CONTINUOUS RENAL REPLACEMENT THERAPY

Special Issues with Continuous Renal Replacement Therapy in Pediatric Patients

Randall Jenkins Department of Pediatrics, Division of Pediatric Nephrology, Emanuel Children’s Hospital and Oregon Health Sciences University, Portland, Oregon

Ten years have passed since the first reports of CRRT in pediatric patients (1, 2). It was well rec- ognized that there are special problems in perform- ing these therapies in children, especially the very small newborn. Initially, few vascular access cath- eters were available which were suitable for place- ment in small children. Early models of hemofilters were often too small or too large in surface area for practical use. Blood priming was often necessary when adult-sized hemofilters were used. Sludging and clotting of systems were frequent problems, making these therapies labor-intensive for health care providers.

At present, some of these issues have been solved while others have not. Special issues must be addressed in the performance of continuous re- nal replacement therapy (CRRT) in pediatric pa- tients to avoid pitfalls and to insure successful treat- ment. Improperly done, pediatric CRRT can be extremely time consuming and can result in inade- quate fluid balance and solute control. Adequate vascular access and proper choice of hemofilters lead the list of key issues. Other special pediatric issues in CRRT include risk of anticoagulation and maintainance of fluid balance. Also discussed are indications for CRRT for infants in metabolic crisis. Some modes of CRRT, such as in combination with an oxygenator circuit, may seldom be seen with adult CRRT. These pediatric issues are addressed with practical solutions offered.

Vascular Access

Perhaps the single most difficult problem with pe- diatric CRRT is obtaining adequate vascular access. Adequate access can make the difference between success and failure, and can reduce the bedside time commitment for the nephrologist and nurse (3). Crucial to success is obtaining enough blood flow. When blood flow is inadequate, sludging, clotting, and low solute clearance are likely to occur (4, 5 ) .

Proper choice of catheter is a key factor in ob-

Address correspondence to: Randall Jenkins MD, Ernanuel Chil- dren’s Hospital, 501 N. Graham, Suite 340. Porfland, Oregon 97227 Seminars in Dialysis-Vol 9, No 2 (Mar-Apr) 1996 pp 179-183

taining enough blood flow. The smallest infants are particularly challenging due to the technical diffi- culty in cannulating small blood vessels and the lack of commercial products designed for CRRT. School-aged children can usually be successfully treated with small adult CAVH catheters or stan- dard pediatric double lumen hemodialysis cathe- ters.

Whether blood flow is achieved with a blood pump, or driven by arteriovenous forces, the same flow principles apply. Flow is proportional to the fourth power of the radius of the catheter and is directly proportional to catheter length; tip design can affect flow as well (6). Catheters should be kept short and should not have sharply constricted tips (4). Maximum blood flow is therefore achieved with the largest diameter possible catheter which can be placed without compromise to the patient. Sug- gested targets for desirable blood flow are shown in Table 1. Systems can be operated at lower blood flow, but are more likely to have inadequate clear- ance values and to require more frequent changing due to clotting (3).

Choice of catheters will depend on whether or not the therapy will be pumped. Pumped therapies may pump from an artery to a vein, or more commonly, from vein to vein. Arteriovenous therapies will al- ways need arterial and venous access. Double lu- men catheters have become increasingly popular for use in venovenous therapies. Some suggested double lumen catheters are listed in Table 1.

Arterial catheters are usually placed in femoral arteries. Other vessels which have been used for arterial access include brachial, radial, and umbili- cal arteries (3, 7). Flows through radial and umbil- ical artery catheters are generally less than those possible through femoral artery catheters and may be inadequate in some situations. Venous catheters can be placed in femoral, subclavian, or jugular veins; the right internal jugular vein usually accom- modates the largest catheter. One can also use an arterial vessel for the afferent limb of CVVH.

Catheter over needle devices are usually thin- walled and therefore have larger inner diameters relative to the outer diameter. However, they are stiffer, more prone to kink, and tend to not be us- able for long periods of time when placed in femoral vessels. Double lumen central venous catheters size 4-6 French usually produce unacceptable blood

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TABLE 1. Suggested equipment, supplies, and operation parameters for CRRT in pediatric patients of varying ages

Option NEONATE INFANT T 0 D D L E R CHILD Acceptable Single 1. 18-22 Ga catheter 1. Cook 5.5 Fr. CAVH 1. Cook 5.5 Fr. CAVH 1. Medcomp 5 Fr.

Lumen Catheters over needle by 2. 16-20 Ga catheter 2. 4-6 Fr. CAVH Medicut, Arrow, over needle 2. Cook 5.5 Fr. CAVH etc. 3. 16 Ga Medcomp

2. 16 Gd5Fr umbilical CAVH 1. Medcomp 7 Fr. HD

Lumen Catheters 2. Vas-Cath 6.5 Fr.* 2. Vas-Cath 6.5 Fr.* Acceptable Double 1. Medcomp 7 Fr. HD 1. Medcomp 7,9 Fr. 1. Medcomp 9 Fr. HD

HD 2. Ouinton 10 Fr. 2. Vas-Cath 6.5 Fr.* catheter

Acceptable Hernofilter 1. Amicon Minifiltert 1. Amicon Minifilter 1. Amicon Minifilter 1. Amicon D-20 2. Amicon Minifilter Plus Plus 2. CGH Multiflow M60

Plus Desirable blood flow > 10

Typical UFR (mlfmin) 0.25-2.0 Typical dialysate flow 1 4

( d m i n )

( d m i n )

> 15

1 4 243

>30

3-6 4-12

>50

5-16 6-16

* Not available in the United States at the present time. f For fluid removal such as might be done in ECMO.

flows. Single lumen central venous access catheters not intended for CAVH or hemodialysis tend to be too long, relatively thick-walled, and narrow tipped. Silastic catheters, with the exception of those few catheters specifically designed for dialy- sis, are not suitable due to thick or soft collapsible walls. Variability of inner diameter of 5 Fr. or 16 gauge catheters has been shown to be as high as 39% with resultant CAVH flow variation up to 370% (8). Therefore, one must be careful when se- lecting catheters not designed for CRRT.

Choice of Hernofilter

The choice of hemofilters is limited and is shown in Table 1. Adult sized hemofilters can be used in very small patients, but result in a problem of large priming volume. Unless these hemofilters (and tub- ing) are primed with donor blood prior to use, small patients might experience hypotension or hypox- emia when initiating therapy. Saline priming is usu- ally safe when the volume is less than 10% of the patient’s blood volume. Children with normal he- rnatocrit may tolerate larger priming volumes, whereas children with low blood hematocrit may become symptomatic more readily. When hemato- crit is relatively normal but the priming volume is high, priming the system with 5% albumin solution can often obviate the need for red cell priming.

When large amounts of donor blood are used, there is risk of acidosis or hyperkalemia at the time flow is initiated. This is particularly a problem when t.he priming volume is similar to or exceeds the pa- t.ients’ entire blood volume. Under these circum- stances, blood used should be either recently do- nated or washed. Consideration should be given to checking pH and potassium of the donor blood be- fore use.

The smallest surface area hernofilter, Amicon Minifilter@ (Amicon, Limerick, Ireland) is too small (0.015 m2) to provide adequate solute control even for neonatal patients. The Minifilter may be useful

for slow continuous ultrafiltration (SCUF) in neo- nates. The Amicon Minifilter Plus@ is of reasonable surface area (0.08 m2) to be adequate for most infants and toddlers. Blood line connectors on both Ami- con pediatric hemofilters are different from stan- dard hemodialyzer blood line connectors. School- aged children can be treated with a variety of he- mofilters. The CGH Multiilow 60 is a particularly good hernofilter for diffusive mode use.

Anticoagulation Risks

Anticoagulation for pediatric CRRT is carried out much in the same way as for adult CRRT. Options include continuous heparin administration and in- termittent bolus administration. Patients with a co- agulopathy or liver failure can often be treated with- out anticoagulation. Anticoagulation with citrate has been used successfully in four pediatric patients with the smallest infant treated weighing less than four kilograms (9).

Of prime importance is avoidance of anticoagula- tion in premature infants. Experience in extracor- poreal membrane oxygenation systems has shown that the risk of intracranial hemorrhage is consid- ered too high for infants of 35 weeks gestation or less.

We have had the promise of heparin bonded CRRT systems for many years. Prior work has shown that the entire system including catheters must be treated for the system to be effective. One such experimental system using ionically bound heparin has recently been reported (10).

Mode of CRRT

All forms of CRRT can be accomplished in pedi- atric patients. These include arteriovenous and ven- ovenous systems, both of which can be operated in a convective (hemofiltration) or diffusive (hernodi- alysis) mode. Combined convective and diffusive modalities can also be done. The principal choices

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to be made when choosing a modality are whether or not to use a dialysate and whether or not to pump the blood. Another choice is whether to augment or control ultrafiltrate or dialysate with pumps, grav- ity, or with a suction canister. Typical flow rates for

I ultrafiltration and dialysate are suggested in Ta- ble 1.

Operation of a system with a dialysate has several advantages over hemofiltration systems. Since ster- ile dialysate is commercially available but not filter replacement fluid (in the U.S), dialysate systems may be started more quickly and with less risk to the patient of complications from an improper dial- ysate mixture. Fluid management is easier when one avoids multiple solutions comprising the filter replacement fluid (FRF).

Clearance of urea and creatinine will increase by addition of a dialysate to CAVH or CVVH (3, 11- 13). For a PAN membrane, this additional clearance in an adult CAVHD system was equal to dialysate

Dialysate will not fully equilibrate with urea and creatinine in most pediatric hemofilters, therefore clearance will be less than dialysate flow ( 3 , 12). Ultrafiltration systems have sieving coefficients for these solutes close to 1.0. Thus, when one de- creases ultrafiltration and FRF and replaces those flows with equivalent flows of dialysate, clearance will drop (12). Therefore, solute clearance will only be higher in dialysate systems as compared to non- dialysate systems when ultrafiltration and FRF are maintained or dialysate flow increased as needed. In adult CAVHD studies, diffusive clearance dimin- ished when blood flow dropped below 50 mLlmin (1 I). One would therefore anticipate decreased dif- fusive clearance in pediatric systems operated with low blood flow. Comprehensive data are not avail- able for diffusive versus convective clearance in pe- diatric hemofilters over a wide range of blood and dialysate or FRF flows.

Predilution CAVH is associated with more stable blood flow and higher ultrafiltration rates than post- dilution CAVH (12). Low blood flow and high ul- trafiltration rates can result in sludging and in- creased probability of clotting the system in postdi- lution CAVH systems. When arterial hematocrit is elevated, the risk of sludging is high (5). Predilution of FRF should markedly reduce that risk.

Pumped systems (venovenous) generally are more reliable than arteriovenous systems for main- taining stable blood flow and getting adequate sol- ute. control and fluid removal (14-16). CVVHD as compared with CAVHD has been shown to result in less heparin usage, longer filter lifespan, and fewer instances of inadequate dialysis (14). Increasing numbers of centers have begun to use venovenous CRRT. The principal drawbacks of venovenous CRRT include necessity for increased nursing train- ing and those problems associated with large prim- ing volumes when commercial CVVH machines are used.

At present there are limited pediatric blood lines

flow (1 1).

for the commercial CVVH pumps, and the smallest hemofilters do not adapt well to the adult blood lines. Bunchman has shown that it is possible to use a hemodialysis pump and air detector module with standard neonatal or pediatric blood lines to bring the extracorporeal volume down to an acceptable size (14). The ability to modify other hemodialysis machines in this manner has not been studied. Ellis has reported using a conventional intravenous infu- sion pump (Baxter Flo-gard 6200, Deerfield, ILL) as the blood pump for CVVH in infants (15). Choos- ing the modality for treating hyperkalemia de- serves special comment. CAVHD has been shown to be more effective than CAVH for correcting hy- perkalemia (3). CVVHD should be the most effec- tive modality for potassium removal. For life- threatening hyperkalemia, standard hemodialysis will provide the most rapid correction of hyperkale- mia and would be preferable to treatment with any mode of CRRT unless appropriate hemodialysis equipment were not available.

Special Applications of CRRT in Pediatric Patients

Inborn Errors of Metabolism

Patients with inborn errors of metabolism can present with coma and profound illness due to marked elevation of ammonia, lactic acid, and other solutes. It is imperative with these infants that am- monia levels be reduced as quickly as possible to prevent toxicity to the brain. Hemodialysis will ac- complish this most expeditiously (16). Clearance with peritoneal dialysis or exchange transfusion is too low to bring these harmful solutes down to ac- ceptable levels (17, 18). CRRT has been reported successful in treatment of neonatal metabolic dis- ease and may be useful when hemodialysis is not possible or once metabolic control is obtained (17, 18).

Maple Syrup Urine Disease was treated success- fully in three patients with CVVH (17). Interest- ingly, one patient appeared to have more effective leucine removal with CVVH as compared with CVVHD. Hyperammonemia has been treated with CAVH (18). One investigator found CVVH com- bined with peritoneal dialysis was insufficient to bring down ammonia levels in one patient until di- alysate flow was added (17). Although direct com- parisons of therapies are not available, one would predict that the pumped therapies with combined diffusive and convective clearance would be the most effective of the continuous therapies in rapid solute removal.

Lactic Acidosis

Lactic acidosis may accompany an inborn error of metabolism, but is more commonly seen in septic shock. Although there is some debate as to the ben- efit or necessity of correcting metabolic acidosis,

182 Jenkins

use of lactate containing dialysate may not be effec- tive in improving acidosis. Bicarbonate dialysate has been effective in correcting severe lactic acido- sis in this setting (19).

CRRT in Extracorporeal Membrane Oxygenation

CRRT has been done on patients on extracorpo- real membrane oxygenation (ECMO) with a variety of systems. A hemofdter can be inserted parallel with the oxygenator (effectively shunting some blood around the oxygenator). On systems using roller pumps, systems can be inserted between the post-oxygenator position and the bladder. The blood pump rate must be increased to accommodate this “steal” of blood diverted from the patient (20).

Regardless of which system is used, one must be careful to avoid excessive flow through the hemo- filter. There is a danger of abruptly reducing the oxygenation patient circuit blood flow or reducing oxygenation saturation upon initiation of hemofilter blood flow. One must remember that in pediatric CAVH, the catheters are the major resistance to blood flow (3,4); there are none in ECMO CRRT. A hernofilter placed in an ECMO circuit where the pressure drop between connections may be as much as 100-200 mmHG will have very high blood flow unless there is limitation added (in addition to the stopcocks and short tubing segments at the ECMO system connections). Practically, this can be done by including six to ten feet of pressure-monitoring intravenous tubing within the hemofilter circuit. This extra resistance brings hemofilter blood flow down to the desirable range of about 30 mL/min & 20 mL/min. Adjustments in this tubing may be nec- essary for unusual circumstances. Ideally, a flow probe should be placed on the hemofilter circuit to be sure that adequate but not excessive blood flow travels through the hemofilter.

Another location of the hemofilter in roller- pumped ECMO systems would be between the pa- tient and the bladder (20). Another method of CRRT with ECMO circuits is to add two take-offs anywhere in the circuit, but preferably not where pressure might be sub-atmospheric or in a manner which bypasses the oxygenator. CVVH or CVVHD could then be done with the take-offs as access. Blood priming would probably be necessary if the additional priming volume were significant. Antico- agulation as being done for the ECMO circuit should be adequate to prevent clotting for the CRRT circuit.

Fluid Balance in Pediatric CRRT

Fluid balance is another special problem for CRRT in small infants. Regardless of which type of system used (except SCUF) the inflow of fluid (FRF or dialysate) must approximate the outflow of fluid (UF or dialysate), with adjustment for other inputs and outputs. Many centers control FRF and

dialysate inflow (if any) with intravenous pumps. Outflow of ultrafiltrate (with or without dialysate) may be controlled by pump or by adjusting the height of the column of fluid extending down from the hemofilter. When pumps are not used, frequent adjustments of the height of the collection con- tainer, or frequent adjustments of FRF, must be made to avoid fluid imbalance. Intravenous pumps may improve predictability of fluid flows as well as provide suction when desired. Piston pumps in one study showed typical errors of between zero and four percent; whereas linear peristaltic pumps gave an error of zero to 10 percent depending on the pressures encountered (21). Periodic checks of the fluid removal and patient weight are therefore nec- essary for safety.

Suction with a vacuum system may also be used to augment ultrafiltration rate. Ultrafiltration in one study doubled, although blood flow was reduced by half (22). Laboratory studies suggest that ultrafiltra- tion rate may peak with moderate suction, but then be reduced as suction is increased (23).

An accurate fluid management system is needed to control the fluid balance in CRRT systems. One such.system recently has been reported, but is not yet commercially available (24). The Amicon Equa- line system@ has been used by Zobel(13), but little has been reported on its limitations or advantages.

Cost Comparison

There are no published data comparing various forms of CRRT among each other in pediatric pa- tients. A cost analysis has been done comparing CAVHD with hemodialysis and continuous cycled peritoneal dialysis ( 2 5 ) . This study showed CAVHD to cost more than three times as much as cycled peritoneal dialysis, and about 60% more than hemodialy sis.

Summary

Pitfalls are plentiful in pediatric CRRT systems. Still, these continuous therapies add to the arma- mentarium of the pediatric nephrologist in taking care of children with renal failure. The key to suc- cess is obtaining adequate vascular access. Ade- quate blood flow makes solute and volume status more easily controlled and reduces clotting and overall labor intensity of the therapy. Perhaps, soon, newer small priming volume tubing systems will become available for commercial CVVH(D) de- vices, and the long-promised heparin bonded sys- tem will become a reality.

References

1. Ronco C, Brendolan A, Bragantini L, Chiarmonte S, Fabris A, Fer- iani M, Frigola A, La Greca G: Treatment of acute renal failure in the newborn by continuous arteriovenous hernofiltration. Transactions American SOC Artf ln tern Organs 31:634-637, 1985

2. Lieberman KV, Nardi L, Bosch JP: Treatment of acute renal failure

PEDIATRIC CRRT 183

in an infant using continuous arteriovenous hemofiltration. J Pediatr 106(4):646-649, 1985

3. Jenkins R , Harrison H, Jackson E, Funk J: Continuous renal replace- ment in infants and toddlers, in Continuous Hemofiltrarion. Contri- butions to Nephrology, edited by Sieberth HG, Mann H, Summvoll HD. Basel, Karger, 1991, 93:245-249

4. Jenkins R, Funk J, Chen B, Thacker D: Effects of access catheter dimensions on blood flow in continuous arteriovenous hemofiltration, in Continuous Hernofiltration. Contributions to Nephrology, edited by Sieberth HG, Mann H, Summvoll HD. Basel, Karger, 1991, 93: 171-174

5. Jenkins R, Funk J , Chen B, Golper T: Operational instability in ex- tracorporeal filtration of blood. Blood Purification 10292-308, 1992

6. Jenkins R, Funk J, Chen B, Golper T: A mathematical model for flow and pressure and ultrafiltration in extracorporeal filtration of blood, Blood Purification 10:282-291, 1992

7. Zobel G, Trop M, Beitzke A, Ring E: Vascular access for continuous arteriovenous hernofiltration in infants and young children. Artificiaf Organs lZ(l):l&19, 1988

8. Jenkins RD, Kuhn RJ, Funk J: Clinical implications of catheter vari- ability on neonatal continuous arteriovenous hemofiltration (CAVH). ASAIO Transactions 34:lObll l , 1988

9. Personal Communication from William Griswold, M.D., University of California, San Diego.

10. Arakawa M, Nagao M, Gejyo F, Terada R, Kabayashi T, Kunitomo T: Development of a new antithrombogenic continuous ultrafiltration system. Artificial Organs 15(3):171-179, 1991

1 1 . Sigler MH, Teehan B P Solute transport in continuous hemodialysis: A new treatment for acute renal failure. Kidney lnternational32:562- 571, 1987

12. Werner HA, Herbertson MJ, Seear MD: Operating characteristics of pediatric continuous arteriovenous hemofiltration in an animal model. Pediarric Nephrology 7: 189-193, 1993

13. Zobel G, Kuttnig M, Ring E: Continuous arteriovenous hemodialysis in critically ill infants. Child Nephrol Urol 10:19&198, 1990

14. Bunchman TE, Norma JM, Kershaw DB, Sedman AB, Custer JR: Continuous venovenous hemodiafiltration in infants and children. American Journal of Kidney Diseases 25(1):17-21, 1995

15. Ellis EN, Pearson D, Robinson L, Belsha CW, Wells TG, Berry P: Pump assisted hemofiltration in infants with acute renal failure. Pe- diatric Nephrology 7:434437, 1993

16. Rutledge SL, Havens PL, Hamond MW, McLean RH, Kan JS, Brusi- low SW: Neonatal hemodialysis: Effective therapy for the encepha- lopathy of inborn errors of metabolism. J Pediatr 116:125-128, 1990

17. Falk MC, Knight JF, Roy LP, Wilchen B, Schell DN, O’Connell AJ, Gillis J: Continuous venovenous haemofiltration in the acute treat- ment of inborn errors of metabolism. Pediatric Nephrology 8:330- 333, 1994

18. Sperl W, Geiger R, Maurer H, Murr C , Schmoigl C, Steichengersdorf E, Sailer M: Continuous arteriovenous haemofiltration in a neonate with hyperammonaemic coma due to citrullinaemia. J Inherited Metab Dis 15:158-159, 1992

19. Jenkins R, Jackson E, Kuhn R, Funk J: Benefit of bicarbonate dial- ysis during CAVHD. ASAlO Transaction 36:M465-M466, 1990

20. Yorgin PD, Kirpekar R, Rhine W D Where should the hemofilter circuit be placed in relation to the extracorporeal membrane oxygen- ation circuit? ASAIO Journol 38:801-803, 1992

21. Jenkins R, Harrison H , Chen B, Arnold D, Funk J: Accuracy of intravenous infusion pumps in continuous renal replacement thera- pies. ASAIO Journal 38:808-810, 1992

22. Zobel G, Ring E , Trop M , Grubbauer HM: Suction-supported con- tinuous arteriovenous hemofiltration in children. Blood Purfication 6:37-42, 1988

23. Jenkins RD, Chen B, Funk JE: Maximum ultrafiltration rate in con- tinuous arteriovenous hemofiltration does not occur at the lowest height of the ultrafiltrate collection chamber. ASAIO Journal 393M618-620, 1993

24. Kitaevich Y , Bissler J, Benzing G, Hemasilpin N, Marchevsky G, McEnery P, Hammitt M: Development of a high-precision continuous extracorporeal hemodidliltration system. Biomedical lnstrumentation and Technology 27(2): 150-156, 1993

25. Reznik VM, Randolph G, Collins CM, Peterson BM, Lemire JM, Mendoza SA: Cost analysis of dialysis modalities for pediatric acute renal failure. Peritoneal Dialysis International 13(4):311-313, 1993