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1

Comparable Clearance of Valproic Acid with High-Flux

Hemodialysis (HFHD) and Continuous Veno-Venous

Hemodiafiltration (CVVHDF)

S. Walters

University of Michigan Health System, C.S. Mott Children’s Hospital,

Ann Arbor, Michigan, USA

[email protected]

Two female cousins (P1, 11 y/o; P2, 16 y/o) presented comatose

after recreational use of an unknown amount of valproic acid, along

with Gabapentin. They were found together, unresponsive. After IV

fluids, NG lavage, activated charcoal and intubation, they were

transferred to our PICU. Laboratory results showed elevated valproic

acid levels (P1, 536.9 ug/mL; P2, 424.5 ug/mL) and hypernatremia.

Within ~4 hours upon arrival to our PICU both patients had an acute

catheter placed for dialysis. P1 received 3 hours of HFHD, while P2

received ~12 hours of CVVHDF. The t1/2 of valproic acid was reduced

to 2.24 hrs during P1’s 3 hour HFHD run, but t1/2 at 11 hrs after

HFHD was 7.44 hrs. P2’s valproic acid t1/2 decreased to 4.42 hrs and

4.71 hrs at 6 hours and 9 hours, respectively after starting CVVHDF.

P1 was hemodynamically unstable during and after HFHD, requiring

vasopressor medications. Both patients had neurologic recovery.

Several case reports have shown hemodialysis to be effective in the

clearance of valproic acid. The pharmacokinetic properties of valproic

acid of low molecular (144 Da), small volume of distribution (0.5–

1 L/kg), along with increased percentage of unbound drug during

acute ingestions most likely facilitate its ability to be cleared by

dialysis. However, hemodynamic instability may prevent a patient

from receiving HFHD. These cases demonstrate that CVVHDF is an

additional valuable therapy in the setting of acute valproic acid

ingestion.

2

Comparative Efficacy of Priming Options for an Infant

on Prolonged Continuous Renal Replacement Therapy (CRRT)

S. Muneeruddin, R. Hopfner, O. Mansoor, R. Fuentes, B. Gelman, T.

Kato, C. Abitbol

University of Miami/Holtz Children’s Hospital, Miami, Florida, USA

[email protected]

CRRT provides life-sustaining treatment for critically ill infants with

technical limitations of requiring an extracorporeal circuit that may

exceed 20% of the blood volume. Consequently, the circuit requires

priming with blood products and/or albumin at the initiation of each

new CRRT system exposing the infant to risks inherent in multiple

transfusions as well as the “bradykinin release syndrome”. It is

recommended that the CRRT system be electively replaced every

72 hours and whenever it clots. We report our experience with a 6 kg

infant who received a multivisceral transplant for liver and intestinal

failure due to microvillous inclusion disease. Post-operatively, she

suffered prolonged oligo-anuria requiring CRRT for 36 days which is

on-going at the time of this report. The PRISMA® M60 with the AN69

membrane was used to deliver continuous veno-venous hemodiafiltra-

tion (CVVHDF) with Prismasate® solutions for replacement and

dialysate. Heparin was used for anticoagulation at a rate of 10–25

units/kg/hour. Three types of prime were used: 1) 5% albumin (5%Alb)

with packed red blood cells (PRBC)(10 ml/kg) pushed separately; 2)

Naturalized blood (nBlood): 100 ml 5%Alb+100 ml PRBC+Heparin

200 units-recirculated for 15 minutes on CVVHD; 3)Elective circuit

exchange of blood from the old circuit to the new circuit (EE-CRRT).

Average lifetime of the circuit was 60±23 hours and was not different

between the priming options. Profound hypotension and cardiac arrest

occurred on one occasion with 5%Alb. Thereafter, only nBlood was

used when elective exchange could not be used. EE-CRRT was

preferred because no hypotension occurred during the exchange and

no blood transfusions were required.

3

Therapeutic Plasma Exchange for Hyperbilirubinemia in Two

Newborns During Extra Corporeal Membrane Oxygenation

L. Koster-Kamphuis, T. Antonius, A. van Heijst

Raboud University Nijmegen Medical Center

Nijmegen, The Netherlands

[email protected]

Background Extra Corporeal Membrane Oxygenation (ECMO) is an

established therapy for respiratory and circulatory failure in newborns.

Therapeutic plasma exchange (TPE) as treatment for hyperbilirubine-

mia in neonates is described. We describe two neonates with

600

500

400

300

200

100

0

Val

proi

c A

cid

Lev

els

(ug/

mL

)

0 6 12 18 24 30 36

Time (hours)

CVVHDF HFHD

Pediatr Nephrol (2008) 23:1897–19061898

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hyperbilirubinemia while on ECMO treated with TPE after insuffi-

cient result of phototherapy and exchange transfusions.

Patients The first patient was an at full term born male infant weighing

3.6 kg, diagnosed with early-onset group B streptococcal sepsis

requiring ECMO for respiratory and circulatory failure. The second

patient was a male infant born at 34 5/7 weeks, weighing 3.4 kg,

requiring ECMO for respiratory failure associated with a ruptured

omphalocele. Both patients developed severe pulmonary hypertension.

In the first days of life both infants developed an unconjugated

hyperbilirubinemia. Despite intensive phototherapy and exchange

transfusions while on ECMO the bilirubin concentration increased

further. TPE was performed to treat the hyperbilirubinemia.

Methods The PRISMA machine was used with TPE 2000 set. The

system was primed with donor blood and connected to the ECMO

circuit between the child and the bladder box. TPE was performed

with fresh frozen plasma as replacement fluid. Blood flow was

100 ml/min in both children. In one child the exchange volume was

250 ml (0.7×estimated total plasma volume) and in the other 500 ml

(1.3×estimated total plasma volume).

Results The TPE had good result in lowering bilirubin values. One

session was sufficient in both children. No serious adverse events

were seen during the treatment.

Conclusion TPE is an effective treatment for unconjugated hyper-

bilirubinemia of the newborn. TPE is possible to perform in

combination with ECMO.

4

Discrepancy Between Prescribed and Delivered Dose

of Continuous Veno-Venous Hemodiafiltration in Pediatric

and Adult Patients

N. Amin, W. A. Jimenez, M. K. Nguyen, B. Gales, G. Ramos, I. B.

Salusky, O. Yadin and J. J. Zaritsky.

Department of Pediatric Nephrology, David Geffen School of

Medicine at UCLA, Los Angeles, California, USA

[email protected]

While much emphasis had been placed on determining the optimal

prescribed dose of continuous renal replacement therapy (CRRT), it has

yet to be shown that the prescribed dose is actually delivered. In order to

determine whether the clearance prescribed during CRRT is achieved,

we performed a prospective study comparing the prescribed clearance

(corrected for time off therapy, body surface area and ultrafiltration) to

the achieved clearance in both adult and pediatric patients receiving

continuous veno-venous hemodiafiltration (CVVHDF) therapy. A total

of 128 daily creatinine clearance (CrCl) measurements were made over

an average of 4.8±2.3 and 6.5±1.6 consecutive days of CVVHDF

therapy in 16 pediatric and 8 adult patients, respectively. The delivered

clearance was only 71% and 74% of the prescribed clearance in the

pediatric and adult populations, respectively (delivered vs. prescribed

dose, P<0.001). The prescribed dose was significantly higher in the

pediatric compared to the adult patients (P<0.005). The principal cause

of temporary cessation of therapy was filter clotting, accounting for 39%

and 49% of total time off CVVHDF in pediatric and adults respectively.

These results demonstrate that in both populations, despite accounting

for time off therapy, the delivered daily CrCl was significantly less than

prescribed. The reasons for this relatively poor delivered dose have yet

to be identified, but may be secondary to inaccuracies in the current

methods used to calculate the prescribed dose or suboptimal CVVHDF

filter performance. Thus, in order to achieve targeted clearance during

CVVHDF therapy, relatively higher CrCl needs to be prescribed.

5

A Retrospective Study of Outcomes in Pediatric

Hematology/oncology Patients Receiving Continuous

Venovenous Hemodialysis (CVVHD)

Y. Avent, N. Henderson, T. Collie, R. F. Tamburro, L. Elbahlawan,

R. R. Morrison, S. Rajasekaran

St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

[email protected]

Background Children undergoing therapy for cancer are prone to

develop tumor lysis, renal failure or fluid overload as a result of

necessary treatments. Often these patients require modalities of renal

replacement therapy such as CVVHD to support and preserve

electrolyte and fluid homeostasis. The purpose of this project was to

assess the impact of this resource intensive therapy on both short-term

ICU survival and long-term survival in oncology patients 6 months

after an episode of CVVHD.

Methods A retrospective review of an institutional database identified all

patients receiving CVVHD in an 8-bed pediatric oncologic ICU from

January 2003 through December 2007. Abstracted data included

demographics, diagnoses, indications for CVVHD, use of vasoactive

medications, respiratory support, electrolyte values, survival to ICU

discharge and 6month survival after treatment with CVVHD. For patients

requiring a second episode of CVVHD, 6 month survival was analyzed

only if onset of the second episode was at least 6 months after the first.

Results 41 patients underwent 48 episodes of CVVHD averaging 172

treatment days/year. The median age of this cohort was 12 years. Of

the 48 episodes of CVVHD, primary indications were acute renal

failure (n=30, 62.5%), fluid overload (n=12, 25%), chronic renal

failure (n=5, 10.4%), and tumor lysis syndrome (n=1, 2.1%). 30

hematopoietic stem cell transplant (HSCT) patients underwent

CVVHD, accounting for an average of 15.9±2.02 days of therapy.

Primary diagnoses prior to HSCT included leukemia/lymphoma (n=

18, 60%), solid tumor/neuro oncology (n=6, 20%) and others (n=6,

20%). Among HSCT patients, survival to ICU discharge occurred

after 13 of 36 (36%) episodes of CVVHD. Six-month survival after

CVVHD occurred in one HSCT patient. 11 non-HSCT patients

received an average of 9.6±2.9 days/year of CVVHD therapy. Of non-

HSCT patients, 9 had leukemia (81.8%), 1 had solid tumor (9.1%) and

1 was pre-transplant (9.1%). Among non-HSCT patients, survival to

ICU discharge occurred after 5 of 12 (42%) episodes of CVVHD.

1899Pediatr Nephrol (2008) 23:1897–1906

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Four non-HSCT patients survived beyond 6 months (36.3%).

Mechanical ventilation, vasoactive infusions and hyperglycemia at

the onset of CVVHD did not impact mortality in this study.

Conclusions CVVHD is an effective renal replacement modality in

critically ill children with cancer. Our 6 month survival rate in non-

HSCT patients compares favorably with that of the general pediatric

ICU population receiving this therapy. While the observed short-term

benefit of CVVHD in HSCT patients is encouraging, it does not

translate into 6 month survival. Further research is required to delineate

factors which may convert the short-term benefits of CVVHD into long

term survival in the high-risk group of HSCT patients.

6

Concurrent Continuous Renal Replacement Therapy (CRRT)

and Plasmapheresis in Pediatrics

D. Eding, L. Jelsma, B. Lovejoy, R. Hackbarth, T. Bunchman

Helen DeVos Children’s Hospital, Grand Rapids, Michigan, USA

[email protected]

Pediatric patients can occasionally require the addition of plasmaphe-

resis therapy to their CRRT treatment. We report a technique combining

CRRT and plasmapheresis using the Gambro Primsaflex and the Cobe

Spectra concurrently. Connections were made by the addition of two 3-

way stopcocks on the access line of the CRRT circuit. Access for

plasmapheresis therapy was connected to the first stopcock, and return

was connected via the second stopcock. Anticoagulation was main-

tained via the plasmapheresis circuit. No CRRT flow adjustments were

required; plasmapheresis flows were adjusted per protocol. This

technique is easily accomplished and done without complications. It

provides optimal therapy for patients requiring both CRRT and

plasmapheresis, preventing disruptions in hemofiltration therapy

7

High Volume Haemofiltration (CVVH) in the Management

of Neonates With Hyperammonaemia

C. Westrope, G. C. Morrison

Birmingham Children’s Hospital

West Midlands, UK

[email protected]

Neonatal hyperammonaemia, due to an inborn error of metabolism

(IEM), may often be severe enough to precipitate coma and result in

patient death. Existing therapies displace ammonia from the serum,

either through biochemical manipulation of nitrogen clearing process-

es, or, by utilizing renal replacement therapies. The latter are

particularly indicated when urgent reduction in the serum ammonia

level is required. Haemodiafiltration (HDF) can offer efficient

ammonia clearance and patient stability, but may be cumbersome.

Given reports that high volume CVVH may offer similar efficacy in

the clearance of ammonia we reviewed our experience of CVVH in a

population of hyperammonaemic neonates.

12 neonates with severe hyperammonaemia (median 880 µmol/L,

range 329 -1887 µmol/L) were admitted to the paediatric intensive care

unit of the Birmingham Children’s Hospital between 2000 and 2007.

The median age was 4 days (range 1–10 days) while the median body

weight was 2.7 kg (range 1.7 – 3.9 kg). In all patients the underlying

diagnosis was unknown at time of admission. Subsequently, hyper-

ammonaemia was found to be secondary to an organic acidaemia in 5

patients, while 7 patients had a urea cycle defect. Prior to initiating

CVVH, 11 children required mechanical ventilation, and 5 had

commenced inotropic support. In addition all were receiving intrave-

nous infusions of two or more of the following agents sodium benzoate,

phenylacetate or arginine All were commenced on high volume CVVH

(median ultrafiltrate flow 111 ml/kg/hr; range 78 – 250 ml/kg/hr)

utilizing the BM 25 (Baxter) or AQUARIUS (Edwards Lifesciences).

Median circuit bloodflowwas 12.1ml/kg/min (range 5.7 – 24.0ml/kg/min).

In those patients whose CVVH was conducted using the BM25, the

FH22 polyamide filter was employed. The AQUARIUS system was

coupled with the HFO7 polyethersulphone filter.

11 patients completed the course of CVVH. One patient experi-

enced an extravasation complication following dialysis catheter

insertion. CVVH was abandoned and peritoneal dialysis therapy was

employed. Two patients experienced acute haemodynamic compro-

mise on initiation of circuit bloodflow. Both were subsequently

stabilized and CVVH continued. The mean decrease in mean

ammonia levels at 12 hours of CVVH was 61% (+/- 7.9%) while at

24 hours the mean ammonia level was decreased by 81% (+/- 3.5%)

and, 9 of 11 patients had achieved “non-toxic” ammonia levels

(<200 µmol/L). No correlation was detected (Pearson coefficient)

between the circuit blood or ultrafiltrate flow and the rapidity of

reduction in serum ammonia. This may be due to small patient

numbers and the confounding effects of co-administered medical

therapies and use of different haemofilters. The mortality in the group

was 50%, all in intensive care.

High volume CVVH can produce a reduction in ammonia load in a

timespan comparable to that of HDF and may simplify the use of

continuous renal replacement therapy in hyperammonaemic conditions.

8

Continuous Renal Replacement Therapy (CRRT)

in the Treatment of Hyperammonemia Associated with Inborn

Errors of Metabolism

D. Eding, H. Marine, N. Hautala, L. Border, J. Harley,

R. Hackbarth, T. Bunchman

Helen DeVos Children’s Hospital

Grand Rapids, Michigan, USA

[email protected]

Children presenting with severe hyperammonemia require rapid

correction of their ammonia levels to minimize neurologic injury.

1900 Pediatr Nephrol (2008) 23:1897–1906

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Two newborns presenting with hyperammonemic encephalopathy

were treated with hemodialysis (HD) then transitioned to continuous

veno-venous hemodiafiltration. CRRT was started using the Gambro

Prismaflex, a blood flow of 25 mL/kg/minute and citrate anti-

coagulation. A M60 filter was utilized on an infant with methylma-

lonic acidemia, with initial flow rates of filter replacement fluid (FRF)

at 1.5 L/hour and dialysate at 2 L/hour. Flow rates were weaned over a

16 hour period and CRRT was discontinued. A HF 1000 filter was

utilized on an infant with a urea cycle defect with both FRF and

dialysate at 4 L/hour. Flow rates were decreased over a 52 hour period

and CRRT was discontinued. Both infants had ammonia levels of over

1000 mcmol/L prior to therapy, which rapidly decreased on HD and

continued to decline on CRRT to levels less than 100 mcmol/L for the

duration of the therapy. Sequential HD/CRRT is effective in the acute

management of hyperammonemia associated with metabolic disease.

9

Inaccuracy of Concomitant CVVH in ECMO Patients

M. I. Paden, C. Reid, S. F. Wagoner, P. Sucosky, L. P. Dasi, A. P.

Yoganathan, J. D. Fortenberry

Emory University/Children’s Healthcare of Atlanta/Georgia Institute

of Technology, Atlanta, Georgia, USA

[email protected]

Introduction: Renal failure complicates care of critically ill children

on ECMO. On ECMO, CVVH can be delivered either by standard

systems (Braun Diapact) or by a simplified system driven by ECMO

pump flow using IV pumps (Weber, 1998). Accuracy concerns exist

for concomitant CVVH and ECMO, due to circuit pressure effects. We

evaluated accuracy of the inline and Diapact systems using an in vitro

ECMO circuit model.

Methods: Two identical saline primed ECMO circuits were used. One

circuit added an inline hemofilter system, using IV pumps (Model 8100,

Alaris Medical Systems) to deliver replacement fluid (RF) and create

ultrafiltrate (UF), that is measured with a urometer (Criticore, Bard) The

other circuit used a Diapact for CVVH. Both methods diverted saline

post ECMOpump but pre-membrane, sent it through a PAN 6 hemofilter,

and returned to the bladder. CVVHwas prescribed with zero balance and

UF rates from 0.5–2 L/hour. RF and UF bags were weighed hourly.

Results: Forty eight hourly measurements were analyzed (26 hrs Alaris,

22 hrs Braun). Adjusting for varying UF rates, the Alaris pump delivered

a median 4.3% (range+3% to -25%) less RF per hour than set and created

a median of 0.8% (+7% to -12%) less UF/hr than prescribed. The Braun

Diapact delivered a median of 1% (+10% to -7%) more RF/hour and

created a median of 1% (+6% to -8%) per hour more UF than prescribed.

Conclusions: In this in vitro CVVH/ECMO model, both IV pump and

Diapact systems had clinically significant error rates, with potential for

unexpected fluid removal or excess delivery. Careful clinical assess-

ment of volume status is essential with concomitant ECMO/CVVH.

Further work is needed to develop more accurate fluid delivery for

CVVH on ECMO.

10

Pediatric CRRT Nurse Model: The Transition to an ICU Based

Model

T. Mottes, J. Vamos, W. Wieneke, J. Juno

University of Michigan Hospitals, Ann Arbor, Michigan, USA

[email protected]

Over the past 16 years our patient activity has increased by 65%, from

14 to 40 patients in the past year. Our current nursing care delivery

model consists of the pediatric dialysis nursing staff providing the set

up, prime and initiation, while the PICU nursing staff provides the

bedside hourly care. The increased activity along with projected

continual growth would stretch our current care delivery model past

its current adaptive potential. Thus, the need to explore other models

became imperative to maintaining our existing level of patient care. Our

new model allows for continued growth, is fiscally responsible,

compliments the excellent nursing bedside care and doesn’t overburden

the nursing staff with its implementation. With those goals in mind, a

model was developed with the care being shifted from the pediatric

dialysis nursing staff to the pediatric ICU nursing staff.

Transition to the new care delivery model necessitated the implemen-

tation of a training program, along with the creation of a nursing

leadership position, the program coordinator, designed to train the ICU

staff to assume the set up and initiation responsibilities. The Initiator

Education program consists of 3 Steps; Hands-on demonstration of the

machine set up and the different initiation procedures, 5 assisted patient

initiations, and ongoing education, including CRRT drills. This training

program is in addition to the current education program for CRRT.

During the transition to it is important that we track the effects on the

nursing staff. To measure these effects a survey tool was developed that

has the staff rank their perceived comfort and knowledge of CRRT.

During the transition period, the survey will be implemented every

4 months, with first survey being just prior to the start of the transition

process. In brief summary, the baseline survey results with 72% of all

CRRT trained nurses responding indicate an overall comfort level

average score of 4.2. During this transition time, evaluating and

trending the data will allow us to adapt to the nursing education needs.

11

AN69 Surface-Treated (AN69ST) Membrane and Hemodynamic

Profile of Critically Ill Children During Initiation of CRRT

W. Kechaou, P. Jouvet, V. Phan, C. Litalien.

Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada

[email protected]

Background: Hypotension secondary to bradykinin release via

contact activation of clotting factor XII by AN69 membrane is a

known complication usually occurring within 15 minutes after the

1901Pediatr Nephrol (2008) 23:1897–1906

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start of CRRT. AN69ST membrane was designed to prevent this pH-

dependent reaction. To date, there are few data regarding the use of

this membrane in children. Objectives: To evaluate the hemodynamic

profile of critically ill children at the start of CRRT when AN69ST

membrane is used. Methods: A retrospective study of critically ill

children who underwent CRRT with AN69ST membrane. Hemody-

namic changes during the first hour after CRRT initiation were

assessed by recording from the charts heart rate and systolic blood

pressure at 10 min intervals, changes in vasoactive score1 and need for

volume and HCO3- administration. Severity of illness, priming

techniques and blood pH were also evaluated. Hemodynamic

instability was defined as hypotension, increase in vasoactive score

or need to administer≥10 ml/kg of volume. Results: Eleven patients

with a median age of 7.5 yrs (5 months–15 yrs) were included. At

CRRT initiation, median PELOD score, blood pH and vasoactive

score were 30 (10–43), 7.33 (7.21–7.46) and 24 (0–97). Priming

techniques were normal saline (8/11), albumine 5% (1/11) and bypass

system described by Brophy (2/11). During the first hour of CRRT, 9

patients remained hemodynamically stable while 2 had an increase in

their vasoactive score from 25 to 27 and from 35 to 50. Both had an

initial PELOD score>40. No volume administration ≥ 10 ml/kg was

required and one patient received HCO3-. Conclusion: AN69ST

membrane was associated with hemodynamic stability at CRRT

initiation in most critically ill children. Further studies are needed to

better evaluate whether or not the use of AN69ST membrane prevents

the occurrence of hypotension at the start of CRRT, especially in

infants less than 10 kg when the bypass system is not used.

Results

12

Ceftriaxone Pharmacokinetics (PK) During Continuous Pediatric

Veno-veno Haemofiltration (CVVH); in vitro model

B. Harvey, D. Yeomanson, T. Johnson, H. Mulla, & A. Mayer

Dept. of PICU Sheffield Children’s Hospital, Sheffield, UK

[email protected]

During CVVH, drug clearance is dependant on many factors. Dose

adjustments assume reduced drug clearance by the renal system and

CVVH. Practice variation(pre-dilution, high volume haemofiltration)

alters drug removal. Dosing during CVVH is complex; under- or

overdosing may occur. We studied the PK of ceftriaxone during

CVVH in an in vitro model Methods: Renoflow filters were used to

model 6 & 20 kg patient. After priming, each circuit and reservoir was

prepared with a known vol. of Hartmann’s, 4.5% HAS or blood using

the Infomed 400. Blood pump speed & exchange rate for each circuit

was protocolised. HBO used as replacement fluid, 70% predilution.

Following paired sampling from circuit and ultrafiltrate fluid,

Ceftriaxone (80 mg/kg) was injected into the post-filter port (time

0). Paired samples were taken at 10 time points (0–720 mins).

Ceftraxione concentrations determined using HPLC.

Conclusion: Estimates of high Sc and short circuit half-life from this

in-vitro model suggest Ceftriaxone is rapid cleared during CVVH

(cleared by 240 min), with important implications for dosing during

in-vivo CVVH. The albumin circuit had the lowest Sc and longest

terminal half-life, reflecting protein binding of drug, Ceftriaxone

clearance may increase in hypoalbuminaemic patients.

13

Pediatric Continuous Renal Replacement Therapy Program:

Maintaining Nursing Skills in a High Risk Low Volume Area

G. Bonin, H. Cooper, C. Press, S. Kowalski, J. Plouffe, K. Pederson,

M. Kesselman, T. Blydt-Hansen

Children’s Hospital Health Sciences Centre

Winnipeg, Manitoba, Canada

[email protected]

The Winnipeg Pediatric Continuous Renal Replacement Therapy

(CRRT) program averaged two-three patients per year up to 2006. The

model of nursing care included training the majority of Pediatric

Intensive Care nurses in CRRT. Nursing education at this time

included a one-day classroom orientation and an annual four-hour

recertification class. Due to the low volume of usage, this large group

of nurses struggled to maintain a basic level of skill and familiarity.

In 2006 the CRRT committee re-evaluated the program. Basic

setup times (>2 hours) and troubleshooting were identified as specific

challenges. The objective was to develop and apply a training and

skills maintenance model to improve the expertise and exposure of

nurses providing CRRT. This model included the following tasks:

1. Select a limited number of nurses who are committed to

developing an enhanced skill-set as “specialists”.

2. Restrict the delivery of CRRT skills to nurses from this select pool.

3. Train nurses to provide basic, then more advanced care:

A. Advanced Users (AU): To act as educators and to perform

advanced troubleshooting.

Filter Fluid Cmax(mg.ml)

Sc MRT(min)

T1/2

(min)

0.7 m2 Albumin 3.5 0.23 236 1640.7 m2 Blood 4.5 0.31 89 620.4 m2 Hartmans 1.65 0.52 178 1240.7 m2 Albumin 2.65 0.64 132 910.7 m2 Blood 6.5 0.51 29 200.7 m2 Hartmans 2.93 0.49 108 75

1 Dose of dopamine + dobutamine + (epinephrine X 100) +(norepinephrine X100) + (phenylephrine X 100) + (milrinone x 10).

1902 Pediatr Nephrol (2008) 23:1897–1906

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B. Super Users (SU): To set up the CRRT circuit including

Albumin and Blood Primes, and to provide typical

troubleshooting.

C. Associates (AS): To perform the daily operation of the

CRRT machine and provide basic trouble shooting

4. The enhanced training program included the following components:

A. Increase initial CRRT education to a day and a half for all

CRRT trained nurses.

B. “Dry lab” every three months to practice set up and trouble

shooting skills.

C. AUs received full day education for new Prismaflex. “Dry

lab” practice once a week to once a month, assistance with

Prismaflex education and development and review of

policies and procedures.

D. Present a Problem of the Month.

E. Monthly CRRT Case reviews.

5. Apply a mix of expertise to each nursing shift: At least one AU,

SU and one AS on each shift. This team provides comprehensive

patient care, and builds capacity for the AS.

6. Invite Clinical Specialists in Pediatric CRRT.

In the two years following the program changes, there has been a

marked increase in the use of CRRT (10 patients/year). This is

attributed to increase nursing expertise and physician confidence.

Specific changes include faster set-up times (<1 hour), more confident

troubleshooting and subjective improvements in nursing independence

and skill at the beside. Ongoing challenges include: a large staff

turnover rate, high acuity preventing nurses from entering the dry lab,

a low volume of trained nurses causing difficulty in scheduling and

CRRT case reviews.

CRRT is being viewed as a safe and available treatment option

where nurses feel they are valuable members of the CRRT team.

14

Children Requiring Continuous Renal Replacement Therapy

(CRRT)

L. Jelsma, D. Eding, C. Metz, A. Neumann, V.Steen, M. Oleniczak,

R. Hackbarth, T. Bunchman

Helen Devos Children’s Hospital, Grand Rapids, Michigan, USA

[email protected]

Two pediatric patients with severe abdominal trauma required CRRT

secondary to renal insufficiency, hypercatabolism and rhabdmyolysis.

Continuous Veno-Venous Hemodiafiltration was initiated using the

Gambro Prismaflex, HF1000 filter, citrate anticoagulation and an

initial blood flow of 150 mL/minute. Patient 1 sustained an abdominal

aortic dissection. Filter replacement fluid (FRF) and dialysate were

started both at 4 L/hour. After a 57 day course paient 1 transitioned to

hemodialysis. Patient 2 sustained blunt abdominal trauma with

abdominal compartment syndrome requiring a left nephrectomy and

decompressive silo. Initial flow rates were FRF at 4 L/hour and dialysate

at 3 L/hour. After a 15 day course patient 2 recovered renal function and

CRRTwas discontinued. CRRT is effective in the management of acute

renal insufficiency in patients with abdominal trauma.

15

Characteristics and Mortality of Paediatric Patients Undergoing

Haemofiltration

L.Byrne, J. White, A. Durward

Pediatric Intensive Care Unit, Evelina Children's Hospital, Guys & St.

Thomas NHS Foundation Trust, London, England, UK

[email protected]

Aim: The aim of this study was to determine the demographic

characteristics of patients receiving haemofiltration (CVVH) in a lead

paediatric intensive care unit (PICU) in United Kingdom with specific

reference to mortality.

Methods: A retrospective review of all patients who received CVVH

(n=28) in our PICU over a two year period commencing January 2006

were identified from our intensive care database and analysed. Patients

were haemofiltered using the Aquarius Platinummachine (Edwards) with

the HF03 and HF07 polysulphone filters at blood flow rates of 100 and

150 ml/min for patients below and above 15 kg respectively. Ultrafiltra-

tion rates of 60 ml/kg/hr were used for patients < 15 kg and 30 ml/kg/hr

above this weight. Demographic characteristics of patient’s receiving

CVVH were compared to those who did not receive this therapy (n=

2475). Peritoneal dialysis patients were not included in analysis (n=52).

Chi squared test was used for categorical data andMannWhitney Test for

continuous data with a p value<0.05 considered significant. Data are

expressed as median and inter-quartile range.

Results: Twenty eight (1.1%) episodes of CVVH were identified from

2337 admissions. Case-mix of haemofiltered patients were sepsis (n=14

including 3 meningococcal), haemolytic uraemic syndrome (n=6), acute

renal failure (n=4), other (n=4 including 1 neonate with urea cycle

defect). The commonest reasons for haemofiltration included anuria

(35.7%), electrolyte abnormality (25%) and fluid overload (17.9%).

CVVH patients received inotropes more frequently (71% vs. 32%, p<

0.0001), were significantly younger, sicker and had higher mortality

1903Pediatr Nephrol (2008) 23:1897–1906

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(28.5% vs. 4%, p<0.0001) than patient’s not dialysed (Table 1). Non

survivors of CVVH had significantly higher mortality risk (PIM2 score

30 (17 to 48) vs. 5 (1 to 10), p<0.0001), shorter length of stay (0.8 days

(0.2 to 4.7) vs. 6.2 (1.8 to 17), p<0.0001) despite similar age and weight

to survivors of haemofiltration (12 kg (8 to 15) vs. 16 (9.8 to 33)

respectively.

Table 1 Demographic characteristics between patients receiving

CVVH and those not receiving this therapy.

PIM = Paediatric Index of Mortality score

Conclusion: Mortality of patients undergoing haemofiltration is high

and strongly influenced by disease severity on admission to PICU.

16

Continuous Renal Replacement Therapy (CRRT) Circuit

to Circuit Exchange

D. Eding, R. Hackbarth, T. Bunchman

Helen DeVos Children’s Hospital, Grand Rapids, Michigan, USA

[email protected]

Children less than 15 kg requiring CRRT present a challenge due to

patient size to total circuit volume ratio necessitating a circuit blood

prime. This can cause hemodynamic, acid base, and electrolyte

disequilibrium. We developed a technique that can be used with

elective circuit changes, or with transition from hemodialysis (HD) to

CRRT. The method allows exchange of patients own blood from old

circuit to new circuit. A second CRRT machine is saline primed. At

circuit transition the patient’s blood is returned via the catheter return

line. Simultaneously the new machine is connected to the dialysis

catheter access line and the patient primes this circuit. Machines are

started at the same time and blood flow rates are identical therefore the

exchange is volume neutral. When exchange is complete therapy is

resumed. This exchange is done over several minutes dependent on

total circuit volume and catheter flow capabilities, limiting the time off

CRRT and avoiding repeated blood exposure to the patient. Method

has been utilized successfully with the Gambro Prismaflex M60 and

HF 1000 circuits.

17

The Use of CVVHD as an Adjunct for the Treatment of Cerebral

Edema Associated with Diabetic Ketoacidosis(DKA)

R. J. Cunningham III, R. C. Gensure, L. A. Kashimawo

Ochsner Children’s Health Center

New Orleans, Louisiana, USA

[email protected]

Cerebral edema is a rare complication of diabaetic ketoacidosis (0.9%

of patients presenting with DKA) with a mortality rate of 20–50% and

of the survivors, 40–50% have significant neurologic deficits. The

incidence and outcome of this condition has not changed appreciably

over the past 20 years. We present a case of severe cerebral edema that

was treated with CVVHD in addition to the standard measures usually

employed in the treatment of this condition. Recovery was complete

and no neurologic deficits were seen on follow up. An 11 y/o known

diabetic (Wt.=56 kg) presented 5 weeks after hurricane Katrina in

ketoacidosis with a pH of 6.8, a bicarbonate of 5 meq/l, & a creatinine

of 1.4 mg/dl. She was given 10 m/kg of 0.9%NS and was begun on IV

insulin (0.1 unit/kg/hr) along with IV fluids (225 cc/hr of 0.45% NS).

She was lethargic, a bit confused but responsive. Fourteen hours later

after continued administration of fluid and insulin, it was noted that

she had decerebrate posturing. A CT scan showed cerebral edema with

effacement of the quadrigeminal cistern. She was intubated, CVVHD

was instituted with Qb=120 cc/min, ultrafiltration rate of 150 cc/hr

and dialysate flow of 100 cc/hr (25 meq/l Bicarbonate bath) & given

IV mannitol (1 gram/kg). Over the next 7 hours, her net balance

decreased by 3000 ml, her pulse rate was up to 160/min (from 110/min),

and urine output had dropped by 50%. Her fluid balance was

maintained but dialysate flow was increased (bicarbonate was still

9 meq/l) to 200 cc/hr. & the patient was responsive to stimuli. Sixteen

hours after initiation, CVVH was discontinued and CT scan showed

improvement. The patient continued to improve, was awake 48 hours

after initiation of CVVH & was discharged on the 5th hospital day.

The aim in using CVVHD was to use osmotic, convective and

hydrostatic forces to encourage movement of fluid from brain to blood

while simultaneously establishing better biochemical control.

CVVH(n=28)

no CVVH(n=2475)

p - value

Age (months) 9.3 (1.3 to 48) 49 (15 to 126) <0.0001Weight (kg) 15 (8 to 28) 7 (3 to 15) <0.0001Mechanicalventilation

23/28 (82%) 1786/2475 (72%) 0.19

Length of PICUstay (days)

5.2 (0.7 to 13) 2.1 (1.1 to 4.1) 0.11

PIM2 score 9.8 (2.7 to 17.8) 2.9 (1.1 to 6.0) 0.001Mortality 8/28 (28.5%) 94/2309 (4.1%) <0.0001

1904 Pediatr Nephrol (2008) 23:1897–1906

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18

Combined Treatment with ECMO and CRRT in Children

After Heart Surgery

M.Yarustovsky, K. Shatalov, M. Abramian, E. Nazarova,

O. Stupchenko

Bakoulev Center for Cardiovascular Surgery, Moscow, Russia

[email protected]

Rather often children with low cardiac output after radical correction

of complex congenital heart disease require ECMO for the support of

hemodynamics, as well as CRRT for the correction of water-

electrolyte and metabolic balance. During 2007 we have followed 7

children aged from 19 days to 10 years. Severity APACHE-II

score was 32,7±5,4. The indications for the combined procedure

were: pronounced heart failure (EF LV=15–25%, PLA=22–30 mm Hg,

CVP=16–20 mm Hg), oligoanuria (diuresis<0,5 ml/kg/hour), K+>

5,5 mmol/l, Cr>200 µmol/l, Ur > 15 mmol/l. The duration of therapy

was from 3 to 10 days. Qp —1,4 – 2,4 l/min., Qb – 2800–3600 turns

\min., FiO2 – 40%, Qо2 – 800 ml/min. Ultrafiltration was carried out

with AV 400 HF (Fresenius). Because of high Qp, ultrafiltration

velocity was regulated with a clamp on the supplying («arterial») line.

UF volume depended on preload and infusion volume indices.

Anticoagulation: heparin (АСТ – not more 250 sec). When it was

necessary to correct metabolic and nitrogen balances, as well as K+>

5,5 mmol/l, dialysis was added (up to 100 ml/min). After ECMO

disconnection 2 children were transferred to peritoneal dialysis.

Mortality in the group was 71.4%. The combination of ECMO and

CRRT is safe and can be effectively used in clinical settings.

19

Animal Model to Study Feasibility of Venovenous Extracorporeal

Membrane Oxygenation Using Renal Replacement Therapy

Platform

A. Divekar, G. Bonin, H. Cooper, A. Gutsol, T. Koga

University of Iowa Children’s Hospital, Iowa City, Iowa, USA

All research done at Children’s Hospital Health Sciences Center,

University of Manitoba, Winnipeg, Canada

[email protected]

Objectives: We have previously reported the first successful adapta-

tion of a renal replacement therapy (RRT) platform to provide

extracorporeal venovenous membrane oxygenation (VV ECMO). This

study was intended to develop an animal model to study feasibility of

delivering VVECMO using RRT platform. Methods: Animals were

handled according to Animal Care Committee guidelines at the

University of Manitoba and Canadian Council on Animal Care. Six

domestic swine (2.4–9 kg) were anesthetized by mask inhalation with

3–5% isoflurane with oxygen and surgical depth of anesthesia was

maintained with 1–3% isoflurane. All animals were mechanically

ventilated. Continuous electrocardiogram, pulse oximetry, invasive

arterial pressure and core temperature was monitored. The femoral

vessels and external jugular vein were isolated by surgical cutdown.

The largest (7–12 French) double lumen cannula was placed in the

femoral and external jugular veins. A Prismaflex continuous RRT

platform with an ST-100 filter was used in CVVHDF mode. A Lilliput

902-D hollow fiber oxygenator was spliced in the return of the circuit

pre-air detection filter in conjunction with a Bio-Medicus heat

exchanger. The circuit was primed with Prismasol-4 and then blood

primed and was normalized against dialysate. Access was through the

external jugular vein and the blood was returned via the femoral vein.

The pre-blood pump rate was 400/min. All animals received 300 U/kg

of heparin sulphate for anticoagulation and activated clotting time was

maintained between 180–220 seconds. Sweep flow through the

oxygenator was 1 lit/min at 100% FiO2. Hypoxemic respiratory

failure was induced by reduction in minute ventilation and decreasing

FiO2 to 10% and documented by arterial blood gas. Flow was initiated

at 50 mL/min increased in 50 mL/min increments to maximum flow of

450 ml/min or until a limiting access/filter/return line pressures were

reached. Blood gas analysis was performed from the access line, post

oxygenator and from animal arterial line. Results: The first three

animals were successfully placed on support and helped identify and

correct several technical problems/limitations. Data from the next 3

animals is reported as mean + /-SD; the partial pressure of oxygen and

carbon-dioxide in mmHg. They weighed 3.57(1.69) kg. The pO2 was

28(3.79) and pCO2 56(18.5) prior to being placed on support. At a

flow of 67(19.37) ml/kg/min there was increase in pO2 to 40(3.1),

oxygen saturation to 78(5.13)% and drop in pCO2 to 31(8.02); at a

flow of 105(42.24) ml/kg/min there was increase in pO2 to 55(11.14),

oxygen saturation to 93(1.53)% and drop in pCO2 to 22(3.0). There

was minimal recirculation. Conclusions: RRT platform can be adapted

to provide VV-ECMO. As expected CO2 removal is very efficient,

improvement in oxygenation is clinically relevant. This animal model

will allow further research to adapt and further refine RRT platforms

and circuits for this modification.

20

Use of Tego Connectors to Prevent Hemodialysis Catheter

Infections in Children

N. G. McAfee, S. Seidel, S. L. Watkins, J. Flynn

Children’s Hospital and Regional Medical Center

Seattle, Washington, USA

[email protected]

PURPOSE: Catheter infections are a significant problem in pediatric

dialysis. To reduce infection rates in our program, we implemented the

use of TEGO™ connectors, which create a closed system, no open

catheter hubs, reducing manipulation and allowing unobstructed flow

rates >600 mL/min while remaining in place.

1905Pediatr Nephrol (2008) 23:1897–1906

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METHODS: We retrospectively analyzed surveillance data collected

in 15 patients (mean age 12.62 years) following 4 quarters of use of

the TEGO™ connectors and compared this to preceding five quarters

of data. The data were then analyzed using Poisson generalized

estimating equations. RESULTS: Infection rates, in number of

infections per 1,000 patient-days, were as follows: 7.8 infections

per 1000 patient-days during the pre-TEGO period vs. 3.65 infections

per 1000 patient-days after the switch to the TEGO™ connector The

BSI Incidence Rate Ratio was 0.47 (95% CI: 0.23 – 0.96), which

indicates that the BSI rate with TEGO was less than half the BSI rate

in the preceding 5 quarters. This is a statistically significantly

reduction (p=0.04).

CONCLUSIONS: Although the small patient numbers in this study

limit the precision of our estimates of the reduction in bloodstream

infections, the current data are promising. We are now trialing these

connectors on our pediatric CRRT patients with central catheters to

see if the same reduction in infections is found.

21

Management of Acute Renal Failure and Increased

Intracranial Pressure with CRRT

R. Gonzales, J. Willoughby, D.M. Ford, G.M. Lum,

M.A. Cadnapaphornchai

The Children’s Hospital, 13123 E. 16thAve. Box B328, Aurora, CO 80045

[email protected]

Multiple trauma is frequently associated with acute brain injury and

acute renal failure (ARF). Intermittent hemodialysis (IHD) can

compromise cerebral perfusion pressure through osmotic shifts and/or

decreased intravascular volume. CRRT has been proposed to provide

greater intracranial stability in this setting. We report the successful use

of CRRT to control increased intracranial pressure (ICP) and hyper-

osmolality in a child with ARF.

Following handlebar injury to the abdomen, an 11-year-old male

complained of severe abdominal pain. He had a grade IV liver

laceration with abdominal compartment syndrome and required

extensive resuscitation including 17 u PRBC and 8 u fresh frozen

plasma. Upon transfer, he was anuric with acute tubular necrosis. He

underwent IHD without complications on hospital days 2 and 3. He

later developed an acutely enlarged and unreactive right pupil. CT

scan showed diffuse cerebral edema. He was treated with mannitol

and hyperventilation. Initial ICP was 23 mm Hg with serum

osmolality (SOsm) 320 mOsm/kg. With concern that IHD might

contribute to cerebral edema and tenuous fluid status, CVVHD was

initiated with dialysate osmolality 292 mOsm/kg. Over the next

5 days, adequate fluid and solute clearance was achieved with

normalization of SOsm and ICP and good neurologic outcome.

320

300

280 0

10

20

30S

Osm

ICP

3 4 5 6 7

Hospital Day

S Osm ICP

1906 Pediatr Nephrol (2008) 23:1897–1906