- Email: [email protected]
DIALYSIS 101
ANESTHESIA AND RENAL CONSIDERATIONS
0889-8537/00 $15.00
+ .OO
DIALYSIS 101 Acute and Chronic Fluid Shifts Samuel A. Irefin, MD
The kidneys are major excretory organs and function in regulating acid/ base balance, electrolyte balance, and maintaining optimal body fluid composition. They also function in eliminating products of metabolism. The inability of the kidneys to perform these functions result in biochemical disturbances, electrolyte abnormalities, and failure to regulate the body’s internal environment. Artificial kidney was first introduced during the Korean War as a choice of renal replacement therapyz9 Since that time, significant advances have been made in different dialysis methods, and renal dialysis have evolved to become the accepted therapeutic intervention for patients who have developed endstage renal disease as well as those patients with acute renal failure. As a renal replacement therapy, dialysis only approximates normal renal function. The developments that have been made in the field of renal dialysis have allowed the procedure to be performed with such techniques such as ultrafiltration, hemodialysis, hemofiltration, hemodiafiltration, and peritoneal dialysis. Choosing an effective renal replacement therapy depends on several conditions. The clinical condition that resulted in the renal failure will dictate the type of therapy chosen (Table l).24 In addition, technical support and personnel play a vital role in renal replacement therapy.
BASIC MECHANISMS OF DIALYSIS The word dialysis was derived from Greek language meaning to ”pass across.” All the mechanisms used in dialysis involve transport process of solutes and water.l0 The membranes that are used in renal replacement therapies consist of
From the Division of Anesthesiology and Critical Care Medicine, Department of General Anesthesia, The Cleveland Clinic Foundation, Cleveland, Ohio
ANESTHESIOLOGY CLINICS OF NORTH AMERICA
VOLUME 18 * NUMBER 4 * DECEMBER 2000
853
Diffusion-based processes using dialysate and semipermeable membrane
Convective-based process using plasma water exchange methods across semipermeable membrane
Combining diffusion and convection (10-L exchanges) for both small and middle molecular loss
Dialysis
Hemofiltration
Hemodiafiltration
Use
Fluid overload High delivery in CRF (ARF) CHF Azotemia Acid I base disorders Electrolyte balance Volume control Azotemia Acid base Electrolyte Volume Cytokines ARF, MOF, CHF, ARDS Azotemia Volume Cytokines ARF, MOF, CHF, ARDS Sepsis
Access
AV WContinuous Intermittent
AV W Continuous Intermittent
AV Continuous W Continuous Intermittent AV Continuous W Continuous Intermittent
CAVHDF CWHDF IHDF
CAVH CWH IH
SCUF CW-UF IUF CAVHD CWHD IHD
Abbreviation
CRF = chronic renal failure, ARF = acute renal failure, CHF = congestive heart failure, AV = atrioventricular, VV = venovenous, MOF = multiorgan failure, ARDS = adult respiratory distress syndrome. (From Parrillo JE, Bone R C Critical Care Medicine. Principles of Diagnosis and Management. Mosby Year Book Inc., 1995, p 234, with permission.)
Definition
Plasma water removal Usually less than 5L/24 hr
Therapy
Ultrafiltration
Table 1. COMMONLY UTILIZED FORMS OF RENAL REPLACEMENT THERAPY
DIALYSIS 101
855
cellulose or synthetic varieties. The artificial synthetic membranes have higher ultrafiltration coefficients and solute permeability. They are employed mainly in those treatments that require a h g h convective component ( e g , hemofiltration). The artificial cellulose membrane possesses low ultrafiltration capacities; they are mainly employed in standard dialysis. The mechanisms that are used in solute and water transport across these membranes are shown in Figure LZ6 J = D T A (Crcldx) m
m
I
I
rn
[s]+ [sb = Sieving
u = (n R T ) I V m
w
m ,
i
..... .... .... ..... ....
g.....
~*.*.'.*.*
C
P
UF = Kf TMP
..... .... ..... Polarization Figure 1. Mechanisms of solute and water transport used for renal replacement therapy. A, Diffusion is directly proportional to diffusivity (D), temperature (T), membrane area (A), and concentration gradient (dc), and is inversely correlated with the membrane thickness (dx). B, Convection depends on ultrafiltration (UF) and membrane sieving capacity (s). C, Osmosis is mostly utilized in peritoneal dialysis. D, Ultrafiltration depends on transmembrane pressure (TMP), and membrane permeability coefficient (Kf). (From Pinksy MR, Dhainnaut J: Pathophysiologic Foundations of Critical Care. Baltimore, Williams and Wilkins, 1993, p 637; with permission.)
856
IREFIN
Removal of solutes by dialysis is achieved by convection, diffusion, osmosis, or a combination of these methods. Convection
Convective mechanism involves transportation of solutes across the membrane by the solvent. The solvent movement takes place in response to certain transmembrane pressure.ll The permeability of the membrane plays an important role in this process. Synthetic membranes retard the movement of proteins and cells but allow the passage of other solutes up to a given molecular size at the same concentration as in plasma water. Solute transport in convection depends on the amount of ultrafiltrate, the sieving capacity of the membrane, and the solute concentration in plasma water. This technique is used in ultrafiltration and hemofiltration. Diffusion
In diffusion-based techniques, solute removal is based on the movement of molecules in all directions, and molecules tend to achieve an equal concentration on both sides of the membrane. This technique is based on the principle of a solute gradient between the blood and the dialysate. The concentration gradient is the driving force for the solute, and the thickness and permeability of the membrane represents the major resistance. Osmosis
In this technique, water movement from the patient is proportional to osmotically active particles in the dialysate. Water moves from the area of high water concentration (i.e., plasma) to the area of low water concentration (i.e., the dialysate).This mechanism is utilized mostly in peritoneal dialysis techruque. Osmosis also requires a semipermeable membrane between the plasma and the dialysate; the peritoneal membrane performs t h s function. DIALYSIS THERAPY The Hemodialysis Procedure
Hemodialysis is a process of detoxification of uremic blood via dialysis of blood. Hemodialysis therapy requires an adequate vascular access, specially trained personnel to carry out the dialysis session, and the right equipment to perform the treatment. Hemodialysis technique entails the diffusion of solutes between the blood and a dialysis solution. Ths results in the removal of metabolic waste products and replenishment of body buffers. Blood is heparinized and pumped through a plastic dialyzer. The amount of heparin used varies from 600 to 800 iu/hr to guarantee a safe anticoagulation with minimal or no systemic effects.6 With hemodialysis, solutes are removed largely through diffusion down a concentration gradient and fluid removal through ultrafiltration using a hydrostatic pressure gradient. This results in the clearance of nitrogenous waste products in
DIALYSIS 101
857
form of blood urea nitrogen concentration. A 3- to 4-hour treatment session can result in 65% to 70% reduction in BUN. The urea clearance rate depends on the surface area of the dialyzer and the permeability of the membrane. Hemodialysis has become the most frequently employed treatment modality for end-stage renal disease. The access to the circulation for hemodialysis may be achieved by either percutaneous insertion of central venous catheters or by surgical creation of arteriovenous shunts. During hemodialysis, small molecular weight solutes are removed faster from the body than medium- to large-sized molecules. Hypotension, secondary to ultrafiltration-induced volume depletion, is the most common complication during hem~dialysis.~ Hypotensive episodes during hemodialysis can also result from arrhythmia, coronary ischemia, or pericardial effusion.I2These episodes can be treated with infusion of crystalloids, reducing rate of ultrafiltration or both. Hemofiltration
Hemofiltration technique employs a convective mode of fluid removal and requires a highly permeable membrane. There is no dialysate flow to the membrane. Rather, there is a removal of fluid across the membrane driven by transmembrane hydrostatic pressure differences. Treatment time depends on the rate of ultrafiltration and the total amount of fluid to be exchanged. Fluid lost its totally or partially replaced with a replacement fluid, and solute concentrations in plasma is lowered. The net weight loss by the patient depends on the difference between ultrafiltration and reinfusion. Different-sized molecules are removed from the body during hemofiltration.'8 Replacement fluid composition when hemofiltration is performed, dictates the resultant end point of therapy; knowing what fluid type is lost helps in choosing the appropriate replacement solution. Hemodiafiltration
Hemodiafiltration employs both diffusive and convective modes of therapy. The combination of small molecular weight substances removed by diffusion and middle molecular weight substances removed by hemofiltration lends superiority to hemodiafiltration technique. Highly permeable membranes are utilized. Hemodiafiltration is a highly complex techmque, and it is utilized mainly to remove substances that are believed to be involved in disease states such as sepsis and multiorgan fai1~re.I~ Recent studies have demonstrated that hemodiafiltration guarantees remarkable sodium and buffer balances and adequate treatment of metabolic acidosis.' Ultrafiltration
Ultrafiltration is the simplest form of dialysis therapy. The main goal of ultrafiltration is fluid removal and can be accomplished as an isolated therapy or in combination with other forms of blood cleaning techniques.21Fluid removed during ultrafiltration depends on the transmembrane pressure gradient and the hydraulic permeability coefficient of the membrane. As a result, syn-
858
IREFIN
thetic membranes are utilized during ultrafiltration therapy. The composition of fluid removed during ultrafiltration of blood has the characteristics of plasmafree water. Peritoneal Dialysis
The technique of peritoneal dialysis involves using the peritoneum as a dialysis and ultrafiltration membrane. Peritoneal dialysis involves infusion of sterile pyrogen-free solution into the peritoneal cavity. The solution is then drained in cycles. Solute removal during peritoneal dialysis results from a combination of diffusive and convective transport as a result of a concentration gradient between blood flowing in the peritoneal capillary network and the dialysate.*O The primary mechanism for small solute removal is diffusion. The peritoneal membrane is highly permeable to low-molecular-weight substances such as urea and creatinine. It was recently demonstrated by Struijk et a P that by increasing the effective peritoneal surface area by increasing the intraperitoneal volume of dialysate can significantly improve the rate of diffusive transport for small solutes. By maintaining a maximal concentration gradient, the rate of diffusive transport can be enhanced. Solute removal also occurs through convection. Osmotic forces cause water to move across the peritoneal membrane into the peritoneal cavity. The frictional forces between the solvent and solutes result in solutes being convectively carried along with water.9 Very high glucose concentrations are present in the dialysate, and as a result, fluid removal is accomplished by establishing a hydro-osmotic gradient with glucose.22 Adequacy of peritoneal dialysis as a renal replacement therapy is difficult to define. Adequacy of peritoneal dialysis can only be ensured when uremic signs and symptoms are prevented. Fung et a17 recently demonstrated that the dose of dialysis, along with nutritional status, predict patient survival on peritoneal dialysis. The major chronic complications of peritoneal dialysis are infection, protein malnutrition, lipid derangements, and inadequate dialysis. Gram-positive organisms, as well as gram-negative organisms and fungal infections, are responsible for peritonitis encountered during peritoneal dialysis. Peritonitis may worsen the patient’s clinical condition and render the treatment dangerous and life threatening.3O Protein malnutrition may occur during peritoneal dialysis as a result of protein losses ranging from 4 to 20 g per day occurring through the dia1y~ate.l~ Protein losses can be exacerbated by concurrent infection. High glucose absorption rates can give rise to lipid abnormalities in patients undergoing peritoneal dialysis. The lipid abnormalities are in the form of low-density lipoproteins.*One of the major problems facing peritoneal dialysis is inadequate dialysis. It has been demonstrated that without residue renal function, it is very difficult to achieve adequate solute clearance rates with peritoneal dia1y~is.l~ Recurrent peritonitis may further impair the solute exchange capabilities of the peritoneal membrane. INTERMITTENT THERAPY VS. CONTINUOUS THERAPY
Although indications for renal replacement therapy have remained constant during the past several decades, the definition of continuous therapy as an alternative to standard hemodialysis is still a matter of discussion and controversy. Nevertheless, the availability of highly permeable membranes has allowed
DIALYSIS 101
859
the development of continuous renal replacement therapy, which gradually remove fluid and solutes, resulting in better hemodynamic stability and better fluid and solute Patients who require continuous renal replacement therapy demonstrate improved hemodynamic stability when compared with those subjected to intermittent therapy as a result of slow removal of fluid and solute.23This form of therapy benefits those patients who have already demonstrated a hemodynamic intolerance to intermittent forms of therapy. ACUTE AND CHRONIC FLUID SHIFTS
During progressive renal insufficiency, disturbances in fluid, acid-base, and electrolytes are seen. The mechanisms of nephron adaption are so closely attuned to physiological needs that balance of water and many solutes is precisely maintained until the very late stages of chronic renal disease. This permits survival with minimal therapeutic intervention. In chronic renal insufficiency, the fraction of water excreted by the surviving nephrons increases progressively and the water balance is maintained until the patient reaches end-stage renal failure? Tonicity of urine becomes fixed and changes little from iso-tonicity. There is the inability to maximally dilute the urine in chronic renal failure as a result of the decrease in functioning renal mass and of the solute diuresis per nephron.z Renal replacement therapies in the form of dialysis are performed, in part, to reduce undesired body excesses of fluid, electrolytes, and hydrogen ions. One of the major recurring problems in dialysis patients is isotonic fluid overload of the extracellular fluid space due to excess fluid consumption. Any fluid taken in excess of residual urine formation and insensible fluid losses will be noted as a weight gain by the patient and an expansion of the extracellular fluid volume. This fluid overload, which can be several liters in magnitude, may be shared by intracellular fluid space as well. Overexpansion of the extracellular fluid volume gives rise to edema formation, congestive heart failure, and, in some instances, frank pulmonary edema. Despite isotonic fluid expansion of patients who present for dialysis, some of these patients develop hemodynamic-significant hypotension that appears to be hypovolemic in nature.15 Several theories have been proposed for the pathogenesis of dialysis hypotension. The acute decrease in plasma osmolality may contribute to significant fluid shifts and hypotension.16Also, the interaction of blood components with the dialyzer may result in complement activation, increased leukocyte adherence, and sequestration in the lungs that potentially contributes to hypotension and hypoxemia.5 Other factors that can contribute to hypotension during dialysis include acquired dysautonomia, primary myocardial disease, substances contained in the dialysate, such as sodium acetate, hypoalbuminemia, and the use of antihypertensive medication between dialysis. There is fluid shift from the extracellular space to the intracellular space in response to changes in serum osmolality. Plasma proteins assume dominance in expressing the fluid status of the patient because capillary basement membranes have low permeability to protein. Therefore, a low plasma concentration of protein or low celluloid osmotic pressure would suggest isotonic fluid overload. In the like manner, a high concentration of plasma protein would be consistent with isotonic volume contraction.16 In hydrostatic ultrafiltration, isotonic fluid is removed from all compartments and there is an increase in colloid osmotic pressure of the vascular component of the extracellular fluid. Water moves freely from the interstitial space to the vascular space, providing appropriate refilling of the vascular space
860
IREFIN
until the available water in the interstitial space is depleted. Great demands are placed on the capacity of the patient to equilibrate fluids quickly among various body fluid spaces and to maintain blood pressure in doing so. For instance, the dialysis patient who has gained 4 kg of excess fluid must lose this in a period of 4 hours. T h s creates a stressful situation for the cardiovascular system. l l u s is in contrast to a person with normally functioning kidneys who achieves In addition, solute levels in the person with necessary ultrafiltration normal renal function are much lower than those in the dialysis patient, thereby minimizing the potential for bidirectional fluid movement from the interstitium. During the initial phase of dialysis, the diffusive losses of urea through the dialyzer are the greatest. This results in associated rapid decrease in serum osmolality and water movement into intracellular fluid space, thus compromising vascular refilling early in dialysis. The decrease in osmolality may be countered by adding an osmotically active ingredient to the blood. SURGERY IN PATIENTS ON DIALYSIS
Patients on dialysis are in a precarious state of homeostasis such that small errors of omission and lack of attention to detail during surgery may lead to significant morbidity. Although both elective and emergent surgical procedures can be performed on these patients with acceptable mortality rates, significant morbidity rates can result from the fragile condition of these chronically ill patients. Significant morbidity may result from hyperkalemia, pneumonia, atelectasis, shunt or fistula occlusion, bleeding, and wound infection in patients on dialysis. In patients on chronic dialysis, hyperkalemia is the most life-threatening electrolyte abnormality in the perioperative period. T h s may necessitate dialysis in the perioperative period. Potassium retention as a result of defect in the underlying renal excretory function; in addition, operative trauma, tissue necrosis, and transfusions may contribute to this potentially lethal complication. It is therefore recommended that dialysis be performed 24 hours preoperatively to allow acid-base, fluid, and potassium adjustments. Also, required transfusions should be given during dialysis, and intraoperative transfusions should be limited to washed packed cells. Potassium-containing fluids and muscle relaxants that release intracellular potassium should be avoided. As a result of preexisting pulmonary abnormalities in uremic patients, postoperative pulmonary complications occur in patients on dialysis. Alveolar diffusion capacity is diminished and dialysis aggravates respiratory muscle weakness, giving rise to decreased functional capacities. It is imperative that preoperative respiratory training be emphasized and chest physical therapy be part of postoperative adjunctive procedure. Patients on dialysis depend on shunts or fistulas for their therapy. It is essential that these be preserved in the perioperative period. Careful positioning to prevent extrinsic occlusion of the shunt is essential. Also, intraoperative hypotension that may predispose fistula to thrombosis should be avoided. Excessive intraoperative and postoperative bleeding are common complications after major surgical procedures in patients on dialysis. Some of the conditions that contribute to bleeding in these patients include deficiency of von Willebrands factor, anemia, uremic thrombocytopathy, and hemodialysis-associated heparin effects. Accumulation of urea results in a decrease in platelet adhesiveness and aggregation. Urea also causes a decrease in platelet factor 3. Consequently,routine coagulation studies are necessary to detect coagulopathes
DIALYSIS 101
861
in patients on dialysis before surgery. Chronic renal failure results in a normocytic, normochromic, and normovolemic anemia, but these patients are able to adjust to low red cell mass by increase in cardiac output and elevation of 2,3diphosphoglycerate (2,3-DPG). Therefore, transfusion to normal hematocrit level is often not necessary. A hemocrit above 25% will avoid anginal symptoms in most of these patients. Chronic renal failure produces immunocompromised and immunodeficiency states characterized by cellular and humoral defects and an increased susceptibility to malignant disease. Many of these immune defects are present in association with protein-calorie malnutrition. Therefore, intensive perioperative nutritional supplementation may be beneficial to patients on dialysis scheduled for surgery.
CONCLUSION Renal replacement therapy in form of dialysis only approximates normal renal function. It has been consistently shown that despite the deficiencies attributed to dialysis, it has extended the lives of patients with end-stage renal disease.17Studies have shown that inadequacies in the prescribed dose of dialysis were contributing to the high mortality rates reported in end-stage renal disease population^.^^ The extent of clarity is unknown. At present, no one dialysis modality is superior to all others for all patients. For patients with severe cardiovascular instability, multiple organ failure, or multiple trauma, continuous renal replacement therapies are preferred alternatives to intermittent hemodialysis. Nevertheless, the use of appropriate forms of therapy as the patient's condition requires allows patients to receive the benefits of all forms when needed. What may be best in one situation may not necessarily be so in another. Overall, the improved physiology with more frequent treatments for fluid removal, regardless of system used, remains self-evident. References 1. B o s h JP, von Albertini 8, Ronco C: Hemofiltration and hemodiafiltration. In Glassock RJ (ed): Current Therapy in Nephrology and Hypertension. Toronto, BC Decker, 1987, pp 258-263 2. Bourgoinie JJ, Jacob AI, Sallman AL, et al: Water, electrolyte, and acid-base abnormalities in chronic renal failure. Semin Nephrol 19-111, 1981 3. Bricker NS: On the meaning of the intact nephron hypothesis. Am J Med 46:l-12,1969 4. Converse RL, Jacobsen TN, Jost CM, et al: Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis-induced hypotension. J Clin Invest 90:1657-65,1992 5. Craddock PR, Fehr J, Daimasso AP, et al: Haemodialysis leukopenia: Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes. J Clin Invest 595379, 1977 6. Farrell PC, Ward RA, Schindhelm K, Gotch F A Precise anticoagulation for routine hemodialysis. J Lab Clin Med 92164, 1978 7. Fung L, Pollock CA, Caterson RJ, et al: Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients. J Am SOCNephrol 7737-744, 1996 8. Heaf J: CAPD adequacy and dialysis morbidity: Detrimental effect of high peritoneal equilibration rate. Renal Failure 17575-587, 1995 9. Heimburger 0, Waniewski A, Werynski A, et al: A quantitative description of solute fluid transport during peritoneal dialysis. Kidney Int 41:1320-1332, 1992
862
IREFIN
10. Henderson LW, Colton CK, Ford C: Kinetics of hemodiafiltration: Clinical characterization of a new blood cleansing modality. J Lab Clin Med 85:372-375, 1975 11. Henderson LW Hernofiltration: From the origin of the new wave. Am J Kidney Dis 28 S3:100-104, 1996 12. Henrich WL: Hemodynamic instability during hemodialysis. Kidney Int 30:605612, 1986 13. Hirasawa H, Sugai T, Ohtake Y, et al: Continuous hernofiltration and hemodiafiltration in the management of multiple organ failure. Contrib Nephrol 93:42, 1991 14. Kawaguchi Y, Hasegawa T, Kubo H, et al: Current issues of continuous ambulatory peritoneal dialysis. Artif Organs 19:1204-1209, 1995 15. Keshaviah P, Shapiro FL: A critical examination of dialysis-induced hypotension. Am J Kidney Dis 2290-301, 1982 16. Kjellstrand CM, Rosa AA, Shidemann J R Hypotension during hemodialysis: Osmolality fall is an important pathogenic factor. Am SOCArtif Intern Organs J 3:11, 1980 17. Lundin PA: Prolonged survival on hemodialysis. In Maher JF (ed): Replacement of Renal Function, 3rd ed. Dordrecht, The Netherlands, Kluwer Academic, 1989, pp 11331140 18. Lysaht MJ, Schmidt B, Gurland HJ: Filtration rates and pressure driving forces in AV filtration. Blood Purif 1:178, 1983 19. Malhotra D, Tzamaloukas AH, Murata GH, et al: Serum albumin in continuous peritoneal dialysis: Its predictors and relationship to urea clearance. Kidney Int 50243249, 1996 20. Maxwell MH, Rockney RE, Kleeman CR, Twiss MR Peritoneal dialysis. I: Technique and application. JAMA 170:917, 1959 21. Mukau L, Latimer RG: Acute hemodialysis in the surgical intensive care unit. Am Surg 54548-552, 1988 22. Nolph KD, Keshaviah P, Emerson P, et al: A new approach to optimizing urea clearances in hemodialysis and continuous ambulatory peritoneal dialysis. ASAIO J 41:M446-M451, 1995 23. Olbricht C, Mueller C, Schurek HJ: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am SOCArtif Intern Organs 28:33-37, 1982 24. Paganini EP: Continuous renal replacement therapy. In Parrilo JE, Bone RC (eds): Critical Care Medicine: Principles of Diagnosis and Management. St. Louis, MosbyYear Book, 1985, p 234 25. Ronco C: Continuous renal replacement therapies: Evolution towards a new era. Semin Dialysis 9:215221, 1996 26. Ronco C, Burchardi H Management of acute renal failure in the critically ill patient. In Pinsky MR, Dhainaut JA (eds): Pathophysiologic Foundation of Critical Care. Baltimore, Williams & Wilkins, 1993, p 637 27. Sargent JA: Shortfalls in the delivery of dialysis. Am J Kidney Dis 15:500-510, 1990 28. Struijk DG, Krediet RT, Koomen GC, et al: A prospective study of peritoneal transport in CAPD patients. Kidney Int 45:1739-1744, 1994 29. Teschan PE, et a1 Prophylactic hemodialysis in the treatment of acute renal failure. Ann Intern Med 53:992-1016, 1960 30. Tzamaloukas AH: Peritonitis in peritoneal dialysis patients: An overview. Adv Ren Replace Ther 3932-236, 1996 31. Wehle 8, Asalsa H, Castenfors J, et al: Hemodynamic changes during sequential ultrafiltration and dialysis. Kidney Int 15:411418, 1979
Address reprint requests to Samuel A. Irefin, MD The Cleveland Clinic Foundation E-31 9500 Euclid Avenue Cleveland, OH 44195 e-mail: [email protected]
0889-8537/00 $15.00
+ .OO
DIALYSIS 101 Acute and Chronic Fluid Shifts Samuel A. Irefin, MD
The kidneys are major excretory organs and function in regulating acid/ base balance, electrolyte balance, and maintaining optimal body fluid composition. They also function in eliminating products of metabolism. The inability of the kidneys to perform these functions result in biochemical disturbances, electrolyte abnormalities, and failure to regulate the body’s internal environment. Artificial kidney was first introduced during the Korean War as a choice of renal replacement therapyz9 Since that time, significant advances have been made in different dialysis methods, and renal dialysis have evolved to become the accepted therapeutic intervention for patients who have developed endstage renal disease as well as those patients with acute renal failure. As a renal replacement therapy, dialysis only approximates normal renal function. The developments that have been made in the field of renal dialysis have allowed the procedure to be performed with such techniques such as ultrafiltration, hemodialysis, hemofiltration, hemodiafiltration, and peritoneal dialysis. Choosing an effective renal replacement therapy depends on several conditions. The clinical condition that resulted in the renal failure will dictate the type of therapy chosen (Table l).24 In addition, technical support and personnel play a vital role in renal replacement therapy.
BASIC MECHANISMS OF DIALYSIS The word dialysis was derived from Greek language meaning to ”pass across.” All the mechanisms used in dialysis involve transport process of solutes and water.l0 The membranes that are used in renal replacement therapies consist of
From the Division of Anesthesiology and Critical Care Medicine, Department of General Anesthesia, The Cleveland Clinic Foundation, Cleveland, Ohio
ANESTHESIOLOGY CLINICS OF NORTH AMERICA
VOLUME 18 * NUMBER 4 * DECEMBER 2000
853
Diffusion-based processes using dialysate and semipermeable membrane
Convective-based process using plasma water exchange methods across semipermeable membrane
Combining diffusion and convection (10-L exchanges) for both small and middle molecular loss
Dialysis
Hemofiltration
Hemodiafiltration
Use
Fluid overload High delivery in CRF (ARF) CHF Azotemia Acid I base disorders Electrolyte balance Volume control Azotemia Acid base Electrolyte Volume Cytokines ARF, MOF, CHF, ARDS Azotemia Volume Cytokines ARF, MOF, CHF, ARDS Sepsis
Access
AV WContinuous Intermittent
AV W Continuous Intermittent
AV Continuous W Continuous Intermittent AV Continuous W Continuous Intermittent
CAVHDF CWHDF IHDF
CAVH CWH IH
SCUF CW-UF IUF CAVHD CWHD IHD
Abbreviation
CRF = chronic renal failure, ARF = acute renal failure, CHF = congestive heart failure, AV = atrioventricular, VV = venovenous, MOF = multiorgan failure, ARDS = adult respiratory distress syndrome. (From Parrillo JE, Bone R C Critical Care Medicine. Principles of Diagnosis and Management. Mosby Year Book Inc., 1995, p 234, with permission.)
Definition
Plasma water removal Usually less than 5L/24 hr
Therapy
Ultrafiltration
Table 1. COMMONLY UTILIZED FORMS OF RENAL REPLACEMENT THERAPY
DIALYSIS 101
855
cellulose or synthetic varieties. The artificial synthetic membranes have higher ultrafiltration coefficients and solute permeability. They are employed mainly in those treatments that require a h g h convective component ( e g , hemofiltration). The artificial cellulose membrane possesses low ultrafiltration capacities; they are mainly employed in standard dialysis. The mechanisms that are used in solute and water transport across these membranes are shown in Figure LZ6 J = D T A (Crcldx) m
m
I
I
rn
[s]+ [sb = Sieving
u = (n R T ) I V m
w
m ,
i
..... .... .... ..... ....
g.....
~*.*.'.*.*
C
P
UF = Kf TMP
..... .... ..... Polarization Figure 1. Mechanisms of solute and water transport used for renal replacement therapy. A, Diffusion is directly proportional to diffusivity (D), temperature (T), membrane area (A), and concentration gradient (dc), and is inversely correlated with the membrane thickness (dx). B, Convection depends on ultrafiltration (UF) and membrane sieving capacity (s). C, Osmosis is mostly utilized in peritoneal dialysis. D, Ultrafiltration depends on transmembrane pressure (TMP), and membrane permeability coefficient (Kf). (From Pinksy MR, Dhainnaut J: Pathophysiologic Foundations of Critical Care. Baltimore, Williams and Wilkins, 1993, p 637; with permission.)
856
IREFIN
Removal of solutes by dialysis is achieved by convection, diffusion, osmosis, or a combination of these methods. Convection
Convective mechanism involves transportation of solutes across the membrane by the solvent. The solvent movement takes place in response to certain transmembrane pressure.ll The permeability of the membrane plays an important role in this process. Synthetic membranes retard the movement of proteins and cells but allow the passage of other solutes up to a given molecular size at the same concentration as in plasma water. Solute transport in convection depends on the amount of ultrafiltrate, the sieving capacity of the membrane, and the solute concentration in plasma water. This technique is used in ultrafiltration and hemofiltration. Diffusion
In diffusion-based techniques, solute removal is based on the movement of molecules in all directions, and molecules tend to achieve an equal concentration on both sides of the membrane. This technique is based on the principle of a solute gradient between the blood and the dialysate. The concentration gradient is the driving force for the solute, and the thickness and permeability of the membrane represents the major resistance. Osmosis
In this technique, water movement from the patient is proportional to osmotically active particles in the dialysate. Water moves from the area of high water concentration (i.e., plasma) to the area of low water concentration (i.e., the dialysate).This mechanism is utilized mostly in peritoneal dialysis techruque. Osmosis also requires a semipermeable membrane between the plasma and the dialysate; the peritoneal membrane performs t h s function. DIALYSIS THERAPY The Hemodialysis Procedure
Hemodialysis is a process of detoxification of uremic blood via dialysis of blood. Hemodialysis therapy requires an adequate vascular access, specially trained personnel to carry out the dialysis session, and the right equipment to perform the treatment. Hemodialysis technique entails the diffusion of solutes between the blood and a dialysis solution. Ths results in the removal of metabolic waste products and replenishment of body buffers. Blood is heparinized and pumped through a plastic dialyzer. The amount of heparin used varies from 600 to 800 iu/hr to guarantee a safe anticoagulation with minimal or no systemic effects.6 With hemodialysis, solutes are removed largely through diffusion down a concentration gradient and fluid removal through ultrafiltration using a hydrostatic pressure gradient. This results in the clearance of nitrogenous waste products in
DIALYSIS 101
857
form of blood urea nitrogen concentration. A 3- to 4-hour treatment session can result in 65% to 70% reduction in BUN. The urea clearance rate depends on the surface area of the dialyzer and the permeability of the membrane. Hemodialysis has become the most frequently employed treatment modality for end-stage renal disease. The access to the circulation for hemodialysis may be achieved by either percutaneous insertion of central venous catheters or by surgical creation of arteriovenous shunts. During hemodialysis, small molecular weight solutes are removed faster from the body than medium- to large-sized molecules. Hypotension, secondary to ultrafiltration-induced volume depletion, is the most common complication during hem~dialysis.~ Hypotensive episodes during hemodialysis can also result from arrhythmia, coronary ischemia, or pericardial effusion.I2These episodes can be treated with infusion of crystalloids, reducing rate of ultrafiltration or both. Hemofiltration
Hemofiltration technique employs a convective mode of fluid removal and requires a highly permeable membrane. There is no dialysate flow to the membrane. Rather, there is a removal of fluid across the membrane driven by transmembrane hydrostatic pressure differences. Treatment time depends on the rate of ultrafiltration and the total amount of fluid to be exchanged. Fluid lost its totally or partially replaced with a replacement fluid, and solute concentrations in plasma is lowered. The net weight loss by the patient depends on the difference between ultrafiltration and reinfusion. Different-sized molecules are removed from the body during hemofiltration.'8 Replacement fluid composition when hemofiltration is performed, dictates the resultant end point of therapy; knowing what fluid type is lost helps in choosing the appropriate replacement solution. Hemodiafiltration
Hemodiafiltration employs both diffusive and convective modes of therapy. The combination of small molecular weight substances removed by diffusion and middle molecular weight substances removed by hemofiltration lends superiority to hemodiafiltration technique. Highly permeable membranes are utilized. Hemodiafiltration is a highly complex techmque, and it is utilized mainly to remove substances that are believed to be involved in disease states such as sepsis and multiorgan fai1~re.I~ Recent studies have demonstrated that hemodiafiltration guarantees remarkable sodium and buffer balances and adequate treatment of metabolic acidosis.' Ultrafiltration
Ultrafiltration is the simplest form of dialysis therapy. The main goal of ultrafiltration is fluid removal and can be accomplished as an isolated therapy or in combination with other forms of blood cleaning techniques.21Fluid removed during ultrafiltration depends on the transmembrane pressure gradient and the hydraulic permeability coefficient of the membrane. As a result, syn-
858
IREFIN
thetic membranes are utilized during ultrafiltration therapy. The composition of fluid removed during ultrafiltration of blood has the characteristics of plasmafree water. Peritoneal Dialysis
The technique of peritoneal dialysis involves using the peritoneum as a dialysis and ultrafiltration membrane. Peritoneal dialysis involves infusion of sterile pyrogen-free solution into the peritoneal cavity. The solution is then drained in cycles. Solute removal during peritoneal dialysis results from a combination of diffusive and convective transport as a result of a concentration gradient between blood flowing in the peritoneal capillary network and the dialysate.*O The primary mechanism for small solute removal is diffusion. The peritoneal membrane is highly permeable to low-molecular-weight substances such as urea and creatinine. It was recently demonstrated by Struijk et a P that by increasing the effective peritoneal surface area by increasing the intraperitoneal volume of dialysate can significantly improve the rate of diffusive transport for small solutes. By maintaining a maximal concentration gradient, the rate of diffusive transport can be enhanced. Solute removal also occurs through convection. Osmotic forces cause water to move across the peritoneal membrane into the peritoneal cavity. The frictional forces between the solvent and solutes result in solutes being convectively carried along with water.9 Very high glucose concentrations are present in the dialysate, and as a result, fluid removal is accomplished by establishing a hydro-osmotic gradient with glucose.22 Adequacy of peritoneal dialysis as a renal replacement therapy is difficult to define. Adequacy of peritoneal dialysis can only be ensured when uremic signs and symptoms are prevented. Fung et a17 recently demonstrated that the dose of dialysis, along with nutritional status, predict patient survival on peritoneal dialysis. The major chronic complications of peritoneal dialysis are infection, protein malnutrition, lipid derangements, and inadequate dialysis. Gram-positive organisms, as well as gram-negative organisms and fungal infections, are responsible for peritonitis encountered during peritoneal dialysis. Peritonitis may worsen the patient’s clinical condition and render the treatment dangerous and life threatening.3O Protein malnutrition may occur during peritoneal dialysis as a result of protein losses ranging from 4 to 20 g per day occurring through the dia1y~ate.l~ Protein losses can be exacerbated by concurrent infection. High glucose absorption rates can give rise to lipid abnormalities in patients undergoing peritoneal dialysis. The lipid abnormalities are in the form of low-density lipoproteins.*One of the major problems facing peritoneal dialysis is inadequate dialysis. It has been demonstrated that without residue renal function, it is very difficult to achieve adequate solute clearance rates with peritoneal dia1y~is.l~ Recurrent peritonitis may further impair the solute exchange capabilities of the peritoneal membrane. INTERMITTENT THERAPY VS. CONTINUOUS THERAPY
Although indications for renal replacement therapy have remained constant during the past several decades, the definition of continuous therapy as an alternative to standard hemodialysis is still a matter of discussion and controversy. Nevertheless, the availability of highly permeable membranes has allowed
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the development of continuous renal replacement therapy, which gradually remove fluid and solutes, resulting in better hemodynamic stability and better fluid and solute Patients who require continuous renal replacement therapy demonstrate improved hemodynamic stability when compared with those subjected to intermittent therapy as a result of slow removal of fluid and solute.23This form of therapy benefits those patients who have already demonstrated a hemodynamic intolerance to intermittent forms of therapy. ACUTE AND CHRONIC FLUID SHIFTS
During progressive renal insufficiency, disturbances in fluid, acid-base, and electrolytes are seen. The mechanisms of nephron adaption are so closely attuned to physiological needs that balance of water and many solutes is precisely maintained until the very late stages of chronic renal disease. This permits survival with minimal therapeutic intervention. In chronic renal insufficiency, the fraction of water excreted by the surviving nephrons increases progressively and the water balance is maintained until the patient reaches end-stage renal failure? Tonicity of urine becomes fixed and changes little from iso-tonicity. There is the inability to maximally dilute the urine in chronic renal failure as a result of the decrease in functioning renal mass and of the solute diuresis per nephron.z Renal replacement therapies in the form of dialysis are performed, in part, to reduce undesired body excesses of fluid, electrolytes, and hydrogen ions. One of the major recurring problems in dialysis patients is isotonic fluid overload of the extracellular fluid space due to excess fluid consumption. Any fluid taken in excess of residual urine formation and insensible fluid losses will be noted as a weight gain by the patient and an expansion of the extracellular fluid volume. This fluid overload, which can be several liters in magnitude, may be shared by intracellular fluid space as well. Overexpansion of the extracellular fluid volume gives rise to edema formation, congestive heart failure, and, in some instances, frank pulmonary edema. Despite isotonic fluid expansion of patients who present for dialysis, some of these patients develop hemodynamic-significant hypotension that appears to be hypovolemic in nature.15 Several theories have been proposed for the pathogenesis of dialysis hypotension. The acute decrease in plasma osmolality may contribute to significant fluid shifts and hypotension.16Also, the interaction of blood components with the dialyzer may result in complement activation, increased leukocyte adherence, and sequestration in the lungs that potentially contributes to hypotension and hypoxemia.5 Other factors that can contribute to hypotension during dialysis include acquired dysautonomia, primary myocardial disease, substances contained in the dialysate, such as sodium acetate, hypoalbuminemia, and the use of antihypertensive medication between dialysis. There is fluid shift from the extracellular space to the intracellular space in response to changes in serum osmolality. Plasma proteins assume dominance in expressing the fluid status of the patient because capillary basement membranes have low permeability to protein. Therefore, a low plasma concentration of protein or low celluloid osmotic pressure would suggest isotonic fluid overload. In the like manner, a high concentration of plasma protein would be consistent with isotonic volume contraction.16 In hydrostatic ultrafiltration, isotonic fluid is removed from all compartments and there is an increase in colloid osmotic pressure of the vascular component of the extracellular fluid. Water moves freely from the interstitial space to the vascular space, providing appropriate refilling of the vascular space
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until the available water in the interstitial space is depleted. Great demands are placed on the capacity of the patient to equilibrate fluids quickly among various body fluid spaces and to maintain blood pressure in doing so. For instance, the dialysis patient who has gained 4 kg of excess fluid must lose this in a period of 4 hours. T h s creates a stressful situation for the cardiovascular system. l l u s is in contrast to a person with normally functioning kidneys who achieves In addition, solute levels in the person with necessary ultrafiltration normal renal function are much lower than those in the dialysis patient, thereby minimizing the potential for bidirectional fluid movement from the interstitium. During the initial phase of dialysis, the diffusive losses of urea through the dialyzer are the greatest. This results in associated rapid decrease in serum osmolality and water movement into intracellular fluid space, thus compromising vascular refilling early in dialysis. The decrease in osmolality may be countered by adding an osmotically active ingredient to the blood. SURGERY IN PATIENTS ON DIALYSIS
Patients on dialysis are in a precarious state of homeostasis such that small errors of omission and lack of attention to detail during surgery may lead to significant morbidity. Although both elective and emergent surgical procedures can be performed on these patients with acceptable mortality rates, significant morbidity rates can result from the fragile condition of these chronically ill patients. Significant morbidity may result from hyperkalemia, pneumonia, atelectasis, shunt or fistula occlusion, bleeding, and wound infection in patients on dialysis. In patients on chronic dialysis, hyperkalemia is the most life-threatening electrolyte abnormality in the perioperative period. T h s may necessitate dialysis in the perioperative period. Potassium retention as a result of defect in the underlying renal excretory function; in addition, operative trauma, tissue necrosis, and transfusions may contribute to this potentially lethal complication. It is therefore recommended that dialysis be performed 24 hours preoperatively to allow acid-base, fluid, and potassium adjustments. Also, required transfusions should be given during dialysis, and intraoperative transfusions should be limited to washed packed cells. Potassium-containing fluids and muscle relaxants that release intracellular potassium should be avoided. As a result of preexisting pulmonary abnormalities in uremic patients, postoperative pulmonary complications occur in patients on dialysis. Alveolar diffusion capacity is diminished and dialysis aggravates respiratory muscle weakness, giving rise to decreased functional capacities. It is imperative that preoperative respiratory training be emphasized and chest physical therapy be part of postoperative adjunctive procedure. Patients on dialysis depend on shunts or fistulas for their therapy. It is essential that these be preserved in the perioperative period. Careful positioning to prevent extrinsic occlusion of the shunt is essential. Also, intraoperative hypotension that may predispose fistula to thrombosis should be avoided. Excessive intraoperative and postoperative bleeding are common complications after major surgical procedures in patients on dialysis. Some of the conditions that contribute to bleeding in these patients include deficiency of von Willebrands factor, anemia, uremic thrombocytopathy, and hemodialysis-associated heparin effects. Accumulation of urea results in a decrease in platelet adhesiveness and aggregation. Urea also causes a decrease in platelet factor 3. Consequently,routine coagulation studies are necessary to detect coagulopathes
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in patients on dialysis before surgery. Chronic renal failure results in a normocytic, normochromic, and normovolemic anemia, but these patients are able to adjust to low red cell mass by increase in cardiac output and elevation of 2,3diphosphoglycerate (2,3-DPG). Therefore, transfusion to normal hematocrit level is often not necessary. A hemocrit above 25% will avoid anginal symptoms in most of these patients. Chronic renal failure produces immunocompromised and immunodeficiency states characterized by cellular and humoral defects and an increased susceptibility to malignant disease. Many of these immune defects are present in association with protein-calorie malnutrition. Therefore, intensive perioperative nutritional supplementation may be beneficial to patients on dialysis scheduled for surgery.
CONCLUSION Renal replacement therapy in form of dialysis only approximates normal renal function. It has been consistently shown that despite the deficiencies attributed to dialysis, it has extended the lives of patients with end-stage renal disease.17Studies have shown that inadequacies in the prescribed dose of dialysis were contributing to the high mortality rates reported in end-stage renal disease population^.^^ The extent of clarity is unknown. At present, no one dialysis modality is superior to all others for all patients. For patients with severe cardiovascular instability, multiple organ failure, or multiple trauma, continuous renal replacement therapies are preferred alternatives to intermittent hemodialysis. Nevertheless, the use of appropriate forms of therapy as the patient's condition requires allows patients to receive the benefits of all forms when needed. What may be best in one situation may not necessarily be so in another. Overall, the improved physiology with more frequent treatments for fluid removal, regardless of system used, remains self-evident. References 1. B o s h JP, von Albertini 8, Ronco C: Hemofiltration and hemodiafiltration. In Glassock RJ (ed): Current Therapy in Nephrology and Hypertension. Toronto, BC Decker, 1987, pp 258-263 2. Bourgoinie JJ, Jacob AI, Sallman AL, et al: Water, electrolyte, and acid-base abnormalities in chronic renal failure. Semin Nephrol 19-111, 1981 3. Bricker NS: On the meaning of the intact nephron hypothesis. Am J Med 46:l-12,1969 4. Converse RL, Jacobsen TN, Jost CM, et al: Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis-induced hypotension. J Clin Invest 90:1657-65,1992 5. Craddock PR, Fehr J, Daimasso AP, et al: Haemodialysis leukopenia: Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes. J Clin Invest 595379, 1977 6. Farrell PC, Ward RA, Schindhelm K, Gotch F A Precise anticoagulation for routine hemodialysis. J Lab Clin Med 92164, 1978 7. Fung L, Pollock CA, Caterson RJ, et al: Dialysis adequacy and nutrition determine prognosis in continuous ambulatory peritoneal dialysis patients. J Am SOCNephrol 7737-744, 1996 8. Heaf J: CAPD adequacy and dialysis morbidity: Detrimental effect of high peritoneal equilibration rate. Renal Failure 17575-587, 1995 9. Heimburger 0, Waniewski A, Werynski A, et al: A quantitative description of solute fluid transport during peritoneal dialysis. Kidney Int 41:1320-1332, 1992
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10. Henderson LW, Colton CK, Ford C: Kinetics of hemodiafiltration: Clinical characterization of a new blood cleansing modality. J Lab Clin Med 85:372-375, 1975 11. Henderson LW Hernofiltration: From the origin of the new wave. Am J Kidney Dis 28 S3:100-104, 1996 12. Henrich WL: Hemodynamic instability during hemodialysis. Kidney Int 30:605612, 1986 13. Hirasawa H, Sugai T, Ohtake Y, et al: Continuous hernofiltration and hemodiafiltration in the management of multiple organ failure. Contrib Nephrol 93:42, 1991 14. Kawaguchi Y, Hasegawa T, Kubo H, et al: Current issues of continuous ambulatory peritoneal dialysis. Artif Organs 19:1204-1209, 1995 15. Keshaviah P, Shapiro FL: A critical examination of dialysis-induced hypotension. Am J Kidney Dis 2290-301, 1982 16. Kjellstrand CM, Rosa AA, Shidemann J R Hypotension during hemodialysis: Osmolality fall is an important pathogenic factor. Am SOCArtif Intern Organs J 3:11, 1980 17. Lundin PA: Prolonged survival on hemodialysis. In Maher JF (ed): Replacement of Renal Function, 3rd ed. Dordrecht, The Netherlands, Kluwer Academic, 1989, pp 11331140 18. Lysaht MJ, Schmidt B, Gurland HJ: Filtration rates and pressure driving forces in AV filtration. Blood Purif 1:178, 1983 19. Malhotra D, Tzamaloukas AH, Murata GH, et al: Serum albumin in continuous peritoneal dialysis: Its predictors and relationship to urea clearance. Kidney Int 50243249, 1996 20. Maxwell MH, Rockney RE, Kleeman CR, Twiss MR Peritoneal dialysis. I: Technique and application. JAMA 170:917, 1959 21. Mukau L, Latimer RG: Acute hemodialysis in the surgical intensive care unit. Am Surg 54548-552, 1988 22. Nolph KD, Keshaviah P, Emerson P, et al: A new approach to optimizing urea clearances in hemodialysis and continuous ambulatory peritoneal dialysis. ASAIO J 41:M446-M451, 1995 23. Olbricht C, Mueller C, Schurek HJ: Treatment of acute renal failure in patients with multiple organ failure by continuous spontaneous hemofiltration. Trans Am SOCArtif Intern Organs 28:33-37, 1982 24. Paganini EP: Continuous renal replacement therapy. In Parrilo JE, Bone RC (eds): Critical Care Medicine: Principles of Diagnosis and Management. St. Louis, MosbyYear Book, 1985, p 234 25. Ronco C: Continuous renal replacement therapies: Evolution towards a new era. Semin Dialysis 9:215221, 1996 26. Ronco C, Burchardi H Management of acute renal failure in the critically ill patient. In Pinsky MR, Dhainaut JA (eds): Pathophysiologic Foundation of Critical Care. Baltimore, Williams & Wilkins, 1993, p 637 27. Sargent JA: Shortfalls in the delivery of dialysis. Am J Kidney Dis 15:500-510, 1990 28. Struijk DG, Krediet RT, Koomen GC, et al: A prospective study of peritoneal transport in CAPD patients. Kidney Int 45:1739-1744, 1994 29. Teschan PE, et a1 Prophylactic hemodialysis in the treatment of acute renal failure. Ann Intern Med 53:992-1016, 1960 30. Tzamaloukas AH: Peritonitis in peritoneal dialysis patients: An overview. Adv Ren Replace Ther 3932-236, 1996 31. Wehle 8, Asalsa H, Castenfors J, et al: Hemodynamic changes during sequential ultrafiltration and dialysis. Kidney Int 15:411418, 1979
Address reprint requests to Samuel A. Irefin, MD The Cleveland Clinic Foundation E-31 9500 Euclid Avenue Cleveland, OH 44195 e-mail: [email protected]