Pediatric Candidates Research Articles

Preventable Death: Children on the Transplant Waiting List

Children, especially those under 5 years of age, have the highest death rate on the transplant waiting list compared to any other age range. This article discusses the concept, supported by OPTN data, that there is an age range of small pediatric donors, which are almost exclusively transplanted into small pediatric transplant candidates. Allocation policies that allow broader sharing of small pediatric donors into small pediatric candidates are likely to decrease death rates of children on the waiting list. As well, although the number of pediatric deceased donors continues to decline, improving consent rates for eligible pediatric donors, and judicious use of pediatric donors after cardiac death, can enhance the pediatric deceased donor supply.

Abstract 6072: Waitlist Mortality for Infants Awaiting Heart Transplantation in the United States in the Current Era: Analysis of Data from the United Network for Organ Sharing

BACKGROUND UNOS (United Network for Organ Sharing) data suggest that of all pediatric transplant candidates, infants awaiting heart transplantation face the highest waitlist mortality. We sought to determine the mortality rate for waitlisted infants in the current era and to identify the risk factors associated with waitlist mortality. METHODS In this multi-center cohort study using the US Scientific Registry of Transplant Recipients, we analyzed all infants <12 months of age listed for first heart transplant between January 1999 and July 2006. Clinical and demographic characteristics were recorded at the time of listing. Multivariate logistic regression modeling was used to identify predictors of waitlist mortality. RESULTS In this six year period, 1133 patients less than 12 months of age were identified with a median age of 1 month (IQR 0 to 5 mo) and median weight of 4.0 kg (IQR 3.2 to 5.6 kg). 516 (45%) were female, 438 (39%) were non-white, 724 (64%) had congenital heart disease (CHD) and 910 (80%) were listed status 1A. Overall, 250 (22%) died while waiting including 179 (72%) listed at age <3 mo, 190 (76%) with CHD, 89 (35%) listed on mechanical ventilation, and 68 (27%) on ECMO. In multivariate analysis, risk factors for waitlist mortality (reported as hazard ratio, 95% CI) included age <3 months (1.5, 1.1–2.0), CHD (2.0, 1.5–2.7), ventilator support (2.0, 1.5–2.7), ECMO support (5.0, 3.6 –7.0) and non-white race (1.7, 1.4 –2.2). CONCLUSION Mortality of infants waiting for heart transplantation remains high with a 22% waitlist mortality in the current era. ECMO support, ventilator support, CHD, age less than 3 months, and non-white race were independently associated with waitlist mortality whereas listing status was not. Measures to improve donor availability for this age group and refinements in organ allocation to lower waitlist mortality are urgently needed.

Patient selection critical for calcineurin inhibitor withdrawal in pediatric kidney transplantation

CNI withdrawal may be employed as a "rescue" strategy for patients with established renal allograft injury and/or declining allograft function, with the aim at eliminating CNI-associated nephrotoxic effects. This analysis reviews outcomes in a pediatric population and identifies risk factors for adverse events post-CNI withdrawal. We performed a retrospective analysis of 17 pediatric renal transplants who underwent CNI withdrawal, with conversion to sirolimus and MMF. Mean CrCl decreased from 64.3 +/- 22 to 59.38 +/- 28.6 mL/min/1.73 m(2) (p = 0.04) at six months and 57.46 +/- 31.1 mL/min/1.73 m(2) (p = 0.02) at 12 months post-withdrawal. Forty-one percent of patients experienced AR. Increased risk for AR was associated with prior AR history, lower sirolimus trough levels, and lower CNIT biopsy scores. Graft loss (24%) was associated with worse CrCl, proteinuria, and histologic chronicity. Proteinuria (spot protein/creatinine ratio) increased from 0.75 +/- 1.0 to 1.71 +/- 2.0 (p = 0.03), unrelated to de novo sirolimus use. Four patients returned to CNI-based immunosuppression due to AR (n = 3) and gastrointestinal side effects (n = 1). Careful selection of pediatric candidates for CNI withdrawal is recommended. Worsening graft function and graft loss may be minimized by selecting patients with high CNIT scores and low biopsy chronicity and excluding patients with prior AR history.

Pediatric intestinal and multivisceral transplantation: a new challenge for the pediatric intensivist.

IntroductionWith increasing survival rates, intestinal transplantation (ITx) and multivisceral transplantation have reached the mainstream of medical care. Pediatric candidates for ITx often suffer from severe multisystem impairments that pose challenges to the medical team. These patients frequently require intensive care preoperatively and have unique intensive care needs postoperatively.MethodsWe reviewed the literature on intensive care of pediatric intestinal transplantation as well as our own experience. This review is not aimed only at pediatric intensivists from ITx centers; these patients frequently require ICU care at other institutions.ResultsPreoperative management focuses on optimization of organ function, minimizing ventilator-induced lung injury, preventing excessive edema yet maintaining adequate organ perfusion, preventing and controlling sepsis and bleeding from varices at enterocutaneous interfaces, and optimizing nutritional support. The goal is to extend life in stable condition to the point of transplantation. Postoperative care focuses on optimizing perfusion of the mesenteric circulation by maintaining intravascular volume, minimizing hypercoagulability, and providing adequate oxygen delivery. Careful monitoring of the stoma and its output and correction of electrolyte imbalances that may require renal replacement therapy is critical, as are monitoring for and aggressively treating infections, which often present with only subtle clinical clues. Signs of intestinal rejection may be non-specific, and early differentiation from other causes of intestinal dysfunction is important. Understanding of the expanding armamentarium of immunosuppressive agents and their side-effects is required.Conclusions As outcomes of ITx improve, transplant teams accept patients with higher pre-operative morbidity and at higher risk for complications. Many ITx patients would benefit from earlier referral for transplant evaluation before severe liver disease, recurrent central venous catheter-related sepsis and venous thromboses develop.

Predominance of Genetic Diagnosis and Imaging Results as Predictors in Determining the Speech Perception Performance Outcome After Cochlear Implantation in Children

To investigate the roles of genetic diagnosis and imaging studies, as well as other prognostic factors, in predicting outcomes in children with cochlear implant. Prospective cohort study. Tertiary referral center. Sixty-seven consecutive children with sensorineural hearing impairment who had at least 3 years of experience with cochlear implant. Imaging of the inner ear was done with high-resolution computed tomography, and mutations were screened in 3 genes commonly associated with pediatric hearing impairment: GJB2, SLC26A4, and the mitochondrial 12S ribosomal RNA gene. Speech perception performance was compared according to genetic diagnosis and imaging data. A general linear model was constructed to demonstrate the predictive values of specific genetic and imaging results after adjusting for other factors. Main Outcome Measure Recognition scores on speech perception tests. Twenty-two children (33%) showed genetic mutations: 18 with SLC26A4 and 4 with GJB2 mutations. According to imaging findings, 33 children (49%) showed inner ear malformations: 9 with a narrow internal auditory canal and 24 with other malformations. All children with SLC26A4 or GJB2 mutations exhibited excellent speech recognition scores, whereas a narrow internal auditory canal was associated with poorer outcomes (P < .001 in all recognition scores). The general linear model confirmed that both a narrow internal auditory canal (P < .001) and SLC26A4 mutations (P = .04) correlated with speech perception outcome. Genetic diagnosis and imaging results are the 2 predominant factors determining the outcome in children with cochlear implants. In pediatric candidates for cochlear implantation, both genetic examination and imaging studies should be included in the battery of preoperative evaluations.

Model for end-stage liver disease (MELD) for liver allocation: A 5-year score card

Model for end-stage liver disease (MELD) for liver allocation: A 5-year score card

Trends in Organ Donation and Transplantation in the United States, 1996–2005

This brief overview of solid organ transplantation in the United States is produced as part of the 2006 OPTN/SRTR Annual Report. The Annual Report is prepared by the Scientific Registry of Transplant Recipients (SRTR) in collaboration with the Organ Procurement and Transplantation Network (OPTN) under contract with the Health Resources and Services Administration (HRSA). The report gathers a large amount of information on many aspects of solid organ transplantation in one publication, making it a valuable resource for patients, the transplant community, the public and the Federal Government.

Renal transplantation in the valve bladder: is bladder augmentation always necessary?

Purpose In patients with a fibrotic bladder secondary to posterior urethral valves (“valve bladder”), pre-emptive bladder augmentation is generally recommended in order to preserve graft function. We report our preliminary experience in children with renal transplantation in valve bladders without a preliminary augmentation. Material and methods Out of 151 pediatric candidates for renal transplantation, 15 presented with a valve bladder and were considered candidates for bladder augmentation. In 10 patients the bladder augmentation was performed prior to renal transplantation. In the remaining 5 patients with oligo/anuria the decision for the bladder augmentation was postponed to the post-transplant period. Serum creatinine, urinary ultrasound, voiding diary were re-evaluated at 1,2,3,4 and 6 months and urodynamics at 6 months follow-up. Results Out of the 5 patients, in two grafts a ureterostomy was performed. The other 3 patients had a graft ureteral reimplantation associated with a transient suprapubic catheter which allowed for frequent bladder emptying and overnight bladder drainage for 2 months. At follow-up the 3 patients had normal renal function with an absence of hydronephrosis. At 6 months bladder capacity improved from av.40% of expected capacity for age (range 30 to 65%) to av.95% (range 90 to 120%), with end filling bladder pressure Conclusions In oligo/anuric valve bladder patients it can be hard to decide whether a poorly compliant bladder is due to fibrosis or to defunctionalisation. Bladder cycling before transplantation is not always tolerated. Furthermore, pre-emptive bladder augmentation can be performed several months before transplantation. We think in selected cases bladder augmentation can be avoided before transplantation, and once the normal diuresis is restored the native bladder can show significant improvement in capacity and compliance. Frequent monitoring of graft function and bladder function is mandatory.

Donation after cardiac death in pediatric critical care*

To describe the unmet need for pediatric organs, the history of donation after cardiac death (DCD), implementation of DCD policies in children's hospitals, and the current U.S. experience with DCD in children. Review of existing literature and national data regarding DCD. Three children's hospitals and a national organ procurement network. Nationwide review of pediatric candidates for transplantation and pediatric DCD donors. None. Interest in DCD has greatly increased over the past several years due to limited organ availability for transplantation. Leading medical groups have evaluated and endorsed DCD, and more hospitals are offering DCD as part of end-of-life care options for dying patients and to increase donation. Children's hospitals need to evaluate this concept and develop ethically sound polices to meet the needs of patients and families. Preliminary reports regarding organ function from DCD donors are promising, and DCD is increasing. The widening gap between the need for organs and the availability of organs from brain-dead donors has led to a resurgence of both interest in and use of organs donated after cardiac death. Children's hospitals need to explore DCD as an option in select circumstances to serve grieving families who would like to donate and to increase organ availability for transplantation. DCD programs are dependent on input and support from critical care providers.

Living donor intestinal transplantation in pediatric recipients

Purpose of review The purpose of this review is to assess the role of intestinal transplant from living donors in the treatment of pediatric patients with irreversible intestinal failure as a potential alternative to cadaver intestinal transplant. Recent findings The use of a living donor for intestinal transplantation has recently been applied in the setting of pediatric candidates. The procedure has some potential advantages in comparison to cadaver intestinal transplantation. Of particular interest is the development of a technique for simultaneous liver/bowel transplant from living donors, because it provides an alternative treatment for a group of patients with a high risk of premature death on the cadaver waiting list. Summary Living donor intestinal transplant can offer considerable advantages in special settings, such as pediatric patients at high risk of premature death as a result of a lack of central venous access or highly sensitized candidates. The recent development of a technique for combined liver/bowel transplant from living donors may prove life-saving in this setting.

Candidates for Intestinal Transplantation: A Multicenter Survey in Europe

Epidemiology of candidacy for intestinal transplantation (ITx) and timing for referral for ITx are unknown. Patient candidacy and physician attitudes toward ITx were investigated among centers that participated in previous European surveys on home parenteral nutrition (HPN). Patients on HPN for benign intestinal failure (IF) were evaluated by a structured questionnaire. Candidacy was assessed by USA Medicare and American Transplantation Society criteria, categorized as: (1) life-threatening HPN complications; (2) high risk of death because of the gastrointestinal disease; (3) IF with high morbidity or patient HPN refusal. Physicians judged candidacy as immediate or potential. Forty-one centers from nine countries enrolled 688 adults (> 18 yr) and 166 pediatric patients; 70% of patients were from five countries which collected 60-100% of their HPN patients. Candidacy was 15.7% in adults and 34.3% in pediatrics (HPN failure, 62.1% and 28.1%; gastrointestinal disease, 25.9% and 59.6%; high morbidity IF or HPN refusal, 12.0% and 12.3%, respectively). Immediate candidacy was required for 14.8% of adult and 15.8% of pediatric candidates (< 50% of candidates because of HPN-related liver failure). Among centers, the candidacy rate ranged 0-100% and was negatively associated with the number of patients enrolled in the survey (R = -0.463, p = 0.002). Among the major contributing countries, candidacy ranged 0.3-0.8/million inhabitants for adults and 0.9-2/million inhabitants < or = 18 yr for pediatric candidates. The rate of candidacy and the indications for ITx candidacy differed greatly among age groups and HPN centers; within countries candidacy was more homogeneous; physicians had a generally reserved attitude toward ITx.

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Pediatric Transplantation in the United States,1995–2004

This article reviews trends in pediatric solid organ transplantation over the last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18 years made up nearly 3% of the 86,378 candidates for organ transplantation and nearly 7% of the 27,031 organ transplant recipients. Children accounted for nearly 14% of the 7152 deceased organ donors. The transplant community recognizes important differences between pediatric and adult organ transplant recipients, including different etiologies of organ failure, surgical procedures that are more complex or technically challenging, effects of development on the pharmacokinetic properties of common immunosuppressants, unique immunological aspects of transplant in the developing immune system and increased susceptibility to posttransplant complications, particularly infectious diseases. For these reasons, and because of the impact of end-stage organ failure on growth and development, the transplant community has generally provided pediatric candidates with special consideration in the allocation of deceased donor organs. Outcomes following kidney, liver and heart transplantation in children often rank among the best. This article emphasizes that the prospects for solid organ transplantation in children, especially those aged 1-10 years are excellent. It also identifies themes warranting further consideration, including organ availability, adolescent survival and challenges facing pediatric transplant clinical research.

Innovative Approaches to Improving Organ Availability for Small Bowel Transplant Candidates

Small bowel transplant candidates have unique features that create special challenges for providing them with organs in a timely manner. More than half of intestinal transplant candidates also need livers. Because there is a greater overall demand for livers than for small bowels, organ allocation in this candidate subset is dictated by the liver allocation policies. However, the extremely high mortality rate associated with patients on the waiting list for combined liver-intestinal transplantation (LIT) attests to the inadequacies of the liver allocation system in recognizing the unique risk factors in patients with intestinal failure who develop end-stage liver disease (ESLD). This report addresses some of the organ allocation issues underlying the discrepancies in waiting list outcomes seen in LIT candidates and discusses possible contributory factors and potential solutions to this problem. The use of living donor and segmental grafts from deceased donors are discussed specifically as potential surgical solutions to the problem, and the potential utility, limitations, and ethical concerns associated with these innovative strategies are discussed.

Trends over a decade of pediatric liver transplantation in the United States

During the last 10 to 15 years, medical and surgical innovations have established pediatric liver transplantation as the optimal therapy for children suffering acute and chronic liver disease. We hypothesized that the profile of current pediatric liver transplant recipients would differ significantly from that of an earlier era. We collected and compared data regarding the characteristics of children undergoing liver transplantation alone in 2 eras separated by more than a decade from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Transplant recipients from March 1, 2002 to December 31, 2004, compared to those from January 1, 1990, to December 31, 1992, tended to be more evenly distributed across age, race/ethnicity, and disease etiology. There was a major shift toward utilization of partial grafts from both deceased and living donors to achieve transplantation for the youngest children (<1 and 1-5 yr) in particular. However, in spite of these innovative transplant strategies and only a modest increase in demand for pediatric liver transplantation, wait list times for both pediatric candidates and recipients have still increased between eras. In conclusion, the sobering reality that mortality on the waiting list remains highest for the youngest pediatric liver candidates frames our challenge for the next decade.

我々の臨床に於ける幼児の人工内耳適応の考え方と療育指導の方法論について

我々の臨床に於ける幼児の人工内耳適応の考え方と療育指導の方法論について

Spoken Word Recognition Development in Children with Residual Hearing Using Cochlear Implants and Hearing Aids in Opposite Ears

With broadening candidacy criteria for cochlear implantation, a greater number of pediatric candidates have usable residual hearing in their nonimplanted ears. This population potentially stands to benefit from continued use of conventional amplification in their nonimplanted ears. The purposes of this investigation were to evaluate whether children with residual hearing in their nonimplanted ears benefit from bilateral use of cochlear implants and hearing aids and to investigate the time course of adaptation to combined use of the devices together. Pediatric cochlear implant recipients with severe sensorineural hearing loss in their nonimplanted ears served as participants. Ten children continued to use hearing aids in their nonimplanted ears after cochlear implantation; 12 children used their cochlear implants exclusively. Participants were tested longitudinally on spoken word recognition measures at 6-month intervals. The children who continued wearing hearing aids were tested in three sensory aid conditions: cochlear implants alone, hearing aids alone, and cochlear implants in conjunction with hearing aids. The children who did not continue hearing aid use were tested after surgery in their only aided condition, cochlear implant alone. The results suggest that children with severe hearing loss who continued using hearing aids in their nonimplanted ears benefited from combining the acoustic input received from a hearing aid with the input received from a cochlear implant, particularly in background noise. However, this benefit emerged with experience. Our findings suggest that it is appropriate to encourage pediatric cochlear implant recipients with severe hearing loss to continue wearing an appropriately fitted hearing aid in the nonimplanted ear to maximally benefit from bilateral stimulation.

Liver transplantation outcomes under the model for end-stage liver disease and pediatric end-stage liver disease

Purpose of review Deceased-donor liver allocation has undergone a significant change in approach and execution with the adoption of the MELD/PELD (model for end-stage liver disease/pediatric end-stage liver disease) system in February 2002. This review focuses on the key reports summarising the results of this allocation system and studies examining different aspects and deficiencies of this system. Recent findings The institution of the MELD/PELD system was preceded by several important analyses in which prospective validation of the MELD and PELD models showed they had a high degree of concordance for predicting mortality risk for adult and pediatric candidates, respectively, who were waiting for liver transplantation. Additional studies documented the rationale for the policy change and outlined the specifics of the system. Results after 1 year of allocation under this new system showed a slight reduction in waiting list mortality and an increase in liver transplant rates compared with liver allocation for the year prior. Other reports examined regional differences in MELD score at transplant, the effect of changes in priority for candidates with hepatocellular carcinoma, the effectiveness of regional review boards for identifying higher-risk candidates, and variations in MELD score calculation due to international normalised ratio laboratory technique differences as well as patient survival. Summary The MELD/PELD-based liver allocation system is a much more objective system that can be quantified and studied for results. Future modifications will be made using this evidence-based approach.

Liver Transplantation in Children Weighting Less Than 6 kg: The Bergamo Experience

Liver transpantation (OLT) remains a major medical and surgical challenge in small patients. From October 1997 through July 2004, 17 babies less than 6 kg underwent 18 OLTs. Median age and weight were 3 months (range = 1 to 9) and 4.7 kg (range = 2.2 to 5.8). Two whole, one reduced, and 15 split-liver grafts (left lateral segments) were obtained from donors of median age and weight of 11.6 years (range = 0.5 to 62) and 50 kg (range = 7 to 63). Donor-to-recipient median weight ratio (D/R) was 9.1 kg (range = 1.3 to 17.6) and median graft-to-recipient weight ratio (GRWR) was 5% (range = 3.1 to 10). The incidence of biliary complications was 23%. The only vascular complication was a portal vein thrombosis (6%). Fourteen patients (79%) are alive with good graft function at a median follow-up of 39 months (range = 0.5 to 74). Three patients (all status 1) died on postoperative day 285 (brain death), 17 (multiorgan failure), and 229 (cardiovascular failure during retransplantation). Actuarial patient survivals at 6 months and 6 years are 94% and 78% while graft survivals are 89% and 74%, respectively. Currently all the patients listed as UNOS status 2 and 3 (73%) at the time of transplant are alive. During the same period one premature neonate (1.8 kg) who presented with fulminant hepatic failure died on the waiting list after 12 days. Our data confirm that the extensive use of a split-liver technique from small adult or pediatric cadaveric donors can offer the benefits of liver transplantation to small pediatric candidates with excellent results.

LIVER TRANSPLANTATION IN CHILDREN WEIGHTING LESS THAN 6 KG. THE BERGAMO EXPERIENCE.

O159 Aims: Liver transplantation (OLTX) remains a major medical and surgical challenge in paediatric patients weighting less than 6 Kg. Methods: From October 1997 through February 2004, 13 babies less than 6.0 Kg.underwent OLTX at the Ospedali Riuniti di Bergamo. They represent 6 % of 217 paediatric candidates for OLTX at our institution. Median age was 5 months (range=1-8); median weight was 5.2 Kg (range, 2.2 to 5.8). The indications were biliary atresia (n=8), neonatal haemochromatosis (n=2), unknown fulminant hepatic failure (n=1), cryptogenic cirrhosis (n=1), haemangio-endothelioma (n=1). Of these 13 patients, 4 were in UNOS status 1, 3 in status 2A and 6 in status 3. One child in UNOS status 1 underwent retransplantation for chronic rejection. One whole, 2 reduced and 11 split liver grafts (left lateral segments) were used. The median donors age and weight were 11 years (range= 0.5-62) and 40 kg (range=7-60) respectively. Donor to recipient median weight ratio (D/R) was 9.2 Kg (range=5.5-17) and median graft-to-recipient weight ratio (GRWR) was 6% (range=3.2-9.3). Results: Surgical complications included biliary strictures (n=3), bile leak (n=1), bowel perforations (n=2), wound dehiscence (n=1) and early portal vein thrombosis (n=1). Biliary anastomotic strictures were successfully treated in 2 cases by percutaneous balloon dilatation and temporary stenting while in one case by surgical redo. The bile leak was managed by percutaneous drainage. Early relaparatomy was necessary to repair bowel perforations (n=2), to achieve abdominal closure (n=1) and to perform portal vein thrombectomy with vascular reconstruction(n=1). Ten children (77%) are alive with a good graft function after a median follow up of 37 months (range=12-69). Three patients died on day 285 (brain death), 17 (multiorgan failure) and 229 (cardiovascular failure) post transplant respectively. In particular the last one died during the retransplant operation and the second received a large graft (D/R =17; GRWR = 8.2). All these patients were in UNOS status 1 at transplantation. Actuarial survival at 5 years is 77%. All the patients who were transplanted in UNOS status 2 or 3 are alive (patient and graft survival=100%) at a median follow up of 41 months (range=12-69). Currently only one of the children who were in UNOS status 1 is alive (patient survival=33%). During the same period one patient died on the waiting list. She was a premature neonate (Kg.1,8) with a fulminant hepatic failure caused by neonatal haemochromatosis in UNOS status 1. Conclusions: Our data confirm that the extensive use of the split liver technique from small adult or pediatric donors can offer the benefits of liver transplantation to very small paediatric candidates with excellent results in elective cases. In our experience patient’s clinical condition (UNOS status 1) and large-for-size grafts (GRWR > 8) are associated with lower survival rate.