Neonatal Hemodialysis and Continuous Renal Replacement Therapy

After completing this article, readers should be able to: Since the mid-1980s, when dialysis manufacturers began making dialyzers and blood circuit paths that required smaller extracorporeal volumes, hemodialysis has been used successfully to manage renal failure in neonates and infants. Compared with peritoneal dialysis (PD), which is analogous to the “family sedan” in the world of dialysis (slower, more predictable, easier to operate), hemodialysis is the “race car.” Hemodialysis is capable of removing fluids and solutes much more rapidly than is PD. Unlike PD, hemodialysis uses catheters that access the intravascular space directly. Despite the advantages of hemodialysis, the process in neonates is technically more challenging than PD due to the very attributes that make it so effective. Rapid removal of intravascular fluids, exceeding the rate of refill from the extravascular space, causes problems with hypotension due to direct reduction in intravascular volume. Similarly, rapid rates of solute clearance can cause problems with increased intracranial pressure. Catheter placement and maintenance of catheter function can constitute a significant obstacle to hemodialysis.Hemofiltration is very similar to hemodialysis in that patient blood is circulated through an artificial kidney. However, hemofiltration differs from hemodialysis in three significant aspects. First, the hemofilter has larger pore sizes than the standard dialyzer, which allows for excellent fluid removal, even with low blood flow rates, and better larger molecule clearance. Second, hemofiltration runs continuously without the continuous presence of a dialysis nurse. Third, typical hemofiltration uses a pre- or postdilution fluid to increase solute clearances. Clearances have been enhanced by the use of blood pumps to ensure constant blood flow to the hemofilter. Initial attempts to perform hemofiltration with arteriovenous blood flow have yielded to the more effective and efficient pump-based venovenous techniques.A noteworthy trend is toward greater use of continuous renal replacement therapy (CRRT) in pediatric intensive care units for the treatment of renal failure, hepatic failure, sepsis, and acute respiratory distress syndrome. With greater experience in using CRRT, its use has increased, and use of hemodialysis has decreased in neonatal intensive care nurseries.Hemodialysis has particular utility in specific clinical situations, including the rapid correction of volume overload, severe hyperkalemia, severe unremitting metabolic acidosis, and the treatment of oxalosis and hyperammonemia. Hemodialysis is used more often in patients who have acute, not chronic, renal failure. If peritoneal dialysis is contraindicated or fails in children who have chronic renal failure, hemodialysis is employed. Most infants require hemodialysis four times weekly to avoid the fluid overload that is a consequence of their liquid nutrition.The success of hemodialysis is largely dependent on appropriate catheter selection and placement. A list of common hemodialysis catheters used in neonates and the mean diameter of the central vessels in a neonate are shown in Tables 1 and 2. Catheters larger than 8 French cannot be used because of the risk of vessel tearing with catheter placement and the higher risk of vascular stenosis and thrombosis. Placement of the hemodialysis catheter in the femoral vein increases the risk of internal iliac and inferior vena cava (IVC) thrombosis. This can be particularly concerning if the patient is a potential renal transplant recipient. Thrombosis of the IVC can make venous access for an adult-sized renal allograft challenging or even impossible. With complete IVC thrombosis, the transplant surgeon must use a pediatric donor allograft, and large collaterals or the ovarian vein must be used as the anastomotic site for the renal vein. Because of these potential difficulties with femoral catheters, the internal jugular vessels are preferred in infants requiring long-term dialysis. Catheters are inserted less frequently in the subclavian vein because they do not function as well as catheters placed in the internal jugular vein. There are also concerns regarding the risk of stenosis of the subclavian vein, which could make subsequent arteriovenous fistula creation much more problematic.Two 5 French catheters (outer diameter of 1.7 mm), a 7 French Tesio catheter, or a 7 or 8 French dual lumen hemodialysis catheter typically are placed. Lines inserted for extracorporeal membrane oxygenation (ECMO) also can be used for hemodialysis. Some investigators have concluded that there may be some advantages to the Tesio-type catheter, including less recirculation and longer function, compared with other types of catheters. Blood flow rates of at least 25 mL/min are required for adequate dialysis. The distal portion of the Ash split catheter separates into two single lumen catheters, but the Ash split catheters are generally too large for use in neonates and infants.Hemodialysis catheters tend to malfunction due to clotting or a catheter tip placement that makes blood flow sporadic relative to position. Although a heparin lock of the catheter with 100 U/mL is considered safe and effective, tissue plasminogen activator is used in some centers to decrease the chances of catheter clotting. Positional catheters are particularly challenging for pediatric hemodialysis nurses, who must maintain the infant or child in the optimal position throughout the hemodialysis session, usually 2 to 4 hours.Line sepsis with organisms including Staphylococcus and Streptococcus sp can cause significant morbidity and mortality in neonates. Recurrent infections often necessitate replacement of the hemodialysis catheter. Alternatives include the use of a vancomycin-heparin catheter lock, which consists of vancomycin 25 mcg/mL and heparin 100 U/mL. However, there are anecdotal reports of fungal sepsis after the use of antibiotic locks. Evaluating parents and other caretakers prior to permanent hemodialysis catheter placement for the presence of S aureus nasal carriage appears to be prudent because treatment with mupirocin nasal ointment eradicates S aureus nasal carriage in 91% immediately after 5 consecutive days of twice-daily therapy.Most manufacturers of dialyzers and dialysis machines have adapted their products for infants. Neonatal blood lines, although similar in appearance to regular adult or pediatric blood lines, have smaller internal luminal diameters. Even the pump header segment has a smaller internal luminal diameter, thus requiring a pump speed four times greater than the blood flow. Dialyzers that have smaller surface areas also are used. The surface area can be reduced by decreasing the length of the dialyzer and the number of hollow fibers within the dialyzer. Some dialyzers require a reduction in the volume of dialysate per minute from 500 to 600 mL/min to 300 to 400 mL/min for the dialyzer/circuit set to work properly.If more than 10% of the neonate’s blood volume (80 mL/kg) is in the extracorporeal circuit, there is a greater risk of hemodynamic instability due to the acute “loss” of blood when exchanged for crystalloid or 5% albumin. Even with neonatal blood lines and a small dialyzer, most neonates weighing less than 8 to 10 kg require at least occasional blood priming. If the hemoglobin level is maintained in the high range of normal or the patient is transfused concurrently during the start of dialysis, the infant may tolerate a crystalloid or 5% albumin prime. Packed red blood cells typically are mixed with normal saline to achieve a hemoglobin concentration of 10 to 13 g/dL (100 to 130 g/L). The citrate concentration in the packed red blood cells decreases when other solutions are added, thus increasing the risk of clotting in the blood circuit path. Some investigators have used normalized blood, which is a mixture of packed red blood cells, 5% albumin, heparin, sodium bicarbonate, and calcium gluconate, to prime the circuit path. Sensitization to human lymphocyte antigens, viral infections, and transfusion reactions are the greatest risks associated with blood primes or sequential transfusions. To avoid these complications, we have developed a rapid exchange technique in which the patient’s blood is transferred, in series, from the old circuit to a new circuit on the second dialysis machine.There is great controversy as to what constitutes adequate dialysis in children. The nephrologist must select the appropriate dialyzer, which should have a surface area of 0.7 to 1 times the body surface area of the patient. Consideration must be given to the dialyzer membrane composition, which influences larger molecule clearance and ultrafiltration effectiveness. The use of high-flux dialyzers, which facilitate better middle molecule clearance, has increased over time. For neonates, neonatal blood lines are used for dialysis. The blood flow rate is influenced by the catheter size and clearance requirements. The duration of dialysis can be calculated using the Kt/V clearance equation, where K=clearance, t=time, V=volume of nitrogen distribution (approximately 0.6×weight in kg). Kt/V values greater than 1.6 generally are believed to be adequate for children.Unlike peritoneal dialysate, which is available in premixed commercial solutions in plastic bags, hemodialysis solution is made by combining purified, but nonsterile, water with a bicarbonate-saturated solution and an acid concentrate (a small amount of acetic acid is added) composed of all of the electrolytes, including sodium, potassium, magnesium, calcium, and dextrose. The dialysis machine continuously monitors the solute concentrations by assessing the conductivity of the dialysis solution prior to pumping it to the dialyzer. The dialysis machine warms the dialysis solution prior to running the solution counter-current to blood flow in the dialyzer. For many neonates, warming the dialysate is insufficient to maintain normal patient temperatures; returning the blood via a warming device sometimes is needed. Increasing the overhead warmer temperature is also helpful. The dialysis solution percolates into the spaces around the dialyzer hollow fibers. The dialysis machine monitors the dialysis effluent for blood prior to its discard into a drain/sewer. The presence of blood in the dialysate indicates that one or more of the dialyzer hollow fibers is defective and losing the patient’s blood. Replacement of the dialyzer, and often the entire circuit, is necessary.The dialysis machine also regulates fluid removal by adjusting the transmembrane pressure (TMP), which is the difference in the pressure between the blood inside the hollow fiber and outside the hollow fiber. Most high-flux dialyzers ultrafiltrate extremely well, thus necessitating very low TMPs, or even may exert positive pressure (negative TMP) to limit ultrafiltration. Balancing pumps on most dialysis machines are very accurate, so continuous weighing of the patient no longer is necessary. It is important to remember that an intravascular fluid shift of as little as 10 mL may have significant hemodynamic implications for a term or preterm infant.If the patient has experienced prolonged uremia (>7 to 14 d) such that the urea nitrogen value is high (>80 mg/dL [28.6 mmol/L]), the dialysis prescription must be modified so there is less time or clearance to avoid disequilibration syndrome. Disequilibration syndrome, characterized by increased intracranial pressure, headaches, nausea, vomiting, seizures, and even coma, is caused by the rapid reduction of serum osmolality associated with the dialytic removal of urea. Rapid decreases in serum osmolality may increase the risk of intraventricular hemorrhage. Thus, the initial dialysis may be shortened in duration or the blood flow rate may be reduced so the blood urea nitrogen falls by only 40%. The use of mannitol and sodium modeling also may ameliorate the effects of falling osmolality. When the initial dialysis is limited in duration, it is usually appropriate to perform dialysis the following day.For patients who have persistent acute renal failure or those who are receiving chronic dialysis, it is appropriate to perform dialysis so there is a greater than 70% reduction in urea compared with predialysis values. Due to fluid considerations, infants may need to be dialyzed more often, with a daily to four times weekly dialysis schedule being optimal.The inherent functions of the kidney include: 1) maintenance of fluid balance, 2) acid-base homeostasis, 3) electrolyte balance, 4) blood pressure control, 5) removal of nitrogenous wastes, 6) production of the active form of vitamin D (1,25 dihydroxyvitamin D), 7) production of erythropoietin, 8) excretion and metabolism of drugs and toxins, and 9) filtering without losing critical serum proteins or blood cells. Hemodialysis cannot effectively replace the synthetic function of the kidney. Thus, most infants require active vitamin D replacement therapy and erythropoietin therapy. Active forms of vitamin D, including calcitriol, doxercalciferol, and paricalcitol, typically are infused intravenously after the dialysis session. Precursor forms of vitamin D cannot be used because they depend on the kidney for conversion to the active form of 1,25 dihydroxyvitamin D. The efficacy of vitamin D therapy is monitored by measuring intact parathyroid hormone levels.Erythropoietin, or the longer acting darbepoetin, commonly is infused intravenously after dialysis to achieve hemoglobin values in the 11 to 12 g/dL (110 to 120 g/L) range. Oral and intravenous iron therapy typically is used to maintain an iron replete state, indicated by ferritin levels greater than 100 ng/mL (100 mcg/L) and transferrin saturation greater than 20%.Hypotension is one of the most common complications experienced during the dialysis of a neonate. The hypotension invariably is due to the excessive removal of intravascular volume within a given time. When fluid is removed, extravascular fluid is mobilized from the interstitial spaces and from intracellular locations. The rate of refill varies between patients and often within the same patient during the dialysis session. Although the monitoring of heart rate, central venous pressure (if available), and blood pressure can provide important clues to the patient’s volume status, the use of devices that continuously monitor the hematocrit are essential for the safe dialysis of neonates. The hematocrit correlates well with the patient’s intravascular volume. As intravascular volume decreases, the hematocrit rises. The rate of hematocrit increase is an excellent predictor for volume depletion-mediated hypotension. Early intervention by reducing the rate of ultrafiltration or infusing a small amount of crystalloid or colloid can prevent hypotension.CRRT has become the mainstay of critical care dialysis treatment due to its ability to remove fluid slowly without causing hypotension and its unparalleled clearances of uremic toxins. In the past, CRRT was primarily continuous arteriovenous hemofiltration, in which the patient’s own blood pressure/cardiac output shunted blood from the arterial side of the circuit, via the hemofilter, to the venous side. Problems with circuit clotting and poor blood flow in the circuit led to increasing disfavor with this approach. Subsequently, the use of CRRT machines with a blood pump has allowed physicians to regulate the blood flow through the hemofilter and to use dual-lumen or two single-lumen venous catheters for CRRT. Venovenous-based CRRT has expanded use of this modality beyond the management of renal failure to use in patients who have sepsis, acute respiratory distress syndrome, or hepatic failure. Thus, use of CRRT is increasing in the neonatal intensive care unit.There are four different types of CRRT commonly used in neonatal intensive care units (Figure 1). Slow continuous ultrafiltration (SCUF) simply uses the hemofilter to ultrafiltrate a regulated amount of fluid per hour. SCUF is used most often in concert with ECMO. The hemofilter afferent limb is placed postpump, with pressure tubing to provide resistance along the circuit path, and the efferent limb is returned to the prepump bladder. A CRRT machine typically is not used to provide SCUF. Ultrafiltration rates typically are regulated using a simple intravenous pump. SCUF provides extremely low clearance rates and is used most often when urine output is not sufficient to maintain the patient in a euvolemic state.Continuous venovenous hemofiltration (CVVH) usually employs a CRRT machine to regulate ultrafiltration, but unlike SCUF, a pre- or postdilution fluid (also known as replacement fluid) is infused into the blood path. When infused at low rates, the replacement fluid may be normal saline. With higher rates, the replacement fluid must the of the blood more Some centers have used premixed dialysis solutions as the replacement use The CRRT machine the volume of fluid that to be from the patient and the entire volume of replacement Most centers to the replacement fluid the hemofilter to the of clotting. When replacement fluid is infused the clearance of urea and other solutes is less than if the fluid was infused including the concentrations are in those who have sepsis, are much better with hemofiltration continuous venovenous than with SCUF. clearance is greater when ultrafiltration rates are higher because of the effects of As water the membrane in to ultrafiltration, including and with the replacement fluid is not but dialysis fluid is infused to the blood flow. dialysis solutions are including those that are The CRRT machine regulates the to remove the volume of the dialysate and the ultrafiltration, hemofiltration with a replacement and dialysis. Clearances are with and may be greater than 100 mL/min per dialysis prescription for CRRT is different than for dialysis. Blood flow rates in mL/min are to surface area or 5 to 10 per minute and are similar to those used in hemodialysis. no manufacturers neonatal blood tubing for CRRT. Blood circuit typically range from to 120 thus requiring blood of the circuit for neonates. hollow fibers can be using or The which often are more for neonates, may a particularly in neonates who are Replacement fluid and dialysis fluid rates are on the clearance. patient fluid removal and replacement fluid rates are to be less than of the blood flow rates of fluid removal to a greater risk of circuit are two for in heparin and typically is as a to infused at a rate of 10 per hour. The of the can be by measuring time which should be maintained at to 100 or by clotting time which should be maintained at to frequently are more with which can be at using However, may not neonatal intensive care the of using the the infant at greater risk of The risk of an intracranial is higher when heparin is particularly in the presence of hemodynamic of the advantages of citrate is that it can be used to provide to only the CRRT circuit path. This is by infusing citrate into the afferent limb of the blood circuit path. is infused via central in a site from the catheter used for CRRT. The citrate is to maintain a circuit calcium at a very low concentration of to Blood not when the calcium is low because of the of and on calcium to form a Initial citrate rates per are two times the blood flow rate is in For if a blood flow rate is the initial citrate is mixed in normal is infused at a rate to times the citrate calcium concentrations should be maintained in the normal range of to The patient and circuit calcium concentrations should be monitored a rate of calcium and citrate can be after which the of monitoring can be decreased in a hypotension due to the can be when using the are at particular risk because of their small blood relative to the blood prime The can be by making that the patient is not and that the of the blood prime is greater than The presence of an who can manage the blood pressure at the time of CRRT is bicarbonate, calcium 5% albumin, and of that are one of normal can be used to maintain normal blood monitoring of the blood with a to the values to the can be very helpful. CRRT slowly and dialysis and replacement fluid within the minute of CRRT also may be of clearance differs in patients receiving CRRT, so in should be made using and the in 2 to the is potential of CRRT. intravascular volume is due to excessive intravascular fluid intravascular volume by continuously monitoring the hematocrit may be a to intravascular volume thus who have and have been receiving CRRT may need to be to daily dialysis for of renal there can be problems with or metabolic when citrate is used. A more rapid dialysis fluid rate can be as can of calcium and reduction in citrate and calcium management of with hemodialysis can be Most infants experience a decrease in blood during hemodialysis. If the child also has an significant hypotension can often are prior to hemodialysis. If the infant at the of dialysis, the can be with less risk of severe hemodialysis and CRRT has to the risks for small neonates or infants. Most infants can be dialyzed successfully acute renal failure or they a renal use of CRRT in the neonatal intensive care is due to continuous fluid removal, which frequently is