Pediatr Transplantation 2014: 18: 586–593

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Pediatric Transplantation DOI: 10.1111/petr.12318

Functional capacity after pediatric liver transplantation: A pilot study Maria da Silva R, Brunow de Carvalho W, Johnston C, Borba de Castro M, Ferreira IM, Patti CL, Anthero de Azevedo R, Miziara Gonzalez A, Moura Linhares M, Augusto Salzedas-Netto A. (2014) Functional capacity after pediatric liver transplantation: A pilot study. Pediatr Transplant, 18: 586–593. DOI: 10.1111/petr.12318. Abstract: 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 9 body weight) with the anthropometric, clinical, and pulmonary functions. In posttransplanted 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.

Ros^angela Maria da Silva1, Werther Brunow de Carvalho2, Cıntia Johnston1, Mariela Borba de Castro1, Israel Manta Ferreira1, Camilla L. Patti3, Ramiro Anthero de Azevedo4, Adriano Miziara Gonzalez4, Marcelo Moura Linhares4 and Alcides Augusto Salzedas-Netto4 1

Department of Pediatrics, Universidade Federal de S~ao Paulo (UNIFESP), S~ao Paulo, Brazil, 2Intensive Care/Neonatology at Children’s Institute, Medical School, University of S~ao Paulo, S~ao Paulo, Brazil, 3 Department of Pharmacology, Universidade Federal de S~ao Paulo (UNIFESP), S~ao Paulo, Brazil, 4Division of Pediatric Liver Transplantation, Department of Surgery, Universidade Federal de S~ao Paulo (UNIFESP), S~ao Paulo, Brazil Key words: liver transplantation – stress test – physical fitness – reproducibility – children – sixmin walk test Ros^angela Maria da Silva, Department of Pediatrics, Universidade Federal de S~ao Paulo (UNIFESP), 04304-000, S~ao Paulo, SP, Brazil Tel.: +55 011 96176 9119 Fax: +55 011 5081 9624 E-mail: [email protected] or [email protected] Accepted for publication 3 June 2014

Pediatric liver transplantation is one of the most successful solid organ transplantations. Over the past two decades, new immunosuppressive therapies, anesthesia, and surgery have contributed to the improvement in patient survival and graft success (1). Despite these continuous improve-

Abbreviations: 6MWD, six-minute walk distance; 6MWT, six-minute walk test; 6MWw, six-minute walk work; AJE, American Journal Experts; ATS, American Thoracic Society; BMI, body mass index; CPET, cardiopulmonary exercise test; DBP, diastolic blood pressure; FVC, forced vital capacity; HR, heart rate; ICC, intraclass correlation; LL, lower limbs; MELD, model end-stage liver disease; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; PEF, peak expiratory flow; PELD, pediatric endstage liver disease; RR, respiratory rate; SBP, systolic blood pressure; SEE, standard error of the estimate; VE, ventilation expired rate; VT, tidal volume.

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ments, several studies (2, 3) have reported functional consequences of liver transplantation, such as intolerance to physical exercises (4). In fact, the exercise capacity of the recipient is remarkably hindered in the postoperative period, regardless of the type of organ transplant (5–9). There is still scarce information (10, 11) concerning the exercise capacity of children and adolescents after liver transplantation. In fact, Unnithan et al. (10) initially characterize the fitness levels of pediatric liver recipients. The authors reported lower exercise capacity in transplanted children than in healthy children with gender- and age-based criterion-referenced standard. Submaximal tests of functional capacity, such as the 6MWT, are easier to conduct compared with the CPET, that is, the gold standard for measuring aerobic capacity (12), especially in

Fitness after liver transplantation

children and adolescents (13), for being practical, safe, inexpensive, and easy to perform. Additionally, the 6MWT replicates the daily activities more effectively compared with other walking tests (14). It has been shown that the distance walked in six min is considered the main outcome to evaluate functional capacity, although this measure does not ponder the influence of body weight as a significant factor. Hence, the use of the product of walked distance and body weight during the 6MWT represents an additional alternative to evaluate the work performed during testing, known as the 6MWw (15–17). The 6MWT, increasingly used in pediatrics, has shown good reliability in healthy children (18, 19) and ones with chronic conditions (17, 20–22). However, from the best of our knowledge, no study has addressed the reproducibility of the 6MWT in children subjected to liver transplantation or examined the use of this test to evaluate physical capacity in such population. The purpose of this study was to evaluate the functional exercise capacity of children and adolescents after liver transplantation, comparing the distance walked in six min with normal values from healthy Brazilian children (23) as well as the reproducibility of the 6MWT in this population. In addition, we aimed to analyze the relationship between the walked distance and the 6MWw with the anthropometric, clinical, and pulmonary functions. Our expectation is that the pediatric liver recipients would show reduced physical fitness compared with healthy children and that the 6MWw measure would express the physical capacity more effectively than distance alone in these patients. Methods Study design A cross-sectional study was prospectively conducted from January 2009 to December 2010.

Subjects From a convenience sample, we evaluated 22 liver-transplanted children and adolescents of both gender, aged 6–17, who were followed up at the Liver Transplant Unit, Discipline of Gastroenterology, Universidade Federal de S~ ao Paulo, Brazil. All patients agreed to participate in the proposed evaluations. The study excluded patients with respiratory diseases and pulmonary complication, heart disease, arthritis, musculoskeletal diseases, orthopedic, psychiatric, and neurological problems that would limit the exercise test and the ability to understand the exercise procedures and children under six yr of age. The patients did not attend any kind of physical training during the study period according to medical recommendations. This study was approved by the ethics committee under the protocol #1563/08.

Procedures During the procedures, all patients were evaluated by a trained physical therapist. Firstly, an interview focused on cardiopulmonary function was performed with the child and their parents or legal guardian and they were queried about clinical history. Secondly, they underwent clinical evaluation, pulmonary function, and physical exercise tests. All of the procedures were performed until three months after transplantation.

Anthropometric measurements Height (m) and weight (kg) of barefoot patients were measured using an anthropometric scale (Filizolaâ, model 31; S~ ao Paulo, SP, Brazil). From these measurements, the BMI was calculated using AnthrosPlus from the World Health Organization Child Growth Standards (24).

Assessment of pulmonary function The PEF (Mini-Wrightâ peak expiratory flow meter; Clement Clarke International Ltd., Essex, UK) was measured according to the Guidelines for Pulmonary Function Tests of The Brazilian Thoracic Society (25). Respiratory muscle strength was determined by the evaluation of the maximal inspiratory or expiratory pressures, according to the ATS (2002) (26). FVC was evaluated (25) by means of an analogue Wright ventilometer (Ferraris Medical Ltd., Mark 8, Hertford, UK). The maximum value out of the three was labeled as the FVC (l). The VE was then calculated by multiplying VT and RR.

Assessment of exercise capacity The 6MWT was performed as recommended by the ATS criteria (27). Each patient walked his/her maximum distance through an empty 20-m-long walk corridor without help from the therapist. The corridor had three-meter interval marks. Heart rate (HR, bpm), RR (breaths/min), partial pressure of end-tidal carbon dioxide (PETCO2, mmHg), and pulse oxyhemoglobin saturation (SpO2%) were evaluated immediately before and after the test and in the third min of the test intercourse, using an oxi-capnograph (Sp Tidal Waveâ, model 715, Novametrix-capnography/oximetry; Respironics, S~ ao Paulo, Brazil). Dyspnea and fatigue in the LL were measured using the Borg scale for perceived exertion with values between 0 and 10 (28). These measurements were recorded at the beginning and at the end of the test. Patients performed only two tests in order to minimize the learning effect. The interval between tests was 30 min. The test was discontinued when signs or symptoms were detected, as recommended by ATS (12). Supplemental oxygen was only administered if the SpO2 was below 85% (12). The physical performance test was determined by total distance walked in meters. Maximum HR was obtained by the formula: HRmax = 210 (0.65 9 age) (29). The distance walked over six min was compared to the normal values obtained by Aquino et al. (23) in healthy Brazilian children from seven to 14 yr of age. For comparative analyses, the higher walked distance was selected. Although the walked distance is considered the main variable to measure the functional capacity, previous studies (15, 16) have shown that 6MWw, defined as the

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Maria da Silva et al. product of the distance (m) and body weight (kg), better correlates with the performance of the patients during the test. The resulting work is expressed in kilograms per body mass per meter walked in the 6MWT.

Statistical analysis The study variables were distributed normally as evaluated by the Kolmogorov–Smirnov test. The results are described as mean, standard deviation, median, minimum, maximum, and 95% confidence interval. The unpaired Student’s t-test was used to compare the Brazilian normal values of distance walked (687 m  80 m) (23) to the studied population. The Pearson correlation test was used to correlate the walked distance in the 6MWT and the 6MWw with anthropometric (age, weight, height, BMI), clinical variables (PELD/MELD score, time of transplant) as well as pulmonary function (FVC, VE, VC, PEF, MIP, and MEP) and variables related to the 6MWT (HR, RR, SBP, DBP, SPO2, PETCO2, Borg scale of dyspnea, and fatigue of the LL). Concerning the Pearson correlation values, we assumed that a correlation value ≥0.7 was strong, 0.4–0.69 values were moderate, and

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-transp...
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