Continuous Arteriovenous Hemofiltration

Renal

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Continuous Arteriovenous Hemofiltration

N. Stanley Nahman, Jr, MD, * and Donald F. MiddendorJ, MD*

Continuous arteriovenous hemofiltration (CA VH) is an extracorporeal method of removing plasma water and solutes via hemofiltration. First described in 1977 by Kramer,23 this simple method of volume control and blood purification has been used on hundreds of patients of all ages for a variety of clinical indications. The understanding and refinement of the technique have spawned the development of continuous bedside hemodialysis, a modality that will see increasing applications in the future. The purpose of this report is to review the general technical aspects of CAVH, clinical applications, including the effects of CA VH on therapeutic drug levels, and future directions, with specific emphasis on continuous arteriovenous hemodialysis (CA VHD).

TECHNICAL CONSIDERATIONS General Principles CAVB is a bedside modality, generally utilized in the intensive care unit (ICV). It does not require specialty-trained personnel such as dialysis nurses or technicians. Once access is established, CA VB can be performed by ICV nursing staff. CA VH works through the use of a highly permeable membrane, which generates an ultrafiltrate that consists of plasma water and unbound solutes *Assistant Professor of Medicine, Renal Division, Department ofInternal Medicine, The Ohio State University Hospitals, Columbus, Ohio Supported in part by KIH Grant DK3948.5.

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of molecular weight less than 50,000 daltons. 41 Water movement across the membrane (ultrafiltration) is proportional to the hydrostatic and osmotic pressure differences (the sum of which equals transmembrane pressure). The ultrafiltration rate may be expressed as follows: Qf

= K

X

TMP

where Qf is the rate of production of ultrafiltrate (mllmin), K is the coefficient of membrane permeability, and TMP is transmembrane pressure. 37 Because K is an intrinsic property of the filter, TMP is the major variable that can be controlled clinically to influence the ultrafiltration rate. 16,26 Transmembrane pressure is dependent upon the arteriovenous pressure difference; hence, the procedure does not require external pumping devices. In addition, when confounding factors are not present (such as the application of negative pressure to the ultrafiltrate space), the system will tend to "autoregulate" itself, i.e., when ultrafiltrate production results in volume depletion and a fall in blood pressure, the arteriovenous pressure differences will drop, resulting in a decrease in TMP and a decline in ultrafiltrate production. 16 The filtration devices are plastic filters that contain highly permeable hollow fibers or plates and are surrounded by an ultrafiltrate space. The filters are composed of various polymers and require minimal blood volume for operation. 32, 38, 39, 45, 46 There are arterial and venous blood ports and a port to drain the ultrafiltrate (Fig. lA). In the case of CAVHD, there is a second ultrafiltrate port to facilitate the circulation of dialysate (Fig. IB). Vascular Access Vascular access may be attained via a previously established internal shunt (as used for hemodialysis), externally placed access such as a Scribner shunt, or after cannulation of the femoral or radial vessels. \Vhen internal or external shunts are not available, some authors have expressed a preference for using the femoral approach. 16, 20 Advantages to femoral access include rapid institution and large vessel size, which allows for placement of large-bore lines that will facilitate blood movement through the filter via a low-resistance pathway. 16 Vascular access in young children and infants represents a unique problem. Under these circumstances, arterial cannulation of umbilical, radial, brachial, or femoral vessels and venous return via umbilical, internal jugular, or femoral veins provide acceptable blood flow. 27, 28,37, 46 Given the smaller size of the cannulas and the lower blood flows in the pediatric setting, variability in catheter size may have significant impact on the function of the filter. 12 Anticoagulation Anticoagulation, usually with heparin, is necessary to prevent blood from clotting and occluding the filter. Heparin is first introduced into the system when the filter is prepared for clinical use. Most manufacturers

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Vascular Access

Replacement Fluid

A

Vascular Access

Replacement Fluid

Dialysate

-

-

- -

L-r-r-----T'"'""T...J

Ultrafiltrate

8 Figure 1. Schematic representation of (A) continuous arteriovenous hemofiltration (CAVH) and (B) continuous arteriovenous hemodialysis (CAVHD).

recommend flushing the filter with 1 to 2 L of saline containing 5000 IV of heparin per !iter. Anticoagulation via a constant heparin infusion is needed to preserve filter patency. s. Ifi. 20 Recommendations concerning the need for and amount of a heparin loading dose vary, and range from no loading dose to 2,000 IV or 10,000 IV of heparin. 16.23.26 The dose of the heparin infusion is generally 10 IV/kg/hr and is administered through the arterial arm of the system (see Fig. 1).16 This dose of heparin mayor may not alter the partial thromboplastin time. 11. 16. 23. 26 Parameters used to titrate the dose of heparin include blood flow through the filter or the partial thromboplastin time, with target times ranging from control values, up to 30 seconds above control or 1.5 times control. 11. 26. 34. 41 To prevent filter clotting without systemic anticoagulation, Kaplan 18 has reported a protocol for regional heparinization. In brief, heparin is infused directly into the filter via the arterial arm of the system, providing

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high local concentrations of heparin. To prevent systemic anticoagulation, protamine sulf~lte is infllsed through the venous side of thc system, eflectively reversing the anticoagulant effects of heparin before it reaches the systemic circulation. 18 Selection and Administration of Replacement Fluids The selection of replacement fluids is dictated by the clinical condition of the patient. Replacement fluids may include standard mixtures such as lactated Ringer's solution, saline with the addition of other buffers or electrolytes, or total parenteral nutrition (TPN) solution. 1,8, ll, 16.26,31 The indications for replacement fluid are hemodynamic and metabolic. Because CAVIl may result in ultrafiltrate production of up to 10 mllmin, hypotension may occur (despite the "autoregulatory" nature of the system), especially in systems that employ negative-pressure devices to enhance ultrafiltrate production or prolong filter life. 22 For this reason, replacement fluid must be administered. Some authors have suggested clamping the ultrafiltrate line to control the production of ultrafiltrate, whereas others recommend increasing replacement fluids, a philosophy with which we concur. 3,34.41 The metabolic disturbances for which specific replacement fluids may be indicated include severe electrolyte disorders, intractable acidosis, and nutritional support. L ~, ll. 16. 26 Replacement fluids may be administered via the arterial arm of the system (proximal to the filter or "predilution") or via the venous ann of the system (distal to the filter or "postdilution"). When compared to postdilution, the advantages of predilution include an increase in urea clearance, more flexibility with suction assistance, and a potential increase in filter life. 13-15 The disadvantages of predilution include increased cost and need of replacement fluids (10 to 30% increase in total volume) and a loss of reliability of ultrafiltrate chemistries in reflecting true plasma-solute losses.13 Total parenteral nutrition solutions are generally administered in a postdilution mode or via a separate venous line. ll Enhanced U1trafiltrate Production with Suction The application of negative pressure to the ultrafiltrate space will promote the movement of ultrafiltrate from the blood space into the ultrafiltrate space.]' 17 The advantages of applying negative pressure to the ultrafiltrate space include enhanced ultrafiltrate production, despite low blood flows and a prolongation of effective filter life. 15, 17 The combination of predilution and suction assistance may result in a marked increase in the efficiency of urea clearance. 13 The major disadvantage of applying suction to the ultrafiltrate space is the loss of "autoregulation," as suggested previously.:] 17 Because suction may increase the risk of volume depletion and hypotension, care must be taken to assess and replace volume losses on a timely basis. INDICATIONS AND ADVANTAGES OF CAVH Indications In the broadest sense, CA VH is indicated for the oliguric patient with hemodynamic instability or severe volume overload. This statement is

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strengthened if eontraindieations to hemodialysis (i. e., hemodynamie instability) and peritoneal dialysis (i. e., abdominal wounds or urgent needs to remove fluid) are also present. S Some of the clinical conditions for which CA VII has been employed are summarized in Table l. Advantages In the appropriate clinical setting, CA VH is suggested to oiler certain specific advantages. When compared to hemodialysis, CA VB allows for less hemodynamic instability, gradual changes in osmolality, no complement activation or leukopenia, and a decreased need for specialized personnel. 8, 21,26,30 Despite these apparent advantages, Kohen et apo demonstrated more complications with CAVII per liter of urea cleared than with intermittent hemodialysis. Continuous arteriovenous hemofiltration is preferred in lieu of peritoneal dialysis when abdominal wounds prohibit its use or for the preservation of abdominal epidermis in anticipation of skin grafting after severe burns. 8, 11

CONTRAINDICATIONS TO CAVH There are no reported absolute contraindications to CA VH. Intuitively, one knows that CA VB should not be used if conventional forms of dialysis can be performed and offer the same results. A relative contraindication to CA VB is active bleeding or the presence of a coagulopathy.8, 16 However, several reports document the use of CAVH (with decreased or no heparin) in patients with eoagulopathy or bleeding. 16, 30

COMPLICATIONS AND PROBLEMS ASSOCIATED WITH CAVH Vascular Access Problems Access problems consisting of arterial or venous thrombosis and local or retroperitoneal bleeding occurred in 16% of over 150 patients studied. 21 These complications were reduced dramatically when heparin dose and catheter type were standardized. 21 Other reported problems include the Table 1. Clinical Uses of CA VH CLl'JICAL EVENTS

Postoperative complications Severe burns Septicemia Pulmonary edema with pericarditis Hyponatremia Severe volume overload Hepatic encephalopathy Hepatorenal syndrome As an aid to parenteral nutrition Criticallv ill children and infants

REFERENCES

1, 3, 6, 11, 16 26, .'33, 16 25 16, 23, 2 18 11, 31 27, 28,

16, 18, 26, 30, 33, 41, 44 34, 41, 44 26

45, 46, 47

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potcntial for infection and arterial thrombosis requiring surgical revision. 16. 47 Potential problems include the usual complications associated with arterial and venous cannulation. 5 Hemofilter Rupture and Tube-Connector Leaks Filter rupture, with blood leakage into the environment or from a communication between the blood and ultrafiltrate space (gross bleeding as opposed to positive hemoglobin by dipstick10) is the major reported problem intrinsic to the filter. :3, 16, 30 This is an uncommon occurrence, however. 3,8 Blood leaks from inadvertent tubing disconnections occur and may result in significant hemorrhage, 16,30 Agitated patients, multiple indwelling lines, monitor wires, and ventilator tubing complicate routine nursing care and may contribute to the risk of inadvertent separation of tubing connections. Securing all connections with tape or glue is recommended. 16, 30, 43 Hemorrhage Hemorrhagic complications may result from anticoagulation or an intrinsic coagulopathy. Ifi, 3(), 33 Hemorrhage may be of sufficient severity to require interruption of therapy, although in one series, some bleeding occurred in all patients but was controllable and never led to the discontinuation of CA VH. 27 :30, 33 Filter Clotting Filter clotting may result in up to 32% of filter failures and may occur secondary to low blood flow, inadequate heparinization, or progressive hemoconcentration as blood moves distally through the filter. 3,8 Blood flow may be optimized by the use of large-bore, low-resistance lines. 16 The problems of inadequate heparinization and hemoconcentration may be minimized by the use of regional heparinization and predilution. I :3 Infection Infection and bacteremia are uncommon, but they remain potential risks of long-term in-dwelling vascular lines. 16 Hemodynamic Instability Hemodynamic instability may occur secondary to hemorrhage, excessive ultrafiltrate removal, or tachydysrhythmias, or with recurrent septic events related to the primary disease. 11,20,30 The cause-and-effect relationship between CAVII and hemorrhage or excessive ultrafiltrate removal is usually evident clinically. When CAVH was compared to intermittent hemodialysis, tachydysrhythmias were demonstrated to occur with both modalities. 20 Such a direct relationship between CA VH and both cardiac rhythm disturbances and septic events is less easily demonstrated in a critically ill patient. Fluid and Electrolyte Disturbances Early in the experience with CA VII, hyperkalemia was reported to occur. 23 \Vith careful patient monitoring and appropriate replacement fluids, reportable electrolyte disturbances are less common. It has been recom-

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mended that if replacement fluid volumes exceed 10 Llday, a particulate debris filter should be placed in the replacement fluid line. 8 Therapeutic Drug Removal The removal of therapeutic drugs by hemofiltration, which necessitates dosage changes, has been recognized and is addressed in the following section.

DRUG PHARMACOKINETICS AND CAVH Parameters Affecting Drug Removal by CAVH Inulin has a molecular weight of 5200 and is filtered freely by CA VH. 10 Likewise, the unbound fraction of drugs with a molecular weight of 5200 or less would be expected to be removed during CA VH therapy.8 Other properties of drugs that may influence their removal by CAVH include hydration radius and molecular charge. 24 Properties of the membrane that may influence drug removal include pore size, membrane charge, length and width of fibers, and the surface area of the filter. 24 Drug Removal and CAVH Aminoglycoside antibiotics, N -acetylprocainamide (a metabolite of procainamide), and cefuroxime are cleared by CAVH.4, 19,42,44 For therapeutic drugs, frequent monitoring of serum levels with appropriate dose adjustment is necessary. 19, 44 The ratio of ultrafiltrate drug level to arterial plasma-water drug level (sieving coefficient) gives an indication of the extent of drug removal by CA VH. 8-10,24 Several lists of drugs and their respective sieving coefficients have been published recently and may serve as a guide to dosing decisions. 8 -1O

CURRENT TRENDS IN BEDSIDE DIALYSIS Because ultrafiltration by CAVH depends solely on TMP and not movement of solutes down an osmotic gradient, large volumes of ultrafiltrate must be produced to generate an acceptable urea clearance. The use of predilution or newer, highly permeable filters may enhance urea clearance, but the production of large volumes of ultrafiltrate may still be necessary to attain acceptable urea clearances. 15, :37, 39 The circulation of dialysate through the ultrafiltrate space (CAVHD), which allows for the transfer of solutes down a concentration gradient, represents another step in the management of the critically ill patient with clinical indications for dialysis. (i,]S, 40 (i

Technical Aspects of CAVHD The major difference between CA VH and CAVHD is the presence of a second ultrafiltrate port to facilitate the circulation of dialysate through

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the ultrafiltrate spacc (see Fig. IB). CAVBD has been performed using conventional hemodialysis filters, modified CA VB filters, and filters specifically designed fell' CA VB D.3 33. 36. 40 Peritoneal dialysate solution (1. 5%) or other dialysate solutions are pumped through the circuit at rates up to 33 ml/min. 29 . 33. 40 The issues relevant to vascular access, anticoagulation, the use of replacement fluids, and predicted complications are the same as for CAVH.J5 Indications for CAVHD The indications for CA VBD parallel those for CAVB, but also include the treatment of acute renal failure, which necessitates dialysis. 5 Clearance of urea is improved with CA VH D, 7. 29 and rates of ultrafiltration production (up to 1000 mllhr) may be comparable to CAVH; thus, the ability to control volume with CA VHD is maintained. 3.5 Clinical Results of CAVHD Several studies have demonstrated CA VHD to offer all of the advantages of CA VH, with the addition of improved urea clearance. 7, 3.3. 40 These data would suggest that CAVHD will likely replace CAVH as the treatment of choice in hemodynamically unstable patients with a clinical indication for dialysis.

SUMMARY CA VH is a bedside form of dialysis that is used in the treatment of fluid and electrolyte disorders seen in critically ill patients. The major advantages of the procedure include (1) gradual, continuous therapy, which is ideal in hemodynamically unstable patients; (2) control of fluid balance; and (3) ease of administration in the lCD. The major disadvantages of CAVIl include (1) a rcquirement for arterial access, (2) the need for anticoagulation, (3) the risks of infection from long-term indwelling vascular lines, and (4) the potential for Significant volume depletion. The effectiveness of CA VB may continue to improve owing to technical developments in filter composition and the application of clinical tactics such as suctionassisted filtration, predilution fluid replacement, or regional heparinization. The next step in bedside dialysis is represented by CAVHD, which offers all of the advantages of CAVH as well as improved urea clearance.

REFERENCES I. Bartlett HH, J\lault JR, Dechert RE, et al: Continuous arteriovenous hemofiltration: Improved survival in surgical acute renal failure? Surgery 100:400-408, 1986 2. Davenport A, \Vill El, Losowsky "IS: Continuous arteriovenous haemofiltration in patients with hepatic encephalopathy and renal failure. Br Med J 295:1028, 1987 3. Domoto DT: Two years clinical experience with continuous arteriovenous hemofiltration in acute renal failure. Trans Am Soc Artif Intern Organs 31:581-585, 198.5 4. Domoto DT, Brown \V\V, Bruggensmith P: Removal of toxic levels of N·acetylprocain·

CO"lTINl10US AHTEHlOVEI'OUS I-IE]\IOFILTHATIO"i

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10. 11. 12. 13. 14. 1.5.

16. 17. 18. 19. 20. 21.

22. 23. 24. 25. 26. 27. 28. 29. 30.

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amide with continuous arteriovenous hemofiltration or coutinllous arteriovenous hemodiafiltration. Ann Intern Med 106:550-552, 1987 Geronemus RP: Slow continuous hemodialysis. Trans Am SOl' Artif Intern Organs 34:5960, 1988 Geronemus R, Schneider N: Continuous arteriovenous hemodialvsis: A new modality for treatment of acute renal failure. Trans Am Soc Artif Intern Organs 30:610-613, 1984 Gibnev RTN, Stollerv DE, Lefebvre RE, et al: Continuolls arteriovenous hemodialvsis: an ~lternative the~apy for acute renal failure associated with critical illness. C~lAJ 139:861-866, 1988 Golper TA: Continuous arteriovenous hemofiltration in acute renal failure. Am J Kidney Dis 6:373-386, 1985 Golper TA, Bennett WM: Drug removal by continuous arteriovenous haemofiltration: A review of the evidence in poisoned patients. ,'.led Toxicol 3:341-349, 1988 Golper TA, \Vedel SK, Kaplan AA, et al: Drug removal during continuous arteriovenous hemofiltration: Theory and clinical observations. Int J Artif Organs 8:,307-312, 1985 Hubsher J, Olshan AI{, Schwartz AB, et al: Continuous arteriovenous hemofiltration ft)r the treatment of anasarca and acute renal bilure in severely burned patients. Trans Am Soc Artif Intern Organs 32:401-404, 1986 Jenkins RD, Kuhn RI. Funk JE: Clinical implications of catheter variability on neonatal continuous arteriovenous hemofiltration. Trans Am Soc Artif Intern Organs 34: 108Ill, 1988 Kaplan AA: Clinical trials with predilution and vacuum suction: enhancing the efficiencv of the CAVH treatment. Trans Am Soc Artif Intern Organs 32:49-51, 1986 Kaplan AA: Enhanced efficiency during continuous arterio-venous hemofiltration: The use of predilution. Int J Artif Organs 9:139-142, 1986 Kaplan AA: Predilution versus postdilution for continuous arteriovenous hemofiltration. Trans Am Soc Artif Organs 31:28-:32, 1985 Kaplan AA, Longnecker HE, Folkert V\V: Continnous arteriovenous hemofiltration. Ann Intern Med 100:358-367, 1984 Kaplan AA, Longnecker HE, Folkert V\V: Suction-assisted continuous arteriovenous hemofiltration. TrallS Am SOl' Artif Organs 29:408-413, 1983 Kaplan AA, Petrillo H: Hegional heparinization for continuous arteriovenous hemofiltration (CAVH). Trans Am SOl' Artif Intern Organs 33:312-315, 1987 Kennedy DJ, Greenberg RN, Miller LW: Continuous hemofiltration. Ann Intern Med 101:145-146, 1984 Kohen JA, Whitley KY, Kjellstrand CM: CAVH vs hemodialysis in acute renal bilnre. Trans Am Artif Intern Organs 31:169-175, 1985 Kramer P, Bohler J, Kehr A, et al: Intensive care potential of continuous arteriovenous hemofiltration. Trans Am Soc Artif Intern Organs 28:28-32, 1982 Kramer P, Seegers A, De Vivie H, et al: Therapeutic potential of hemofiItration. Clin Nephrol 11:145-149, 1979 Kramer P, \Vigger \V, Rieger J, et al: Arteriovenous haemofiltration: A new and simple method for treatment of over-hydrated patients resistant to diuretics. Klin \Vochcnschr 55:1121-1122, 1977 Kronfol NO, Lau All, Colon-Hivera J, et al: Effect of CAVH membrane types on drugsieving coefficient and c1earanccs. Trans Am Soc Artif Organs 32:85-87, 1986 Lamer AI. Vickers CH, Adu D, et al: Correction of severe hyponatraemia by continuous arteriovenous haemofiItration before liver transplantation. Br Med J 297:1514-1515, 1988 Lauer A, Saccaggi A, Ronco C, et al: Continuous arteriovenous hemofiItration in the critically ill patient: Clinical use and operational charactcristics. Ann Intern Med 99:455-460, 1983 Leone MH, Jenkins RD, Golper TA, et al: Early experience with continuous arteriovenous hemofiltration in critically ill pediatric patients. Crit Care Med 14:1058-1063, 1986 Lieberman KV, Nardi L, Bosch JP: Treatment of acnte renal failure in an infant using continuous arteriovenous hemofiltration. J Pediatr 106:646-648, 1985 Maher ER, Hart L, Levy D, et al: Comparison of continuous arteriovenous haemofiltration and haemodialysis in acute renal failure. Lancet 1: 129, 1988 Mault JR, Dechert RE, Lees P, et al: Continuous arteriovenous filtration: An effective treatment for surgical acutc renal failure. Surgery 101:478-484, 1987

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31. Mault JR, Kresowik TF, Dechert HE, et al: Continuous arteriovenous hemofiltration: The answer to starvation in acute renal failure? Trans Am Soc Artif Intern Organs 30:203206, 1984 3 0 Mineshima M, Yamagata K, Era K, et al: Kinetic comparison ofhemofilters for continuous arteriovenous hem~filtration (CAVH). Trans Am Soc Artif Intern Organs 31:660-663, 1985 33. Olbricht C, Mueller C, Schurek HJ, et al: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am Soc Artif Intern Organs 28:33-37, 1982 34. Ossenkoppele CJ, Van Der Meulen J, Bronsveld W, et al: Continuous arteriovenous hemofiltration as an adjunctive therapy for septic shock. Crit Care Med 13: 102-104, 1985 35. Pattison ME, Lee SM, Ogden DA: Continuous arteriovenous hemodiafiltration: An aggressive approach to the management of acute renal failure. Am J Kidney Dis 11:4347, 1988 36. Honco C, Bragantini L, Brendolan A, et al: Arteriovenous hemodiafiltration (AVHDF) combined with continuous arteriovenous hemofiltration (CAVH). Trans Am Soc Artif Intern Organs 31:349-353, 1985 37. Honco C, Brendolan A, Bragantini L, et al: Treatment of acute renal failure in newborns by continuous arterio-venous hemofiltration. Kidney Int 29:908-915, 1986 38. Ronco C, Brendolan A, Bragantini L, et al: Continuous arteriovenous hemofiltration with AN69S membrane: Procedures and experience. Kidney Int 33:S150-S153, 1988 39. Honco C, Brendolan A, Bragantini L, et al: Technical and clinical evaluation of a new polyamide hollow fiber hemofilter for CAVH. Int J Artif Organs 11:33-38, 1988 40. Stevens PE, Davies SP, Brown EA, et al: Continuous arteriovenous haemodialysis in critically ill patients. Lancet 2:150-152, 1988 41. Synhaivsky A, Kurtz SB, Wochos SN, et al: Acute renal failure treated by slow continuous ultrafiltration: Preliminary report. Mayo Clin Proc 58:729-733, 1983 42. Weiss LC, Danielson BC, Cralmen A, et al: Pharmacokinetics of intravenous cefuroxime during intermittent and continuous arteriovenous hemofiltration. Clin Nephrol 30:282286, 1988 43. Whiltaker AA, Brown CS, Crabenbauer KA, et al: Preventing complications in continuous arteriovenous hemofiltration. Dimens Crit Care Nurs 5:72-79, 1986 44. Zarowitz BJ, Anandan JV, Dumler F, et al: Continuous arteriovenous hemofiltration of aminoglycoside antibiotics in critically ill patients. J Clin Pharmacol 26:686-689, 1986 45. Zobel C: Continuous arteriovenous hemofiitration. Crit Care Med 15:893-894, 1987 46. Zobel C, Trop M, Beitzke A, et al: Vascular access for continuous arteriovenous hemofiitration in infants and young children. Artif Organs 12:16-19, 1988 47. Zobel C, Trop M, Ring E, et al: Continuous arteriovenous hemofiitration in critically ill children with acute renal failure. Crit Care Med 15:699-700, 1987

Address reprint requests to N. Stanley Nahman, Jr, MD Department of Internal Medicine The Ohio State University Hospitals N-21O Means Hall 1654 Upham Drive Columbus, OH 43210