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CJASN ePress. Published on August 28, 2019 as doi: 10.2215/CJN.03240319

Article

Kidney Support in Children using an Ultrafiltration Device

A Multicenter, Retrospective Study

Shina Menon, 1 John Broderick, 2,3 Raj Munshi, 1 Lynn Dill, 4 Bradley DePaoli, 2 Sahar Fathallah-Shaykh, 4 Donna Claes, 2,3 Stuart L. Goldstein, 2,3 and David J. Askenazi 4

Abstract Background and objectives Provision of kidney replacement therapy (KRT) to manage kidney injury and volume overload in critically ill neonates and small children is technically challenging. The use of machines designed for adult-sized patients, necessitates large catheters, a high extracorporeal volume relative to patient size, and need for blood priming. The Aquadex FlexFlow System (CHF Solutions Inc., Eden Prairie, MN) is an ultra ltration device designed for uid removal in adults with diuretic resistant heart failure. It has an extracorporeal volume of 33 ml, which can potentially mitigate some complications seen at onset of KRT in smaller infants.

Design, setting, participants, & measurements In this multicenter, retrospective case series of children who received KRT with an ultraltration device ( n=119 admissions, 884 circuits), we report demographics, circuit characteristics, complications, and short- andlong-term outcomes.Patientswere grouped according toweight ( ,10, 1020, and .20 kg), and received one of three modalities: slow continuous ultraltration, continuous venovenous hemo ltration (CVVH), or prolonged intermittent KRT. Our primary outcome was survival to end of KRT.

Results Treatment patterns and outcomes varied between the groups. In patients who weighed ,10 kg, the primary indication was AKI in 40%, volume overload in 46%, and ESKD in 14%. These patients primarily received CVVH (66%, n=48) and prolonged intermittent KRT (21%, n=15). In the group weighing . 20 kg, volume overload was the primary indication in 91% and slow continuous ultraltration was the most common modality. Patients , 10 kg had lower KRT survival than those . 20 kg (60% versus 97%), more volume overload at onset, and received KRT for a longer duration. Cardiovascular complications at initiation were seen in 3% of treatments and none were severe. Complications during therapy were seen in 15% treatments and most were vascular access related.

Conclusions We report the rst pediatric experience using an ultra ltration device to provide a range of therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultra ltration. We were able to initiate KRT with minimal complications, particularly in critically ill neonates. There is an unmet need for devices speci cally designed for younger patients. Having siz e-appropriate machines will improve the care of smaller children who require kidney support. CJASN 14: ccc ccc , 2019. doi: https://doi.org/10.2215/CJN.03240319

Introduction

AKI and volume overload are common and are associated with morbidity and mortality in critically ill neonates and children (1 3). In recent years, continuous renal replace ment therapy (CRRT) has emerged as the preferred modality to provide kidney support to such children (4). CRRT is used sparingly in neonates and is associated with worse outcomes compared with larger children (5,6). The main reasons for the lower use of CRRT in infants are that it is technically challenging and has higher risk of complications than in older and larger children (weighing . 10 kg). Machines designed for adult-sized patients require larger catheters, tubing, and lters, which result in a high extracorporeal volume relative to patient size (6,7). In the United

States, there are no CRRT machines approved by the US Food and Drug Administration (FDA) for use in children , 20 kg; nevertheless, existing CRRT ma- chines approved for use in older children are used off- label in small children. To reduce the complications at KRT initiation from large extracorporeal volume, most centers prime the circuit with blood when the extracorporeal volume is . 10% of total blood volume. Although blood primes are generally safe, they can result in hypocalcemia, hy perkalemia, acidosis, thrombocytopenia, and coagulopathy around initia- tion. A recent single study evaluation of hemody- namic stability in neonates (eight patients, 70 sessions) after CRRT initiation showed that 55% of sessions had intradialytic hypotension, most of which occurred shortly after CRRT initiation (8).

1 Division of Pediatric Nephrology, Seattle Children’s Hospital, University of Washington, Seattle, Washington; 2 Center for Acute Care Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 3 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; and 4 Division of Pediatric Nephrology, University of Alabama at Birmingham, Birmingham, Alabama

Correspondence:

Dr. Shina Menon, Division of Pediatric Nephrology, Seattle Children’s Hospital, Seattle, WA 98145- 5005. Email: shina. menon@ seattlechildrens.org

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Furthermore, dialysis machines with smaller extracor- poreal volume may provide an option for KRT to neonates with ESKD who are unable to initiate peritoneal dialysis (PD) because of their small size, recent abdominal surgery, or abdominal wall defect. Novel machines designed for neonates are used in a few centers in Europe, but are not currently available in the United States (9,10). The Aquadex FlexFlow System (Aquadex; CHF Solutions Inc., Eden Prairie, MN) is FDA- approved for isolated ultra ltration (UF) in adults with diuretic-resistant congestive heart failure (11,12). With an extracorporeal volume of 33 ml, it can mitigate some complications seen at CRRT initiation in smaller infants. Askenazi et al. (7) published a case series of continuous venovenous hemo ltration (CVVH) in 12 infants and small children by adapting the device. They were able to initiate CVVH with minimal complications (7). Volume overload is common in critically ill children (13,14). Although volume overload and AKI are often interrelated and have similar deleterious effects, they may not always occur together. Volume overload may be seen without signicant kidney dysfunction, as in patients with congestive heart failure or nephrotic syndrome. These children are often managed conservatively with diuretics and an ultraltration device has not been widely used (15). Given that volume overload, with or without AKI, is a common indication for kidney support in children, the paucity of data on its use in pediatrics is surprising. We performed a multicenter study to report the charac- teristics of children who received kidney support with Aquadex. We describe demographics and short- and long- term outcomes in these patients. We also report differences in KRT modality (slow continuous ultra ltration versus CVVH versus prolonged inter mittent kidney replace- ment therapy), circuit charac teristics, and complications during KRT.

Materials and Methods

Study Design and Population This is a multicenter, descriptive, retrospective case series of children aged 0 20 years, who received KRT with an ultra ltration device from January 2012 to March 2018 at three United States pediatric hospitals (Seattle Children s Hospital [SCH], Seattle, WA; Children s of Alabama [COA], Birmingham, AL, and Cincinnati Child- ren s Hospital Medical Center [CCHMC], Cincinnati, OH). Patients were included from the intensive care units, inpatient oors, and chronic dialysis units. For each pa- tient, the decision to initiate KRT and the modality pre- scribed was per clinician discretion, after reviewing the options of care with the primary team and family. Clin- ical informed caregiver consent for KRT was obtained in accordance with policies for all acute KRT procedures (hemodialysis, PD, CRRT) at each institution. Local insti- tutional review boards at each center approved the study, with a waiver of informed research consent. Demographic, clinical, and circuit data were collected through medical record review, and from institutional CRRT clinical quality improvement databases. Data in- cluded sex, age/weight at admi ssion, primary indication for KRT (AKI, electrolyte abnormalities, volume overload,

and ESKD), percent uid overload (volume overload%), and catheter location and size. Volume overload% was calculated with the formula described by Selewski et al. (16):

Volume overload % ¼ ½CRRT initiation weight ð kg Þ

Hospital admission weight ð kgÞ =

Hospital admission weight ð kgÞ 3 100% :

Circuit data included maximal blood pump ow rate, complications at initiation and during therapy, and anti- coagulation method. We looked at overall circuit life and the proportion of CVVH circuits that survived to 60 hours. For the latter metric, we censored circuits that were dis- connected for procedures or other patient-related issues as has been described previously by the Prospective Pediatric CRRT (ppCRRT) registry (17). The primary outcome was patient survival to end of KRT using the ultra ltration device, i.e. , the patient no longer needed KRT or was transitioned to another modality. Secondary outcomes included survival and kidney func- tion at 1 year or last follow up. Patients were grouped by weight (,10, 1020, and .20 kg) for analyses. We chose these categories on the basis of previ- ous studies that have looked at CRRT in patients , 10 kg, and because CRRT machines are FDA-approved for children .20 kg (5,6,18).

Treatment Modality Kidney support modalities included CVVH, prolonged intermittent KRT, or slow continuous ultra ltration (Sup- plemental Table 1). The three centers differed in their choice of therapy. CVVH was primarily used at SCH and COA, prolonge d intermittent KRT was primarily used at CCHMC, and slow continuous ultra ltration was per- formed at all three. CVVH was provided using replacement uids as pre- viously described (7). Brie y, this device uses the UF 500 lter set, which has a polysulfone membrane with a 0.12 m 2 surface area and a 33 ml ECV. The set has pre- and post lter pigtail ports, an air detector, and a blood-leak detector. The blood pump can run at 10 40 ml/min (at intervals of ve). The ef uent dose used for CVVH was 24 ml/kg per h (at COA) or 2000 ml/1.73 m 2 per hour (at SCH and CCHMC), which is within the maximum UF rate of the device. The UF pump has a range of 0 500 ml/h (at intervals of 10 ml/h) and an accuracy of 6 10% of setting. Pre- or post lter replacement uid was infused with an Alaris (Becton, Dickinson and Company, Franklin Lakes, NJ) uid infusion system via the proximal or distal pigtail, respectively. Prismasol or phoxillum (Gambro Renal Prod- ucts, Inc., Daytona Beach, FL) was used as replacement uid. UF rates were on the basis of the hourly uid intake and overall desired uid balance. CVVH circuits were changed at least every 72 hours per manufacturer protocol. During CVVH or prolonged intermittent KRT, heparin anti- coagulation was infused through a y-connector on the withdrawal (access) line. L aboratory analysis to assess anticoagulation was drawn from the post lter pigtail. A blood warmer (AstoFlo Plus Stihler Electronic; Stuttgart, Germany or HOTLINE Blood and Fluid Warmer; Smiths

CJASN 14: ccc ccc , October, 2019

Pediatric KRT using an Ultrafiltration Device, Menon et al. 3

Medical, Dublin, OH) was placed on the infusion line if required. Slow continuous ultra ltration was used to treat isolated volume overload. This did not involve provision of re- placement uid and the duration of therapy was typically 6 hours. Therapy was labeled as prolonged intermittent KRT when hemo ltration (similar to CVVH above) was performed for an extended period of 6 8 hours, either daily or multiple times per week. The dose used for prolonged intermittent KRT was 2000 ml/1.73 m 2 per hour for 68 hours. The typical blood pump speed (Qb) was 3040 ml/min. Circuits were primed with packed red blood cells (pRBCs) or crystalloid. Crystalloid primes were used if the extracorporeal volume was , 10% of total blood volume, and the patient was clinically stable. If extracor- poreal volume $10% of total blood volume, the circuit was primed with pRBCs per each institution s protocol. At SCH, pRBCs are mixed 1:1 with 5% albumin for the prime. At COA, prime includes pRBCs and sodium bicarbonate in equal parts, and CCHMC uses pRBCs only. Calcium gluconate was given for all initiations at COA, and at SCH and CCHMC was given per clinician decision. If a blood primed circuit was undergoing a planned circuit change, the new circuit was crossprimed with blood from the expiring circuit, when possible.

Statistics The Shapiro Wilk test was used to check for normal distribution. Data were not normally distributed, so con- tinuous variables are reported as median (with inter- quartile range [IQR]). Categorical variables are reported as number and percentage. For analysis, R program was used (R Core Team, 2018; https://www.R-project.org/.)

Results

Patient Characteristics We present data on 117 unique patients (Figure 1). Patients were divided into three groups by weight ( , 10 kg, n =72; 10 20 kg, n =13; . 20 kg, n =32). Two patients in the . 20 kg group had a repeat admission requiring KRT with the ultra ltration device . 12 months after the rst admis- sion; thus there were a total of 119 separate hospital encounters (Table 1). For the short-term outcomes, we evaluated all 119 encounters individually; for long-term outcomes, we looked at 117 patients and considered the rst encounter. The median age and weight at onset of KRT are shown in Table 1. In the , 10 kg group, 44 (61%) were , 30 days old and 58 (82%) weighed , 5 kg. Most patients had an underlying kidney or cardiac disease; however, the indication for KRT was different between the groups. In , 10 kg group, the primary indi- cation was AKI and electrolyte abnormalities in 25%, volume overload in 46%, AKI and volume overload in 15%, and ESKD (with relative or absolute contraindica- tion for PD) in 14%. These patients primarily received CVVH (66%, n =48) and prolonged intermittent KRT (21%, n =15). In patients weighing . 20 kg, volume overload was the primary indication in most (91%, n =31) and slow continuous ultra ltration was the most common modality (94%, n =32).

Primary Outcome Of the 72 patients , 10 kg, 43 (60%) patients survived to end of KRT with the ultra ltration device or transitioned to another modality of kidney support, and 23 (32%) survived to hospital discharge. Among patients . 20 kg, 33 (97%) survived to KRT discontinuation and 23 (68%) survived to hospital discharge.

Secondary Outcomes We looked at survival and kidney outcomes at last follow-up for patients who were discharged from the hospital (Table 2). In the , 10 kg group, of the 23 who survived to hospital discharge, two were transferred to another facility and 12 survived to last follow-up. The median follow-up duration was 13 months (IQR, 12 24) and age at last follow-up was 16 months (IQR, 12 25). In this group, ve patients had ESKD, including two who subsequently received a kidney transplant. Of those, three patients had initiated KRT for underlying CKD and two progressed to ESKD from AKI. After excluding those with ESKD, median eGFR at follow-up was 111 ml/min per 1.73 m 2 (IQR, 102 131). In the entire cohort, hype rtension was present in 15 (60%) patients and proteinuria ( . 0.2 mg protein/mg creatinine on a spot sample) was seen in six patients at last follow-up.

Circuit Characteristics and Outcomes We report on 884 circuits used over 2338 days. Of these,

157 circuits were for slow continuous ultra ltration, 190

for prolonged intermittent KRT, and 537 for CVVH (Supple- mental Table 2). We looked at complications at initiation and during KRT, according to weight (Table 3). The right internal jugular vein was the most common location for vascular access, followed by the femoral vein. Heparin was used in . 80% circuits ( n =731). No antico- agulation was used in 126 circuits (14%). Citrate anti- coagulation was attempted in one patient (two circuits). However, it was not successful because of the need for multiple lines and a nonintegrated system. The median circuit life for the 537 CVVH circuits was 66 hours (IQR, 30 71). Of the CVVH circuits, 71 out of 537 (13%) were discontinued because of patient issues (with- drawal of cardiopulmonary support, elective therapeutic plasmapheresis, radiologic and/or surgical procedures, or improvement in patient condition and trial off CVVH) and ten out of 537 (2%) circuits underwent planned change before 60 hours for staff scheduling reasons. After censoring circuits that were changed because of patient issues or scheduling, we evaluated the remaining

456 out of 537 (85%) circuits and found that 309 (68%) of

these circuits lasted for $ 60 hours, whereas 147 out of

309 (32%) had circuit loss, de ned as unplanned, early

termination at , 60 hours. The reasons for early termi- nation include clot in the circuit (98 out of 147, 67%), problems with vascular ac cess (32 out of 147, 22%), machine malfunction (14 out of 147, 9%), and unknown (three out of 147, 2.0%). Overall, only 28 out of 884 (3%) circuit initiations required an increase in cardiovascular support, and most (24 out of 28, 86%) were in the group weighing # 10 kg (Table 3). In this group, the interventions included extra

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Children who received KRT using an ultrafiltration device N =117

who received KRT using an ultrafiltration device N =117 Treatment Modality Weight 10-20 kg, N =13
who received KRT using an ultrafiltration device N =117 Treatment Modality Weight 10-20 kg, N =13
who received KRT using an ultrafiltration device N =117 Treatment Modality Weight 10-20 kg, N =13

Treatment Modality

Weight 10-20 kg,

N =13

device N =117 Treatment Modality Weight 10-20 kg, N =13 Weight 10 kg, N =72 Weight

Weight 10 kg,

N =72

Modality Weight 10-20 kg, N =13 Weight 10 kg, N =72 Weight > 20 kg, N

Weight > 20 kg,

N =32 *

N =13 Weight 10 kg, N =72 Weight > 20 kg, N =32 * SCUF 9

SCUF 9

Prolonged intermittent

KRT 15

CVVH 48

49 died:

29

20

prior to discharge

on KRT

came off KRT, but died

20 prior to discharge on KRT came off KRT, but died Hospital Mortality Survival and Kidney

Hospital Mortality

Survival and Kidney Outcome at Discharge

SCUF 5

CVVH 8

2 died:

Came off KRT, but died prior to discharge

5 CVVH 8 2 died: Came off KRT, but died prior to discharge SCUF 30 *

SCUF 30 * CVVH 2

11 died:

1 on KRT 10 came off KRT, but died prior to discharge

1 on KRT 10 came off KRT, but died prior to discharge   N =23  
 

N =23

 
N =11 Normal kidney function=3 Chronic Kidney Disease=8 2: died after discharge 1: Transferred
N
=11
Normal kidney function=3
Chronic Kidney Disease=8
2: died after discharge
1: Transferred
N =11 Normal kidney function=3 Chronic Kidney Disease=8 2: died after discharge 1: Transferred

N =21

Normal kidney function=10 Acute Kidney Disease=1 Chronic Kidney Disease=11 Not known=1

Normal kidney function=4 Acute Kidney Disease=7 Chronic Kidney Disease=10

           

9: died after discharge 2: Transferred

 

7: died after discharge

 
  Survival and Kidney Outcome at Follow up    

Survival and Kidney Outcome at Follow up

 
  Survival and Kidney Outcome at Follow up    
 
 

N

=12

 

N =8 Normal kidney function=4 Chronic Kidney Disease=1

N

=14

Normal kidney function=5 Chronic Kidney Disease=2

Normal kidney function=3 Chronic Kidney Disease=6 Kidney transplant=4

Dialysis=3

Dialysis=1

Kidney transplant=2

Kidney transplant=2

Unknown=1

Figure 1. | Flow diagram of all children who initiated kidney replacement therapy using an ultrafiltration device, according to their weight at initiation, through hospital discharge and follow-up. *Two patients had two admissions . 12 months apart. For this figure, their first admission was used. KRT, kidney replacement therapy; SCUF, slow continuous ultrafiltration; CVVH, continuous venovenous hemofiltration.

volume of saline, 5% albumin, or pRBCs in 17 out of 24 (70%), and a new inotrop e or an increase in dose of inotropes in eight patients. Four patients in the group weighing 10 20 kg had cardiorespiratory complications at circuit initiation. No complications at circuit initiation were

seen in the . 20 kg group (Table 3). None had severe decompensation associated with circuit initiation. Overall, complications during therapy were seen in 132 out of 884 treatments (15%). In the group weighing , 10 kg, complications were seen in 106 treatments (15%) and were

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Pediatric KRT using an Ultrafiltration Device, Menon et al. 5

Table 1. Patient characteristics

Characteristic

Group 1 (Weight , 10 kgs)

Group 2 (Weight 10 20 kgs)

Group 3 (Weight . 20 kgs)

 

n

=72

n

=13

n

=34 a

Age at rst KRT Patient location Neonatal ICU Cardiac ICU Pediatric ICU Dialysis unit Inpatient oor Base weight, kg Weight at onset of therapy, kg Female Primary disease Cardiac Kidney Other Primary indication Volume overload AKI and electrolyte abnormalities AKI and volume overload ESKD Treatment modality Slow continuous ultra ltration Prolonged intermittent KRT CVVH Volume overload at onset of KRT (%) Days in hospital before KRT Days in ICU before KRT Days on Ultra ltration Device Number of circuits Initial catheter site Right internal jugular Femoral Other Initial catheter size 6 Fr 7 8 Fr 9 10 Fr 12 14 Fr Other Treatment course survival Hospital survival Kidney outcome at discharge among survivors Normal kidney function Acute kidney disease CKD Not known

19 (7, 87) d

26 (17, 38) mo

190 (158, 258) mo

46 (64)

 

1 (8)

0

13 (18)

3 (23)

 

12 (35) 16 (47) 4 (12)

12 (17)

8 (62)

1 (1)

1 (8)

 

0

0

3.2 (2.6, 4.3) 4.1 (3.1, 5.6) 34 (47)

12.3 (11.5, 13.7) 15.1 (12.9, 15.9) 3 (23)

2 (6) 58.7 (37.1, 77) 60.1 (38.2, 79.2) 20 (59)

21 (29)

 

2 (15)

13 (38)

31 (43)

7 (54)

8 (24)

20 (28)

4 (31)

13 (38)

33 (46)

7 (54)

31 (91)

18 (25)

2 (15)

0

11 (15)

1(8)

2 (6)

10 (14)

3 (23)

1 (3)

9 (12) 15 (21) 48 (67) 20 (5, 40) 13 (3, 28) 12 (2, 23) 9 (3, 33) 4 (2, 10)

5 (38)

32 (94)

0

0

8 (62) 20 (8, 23) 21 (7, 88) 11 (3, 97) 7 (5, 14) 3 (2, 6)

2 (6) 7 (3, 11) 11 (3, 35) 6 (2, 20) 1 (1, 3) 2 (1, 3)

46 (64)

 

6 (46)

19 (56)

19 (26)

3 (23)

7 (21)

7 (10)

4 (31)

8 (24)

25 (35)

3 (23)

1 (3)

37 (51)

7 (54)

5 (15)

5 (7)

2 (15)

8 (23)

 

0

1 (8)

20 (59)

5 (7)

 

0

0

43 (60)

13 (100) 11 (85) ( n =11)

 

33 (97)

23 (32)

23 (68)

( n

=23)

n =23

10

3

4

1

0

7

11

8

12

1

0

0

Continuous variables are shown as median (interquartile range) and categorical variables as number (percentage). The percentages may not add up to 100 because of rounding. KRT, kidney replacement therapy; d, days; mo, months; ICU, intensive care unit; CVVH, continuous venovenous hemo ltration. a Two patients had repeat admissions . 12 months apart requiring KRT and are counted as separate.

primarily vascular access related, with a clot in 37 and catheter malfunction in 12. Bleeding was seen in 17, primarily oozing from catheter insertion sites that im- proved with modi cation of anticoagulation. None had known cerebral or pulmonary hemorrhage attributed to KRT. Hypothermia was seen in four treatments in this group. Clot in the line and hypotension during treatment were the commonest complications in patients weighing 10 20 kg and . 20 kg. Other rare complications (seen in four or fewer treatments each across the entire cohort) included thrombocytopenia, seizure, arrhythmias, acidosis, and hypomagnesemia.

Discussion

We report a three-center experience with an ultraltra- tion device, in children. We used it to provide a range of kidney supportive therapies, including CVVH, prolonged intermittent KRT, and slow continuous ultraltration. Adapt- ing this system to provide CVVH allowed us to initiate KRT with minimal complications in critically ill neonates. More than 50% of infants weighing , 10 kg survived to come off KRT with this device or transition to another modality of kidney support. We were also able to provide kidney support to neonates with ESKD who were unable to receive PD. In patients weighing .20 kg, who primarily

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Table 2. Outcomes at last follow-up of unique patients who survived to hospital discharge

 
 

Characteristics

Group 1 (Weight , 10 kg),

Group 2 (Weight 10 20 kg),

Group 3 (Weight .20 kg),

 

n

=23

n

=11

n

=21 a

Outcome at last follow up

Expired=9

Expired=2

Expired=7

Alive=12

Alive=8

Alive=14

Transferred=2

Transferred=1

Transferred=1

 

Age, mo Median follow-up duration, months Kidney outcome eGFR .150 eGFR 90 150 eGFR 60 90

16 (12, 25) 13 (12, 24)

41 (35, 57) 20 (19, 26)

 

221 (192, 259) 27 (22, 46)

n =12

 

n =8

n =14

 

1

0

0

5

4

3

0

1

2

 

eGFR

,60

1

0

4

eGFR

,15

3

1

0

Kidney transplant

 

2

2

4

   

0

0

1

Unknown Median eGFR at last follow up b

111 (102, 131)

98 (94, 124)

66 (53, 102)

eGFR, estimated Glomerular Filtration Rate. eGFR is reported in ml/min per 1.73 m 2 .

 

a

Two patients had repeat admissions requiring kidney replacement therapy. Follow-up data are from their rst admission. b After excluding those with eGFR ,15.

received slow continuous ultraltration, 97% survived to end of therapy. In addition, we were able to manage a small group of patients with volume overload in the outpatient dialysis unit. Many of our patients who received CVVH were small, young, and critically ill. Because of the challenges pre- viously discussed, a majority of these may not have traditionally received KRT (2,6). The main advantage to the use of this device is the ability to initiate therapy with excellent hemodynamic stability. Fewer than 4% treat- ments had any complications reported at initiation, and none were serious enough to interrupt initiation. The incidence of cardiopulmonary complications at circuit initiation in infants using other machines has not been widely reported. A recent study reported hypotension at onset in 55% of CRRT sessions in neonates with 25% showing recovery within 60 minutes (8). In addition, use of machines with smaller lters (and corresponding tubing sets with lower extracorporeal vol- ume) help reduce the frequent exposure to blood products for blood prime and allow for smaller vascular access and lower blood ow rates (18 20). Using the rule that anyone with extracorporeal volume . 10% receives a blood prime, the smallest available lter most commonly used in the United States (Prisma ex M60; extracorporeal volume 93 ml) necessitates blood prime for anyone weighing , 11.5 kg. By using the ultra ltration device, we were able to avoid blood prime for 23 patients weighing between 4 and 11.5 kg. Complications during ther apy were also infrequent, and mostly related to vascular access (clot or catheter malfunction) or minor bleeding at catheter insertion sites. Hypothermia was reported in four treatments and all were before the use of an in-line blood warmer. Once again, there are limited reports on complications of CRRT in infants. This ultra ltration device has not been widely used in children even for its traditional indication of slow contin- uous ultra ltration (15). Although it is FDA-approved in

patients weighing . 20 kg, we included these patients in our study to highlight the clinical use of this device in the pediatric setting, particularly in patients with congenital heart disease and cardiomyopathies with associated heart failure. In our study, 50 patients (40%) underwent 157 treatments for UF only. Of these, six patients were able to receive treatment in the dialysis unit. The ease of doing UF and a low rate of complications suggests a promising role for this therapy in the ambulatory management of patients with diuretic-resistant volume overload, such as those with steroid-resistant nephrotic syndrome or con- gestive heart failure. Our intensive care unit and hospital survival rate for patients , 10 kg was 32%, which is lower than some previous studies. Symons et al. (5) reported 38% survival to intensive care unit discharge in children , 10 kg; however, in the # 3kg subgroup the survival was only 25%. Data from the ppCRRT registry reported an intensive care unit survival rate of 44% in children # 5 kg (6). A more recent study showed a higher intensive care unit survival rate (57%) in infants , 10 kg receiving CVVH (18). However, 28% of their cohort had inborn errors of metabolism, which typically has better outcomes. They also did not include patients with complex cardiac problems who have higher mortality and the smallest patient weighed 2 kg. The lower survival in our cohort likely re ects the fact that our patients were more premature, had lower weight, and more comorbidity. In our cohort, six patients weighed ,2 kg and the smallest patient was 1.4 kg. KRT using existing dialysis machines would have been difcult and they may not have received KRT without this adapted system. Our 1-year survival for children , 10 kg was 52%; in the subset of patients who were # 30 days at initiation of KRT, it was 16%. This low rate was also secondary to fa ctors mentioned above. Limited data are available on the long-term outcomes of children who start KRT at a younger age. In the multinational study by van Stralen et al. (21), children with ESKD who started KRT in the neonatal period had an estimated 2-year survival of 81% and 5-year

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Pediatric KRT using an Ultrafiltration Device, Menon et al. 7

Table 3. Circuit characteristics by patient weight

 
 

Characteristic

Group 1 (Weight , 10 kg), n =711

Group 2 (Weight 10 20 kg), n =66

Group 3 (Weight . 20 kg), n =107

Blood ow rate, ml/min Cardiorespiratory support at initiation (or with complications at initiation) Type of support needed a Normal saline Inotrope Calcium chloride Albumin Sodium bicarbonate Blood transfusion Circuits with complications during therapy Type of complication a Hypothermia Bleeding Hypotension b Clot Thrombocytopenia Seizure Catheter malfunction Other Anticoagulation Heparin Citrate Argatroban None Unknown/other

40 (30, 40) 24 (3)

40 (30, 40) 4 (7)

40 (40, 40)

0

4

1

8

1

2

8

1

2

5

106 (15)

12 (18)

15 (14)

4

17

30

3

4

37

9

6

2

2

12

8

3

616

47

68

2

0

11

3

91

5

30

2

3

6

Continuous variables are shown as median (interquartile range) and categorical data as number (%). , zero.

 

a

Some patients needed more than one intervention or had multiple complications. b Hypotension was de ned as needing bolus of uid, new inotrope requirement, or an increase in rate of existing inotrope infusion.

survival of 76%. They did not include children in whom kidney support was withheld or withdrawn early because of various reasons, or those who died shortly after initiation, thus potentially overestimating their survival rates. Another study reported 65.3% (32 out of 49) mortality in neonates who started CRRT in the rst 30 days of life (22). The median age of death was 22 days, with 56% of the total deaths occurring within the rst 30 days of life, and 94% within the rst year. The authors did not comment on long term kidney outcomes (20). Nishimi et al. (8) reported 75% mortality in neonates who underwent CRRT; ve out of eight died within 3 months, and one died at 2 years. Although we have been able to successfully provide CVVH using an ultra ltration device, it has certain limita- tions. As it was designed for slow continuous ultraltration, it does not have a pump to provide countercurrent dialysis and can only provide CVVH. The replacement uid and heparin infusions have to be given through separate ow regulators external to the device that are not integrated with it. This requires extra vigilance on the part of the nursing staff in case either the CRRT pump or the replacement uid ow regulator is not running. The accuracy of the UF pump is 610% of setting, which can be a clinically signicant volume change for smaller patients. Additionally, although the extracorporeal volume is low (33 ml), infants weighing , 4 kg will still require a blood prime (for extracorporeal volume . 10%). The ultra ltration device has a sensor that allows non- invasive monitoring of hematocrit and can be used to guide UF. Changes in hematocrit are inversely proportional to

changes in patient blood volume. A typical setting alerts the clinician when the patient s blood volume change exceeds 10%. This technology has been previously used in the maintenance hemodialysis setting to reduce intradia- lytic events related to UF (23,24). There are limited data on its use in acute KRT. We used noninvasive monitoring in some of our older patients to guide UF. However, we do not have data on this. These problems can be addressed by machines speci - cally developed for providing kidney support to small children. The Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) is a pump-driven machine with lters available in three sizes (ranging in volume from 27.2 to 41.5 ml) (9). It can be used with catheters as small as 4 Fr to provide blood ow rates of 5 50 ml/min (25). The Newcastle Infant Dialysis and Ultra ltration System (NIDUS) has been designed to provide continuous veno- venous hemodialysis to infants between 800 g and 8 kg (10). It is a syringe-driven system (extracorporeal volume of 10 ml) that withdraws 5 12.5 ml of blood and passes it through a dialysis lter before returning to the patient. NIDUS can be used with a 4 Fr single-lumen catheter. Despite being able to provide kidney support success- fully to a large cohort, we acknowledge certain limita- tions in our study. Being a re trospective study, we were dependent on data available in our quality improvement database and medical records. In certain cases where the reason for escalation of inotropic support was not specied, we assumed it to be secondary to CRRT initiation. Infor- mation on complications of access placement, including the

8 CJASN

need for multiple catheters was not collected and included in this analysis. Furthermore, as a retrospective study, the data are subject to center and patient selection bias. In conclusion, we report the rst large experience in pediatrics using an ultra ltration device, both for UF and for modi ed CVVH. This study speaks to the unmet need for devices speci cally designed for younger patients. With the use of a machine with small extracorporeal volume, we could initiate CRRT safely without signi cant cardiovas- cular decompensation. Having more size-appropriate ma- chines will shift the bene t risk equation such that small children can get the bene t of kidney support to a level that is closer to larger children and older patients.

Disclosures Dr. Goldstein reports personal fees from and a position as a consultant to CHF Solutions Inc. which manufactures the Aquadex device. Dr. Goldstein also consults for Medtronic Inc. (Minneapolis, MN) which manufactures a CRRT device. Dr. Goldstein receives grant funding from and serves as a consultant and on a Speaker s Bureau for Baxter Healthcare, Inc. (McGaw Park, IL), which manu- facturers a CRRT device. Dr. Askenazi is on a Speakers Bureau for Baxter Healthcare, Inc. (McGaw Park, IL). Dr. Askenazi is also a consultant for CHF Solutions Inc. Dr. Askenazi reports an education grant for neonatal AKI from CHF Solutions Inc. Dr. Broderick, Dr. Claes, Dr. DePaoli, Ms. Dill, Dr. Menon, Dr. Munshi, and Dr. Fathallah-Shaykh have nothing to disclose.

Funding The authors have nothing to disclose.

Supplemental Material This article contains the following supplemental material online at http://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/

Supplemental Table 1. Description of the kidney replacement therapy modality used. Supplemental Table 2. Circuit characteristics by treatment modality.

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Received: March 15, 2019 Accepted: July 17, 2019

S.M. and J.B. contributed equally to this work.

Published online ahead of print. Publication date available at www.cjasn.org.