renal failure and renal replacement therapy

Renal failure and renal replacement therapy

Norma J. Maxvold, MDa, Timothy E. Bunchman, MDb,*aDepartment of Pediatric Critical Care, Children’s Hospital of Alabama,

University of Alabama at Birmingham, 1600 7th Avenue, Birmingham, AL 35233, USAbDepartment of Pediatric Nephrology and Transplantation, Children’s Hospital of Alabama,

University of Alabama at Birmingham, 1600 7th Avenue, Birmingham, AL 35233, USA

This article provides an overview of current knowledge, opinion, and evidence

to the extent that is currently available for approaching a child with acute renal

failure (ARF). Over the last 2 decades the treatment of ARF has changed

remarkably [1,2] because of generally improved care of children, a shift toward

continuous treatment modalities, research and advances in vascular access, and

the understanding that children with ARF usually have a high chance of recovery.

Acute renal failure often occurs in the face of multiorgan system failure (MOSF)

as a consequence of sepsis, solid or bone marrow transplantation, or acute

respiratory disease syndrome [2–4].

The authors present the shared perspective of a pediatric intensivist and a

pediatric nephrologist who have worked together for more than 10 years caring

for children with ARF and MOSF. They have reviewed current literature and

address what is known, what is bias, and what is open for research.

Pathophysiology

The causes of ARF can be divided into prerenal causes, intrarenal causes, and

postrenal causes [5]. In a child with MSOF, the cause is often multifactorial. In

the evaluation of a child with ARF, the obvious issue is to make certain that there

is adequate perfusion pressure and intravascular volume integrity with no

evidence of obstruction. In an examination report, this finding is often identified

as ‘‘warm, well-perfused with good blood pressure, good pulses, no evidence of

tense ascites, with a Foley catheter in place.’’ Laboratory results should provide

0749-0704/03/$ – see front matter D 2003 Elsevier Inc. All rights reserved.

doi:10.1016/S0749-0704(03)00010-1

* Corresponding author. Department of Pediatric Nephrology and Transplantation, Children’s

Hospital of Alabama, University of Alabama at Birmingham, CHT 735, 1600 7th Avenue,

Birmingham, AL 35233.

E-mail address: [email protected] (T.E. Bunchman).

Crit Care Clin 19 (2003) 563–575

evidence that a fractional excretion of sodium (FeNa) is not compatible with a

prerenal state (ie, low), with adequate osmolality and oncotic pressure and

without confounding variables that would result in an ongoing insult (ie, tumor

lysis syndrome or rhabdomyolysis), and with adequate volume resuscitation.

Etiology

There is no consensus regarding the definition of ARF. Many programs

consider a child as having ARF when there is a change from baseline levels of

more than 50% of serum creatinine or a blood nitrogen urea level above 40 mg/dL

or when urine output is insufficient to make accommodate medications, vaso-

pressor agents, or adequate nutrition. Because these definitions vary considerably

from program to program and from clinician to clinician, the decision concerning

the need for renal replacement therapy (RRT), as well as the overall care of the

child, varies considerably. During the past decade, many authors have addressed

the causes of ARF at admission to a pediatric ICU (PICU) or developing during

the stay in a PICU [2–4,6,7]. The population with ARF varies depending on the

author, the type of population served by the hospital, and the presence or absence

of programs in cardiac surgery program, extracorporeal membrane oxygenation

(ECMO), bone marrow transplantation, or solid-organ transplantation. The single

most common cause of ARF in children throughout the world continues to be

related to the hemolytic uremic syndrome (HUS) or volume depletion from

diarrhea-induced ARF with or without evidence of HUS [7]. Often these children

have been ill for a period of time before clinical identification of ARF, and poor

nutrition potentially affects their treatment and outcome.

Work by Menster et al [8] and Parekh et al [9] identified the typical causes of

ARF seen in economically developed societies as (1) previously unrecognized

congenital renal disease presenting as ARF and (2) toxic insults related to other

disease processes. In contrast, Goldstein et al [4] noted sepsis or shock as the

causes in their cohort of children who underwent hemofiltration for treatment of

ARF/MOSF. Therefore, the population surveyed influences the definition of ARF

as well as the decision concerning the need for RRT.

Options for renal replacement therapy

Before the late 1980s the options for RRT modality were limited to either

peritoneal dialysis or hemodialysis [1,10–12]. Since the initial paper by Ronco

et al [13] looking at continuous arterial venous hemofiltration (CAVH) in an

infant, the use of hemofiltration has become more common. This practice has

been further influenced by the newest generation of more user-friendly machines

that employ thermic controllers and more accurate ultrafiltration controllers.

Local experience and the clinical circumstances of the child mostly influence the

choice of peritoneal dialysis, hemodialysis, or hemofiltration. For example,

peritoneal dialysis is avoided in children with intra-abdominal catastrophes,

N.J. Maxvold, T.E. Bunchman / Crit Care Clin 19 (2003) 563–575564

whereas hemodialysis or hemofiltration is precluded when vascular access is

unobtainable. Surveys within the pediatric nephrology literature over the past

6 years have confirmed clinicians’ experience of a trend away from peritoneal

dialysis toward hemofiltration when a continuous renal replacement therapy

(CRRT) is needed. Hemodialysis still remains the mainstay for the less sick child

with ARF and the therapy for the child with intoxication [1,14–17]. Because of

this trend, and because this article addresses the treatment of ARF in the PICU,

this discussion focuses on hemofiltration.

Hemofiltration for acute renal failure

The treatment of ARF with hemofiltration can be continuous arterial venous

hemofiltration with or without dialysis (CAVH[D]) or continuous veno-venous

hemofiltration with or without dialysis (CVVH[D]) [18,19]. Pediatric studies to

date have demonstrated the ease and simplicity of CAVH but have also demon-

strated the lack of obtainable prescription for CRRT when using CAVH [20].

Blood flow for CAVH depends on adequate cardiac output and is negatively

influenced by a high hematocrit, making CAVH mostly of historical interest.

Pump-assisted CVVH[D] is consider the standard for CRRT in children and

adults. This form of CRRT can be convective (CVVH), diffusive (CVVHD), or a

combination of both continuous veno-venous diahemofiltration (CVVHDF). The

choice between CVVH and CVVHD is often based on local standard, on the desire

for larger molecule clearance (improved with CVVH but dependent on the sieving

coefficient of the solute), and on the availability of replacement or dialysis

solutions. Data to date in both adults and children have shown when the

prescription is similar with the single variable of replacement or dialysate fluid,

urea clearance is similar [21]. Because the goal of most CRRT is to maintain

adequate volume status of the child, room for nutrition, and solute clearance, the

final decision of convective or diffusive treatment is often related to availability of

solutions for these therapies.

Access for continual renal replacement therapy

Access for CRRT depends on the size of the child, the necessary blood flow

rates, and, more recently, the choice of anticoagulation (Table 1). Access is needed

to maintain blood flow rates in the range of 10 to 70 mL/min in children weighing

less than 15 kg, 50 to 100 mL/min in children weighing 15 to 30 kg, and 100 too

250 mL/min in children weighing more than 30 kg. Dialysate or replacement fluid

becomes saturated with solute at commonly used rates of 2 L/hour (in contrast, the

dialysate flow rate in hemodialysis is 30–40 L/hour); therefore higher blood flow

rates have little effect on solute clearance and only tend to cause more alarms from

flow resistance. Triple-lumen access is helpful in the setting of inadequate

vascular access for the patient as well as in the setting of citrate anticoagulation

N.J. Maxvold, T.E. Bunchman / Crit Care Clin 19 (2003) 563–575 565

where a third lumen is needed for calcium infusion to offset the potential hypo-

calcemia related to citrate use. Triple-lumen access for hemodialysis or hemofil-

tration is not available in a size smaller than 12 French, but the authors’ program

has used triple-lumen 7-F central venous catheters in infants for hemofiltration

with varying success.

Machinery for continual renal replacement therapy

Since the mid-1990s many companies have produced hemofiltration

machinery that is applicable to infants, children, and larger children. These

machines all share accurate ultrafiltrate monitors, accurate thermic controllers, a

reasonable range of blood flow, dialysate, and replacement fluid rates, and are

user-friendly. Equipment such as the Diapact (B. Braun, Bethlehem, PA), BM-25

(Baxter Health Care, Deerfield, IL), Prisma (Gambro Renal Products, Lakewood,

CO) are currently available. The 800H(K) machine (Fresenius Medical Care,

Lexington, MA) is a hemodialysis machine that has the added advantage of being

adaptable for CVVHD. Newer-generation machines including the Aquarius

(Edwards Lifesciences [Canada], Mississauga, Ontario) and the Accura (Baxter

Health Care, Deerfield, IL) are currently coming to the market. These newer

machines have encompassed the benefits of previous machines and allow more

flexibility of blood flow rates, dialysate flow rates, and replacement rates. Most of

these machines have the flexibility of different-sized circuits (ie, extracorporeal

blood volumes) and allow the user a choice of membranes. Only the Gambro

Prisma has contained membrane and blood lines providing easy and rapid

Table 1

Suggested size and selection of hemofiltration vascular access for pediatric patients

Patient weight Catheter size and source Site of insertion

Neonate Single-lumen 5 F (Cooka) Femoral artery or vein

Dual-lumen 7.0 F (Cook/Medcompa,b) Internal/external jugular,

subclavian or femoral vein

3–6 kg Dual-lumen 7.0 F (Cook/Medcompa,b) Internal/external jugular,


Triple-lumen 7.0 F (Medcomp, Arrowb,c) Internal/external jugular,


6–30 kg Dual-lumen 8.0 F (Arrow, Kendallc,d) Internal/external jugular,


> 15–kg Dual-lumen 9.0 F (Medcompb) Internal/external jugular,


> 30 kg Dual-lumen 10.0 F (Arrow, Kendallc,d) Internal/external jugular,


> 30 kg Triple-lumen 12 F (Arrow, Kendallc,d) Internal/external jugular,


a Cook Critical Care, Bloomington, IN.b Medcomp, Harleysville, PA.c Arrow International Reading, PA.d Kendall Health Care Products, Mansfield, MA.


implementation of CRRTwith a single cassette system. The choice of machines is

usually influenced by hospital and service contracts and somewhat by experiential

advice from other programs.

Membranes

The choice of membrane for CRRT depends on the machine, the need for

convective or diffusive clearance, and the size of the child. The Gambro Prisma

has a membrane (AN-69) that is part of the cassette that comes with the machine.

This membrane has been shown to be biocompatible and can be used for either

convective or diffusive clearance. Alternately, polysulfone membranes are also

biocompatible and offer a variety of sizes with the same convective and diffusive

flexibility. Use of these biocompatible membranes has positively affected

recovery of renal function, with less oliguria and with overall improved survival

rates in studies of hemodialysis in adults with ARF [22]. A similar comparison of

membranes has not occurred to date in either pediatric or adult CRRT, but all

membranes used in CRRT are considered biocompatible. One unique problem

that occurs with the AN-69 membrane is that of a bradykinin reaction when the

membrane interacts with acidotic plasma. Work by Brophy et al [23] has shown

that when a blood prime occurs with the use of the AN-69 membrane, the pH of

blood-banked blood (pH of 6.2–6.4) begins a series of events that results in

production of bradykinin within the circuit, resulting in a clinical event of

anaphylaxis. Adult programs have also reported this event when acidotic patients

are treated using a machine with an AN-69 membrane. Brophy’s work demon-

strated that the use of a buffering system or a bypass maneuver could easily avoid

the risk of this reaction.

Solutions for continual renal replacement therapy

Until the fall of 2000, the only solution approved by the Food and Drug Ad-

ministration (FDA) for dialysis was Hemofiltration Solution (Baxter Health Care,

Deerfield, IL), which has lactate as a buffer. Alternatively, peritoneal dialysis

solutions (also lactate-based and containing high glucose concentrations) have

been used. Programs have reported that detectable plasma levels of lactate are

demonstrated when lactate-based solutions are used for CRRT. This observation

raised the question of whether the lactate was from the solution or from the

development of lactic acidosis from the patient [24]. As with hemodialysis in

1980s, when the buffer was changed from acetate to bicarbonate, many programs

have begun to employ pharmacy-made solutions with bicarbonate as the buffer.

Barenbrock et al [24] recently demonstrated detectable plasma lactate levels and

hemodynamic compromise in patients when lactate-based hemofiltration solutions

rather than bicarbonate-based were used [24]. In the fall of 2000, the first FDA

bicarbonate-based solution became available for CVVHD (Normocarb1, Dialysis


Solution, Richmond Hills, Ontario, Canada) with other companies to follow [25].

This development has allowed many programs to maintain a bicarbonate-based

dialysis solution with less expense and less risk of pharmacy error than with a

customized pharmacy-made solution. An additional advantage of Normocarb1 is

that it is the only calcium-free solution currently available, allowing ease of use

with citrate anticoagulation; if heparin is preferred, the calcium chloride can be

added to physiologic doses. At the time of this writing, there is not an FDA-

approved bicarbonate solution for replacement fluid, but submissions for 510K

approval are in process and are expected to be available in the first quarter of 2003.

Anticoagulation treatment

Anticoagulation treatment is needed to maintain the patency of an extracorpo-

real circuit. Studies have demonstrated that in coagulopathic patients the use of

normal saline flushes or no anticoagulation will result in a shorter circuit lifespan

than when anticoagulation is used. Historically heparin has been the mainstay of

anticoagulation for CRRT [3,18,26–28]. A standard protocol includes an initial

bolus of 10 to 30 units/kg of heparin (assuming that the initial activated clotting

time [ACT], or partial thromboplastin time [PTT] is normal) and maintaining a

continuous infusion at a rate between 10 and 30 units/kg/hour to target a ACT of

170 to 220 seconds or a PTT of two times normal. The use of heparin has the

advantage of being familiar to many clinicians and easily controlled with bedside

ACT monitoring. The risk of heparin use is excessive anticoagulation resulting in

an increased incidence of clinically significant bleeding. Furthermore, with the

recent availability of activated protein C in the therapy of sepsis, heparin may

further increase the risk of serious bleeding.

An alternative to heparin anticoagulation is citrate. In the early 1990s, Mehta

et al [29] championed the use of citrate as a form of anticoagulation for CRRT. In

this model, citrate is infused postpatient but prefilter to bind the calcium that is in

the hemofiltration circuit. When calcium is bound with citrate, the blood looses its

ability to coagulate, so the patency of the hemofiltration circuit is maintained. The

usual target for the ionized calcium (ICa) of the circuit is 0.25 to 0.4 mmols/L. To

prevent citrate toxicity in the patient, calcium then is infused independent of the

hemofiltration circuit back to the patient, targeting the patient’s ICa to a phys-

iologic level of 1.1 to 1.3 mmol/L. Protocols vary as to the source of the citrate

from a 4% sodium citrate solution with total sodium of 440 mEq/L to the 2%

citrate solution (220 mEq/L of sodium) of ACD-A (Baxter Health Care, Deerfield,

IL) [25,29,30]. Depending on the source of the citrate, one may need to prescribe a

normal sodium dialysis/replacement solution or a hyponatremic dialysis/replace-

ment solution. The only way to obtain a hyponatremic dialysis/replacement

solution is to have pharmacy custom-make the solutions, increasing both the risk

of error at the time of production and the cost. As a result, many programs prefer

ACD-A solution that can be combined with an industry-produced dialysis solution

that is calcium free (ie, Normocarb1).


The use of citrate anticoagulation has two primary side effects, metabolic

alkalosis and citrate loc (a term meaning excessive citrate) or citrate toxicity.

Metabolic alkalosis is a predicable side effect of citrate, because 1 mmol of citrate

converts to 3 mmol of bicarbonate in the presence of normal hepatic function. The

metabolic alkalosis may be further potentiated by bicarbonate in the Normocarb1,

along with acetate from the total parenteral nutrition (TPN) and acid and chloride

loss from nasogastric suction. This alkalosis can be easily remedied by reducing

the rate of the Normocarb1 and replacing the difference with normal saline. The

pH of normal saline is 5 to 5.4, and this acid load will offset the side effect of

metabolic alkalosis. Citrate LOC is a situation in which the citrate delivery

exceeds the citrate clearance. Citrate is cleared by the liver and by the hemofiltra-

tion membrane. Citrate LOC is observed clinically as rising total calcium and

decreasing Ica levels. This gap is caused by the citrate’s being bound to the

calcium. This situation is easily remedied by withholding the citrate dose for 30

minutes and then restarting it at a reduced rate. The findings of citrate LOC in a

previously stable patient may be a sign of worsening hepatic function and may

warrant further investigation of hepatic function. Although no prospective adult or

pediatric study has shown one anticoagulant to be superior to another, many

programs have reported less work at bedside and longer circuit life with the use of

citrate anticoagulation.

When to commence continual renal replacement therapy

A debate that will continue for decades is when to begin CRRT [31–36].

Advocates of early intervention argue it is better to initiate CRRT early because

(1) access is easier, (2) the staff has more opportunity at bedside to become more

comfortable with CRRT, (3) data by Ronco et al [37] in escalating the CVVH

dose indicate that survivors had a lower serum urea nitrogen than nonsurvivors,

and (4) data by Goldstein et al [4] show that survivors had less fluid accumulation

than nonsurvivors. Opponents of early use argue that (1) no prospective data

show that early intervention affects outcome, (2) placing the access adds risk to

the patient, (3) fluid removal adds risk to the patient, and (4) CRRT adds con-

fusion to bedside.

Both these positions will continue to find adherents, because the large,

randomized study by Mehta et al [36] to evaluate CRRT versus intermittent

hemodialysis began with more than 800 adults but ended with only approx-

imately 160 patients over a 5-year period [36]. Styles of practice and practice

bias will influence decision-making. Both positions have some validity,

because the limited prospective studies have not shown benefit, but the

authors know of no prospective study for ventilator use in children with

respiratory failure. The argument of excessive ultrafiltration is not valid with

the new hemofiltration systems that have accurate ultrafiltration controllers,

and one can provide solute clearance without ultrafiltration. Both Ronco’s

work [34] that was designed to examine escalating doses of replacement fluid


and showed that the beginning serum urea nitrogen level predicted outcome

and Goldstein’s work [4] were retrospective. Nevertheless, proponents of a

prospective study understand that styles of practice and patient populations

vary from program to program and thus appreciate the real difficulties in

designing such a trial. One final factor to consider is that, like many therapies

and procedures, infrequent use increases anxiety when a modality is employed

and carries an increased risk of complications. This anxiety may be offset with

more frequent use of CRRT that allows for more familiarity and experience

with the modality.

Nutrition in acute renal failure

Children with ARF often have inadequate nutrition. Often these patients have

a pre-existing illness before the onset of ARF (eg, postoperative ARF in infants

following repair of congenital heart disease) or have a disease that affects ab-

sorption (eg, HUS). This situation can be further exacerbated by the tendency to

restrict fluid intake in a child with ARF, often compromising overall nutrition.

Work by Bartlett in the 1980s demonstrated that inadequate nutrition had a

negative effect on patient survival in an adult surgical population [38]. Similar

studies have not been performed in a pediatric population, but common wisdom

would suggest that findings would be similar. Many programs use CRRT as a

way to deliver at least 100% recommended dietary allowance (RDA) of

nutrition either by TPN or, preferably, by enteral nutrition. The continuous

aspect of CRRT lends itself well to a continuous delivery of nutrition. A

question that arises is whether the loss of nutrition on CRRT exceeds the

delivery of nutrition and the patient’s needs. In separate studies, Davies [39],

Davenport [40], and Mokrzycki [41] have demonstrated that the rate at which

CRRT (either CVVH or CVVHD) is prescribed affects amino acid losses with

the potential risk of a negative protein balance. In a prospective study by these

authors [21], children were randomly assigned to receive either CVVH or

CVVHD for the first 24 hours with subsequent crossover to the opposite therapy

for the next 24 hours. During that time, the hemofiltration prescription of the

membrane, the blood flow rate, and the net ultrafiltration were fixed. The only

variable was that for 1 24-hour period dialysate was delivered at 2000 mL/hour/

1.73m2 and for the alternative 24 hours prefilter replacement fluid was delivered

at 2000 mL/hour/1.73m2. All children received TPN with 1.5 g/kg/day of amino

acid proteins; daily energy expenditure was measured by indirect calorimetry.

Both prescriptions resulted in a negative nitrogen balance and an average loss

of amino acids of approximately 10 g/1.73m2 (�10% of protein intake). A

recent paper by Bellomo et al [42] looked at a prospective analysis of delivery

of 2.5 g/kg/day with CVVHDF and again noted that nitrogen balance was

improved but the overall nitrogen balance remained negative [42]. Both these

prospective articles demonstrated that there was no risk from this high level of

protein delivery. Work by Maxvold [21] also demonstrated a further potential


complication of CRRT caused by a predominant loss of glutamine. Glutamine is

needed for protein production and is the major intracellular amino acid–

regulating signal trafficking of proteins. This predominant loss coupled with

the fact that many amino acid TPN preparations are deficient in glutamine

places the patient at risk for glutamine deficiency. This preferential clearance of

glutamine places these highly catabolic patients further at risk for negative

balances and worsening glutamine total body deficits. Ongoing work in

glutamine supplementation in hypermetabolic patients (eg, those with sepsis

or ARF or recipients of bone marrow transplants) continues to evaluate the role

of the nonessential but increasingly obvious key nutrient for cellular recovery

[43–46].

Many of the replacement or dialysis solutions have no glucose. Glucose,

because of its small size, has a sieving coefficient of 1. Therefore in a patient with

a serum glucose level of 100 mg/dL receiving replacement or dialysate at a rate of

2 L/hour, 48 L containing 48 g of glucose may be lost in a single day. This loss

represents approximately 200 calories as the result of glucose clearance becoming

negligible in a patient with multiple intravenous pumps all containing dextrose-

containing fluids.

Vasopressor and continual renal replacement therapy

Much of the early experience with CRRT was in the care of critically ill

patients requiring cardiovascular support. The ability of CRRT to provide a

controllable, steady titration of excess body volume brought CRRT to the ICU.

Whenever dialysis is implemented, adjustments of drugs are necessary because of

altered kinetics, potential drug/hemofiltration membrane interactions and alter-

ations of the volume of distribution (Vd) as the body edema lessens with ongoing

ultrafiltration. Data are available for clearance of drugs with CRRT [47–49].

Schetz et al [50] in a review of extracorporeal drug removal nicely demonstrated

the lack of effect on many of the cardiovascular drugs (eg, dopamine, dobu-

tamine, norepinephrine, and epinephrine) by CRRT [50]. Although these drugs

are not protein-bound and their molecular weights are below that of similar

molecules normally cleared by CRRT, the investigators observed that the rapid,

endogenous metabolism of these drugs by nonrenal mechanisms made elimina-

tion by CRRT minimal. Exceptions to these findings were milrinone, digoxin,

atenolol, and clonidine, which require dose adjustments when used with CRRT

[51,52].

Recent work by Ronco et al [53] found an actual improvement in the mean

arterial pressure (MAP) when patients with sepsis and MOSF were placed on

CRRT. This improvement was further augmented when CRRT was coupled with

plasma absorption. They postulated improvement in leukocyte responsiveness to

lipopolysaccharide as a potential explanation for this occurrence. The application

of coupled plasma absorption with filtration is just beginning to develop. The

hope of reestablishing a balanced state of pro- and anti-inflammatory mediators


in the systemic vascular bed continues to challenge those who care for critically

ill patients.

Outcome in acute renal failure

The outcome of children with ARF is as varied as the causes for developing

ARF/MOSF. Single-center studies have identified outcome by disease and

modality [2–4,7]. Work by Fleming et al [54] showed that the use of CRRT is

superior to peritoneal dialysis in the postoperative cardiac population, allowing

improved clearance and increased provision of nutritional support, but survival

could not be addressed because of small numbers. Goldstein’s work [4] with

CRRT in sepsis showed that accumulated fluid overload at the time of commenc-

ing CRRT had a negative impact on outcome, in that average fluid accumulation in

survivors (16%) was significantly less that in nonsurvivors (34%). The use of the

pediatric risk of mortality (PRISM) score did not correlate with outcome in this

population. A presentation at the Second International Conference on Pediatric

Renal Replacement Therapy (June 2002) expanded on Goldstein’s work. Data

were presented on 50 children from five separate centers with an overall survival

rate of 60% (S. Goldstein, personal communication). Using Goldstein’s model of

fluid overload at the time of commencing CRRT, investigators observed that

survivors had an average fluid overload of 8%, whereas nonsurvivors had a fluid

overload of 16%. These authors analyzed a large series of children with ARF

treated by peritoneal dialysis, hemodialysis, or CRRT and identified the under-

lying disease and the use of vasopressor agents as factors predicting outcome [3].

Concerns about use of CRRT in smaller children have been well addressed by

Zobel et al [55] who showed that CVVH[D] in infants has a more effective

clearance then CAVH[D]. These authors noted that CVVH[D] requires less anti-

coagulation and requires less-frequent changes to another form of RRT than

CAVH[D] [20]. In a study of 86 infants weighing less than 10 kg who required

CVVH[D], Symons et al [56] showed that, except in infants weighing less than

3 kg, there was no difference in survival when compared with older children [56].

Recently, Clermont et al looked at four groups of adult ICU patients in which

the overall incidence of ARF was 17% in 1530 admissions [33]. They compared

survival rates of patients without ARF, of those with ARF who did not require

dialysis, of those with ARF who required dialysis, and of those with end-stage

renal disease already undergoing (and continuing with) dialysis. The ICU mor-

tality rates were 5% in those without renal disease, 11% in those with end-stage

renal disease, 23% in the nondialyzed ARF population, and 57% in those with

ARF on acute dialysis. The investigators pointed out that the Acute Physiology

and Chronic Health Evaluation (APACHE III) score predicted outcome only in

those without ARF but overall was less predicative of mortality.

Clearly the outcome of children or adults with ARF is related to the overall

severity of illness. Current scoring systems (APACHE, PRISM) do not adequately

capture or predict the confounding variables that occur in this population.


Summary

Continuous renal replacement therapy is an effective means for fluid and solute

management in ARF/MOSF. Prospective studies have examined issues of anti-

coagulation, the impact of replacement/dialysis, the effects of bicarbonate- versus

lactate-based solutions, and nutritional and medication clearance. Speculation and

bias exists concerning when and for what indications CRRT should be initiated.

Many clinicians, supported by data from Ronco and Goldstein [4,37], would

contest that early institution is better if the risks (eg, access, anticoagulation) are

minimal and the possible benefits are maximal. The authors, examining the issues

as an intensivist and as a nephrologist, believe that early institution, aggressive

replacement/dialysis, and use of citrate-based replacement fluids provide sub-

stantive advantages. With the advent of Ronco’s recent data on sepsis managed

with filtration and plasma absorption, the indication for use of CRRT in MOSF

may become more evident regardless of the presence or absence of ARF [53].

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