resultsCRRT w
14、as the most common choice of initial RRT treatment, with 80% of patients on CRRT; IHD use was mostly restricted to ICUs in north and south America, where it was used as initial therapy in 3040% of patients, while, by contrast, CRRT is used first in 100% of ICUs in Australia.Among patients receiving
15、CRRT, however, marked variation in the modality, intensity, timing was observed Making it difficult to compare outcomes between patients on CRRT and those on IHDNat. Rev. Nephrol. 2010:6:521529.Type of therapyNat. Rev. Nephrol. 2010:6:521529.v 有些研究表明在有些研究表明在ICU不稳定的患者中应用不稳定的患者中应用IHD也不会存在明显的也不会存在明显的问题
16、问题, 有有RCTs并没有显示出并没有显示出CRRT优于优于IHDType of therapyKidney Int 2009,76:422-427.BMC Nephrol 2010, 11:32.Nephrol Dial Transplant 2009, 24:512-518.Lancet 2006,368:379-385. 对于依赖血管活性药物的对于依赖血管活性药物的AKI患者，患者，CRRT才是最适合的；才是最适合的； 依赖血管活性药物的依赖血管活性药物的AKI患者将来接受长期透析的几率患者将来接受长期透析的几率CRRT 间断性间断性治疗；治疗； AKI的急性期推荐应用的急性期推荐应用C
17、RRT，尤其是对于严重血流动力学不稳定、需，尤其是对于严重血流动力学不稳定、需大量清除液体以便于进行更有效药物治疗的患者。大量清除液体以便于进行更有效药物治疗的患者。Crit Care Med 2008, 36:610-617.Kidney Int 2009,76:422-427.Nat Rev Nephrol 2010, 9:521-529.Clin Pharmacol Ther 2009, 86:562-565.v 目前共识：目前共识：ContentsIntroduction1 Type of therapy2Timing of CRRT3Dose of CRRT4Conclusions5
18、6Timing of CRRTv The right time to start RRT is still a topic of debate.v 主要的原因的是：主要的原因的是： 没有一个明确的、协商一致的没有一个明确的、协商一致的AKI定义能够根据肾损伤程度对患者进行分级定义能够根据肾损伤程度对患者进行分级 研究时很难获得同种类相同特征的患者组人群研究时很难获得同种类相同特征的患者组人群v RIFLE和和AKIN分级标准使对于分级标准使对于AKI的研究向前迈进了一大步的研究向前迈进了一大步v 两种分级标准均能使临床医生警惕两种分级标准均能使临床医生警惕AKI的出现，进行早期干预的出现，进行
19、早期干预Crit Care 2009, 13:211.Timing of CRRTv There is significant variation in the timing of initiation of RRT, with up to two-fold differences in the reported values of BUN, creatinine, or urine output at RRT initiation.Clinical studies evaluating the timing of initiation of CRRT in critically ill pa
20、tientsTiming of CRRTvIn the above-mentioned studies there is a clear trend toward a better outcome with earlier timing of RRT. vIn the absence of large RCTs comparing early to late initiation of RRT, no firm overall recommendations for timing of RRT can be made. Timing of CRRTv 目前广为接受的目前广为接受的Septic
21、AKI开始开始RRT时机，尤其是在时机，尤其是在septic shock 时：时：RIFLE injury stage (or AKIN stage 2) v but consensus on this topic awaits results from large-scale RCTs.Timing of CRRTv 除除AKI外，患者的一些其他情况也需要行早期外，患者的一些其他情况也需要行早期RRT治疗：治疗： mainly pediatric, treated by ECMO for severe ARDS. Fluid overload definitely plays a role
22、in timing, because CRRT proved successful in patients without AKI but refractory to diuretics. v 治疗时机的标准在不断发展，包括：治疗时机的标准在不断发展，包括： severity of organ dysfunction (SOFA score)； severity of AKI (RIFLE or AKIN stage)； fluid overload status； time from admission； biomarker use, etc.v 但他们在日常临床实践中的应用价值仍然需要评估
23、但他们在日常临床实践中的应用价值仍然需要评估Kidney Int 2010, 77:469-470.Kidney Int 2009, 76:1289-1292J Am Soc Nephrol 2011, 22:810-820.Timing of CRRTv When initiation of RRT is considered, it is important to realize that: the consequences of ureamic toxicity, metabolic acidosis and/or fluid overload are likely to be more
24、 severe in the critically ill patient. Moreover, renal function is unlikely to recover within a short period during persistent and severe failure of other organs. Furthermore, various inflammatory mediators are cleared by the kidney.Timing of CRRTv 最近的一项前瞻性研究和两项最近的一项前瞻性研究和两项meta-analysis明确地支持明确地支持ea
25、rly timingThe findings of these studies support earlier initiation of acute RRTIn the absence of new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be madeContentsIntroduction1 Type of therapy2Timing of CRRT3Dose of CRRT4Conclusions56Dose or intensity
26、 of CRRTDose or intensity of CRRTDose or intensity of CRRTv Both the ATN and RENAL studies failed to detect any survival benefit from more-intensive RRT And no significant differences in mortality rates were observed between high-intensity and low-intensity treatment in subgroups in either study.The
27、se results provide definitive evidence to recommend that escalation of CRRT intensity to beyond conventional doses of 25 ml/kg/h is not beneficial for unselected ICU patients with AKI.Possible relationship between delivered dose of CRRT and survival, with results from the ATN and RENAL trials illust
28、rated. Dose or intensity of CRRTv 而关于而关于non-septic AKI 的治疗剂量，的治疗剂量，RENAL研究得到了一个明确的答案研究得到了一个明确的答案: Randomized Evaluation of Normal versus Augmented Levels (RENAL) study: v no beneficial effect of CVVHDF at 40 ml/kg/h compared with 25 ml/kg/h.v Therefore, current consensus suggests a hemofiltration do
29、se of 25 ml/kg/h in non-septic AKI with no additional benefit from a dose increase.N Engl J Med 2009, 361:1627-1638.Dose or intensity of CRRTv 然而，然而， 需要强调的是：需要强调的是： 专家的意见是患者治疗剂量要足够，至少专家的意见是患者治疗剂量要足够，至少25 ml/kg/h25 ml/kg/h。 但实际中由于存在可预测的但实际中由于存在可预测的（bags change, nursing.）和不可预测的和不可预测的（surgery, clotting
30、.）治疗中断，意味着剂量要在治疗中断，意味着剂量要在30-35 ml/kg/h30-35 ml/kg/h； Septic AKI患者的治疗剂量目前仍存在争议，一些小的前瞻随机研究患者的治疗剂量目前仍存在争议，一些小的前瞻随机研究表明高剂量的血液滤过是有益的。表明高剂量的血液滤过是有益的。 多中心的多中心的 “IVOIRE study” (hIgh Volume in Intensive care)，在，在sepsis引起的引起的AKI，休克和多脏衰患者中，比较，休克和多脏衰患者中，比较35 ml/kg/h vs. 70 ml/kg/h ，不久后，可能会对治疗剂量的争论有所定论。不久后，可能会对
31、治疗剂量的争论有所定论。Joannes-Boyau O, Honore PM: Hemofiltration Study: IVOIRE Study: clinicaltrials.gov ID NCT00241228., last Accessed in June 2011.Crit Care 2009, 13:R57.J Nephrol 2011, 24:165-176.Dose or intensity of CRRTv “IVOIRE study” (hIgh Volume in Intensive care)初步结果：初步结果： Although patients included
32、were more severely ill, overall mortality in the IVOIRE study remains very low (39% at 28 days and 52% at 90 days) compared with the RENAL study. This may be due to the earlier start of treatment at the renal injury level. Awaiting results from this important trial, 35 ml/kg/h should remain the stan
33、dard dose in septic AKI, particularly in the presence of shock.Joannes-Boyau O, Honore PM: Hemofiltration Study: IVOIRE Study: clinicaltrials.gov ID NCT00241228., last Accessed in June 2011.ContentsIntroduction1 Type of therapy2Timing of CRRT3Dose of CRRT4Conclusions56RRT in ICU: PreferencevDecision
34、 about which technique to use depends on:v1. What we want to remove from the plasma RRT in ICU: Preference v2. The patients cardiovascular statusCRRT causes less rapid fluid shifts and is the preferred option if there is any degree of cardiovascular instability.v3. The availability of resourcesCRRT
35、is more labour intensive and more expensive than IHDAvailability of equipment may dictate the form of RRTRRT in ICU: Preference v4. The clinicians experienceIt is wise to use a form of RRT that is familiar to all the staff involvedv5. Other specific clinical considerationsConvective modes of RRT may
36、 be beneficial if the patient has septic shockCRRT can aid feeding regimes by improving fluid managementCRRT may be associated with better cerebral perfusion in patients with an acute brain injury or fulminant hepatic failure许多问题悬而未决许多问题悬而未决标准与个体化标准与个体化You are unique!Standard!Key Pointsv It is recom
37、mended to define ARF according to the RIFLE classification system into ARFrisk, ARFinjury and ARFfailure.v It is recommended to base the decision when to start RRT not only on the severity of ARF, but also on the severity of other organ failure. v Initiation of RRT is to be considered in oliguric pa
38、tients (RIFLErisk-oliguria or RIFLEinjury-oliguria), despite adequate fluid resuscitation, and/or a persisting steep rise in serum creatinine. Key Pointsv RRT may be postponed when the underlying disease is improving, other organ failure recovering and the slope in the serum creatinine rise declines
39、, in order to see if renal function is also recovering.v It is recommended to continue RRT as long as the criteria defining severe oliguric ARF (RIFLEfailure-oliguria) are present. If the clinical condition improves, it may be considered to wait before connecting a new circuit to see whether renal f
40、unction recovers. RRT should be restarted in case of clinical or metabolic deterioration.Key Pointsv The recommended delivered (not prescribed) ultrafiltrate (dialysate) flow during CVVH(D) is 35 mL/kg/h in postdilution. A higher dose applied for a short period may be considered in Sepsis/SIRS. The
41、dose needs to be adjusted for predilution.v In non-shock patients, continuous and intermittent treatments are equivalent regarding survival. However, CRRT is recommended over IHD for patients with ARF who have, or are at risk for, cerebral oedema. CRRT is preferred in the management of patients with ARF and shock.
