Continuous renal replacement therapy (CRRT) in children using the AQUARIUS™

Hothi, Daljit Kaur; St George-Hyslop, Cecilia; Geary, Denis; Bohn, Desmond; Harvey, Elizabeth

doi:10.1093/ndt/gfl265

AQUARIUS™, continuous renal replacement therapy, children

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 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

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.

Results

Table 1 shows 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.

Table 1.

Patient characteristics

Patient	Age	Weight (kg)	Disease	Organ failure	Coagulopathy	Baseline urine output (ml/kg/h)
1	11 m	7.5	Post BM transplant pneumonia	Renal	No	2.6
				Pulmonary
2	4 d	3.0	Hyperammonaemia		No	1.6
3	8.5 m	6.3	Macrophage activation syndrome	Multiple organ failure	Yes	1.0
4	10 m	7.3	Neonatal liver failure	Multiple organ failure	Yes	0.1
5	4 d	3.1	Hyperammonemia		No	3.1
6	16 y	58.6	Gram positive sepsis	Multiple organ failure	Yes	0.0
			Intracerebral haemorrhage
			DKA
7	3 m	7.8	Gram positive sepsis	Pulmonary	No	0.9
			Cardiac arrhythmias	Renal
8	15 y	50	Reyes syndrome	Renal	Yes	4.5
			Pneumonia	Liver
			Intracranial hypertension
9	6 y	36.5	Post BM transplant	Liver	Yes	0.6
			Adenovirus viraemia	Renal
10	3 y	13.0	Diarrhoea + HUS (CNS involvement)	Renal	Yes	0.0
11	6 m	6.8	Congenital heart disease	Multiple organ failure	No	0.1

Patient	Age	Weight (kg)	Disease	Organ failure	Coagulopathy	Baseline urine output (ml/kg/h)
1	11 m	7.5	Post BM transplant pneumonia	Renal	No	2.6
				Pulmonary
2	4 d	3.0	Hyperammonaemia		No	1.6
3	8.5 m	6.3	Macrophage activation syndrome	Multiple organ failure	Yes	1.0
4	10 m	7.3	Neonatal liver failure	Multiple organ failure	Yes	0.1
5	4 d	3.1	Hyperammonemia		No	3.1
6	16 y	58.6	Gram positive sepsis	Multiple organ failure	Yes	0.0
			Intracerebral haemorrhage
			DKA
7	3 m	7.8	Gram positive sepsis	Pulmonary	No	0.9
			Cardiac arrhythmias	Renal
8	15 y	50	Reyes syndrome	Renal	Yes	4.5
			Pneumonia	Liver
			Intracranial hypertension
9	6 y	36.5	Post BM transplant	Liver	Yes	0.6
			Adenovirus viraemia	Renal
10	3 y	13.0	Diarrhoea + HUS (CNS involvement)	Renal	Yes	0.0
11	6 m	6.8	Congenital heart disease	Multiple organ failure	No	0.1

DKA, diabetic ketoacidosis; BM, bone marrow; HUS, haemolytic uremic syndrome; CNS, central nervous system. Age represented as months (m), years (y) and days (d).

Open in new tab

Table 1.

Patient characteristics

Patient	Age	Weight (kg)	Disease	Organ failure	Coagulopathy	Baseline urine output (ml/kg/h)
1	11 m	7.5	Post BM transplant pneumonia	Renal	No	2.6
				Pulmonary
2	4 d	3.0	Hyperammonaemia		No	1.6
3	8.5 m	6.3	Macrophage activation syndrome	Multiple organ failure	Yes	1.0
4	10 m	7.3	Neonatal liver failure	Multiple organ failure	Yes	0.1
5	4 d	3.1	Hyperammonemia		No	3.1
6	16 y	58.6	Gram positive sepsis	Multiple organ failure	Yes	0.0
			Intracerebral haemorrhage
			DKA
7	3 m	7.8	Gram positive sepsis	Pulmonary	No	0.9
			Cardiac arrhythmias	Renal
8	15 y	50	Reyes syndrome	Renal	Yes	4.5
			Pneumonia	Liver
			Intracranial hypertension
9	6 y	36.5	Post BM transplant	Liver	Yes	0.6
			Adenovirus viraemia	Renal
10	3 y	13.0	Diarrhoea + HUS (CNS involvement)	Renal	Yes	0.0
11	6 m	6.8	Congenital heart disease	Multiple organ failure	No	0.1

Patient	Age	Weight (kg)	Disease	Organ failure	Coagulopathy	Baseline urine output (ml/kg/h)
1	11 m	7.5	Post BM transplant pneumonia	Renal	No	2.6
				Pulmonary
2	4 d	3.0	Hyperammonaemia		No	1.6
3	8.5 m	6.3	Macrophage activation syndrome	Multiple organ failure	Yes	1.0
4	10 m	7.3	Neonatal liver failure	Multiple organ failure	Yes	0.1
5	4 d	3.1	Hyperammonemia		No	3.1
6	16 y	58.6	Gram positive sepsis	Multiple organ failure	Yes	0.0
			Intracerebral haemorrhage
			DKA
7	3 m	7.8	Gram positive sepsis	Pulmonary	No	0.9
			Cardiac arrhythmias	Renal
8	15 y	50	Reyes syndrome	Renal	Yes	4.5
			Pneumonia	Liver
			Intracranial hypertension
9	6 y	36.5	Post BM transplant	Liver	Yes	0.6
			Adenovirus viraemia	Renal
10	3 y	13.0	Diarrhoea + HUS (CNS involvement)	Renal	Yes	0.0
11	6 m	6.8	Congenital heart disease	Multiple organ failure	No	0.1

DKA, diabetic ketoacidosis; BM, bone marrow; HUS, haemolytic uremic syndrome; CNS, central nervous system. Age represented as months (m), years (y) and days (d).

Open in new tab

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.

Table 2.

CRRT prescriptions, access, tubing and cardiovascular profile on initiating therapy

Patient	Access	Aquamax filter/tubing	CRRT mode	Blood flow (ml/min)	Dialysate flow (ml/1.73 m²/h)	Pre/post dilution flow (ml/1.73 m²/h)	Systemic anti-coagulation	Circuit life (h)	Duration of therapy (h)	Inotropes	Pre-CRRT BP	BP post-initiating CRRT	Blood prime
1	8F-12cm Hospal	HFO3/aqualine S	CVVH	50–60	–	Pre: 2160	Heparin	54	201	Dopamine	113/55	111/50	Yes
			CVVH	50–60	–	Pre: 870+ Post: 1300	Heparin	72–78
2	6.5F Gamcath	HFO3/aqualine S	CVVHD	50–60	1650–3700	–	Heparin	1–20	23	Dopamine	56/44	89/55	Yes
3	6.5F Gamcath	HFO3/aqualine S	CVVH	30–50	–	Pre: 1900–3300	Heparin	16–38	371	Milrinone, dopamine, epinephrine	110/78	105/75	Yes
			CVVHD	50	1400–2800	–	Citrate	6–52
4	Med comp 10 F Splitcath	HFO3/aqualine S	CVVHD	50–80	1050–4200	–	Heparin	17	34	81/49	116/73	Yes
5	6.5F Gamcath	HFO3/aqualine S	CVVHD	30–40	2900–3850	–	Heparin	44	44		64/39	68/48	Yes
6	11.5F-12 cm Mahurkar	HFO7/aqualine	CVVH	100–160	–	Pre: 2700	Heparin	20–25	78	Milrinone, dopamine	105/64	112/64	No
			CVVH	130	–	Post: 2700	None	2
			CVVH	100–160	–	Pre: 2700	None	11
			CVVHD	130	2700	–	Citrate	1
7	6.5F Gamcath	HFO3/aqualine S	CVVH	50	–	Pre: 2160–2600	Heparin	8–20	53	Milrinone, dopamine, epinephrine	105/52	91/48	Yes
8	11.5F-12 cm Quinton	HFO7/aqualine	CVVHD	90–100	1000–2100	–	Heparin	16–25	41	Dopamine, epinephrine, norepinephrine	141/65	128/86	No
9	11.5F Quinton	HFO7/aqualine	CVVHD	70–150	1900	–	Heparin	3–27	30		114/68	116/78	No
10	8F-12 cm Hospal	HFO3/aqualine S	CVVHD	50	1900	–	None	4–12	31		98/57	99/49	Yes
			CVVHDF	50	1900	Post: 1900	None	15
11	R carotid artery 12F, L.int jug 14F	HFO3/aqualine	CVVHD +ECMO*	50	2000	–	Heparin	72	72	Milrinone, dopamine	46/43	46/44	Yes

Patient	Access	Aquamax filter/tubing	CRRT mode	Blood flow (ml/min)	Dialysate flow (ml/1.73 m²/h)	Pre/post dilution flow (ml/1.73 m²/h)	Systemic anti-coagulation	Circuit life (h)	Duration of therapy (h)	Inotropes	Pre-CRRT BP	BP post-initiating CRRT	Blood prime
1	8F-12cm Hospal	HFO3/aqualine S	CVVH	50–60	–	Pre: 2160	Heparin	54	201	Dopamine	113/55	111/50	Yes
			CVVH	50–60	–	Pre: 870+ Post: 1300	Heparin	72–78
2	6.5F Gamcath	HFO3/aqualine S	CVVHD	50–60	1650–3700	–	Heparin	1–20	23	Dopamine	56/44	89/55	Yes
3	6.5F Gamcath	HFO3/aqualine S	CVVH	30–50	–	Pre: 1900–3300	Heparin	16–38	371	Milrinone, dopamine, epinephrine	110/78	105/75	Yes
			CVVHD	50	1400–2800	–	Citrate	6–52
4	Med comp 10 F Splitcath	HFO3/aqualine S	CVVHD	50–80	1050–4200	–	Heparin	17	34	81/49	116/73	Yes
5	6.5F Gamcath	HFO3/aqualine S	CVVHD	30–40	2900–3850	–	Heparin	44	44		64/39	68/48	Yes
6	11.5F-12 cm Mahurkar	HFO7/aqualine	CVVH	100–160	–	Pre: 2700	Heparin	20–25	78	Milrinone, dopamine	105/64	112/64	No
			CVVH	130	–	Post: 2700	None	2
			CVVH	100–160	–	Pre: 2700	None	11
			CVVHD	130	2700	–	Citrate	1
7	6.5F Gamcath	HFO3/aqualine S	CVVH	50	–	Pre: 2160–2600	Heparin	8–20	53	Milrinone, dopamine, epinephrine	105/52	91/48	Yes
8	11.5F-12 cm Quinton	HFO7/aqualine	CVVHD	90–100	1000–2100	–	Heparin	16–25	41	Dopamine, epinephrine, norepinephrine	141/65	128/86	No
9	11.5F Quinton	HFO7/aqualine	CVVHD	70–150	1900	–	Heparin	3–27	30		114/68	116/78	No
10	8F-12 cm Hospal	HFO3/aqualine S	CVVHD	50	1900	–	None	4–12	31		98/57	99/49	Yes
			CVVHDF	50	1900	Post: 1900	None	15
11	R carotid artery 12F, L.int jug 14F	HFO3/aqualine	CVVHD +ECMO*	50	2000	–	Heparin	72	72	Milrinone, dopamine	46/43	46/44	Yes

*‘Medtronic 1/4’ Carmeda coated circuit; oxygenator — Medos Hilite 2400 LT; priming volume — 400 ml.

Open in new tab

Table 2.

CRRT prescriptions, access, tubing and cardiovascular profile on initiating therapy

Patient	Access	Aquamax filter/tubing	CRRT mode	Blood flow (ml/min)	Dialysate flow (ml/1.73 m²/h)	Pre/post dilution flow (ml/1.73 m²/h)	Systemic anti-coagulation	Circuit life (h)	Duration of therapy (h)	Inotropes	Pre-CRRT BP	BP post-initiating CRRT	Blood prime
1	8F-12cm Hospal	HFO3/aqualine S	CVVH	50–60	–	Pre: 2160	Heparin	54	201	Dopamine	113/55	111/50	Yes
			CVVH	50–60	–	Pre: 870+ Post: 1300	Heparin	72–78
2	6.5F Gamcath	HFO3/aqualine S	CVVHD	50–60	1650–3700	–	Heparin	1–20	23	Dopamine	56/44	89/55	Yes
3	6.5F Gamcath	HFO3/aqualine S	CVVH	30–50	–	Pre: 1900–3300	Heparin	16–38	371	Milrinone, dopamine, epinephrine	110/78	105/75	Yes
			CVVHD	50	1400–2800	–	Citrate	6–52
4	Med comp 10 F Splitcath	HFO3/aqualine S	CVVHD	50–80	1050–4200	–	Heparin	17	34	81/49	116/73	Yes
5	6.5F Gamcath	HFO3/aqualine S	CVVHD	30–40	2900–3850	–	Heparin	44	44		64/39	68/48	Yes
6	11.5F-12 cm Mahurkar	HFO7/aqualine	CVVH	100–160	–	Pre: 2700	Heparin	20–25	78	Milrinone, dopamine	105/64	112/64	No
			CVVH	130	–	Post: 2700	None	2
			CVVH	100–160	–	Pre: 2700	None	11
			CVVHD	130	2700	–	Citrate	1
7	6.5F Gamcath	HFO3/aqualine S	CVVH	50	–	Pre: 2160–2600	Heparin	8–20	53	Milrinone, dopamine, epinephrine	105/52	91/48	Yes
8	11.5F-12 cm Quinton	HFO7/aqualine	CVVHD	90–100	1000–2100	–	Heparin	16–25	41	Dopamine, epinephrine, norepinephrine	141/65	128/86	No
9	11.5F Quinton	HFO7/aqualine	CVVHD	70–150	1900	–	Heparin	3–27	30		114/68	116/78	No
10	8F-12 cm Hospal	HFO3/aqualine S	CVVHD	50	1900	–	None	4–12	31		98/57	99/49	Yes
			CVVHDF	50	1900	Post: 1900	None	15
11	R carotid artery 12F, L.int jug 14F	HFO3/aqualine	CVVHD +ECMO*	50	2000	–	Heparin	72	72	Milrinone, dopamine	46/43	46/44	Yes

Patient	Access	Aquamax filter/tubing	CRRT mode	Blood flow (ml/min)	Dialysate flow (ml/1.73 m²/h)	Pre/post dilution flow (ml/1.73 m²/h)	Systemic anti-coagulation	Circuit life (h)	Duration of therapy (h)	Inotropes	Pre-CRRT BP	BP post-initiating CRRT	Blood prime
1	8F-12cm Hospal	HFO3/aqualine S	CVVH	50–60	–	Pre: 2160	Heparin	54	201	Dopamine	113/55	111/50	Yes
			CVVH	50–60	–	Pre: 870+ Post: 1300	Heparin	72–78
2	6.5F Gamcath	HFO3/aqualine S	CVVHD	50–60	1650–3700	–	Heparin	1–20	23	Dopamine	56/44	89/55	Yes
3	6.5F Gamcath	HFO3/aqualine S	CVVH	30–50	–	Pre: 1900–3300	Heparin	16–38	371	Milrinone, dopamine, epinephrine	110/78	105/75	Yes
			CVVHD	50	1400–2800	–	Citrate	6–52
4	Med comp 10 F Splitcath	HFO3/aqualine S	CVVHD	50–80	1050–4200	–	Heparin	17	34	81/49	116/73	Yes
5	6.5F Gamcath	HFO3/aqualine S	CVVHD	30–40	2900–3850	–	Heparin	44	44		64/39	68/48	Yes
6	11.5F-12 cm Mahurkar	HFO7/aqualine	CVVH	100–160	–	Pre: 2700	Heparin	20–25	78	Milrinone, dopamine	105/64	112/64	No
			CVVH	130	–	Post: 2700	None	2
			CVVH	100–160	–	Pre: 2700	None	11
			CVVHD	130	2700	–	Citrate	1
7	6.5F Gamcath	HFO3/aqualine S	CVVH	50	–	Pre: 2160–2600	Heparin	8–20	53	Milrinone, dopamine, epinephrine	105/52	91/48	Yes
8	11.5F-12 cm Quinton	HFO7/aqualine	CVVHD	90–100	1000–2100	–	Heparin	16–25	41	Dopamine, epinephrine, norepinephrine	141/65	128/86	No
9	11.5F Quinton	HFO7/aqualine	CVVHD	70–150	1900	–	Heparin	3–27	30		114/68	116/78	No
10	8F-12 cm Hospal	HFO3/aqualine S	CVVHD	50	1900	–	None	4–12	31		98/57	99/49	Yes
			CVVHDF	50	1900	Post: 1900	None	15
11	R carotid artery 12F, L.int jug 14F	HFO3/aqualine	CVVHD +ECMO*	50	2000	–	Heparin	72	72	Milrinone, dopamine	46/43	46/44	Yes

*‘Medtronic 1/4’ Carmeda coated circuit; oxygenator — Medos Hilite 2400 LT; priming volume — 400 ml.

Open in new tab

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 3 and in the discussion.

Table 3.

Technical problems encountered with the AQUARIUS™, and possible solutions

Problem (consequences)	Explanation, actual and theoretical solutions
(1) Maintaining normothermia	Addition of the Hotline™ to CRRT circuit
(2) Frequent TMP alarms, with minute-to-minute variation between high and low pressures (frequent interruptions to treatment and increased clotting tendency)	Pumps speed up and down to give the desired fluid delivery and loss
	Revision of the software led to a partial resolution but also increased the minimum replacement and dialysis fluid rates in the paediatric mode from 100 ml/h to ≥600 ml/h. By maintaining these higher rates the issue has largely resolved
(3) The minimum recommended dialysate and replacement fluid rate in the paediatric program is 600 ml/h (excessive clearance of drugs and solutes)
(4) Balance alarms	Malfunction of the effluent pump resolved by revising the software. Alarms decreased by keeping the dialysate and replacement fluid rate ≥600 ml/h
• frequent balance alarms (stopping the blood pump if deviation >20 ml in the paediatric program)	Persistence of balance alarms—possibly from partial obstruction of the substitution fluid flow exiting from the bags (cone port connection difficult & the broken seal occludes the water channel; spiking the bag may cause kinking of tubing).
• sudden spinning of effluent pump [excessive ultrafiltration (UF)]	PRISMA™ effluent bags not used on AQUARIUS™ (PRISMA™ fill top-down, AQUARIUS™ from bottom-up)
• dialysate leak with PRISMA™ effluent bags (inaccurate balance records)
(5) Negative ‘pressure drop’ i.e. return pressure > access pressure	More likely with low blood-flow rate, small filter, addition of the Hotline™ to the circuit or post-dilutional CVVHDF
	Lower limit: −30 mmHg
	Increase the pre-dilution or blood-flow rate
(6) Recurrent clots in the circuit, especially in the bubble chamber	Maintain ACT 170–220 if low blood flow rate, or history of recurrent clotting
	Limit the filtration fraction (<20%)
	Prophylactic circuit change 48 h
	Consider pre-filtered normal saline infusion or dilute the heparin and run from a separate infusion pump
(7) Single weigh scale for dialysate and replacement fluid (only one solution can be used in the CVVHDF mode; high risk of developing metabolic alkalosis on citrate anticoagulation with commercially available solutions)	Citrate anticoagulation with a pharmacy-prepared low-bicarbonate solution
	CVVHD using an external infusion to give normal saline (declined for safety issues)
	Consider heparin-free or tight heparin protocols in conjunction with frequent saline flushes pre-filter
(8) Only post-dilutional CVVHDF is possible (increased risk of clotting; negative ‘pressure drop’)	In the CVVHDF mode the pre-filter pump drives the dialysate and the post-filter pump drives the replacement fluid
(9) Leak from the back of the return-pressure sensor (once—during therapy; multiple—on dismantling)	If sudden drop in return-pressure check for a blood leak
	Policy of wearing gloves on dismantling
(10) Master keyboard failure during priming (frequent attempts of priming resulting in excessive waste)	Resolved by pressing the blood pump so that the screen and pump communicate
	The software is currently undergoing revision

Problem (consequences)	Explanation, actual and theoretical solutions
(1) Maintaining normothermia	Addition of the Hotline™ to CRRT circuit
(2) Frequent TMP alarms, with minute-to-minute variation between high and low pressures (frequent interruptions to treatment and increased clotting tendency)	Pumps speed up and down to give the desired fluid delivery and loss
	Revision of the software led to a partial resolution but also increased the minimum replacement and dialysis fluid rates in the paediatric mode from 100 ml/h to ≥600 ml/h. By maintaining these higher rates the issue has largely resolved
(3) The minimum recommended dialysate and replacement fluid rate in the paediatric program is 600 ml/h (excessive clearance of drugs and solutes)
(4) Balance alarms	Malfunction of the effluent pump resolved by revising the software. Alarms decreased by keeping the dialysate and replacement fluid rate ≥600 ml/h
• frequent balance alarms (stopping the blood pump if deviation >20 ml in the paediatric program)	Persistence of balance alarms—possibly from partial obstruction of the substitution fluid flow exiting from the bags (cone port connection difficult & the broken seal occludes the water channel; spiking the bag may cause kinking of tubing).
• sudden spinning of effluent pump [excessive ultrafiltration (UF)]	PRISMA™ effluent bags not used on AQUARIUS™ (PRISMA™ fill top-down, AQUARIUS™ from bottom-up)
• dialysate leak with PRISMA™ effluent bags (inaccurate balance records)
(5) Negative ‘pressure drop’ i.e. return pressure > access pressure	More likely with low blood-flow rate, small filter, addition of the Hotline™ to the circuit or post-dilutional CVVHDF
	Lower limit: −30 mmHg
	Increase the pre-dilution or blood-flow rate
(6) Recurrent clots in the circuit, especially in the bubble chamber	Maintain ACT 170–220 if low blood flow rate, or history of recurrent clotting
	Limit the filtration fraction (<20%)
	Prophylactic circuit change 48 h
	Consider pre-filtered normal saline infusion or dilute the heparin and run from a separate infusion pump
(7) Single weigh scale for dialysate and replacement fluid (only one solution can be used in the CVVHDF mode; high risk of developing metabolic alkalosis on citrate anticoagulation with commercially available solutions)	Citrate anticoagulation with a pharmacy-prepared low-bicarbonate solution
	CVVHD using an external infusion to give normal saline (declined for safety issues)
	Consider heparin-free or tight heparin protocols in conjunction with frequent saline flushes pre-filter
(8) Only post-dilutional CVVHDF is possible (increased risk of clotting; negative ‘pressure drop’)	In the CVVHDF mode the pre-filter pump drives the dialysate and the post-filter pump drives the replacement fluid
(9) Leak from the back of the return-pressure sensor (once—during therapy; multiple—on dismantling)	If sudden drop in return-pressure check for a blood leak
	Policy of wearing gloves on dismantling
(10) Master keyboard failure during priming (frequent attempts of priming resulting in excessive waste)	Resolved by pressing the blood pump so that the screen and pump communicate
	The software is currently undergoing revision

Hotline™ (Smiths-Level 1 Inc., Rockland, MA, USA); PRISMA™ (Gambro AB, Stockholm, Sweden); AQUARIUS™ (Edwards Lifesciences AG, Irvine, CA, USA).

Open in new tab

Table 3.

Technical problems encountered with the AQUARIUS™, and possible solutions

Problem (consequences)	Explanation, actual and theoretical solutions
(1) Maintaining normothermia	Addition of the Hotline™ to CRRT circuit
(2) Frequent TMP alarms, with minute-to-minute variation between high and low pressures (frequent interruptions to treatment and increased clotting tendency)	Pumps speed up and down to give the desired fluid delivery and loss
	Revision of the software led to a partial resolution but also increased the minimum replacement and dialysis fluid rates in the paediatric mode from 100 ml/h to ≥600 ml/h. By maintaining these higher rates the issue has largely resolved
(3) The minimum recommended dialysate and replacement fluid rate in the paediatric program is 600 ml/h (excessive clearance of drugs and solutes)
(4) Balance alarms	Malfunction of the effluent pump resolved by revising the software. Alarms decreased by keeping the dialysate and replacement fluid rate ≥600 ml/h
• frequent balance alarms (stopping the blood pump if deviation >20 ml in the paediatric program)	Persistence of balance alarms—possibly from partial obstruction of the substitution fluid flow exiting from the bags (cone port connection difficult & the broken seal occludes the water channel; spiking the bag may cause kinking of tubing).
• sudden spinning of effluent pump [excessive ultrafiltration (UF)]	PRISMA™ effluent bags not used on AQUARIUS™ (PRISMA™ fill top-down, AQUARIUS™ from bottom-up)
• dialysate leak with PRISMA™ effluent bags (inaccurate balance records)
(5) Negative ‘pressure drop’ i.e. return pressure > access pressure	More likely with low blood-flow rate, small filter, addition of the Hotline™ to the circuit or post-dilutional CVVHDF
	Lower limit: −30 mmHg
	Increase the pre-dilution or blood-flow rate
(6) Recurrent clots in the circuit, especially in the bubble chamber	Maintain ACT 170–220 if low blood flow rate, or history of recurrent clotting
	Limit the filtration fraction (<20%)
	Prophylactic circuit change 48 h
	Consider pre-filtered normal saline infusion or dilute the heparin and run from a separate infusion pump
(7) Single weigh scale for dialysate and replacement fluid (only one solution can be used in the CVVHDF mode; high risk of developing metabolic alkalosis on citrate anticoagulation with commercially available solutions)	Citrate anticoagulation with a pharmacy-prepared low-bicarbonate solution
	CVVHD using an external infusion to give normal saline (declined for safety issues)
	Consider heparin-free or tight heparin protocols in conjunction with frequent saline flushes pre-filter
(8) Only post-dilutional CVVHDF is possible (increased risk of clotting; negative ‘pressure drop’)	In the CVVHDF mode the pre-filter pump drives the dialysate and the post-filter pump drives the replacement fluid
(9) Leak from the back of the return-pressure sensor (once—during therapy; multiple—on dismantling)	If sudden drop in return-pressure check for a blood leak
	Policy of wearing gloves on dismantling
(10) Master keyboard failure during priming (frequent attempts of priming resulting in excessive waste)	Resolved by pressing the blood pump so that the screen and pump communicate
	The software is currently undergoing revision

Problem (consequences)	Explanation, actual and theoretical solutions
(1) Maintaining normothermia	Addition of the Hotline™ to CRRT circuit
(2) Frequent TMP alarms, with minute-to-minute variation between high and low pressures (frequent interruptions to treatment and increased clotting tendency)	Pumps speed up and down to give the desired fluid delivery and loss
	Revision of the software led to a partial resolution but also increased the minimum replacement and dialysis fluid rates in the paediatric mode from 100 ml/h to ≥600 ml/h. By maintaining these higher rates the issue has largely resolved
(3) The minimum recommended dialysate and replacement fluid rate in the paediatric program is 600 ml/h (excessive clearance of drugs and solutes)
(4) Balance alarms	Malfunction of the effluent pump resolved by revising the software. Alarms decreased by keeping the dialysate and replacement fluid rate ≥600 ml/h
• frequent balance alarms (stopping the blood pump if deviation >20 ml in the paediatric program)	Persistence of balance alarms—possibly from partial obstruction of the substitution fluid flow exiting from the bags (cone port connection difficult & the broken seal occludes the water channel; spiking the bag may cause kinking of tubing).
• sudden spinning of effluent pump [excessive ultrafiltration (UF)]	PRISMA™ effluent bags not used on AQUARIUS™ (PRISMA™ fill top-down, AQUARIUS™ from bottom-up)
• dialysate leak with PRISMA™ effluent bags (inaccurate balance records)
(5) Negative ‘pressure drop’ i.e. return pressure > access pressure	More likely with low blood-flow rate, small filter, addition of the Hotline™ to the circuit or post-dilutional CVVHDF
	Lower limit: −30 mmHg
	Increase the pre-dilution or blood-flow rate
(6) Recurrent clots in the circuit, especially in the bubble chamber	Maintain ACT 170–220 if low blood flow rate, or history of recurrent clotting
	Limit the filtration fraction (<20%)
	Prophylactic circuit change 48 h
	Consider pre-filtered normal saline infusion or dilute the heparin and run from a separate infusion pump
(7) Single weigh scale for dialysate and replacement fluid (only one solution can be used in the CVVHDF mode; high risk of developing metabolic alkalosis on citrate anticoagulation with commercially available solutions)	Citrate anticoagulation with a pharmacy-prepared low-bicarbonate solution
	CVVHD using an external infusion to give normal saline (declined for safety issues)
	Consider heparin-free or tight heparin protocols in conjunction with frequent saline flushes pre-filter
(8) Only post-dilutional CVVHDF is possible (increased risk of clotting; negative ‘pressure drop’)	In the CVVHDF mode the pre-filter pump drives the dialysate and the post-filter pump drives the replacement fluid
(9) Leak from the back of the return-pressure sensor (once—during therapy; multiple—on dismantling)	If sudden drop in return-pressure check for a blood leak
	Policy of wearing gloves on dismantling
(10) Master keyboard failure during priming (frequent attempts of priming resulting in excessive waste)	Resolved by pressing the blood pump so that the screen and pump communicate
	The software is currently undergoing revision

Hotline™ (Smiths-Level 1 Inc., Rockland, MA, USA); PRISMA™ (Gambro AB, Stockholm, Sweden); AQUARIUS™ (Edwards Lifesciences AG, Irvine, CA, USA).

Open in new tab

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.

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.

Conflict of interest statement. None declared.

References

1

Warady B, Bunchman T. Dialysis therapy for children with acute renal failure: survey results.

Pediatr Nephrol

2000

;

15

:

11

–13

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

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

5

Lacour F, Maheut H. AN69 membrane and conversion enzyme inhibitors: prevention of anaphylactic shock by alkaline rinsing?.

Nephrologie

1992

;

13

:

135

–136

6

Tournier O, Delaunay M.

The AN-69 dialysis membrane

. Hospital Product Pamphlet

1995

1

–36

7

Renaux JL, Thomas M.

Hypersensitivity reactions and dialysis membranes

. Hospital Product Pamphlet

1996

1

–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

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

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

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

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

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

Author notes

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

Download all slides

Month:	Total Views:
January 2017	11
February 2017	17
March 2017	22
April 2017	7
May 2017	11
June 2017	15
July 2017	10
August 2017	20
September 2017	15
October 2017	18
November 2017	17
December 2017	91
January 2018	77
February 2018	52
March 2018	87
April 2018	49
May 2018	56
June 2018	53
July 2018	38
August 2018	30
September 2018	32
October 2018	28
November 2018	44
December 2018	64
January 2019	31
February 2019	50
March 2019	58
April 2019	74
May 2019	51
June 2019	36
July 2019	38
August 2019	45
September 2019	50
October 2019	50
November 2019	37
December 2019	42
January 2020	42
February 2020	48
March 2020	37
April 2020	46
May 2020	25
June 2020	37
July 2020	66
August 2020	31
September 2020	40
October 2020	39
November 2020	31
December 2020	40
January 2021	47
February 2021	42
March 2021	34
April 2021	40
May 2021	49
June 2021	35
July 2021	34
August 2021	31
September 2021	28
October 2021	37
November 2021	16
December 2021	27
January 2022	32
February 2022	31
March 2022	30
April 2022	55
May 2022	40
June 2022	25
July 2022	41
August 2022	33
September 2022	30
October 2022	34
November 2022	28
December 2022	18
January 2023	27
February 2023	15
March 2023	10
April 2023	17
May 2023	21
June 2023	23
July 2023	14
August 2023	21
September 2023	57
October 2023	33
November 2023	40
December 2023	35
January 2024	39
February 2024	31
March 2024	63
April 2024	23

Article Contents

Continuous renal replacement therapy (CRRT) in children using the AQUARIUS™

Introduction

Methods

Results

Discussion

Benefits

(1) Hypothermia

(2) and (3) TMP alarms and minimum substitution fluid rate

(4) Balance alarms

(5) Negative ‘pressure drop’

(6) Recurrent clots

(7) Single substitution fluid weighing scale

(8) Post-dilutional CVVHDF

(9) Return-pressure-sensor leak

(10) Master keyboard failure

Conclusion

References

Author notes

Comments

Citations

Views

Altmetric

Email alerts

Citing articles via

Latest

Most Read

Most Cited

Article Contents

Continuous renal replacement therapy (CRRT) in children using the AQUARIUS™

Introduction

Methods

Results

Discussion

Benefits

(1) Hypothermia

(2) and (3) TMP alarms and minimum substitution fluid rate

(4) Balance alarms

(5) Negative ‘pressure drop’

(6) Recurrent clots

(7) Single substitution fluid weighing scale

(8) Post-dilutional CVVHDF

(9) Return-pressure-sensor leak

(10) Master keyboard failure

Conclusion

References

Author notes

Comments

Citations

Views

Altmetric

Email alerts

Citing articles via

Latest

Most Read

Most Cited

This Feature Is Available To Subscribers Only