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NDT Advance Access originally published online on May 30, 2006
Nephrology Dialysis Transplantation 2006 21(8):2296-2300; doi:10.1093/ndt/gfl265
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Technical Note

Continuous renal replacement therapy (CRRT) in children using the AQUARIUSTM

Daljit Kaur Hothi1, Cecilia St George-Hyslop2, Denis Geary1, Desmond Bohn2 and Elizabeth Harvey1

1 Division of Nephrology and 2 Pediatric Critical Care Unit, Hospital for Sick Children, Toronto, Canada

Correspondence and offprint requests to: Dr Elizabeth Harvey, Division of Nephrology, Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8 Ontario, Canada. Email: elizabeth.harvey{at}sickkids.ca

Keywords: AQUARIUSTM; continuous renal replacement therapy; children



   Introduction
Top
 Introduction
Methods
 Results
 Discussion
 Conclusion
 References
 
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 PRISMATM (Gambro AB, Stockholm, Sweden) circuits designed for adult use. A ‘Hot-LineTM’(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 M10TM, 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 PRISMATM 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 AQUARIUSTM (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 AQUAMAXTM (Edwards Lifesciences AG, Irvine, CA, USA) polyethersulphone filters (HFO3—0.3 m2 surface area, priming volume of 32 ml or HFO7—0.7 m2 surface 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.



   Methods
Top
 Introduction
 Methods
Results
 Discussion
 Conclusion
 References
 
We conducted a Research Ethics Board-approved retrospective chart review of the first 11 children treated with the AQUARIUSTM 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.



   Results
Top
 Introduction
 Methods
 Results
Discussion
 Conclusion
 References
 
Table 1 shows the characteristics of the 11 children treated with the AQUARIUSTM. Their mean age was 3.93 ± 5.99 years (mean ± SD) and mean weight 18.2 ± 20.2 kg.


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  		Table 1. Patient characteristics

 
Table 2 outlines 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.


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  		Table 2. CRRT prescriptions, access, tubing and cardiovascular profile on initiating therapy

 
The AQUARIUSTM 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 HotlineTM 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 AQUARIUSTM and AQUAMAXTM, we refer the reader to the company literature [9,10]. The benefits and technical issues are outlined in Table 3 and in the discussion.


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  		Table 3. Technical problems encountered with the AQUARIUSTM, and possible solutions

 


   Discussion
Top
 Introduction
 Methods
 Results
 Discussion
Conclusion
 References
 
Benefits
With the AQUARIUSTM 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 AQUARIUSTM 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 HotlineTM 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 PRISMATM bags on the AQUARIUSTM 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 AQUARIUSTM 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. NormocarbTM (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 HotlineTM 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.



   Conclusion
Top
 Introduction
 Methods
 Results
 Discussion
 Conclusion
References
 
In our unit the leading cause of morbidity during initiation of CRRT is haemodynamic instability particularly using blood primes. By using the AQUARIUSTM and AQUAMAXTM 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.

Conflict of interest statement. None declared.



   References
Top
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Warady B, Bunchman T. Dialysis therapy for children with acute renal failure: survey results. Pediatr Nephrol 2000; 15: 11–13[CrossRef][Web of Science][Medline]
  2. Burchardi H. Renal replacement therapy (RRT) in the ICU: criteria for initiating RRT. In: Ronco C, Bellomo R, La Greca G., eds. Blood Purification in Intensive Care (Contributions to Nephrology V 132- Berlyne GM and Ronco C). Karger New York: 2001; 171–180
  3. Goldstein S, Currier H, Graf J, Cosio CC, Brewer ED, Sachdeva R. Outcome in children receiving continuous venovenous hemofiltartion. Pediatrics 2001; 107: 1309–1312[Abstract/Free Full Text]
  4. Symons JM, Brody PD, Gregory MJ, et al. Continuous renal replacement therapy in children up to 10 kg. Am J Kidney Dis 2003; 41: 984–989[CrossRef][Web of Science]
  5. Lacour F, Maheut H. AN69 membrane and conversion enzyme inhibitors: prevention of anaphylactic shock by alkaline rinsing?. Nephrologie 1992; 13: 135–136[Web of Science][Medline]
  6. Tournier O, Delaunay M. The AN-69 dialysis membrane. Hospital Product Pamphlet 19951–36
  7. Renaux JL, Thomas M. Hypersensitivity reactions and dialysis membranes. Hospital Product Pamphlet 19961–19
  8. Bunchman TE, Maxvold NJ, Barnett J, Hutchings A, Benfield MR. Pediatric hemofiltration: Normocarb® dialysate solution with citrate anticoagulation. Pediatr Nephrol 2002; 17: 150–154[CrossRef][Web of Science][Medline]
  9. Edwards Lifesciences SA. Edwards Aquarius – Setting new standards for acute blood purification. Product Pamphlet 2002; Aquarius Specifications
  10. Edwards Lifesciences SA. Aquamax filters. Product Specification Pamphlet 2002
  11. Schaefer RM, Kulzer P, Gilge U, Schaefer L, Heidland A. Clinical evaluation of the new, steam-sterilized polysulfone high-flux dialyzer. Clin Nephrol 1994; 42 [Suppl 1]: S21–S25
  12. Descamps-Latscha B, Herbelin A, Nguyen AT, et al. Soluble CD23 as an effector of immune dysregulation in chronic uremia and dialysis. Kidney Int 1993; 43: 878–884[Web of Science][Medline]
  13. Lonnemann G, Schindler R, Dinarello CA, Koch KM. Removal of circulating cytokines by hemodialysis membranes in vitro. In; Faist E, Meakins J, Schildberg FW, eds. Host Defense Dysfunction in Trauma, Shock and Sepsis,Springer Verlag, Berlin: 1993; 613–623
  14. Hospal AG. The Nephral ST series. Product Specification Pamphlet 2005
  15. Mehta RL, McDonald BR, Aguilar MM, Ward DM. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int 1990; 38: 976–981[Web of Science][Medline]
  16. Tolwani A, Campbell R, Schenk M, Allon M, Warnock DG. Simplified citrate anticoagulation for continuous renal replacement therapy. Kidney Int 2001; 60: 370–374[CrossRef][Web of Science][Medline]
  17. Chadha V, Garg U, Warady BA, Alon US. Citrate clearance in children receiving continuous venovenous renal replacement therapy. Pediatr Nephrol 2002; 17: 819–824[CrossRef][Web of Science][Medline]
  18. Parakininkas D, Greenbaum LA. Comparison of solute clearance in three modes of continuous renal replacement therapy. Pediatr Crit Care Med 2004; 5: 269–274[CrossRef][Medline]
Received for publication: 27. 3.06
Accepted in revised form: 19. 4.06


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