Kidney International, Vol. 56, Suppl. 72 (1999), pp. S-56–S-61

CRRT IN THE CRITICALLY ILL

Metabolic aspects of continuous renal replacement therapies

WILFRED DRUML

Department of Medicine III, Division of Nephrology, Vienna General Hospital, Vienna, Austria

Metabolic aspects of continuous renal replacement therapies. ing hemodialysis therapy, have been regarded as detri-Continuous renal replacement therapies (CRRTs) are associ- mental to the patient’s health.ated with a broad pattern of additional metabolic effects be- Continuous renal replacement therapies (CRRTs)yond renal detoxification. Because of the continuous mode of

have become the first line of renal replacement therapytherapy and the high fluid turnover usually associated within critically ill patients with acute renal failure. Also,CRRTs, these side effects can become clinically relevant. With

many CRRT systems currently used, heat loss is considerable, CRRTs are associated with a broad spectrum of meta-but CRRTs can also be used to modulate body temperature bolic side effects that become clinically relevant becausein hyperpyrectic patients. Inappropriate glucose concentrations of the continuous mode of therapy lasting several daysof some substitution fluids can result in excessive glucose in-

or even weeks, and the high turnover of fluids usedtake. Most substitution and/or dialysate fluids used for CRRTsas the fluid replacement or dialysate. Not all of thesecontain lactate as organic anion. In disease states with impaired

lactate utilization, such as acute or chronic liver failure, and/ additional effects are necessarily undesirable, as severalor with increased endogenous lactate formation such as in metabolic consequences of CRRTs can be beneficial inshock states, this can result in hyperlactemia and is potentially certain clinical conditions [1, 2]. Knowledge of theseassociated with various adverse side effects. Small molecular

additional metabolic effects is mandatory for designingweight substances such as amino acids or water-soluble vitaminsan optimal nutritional regimen for patients treated withare lost in relevant amounts. With convective clearance and

the high molecular cut-off of synthetic membranes, medium- CRRTs [3].sized molecules such as hormones and cytokines are also filtered,but the pathophysiologic relevance of this observation remainsto be specified. Moreover, synthetic membranes used for CRRTs HEAT LOSShave adsorptive properties for a variety of molecules, such

Continuous hemofiltration will induce a considerableas cytokines, complement factors, and endotoxin. Continuousheat loss—as in many instances—during the use of CRRTblood membrane interactions cause the phenomena of bioin-

compatibility and a low-grade inflammatory reaction with po- systems without warming equipment for blood or fortentially adverse consequences on protein metabolism and im- substitution fluid. Even newer systems that heat onlymunocompetence. In designing a nutritional program for a the substitution fluid result in a negative temperaturepatient on CRRT, these metabolic effects—especially the loss

balance for the patient. Depending on the extent of fluidof nutritional substrates—must be considered. Certainly, mostturnover, this caloric loss can account for as much asof these side effects, such as the excessive load of lactate or

the loss of nutrients, are undesirable. However, some side ef- 1500 kcal/day and will usually result in a fall in bodyfects, such as the modulation of body temperature and the temperature [4, 5].elimination of endotoxin and/or mediators, might be at least

In several clinical conditions, treatment-induced hypo-potentially beneficial.thermia can be a desired effect, for example, in hyperpyr-ectic states and in multiple organ failure associated withcardiovascular instability. A reduction of body tempera-Obviously, the primary intention to initiate renal re-ture in these conditions can reduce oxygen consumption,placement is to reverse the metabolic consequences in-improve cardiovascular stability, and may also mitigateduced by renal shutdown. Nevertheless, besides this pre-the extent of protein catabolism.dominant metabolic function, various renal replacement

Thus, CRRTs can contribute to a reduction of oxygentherapies are associated with many other metabolic sideconsumption in clinical states associated with hypermeta-effects. Usually most of these additional effects, such asbolism, and may help optimize the relationship betweenloss of nutrients or induction of protein catabolism dur-oxygen consumption (fall in VO2 by the reduction ofbody temperature) and oxygen delivery (DO2) [5]. How-ever, if intravascular volume is depleted by vigorousKey words: CRRT, metabolism, nutrition, hyperlactemia, dialysis

membrane. dehydration [as has been advocated in the treatment ofacute respiratory distress syndrome (ARDS)], continu- 1999 by the International Society of Nephrology

S-56

Druml: Metabolic aspects of CRRTs S-57

ous hemofiltration will result in a fall in DO2 and may contain glucose in a concentration of 100 to 180 mg/dlin order to maintain a zero glucose balance.actually may deteriorate the VO2/DO2 relationship.

A decrease in temperature of returning venous bloodhas been identified as an important factor for hemody-

LACTATE, ACETATE, OR CITRATE INTAKEnamic stability during renal replacement therapy. Recent

Most available substitution solutions for CRRTs con-studies have clearly demonstrated that extracorporealtain lactate as an organic anion. Unfortunately, DL-lac-blood temperature is the main determinant of bloodtate is still in use in several countries. This should bepressure response during hemofiltration and hemodialy-replaced by pure L-lactate because of the potential toxicsis [6, 7].side-effects induced by the unphysiologic D-lactate.Potentially, the therapy-associated heat loss may also

Depending on the filtered volume/day and the amountgenerate untoward effects by blunting the metabolic re-of fluid replacement, the organism is exposed to a poten-sponse to infection and/or injury. Fever certainly is atially relevant if not excessive amount of lactate. This mayphysiological phenomenon that is relevant for the con-amount to as much as 2000 mmol/day and can equal thetrol of infection and expression of heat shock proteins.endogenous lactate turnover rate during physiologicalTherapy-induced hypothermia might thus impair immu-conditions (about 2400 mmol/24 hr in healthy subjects).nocompetence of the organism.

This lactate load gains clinical relevance in diseaseSeveral modern hemofiltration machines include astates in which either endogenous lactate utilization isheating system by which the blood line or the substitutionimpaired (such as in acute or chronic liver failure) or influid can be warmed as desired.clinical conditions associated with an increased lactateCaloric loss during CRRTs should be considered whenformation because of an impairment of microvascularcalculating the energy balance of a patient, and mustperfusion, such as in circulatory shock, septic shock, orbe compensated for by increasing the intake of energyhypoxic states. Under these conditions, any renal re-substrates such as glucose or fat emulsions during nutri-placement therapy using lactate-containing solutions willtional therapy. On the other hand, hemofiltration fluidsincrease plasma lactate concentrations.contain lactate, which are anions that when oxidated can

Recent evidence suggests that hyperlactemia inducedpartially substitute for the heat loss.by exogenous lactate infusion may present more thanjust a deranged laboratory value; it can assume patho-

GLUCOSE BALANCE physiological relevance. Several adverse consequencessuch as an impairment of myocardial contractility, inhibi-Glucose balance during CRRT is obviously dependent

on the glucose concentration of the substitution fluid. tion of endogenous lactate metabolism, and aggravationof insulin resistance have been reported [9–11]. Further-The use of glucose-free solutions does not contribute to

an improvement—as has been falsely assumed—in the more, it was suggested that lactate-containing substitu-tion fluids may promote protein catabolism. Moreover,metabolic control in patients with impaired glucose utili-

zation, for example, in most patients with acute disease with the impairment of interconversion of lactate to bi-carbonate, the control of acid-base balance is blunted.states. This plainly results in a glucose loss accounting

for 40 to 80 g/day depending on the filtration volume, The clinically acceptable extent of blood lactate levelelevation during therapy remains to be defined, but iswhich must be compensated for by an activation of en-

dogenous gluconeogenesis mainly from amino acids, thus usually regarded to be within the range of 3 to 4 mmol/liter.promoting protein breakdown. Glucose loss during the

use of glucose-free solutions must be considered when Lactate, acetate, and citrate are energy-yielding sub-strates that are metabolized in the tricarbonic acid cycleevaluating the energy balance of the patient, and it must

be replaced by nutritional therapy. and generate bicarbonate. Little is known on the impactof these compounds on energy metabolism in the criti-In contrast, in several institutions, solutions designed

for peritoneal dialysis have been used for CRRT. These cally ill patient. Lactate is used as an energy substrate byseveral tissues, including the myocardium, and in sharpsolutions have extreme glucose concentrations of 1240

to 3600 mg/dl, and should no longer be used because of contrast to the potential side effects of excessive lactateintake mentioned earlier in this article, there is also evi-the associated excessive glucose uptake [8]. Nutritional

therapy should be separated from renal replacement ther- dence that lactate might support myocardial functions[12]. Nevertheless, the lactate load may correspond toapy. It should be kept in mind that with modern nutri-

tional support, recommendations for glucose intake have an caloric intake of up to 500 kcal, which should beconsidered in calculating the energy balance of patients.been reduced during recent years and should be re-

stricted to a maximal amount of 5 g of glucose/kg body In all clinical conditions associated either with an in-creased endogenous lactate production (such as in circu-wt/day.

Thus, the substitution fluids used in CRRTs should latory shock) or an impaired lactate utilization (espe-

Druml: Metabolic aspects of CRRTsS-58

cially in patients with liver failure), acetate- and lactate- tional to the filtered volume and the plasma concentra-containing substitution fluids should be replaced by bi- tion of the substrate, and can thus be easily estimatedcarbonate-buffered substitution fluids, which have be- from the average plasma concentration and the fluidcome available in several countries. turnover. During continuous hemodialysis and/or hemo-

Acetate-containing solutions are restricted to special dialfiltration, which have become increasingly popularindications, such as patients with hyperlactemia and asso- during the recent years, this loss of low molecular weightciated metabolic alkalosis. The infusion of large amounts substances is even augmented by diffusive transport.of acetate during CRRT is associated with well-docu-mented side effects in intensive care patients, such as Amino acidssystemic vasodilation and reduction of myocardial con- Because of their small molecular size (mean moleculartractility, and it may also aggravate cardiovascular insta- weight 145 Daltons), the sieving coefficient of aminobility. acids approximates 1.0; thus, CRRT will result in the

Regional citrate anticoagulation is increasingly used elimination of amino acids from the bloodstream. Duringduring CRRTs [13–15]. During this type of anticoagula- postdilutional hemofiltration this loss accounts for ap-tion, bicarbonate and/or lactate concentrations must be proximately 0.25 g amino acids/liter filtered volume. Dif-reduced to avoid inducing metabolic alkalosis associated fusive clearance of amino acids during continuous hemo-with excessive organic anion infusion. Little is known

dialysis increases these losses. Depending on filtrateabout citrate utilization in the critically ill. However, in

volume per day and/or dialysate flow, amino acid losspatients on chronic hemodialysis therapy with minimalwill account for 6 to 15 g amino acids/day during CRRTresidual renal function, lactate elimination is not grossly[19–21].retarded (abstract; Apsner et al, Wien Klin Wochschr

Because the actual amount of an amino acid lost dur-110(Suppl 4):3A, 1998).ing CRRT is dependent on the plasma concentration,amino acids with high plasma levels are eliminated at a

ELECTROLYTE DERANGEMENTS higher rate. The elimination of glutamine, the aminoacid with the highest plasma concentration of all aminoMost available substitution fluids used in CRRTs haveacids, is also most pronounced during CRRT [22]. How-originally been designed for intermittent hemofiltrationever, this also has a therapeutic aspect, because duringin chronic renal failure patients. The use of these solu-CRRT, derangements of the plasma amino acid profiletions can induce pronounced electrolyte derangements in

patients with acute renal failure. The inadequate sodium can be avoided, and imbalances of amino acid concentra-concentration for replacement of large quantities of tions are smoothed.plasma water (with a higher sodium concentration) will In patients with acute renal failure treated by CRRTs,result in a negative sodium balance and hyponatremia nutritional solutions obviously must be given during ex-in a considerable fraction of patients. tracorporeal therapy. The endogenous clearance of

Most solutions do not contain phosphate and can ag- amino acids is in the range of 80 to 1800 ml/min andgravate hypophosphatemia, which can frequently de- thus exceeds dialytic clearance 10 to 100 times, so infu-velop in patients with acute renal failure. The concomi- sion results in minimal increases in plasma amino acidtant use of phosphate-free parenteral nutrition increases concentrations [3, 23]. Consequently, a small fraction ofthe risk of phosphate depletion [16–18]. only the infused amino acids will be removed in addition

Similarly, because many of these substitution fluids to the basal amino acid elimination, and the nutritionalare free of magnesium, a negative magnesium balance solution infused during hemodialysis/CRRT does notis induced by CRRT. Hypomagnesemia can also evolve substantially augment amino acid losses. Only about 10when citrate is used as an anticoagulant that not only to 15% of the amino acids given are lost in the dialysate/complexes with calcium but also with magnesium. hemofiltrate [19, 20, 23]. During clinically relevant infu-

During use of citrate anticoagulation, profound hypo-sion rates, amino acid loss is not correlated to amino

calcemia can occur with insufficient calcium supplemen-acid intake. However, any exaggerated intake of aminotation.acids (some authors administer up to 2.5 g amino acids/kg/day) must also increase the therapy-induced amino

LOSS OF NUTRIENTS acid elimination [21].When designing a nutritional program, this obligatoryWater soluble molecules with a low molecular size

loss of substrates must be considered in estimation ofand low protein binding, such as amino acids or waternitrogen requirements. Amino acid supply should besoluble vitamins, are eliminated during CRRT, resultingraised by approximately 0.2 g/kg/day to compensate forin a considerable loss of several nutritional substrates.

During postdilutional hemofiltration, this loss is propor- these therapy-associated losses [3].

Druml: Metabolic aspects of CRRTs S-59

Micronutrients of mediators is achieved by CRRT [31]. Obviously, theconvective clearance does not only extend to “bad mole-It is well documented that water soluble vitamins arecules” (mediators), which are implicated in the evolutioneliminated by conventional hemodialysis [24]. For CRRT,of the systemic inflammatory response syndrome andfew balanced studies are available. Relevant amounts ofmultiple organ dysfunction syndrome, but also to othervitamin C are lost during continuous hemofiltration [25].immunomodulatory substances. Potentially, the subtleIn a patient on CRRT, vitamin B1 (thiamine) depletionbalance between pro-inflammatory and anti-inflamma-was induced during CRRT, resulting in lactic acidosistory factors can be affected during CRRT. There is evi-and right ventricular dysfunction of the heart [26]. Thedence that CRRTs attenuate the up-regulation of phago-loss of nutritional antioxidants during CRRT can con-cytosis of polymorphonuclear leukocytes and can impairtribute to the profound impairment of the oxygen radicalthe host response to infection [32].scavenger system present in critically ill patients (ab-

An example of the potential elimination of “benefi-stract; Druml et al, J Am Soc Nephrol 4:314A, 1993).cial” molecules during CRRT is hormones. For catechol-Fat soluble vitamins are bound to transport proteinsamines the extracorporeal extraction rate is high, butand/or transported by plasma lipoproteins. Thus, the low

concentrations observed in patients with acute renal fail- nevertheless, this does not affect plasma concentrationure are not caused by elimination during CRRT [27]. and the need for exogenous catecholamine infusion, and

Also, a loss of trace elements is negligible during does not impair cardiovascular stability [33]. Similarly,CRRT because of the high protein binding [28]. De- insulin has excellent filtration properties, but this factcreased plasma concentrations of some trace elements, obviously does not aggravate glucose intolerance, in-especially selenium, seen in patients with acute renal crease insulin requirements, or even induce a diabeticfailure again are not induced by extracorporeal elimina- state during treatment. Again, the amount eliminated intion, but rather by an internal redistribution between the extracorporeal circuit is so small in relationship tovarious tissues. Because many substitution fluids contain whole body turnover that the fraction lost is not relevant.undefined and variable amounts of various trace ele- Because the molecular cut-off curve of modern mem-ments, it is difficult to assess trace element balances in branes for CRRT is not very steep, proteins of a higherpatients on CRRT. molecular weight are to some extent eliminated. Protein

losses, however, are moderately higher during convec-tion-based CRRT (60 mg/liter) than during diffusion-ELIMINATION OF PEPTIDES ANDbased CRRT (27 mg/liter), and can vary between 1.2SHORT-CHAIN PROTEINSand 7.5 g/day [34].The convective transport of continuous hemofiltration

or hemodiafiltration is characterized by a near linearclearance of molecules up to a molecular weight defined ADSORPTIVE PROPERTIES OFby the pore size of the filtration membrane. The “cut- ARTIFICIAL MEMBRANESoff” of the commonly used filtration membranes ranges

Elimination of substances during CRRT is not onlybetween 20 and 40 kDa, and thus, small proteins, suchmediated by convection and/or diffusion, but also byas peptide hormones (insulin, catecholamines) but po-the adsorption of proteins (hormones, interleukins, andtentially also mediators and cytokines, are filtered.other potential mediators) and possibly also of endotox-In fact, many peptides can be detected in the filtrateins to the membrane. The adsorptive properties are de-[29]. To discuss the pathophysiological relevance of thetermined by the membrane material used. Adsorptionelimination of a substance by hemofiltration, two pointsof complement factor D is most pronounced with mem-must be considered: (a) the magnitude of the circulatingbranes composed of polyacrylonitrile. Endotoxin ad-pool as a fraction of total pool of a putative molecule,sorption is highest with polyamide [35, 36]. Again, theand (b) the amount eliminated in relation to the half-clinical relevance of these properties of synthetic mem-life and whole body turnover. Even if a compound isbranes remains to be specified.filtered with a sieving coefficient of 1.0, the eliminated

When assessing the potential clinical relevance ofamount is negligible when the endogenous turnover ratethese mechanisms, it must be considered that the adsorp-is high, which exists for all mediators and hormones.tive effect is for a limited duration. After saturation ofPotential elimination of putative “mediators” involvedthe membrane, adsorption sharply decreases, and thus,in the development and/or maintenance of sepsis and/orcertainly after four to eight hours of treatment no furthermultiple organ dysfunction syndrome (MODS), such asadsorptive effectivity can be expected. If an adsorptivetumor necrosis factor-a or interleukins, has recently beenproperty of the membrane is a therapeutically desiredanalyzed in several reviews and beyond the scope of thiseffect, this suggests that the filters must be regularlyarticle [29, 30]. Currently, there is no evidence from

clinical studies that a quantitatively relevant elimination replaced (maximal filter time 8 to 12 hr).

Druml: Metabolic aspects of CRRTsS-60

Reprint requests to Wilfred Druml, M.D., Klinik fur Innere MedizinPOTENTIAL METABOLICIII, Division of Nephrology, Wahringer Gurtel 18-20, A-1090 Vienna,

CONSEQUENCES OF PROLONGED Austria.E-mail: wilfred.druml@akh-wien.ac.atBLOOD–MEMBRANE INTERACTIONS

Any extracorporal circuit induces the obligatory phe-REFERENCESnomena of bioincompatibility by blood–membrane inter-

1. Druml W: Impact of continuous renal replacement therapies onactions. Most synthetic membrane materials used inmetabolism. Int J Artif Organs 19:118–120, 1996CRRTs are characterized by a high biocompatibility, but

2. Frankenfeld DC, Reynolds HN: Nutritional effects of continu-nevertheless, prolonged contact of blood with artificial ous hemodiafiltration. Nutrition 11:388–393, 1995

3. Druml W: Nutritional support in acute renal failure, in Nutritionsurfaces will induce a “low-grade” activation of severaland the Kidney, edited by Mitch WE, Klahr S, Boston, Littlebiological cascade systems (such as coagulation factors, Brown, 1998, pp 314–345

complement, and kinins) and, secondarily, activation of 4. Matamis D, Tsagourias M, Koletsos K, Riggos D, MavromatidisK, Sombolos K, Bursztein S: Influence of continuous haemofiltra-cellular factors (platelets, polymorphonuclear cells, mono-tion-related hypothermia on haemodynamic variables and gas ex-cytes, basophils). For these reasons, nonsynthetic, low- change in septic patients. Intensive Care Med 20:431–436, 1994

biocompatible membrane materials such as cuprophane 5. Yagi N, Leblanc M, Sakai K, Wright EJ, Paganini EP: Coolingeffect of continuous renal replacement therapy in critically ill pa-should no longer be used in intensive care patients [37].tients. Am J Kidney Dis 32:1023–1030, 1998

Investigations using sham dialysis in healthy subjects 6. Schneditz D, Martin K, Kramer M, Kenner T, Skrabal FL:Effect of controlled extracorporeal blood cooling on ultrafiltration-have clearly demonstrated that any extracorporal circuitinduced blood, changes during hemodialysis. J Am Soc Nephrolcan activate protein catabolism, the extent of which de-8:956–964, 1997

pends on the biocompatibility of the membrane used 7. Van Kuijk WHM, Hillion D, Saviou C, Leunissen KML: Criticalrole of the extracorporeal blood temperature in the hemodynamic[38]. Potentially, this untoward effect is mediated as typeresponse during hemofiltration. J Am Soc Nephrol 8:949–955, 1997of chronic inflammatory process by activation of tumor 8. Monaghan R, Watters JM, Clancey SM, Moulton SB, Rabin

necrosis factor-a. This promotion of protein degradation EZ: Uptake of glucose during continuous arteriovenous hemofil-tration. Crit Care Med 21:1159–1163, 1993is evident until several hours after terminating the extra-

9. Yatani A, Fujiono T, Kinoshita K, Goto M: Excess lactate modu-corporal circulation. These phenomena have not been lates ionic currents and tension components in frog atrial muscle.systematically investigated during continuous renal re- J Mol Cell Cardiol 13:147–161, 1981

10. Cross HR, Clarke K, Opie LH, Radda GK: Is lactate-inducedplacement modalities. In a study of a nonrenal indica-myocardial ischaemic injury mediated by decreased pH or in-

tions for CRRT in trauma patients with normal renal creased intracellular lactate? J Mol Cell Cardiol 27:1369–1381, 199511. Lovejoy J, Newby FD, Gebhart SSP, DiGirolamo M: Insulinfunction, the plasma concentration of C-reactive protein

resistance in obesity is associated with elevated lactate levels andwas higher in the filtered patients than in the controldiminished lactate appearance following intravenous glucose and

group, suggesting that there was also an induction of insulin. Metabolism 41:22–27, 199212. Teoh KH, Mickle DAG, Weisel RD, Madonic MM, Ivanov J,an inflammatory reaction by the extracorporeal circuit

Harding RD, Romaschin AD, Mullen JC: Improving myocardialduring CRRT [39, 40]. metabolic and functional recovery after cardiac arrest. J ThoracCardiovasc Surg 95:788–798, 1988

13. Ashton DN, Mehta RL, Ward DM, McDonald BR, AguilarMM: Recent advances in continuous renal replacement therapy:CONCLUSIONSCitrate anticoagulated continuous arteriovenous hemodialysis.

Continuous renal replacement therapies are associ- ANNA J 18:263–267, 199114. Apsner R, Druml W: More on anticoagulation for continuousated with a broad spectrum of metabolic side effects.

hemofiltration. N Engl J Med 338:131–132, 1998Obviously, most of these side effects, such as the loss of15. Palson R, Niles JL: Regional citrate anticoagulation in continuous

nutrients (amino acids, vitamins) and the excessive lac- venovenous hemofiltration in critically ill patients with a high riskof bleeding. Kidney Int 55:1991–1997, 1999tate load are undesired. Nevertheless, some of the meta-

16. Kleinberger G, Gabl F, Gassner A, Lochs H, Pall H, Pichlerbolic side effects, such as the reduction of body tempera- M: Hypophosphatemia during parenteral nutrition in patients withture by heat loss, can also be beneficial. Currently, there renal failure. Wien Klin Wochenschr 90:169–172, 1978

17. Kurtin P, Kouba J: Profound hypophosphatemia in the course ofis no evidence from clinical studies that a quantitativeacute renal failure. Am J Kidney Dis 10:346–349, 1987elimination of cytokines and/or endotoxin is induced by 18. Marik PE, Bedigian MK: Refeeding hypophosphatemia in criti-cally ill patients in an intensive care unit. Arch Surg 131:1043–1047,CRRT. Knowledge of these additional metabolic effects1996is mandatory for avoiding the development of serious

19. Davies SP, Reaveley DA, Brown EA, Kox WJ: Amino acidmetabolic derangements during CRRT, and for design- clearances and daily losses in patients with acute renal failure

treated by continuous arteriovenous hemodialysis. Crit Care Meding an optimal nutritional program for patients on CRRT19:1510–1515, 1991that is adaptable to their altering needs.

20. Davenport A, Roberts NB: Amino acid losses during continuoushigh-flux hemofiltration in the critically ill patient. Crit Care Med17:1010–1015, 1989ACKNOWLEDGMENTS

21. Frankenfeld DC, Badellino MM, Reynolds N, Wiles CE,Portions of this article were presented at the 4th International Con- Siegel JH, Goodarzi S: Amino acid loss and plasma concentration

ference on Continuous Hemofiltration, Darmstadt, May 14th and 15th, during continuous hemofiltration. J Parenter Enteral Nutr 17:551–561, 19931999.

Druml: Metabolic aspects of CRRTs S-61

22. Novak I, Sramek V, Pittrova H, Rusavy Z, Tesinsky P, Lacigova 31. Druml W: Prophylactic use of CRRT in patients with normal renalfunction. Am J Kidney Dis 28(Suppl 3):S114–S120, 1996S, Eiselt M, Kohoutkova L, Vesla E, Opatrny K: Glutamine

32. Discipio AW, Burchard KW: Continuous arteriovenous hemofil-and other amino acid losses during continuous venovenous hemo-tration attenuates polymorphnuclear leukocyte phagocytosis indiafiltration. Artif Organs 21:359–363, 1997porcine intra-abdominal sepsis. Am J Surg 173:174–180, 199723. Druml W: Nutritional considerations in the treatment of acute

33. Bellomo R, McGrath B, Boyce N: In vivo catecholamine extrac-renal failure in septic patients. Nephrol Dial Transplant 9(Suppltion during continuous hemodiafiltration in inotrope-dependent4):219–223, 1994patients Trans Am Soc Intern Organs 37:324–325, 199124. Descombe E, Hanck A, Fellay G: Water soluble vitamins in

34. Mokrzycki MH, Kaplan AA: Protein losses in continuous renalchronic hemodialysis patients and need for supplementation. Kid-replacement therapies. J Am Soc Nephrol 7:2259–2263, 1996ney Int 43:1319–1323, 1993

35. Gasche Y, Pascual M, Suter PM, Favre H, Chevrolet JC, Schif-25. Story DA, Ronco C, Bellomo R: Trace element and vitaminferli JA: Complement depletion during haemofiltration with poly-concentrations and losses in critically ill patients treated with con-acrylonitrile membranes. Nephrol Dial Transplant 11:117–119,tinuous venovenous hemofiltration. Crit Care Med 27:220–223,19961999

36. Dinarello CA, Lonnemann G, Maxwell R, Shaldon S: Ultrafil-26. Madl Ch, Kranz A, Liebisch B, Traindl O, Lenz K, Druml W:tration to reject human interleukin-1-inducing substances derivedLactic acidosis in thiamine deficiency. Clin Nutr 12:108–111, 1993from bacterial cultures. J Clin Microbiol 25:1233–1238, 198727. Druml W, Schwazenhofer M, Apsner R, Horl WH: Fat soluble 37. Himmelfarb J, Tolkoff R, Chandran P, Parker RA, Wingard

vitamins in acute renal failure. Miner Electrolyte Metab 24:220–226, RL, Hakim R: A multicenter comparison of dialysis membranes1998 in the treatment of acute renal failure requiring dialysis. J Am Soc

28. Konig JS, Fischer M, Bulant E, Tiran B, Elmadfa I, Druml W: Nephrol 9:257–266, 1998Antioxidant status in patients on chronic hemodialyis therapy: 38. Bergstrom J: Factors causing catabolism in maintenance hemodial-Impact of parenteral selenium supplementation. Wien Klin Wo- ysis patients. Miner Electrolyte Metab 18:280–283, 1992chenschr 109:13–19, 1997 39. Gutierrez A, Alvestrand A, Bergstrom J: Membrane selection

29. Hoffmann JN, Hart WH, Deppisch R, Faist E, Jochum M, In- and muscle protein catabolism. Kidney Int 42(Suppl 38):S86–S90,thorn D: Hemofiltration in human sepsis: Evidence for elimination 1992of immunomodulatory substances. Kidney Int 48:1563–1570, 1995 40. Riegel W, Ziegenfuss T, Rose Bauer M, Marzi I: Influence

30. Silvester W: Mediator removal with CRRT: Complement and of venovenous hemofiltration on posttraumatic inflammation andhemodynamics. Contrib Nephrol 116:56–61, 1995cytokines. Am J Kidney Dis 30(Suppl 4):S38–S43, 1997