Arrhythmias after pediatric lung transplantation

Atrial arrhythmias have been reported after congenital heart surgery involving extensive atrial suture lines. Experimental studies involving bilateral lung transplantation (Tx) suggest that the left atrial suture lines predispose to atrial flutter. The overall incidence and type of arrhythmias after pediatric lung Tx have not previously been described and therefore the purpose of this study was to prospectively screen and describe arrhythmias in a subset of our lung transplant population. Over a 1-yr study period, all recipients of bilateral lung Tx were admitted to a full-disclosure telemetry unit. Single-lead electrocardiograms were recorded continuously and reviewed daily via a beat-by-beat analysis. A total of 314 patient days (range 9-93, median 43 days) were recorded from seven patients. The incidence of arrhythmias observed per total patient days included junctional escape rhythm (4.8%), non-sustained ventricular tachycardia (4.1%), accelerated junctional (2.5%), sinus bradycardia (2.2%), non-sustained supraventricular tachycardia (1.3%), ectopic atrial tachycardia (1.0%), sustained ventricular tachycardia (0.3%), junctional ectopic tachycardia (0.3%), and second degree heart block (0.3%). No patient had sustained supraventricular tachycardia, atrial flutter, atrial fibrillation, or complete heart block. Arrhythmias were treated in two patients. During the follow-up period, one patient received amiodarone for ventricular tachycardia (which was also noted and treated prior to transplant). We conclude that among pediatric lung transplant recipients admitted for their transplant surgery, arrhythmia is uncommon and rarely requires therapy.     

Long‐term impact of respiratory viral infection after pediatric lung transplantation

Liu M, Mallory GB, Schecter MG, Worley S, Arrigain S, Robertson J, Elidemir O, Danziger‐Isakov LA. Long‐term impact of respiratory viral infection after pediatric lung transplantation.
Pediatr Transplantation 2010: 14:431–436. © 2010 John Wiley & Sons A/S. Abstract: To evaluate the epidemiology and to investigate the impact of RVI on chronic allograft rejection after pediatric lung transplantation, a retrospective study of pediatric lung transplant recipients from 2002 to 2007 was conducted. Association between RVI and continuous and categorical risk factors was assessed using Wilcoxon rank‐sum tests and Fisher’s exact tests, respectively. Association between risk factors and outcomes were assessed using Cox proportional hazards models. Fifty‐five subjects were followed for a mean of 674 days (range 14–1790). Twenty‐eight (51%) developed 51 RVI at a median of 144 days post‐transplant (mean 246; range 1–1276); 41% of infections were diagnosed within 90 days. Twenty‐five subjects developed 39 LRI, and eight subjects had 11 URI. Organisms recovered included rhinovirus (n = 14), adenovirus (n = 10), parainfluenza (n = 10), influenza (n = 5), and RSV (n = 4). Three subjects expired secondary to their RVI (two adenovirus, one RSV). Younger age and prior CMV infection were risks for RVI (HR 2.4 95% CI 1.1–5.3 and 17.0; 3.0–96.2, respectively). RVI was not associated with the development of chronic allograft rejection (p = 0.25) or death during the study period. RVI occurs in the majority of pediatric lung transplant recipients, but was not associated with mortality or chronic allograft rejection.     

Intra‐operative extracorporeal membrane oxygenation use in pediatric lung transplantation – The Zurich experience

There is a lack of data regarding use of ECMO in children undergoing lung transplantation. We evaluated our experience of ECMO in pediatric lung transplant recipients. All patients (<18 yr) who underwent lung transplants between 1997 and 2011 were included (17 children; nine males; median age 16 yr), and the use of intra‐operative ECMO evaluated. Transplant procedures were carried out with intra‐operative ECMO in seven children (all bilateral lung transplants). Demographics of ECMO and non‐ECMO patients were comparable. One child was already on ECMO pre‐operative. Lung graft size reduction was undertaken in five ECMO and four non‐ECMO cases, respectively. Five patients were taken off ECMO intra‐operatively; the other patients were weaned off ECMO within 48 h post‐operatively. Three‐months survival was 100%. By 12 months post‐transplantation, one patient each died in the ECMO and in the non‐ECMO group. At the end of the study, six of seven ECMO cases were still alive (median survival 48.5 months); one patient required a retransplant at 53 months. Our small case series suggests that lung transplant procedures can be safely carried out in selected children on intra‐operative ECMO support; however, our pediatric experience regarding this scenario is very limited but probably almost unique.     

Correlation between 6‐min walk test and exercise stress test in healthy children

Aim: To investigate the correlation between 6‐min walk test (SMWT) and incremental treadmill exercise stress test (EST) as indicators for the functional capacity in children. Methods: Healthy children aged 9–12 years were included. The anthropometric data, SMWT and EST were prospectively measured using the standard protocols. Various parameters were analysed to define the correlation between SMWT and EST. Results: A total of 100 subjects (53 boys) aged 10.3 ± 1.0 years participated in the study. The SMWT distance was 586.1 ± 44.0 m. Height (r = 0.59, R² = 35%), length of the leg (r = 0.64, R² = 41%), heart rate at the end of SMWT (r = 0.59, R² = 35%) and heart rate difference at the end of SMWT (r = 0.71, R² = 50%) were found to have significant correlation with SMWT distance. The estimated maximal oxygen consumption (eVO2) obtained during the EST tended to be greater in boys than in girls. Among the parameters obtained during EST, maximal heart rate (r = 0.33, R² = 11%) and the eVO2 (r = 0.54, R² = 53%) were found to have significant correlation with SMWT. Conclusions: SMWT distance is significantly correlated with the eVO2 obtained during the EST. This indicates that SMWT is also one of the predictive markers for EST performance.     

Functional capacity after pediatric liver transplantation: A pilot study

The prospective cross‐sectional study investigated the 6MWT performance in pediatric group of liver transplant recipients (6–17 yr, median post‐transplantation time of 22 months) and compared to the normal values obtained in healthy children as well as evaluated the reproducibility of the 6MWT. We analyzed the relationship between walked distance and the 6MWw, distance walked × body weight) with the anthropometric, clinical, and pulmonary functions. In post‐transplanted group, the average walked distance was significantly shorter compared with control (687 ± 80 m vs. 511 ± 72 m, p < 0.001). The calculated ICC coefficient confirmed the reproducibility among tests. The Pearson correlation revealed that only walked distance in the 6MWT was moderately correlated with tidal volume. Conversely, the 6MWw was significantly correlated with age, weight, height, BMI, FVC, PEF rate, and volume expiratory. According to multiple regression analysis, age, VE and FVC factors explained 80% of the variance in the 6MWw. In conclusion, the pediatric liver transplant recipients' performance in the 6MWT is significantly lower than the values for healthy children of the same age. Notably, the 6MWw may provide relevant information, constituting an additional parameter in the determination of functional capacity.     

Intra‐arterial nitroglycerin for intra‐operative arterial vasospasm during pediatric renal transplantation

Intra‐operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end‐organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra‐operative intra‐arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three‐yr‐old girl with end‐stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 μg (0.4 mL of a 100 μg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra‐arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra‐arterial nitroglycerin is a promising option for intra‐operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion.     

Induction regimens and post‐transplantation lymphoproliferative disorder after pediatric intestinal transplantation: Single‐center experience

Pediatric recipients of intestinal transplants have a high incidence of PTLD, but the impact of specific induction immunosuppression agents is unclear. In this single‐center retrospective review from 2000 to 2017, we describe the incidence, characteristics, and outcomes of PTLD after primary intestinal transplantation in 173 children with or without liver, after induction with rATG, alemtuzumab, or anti‐IL‐2R agents. Thirty cases of PTLD occurred among 28 children, 28 EBV+ and 2 EBV?. Although not statistically significant, the PTLD incidence was higher after isolated intestinal transplant compared with liver‐inclusive allograft (19.3% vs 13.3%, P = .393) and after induction with anti‐IL‐2R antibody and alemtuzumab compared with rATG (28.6% and 27.3% vs 13.3%, P = .076). The 30 PTLD cases included 13 monomorphic PTLD, 13 polymorphic PTLD, one spindle cell, one Burkitt lymphoma, and two cases too necrotic to classify. After reduction of immunosuppression, management was based on disease histology and extent. Resection with or without rituximab was used for polymorphic tumors and limited disease extent, whereas chemotherapy was used for diffuse disease. Of the 28 patients, 11 recovered with functioning allografts (39.3%), 10 recovered after enterectomy (35.7%), and seven patients died (25%), three due to PTLD and four due to other causes. All who died of progressive PTLD had received chemotherapy, highlighting the mortality of PTLD, toxicity of treatment and need for novel agents. Alemtuzumab is no longer used for induction at our center.     

Urological complications,vesicoureteral reflux,and long‐term graft survival rate after pediatric kidney transplantation

To describe a single‐center experience with kidney transplantation and then study some donor and recipient features that may impact on graft survival and urological complication rates. We reviewed our database searching for pediatric patients who underwent kidney transplantation from August 1985 through November 2012. Preoperative data and postoperative complications were recorded. Graft survival rates were analyzed and compared based on the type of donor, donor's age from deceased donors, and recipients' ESRD cause. Kaplan–Meier curves with log rank and Wilcoxon tests were used to perform the comparisons. There were 305 pediatric kidney transplants. The mean recipient's age was 11.7 yr. The mean follow‐up was 11.0 yr. Arterial and venous thrombosis rates were 1.6% and 2.3%, respectively, while urinary fistula and symptomatic vesicoureteral reflux were diagnosed in 2.9% and 3.6% of cases, respectively. Deceased kidney transplantation had a lower graft survival rate than living kidney transplantation (log rank, p = 0.005). Donor's age (p = 0.420) and ESRD cause (p = 0.679) were not significantly related to graft survival rate. In long‐term follow‐up, type of donor, but not donor's age, impacts on graft survival rate. ESRD cause has no impact on graft survival rate, showing that well‐evaluated recipients may have good outcomes.     

Sirolimus‐induced interstitial lung disease following pediatric stem cell transplantation

Sirolimus‐induced ILD is a known but rare complication in adults who have undergone SOT. However, little is known about this adverse effect in children. Diagnosis of sirolimus‐induced ILD can be challenging, especially in patients who have difficulty participating in lung function testing. We present a case of presumed sirolimus‐induced ILD in a pediatric stem cell transplant patient who developed polycythemia and hypoxemia. To our knowledge, no other cases of sirolimus‐induced pulmonary toxicity in children after HCT have been reported.     

Impact of congenital heart disease on outcomes of pediatric heart‐lung transplantation

HLT is reserved for children with cardiopulmonary disease not amendable to alternative therapies. Children with CHD with or without ES may be considered for HLT. Outcomes of HLT in this population are not well described. To test the hypothesis that CHD without ES is associated with worse graft survival and identify factors associated with poor outcome, a retrospective analysis of the UNOS database was performed. One hundred and seventy‐eight pediatric HLTs were performed between 1987 and 2011. CHD was the diagnosis in 65 patients, of which 34 had CHD without ES. Patients with CHD without ES had decreased patient survival (median 1.31 yr) compared with CHD with ES (4.80 yr, p = 0.05). On multivariable analysis, the following were associated with graft failure: CHD without ES (adjusted HR 1.69, 95% CI 1.09–2.62), younger age (1.04, 1.01–1.08), pretransplant mechanical ventilation (1.75, 1.01–3.06), pretransplant ECMO (3.07, 1.32–7.12), pretransplant PRAs (1.53, 1.06–2.20), and transplant era (1.85, 1.16–2.94). In children with CHD who require HLT, underlying physiology influences outcomes. Those without ES have a worse prognosis. The diagnosis of CHD without ES and preoperative factors may inform decisions in a complex patient population.     

Variability in standard care for cytomegalovirus prevention and detection in pediatric lung transplantation: survey of eight pediatric lung transplant programs

Cytomegalovirus (CMV) infection after pediatric lung transplantation is a significant risk factor for morbidity and mortality in the first year after transplantation. Multiple strategies have been reported for CMV prevention among adult lung transplant programs. In contrast, little information has been reported regarding protocols for prevention and detection of CMV from pediatric programs. We conducted a survey to better understand the range of practice patterns for CMV prevention and detection at pediatric lung transplant centers. A self-administered questionnaire was distributed to 11 pediatric lung transplant centers identified through the International Pediatric Lung Transplant Collaborative in September 2002. A member of the lung transplant team from each institution was asked to provide the methods of CMV prevention and surveillance. Eight of 11 centers surveyed responded to the questionnaire accounting for 45.6% (26 of 57) and 100% (three of three) of the pediatric lung transplants performed in the US and UK in 2001, respectively. All centers used prophylactic therapy against CMV with either ganciclovir or valganciclovir with duration ranging from 3.5 wk to indefinitely. Most centers (six of eight) prescribed a prophylactic regimen based on donor and recipient CMV serostatus. Half (four of eight) of the centers report using CMV hyperimmune globulin in addition to an antiviral agent. Method for CMV detection varied widely, including use of conventional viral culture (n = 1), antigenemia (n = 7), and polymerase chain reaction (n = 2). A wide range of strategies is used to prevent and detect CMV in pediatric lung transplant recipients with little empiric evidence demonstrating the optimal approach. A retrospective analysis among these centers is being conducted to evaluate the efficacy of these approaches.     

Donor–recipient height ratio and outcomes in pediatric heart transplantation

Height matching in pediatric HTx has been proposed as a superior method of evaluating graft size, but no studies have examined survival advantage for height‐matched donor–recipient pairs. We hypothesized that in pediatric patients with DCM, an oversized donor improves survival and aimed to define the optimal height ratio in this patient group. Pediatric primary HTx recipients with DCM between 10/89 and 09/12 were identified in the OPTN database. Patients were stratified into three donor–recipient height and weight ratio categories. One‐ and five‐yr survival was compared using Kaplan–Meier analysis and HRs were computed. A total of 2133 children with DCM who underwent HTx during the study period were included. Unadjusted one‐yr survival was worse for DRHR <0.87 (HR, 2.15 [95% CL, 1.30, 3.53]; p < 0.01). This difference was not present at five yr post‐HTx or when stratified by weight. After adjustment for other risk factors affecting transplant survival, height matching was no longer significant. Although height matching appears to predict short‐term survival better than weight in pediatric HTx recipients with DCM, other factors play a more important role as height matching loses significance in multivariate analysis.     

The incidence of autoimmune hemolytic anemia in pediatric hematopoietic stem cell recipients post‐first and post‐second hematopoietic stem cell transplant

The reported incidence of post‐allogeneic HSCT AIHA was between 4.4% and 6% following a single transplant. Cord blood transplantation, T‐cell depletion, and chronic GvHD are significantly associated with post‐transplant AIHA. During an 11‐yr period, data for 500 pediatric HSCT recipients were eligible for evaluation of the incidence of AIHA post‐first and post‐second transplants. Demographic, transplant, and post‐transplant‐related variables were analyzed. Twelve of 500 (2.4%) recipients at a median of 273 days and seven of 72 (9.7%) recipients at a median of 157 days developed AIHA post‐first and post‐second HSCT, respectively. Post‐first HSCT, none of the MRD recipients developed AIHA (0/175 MRD vs. 12/325 other donors, p = 0.04). Four of 12 required a second HSCT to control the AIHA. After the second HSCT, MUD was significantly associated with the development of AIHA. No other variables were associated with the post‐second transplant AIHA. The incidence of AIHA post‐first and post‐second HSCT was less than the reported. The increased incidence of AIHA among recipients of second HSCT is most likely due to the profound immune dysregulation. A much larger, prospective study would be needed to evaluate the incidence, complications, and management of post‐transplant AIHA.     

Liver abnormalities and post‐transplant survival in pediatric Fontan patients

The impact of liver parenchymal abnormalities on survival post‐heart transplant remains unknown in pediatric Fontan patients. We assessed pediatric Fontan patients who underwent heart transplant and had documented pretransplant hepatic ultrasound (U/S) studies. Liver U/S findings were classified as normal (Group 1), mildly abnormal (Group 2, hepatomegaly/vascular congestion), or severely abnormal (Group 3, heterogeneous echotexture/nodularity). Among 30 study patients, 8 were classified as Group 1, 14 as Group 2, while 8 met Group 3 criteria. Pretransplant liver biochemistry and synthetic function were similar in all groups. Six Group 3 patients underwent liver biopsy; 4 demonstrated perisinusoidal or centrilobular fibrosis, and 2 had cirrhosis. Overall mortality was 30% (n = 9). Median follow‐up was 5 years (range, 0.25‐13 years). One‐year survival was similar among all 3 groups (P = .37), with a trend toward higher cumulative 5‐year survival in Group 1 (100%). The majority of pediatric Fontan patients who underwent heart transplant demonstrated abnormal preoperative liver ultrasound findings. Heterogeneous echotexture or nodularity detected on U/S frequently indicates underlying liver parenchymal abnormalities. The presence of severe liver abnormalities was not associated with higher early mortality post‐heart transplant in pediatric Fontan patients; however, late outcomes must be further elucidated.     

Variability in immunization guidelines in children before and after lung transplantation

Lung transplant candidates and recipients are at high risk of infections from vaccine-preventable diseases. However, well-established guidelines neither exist for pre- and post-transplant vaccination nor do monitoring guidelines for pediatric lung transplant recipients. To ascertain the current vaccination and monitoring practices of pediatric lung transplant centers, a self-administered questionnaire was distributed to the 18 pediatric lung transplant centers within the International Pediatric Lung Transplant Collaborative in April 2006. Sixteen of 18 centers (89%) surveyed responded. Pretransplant, national vaccination guidelines are followed. Eleven centers reported following standardized vaccination guidelines post-transplant. Vaccines were more commonly provided by the primary-care physician pretransplant (69%) rather than post-transplant (38%). Post-transplant, 50% of the centers recommend live vaccines for household contacts but not for the transplant recipient. Pretransplant monitoring of response to prior vaccination was performed inconsistently except for varicella (88%). Only 44% of the transplant centers measure for response to vaccination post-transplant, mostly hepatitis B. Current vaccination practices of pediatric lung transplant centers are heterogeneous. The lung transplant community would be well served by studies designed to evaluate the efficacy of vaccinations in this population.     

High‐risk age window for mortality in children with cystic fibrosis after lung transplantation

LTx in children with CF remains controversial. The UNOS database was queried from 1987 to 2013 for CF patients <18 yr of age at time of transplant. PCHR model was used to quantify hazard of mortality. 489 recipients were included in the survival analysis. The hazard function of post‐transplant mortality was plotted over attained age to identify age window of highest risk, which was 16–20 yr. Unadjusted PCHR model revealed ages immediately after the high‐risk window were characterized by lower hazard of mortality (HR = 0.472; 95% CI = 0.302, 0.738; p = 0.001). After adjusting for potential confounders, the decline in mortality hazard immediately after the high‐risk window remained statistically significant (HR = 0.394; 95% CI: 0.211, 0.737; p = 0.004). Hazard of mortality in children with CF after LTx was highest between 16 and 20 yr of attained age and declined thereafter.     

Long‐term outcomes of simultaneous heart and kidney transplantation in pediatric recipients

Pediatric sHKTx has become an effective therapy for patients with combined cardiac and renal failure. Often, these patients develop human leukocyte antigen antibodies from their previous allografts and are therefore more difficult to re‐transplant. We describe the largest case series of a predominantly sensitized pediatric sHKTx with emphasis on medical management and patient outcomes. Demographics, clinical characteristics, antibody, and biopsy data were retrospectively collected from University of California, Los Angeles database and correlated with short‐ and long‐term patient and allograft outcomes of all sHKTx performed between 2002 and 2015. We identified seven pediatric patients who underwent sHKTx at our center. Mean age at time of sHKTx was 13.7 years and 85.7% were re‐graft patients. 57.1% were sensitized with cPRA >50% and another 57.1% had preformed donor‐specific antibody. Five‐year renal allograft survival and patient survival was 85.7% for both end‐points. The remaining six patients are all alive (mean follow‐up 78.5 months) with good kidney and heart function. sHKTx in a population with increased immunological risk can be associated with good long‐term outcomes and offers potential guidance to the pediatric transplant community where data are limited.     

Persistence of post‐operative color Doppler abnormalities is linked to reduced graft survival in pediatric patients after liver transplantation

Color Doppler US is a readily available imaging modality for the evaluation of liver transplants. The aim of our study was to evaluate the temporal course of color Doppler US findings in children after LTX and to investigate the effect of resolving and persisting abnormalities during follow‐up on long‐term outcome. All children who underwent LTX during January 2000 until December 2003 (155 LTX in 137 patients, 75 male and 62 female; mean age at LTX 4.1 ± 4.8 years; range, 0.1‐16.3 years) were retrospectively evaluated. Following a predefined ultrasound protocol with prospective documentation, intraoperative, post‐operative, and follow‐up examinations were evaluated for color Doppler abnormalities. The time of occurrence and temporal course of the findings were recorded. Graft survival rates and graft survival times were compared. Abnormal color Doppler US examinations were noted in 98 of 155 grafts during the entire observational period (63.2%). In 57 of 98 grafts (58.2%), abnormalities were limited to the perioperative period (<30 days after LTX). Survival of grafts with transient perioperative abnormalities was similar to transplantations with regular color Doppler US examinations (graft survival rates, 80.7% vs 84.2%, P = .622; mean graft survival time, 2596.92 vs 2511.40 days, P = .67). Grafts with persisting color Doppler US abnormalities in the follow‐up period (>30 days after LTX; 37/98 LTX, 37.8%) showed reduced survival compared with regular courses (graft survival rate 62.2% vs 80.7%, P = .047), indicating underlying organ‐specific alterations. Standardized longitudinal evaluation during the perioperative and the follow‐up period can enhance the prognostic capabilities of color Doppler US in children following LTX.     

Long‐term outcomes and predictors in pediatric liver retransplantation

Historically, 9–29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed. Kaplan–Meier estimates were used to depict patient and graft survival. Predictors of survival were analyzed using a series of Cox proportional hazards models. Predictors were analyzed separately for patients who had “early” (≤30 days after primary transplant) and “late” retransplants. Eighty‐four patients underwent retransplant at a median time of 241 days. Sixty percent had late retransplants. At one, five, and 10 yr, actuarial patient and graft survival were 73%/71%, 66%/63%, and 58%/53%, respectively. Since 2002, patient and graft survival improved to 86%/86% at one yr and 93%/87% at five yr. While operative complications were a common cause of death after earlier retransplants, since 2002, infection has been the only cause of death. Significant morbidities at five‐yr follow‐up include renal dysfunction (15%), diabetes (13%), hypertension (26%), chronic rejection (7%), and PTLD (2%). Current survival after pediatric liver retransplantation has improved significantly, but long‐term immunosuppressant morbidity remains an opportunity for improvement.