Neonatal Peritoneal Dialysis

Abstract

After completing this article, readers should be able to: Peritoneal dialysis (PD) is generally considered the optimal dialysis modality for neonates. PD allows for the slow removal of fluid and solutes while avoiding hemodynamic instability. It is technically simple and, when necessary, can be performed continuously in the neonate hospitalized in the neonatal intensive care unit.In this review, we discuss the salient features of neonatal PD, including the rationale and indications for PD, its advantages and disadvantages, the PD prescription, nutritional considerations for the neonate undergoing PD, and the management of peritonitis.Acute renal failure is common, occurring in as many as 23% of neonates hospitalized in neonatal intensive care units. There are excellent reviews in the literature that discuss the causes, pathophysiology, and medical management of acute renal failure in the neonate (see Acute Renal Failure Management in the Neonate in this issue of NeoReviews). A partial list of the causes of acute renal failure in neonates is provided in Table 1.The decision to initiate dialysis typically is necessitated by recalcitrant electrolyte abnormalities, worsening uremia, fluid overload, persistent acid-base abnormalities, or the requirement for increased fluid intake to achieve adequate nutrition in a patient who has oliguria or anuria. There may be a reluctance to initiate dialysis due to the transient nature of acute renal failure, the general effectiveness of medical management, and the perceived risks associated with PD or hemodialysis. The advantages and disadvantages of the different dialysis modalities available are reviewed in Table 2.For the neonate who has acute renal failure and typically requires a relatively brief duration of dialysis, the decision to perform dialysis is affected largely by the size of the infant. Although effective and successful dialysis has been reported in infants weighing less than 1 kg, these cases are fraught with difficulty. Table 3 provides a list of catheters that can be used for PD in neonates and infants.When managed properly, dialysis is a lifesaving technique in neonates who have acute renal failure; outcome studies have reported survival rates of 50% to 90%. Neonates who have nonoliguric renal failure may have a better prognosis. Many of the neonates dialyzed for acute renal failure who die have complications not related to their dialysis or acute renal failure. There are concerns that the initiation of dialysis may lead to decreased urine output and decreased intravascular volume, which negatively affects renal recovery. Because of the difficulties in regulating ultrafiltration amounts, it is possible that the neonate receiving PD may become intravascularly depleted to the point of clinically significant hypotension. These factors need to be considered whenever dialysis is initiated for the neonate experiencing acute renal failure.The decision to initiate dialysis or continue dialysis for the neonate who has chronic renal failure often is more difficult than the decision to initiate dialysis for the management of acute renal failure. Chronic dialysis in the neonate should be used as a “bridge” to renal transplantation. Lifelong dialysis is not an option for neonates due to the diminished quality of life, greater mortality, and steady loss of vascular access or peritoneal function. The risk of mortality for an infant dialyzed for the first year after birth is in excess of 15%. Interestingly, some of these deaths are characterized as sudden infant deaths. Other infants succumb to sepsis or the complications of severe hypertension.Most transplant centers perform a deceased or living related donor renal transplant when the infant weighs approximately 10 kg or more. Outcomes in infants receiving renal transplants have improved dramatically over the last few years and now can be characterized as being excellent, with graft and patient survival rates approaching 100% at 2 years posttransplant and more than 80% at 8 years posttransplant. In a recent review of renal transplant outcomes in infants, Sarwal and associates found that renal allograft recipients ages 0 to 5 years who received adult-size kidneys without acute tubular necrosis had significantly better long-term graft survival rates than other age groups. In infants 0 to 2.5 years old who received a living related donor renal transplant without acute tubular necrosis, projected graft half-life was 26.3±5 years. However, despite excellent results with renal transplantation, some infants who have severe organ dysfunction (lung, brain, or irreparable heart disease/malformation) should not be dialyzed and transplanted if the only benefit is to prolong life.PD is considered to be the best long-term dialytic modality for neonates. It is technically simple, can be performed at home, allows for slow fluid removal (which is better tolerated from a hemodynamic standpoint), and avoids a key problem that occurs with hemodialysis catheters—the sclerosis or thrombosis of blood vessels that are likely to be needed for renal transplantation in the future.The peritoneal membrane, which overlays the vessels surrounding the visceral and parietal surfaces in the abdomen, acts as a semipermeable membrane to fluid and solutes. Recent research has indicated that there are three distinct sizes of pores: ultrasmall, small, and large. These pores play a role in regulating the permeability of the membrane. Although ultrasmall pores account for only 1% to 2% of the total peritoneal pore area, 40% of the water flow occurs through these pores. Subject to concentration gradients and osmotic gradients, the small pores are responsible for the transit of most of the water and solute across the membrane. Large pores, accounting for 5% to 7% of the total pore area, allow for the movement of large proteins, including albumin and immune globulin, in response to hydrostatic pressure.Any dialytic modality must accomplish two goals. First, high levels of nitrogenous wastes must be removed while maintaining electrolyte and acid-base stability. The process of diffusion or dialysis achieves this goal. Second, accumulated fluid, not removed by the kidneys, must be removed so the neonate can receive sufficient nutrition. This process is called ultrafiltration.PD facilitates fluid removal and solute removal by placing a hyperosmolar solution composed of dextrose, sodium, chloride, lactate, magnesium, and calcium in the peritoneum (Table 4). Fluid removal can be increased by increasing either the PD dextrose concentration, the amount of fluid in the peritoneum, or the frequency of exchanges. Commercially available PD solutions have dextrose concentrations of 1.5% (1,500 mg/dL), 2.5% (2,500 mg/dL), and 4.25% (4,250 mg/dL). The higher the dextrose concentration, the greater the fluid osmolality. For example, 1.5% dextrose PD fluid has an osmolality of approximately 347 mmol/L, while 4.25% dextrose PD fluid has an osmolality of approximately 500 mmol/L. The amount of fluid that can be removed from an infant correlates positively with PD fluid osmolality. From a practical standpoint, the PD dextrose concentration can be adjusted more finely to achieve the desired rate of fluid removal by mixing ratios of differing dextrose-containing PD fluids.Despite the great value of dextrose in this application, it is hampered by being easily absorbed from the peritoneum. This is particularly challenging for neonates, who often have high-transport peritoneal membranes that facilitate rapid absorption of dextrose and rapid diffusion of solutes such as urea and creatinine. For many neonates, the rapid uptake of dextrose reduces ultrafiltration relative to older children, who have comparably lower transport membranes. Often, this means that high dextrose concentrations (2.5% to 4.25%) are used initially to achieve adequate fluid removal in neonates, especially in neonates who receive initial low PD volumes of less than 10 mL/kg. The use of more PD fluid in the abdomen correlates with greater ultrafiltration as more of the peritoneal membrane is in contact with the PD fluid and there is a greater total amount of dextrose to achieve ultrafiltration. However, when more PD fluid is placed in the abdomen, there is a greater risk of leakage around a newly placed catheter.PD cannot be used successfully for every neonate who has renal failure. Those who have significant pulmonary disease may experience worsening respiratory status or ventilatory parameters due to the limitation of diaphragmatic excursion when there is a significant amount of fluid in the abdomen. Diaphragmatic hernias, which typically occur on the left side of the abdomen, may allow significant amounts of PD fluid to enter the pleural space from the abdomen, thus compromising the neonate’s respiratory status. Recognition of this problem can be expedited by testing the glucose concentration of the fluid removed from the chest. Patients in whom PD fluid leaks into the pleural space can be expected to have high pleural fluid dextrose values.Neonates who have abdominal wall defects, including omphalocele or gastroschisis, are not candidates for PD. Infants who have had frequent or extensive abdominal surgery may have a relative contraindication to PD due to the development of adhesions that limit the contact of dialysis fluid with the surface of the peritoneum. Other relative contraindications to PD include vesicostomies, colostomies, prune belly syndrome, necrotizing enterocolitis, and malignancies.PD catheters (Table 3) are fabricated of soft Silastic®, which is smooth silicone polymer of methyl-silicate, either in curled or straight configurations. Most of the catheters have side holes that allow for easy ingress and egress of fluid regardless of the catheter position in the peritoneum. Permanent catheters have cuffs, which typically are fabricated from Dacron®. The distal cuff, which should be placed approximately 2 cm proximal to the exit site, acts as a barrier to bacterial transgression along the catheter into the peritoneum. Pig-tail catheters and straight catheters without cuffs have been used in neonates who are anticipated to need PD access for a brief period of time.Catheters can be inserted either through the linea alba or laterally or paramedially through the rectus muscle directly into the peritoneum. For permanent catheters, the catheter is tunneled under the skin and should exit facing downward (caudad). For very small neonates, the PD catheter is inserted directly through the abdominal wall, without tunneling. It is desirable to place the PD catheter exit site outside of the diaper area to decrease the risk of soaking the PD catheter exit site with urine or contaminating the site with feces. In an effort to achieve an optimal water-tight seal without having bacterial colonization along the PD catheter, some programs place the entire external portion of the catheter in the tunnel for 2 weeks, then perform a second procedure to expose the external portion of the catheter.The PD catheter tip generally is placed in the lower portion of the pelvis. There can be occasional problems with pain during fill and drain cycles if the catheter is adjacent to the rectum. Significant problems with hydrocele formation in neonates receiving PD have been reported. Laparoscopic closure of the hydrocele is possible at the time of PD catheter placement.The PD catheter can become occluded with fibrin or adjacent bowel. Initial PD prescriptions often add heparin (125 to 250 U/L) to the PD fluid for at least the first 1 to 2 weeks of dialysis. Proactive treatment of constipation can be extremely helpful in decreasing problems related to PD catheter function. Prolonged antimicrobial prophylaxis after PD catheter insertion is not recommended.The dialysis prescription is written with four major parameters: 1) PD fluid composition; 2) volume of PD fluid per exchange; 3) frequency and duration of exchanges, including the fill, dwell, and drain times; and 4) monitoring of patient weights and the PD fluid for signs of peritonitis. As mentioned previously, a higher PD dextrose concentration of 2.5% to 4.25% usually is selected if the patient is experiencing fluid overload or if a significant amount of intravenous or feeding volume is required. Unless the surgeons who placed the PD catheter suggest otherwise, the initial volume of fluid placed in the abdomen should be approximately 10 mL/kg per exchange. To reduce the risk of leakage around the catheter, the PD fluid volume is not increased for 1 week. For patients who have acute renal failure, it may be necessary to add potassium chloride (1 to 4 mEq/L) to the dialysis fluid to maintain potassium homeostasis. Potassium chloride is not added to the PD fluid of infants who have end-stage renal disease, although potassium supplementation can be provided orally or mixed into the feedings (rarely). The PD prescription usually starts with hourly exchanges for 24 h/d. After 1 week, once the risk of leakage around the PD catheter begins to decrease, the PD fluid volume is increased slowly over a course of weeks toward the maximum of 35 to 40 mL/kg. As the volume is increased, the total cumulative duration of the exchanges is decreased toward 8 to 15 h/d.Mathematical equations have been developed as a means to assess the adequacy of clearance by PD. The most commonly used equations to determine the efficacy of PD are the Kt/V equation and peritoneal equilibration testing (PET). Kt/V determines the adequacy of dialysis by determining the clearance of creatinine or urea relative to total body water (K=clearance, t=time, V=volume of distribution). Consensus statements indicate that a Kt/V value of 2 to 2.2 may be optimal for infants and children receiving PD. Although there is a bias toward better outcomes with greater dialysis, the CANUSA and ADAMEX studies, which were studies of adults receiving dialysis, failed to show a benefit for patients who had higher Kt/V values. Similar studies evaluating dialysis adequacy have not been performed for neonates. PET has been used extensively in pediatric patients to determine the permeability of the peritoneal membrane. Patients are categorized into high-, high average-, low average-, and low-transport groups. In general, patients in high-transport groups have excellent Kt/V values because urea and creatinine diffuse well, but have poor ultrafiltration rates because the dextrose diffuses quickly across the membrane, thereby rapidly decreasing the osmolality gradient needed for ultrafiltration. Many neonates have high-transport membranes.Nutrition is a major consideration for neonates who need dialysis. Several studies have demonstrated excellent infant growth, even in the context of poor renal function, when nutritional supplementation is provided. A goal of 100 to 140 kcal/kg per day often is needed to achieve sustained growth in the normal range. Patients may receive as much as 20% of their caloric needs from absorbed PD dextrose. Formulas low in phosphorous and potassium usually are chosen. Supplementation with carbohydrate, protein, fat (medium-chain triglyceride oil), and fat plus carbohydrate often is required to achieve the appropriate amounts of calories and nutrients. Caloric concentrations of these feedings frequently approach or exceed 1 kcal/mL. Unfortunately, nearly all neonates on dialysis need nasogastric or gastrostomy feedings to receive adequate calories. The implementation of nasogastric feedings does not require surgery or even transient discontinuation of PD. However, long-term nasogastric feedings may be complicated by oral aversion or parental and infant emotional trauma with repeated nasogastric tube insertions. Conversely, some investigators have reported that placement of a gastrostomy tube in an infant receiving PD is associated with a greater risk of fungal peritonitis.Vitamins and trace minerals are essential for the normal growth and development of infants. Supplementation with vitamins and trace minerals is necessary for infants on PD because deficiencies of water-soluble vitamins and minerals can occur with poor nutritional intake, dietary restrictions, and increased losses with dialysis. Needs also may be increased due to altered metabolism from drugs, uremia, and comorbidities. One quarter of a multivitamin tablet designed for patients receiving dialysis can be crushed and administered daily to the neonate receiving PD to provide supplementation of vitamin C, folic acid, niacin, thiamine, riboflavin, pyridoxine, pantothenic acid, biotin, and cyanocobalamin.Given the relatively high ultrafiltration rates required to maintain fluid balance, many neonates require sodium supplementation. Ultrafiltrate sodium values are approximately 70 to 100 mEq/L (70 to 100 mmol/L). If a 3-kg infant has 300 mL of ultrafiltrate per day, sodium losses can approximate 10 mEq/kg (10 mmol/kg) per day. Failure to add sodium chloride in the feedings can lead to catastrophic hyponatremia. In some cases, sodium bicarbonate is added to the feedings to maintain normal serum bicarbonate values. With rigorous dialysis, neonates may develop hypophosphatemia due to excessive losses with dialysis. Sodium phosphate or, in rare cases, sodium plus potassium phosphate can be added to feedings to maintain a normal serum phosphorus level, which is important for normal bone mineralization.Some neonates have extensive losses of albumin and immunoglobulin with PD. Avoidance of overdialyzing can reduce the losses of these critical proteins. Low serum albumin levels may lead to diminished ultrafiltration due to the reduction of oncotic pressure in the intravascular space. In rare cases, neonates may require intravenous 25% albumin infusions to maintain serum albumin levels between 2.5 and 3 g/dL (25 and 30 g/L). Increased dietary protein of 3 to 4 g/kg per day can help to maintain a more normal serum albumin concentration. Because carnitine deficiency is common in neonates undergoing dialysis, dietary supplementation with carnitine also may be necessary.The use of intravenous immune globulin (IVIG) in neonates is controversial. Bouts and associates found that immunoglobulin deficiencies occurred more frequently in children receiving peritoneal dialysis, likely due to protein losses in PD effluent, and that a high incidence of peritonitis was associated with reduced serum immunoglobulin levels. However, the use of IVIG may cause anaphylaxis, hypotension, fever, or hypertension (due to an increase in intravascular volume). IVIG use should be discouraged in neonates who have significant lung and heart disease, including left ventricular hypertrophy, because of a low tolerance for anaphylactic events.Bacterial peritonitis often is caused by a tunnel infection or an inadvertent break in the sterile handling of the PD catheter tubing set or transfer set. The clinical signs and symptoms of peritonitis include cloudy peritoneal fluid, feeding intolerance, irritability, pain, and fever. However, lack of a fever does not exclude the possibility of peritonitis. Peritonitis can be diagnosed by performing a peritoneal fluid cell count, differential count, Gram stain, and culture. A presumptive diagnosis of peritonitis can be made when there are more than 100 leukocytes/mm3, with more than 50% polymorphonuclear cells. Fluid that has been in the peritoneum for more than 4 hours may have more than 100 leukocytes/mm3 due to the normal egress of leukocytes into the peritoneum. In this situation, the differential count should be normal, and treatment with antibiotics is not indicated.The treatment of peritonitis in children has been well defined by the Clinical Process for Optimal Outcomes guidelines published by the International Society for Peritoneal Dialysis (ISPD) Advisory Committee on Peritonitis Management in Pediatric Patients. Although intravenous therapy is effective in the treatment of bacterial peritonitis, neonates are treated empirically using intraperitoneal vancomycin and ceftazidime. After obtaining fluid for cell count, differential count, Gram stain, and culture, two to three rapid PD exchanges can be used to reduce pain followed by a loading dose of intraperitoneal antibiotics (vancomycin 500 mg/L, ceftazidime 250 mg/L) in the abdomen for 4 hours. Heparin (125 to 250 U/L) is added to the PD fluid to reduce problems related to fibrin, which is increased during peritonitis. After the initial loading dose of intraperitoneal antibiotics, the antibiotic doses are reduced (vancomycin 30 mg/L, ceftazidime 125 mg/L), and the patient is maintained on continuous (24 h/d) dialysis, often with longer exchange times. Because of the increased risk of secondary fungal peritonitis, consideration should be given to initiating prophylactic antifungal therapy consisting of either oral nystatin or fluconazole. When the PD fluid clears and the leukocyte count is less than 100/mm3, the dialysis prescription prior to the patient’s episode of peritonitis can be resumed, provided that intraperitoneal antibiotics are continued for 2 to 3 weeks. Patient outcomes after bacterial peritonitis are generally good, with most children able to continue PD without removal of their PD catheter.Fungal peritonitis, typically caused by Candida sp, is more common in PD-dependent neonates who have recently received antibiotic therapy. Treatment with intravenous amphotericin, liposomal amphotericin, fluconazole, itraconazole, or caspofungin is rarely sufficient to clear the infection. In a reported cohort series, PD catheter removal was necessary in 90% of children who had fungal peritonitis, and 24% of the children who had an episode of fungal peritonitis remained on hemodialysis 6 months later.Occasionally, infants present with cloudy peritoneal fluid but do not have other indicators of infection; examination of the peritoneal fluid reveals large numbers of eosinophils. Eosinophilic peritonitis, diagnosed when eosinophils represent more than 10% of the total dialysate polymorphonuclear leukocyte count, commonly is associated with the development of cloudy effluent in an asymptomatic patient new to PD. Although the exact mechanism of eosinophilic peritonitis is not known, it is believed that an allergic reaction to the PD catheter material or to components of the dialysis fluid is most likely. Reduction of the PD fluid dextrose concentrations and time on PD typically enhances the speed of spontaneous resolution.Peritoneal fluid leakage around the PD catheter and along the tunnel is a serious problem that can increase the risk of bacterial and fungal peritonitis. PD can be confirmed as the source of a PD catheter exit site leak when a dextrose-detecting strip dipped in the liquid indicates a high dextrose concentration. Management strategies include discontinuation of PD in favor of hemodialysis, placement of a new PD catheter (rare), temporary discontinuation of PD for 2 to 7 days, or substantially decreasing the PD fill volume.Extravasation of PD fluid through a diaphragmatic hernia into the pleural space is a contraindication for continuation of the therapy. Any patient who has a diaphragmatic hernia should be considered for conversion to hemodialysis.PD is a basic, rational, and feasible mode of dialysis for neonates who have renal failure. In the acute setting of a neonatal intensive care unit, continuous PD performed in a neonate who has acute renal failure provides a technically simple method of steady fluid and solute removal and correction of electrolyte abnormalities with less risk of hemodynamic instability. Outside of the hospital, PD is a practical mode of dialysis for infants who have chronic renal failure and allows for daily, home-based, renal replacement therapy.