In NICUs, the use of dialysis in premature infants who are susceptible to AKI owing to their immaturity or exposure to infection and toxins is gradually increasing [4, 5, 17]. However, to date, there is no guideline-based evidence regarding the indications and methods of RRT for premature infants. If renal failure has not been resolved despite medical treatments, the timing and method of dialysis are selected on the basis of the decision of the primary care physician [8, 20, 21]. As a result, the prognosis of premature infants with AKI treated with RRT is expected to change. Especially, ELBW infants are at very high risk for AKI, but few studies have suggested criteria for successful dialysis in ELBW infants with AKI. Although a recent study reported the experience of PD in 3 ELBW infants, all infants were applied different types of the peritoneal catheters and technical methods without same guideline . Therefore, despite dialysis, their mortality is quite high because patients' organs are immature and, therefore, often have other organ failures .
Although infrequently reported , hemodialysis (HD) still may not be the treatment of choice in neonatal overdoses for the following reasons: (1) extracorporeal blood volumes for hemoperfusion are relatively large and maintenance of the circulatory dynamics in premature infants is challenging; (2) hemoperfusion filters require heparin to maintain patency; and (3) thrombocytopenia is a common complication of hemoperfusion. These factors can increase the risk of intracranial hemorrhage in neonates [20, 24]. Especially in ELBW infants, who have unstable blood pressure and in whom obtaining vascular access is difficult, HD can be barely applied effectively. Alternatively, continuous renal replacement therapy (CRRT) is also challenging in severely ill neonates where PD may not be suitable such as for patients with previous abdominal surgery. There are some limitations of CRRT in neonates. These include vascular access, bleeding complications, and lack of neonate-specific devices. An adequately-sized central venous access is needed to accommodate adequate blood flow rates and a CRRT machine meant for neonates should be adapted [26, 27]. A few studies have reported the use of CRRT in the NICU [25-27]. Although CRRT practices can be modified to fit the needs of neonates including preterms, there is a need for a device designed specifically for this population [25-27].
Over the years, PD has become an effective and increasingly popular alternative to HD in the management of critically ill neonates, including premature infants [9, 28]. PD has been relatively safe, technically simple, and cost-effective. It can also be applied in hemodynamically unstable premature infants [2, 8, 12, 28]. The catheter design, implantation site, and system configuration used to perform dialysis determine the effectiveness of PD in premature infants. However, the most common difficulty in PD is the introduction of a suitable peritoneal catheter for these patients. Obtaining catheter access for PD is more difficult in ELBW infants than in older neonates because of their small size and inelastic abdominal wall.
Permanent PD catheters (e.g., Tenckhoff catheter) with cuffs are very rigid and long for the small intra-abdominal cavities of infants. They need to be tunneled under the skin. However, for ELBW infants, PD catheters are inserted directly through the abdominal wall, without tunneling. Therefore, the insertion of permanent PD catheters among them is not easy. Conversely, temporary PD catheters are generally inserted along with IV catheters or commercially available peritoneal catheters . Other alternatives are feeding tubes, suction catheters, neonatal chest drains, and Foley catheters [29-31]. In our study, although PD catheters were inserted to 8 of the 12 patients, IV catheters (e.g., ARROW® CVC and venous umbilical catheter) were inserted initially in another four patients owing to their low body weight. When IV catheters were used, we manually created some side holes during the procedure. We expected these holes to have better permeability to the membrane. Although these holes could have rough edges which may cause bowel perforation or intraperitoneal hemorrhage, no such complications were observed in our population. PD worked effectively in two ELBW infants with smaller-sized catheters. There was no difference in the risks of leakage, hemorrhage, and peritonitis according to the type of catheters.
Some complications associated with PD in premature infants include mechanical dysfunctions, such as dialysate leakage and catheter obstruction requiring revision or reinsertion, intraperitoneal hemorrhage, and bowel perforation [17, 20, 32]. 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 [21, 33]. In this study, the complications observed in relation to PD were mainly caused by catheter-related dialysate leakage, which was resolved after adjustment of the dwell volume or reinsertion of the catheter on the other side. In a previous study, a tissue adhesive, i.e., commercially available fibrin glue, was used at the insertion site . Therefore, selection of an optimal catheter for PD is very important to minimize the complications associated with PD access. For peritonitis, the use of prophylactic antibiotics should be carefully considered with advantages of infection prevention and disadvantages of antibiotic-resistant bacterial generation [28, 31]. The efficacy of PD in ELBW infants is affected by many factors. In ELBW infants with hypotension, peripheral perfusion is insufficient for adequate exchange. Otherwise, if they develop sepsis, which increases vessel permeability, rapid solute removal and UF capacity reduction with gradient loss may occur .
Increasing the number of exchanges, administration of large volumes of dialysate, or adjustment of the concentration of glucose in dialysis fluids may be helpful in improving dialysis efficiency . Although the number of exchanges may vary, approximately 24 exchanges per day are employed for PD. The number of exchanges is determined by the amount of fluid and solute removal required. A total of 20-40 cycles can be used; further, the procedure can be continued until the desired effect is obtained [35, 36]. The size of the peritoneal cavity, weight of the infant, presence of pulmonary or other diseases, and degree of uremic toxicity may influence the exchange volume [12, 37]. Additionally, it is rational to initiate PD using 2.5% dialysate solution to achieve better UF [12, 37]. Estimation of the peritoneal equilibration rate is necessary for optimal dialysis; however, practically frequent blood and dialysis fluid samplings are risky for ELBW infants. In our study, PD was started at a rate of 10 mL/kg, which was increased to 20-30 mL/kg at 60-120 min/cycle continuing for 24 hours.
In this study, we emphasized the major technical challenges and lack of appropriate devices to perform PD in ELBW infants with AKI. As a result, the mortality rate of the ELBW infants treated with PD was quite high (91.7%) in this study. In addition, most of the patients had findings compatible with disseminated intravascular coagulation features. In a previous study, the mortality rate was 79% in ELBW infants treated with PD; they were assumed to have died owing to underlying medical conditions and multi-organ failure rather than renal failure [20, 28]. Herein, five ELBW infants had accompanying congenital heart disease and twin-to-twin transfusion. There were concerns on negative renal recovery; initiation of dialysis may decrease the urine output and intravascular volume. These could aggravate underlying diseases, including congenital heart disease, which would consequently affect the mortality rate of ELBW infants. However, the strength of the study is that it provides data on the effect of dialysis in ELBW infants with congenital heart disease or twin-to-twin transfusion; this effect has previously been monitored in only a few studies.
In this study, the main issue was whether this population should be resuscitated. It can be very difficult to decide whether to resuscitate ELBW infants with AKI who are less likely to survive. Since these infants may face various disabilities, chronic illnesses, multiple surgeries, and severe care dependency, deciding whether to resuscitate is both a clinical and an ethical decision . A recent study has reported the degree of medical uncertainty and the fact that parents will deal with the consequences of decision making, highlighting the importance of providing a wide range of discretion in parental decision-making authority . However, neonatologists are unable to determine the individual prognosis at birth and resuscitation has to be provided quickly for it to be successful. We continue to face great opportunities disguised as insoluble problems. Although the patients in this study had quite a high mortality rate, we expect our medical challenges to produce better prognosis in this population as the limit of viability gradually decreases. Defining these limits is important for developing local guidelines that will provide standards of practice to improve the morbidity and mortality of ELBW infants and for counseling parents . Therefore, we hope that our study would be useful for developing local guidelines to both support health care practitioners and provide consistency of care for extremely preterm infants.
Recent studies have shown that acute PD is still an appropriate treatment option for VLBW newborns with AKI [15, 32, 40]. Furthermore, some studies have reported PD experiences in extremely immature infants [14, 17, 20-23, 31, 40, 41]. Although this study has an increased mortality rate for ELBW infants who underwent PD, these technical challenges can be overcome. Improvised PD systems and catheters in ELBW infants may produce results comparable to those of VLBW infants. The outcomes of ELBW infants with AKI would then be greatly improved.
Our study also has some limitations. First, it was a retrospective study of a relatively small number of infants conducted at a single center; thus, the findings might not extrapolate to a larger population. Second, our data do not provide evidence regarding whether nutritional intake of ELBW infants causes high morbidity and mortality rates in maintenance dialysis. Lastly, this study did not include premature infants with contraindications of PD, such as NEC, severe respiratory failure, and hemorrhagic tendency. The intrusion of the peritoneal cavity or placement of multiple abdominal drains can be attributed to these contraindications. Given the available data on the comparison between ELBW infants with and without PD for AKI, we should consider the technical difficulties of PD and alternatives to HD for the treatment of premature infants.