e5 170 Pollack MM, Holubkov R, Funai T, et al Relationship between the functional status scale and the pediatric overall performance cate gory and pediatric cerebral performance category scales JAMA P[.]
e5 157 Bennett CC, Johnson A, Field DJ, Elbourne D, UK Collaborative ECMO Trial Group UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation: follow-up to age years Lancet 2001;357:1094-1096 158 Polito A, Barrett CS, Rycus PT, Favia I, Cogo PE, Thiagarajan RR Neurologic injury in neonates with congenital heart disease during ECMO: an analysis of the ELSO registry ASAIO J 2015;61:43-48 159 Teele SA, Salvin JW, Barrett CS, et al The association of carotid artery cannulation and neurologic injury in pediatric patients supported with venoarterial ECMO Pediatr Crit Care Med 2014;15:355-361 160 Di Gennaro JL, Chan T, Farris RWD, Weiss NS, McMullan DM Increased stroke risk in children and young adults on ECMO with carotid cannulation ASAIO J 2019;65:718-724 161 Spoel M, van der Cammen-van Zijp MH, Hop WC, Tibboel D, de Jongste JC, Ijsselstijn H Lung function in young adults with CDH: a longitudinal evaluation Pediatr Pulmonol 2013;48:130-137 162 Zwiers AJ, Ijsselstijn H, van Rosmalen J, et al CKD and hypertension during long-term follow-up in children and adolescents previously treated with extracorporeal membrane oxygenation Clin J Am Soc Nephrol 2014;9(12):2070-2078 163 Ijsselstijn H, van Heijst AF Long-term outcome of children treated with neonatal extracorporeal membrane oxygenation: increasing problems with increasing age Semin Perinatol 2014;38:114-121 164 van der Cammen-van Zijp MH, Janssen AJ, Raets MM, et al Motor performance after neonatal extracorporeal membrane oxygenation: a longitudinal evaluation Pediatrics 2014;134:e427-e435 165 Toussaint LC, van der Cammen-van Zijp MH, Janssen AJ, Tibboel D, van Heijst AF, IJsselstijn H Perceived motor competence differs from actual performance in 8-year-old neonatal ECMO survivors Pediatrics 2016;137:e20152724 166 Schiller RM, Madderom MJ, Reuser JJ, et al Neuropsychological follow-up after neonatal ECMO Pediatrics 2016;138:e20161313 167 Madderom MJ, Reuser JJ, Utens EM, et al Neurodevelopmental, educational and behavioral outcome at years after neonatal ECMO: a nationwide multicenter study Intensive Care Med 2013;39:1584-1593 168 Leeuwen L, Schiller RM, Rietman AB, et al Risk factors of impaired neuropsychologic outcome in school-aged survivors of neonatal critical illness Crit Care Med 2018;46:401-410 169 Schiller RM, Madderom MJ, van Rosmalen J, et al Working memory training following neonatal critical illness: a randomized controlled trial Crit Care Med 2018;46:1158-1166 170 Pollack MM, Holubkov R, Funai T, et al Relationship between the functional status scale and the pediatric overall performance category and pediatric cerebral performance category scales JAMA Pediatr 2014;168:671-676 171 Engle WA, West KW, Hocutt GA, et al Adult outcomes after newborn respiratory failure treated with extracorporeal membrane oxygenation Pediatr Crit Care Med 2017;18:73-79 172 IJsselstijn H, Hunfeld M, Schiller RM, et al Improving long-term outcomes after extracorporeal membrane oxygenation: from observational follow-up programs toward risk stratification Front Pediatr 2018;6:177 173 Rochow N, Chan EC, Wu WI, et al Artificial placenta—lung assist devices for term and preterm newborns with respiratory failure Int J Artif Organs 2013;36(6):377-391 174 Maul TM, Kuch BA, Wearden PD Development of risk indices for neonatal respiratory extracorporeal membrane oxygenation ASAIO J 2016;62:584-590 175 Barbaro RP, Bartlett RH, Chapman RL, et al Development and validation of the neonatal risk estimate score for children using extracorporeal life support J Pediatr 2016;173:56-61 176 Barbaro RP, Boonstra PS, Paden ML, et al Development and validation of the pediatric risk estimate score for children using extracorporeal respiratory support (Ped-RESCUERS) Intensive Care Med 2016;42:879-888 177 Bailly DK, Reeder RW, Zabrocki LA, et al Development and validation of a score to predict mortality in children undergoing extracorporeal membrane oxygenation for respiratory failure: pediatric pulmonary rescue with extracorporeal membrane oxygenation prediction score Crit Care Med 2017;45:e58-e66 178 Schmidt M, Bailey M, Sheldrake J, et al Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score Am J Respir Crit Care Med 2014;189:1374-1382 179 Bailly DK, Reeder RW, Winder M, et al Development of the pediatric extracorporeal membrane oxygenation prediction model for risk-adjusting mortality Pediatr Crit Care Med 2019;20: 426-434 180 Schmidt M, Burrell A, Roberts L, et al Predicting survival after ECMO for refractory cardiogenic shock: the survival after venoarterial-ECMO (SAVE)-score Eur Heart J 2015;36:2246-2256 181 Guner YS, Nguyen DV, Zhang L Development and validation of extracorporeal membrane oxygenation mortality-risk models for congenital diaphragmatic hernia ASAIO J 2018;64:785-794 e6 Abstract: Extracorporeal life support, commonly known as extracorporeal membrane oxygenation (ECMO), is a modified form of cardiopulmonary bypass that can support heart, lung, or multiple organs until recovery or bridge to another device or transplant occurs ECMO can be provided in a venoarterial or venovenous mode New technology has resulted in expansion to new patient groups, especially in adults, and a transition from roller pump/ silicone membrane lungs to centrifugal pump/hollow fiber membrane lung systems Bleeding and thrombosis remain major complications and increase morbidity and mortality This chapter provides an overview of cannulation techniques, current practice, general management, outcomes, and future directions Key words: extracorporeal life support, extracorporeal membrane oxygenation, ECMO, pediatric, neonatal, children, outcomes, cannulation 57 Pediatric Lung Transplantation CAROL CONRAD PEARLS • Pediatric lung transplantation is an accepted option for children of all ages who have end-stage, life-threatening disease and all medical options for treatment have been exhausted • Outcomes in pediatric lung transplantation are as good as adult outcomes, including infants • Most gains in survival posttransplantation have been brought by improved surgical techniques and preservation fluids for the lung graft • Chronic lung allograft dysfunction is the limiting factor to longterm survival after lung transplantation In 1998, the American Society of Transplantation (AST), International Society of Heart and Lung Transplantation (ISHLT), and American Thoracic Society (ATS) jointly published international guidelines for the selection of adult lung transplant candidates These recommendations were formulated among collaborators from the International Pediatric Lung Transplant Collaborative in 2007.1 This report represents the first set of guidelines specifically designed for children who may require a lung transplant From the first pediatric lung transplantations in 1986 through 2017, there have been a total of 2346 such procedures performed (100 annually) and an additional 735 pediatric heart-lung transplantations The majority of the lung transplantations in any given year are performed in older children (11–17 years); cystic fibrosis (CF) is the most common diagnosis in this age group Infants are transplanted with low frequency—less than per year globally The primary indications for referral have broadened with improvement in medical therapies for CF and primary pulmonary arterial hypertension (PAH) Infants with congenital end-stage lung disease is an increasingly frequent indication for lung transplantation The leading lung disease diagnoses resulting in the need for transplant change with the recipient age group CF is most frequent in children aged 11 years or greater—63% compared with 51% in younger children aged to 10 years In infants, the combined forms of pulmonary hypertension (PH) accounted for 38% of all transplants, the next largest cohort being surfactant disorders (20%; Table 57.1).2 (2) reliable access to transplant services and medications after transplantation; and (3) assurance that the patient and support system can and will adhere to the rigorous therapeutic plan before and after the transplantation Indications Lung transplantation is considered in selected children with endstage or progressive lung disease or life-threatening pulmonary vascular disease for which there is no other medical therapy Regardless of the underlying diagnosis, all candidates require (1) a clear diagnosis and well-delineated trajectory of illness such that the child is at high risk of death despite optimal medical therapy; Contraindications Comorbid disorders can complicate the procedure and compromise the outcome Box 57.1 includes several relative contraindications, though there is significant variability between centers Most pediatric centers will use mechanical ventilation for patients who develop respiratory failure after listing despite the fact that mechanical ventilation is a risk factor for mortality.2,3 More recently, extracorporeal support has been used to bridge pediatric and adult patients to transplant, including venovenous extracorporeal membrane oxygenation (VV ECMO)4–6 and pumpless, low-resistance membrane oxygenator devices The early experiences for patients undergoing lung transplantation directly from ECMO had poor outcomes, with an overall survival rate of only 40%.7 Since then, single-center reports of outcomes after VV ECMO show that, with careful selection and emphasis on rehabilitation, the short-term survival is similar to those who were not supported pretransplant with VV ECMO In an optimal setting that incorporates experienced physical therapists, following lung transplantation, these patients can be ambulatory less than week posttransplantation.8–10 Some centers use central transthoracic placement of the ECMO catheters to allow patients to move their heads freely and ambulate more easily Another advantage of this mode is that it prevents recirculation and minimizes damage to the tricuspid valve.11 Paracorporeal membrane oxygenation has been used in a subset of infants and children The method entails use of a membrane oxygenator interposed between the pulmonary artery (PA) to left atrium (LA) that serves as a pumpless oxygenator to allow for extubation and rehabilitation while awaiting lung transplantation.12 679 680 S E C T I O N V Pediatric Critical Care: Pulmonary TABLE Pediatric Lung Transplants (January 2000 to June 2017): Diagnosis by Age Group 57.1 Diagnosis ,1 Year 1–5 Years 6–10 Years 11–17 Years CF (0.0%) (3.4%) 125 (51%) 859 (66.3%) (7.9%) (6.8%) (2.4%) 39 (3.0%) (11.1%) (7.7%) 22 (9.0%) 50 (3.9%) IPAH (14.3%) 33 (28.2%) 25 (10.2%) 111 (8.6%) PH, not IPAH 15 (23.8%) 26 (22.2%) 10 (4.1%) 27 (2.1%) ABCA3 (7.9%) (4.3%) (0.8%) (0.1%) Surfactant protein B deficiency 13 (20.6%) (3.4%) (0.4%) (0%) Other (14.4%) 18 (15.5) 40 (11.5%) 143 (11.1) ILD ILD, other a a Secondary to systemic disorder ABCA3, ATP binding cassette subtype transporter mutation; CF, cystic fibrosis; ILD, interstitial lung disease; IPAH, idiopathic pulmonary arterial hypertension; OB, obliterative bronchiolitis; PH, pulmonary hypertension; SFTPB, surfactant protein B mutation • BOX 57.1 Most Commonly Agreed Upon Contraindications Absolute Contraindications Relative Contraindications Active malignancy Sepsis Active tuberculosis Severe neuromuscular disease Documented, refractory nonadherence Multiple organ dysfunction Acquired immunodeficiency syndrome Hepatitis C with histologic liver disease Untreatable bleeding diathesis Psychiatric or psychologic conditions associated with the inability to cooperate with the medical/allied healthcare team and/or adhere with complex medical therapy Absence of an adequate or reliable social support system Pleurodesis Renal insufficiency Markedly abnormal body mass index Mechanical ventilation or ECMOa Scoliosis Poorly controlled diabetes mellitus Osteoporosis Hepatitis B surface antigen positive High inotrope requirements Deconditioned physical state Highly sensitized to HLA antigens Chronic airway infections with multiply resistant organisms a Some transplant centers consider venoarterial ECMO an absolute contraindication However, increasing experience with V-V ECMO (ambulatory ECMO) demonstrates improving short-term outcomes; thus, V-V ECMO is a relative contraindication ECMO, Extracorporeal membrane oxygenation; HLA, human leukocyte antigen; V-V, venovenous Survival and Outcomes Despite improvements in clinical outcome, morbidity and mortality associated with lung transplantation remains high Mortality is greatest in the first year, with approximately 10% to 15% of all recipients dying owing to infection, cardiovascular failure, and/ or multiorgan failure Nevertheless, the overall median survival rate has improved over the past 30 years Survival is similar between CF patients and children with other diagnoses (Fig 57.1) Survival is also similar among all pediatric recipients, including infants, when conditional survival to year is considered (Fig 57.2) Before 2000, median survival was 3.3 years among all children but has improved substantially to 5.8 years after 2000 Upon conditional analysis limited to survival to year, pediatric median survival surpasses that of adults to 8.9 versus 8.2 years (Fig 57.3).2 Single-lung transplantation has not been applied to the pediatric population for over a decade, as mortality is 40% in the first year and the survival of those few recipients was significantly decreased (median survival, 2.2 years) compared with patients who undergo bilateral sequential lung transplantation.13,14 Extended survival is compromised by chronic lung allograft dysfunction (CLAD), previously termed bronchiolitis obliterans syndrome (BOS) CLAD is thought to emerge as a result of various injuries to the graft that result in chronic active inflammation and a dysregulated injury response to various insults, including acute rejection and infection The measured pulmonary mechanics of the graft encompasses a spectrum of phenotypes spanning between obstructive and restrictive phenotypes, as detected by pulmonary function testing (PFT) BOS is characterized by progressive airflow obstruction due to fibrotic obliteration of the small airways Restrictive allograft syndrome (RAS) is characterized by restrictive lung function mechanics; studies may demonstrate elements of both.15 Within years of transplantation, fewer than 50% of transplant recipients are free from BOS2 (Fig 57.4) Significant study has been applied to identify the etiologies of CLAD, yet the pathophysiology is not well characterized Treatments are generally palliative rather than curative.16,17 Evaluation of the Donor Criteria to assess the acceptability of lung donors have been developed Box 57.2 describes the criteria used to define an ideal donor These criteria have been developed largely from clinical experience rather than from large multicenter trials Specific criteria CHAPTER 57 Pediatric Lung Transplantation 100 ILD (N = 98) CF (N = 1,203) ILD other (N = 96) IPAH (N = 217) 75 Survival (%) OB (non-Retx) (N = 100) PH-not IPAH (N = 115) 50 25 No pairwise comparisons were significant at P < 05 Median survival (years): CF = 5.4; ILD = 4.4; ILD other = 6.3; OB (non-Retx) = NA; IPAH = 7.2 0 Years 10 11 12 • Fig 57.1 Kaplan-Meier survival by diagnosis (transplantation performed January 1994 to June 2016) CF, Cystic fibrosis; ILD, interstitial lung disease; IPAH, idiopathic pulmonary arterial hypertension; non-Retx, non-retransplant; OB, obliterative bronchiolitis; PH, pulmonary hypertension 100 No pairwise comparisons were significant at P < 05 Survival (%) 75