Extended daily dialysis: A new approach to renal replacement for acute renal failure in the intensive care unit

Extended Daily Dialysis: A New Approach to Renal Replacement for Acute Renal Failure in the Intensive Care Unit Victoria A. Kumar, MD, Maureen Craig, RN, MSN, Thomas A. Depner, MD, and Jane Y. Yeun, MD ● Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P ⴝ 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P ⴝ 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P ⴝ 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P ⴝ 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform. © 2000 by the National Kidney Foundation, Inc. INDEX WORDS: Acute renal failure (ARF); continuous venovenous hemofiltration (CVVH); continuous renal replacement therapy; critical care; dialysis.

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ONTINUOUS RENAL replacement therapies in the setting of acute renal failure (ARF) offer greater hemodynamic stability and an effective means for volume removal in the critically ill, hypotensive patient. The original method, termed continuous arteriovenous hemofiltration, relied on the patient’s own blood pressure as the driving force for the system.1 The need for increased solute clearance and safer vascular access led to continuous venovenous hemofiltration (CVVH), which requires a blood pump but improves ultrafiltration (UF) and convective clearance.2 The technique was later modified when a high-flux dialyzer was substituted From the Department of Medicine, Division of Nephrology, University of California Davis, Sacramento; and the Department of Veteran’s Affairs Northern California Health Care System, Pleasant Hill, CA. Received December 20, 1999; accepted in revised form March 24, 2000. Address reprint requests to Victoria A. Kumar, MD, Associate Physician Diplomate, Nephrology Division, University of California Davis Medical Center, 4150 V St, Suite 3500, Sacramento, CA 95817. E-mail: [email protected] © 2000 by the National Kidney Foundation, Inc. 0272-6386/00/3602-0008$3.00/0 doi:10.1053/ajkd.2000.8973 294

for the blood filter, allowing simultaneous venovenous filtration and dialysis. The addition of dialysis further improved urea clearance while maintaining hemodynamic stability. Despite the technical advances made in continuous therapies, including improved clearance and control of uremia, an improvement in patient outcomes has not been clearly shown for critically ill patients with ARF.3,4 One reason for the lack of improved outcome may be that the high mortality rate observed (64% to 100% in the United States) is independent of the renal failure.5-7 A beneficial effect of CVVH on patient outcome may be difficult to show in this population, especially in the setting of multiorgan failure. Although the optimum modality used to treat patients with ARF remains uncertain, intensive care unit (ICU) patients appear to benefit from a greater dose of dialysis.8 Continuous therapies have several inherent disadvantages, including continuous anticoagulation, patient immobility, intensive nursing requirements, and increased expense. In our experience, the initiation of CVVH requires at least several hours for mobilization of both dialysis and ICU nursing staff and to mix the appropriate replace-

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ment fluid. When small changes in the composition of replacement fluid are made, numerous bags of previously mixed fluid are often discarded. Frequent measurements of serum electrolytes, precise monitoring of intake and output, and frequent adjustments of the replacement fluid rate are required to guard against fluid imbalance. If the patient must be moved to another location, continuous therapies must be halted and may not be restarted for many hours. This delay adversely impacts on solute clearance and UF. To circumvent these problems, we designed a treatment plan for the critically ill patient that includes the major advantages of CVVH but uses conventional hemodialysis instead of hemofiltration. The dialysis is performed daily at slow flow rates over an extended treatment time (EDD). This approach also offers many of the benefits recently proposed for daily outpatient hemodialysis9 and nightly hemodialysis.10 Our initial experience with EDD, although limited, has been overwhelmingly positive. METHODS Between February 1997 and April 1999, a total of 28 ICU patients with ARF underwent EDD at the University of California Davis Medical Center (Sacramento, CA), and 17 patients underwent CVVH. The choice of modality was made by the attending nephrologist but was based largely on availability of equipment and not on the clinical status of the patient. There were several machines available each day on which EDD could be performed, whereas only a single machine was available for CVVH at a given time. If continuous anticoagulation was contraindicated, then CVVH was not used. Each patient was treated for 3 or more consecutive days. Three EDD patients were excluded because of the loss and/or unavailability of their medical records. In 9 patients, the initial renal replacement therapy was changed after several days of therapy. Of these, 5 patients started on CVVH therapy were changed to either EDD or intermittent hemodialysis. The reasons for the change of modality were recurrent clotting, technical difficulty, or improved clinical status of the patient. Of the 4 patients who discontinued EDD therapy, all were changed to intermittent hemodialysis because of improved clinical status. For these 9 patients, mortality rates were examined on an intention-to-treat basis; thus, only data from the initial method of treatment were considered. Type of treatment, effective duration of treatment, volume of ultrafiltrate and replacement fluid, daily dose of heparin, episodes of dialyzer clotting, number and type of pressor support, and number of episodes of hypotension were recorded for each treatment day. The Acute Physiology and Chronic Health Evaluation (APACHE) II11 scores were obtained at the time of admission to the ICU. For both types

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of treatment, replacement fluid was defined as all fluid administered through the dialyzer during treatment. For CVVH, net UF was defined as the difference between volume of effluent and standard replacement fluid in milliliters per day. For EDD, net UF was defined as the difference between volume of ultrafiltrate and all fluid infused into the dialyzer in milliliters per day. A single episode of hypotension was defined as an acute decrease in systolic blood pressure to less than 90 mm Hg. Most patients with hypotension had an absolute mean arterial pressure (MAP) less than 60 mm Hg. A given MAP was defined as the sum of two thirds of the diastolic blood pressure and one third of the systolic blood pressure. Although blood pressures were measured frequently during treatment, only MAPs obtained just before the initiation of treatment (pre-MAP), midway through treatment (midMAP), and at the end of treatment (end-MAP) were used for analysis. When available, daily weights were obtained, as well as net 24-hour fluid balance.

EDD EDD was performed using a Fresenius 2008H delivery system (Fresenius USA Inc, Walnut Creek, CA) and a Toray model 2.0 dialyzer (Toray Industries Inc, Tokyo, Japan). Vascular access was obtained through dual-lumen central venous catheters (tunneled or nontunneled), regardless of treatment type. Patients underwent dialysis during daylight hours in the ICU for 6 to 8 hours using a blood flow rate of 200 mL/min and a dialysate flow rate of 300 mL/min. Dialysate potassium concentration initially varied but usually was adjusted to 4 mEq/L after 2 to 3 days. The final dialysate bicarbonate concentration was 30 to 35 mEq/L. Most patients required daily supplementation of phosphorus 3 to 4 days after the initiation of EDD to prevent hypophosphatemia. Heparin anticoagulation was initiated with a 1,000-U bolus of heparin followed by an infusion of 500 U/h and was titrated as needed to prevent clotting of the system. When heparin-free dialysis was performed, the dialyzer was flushed every 30 minutes with 150 to 200 mL of normal saline. A nephrology nurse, who monitored two patients undergoing EDD at a given time, set up the dialysis system. The nurse was able to monitor a given patient every 15 to 30 minutes depending on the needs of the patient. The ICU nurse monitored alarms and called the dialysis nurse if problems arose but otherwise had minimal involvement with the treatment. The ICU nurse-patient staffing ratio was dependent on patient acuity and was not affected by the use of EDD.

CVVH CVVH initiated before August 1998 was performed using a Baxter BM-11 blood pump (Baxter Healthcare Corp, Deerfield, IL). After this date, a Cobe Prisma integrated monitor (Gambro Healthcare, Lakewood, CO) with an AN69 filter (Hospal, France) was used. Blood flow rate was 170 mL/min. The effluent filtration rate was 1,000 to 2,000 mL/h; replacement fluid and net UF rates varied with the clinical status of the patient. If urea clearance was considered inadequate by the attending nephrologist (based on

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predialysis blood urea nitrogen levels), dialysis was added to the procedure at a dialysate flow rate of 1,000 mL/h (1.5% Dianeal; Baxter Healthcare Corp). Heparin anticoagulation was initiated with a 25-U/kg bolus followed by 10 U/kg/h continuously and adjusted as needed to achieve a partial thromboplastin time of 45 to 65 seconds. CVVH was set up by a nephrology nurse and then monitored continuously by an ICU nurse. The ICU nursepatient staffing ratio was 1:1 regardless of the acuity of the patient.

Total no. of treatment days Median duration of daily treatment (h) Median no. of treatments performed per patient

EDD

CVVH

367

113

7.5 (6-8)

19.5 (13.4-24)

9 (3-39)

6 (3-15)

NOTE. Ranges given for 25th and 75th percentile.

Statistics All data are reported as the median, with a range from 25th to 75th percentile, unless otherwise stated. Analysis of variance was performed using Mann-Whitney rank-sum test or Friedman repeated-measures analysis of variance on ranks. P less than 0.05 is considered significant.

RESULTS

Medical records of ICU patients with ARF were reviewed. Twenty-five patients were treated with EDD, whereas 17 patients underwent CVVH or CVVH-diafiltration (CVVH-DF). The primary diagnosis, cause of ARF, age, and sex are listed in Table 1. APACHE II scores were 20.1 ⫾ 7.9 for EDD patients and 17.7 ⫾ 7.3 for CVVH patients (P ⫽ 0.310; Table 1). Median MAP just before the initiation of therapy was 67 mm Hg (range, 65 to 75 mm Hg) for CVVH and 70 mm Hg (range, 60 to 83 mm Hg) for EDD (P ⫽ not significant). Treatment days totaled 480: 367 days for EDD Table 1.

Table 2. Total Number, Duration, and Median Number of Treatments Performed

Individual Patient Characteristics by Treatment Type EDD

No. of patients Average age (y) Men Women Average APACHE II Primary diagnosis Medical/sepsis Surgical/pancreatitis Trauma/burn Hepatic failure Cause of ARF ATN Multifactorial Acute GN Hepatorenal

25 50.8 ⫾ 15.6 15 10 20.1 ⫾ 7.9

CVVH

17 48.9 ⫾ 20.2 12 5 17.7 ⫾ 7.3

12 5 5 3

9 3 3 2

9 14 1 1

9 7 1 0

and 113 days for CVVH. The duration of treatment per day was significantly different, with a median of 7.5 h/d (range, 6 to 8 h/d) for EDD and 19.5 h/d for CVVH (range, 13.4 to 24 h/d; P ⬍ 0.001). The percentage of prescribed treatment time delivered was 93.7% for EDD and 81.3% for CVVH. The total number of treatment days ranged from 3 to 15 days for CVVH, with a median of 6 days, and 3 to 39 days for EDD, with a median of 9 days (Table 2). MAP was 70 mm Hg pretreatment (range, 62 to 84 mm Hg, 25th and 75th percentiles), 70 mm Hg midtreatment (range, 63 to 80 mm Hg), and 71 mm Hg at the end of treatment (range, 63 to 83 mm Hg) in patients treated with EDD (Table 3; P ⫽ 0.12). MAP for CVVH at similar points were 67 mm Hg (range, 62 to 77 mm Hg), 68 mm Hg (range, 61 to 77 mm Hg), and 69 mm Hg (range, 61 to 78 mm Hg; P ⫽ 0.80). When MAPs were compared between the two treatment modalities, they did not differ significantly (Fig 1). Episodes of hypotension totaled 358 during EDD treatments versus 165 during CVVH. Inotropes or vasoconstrictors were used during 79 CVVH treatments (69.9%) compared with 220 EDD treatments (59.9%; Fig 2). Adequate UF was achieved with either treatTable 3. Median MAP Just Before Initiation of Treatment, Midway Through Treatment, and Just Before Treatment Was Terminated CVVH

Abbreviations: ATN, acute tubular necrosis; GN, glomerulonephritis.

Pre-MAP (mm Hg) 67 (61.8-77.3) Mid-MAP (mm Hg) 68 (61-77) End-MAP (mm Hg) 69 (60.8-78)

EDD

70 (62-83.8) 70 (63-80) 71 (63-83)

NOTE. Ranges given for 25th and 75th percentile. Abbreviation: NS, not significant.

P

NS NS NS

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Fig 1. Comparison of MAP during (■) EDD versus ( ) CVVH.

ment modality, with a net UF volume of 3,000 mL/d during EDD (range, 1,763 to 4,445 mL/d, 25th and 75th percentiles) and 3,028 mL/d (range, 1,785 to 4,707 mL/d) during CVVH (P ⫽ 0.514). The volume of replacement fluid administered during treatment was 500 mL/d for EDD (range, 300 to 800 mL/d) and 16,637 mL/d for CVVH (range, 11,301 to 20,433 mL/d; P ⬍ 0.001; Fig 3). Patients treated with EDD required significantly less heparin (4,000 U/d; range, 0 to 5,800 U/d) than those treated with CVVH (21,100 U/d; range, 8,825 to 31,275 U/d; P ⬍ 0.001). The average amount of heparin used per treatment hour was 657 U/h for EDD versus 1,252 U/h for CVVH. Heparin was not prescribed on 117 EDD treatment days (31.9%), whereas it was omitted on only 3 CVVH treatment days (2.7%). Forty-

one episodes of clotting occurred during EDD when heparin was omitted (35%). Overall, the EDD system clotted 84 times during 367 days of treatment (22.9%), whereas the CVVH system clotted 31 times during 113 days of treatment (27.4%). Excluding all heparin-free days of treatment, the percentage of clotting was 17.2% for EDD and 27.3% for CVVH. Of the patients treated with EDD, 21 of 25 patients died, whereas 11 of 17 patients treated with CVVH died (during their hospitalization). DISCUSSION

Overall, EDD was tolerated well by critically ill patients and appeared to offer many of the same benefits provided by CVVH while avoiding many of its drawbacks. EDD was widely accepted by the ICU and dialysis nursing staff

Fig 2. Percentage of treatment days requiring inotropic support. (■) EDD; ( ) CVVH.

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Fig 3. Median volume of (■) fluid replaced during treatment and ( ) net UF.

because of the technical familiarity and relative ease of the technique. The initiation of EDD required no advance preparation other than scheduling and notifying a dialysis nurse. Procedures or studies that required moving the patient to another location were scheduled to not interrupt daily dialysis. MAPs were similar and well maintained regardless of treatment modality. Although mean pressures were slightly greater for patients treated with EDD, this difference was small and not statistically significant (Table 3). Hypotension requiring an intervention was common during both treatment modalities. A single inotropic agent was required during 39.2% of EDD treatments and 47.8% of CVVH treatments (Fig 2). One of the main goals of continuous renal replacement therapy in the critically ill (and often anuric) patient is to provide adequate control of extracellular volume while maintaining hemodynamic stability. Significant UF was possible using EDD, with a median UF of 3,000 mL/treatment (Fig 3). This did not necessarily mean that the patient achieved overall negative fluid balance, but it allowed for the replacement of vital fluids, including total parenteral nutrition, blood products, and various intravenous infusions. When CVVH was used, the large filtrate volumes (often ⬎24 L/d) also allowed the replacement of vital fluids. A direct comparison of the net volume removed by either modality is difficult given that the main method of solute clearance is diffusion for EDD and convection for CVVH, but the liberal amount of ultrafiltrate achieved using EDD permitted the infusion of necessary fluids, even in the anuric patient. Fur-

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thermore, the median daily volume of all fluids replaced during hemofiltration (other than the standard replacement solution) did not differ significantly from the median daily UF volume achieved with EDD. For patients with a severe bleeding diathesis, EDD may offer an advantage over CVVH. Patients treated with EDD required significantly less heparin than those treated with CVVH (median, 4,000 versus 21,100 U/d). Furthermore, EDD was performed without the use of heparin in 31.9% of all cases, whereas only three cases of CVVH could be performed without heparin. The increased incidence of dialyzer clotting during EDD probably resulted from attempts to minimize heparin-induced bleeding in patients who were not excluded from this modality by virtue of a bleeding tendency. Once EDD was initiated, it was performed daily and continued for many days longer than CVVH. The median duration of a single EDD treatment was 7.5 hours, which allowed ample time during the remainder of the day for procedures requiring patient mobility. The total number of treatments performed per patient ranged from 3 to 39 for EDD and 3 to 15 treatment days for CVVH. This could imply that patients who underwent CVVH were more severely ill and experienced earlier mortality than those who underwent EDD, but our data do not support this theory. It could also imply earlier recovery of renal function in patients treated with CVVH; however, only a single patient discontinued CVVH because of recovery of renal function. However, we noted that 5 of 17 patients who initially underwent CVVH were later changed to another renal replacement therapy (either EDD or intermittent hemodialysis). A change in modality reflected either a response to technical difficulties with the procedure (primarily recurrent clotting of the system) or improved hemodynamic stability of the patient. If the system was running without difficulties, it was usually not halted for a change of modality. Although continuous therapies may be superior to EDD for the removal of septic mediators, this potential benefit remains controversial.12-14 Although continuous renal replacement therapy performed with polyacrylonitrile membranes could theoretically remove inflammatory media-

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Fig 4. Daily pretreatment blood urea nitrogen levels for (■) a single patient treated with EDD and (}) a single patient treated with CVVH. The patient treated with CVVH eventually was placed on EDD therapy because of recurrent clotting and a very high heparin requirement and later recovered renal function. For the patient treated strictly with EDD, treatment continued for several more days until she died.

tors if the membrane were changed frequently, clinical studies have not consistently confirmed this.15 Furthermore, extracorporeal clearance of septic mediators may be inconsequential compared with their endogenous production. Although it is beyond the scope of this report to provide a full comparison of solute clearance between the two treatment modalities, good control of pretreatment blood urea nitrogen and

serum bicarbonate levels was achieved when EDD was used (Figs 4 and 5). Normalization of other serum electrolyte levels was also achieved, although serum phosphorus usually required supplementation 3 to 4 days after the initiation of EDD. In summary, EDD appears to be a promising technique for the treatment of critically ill patients with ARF. It offers several advantages over

Fig 5. Daily pretreatment serum bicarbonate levels for (■) a single patient treated with EDD and (}) a single patient treated with CVVH. (Same patients as in Fig 4.)

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CVVH, including less cumbersome technique, patient mobility, and decreased requirements for anticoagulation, while providing similar hemodynamic stability and volume control. A randomized, prospective trial comparing the two treatment modalities in a larger cohort of patients is necessary to determine the relative impact of EDD on mortality. REFERENCES 1. Kramer P, Wigger W, Riegler J, Matthaei D, Scheler F: Arteriovenous haemofiltration: A new and simple method for treatment of over-hydrated patients resistant to diuretic. Klin Wochenschr 55:1121-1122, 1977 2. Bischoff K, Doehn M: Kontinuerliche pumpen-getriebene Ultrafiltration bei Nierenversagen, in Kramer P (ed): Arterio-venose Hamofiltration-Nieren-(Ersatz) Therapie im Inttensivepflegebereich. Gottingen, Germany, Vandenhoeck & Ruprecht, 1982, pp 227-232 3. van Bommel EF, Bouvy ND, So KL, Zietse R, Vincent HH, Bruining HA, Weimar W: Acute dialytic support for the critically ill: Intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol 15:192-200, 1995 4. Kierdorf H, Sieberth HG: Continuous treatment modalities in acute renal failure. Nephrol Dial Transplant 10:20012008, 1995 5. Spiegel DM, Ullion ME, Zerbe GO, Berl T: Determinants of survival and recovery in acute renal failure patients dialyzed in intensive care units. Am J Nephrol 11:44-47, 1991 6. Cioffi WG, Ashikaga T, Gamelli R: Probability of

surviving postoperative acute renal failure. Ann Surg 200: 205-211, 1984 7. Routh GS, Briggs JD, Mone JG, Ledingham IM: Survival from acute renal failure with and without multiple organ dysfunction. Postgrad Med J 56:244-247, 1980 8. Schiffl H, Lang S, Konig A, Held A: Dose on intermittent hemodialysis and outcome of acute renal failure: A prospective randomized study. J Am Soc Nephrol 8:290A, 1997 (abstr) 9. Pierratos A: Daily hemodialysis: Why the renewed interest? Am J Kidney Dis 6:S76-S82, 1998 (suppl 4) 10. Pierratos A, Ouwendyk M, Francoeur R, Vas S, Raj DS, Ecclestone AM, Langos U, Uldall R: Nocturnal hemodialysis: Three year experience. J Am Soc Nephrol 95:859868, 1998 11. Knaus WA, Draper EA, Wagner DP, Zimmerman FE: Apache II: A severity of disease classification system. Crit Care Med 13:818-829, 1985 12. Barrera P, Janssen EM, Demacker PN, Wetzels JF, van der Meer JW: Removal of interleukin-1␤ and tumor necrosis factor from human plasma by in vitro dialysis with polyacrylonitrile membranes. Lymphokine Cytokine Res 11:99-104, 1992 13. Goldfarb S, Golper TA: Proinflammatory cytokines and hemofiltration membranes. J Am Soc Nephrol 5:228232, 1994 14. Hakim RM: Clinical implications of hemodialysis membrane biocompatibility. Kidney Int 44:484-494, 1993 15. Bellomo R, Tipping P, Boyce N: Continuous venovenous hemofiltration with dialysis removes cytokines from the circulation of septic patients. Crit Care Med 21:522-526, 1993