Long-Term Inhalative Sedation in Children With Pulmonary Diseases.

OBJECTIVES: To describe safety and feasibility of long-term inhalative sedation (LTIS) in children with severe respiratory diseases compared to patients with normal lung function with respect to recent studies that showed beneficial effects in adult patients with acute respiratory distress syndrome (ARDS). DESIGN: Single-center retrospective study. SETTING: 12-bed pediatric intensive care unit (PICU) in a tertiary-care academic medical center in Germany. PATIENTS: All patients treated in our PICU with LTIS using the AnaConDa® device between July 2011 and July 2019. MEASUREMENTS AND MAIN RESULTS: Thirty-seven courses of LTIS in 29 patients were analyzed. LTIS was feasible in both groups, but concomitant intravenous sedatives could be reduced more rapidly in children with lung diseases. Cardiocirculatory depression requiring vasopressors was observed in all patients. However, severe side effects only rarely occured. CONCLUSIONS: In this largest cohort of children treated with LTIS reported so far, LTIS was feasible even in children with severely impaired lung function. From our data, a prospective trial on the use of LTIS in children with ARDS seems justified. However, a thorough monitoring of cardiocirculatory side effects is mandatory.

Iatrogenic severe hyperglycemia due to parenteral administration of glucose in children - a case series.

BACKGROUND: Iatrogenic severe hyperglycemia (ISH) caused by glucose-containing i.v. solution is a potentially fatal treatment error. The objective of this study was to investigate the causes, circumstances, course of disease, and complications of ISH > 300 mg/dl (16.7 mmol/l) in neonates and children. METHODS: We emailed a survey to 105 neonatal and pediatric intensive care units in Germany, Austria, and Switzerland, asking to retrospectively report cases of ISH. RESULTS: We received 11 reports about premature infants to children. Four patients (36%) had poor outcome: 2 died and 2 suffered persistent sequelae. The highest observed blood glucose was at median 983 mg/dl (54.6 mmol/l) (range 594-2240 mg/dl; 33.0-124.3 mmol/l) and median time to normoglycemia was 7 h (range 2-23). Blood glucose was higher and time to normoglycemia longer in patients with poor outcome. Invasive therapy was required in 73% (mechanical ventilation) and 50% (vasopressor therapy) of patients, respectively. Administration of insulin did not differ between outcome groups. Patients with poor outcome showed coma (100% vs. 40%) and seizures (75% vs. 29%) more frequently than those with good outcome. CONCLUSIONS: ISH is a severe condition with high morbidity and mortality. Further research to amplify the understanding of this condition is needed, but focus should largely be held on its prevention.

Publication bias in pediatric emergence delirium: a cross-sectional analysis of ClinicalTrials.gov and ClinicalTrialsRegister.eu.

OBJECTIVES: Emergence delirium (ED) is a frequent and potentially serious complication of general anaesthesia in children. Although there are various treatment strategies, no general management recommendations can be made. Selective reporting of study results may impair clinical decision-making. We, therefore, analysed whether the results of completed registered clinical studies in patients with paediatric ED are publicly available or remain unpublished. DESIGN: Cross-sectional analysis. SETTING: ClinicalTrials.gov and ClinicalTrialsRegister.eu. PARTICIPANTS AND OUTCOME MEASURES: We determined the proportion of published and unpublished studies registered at ClinicalTrials.gov and ClinicalTrialsRegister.eu that were marked as completed by 1st September 2018. The major trial and literature databases were used to search for publications. In addition, the study investigators were contacted directly. For published trials, time to publication was calculated as the difference in months between study completion date and publication date. RESULTS: Of the 44 registered studies on paediatric ED, only 24 (54%) were published by September 2019. Published trials contained data from n=2556 patients, whereas n=1644 patients were enrolled in unpublished trials. Median time to publication was 19 months. Studies completed in recent years were published faster, but still only 9 of 24 trials were published within 12 months of completion. CONCLUSION: There is a distinct publication gap in clinical research in paediatric ED that may have an impact on meta-analyses and clinical practice.

Decision-making in acute viral bronchiolitis: A universal guideline and a publication gap.

BACKGROUND: Acute viral bronchiolitis is very common in infants and children up to 2 years. Some patients develop serious respiratory symptoms and need to be hospitalized. In 2014, the American Academy of Pediatrics (AAP) published a guideline on acute bronchiolitis which has gained global acceptance. We hypothesized that a publication gap, which is increasingly perceived in clinical medicine, might have also affected these universal recommendations. METHODS: We determined the proportion of published and unpublished studies registered at ClinicalTrials.gov that were marked as completed by October 1st 2018. The major trial and literature databases were used to search for publications. In addition, the study investigators were contacted directly. RESULTS: Of the 69 registered studies on the treatment of acute viral bronchiolitis, only 50 (72%) have been published by November 2019. Published trials contained data from n = 9403 patients, whereas n = 4687 patients were enrolled in unpublished trials. Median time to publication was 20 months, and only 8 of 50 trials were published within 12 months after completion. Only 40% of the clinical trials that were completed after the release of the AAP guideline were subsequently published as compared to 80% before 2014. CONCLUSION: There is a significant publication gap regarding therapy of acute viral bronchiolitis that may have influenced certain recommendations of the AAP guideline. In turn, recommendations of the guideline might have discouraged investigators to publish their results after its release.

Cholinesterases and Anticholinergic Medications in Postoperative Pediatric Delirium.

OBJECTIVES: To describe the relationships between anticholinergic drug exposure, cholinesterase enzyme activity, inflammation, and the development of postoperative delirium in children. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed PICU in a tertiary-care academic medical center in Germany. PATIENTS: A consecutive cohort of children admitted after major elective surgery. INTERVENTIONS: Children were screened for delirium bid over 5 consecutive postoperative days. Acetylcholinesterase and butyrylcholinesterase plasma activity levels were measured prior to surgery and once daily during the 5 day study period. Number of anticholinergic drugs and Anticholinergic Drug Scale score were calculated for each patient. MEASUREMENTS AND MAIN RESULTS: Ninety-three children (age range, 0-17 yr) were included. The number of anticholinergic drugs as well as the Anticholinergic Drug Scale score were significantly correlated with development of postoperative delirium, independently of disease severity. Baseline cholinesterase enzyme levels did not differ between patients who did and did not develop postoperative delirium. Butyrylcholinesterase levels, but not acetylcholinesterase levels, dropped by 33% postoperatively, independent of the presence of postoperative delirium. Postoperative butyrylcholinesterase levels were inversely related to number of anticholinergic drugs, Anticholinergic Drug Scale score, and C-reactive protein levels. CONCLUSIONS: Anticholinergic drug exposure was related to development of postoperative delirium in this cohort, with demonstration of a dose-response relationship. As there are alternative options available for many of these medications, it may be reasonable to avoid anticholinergic exposure in the PICU whenever possible.

Severe Human Bocavirus 1 Respiratory Tract Infection in an Immunodeficient Child With Fatal Outcome.

We report a case of lower respiratory tract infection with human bocavirus 1 (HboV1) in an immunodeficient 6-month-old boy leading to respiratory failure with fatal outcome. Polymerase chain reaction of serum/tracheal secretions revealed exceptionally high HboV1-DNA levels and immunoassays showed seroconversion indicating an acute primary HboV1 infection. All assays for other pathogens were negative, strongly suggesting that HboV1 was the causative agent in this case.

High blood pressure, a red flag for the neonatal manifestation of urea cycle disorders.

BACKGROUND: Neonatal manifestation of life-threatening hyperammonemic encephalopathy in urea cycle disorders (UCD) is often misdiagnosed as neonatal sepsis, resulting in significantly delayed start of specific treatment and poor outcome. The major aim of this study was to identify specific initial symptoms or signs to clinically distinguish hyperammonemic encephalopathy in neonates from neonatal sepsis in order to identify affected individuals with UCD and to start metabolic therapy without delay. Furthermore, we evaluated the impact of diagnostic delay, peak plasma ammonium (NH4+) concentration, mode of emergency treatment and transfer to a tertiary referral center on the outcome. METHODS: Detailed information of 17 patients (born between 1994 and 2012) with confirmed diagnosis of UCD and neonatal hyperammonemic encephalopathy were collected from the original medical records. RESULTS: The initially suspected diagnosis was neonatal sepsis in all patients, but was not confirmed in any of them. Unlike neonatal sepsis and not previously reported blood pressure increased above the 95th percentile in 13 (81%) of UCD patients before emergency treatment was started. Respiratory alkalosis was found in 11 (65%) of UCD patients, and in 14 (81%) plasma NH4+concentrations further increased despite initiation of metabolic therapy. CONCLUSION: Detection of high blood pressure could be a valuable parameter for distinguishing neonatal sepsis from neonatal manifestation of UCD. Since high blood pressure is not typical for neonatal sepsis, other reasons such as encephalopathy and especially hyperammonemic encephalopathy (caused by e.g. UCD) should be searched for immediately. However, our result that the majority of newborns with UCD initially present with high blood pressure has to be evaluated in larger patient cohorts.

Pediatric in-hospital emergencies: real life experiences, previous training and the need for training among physicians and nurses.

OBJECTIVE: Pediatric emergencies challenge professional teams by demanding substantial cognitive effort, skills and effective teamwork. Educational designs for team trainings must be aligned to the needs of participants in order to increase effectiveness. To assess these needs, a survey among physicians and nurses of a tertiary pediatric center in Germany was conducted, focusing on previous experience, previous training in emergency care, and individual training needs. RESULTS: Fifty-three physicians and 75 nurses participated. Most frequently experienced emergencies were respiratory failure, resuscitation, seizure, shock/sepsis and arrhythmia. Resuscitations were perceived as being particularly precarious. Team collaboration and communication were major issues arising from previous emergency situations, but perceptions differed between physicians and nurses. Regarding previous training, physicians were accustomed to self-directed learning, whereas nurses usually attended practical courses. Both physicians and nurses rated themselves as having moderate levels of knowledge and skills for pediatric emergencies, though residents reported the significantly lowest preparedness. Both professions reported a high need for training of basic procedures and emergency algorithms, physicians even more than nurses.

ARFI shear-wave elastography with simulation of acute urinary tract obstruction in an ex vivo porcine kidney model.

METHODS: A total of 20 heparinized pig kidneys were investigated at 10 intrapelvic hydrostatic pressure steps (0-90 mmHg). SWE (ARFI; Virtual TouchTM IQ, Siemens) measurements were taken at three different measuring regions and in two measuring sequences using a linear ultrasonography probe (9L4, Siemens). Median values of 10 shear-wave speed (SWS) measurements were calculated for each pressure step. Logarithmic transformed median SWS values were analyzed in a linear mixed model. RESULTS: SWS increased significantly with increasing intrapelvic pressure. Median SWS for all kidneys in both measuring sequences and all measuring regions was 1.47 m/s (interquartile range [IQR], 0.38 m/s) at 0 mmHg, 1.94 m/s (IQR, 0.42 m/s) at 30 mmHg, 2.07 m/s (IQR, 0.43 m/s) at 60 mmHg, 2.24 m/s (IQR, 0.49 m/s) at 90 mmHg. The correlation between pelvic pressure increase and median SWS values for the central parenchyma was significantly higher compared with the peripheral parenchyma. CONCLUSION: Acutely increased renal pelvic pressure correlates with increasing SWS values in ARFI elastography in an ex vivo porcine kidney model.

Cognitive and Behavioral Consequences of Pediatric Delirium: A Pilot Study.

OBJECTIVES: To investigate the long-term impact of postoperative delirium in children. DESIGN: Single-center point prevalence study. SETTING: Twenty-two bed PICU. PATIENTS: Forty-seven patients 1-16 years old. INTERVENTIONS: Standardized neuropsychologic follow-up investigation after a mean time of 17.7 ± 2.9 months after PICU discharge. MEASUREMENTS AND MAIN RESULTS: Pediatric delirium did not have significant long-term impact on global cognition, executive functions, or behavior. Severity of delirium did not influence the outcome. Different predictors were identified for later cognitive functioning, executive functions, and behavioral problems. Younger age was confirmed to be a relevant risk factor for delirium as well as for the cognitive and behavioral outcome. CONCLUSIONS: Contrary to the findings in adults, there was no clear association between pediatric delirium and long-term cognition or behavior in this cohort. However, this is a first pilot study with several limitations that should promote more comprehensive prospective trials.

Risk Factors for the Development of Postoperative Delirium in Pediatric Intensive Care Patients.

OBJECTIVES: To determine and quantify risk factors for postoperative pediatric delirium. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed PICU in a tertiary care academic medical center in Germany. PATIENTS: All children admitted after major elective surgery (n = 93; 0-17 yr). INTERVENTIONS: After awakening, children were screened for delirium using the Cornell Assessment of Pediatric Delirium bid over a period of 5 days. Demographic and clinical data were collected from the initiation of general anesthesia. MEASUREMENTS AND MAIN RESULTS: A total of 61 patients (66%) were delirious. Younger children developed delirium more frequently, and the symptoms were more pronounced. The number of preceding operations did not influence the risk of delirium. Total IV anesthesia had a lower risk than inhalational anesthesia (p < 0.05). Duration of anesthesia was similar in all groups. Patients with delirium had a longer duration of mechanical ventilation in the PICU (p < 0.001). Significant differences in cumulative doses of various medications (e.g., sedatives, analgesics, and anticholinergics) were noted between groups; these differences were independent of disease severity. Invasive catheters and respiratory devices (p < 0.01) as well as infections (p < 0.001) increased risk of delirium. CONCLUSIONS: A high prevalence of delirium was noted in the PICU, and several perioperative risk factors were identified. Our data may be a base for development of strategies to prevent and treat postoperative delirium in children.

Human heterologous liver cells transiently improve hyperammonemia and ureagenesis in individuals with severe urea cycle disorders.

BACKGROUND: Urea cycle disorders (UCDs) still have a poor prognosis despite several therapeutic advancements. As liver transplantation can provide a cure, liver cell therapy (LCT) might be a new therapeutic option in these patients. METHODS: Twelve patients with severe UCDs were included in this prospective clinical trial. Patients received up to six infusions of cryopreserved human heterologous liver cells via a surgically placed catheter in the portal vein. Portal vein pressure, portal vein flow, and vital signs were monitored continuously. Calcineurin inhibitors and steroids were used for immunosuppression. In four patients, ureagenesis was determined with stable isotopes. Number and severity of hyperammonemic events and side effects of immunosuppression were analyzed during an observation period of up to 2 years. RESULTS: No study-related mortality was observed. The application catheter dislocated in two children. No significant side effects of catheter application or cell infusion were noted in the other ten patients. The overall incidence of infections did not differ significantly from a historical control group, and no specific side effects of immunosuppression were found. Seven patients were treated per protocol and could be analyzed for efficacy. Severe metabolic crises could be prevented in all of these patients, moderate crises in four of seven. Ureagenesis increased after cell infusion in all patients investigated. CONCLUSIONS: We found a favorable safety profile with respect to catheter placement, intraportal liver cell infusion, and immunosuppression. More than half of the children treated per protocol experienced metabolic stabilization and could be safely bridged to liver transplantation.

Patterns of Postoperative Delirium in Children.

OBJECTIVE: Intensive care delirium is a substantial problem in adults. Intensive care delirium is increasingly recognized in pediatrics in parallel with the development of specific scoring systems for children. However, little is known about the fluctuating course of intensive care delirium in children after surgery and possible implications on diagnostic and therapeutic strategies. DESIGN: Patients that needed treatment in the PICU following elective surgery were screened for intensive care delirium with the Cornell Assessment of Pediatric Delirium. When the patients were awake (Richmond Agitation and Sedation Score > -3), two trained investigators conducted the Cornell Assessment of Pediatric Delirium twice daily for five consecutive days. PATIENTS: Ninety-three patients aged 0 to 17 years. INTERVENTIONS: Eight hundred forty-five assessments completed. MEASUREMENTS AND MAIN RESULTS: Of the 845 scores, 230 were consistent with delirium (27.2%). Sixty-one patients (65.5%) were diagnosed with intensive care delirium. Half of these patients (n = 30; 32.2%) had a short-lasting delirium that resolved within 24 hours, and half (n = 31; 33.3%) had delirium of longer duration. Delirium could be clearly distinguished from sedation by analysis of individual test items of the Cornell Assessment of Pediatric Delirium. Time spent delirious had a measurable effect on outcome variables, including hospital length of stay. CONCLUSION: Most postoperative PICU patients develop intensive care delirium. Some have a short-lasting course, which underlines the need for early screening. Our findings support the view of delirium as a continuum of acute neurocognitive disorder. Further research is needed to investigate prophylactic and treatment approaches for intensive care delirium.

In vivo monitoring of urea cycle activity with (13)C-acetate as a tracer of ureagenesis.

BACKGROUND: The hepatic urea cycle is the main metabolic pathway for detoxification of ammonia. Inborn errors of urea cycle function present with severe hyperammonemia and a high case fatality rate. Long-term prognosis depends on the residual activity of the defective enzyme. A reliable method to estimate urea cycle activity in-vivo does not exist yet. The aim of this study was to evaluate a practical method to quantify (13)C-urea production as a marker for urea cycle function in healthy subjects, patients with confirmed urea cycle defect (UCD) and asymptomatic carriers of UCD mutations. METHODS: (13)C-labeled sodium acetate was applied orally in a single dose to 47 subjects (10 healthy subjects, 28 symptomatic patients, 9 asymptomatic carriers). RESULTS: The oral (13)C-ureagenesis assay is a safe method. While healthy subjects and asymptomatic carriers did not differ with regards to kinetic variables for urea cycle flux, symptomatic patients had lower (13)C-plasma urea levels. Although the (13)C-ureagenesis assay revealed no significant differences between individual urea cycle enzyme defects, it reflected the heterogeneity between different clinical subgroups, including male neonatal onset ornithine carbamoyltransferase deficiency. Applying the (13)C-urea area under the curve can differentiate between severe from more mildly affected neonates. Late onset patients differ significantly from neonates, carriers and healthy subjects. CONCLUSION: This study evaluated the oral (13)C-ureagenesis assay as a sensitive in-vivo measure for ureagenesis capacity. The assay has the potential to become a reliable tool to differentiate UCD patient subgroups, follow changes in ureagenesis capacity and could be helpful in monitoring novel therapies of UCD.

Liver cell transplantation in severe infantile oxalosis--a potential bridging procedure to orthotopic liver transplantation?

BACKGROUND: The infantile form of primary hyperoxaluria type I (PHI) is the most devastating PH subtype leading to early end-stage renal failure and severe systemic oxalosis. Combined or sequential liver-kidney transplantation (LKTx) is the only curative option but it involves substantial risks, especially in critically ill infants. The procedure also requires resources that are simply not available to many children suffering from PHI worldwide. Less invasive and less complex therapeutic interventions allowing a better timing are clearly needed. Liver cell transplantation (LCT) may expand the narrow spectrum of auxiliary measures to buy time until LKTx for infants can be performed more safely. METHODS: We performed LCT (male neonate donor) in a 15-month-old female in reduced general condition suffering from systemic oxalosis. Renal replacement therapy, initiated at the age of 3 months, was complicated by continuous haemodialysis access problems. Living donor liver transplantation was not available for this patient. Plasma oxalate (Pox) was used as the primary outcome measure. RESULTS: Pox decreased from 104.3±8.4 prior to 70.0±15.0 µmol/L from Day 14 to Day 56 after LCT. A significant persistent Pox reduction (P<0.001) comparing mean levels prior to (103.8 µmol/L) and after Day 14 of LCT until LKTx (77.3 µmol/L) was seen, although a secondary increase and wider range of Pox was also observed. In parallel, the patient's clinical situation markedly improved and the girl received a cadaveric LKTx 12 months after LCT. However, biopsy specimens taken from the explanted liver did not show male donor cells by amelogenin polymerase chain reaction. CONCLUSIONS: With due caution, our pilot data indicate that LCT in infantile oxalosis warrants further investigation. Improvement of protocol and methodology is clearly needed in order to develop a procedure that could assist in the cure of PHI.

Comparison of Molecular Adsorbents Recirculating System (MARS) dialysis with combined plasma exchange and haemodialysis in children with acute liver failure.

BACKGROUND: Molecular Adsorbents Recirculating System (MARS) is an extracorporeal liver support system eliminating albumin-bound and water-soluble substances. While it is increasingly applied in patients with acute liver failure (ALF), no comparison with standard dialysis methods has yet been performed. METHODS: This is an analysis of ten children (0.1-18 years) with ALF, who underwent a total of 22 MARS sessions. Standard adult MARS sets were used in seven (23.5-72 kg) and MARS Mini in three children (2.8-13 kg). In eight children, MARS was alternated with combined plasma exchange (PE) and haemodialysis (HD) treatments. Mean treatment duration was 7.2 (6-10) h for MARS and 5.7 (4.5-6.6) h for PE/HD. RESULTS: Standard MARS treatment only slightly decreased serum bilirubin (16.3 ± 6.5-13.8 ± 5.9 mg/dL) and ammonia (113 ± 62-99 ± 68 µmol/L) and international normalized ratio (INR) tended to increase (1.5 ± 0.3 and 2 ± 1.1). Mini-MARS did not reduce serum bilirubin (19.7 ± 3-20.5 ± 3.2 mg/dL), ammonia slightly decreased (70 ± 24-56 ± 9 µmol/L) and INR increased (2.5 ± 0.7-2.9 ± 1.1, all P = n.s.). In contrast, PE/HD reduced serum bilirubin (23 ± 8.4-14.7 ± 7 mg/dL), ammonia (120 ± 60-70 ± 40 µmol/L) and INR (2.4 ± 0.8-1.4 ± 0.1, all P < 0.05). Intraindividual comparison showed a slight increase in bilirubin by 2 ± 22% with MARS and a reduction by 37 ± 11% with PE/HD (P < 0.001 versus MARS) and a decrease in ammonia of 18 ± 27 and 39 ± 23% (P < 0.05). INR increased during MARS by 26 ± 41% and decreased with PE/HD by 37 ± 20% (P < 0.01). All treatment sessions were well tolerated. Five children died, including the three children treated with Mini-MARS. CONCLUSION: Our experience suggests superior efficacy of combined PE/HD as compared to intermittent MARS therapy for treating ALF.

Liver, liver cell and stem cell transplantation for the treatment of urea cycle defects.

Despite advances in pharmacological therapy of urea cycle disorders (UCDs), the overall long-term prognosis is poor, especially for neonatal manifestations. Transplantation of liver tissue or isolated cells appears suitable for transfer of the missing enzyme. Liver transplantation (LT) for UCDs has an excellent 5-year survival rate of approximately 90% and is the only way to completely cure the disease. However, major neurological damage can only be prevented if the operation is performed during the first months of life. Unfortunately, such early LTs have a substantial risk for peri- and postoperative complications, mostly caused by a relatively large liver graft. Liver cell transplantation (LCT) is less invasive than LT, but has still to be regarded as an experimental therapy with about 100 patients treated since its first use in 1993. UCDs are a model disease for LCT, because of the poor prognosis, mainly hepatic enzyme defects, and excellent outcome after LT. So far, 10 children underwent LCT for UCDs with very few technical complications and encouraging clinical results. A first prospective study on its use in severe neonatal UCDs has recently started. However, availability of hepatocytes is limited by the scarcity of donor livers; therefore the use of stem cells is under investigation. Several different cell types may be regarded as liver stem cells, and in vivo transformation into hepatocyte-like cells has been shown in animal studies. However, a clear proof of principle in animal models of human metabolic disease is still missing, which is the prerequisite for clinical application in humans.

Monitoring of intraportal liver cell application in children.

Despite recent advances and promising results in children, liver cell transplantation (LCT) should still be regarded as an experimental therapy. Several substantial complications are known from animal studies and individual patients. However, safety data on liver cell infusion in children are scarce. We used LCT in four children of different ages (3 weeks to 11 years, 3-40 kg) and underlying diseases [acute liver failure (n = 1), urea cycle disorders (n = 2), and Crigler-Najjar syndrome (n = 1)]. Vital parameters, portal vein flow (PVF), portal vein pressure (PVP), and liver enzymes were measured every 5 min during cell application and hourly thereafter between applications. An application protocol with discontinuation rules depending on changes in PVF and PVP was developed and successfully applied. Application was feasible in all children despite the catastrophic overall condition of the patient with acute liver failure. No application-related changes in vital parameters were found, and none of the children experienced clinical signs of portal vein thrombosis, pulmonary embolism, or anaphylactic reactions. Time courses for changes in PVF, PVP, and liver enzymes were obtained. Thorough monitoring of portal vein pressure and duplex sonography according to a defined protocol is likely to increase safety of cell application in pediatric LCT.

A new pediatric liver transplantation program in Southern Germany. The Heidelberg experience.

pLTx is a highly complex procedure. It can only be performed safely by experienced teams. Starting a new pLTx program in a country with established centers must therefore avoid a learning curve. We have initiated a liver transplantation program for children in 2003. Medical standards were defined by a team of surgeons, pediatricians, radiologists, anesthesiologists, and pathologists before the first transplantation. An external expert in the field of pLTx supervised the whole process. In a pilot phase, six children weighing more than 20 kg were successfully transplanted. Following this series, the clinical pathways were re-evaluated, and the program was opened for children of all age groups. Between 2003 and 2008, 32 children received 34 organs. Sixty-eight percent of patients received a split-liver, 26% a full size organ, and 6% a reduced size graft. Four LRLTx were performed. Patient survival rate was 91%. We conclude that a new pLTx program can be established without a significant learning curve regarding mortality if a strict strategy of team-building is followed. In the pilot phase, small children and infants have to be referred and transplanted in an established center. An interdisciplinary team of specialists closely working together is the key for sustained success.