目前国内来说，没有一本专门讲小孩的连续性血液净化，包括王质刚老师的《血液净化学》和黎老的《连续性血液净化》，谈到小儿连续性血液净化的内容都很少，教科书上说的都是5岁以下的建议行腹膜透析，虽然PD有许多优点为，但我不认为它能等同CBP，临床上也有许多的需要。简单说，就如腹部手术后的MODS你能行腹透吗？
但是在开展中又会碰到许多难题：液体量的计算，（这个书上倒是有些介绍），透析剂量昵，抗凝方案呢？特别是抗凝方案，国内大部分都说了肝素或无肝素抗凝，那么枸橼酸呢？有人用吗，怎么用？其它的呢？想提出来请各位大师谈谈看法，敬请賜教！
这第一个是国内同道的综述，（不是针对作者，谢谢理解）后面是国外的两篇文章 Continuous Renal Replacement Therapy and Plasma Exchange in Newborns and Infants。2outcome in children receiving continuous venovenous hemofiltration.相信大家知道 children newborn infant 的区别。我们还有许多事情要做，当然也包括儿童适用的CBP设备。
这是另一篇Continuous renal replacement therapy (CRRT) in children using the AQUARIUS?
Introduction
Continuous renal replacement therapy (CRRT) is the preferred choice for blood purification and volume control in critically ill children [1,2]. The reported overall survival rate for children requiring CRRT is 60% [3], and mortality in infants is comparable with that of older children and adolescents [4].
It is imperative in paediatric CRRT that equipment be adaptable to accommodate large variations in size (2–100?kg). Until recently at the Hospital for Sick Children, CRRT was provided using the PRISMA? (Gambro AB, Stockholm, Sweden) circuits designed for adult use. A ‘Hot-Line?’(Smiths-Level 1 Inc., Rockland, MA) blood warmer prevented hypothermia but increased the extracorporeal circuit volume by 25?ml, which then exceeded 10% of the blood volume for patients weighing <15?kg. The PRISMA M10?, a 50?ml paediatric circuit, reduced the weight for a blood prime to ≤8?kg, but we elected not to use it given its limited functional capabilities based on product specifications. The PRISMA? haemofilter AN69 membrane is associated with a ‘bradykinin release phenomenon’ on contact with acidotic blood including a blood prime [5], producing transient, but potentially life-threatening cardiovascular instability [6,7]. Protocols to overcome this, incorporating administration of large doses of alkali and calcium to the patient [8], are labour-intensive and were, in our experience, largely unsuccessful.
To address these concerns, the AQUARIUS? (Edwards Lifesciences AG, Irvine, CA, USA) was purchased in 2004. In the paediatric programme the machine's specifications include a scale accuracy of ±20?ml and the ability to support a blood-flow rate of 10 to 200?ml/min, a pre-dilution rate of 0 or 100–6000?ml/h and post-dilution rate of 0 or 100–4000?ml/h [9]. In conjunction with this we introduced the AQUAMAX? (Edwards Lifesciences AG, Irvine, CA, USA) polyethersulphone filters (HFO3—0.3?m2surface area, priming volume of 32?ml or HFO7—0.7?m2surface area, priming volume of 54?ml) and Aqualine tubing (Aqualine—110?ml priming volume and paediatric Aqualine S—64?ml priming volume) [10]. We report 14 months of clinical experience of CRRT with this equipment in the first 11 children, highlighting the success, benefits and technical issues.
Previous SectionNext Section
Methods
We conducted a Research Ethics Board-approved retrospective chart review of the first 11 children treated with the AQUARIUS? from August 2004 to October 2005 to obtain information on demographic factors, CCRT prescription, circuit life span, haemodynamic stability on initiating therapy, feasibility and technical problems. The patients were co-managed by the intensivists and nephrologists with CRRT orders written by the attending nephrologist.
Previous SectionNext Section
Results
Table 1shows the characteristics of the 11 children treated with the AQUARIUS?. Their mean age was 3.93 ± 5.99 years (mean ± SD) and mean weight 18.2 ± 20.2?kg.
View this table:
In this windowIn a new windowTable 1.
Patient characteristics
Table 2outlines the CRRT prescription. The continuous renal replacement therapy (CRRT) circuit was incorporated into an extracorporeal membrane oxygenation (ECMO) circuit in one patient. Initial placement of the access and return lines pre-oxygenator resulted in high access and transmembrane pressures (TMP) and was resolved by placing the access line post-oxygenator. The mean duration of therapy was 88.9 ± 106?h (range 23–371?h) and the mean circuit lifespan was 25.8 ± 21.1?h (range 1–75?h) (Table 2). Heparin was used exclusively in five patients; citrate anticoagulation was attempted in two patients both of whom developed metabolic alkalosis, and no anticoagulation was attempted in two patients which shortened the circuit life to 10.6 ± 4.4?h.
View this table:
In this windowIn a new windowTable 2.
CRRT prescriptions, access, tubing and cardiovascular profile on initiating therapy
The AQUARIUS? fluid warmer was able to maintain normothermia in the three older children, but not in six children below 1 year of age. One child was febrile and required no warming, and the remaining patient was on an ECMO circuit. The Hotline? restored normothermia but increased the extracorporeal volume by 25?ml.
All patients were haemodynamically stable on initiating CRRT (Table 2). The difference in the systolic and diastolic blood pressure (BP) before and after starting was ?4.36?mmHg [95% confidence interval (CI) ?15.1 to 6.4] and ?5.09?mmHg (95% CI ?12.29 to 2.11), respectively.
Among the 11 children receiving CRRT, 7 survived, achieving an overall survival rate of 64%.
For full specifications of the AQUARIUS? and AQUAMAX?, we refer the reader to the company literature [9,10]. The benefits and technical issues are outlined in Table 3and in the discussion.
View this table:
In this windowIn a new windowTable 3.
Technical problems encountered with the AQUARIUS?, and possible solutions
Previous SectionNext Section
Discussion
Benefits
With the AQUARIUS? it was feasible to perform CRRT on children of all ages. The circuit was easily incorporated into an ECMO circuit. Universal demonstration of haemodynamic stability on initiating therapy supports the absence of bradykinin-mediated membrane reactions.
Synthetic dialysers such as the AN69 and polysulphone membranes are ideal for convective therapies as they are highly permeable, thick-walled membranes and can therefore tolerate high transmembrane pressures while achieving good middle-molecule clearance. In vitro data suggest that AN69 membranes are more biocompatible than polysulphone membranes resulting in less complement [11], B-cell and monocyte activation [12] and have superior protein and cytokine adsorption abilities [13]. In practical terms, these benefits became insignificant when faced with the possibility of severe life-threatening membrane reactions. New surface-treated AN69ST membranes hold the promise of complete suppression of potential blood–membrane contact reactions, independent of pH [14], but paediatric safety and efficacy data are currently not available.
Application of the AQUARIUS? circuit did expose several technical issues, which have been summarized in point format in Table 3:
(1) Hypothermia
The fluid warmer was insufficient to prevent hypothermia in all infants despite additional warming strategies such as overhead radiant heaters. The Hotline? blood warmer remedied the hypothermia but at the expense of adding 25?ml to the extracorporeal circuit volume.
(2) and (3) TMP alarms and minimum substitution fluid rate
Minute-to-minute variations in the TMP interrupted the treatment and became more prevalent if a zero hourly fluid balance was prescribed. We believe this occurred because the pumps were changing speed to maintain the 20?ml error in fluid balance throughout the therapy. New software (v4.01.01) has resolved the issue but at the cost of pushing the minimum recommended dialysate or replacement fluid rates in the paediatric setting to 600?ml/h. This places infants at risk of excessive drug and solute clearance and disequilibrium. Dialysate has a smaller effect on TMP; therefore, on continuous veno-venous haemodialysis (CVVHD) reduced dialysate flow, and thus reduced clearance, may be possible without triggering TMP alarms. We have not yet formally tested this theory.
(4) Balance alarms
The aforementioned software issue also resulted in sudden spinning of the effluent pump that has resolved with the software upgrade; however, balance alarms persist. One cause was the use of PRISMA? bags on the AQUARIUS? resulting in dialysate leak. The design of the connection between the substitution fluid bags and the circuit also appears to cause intermittent obstruction to flow. Finally, during periods of high pump-generated filtrate pressures, balance alarms are triggered. This can be remedied by allowing a higher ultrafiltrate rate or switching to convective therapies and increasing the pre-dilution rate.
(5) Negative ‘pressure drop’
The negative pressure drop refers to higher hydraulic pressure on the venous side compared with the arterial side of the haemofilter. This can be overcome by increasing the blood flow (limited by access in infants) or switching to continuous veno-venous haemofiltration (CVVH) and increasing pre-dilution-flow rates to make the TMP trend positive.
(6) Recurrent clots
In the absence of a coagulopathy, if the circuit lifespan was <24?h, the target activated clotting time was increased to 170–220?s for subsequent circuits. Other solutions are outlined in Table 3.
(7) Single substitution fluid weighing scale
Citrate chelation of calcium produces regional anticoagulation but can result in alkalosis when used in conjunction with commercially available solutions [15–16]. This can be corrected by converting to CVVHDF, infusing normal saline as the replacement fluid [17].
The AQUARIUS? has two weigh scales, one for the effluent fluid and the other for dialysate or replacement fluid. During continuous veno-venous haemodialfiltration (CVVHDF), different dialysate and replacement fluid rates can be employed but only one substitution fluid can be used. Normocarb? (Dialysis Solutions Inc., Whitby, Canada), our solution of choice, contains 35?mmol/l bicarbonate making it unsuitable for alkalotic patients. Furthermore, it is not licensed for infusion. Therefore citrate anticoagulation cannot be applied without a custom-made solution. A theoretical alternative includes CVVHD with a lower bicarbonate, calcium-free dialysate and higher dialysate flow rates.
(8) Post-dilutional CVVHDF
This increases the risk of filter clotting, and in circuits with the Hotline? warmer, will push return pressures higher and may, compared with pre-dilutional CVVHDF, push clearance rates higher [18] in the already vulnerable infants.
(9) Return-pressure-sensor leak
We have alerted the company and have increased vigilance for sudden drops in the access and return pressures.
(10) Master keyboard failure
The keyboard failure during priming is essentially a software issue that is undergoing revision. In the interim, pressing the blood pump prompts the screen and pump to communicate.
Previous SectionNext Section
Conclusion
In our unit the leading cause of morbidity during initiation of CRRT is haemodynamic instability particularly using blood primes. By using the AQUARIUS? and AQUAMAX? filters, we saw an improvement in patient well-being, a reduction in acute adverse effects on initiating therapy and the safer and broader applicability of CRRT in children of all ages. The trade-off, however, was a number of technical issues. Some have been resolved, but of those remaining, the absence of safe and simple protocols for citrate anticoagulation and the obligatory 600?ml/h minimum replacement and dialysate fluid rates have the greatest potential impact on patient care.
儿科急性肾衰推荐使用的模式选择
Flynn JT. Choice of dialysis modality for management of pediatric ARF. Pediatr Nephrol 2002
导管
患者 导管大小 插入位置
新生儿 3.5-5 Fr UAC
5.0-8.5 Fr UVC
5 Fr 单腔 x2 股静脉 / UVC
6.5 Fr 双腔 股静脉 / UVC
5-15 kg8 Fr 双腔 股静脉/锁骨下/IJ
16-30 kg 9 Fr 双腔 股静脉/锁骨下 /IJ
> 30 kg11.5 Fr 双腔 股静脉/锁骨下 /IJ
CVVH 的不同剂量对ARF结果的影响。一项前瞻性随机试验,最小UF至少应达到35ml/kg/h ， ( 2000 ml/1.73m2/h 适用于儿童)Ronco et al Lancet 2000;351: 26-30抗凝：肝素负荷量 10-20 U/kg，维持量5-20 U/kg/小时，保持活化凝血时间在 170-220 秒低分子量肝素局部枸橼酸盐抗凝剂局部抗凝剂的作用取决于枸橼酸螯合钙的能力，需要含有置换液的无钙的特殊枸橼酸钠，通过另一中心管道输入氯化钙 ，Excellent filter patency rates，低钙血症和代谢性碱中毒的风险 Setup of the use of Normocarb as replacement solution for CVVH, along with ACD-A as citrate solution for anticoagulation and calcium chloride as solution for normalization of patient calcium levels. Note that calcium chloride requires infusion in tubing independent of the CRRT circuit, or if a triple-lumen access is available, calcium can be infused in the third lumen.Bunchman T. Peditric Convective HF: Normlcarb Replacement Fluid and Citrate Anticoagulation. Am. J. Kid. Dis. 2003无抗凝剂 ( 血小板 2 , 和APTT > 60秒, active bleeding )处方BFR : 4-6 ml/kg/min使用CVVH、CVVHD或 CVVHDF置换液 (碳酸氢盐)2000 ml/1.73m2/h透析液2000 ml/1.73m2/h 例如：一个10 kg的小孩( BSA 0.5 m2),透析液和置换液都应是 700ml/小时
抗凝剂：肝素或枸橼酸盐
