How Low Can We Go? The Changing Landscape of Extracorporeal Support in Infants* Heidi J. Dalton, MD, FCCM Critical Care Medicine Phoenix Children’s Hospital University of Arizona College of Medicine in Phoenix Phoenix, AZ
O
ver the past 10 years, the field of cardiopulmonary bypass in children has advanced at an exponential pace. As bypass technology and surgical expertise has advanced, complex surgical procedures for lesions once deemed inoperable have developed and mortality in infants has decreased (1–3). These initiatives have also helped advance the field of extracorporeal support (ECLS) outside the operating theater. A major factor in eligibility for operative repair or ECLS initiation has been gestational age and/or weights, as these characteristics have resulted in high mortality (4–6). This changing landscape is evidenced by reports such as the recent review of 3,022 infants undergoing cardiac surgery reported to the Society of Thoracic Surgeons (STS) database (2002–2004). Over 500 of the 3,022 infants analyzed had received operative repair at weights less than 2.5 kg. Although these infants had increased risk of death as compared with larger patients (weights of 2.5–4 kg), survival rates of 70–90% were obtained (7) Single-center reports evaluating weight and gestation are also somewhat encouraging, with some sites finding little effect on outcome (8–10). As infants undergoing cardiac surgery are fragile with minimal cardiopulmonary reserve, they are prone to sudden deterioration which can lead to acute arrest. ECLS applied during active cardiac arrest is termed extracorporeal cardiopulmonary resuscitation (ECPR) (11). Now reported in over 3,000 patients from newborn to adult, infants following surgical repair of congenital heart defects form the largest group of ECPR recipients (12, 13). In this issue of Pediatric Critical Care Medicine, McMullan et al (14) describe the outcome of infants less than or equal to 30 days of age undergoing ECPR, with a special focus on the effects of weight and gestational age on survival. The data from this review are encouraging in that 39% of infants receiving ECPR and 20% of children less than 2 kg survived. It adds to the small amount of literature that
*See also p. e9. Key Words: extracorporeal membrane oxygenation; infant; mortality; premature; weight Dr. Dalton is on the steering committee for the Extracorporeal Life Support Organization organization and received grant support from National Institutes of Health (not related to this article). Copyright © 2013 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/01.pcc.0000436199.92465.f9
88
www.pccmjournal.org
describes the adverse effects of weight on intracranial hemorrhage and death but delineates no specific cutoff for gestational age or weight which precludes survival from ECLS (15). One wishes, however, that more specific details were available from which to identify factors associated with outcome from ECPR. As mentioned in the text, the Extracorporeal Life Support Organization (ELSO) registry does not include information on cardiopulmonary resuscitation (CPR) duration, etiology, and other factors which have been reported to influence outcome from resuscitation (16–18). An ECPR addendum to address these limitations has been developed and is soon to become web based. By the same token, a Cardiac Addendum to the ELSO registry exists to provide more in-depth information regarding surgical repairs, diagnosis, residual lesions and, other factors which have been shown to influence outcome from cardiopulmonary bypass. As these ELSO database extensions are used, a clearer picture of patients receiving ECPR and factors associated with outcome can be drawn. Another method to obtain needed data points would be to link ELSO information with other databases. Registries such as the STS, the Get with the Guidelines CPR database (formerly the National Registry of Cardiopulmonary Resuscitation registry), Child Health Care of America/Pediatric Health Information System, and ELSO could be queried for specific data points and a more complete picture of the patient and outcome factors examined. This could reduce the “work” and personnel costs involved in registry completion, as demographic data which is required by all would not require repetitive data entry. Data analysis combining specific items taken from linked database evaluation may improve vital information to improve outcome, reduce healthcare costs, and guide intervention and research efforts for the future. Efforts to “link and share” database information are underway among many organizations, but Health Information Portability and Accountability Act limitations make it confusing and potentially difficult to achieve such goals. Issues over who “owns” data, how it is shared, and other factors will also require resolution. The ability to have a single database to collect all data is likely impossible, as details which would be crucial in answering some questions would be irrelevant in others. The impact of the electronic health record and technology on this area of research is unknown but holds great promise. Another comment concerns the issue of transparency. Hospitals are now required to report outcomes in a wide variety of ways, and comparison among sites is becoming commonplace (19–21). Data suggest that for complex patients, volume, environment, and expertise play a role in patient outcome and resource use (22–24). Based on its origin as a voluntary database for reporting case series of patients and providing conglomerate quality assurance data for patients undergoing ECLS, January 2014 • Volume 15 • Number 1
Editorials
ELSO has remained opaque in identifying specific centers data and has limited its registry primarily to elements involved in ECLS and patient-specific data. There is no policy that mandates reporting of all patients receiving ECLS at a specific center or that centers providing ECLS (either nationally or internationally) report data to ELSO or another group, thus limiting the quality control and global ECLS overview which is a goal of ELSO. Addressing this issue is timely, as new technology and interest in ECLS is leading to many new centers opening ECLS services, particularly among adult providers. The need to examine the role of expertise, patient-specific and center-specific elements, and outcomes are paramount as ECLS expands. A recent review of ECLS patients reported to an administrative database (Healthcare Cost and Utilization Project Kids’ Inpatient Database) found that outcome was worse and resource use higher in centers supporting lees than 6 patients per year (25). As there is little specific ECLS data contained within this registry, however, the ability to draw conclusions from such reports is limited. More open evaluation between sites of ECLS-specific data contained within the ELSO registry may add important factors to guide ECLS practice and care. One small step in this direction is the establishment of the ELSO “Center of Excellence” award. This designation is obtained by formal peer evaluation based on seven specific focus areas regarding a center’s ECLS program. The Center of Excellence designation is noted as a part of U.S. News and World Report evaluation. Additionally, the ELSO registry is becoming web based, allowing centers to perform comparisons between their site regarding outcome, complications, and other factors to the ELSO registry as a whole. One final comment involves the major complications related to death both among premature and low weight patients and overall ECLS recipients. Bleeding and thrombosis remain the most common and severe complications related to ECLS, and intracranial hemorrhage among low weight and premature infants remains a major cause of death. Improving transparency in practice and evaluating outcome may also provide new data related to these complications. Such data can drive development of standardized and optimized protocols and algorithms for care among ECLS patients which can one day perhaps be universally applied. ECPR is one of many exciting and vibrant areas within ECLS that deserve ongoing evaluation in a detailed approach that can help optimize patient care and outcome. The review by McMullan et al (14) adds to the body of literature regarding ECPR in small patients and leaves us asking for more.
REFERENCES
1. Alsoufi B, Manlhiot C, Awan A, et al: Current outcomes of the Glenn bidirectional cavopulmonary connection for single ventricle palliation. Eur J Cardiothorac Surg 2012; 42:42–48; discussion: 48–49 2. Feinstein JA, Benson DW, Dubin, et al: Hypoplastic left heart syndrome: Current considerations and expectations. J Am Coll Cardiol 2012; 59(1 Suppl):S1–S42 3. Chang AC, Hanley LF, Lock JE, et al: Management and outcome of low birth weight neonates with congenital heart disease. J Pediatr 1994; 124:461–466
Pediatric Critical Care Medicine
4. Costello JM, Polito A, Brown DW, et al: Birth before 39 weeks’ gestation is associated with worse outcomes in neonates with heart disease. Pediatrics 2010; 126:277–284 5. Bui KC, LaClair P, Vanderkerhove J, et al: ECMO in premature infants. Review of factors associated with mortality. ASAIO Trans 1991; 37:54–59 6. Makhoul IR, Bui KC, Fung TC, et al: Predictors of neonatal mortality in 1,500–1,999 g premature infants with respiratory failure. Basis for ECMO therapeutic trial. ASAIO J 1994; 40:27–32 7. Curzon CL, Milford-Beland S, Li JS, et al: Cardiac surgery in infants with low birth weight is associated with increased mortality: Analysis of the Society of Thoracic Surgeons Congenital Heart Database. J Thorac Cardiovasc Surg 2008; 135:546–551 8. Azakie A, Lavrsen MJ, Johnson NC, et al: Early outcomes of primary sutureless repair of the pulmonary veins. Ann Thorac Surg 2011; 92; 666–671; discussion: 671–672 9. Oppido G, Pace Napoleone C, Formigari R, et al: Outcome of cardiac surgery in low birth weight and premature infants. Eur J Cardiothorac Surg 2004; 26:44–53 10. Ades AM, Dominquez TE, Nicolson SC, et al: Morbidity and mortality after surgery for congenital cardiac disease in the infant born with low weight. Cardiol Young 2010; 20: 8–17 11. Chai PJ, Jacob JP, Dalton HJ, et al: Extracorporeal cardiopulmonary resuscitation for post-operative cardiac arrest: Indications, techniques, controversies, and early results—What is known (and unknown). Cardiol Young 2011; 21(Suppl 2):109–117 12. Raymond TT, Cunnygham CB, Thompson MT, et al: Outcomes among neonates, infants, and children after extracorporeal cardiopulmonary resuscitation for refractory inhospital pediatric cardiac arrest: A report from the National Registry of Cardiopulmonary Resuscitation. Pediatr Crit Care Med 2010; 11:362–371 13. Undar A, McKenzie DE, McGarry MC, et al: Outcomes of congenital heart surgery patients after extracorporeal life support at Texas Children’s Hospital. Artif Organs 2004; 28:963–966 14. McMullan DM, Thiagarajan RR, Smith KM, et al: Extracorporeal Cardiopulmonary Resuscitation Outcomes in Term and Premature Neonates. Pediatr Crit Care Med 2014; 15:e9–e16 15. Rozmiarek AJ, Qureshi FG, Cassidy L, et al: How low can you go? Effectiveness and safety of extracorporeal membrane oxygenation in low-birth-weight neonates. J Pediatr Surg 2004; 39:845–847 16. Berg RA, Bobrow BJ: Cardiac resuscitation: Is an advanced airway harmful during out-of-hospital CPR? Nat Rev Cardiol 2013; 10:188–189 17. Doski JJ, Butler TJ, Louder DS, et al: Outcome of infants requiring cardiopulmonary resuscitation before extracorporeal membrane oxygenation. J Pediatr Surg 1997; 32:1318–1321 18. Moler FW, Meert K, Donaldson AE, et al: In-hospital versus out-ofhospital pediatric cardiac arrest: A multicenter cohort study. Crit Care Med 2009; 37:2259–2267 19. Becker C: Consumers are king. From IT projects to quality initiatives to improved transparency, in ‘07 it’s all about making the healthcare experience better, safer. Mod Health 2007; 37:24–28 20. Craven, Ober: Transparency in reimbursement policy rewards clinical excellence: The pay-for-performance era means quality and revenue are no longer separate issues for healthcare providers. J Infus Nurs 2007; 30:18–19 21. Russell TR: Nothing to hide: Transparency in healthcare. MedGenMed 2006; 8:83 22. Shuhaiber JH, Moore J, Dyke DB: The effect of transplant center volume on survival after heart transplantation: A multicenter study. J Thorac Cardiovasc Surg 2010; 139:1064–1069 23. Checchia PA, McCollegan J, Daher N, et al: The effect of surgical case volume on outcome after the Norwood procedure. J Thorac Cardiovasc Surg 2005; 129:754–759 24. Birkmeyer JD: Relation of surgical volume to outcome. Ann Surg 2000; 232:724–725 25. Karamlou T, Vafaeezadeh M, Parrish AM, et al: Increased extracorporeal membrane oxygenation center case volume is associated with improved extracorporeal membrane oxygenation survival among pediatric patients. J Thorac Cardiovasc Surg 2013; 145:470–475 www.pccmjournal.org
89
O
ver the past 10 years, the field of cardiopulmonary bypass in children has advanced at an exponential pace. As bypass technology and surgical expertise has advanced, complex surgical procedures for lesions once deemed inoperable have developed and mortality in infants has decreased (1–3). These initiatives have also helped advance the field of extracorporeal support (ECLS) outside the operating theater. A major factor in eligibility for operative repair or ECLS initiation has been gestational age and/or weights, as these characteristics have resulted in high mortality (4–6). This changing landscape is evidenced by reports such as the recent review of 3,022 infants undergoing cardiac surgery reported to the Society of Thoracic Surgeons (STS) database (2002–2004). Over 500 of the 3,022 infants analyzed had received operative repair at weights less than 2.5 kg. Although these infants had increased risk of death as compared with larger patients (weights of 2.5–4 kg), survival rates of 70–90% were obtained (7) Single-center reports evaluating weight and gestation are also somewhat encouraging, with some sites finding little effect on outcome (8–10). As infants undergoing cardiac surgery are fragile with minimal cardiopulmonary reserve, they are prone to sudden deterioration which can lead to acute arrest. ECLS applied during active cardiac arrest is termed extracorporeal cardiopulmonary resuscitation (ECPR) (11). Now reported in over 3,000 patients from newborn to adult, infants following surgical repair of congenital heart defects form the largest group of ECPR recipients (12, 13). In this issue of Pediatric Critical Care Medicine, McMullan et al (14) describe the outcome of infants less than or equal to 30 days of age undergoing ECPR, with a special focus on the effects of weight and gestational age on survival. The data from this review are encouraging in that 39% of infants receiving ECPR and 20% of children less than 2 kg survived. It adds to the small amount of literature that
*See also p. e9. Key Words: extracorporeal membrane oxygenation; infant; mortality; premature; weight Dr. Dalton is on the steering committee for the Extracorporeal Life Support Organization organization and received grant support from National Institutes of Health (not related to this article). Copyright © 2013 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/01.pcc.0000436199.92465.f9
88
www.pccmjournal.org
describes the adverse effects of weight on intracranial hemorrhage and death but delineates no specific cutoff for gestational age or weight which precludes survival from ECLS (15). One wishes, however, that more specific details were available from which to identify factors associated with outcome from ECPR. As mentioned in the text, the Extracorporeal Life Support Organization (ELSO) registry does not include information on cardiopulmonary resuscitation (CPR) duration, etiology, and other factors which have been reported to influence outcome from resuscitation (16–18). An ECPR addendum to address these limitations has been developed and is soon to become web based. By the same token, a Cardiac Addendum to the ELSO registry exists to provide more in-depth information regarding surgical repairs, diagnosis, residual lesions and, other factors which have been shown to influence outcome from cardiopulmonary bypass. As these ELSO database extensions are used, a clearer picture of patients receiving ECPR and factors associated with outcome can be drawn. Another method to obtain needed data points would be to link ELSO information with other databases. Registries such as the STS, the Get with the Guidelines CPR database (formerly the National Registry of Cardiopulmonary Resuscitation registry), Child Health Care of America/Pediatric Health Information System, and ELSO could be queried for specific data points and a more complete picture of the patient and outcome factors examined. This could reduce the “work” and personnel costs involved in registry completion, as demographic data which is required by all would not require repetitive data entry. Data analysis combining specific items taken from linked database evaluation may improve vital information to improve outcome, reduce healthcare costs, and guide intervention and research efforts for the future. Efforts to “link and share” database information are underway among many organizations, but Health Information Portability and Accountability Act limitations make it confusing and potentially difficult to achieve such goals. Issues over who “owns” data, how it is shared, and other factors will also require resolution. The ability to have a single database to collect all data is likely impossible, as details which would be crucial in answering some questions would be irrelevant in others. The impact of the electronic health record and technology on this area of research is unknown but holds great promise. Another comment concerns the issue of transparency. Hospitals are now required to report outcomes in a wide variety of ways, and comparison among sites is becoming commonplace (19–21). Data suggest that for complex patients, volume, environment, and expertise play a role in patient outcome and resource use (22–24). Based on its origin as a voluntary database for reporting case series of patients and providing conglomerate quality assurance data for patients undergoing ECLS, January 2014 • Volume 15 • Number 1
Editorials
ELSO has remained opaque in identifying specific centers data and has limited its registry primarily to elements involved in ECLS and patient-specific data. There is no policy that mandates reporting of all patients receiving ECLS at a specific center or that centers providing ECLS (either nationally or internationally) report data to ELSO or another group, thus limiting the quality control and global ECLS overview which is a goal of ELSO. Addressing this issue is timely, as new technology and interest in ECLS is leading to many new centers opening ECLS services, particularly among adult providers. The need to examine the role of expertise, patient-specific and center-specific elements, and outcomes are paramount as ECLS expands. A recent review of ECLS patients reported to an administrative database (Healthcare Cost and Utilization Project Kids’ Inpatient Database) found that outcome was worse and resource use higher in centers supporting lees than 6 patients per year (25). As there is little specific ECLS data contained within this registry, however, the ability to draw conclusions from such reports is limited. More open evaluation between sites of ECLS-specific data contained within the ELSO registry may add important factors to guide ECLS practice and care. One small step in this direction is the establishment of the ELSO “Center of Excellence” award. This designation is obtained by formal peer evaluation based on seven specific focus areas regarding a center’s ECLS program. The Center of Excellence designation is noted as a part of U.S. News and World Report evaluation. Additionally, the ELSO registry is becoming web based, allowing centers to perform comparisons between their site regarding outcome, complications, and other factors to the ELSO registry as a whole. One final comment involves the major complications related to death both among premature and low weight patients and overall ECLS recipients. Bleeding and thrombosis remain the most common and severe complications related to ECLS, and intracranial hemorrhage among low weight and premature infants remains a major cause of death. Improving transparency in practice and evaluating outcome may also provide new data related to these complications. Such data can drive development of standardized and optimized protocols and algorithms for care among ECLS patients which can one day perhaps be universally applied. ECPR is one of many exciting and vibrant areas within ECLS that deserve ongoing evaluation in a detailed approach that can help optimize patient care and outcome. The review by McMullan et al (14) adds to the body of literature regarding ECPR in small patients and leaves us asking for more.
REFERENCES
1. Alsoufi B, Manlhiot C, Awan A, et al: Current outcomes of the Glenn bidirectional cavopulmonary connection for single ventricle palliation. Eur J Cardiothorac Surg 2012; 42:42–48; discussion: 48–49 2. Feinstein JA, Benson DW, Dubin, et al: Hypoplastic left heart syndrome: Current considerations and expectations. J Am Coll Cardiol 2012; 59(1 Suppl):S1–S42 3. Chang AC, Hanley LF, Lock JE, et al: Management and outcome of low birth weight neonates with congenital heart disease. J Pediatr 1994; 124:461–466
Pediatric Critical Care Medicine
4. Costello JM, Polito A, Brown DW, et al: Birth before 39 weeks’ gestation is associated with worse outcomes in neonates with heart disease. Pediatrics 2010; 126:277–284 5. Bui KC, LaClair P, Vanderkerhove J, et al: ECMO in premature infants. Review of factors associated with mortality. ASAIO Trans 1991; 37:54–59 6. Makhoul IR, Bui KC, Fung TC, et al: Predictors of neonatal mortality in 1,500–1,999 g premature infants with respiratory failure. Basis for ECMO therapeutic trial. ASAIO J 1994; 40:27–32 7. Curzon CL, Milford-Beland S, Li JS, et al: Cardiac surgery in infants with low birth weight is associated with increased mortality: Analysis of the Society of Thoracic Surgeons Congenital Heart Database. J Thorac Cardiovasc Surg 2008; 135:546–551 8. Azakie A, Lavrsen MJ, Johnson NC, et al: Early outcomes of primary sutureless repair of the pulmonary veins. Ann Thorac Surg 2011; 92; 666–671; discussion: 671–672 9. Oppido G, Pace Napoleone C, Formigari R, et al: Outcome of cardiac surgery in low birth weight and premature infants. Eur J Cardiothorac Surg 2004; 26:44–53 10. Ades AM, Dominquez TE, Nicolson SC, et al: Morbidity and mortality after surgery for congenital cardiac disease in the infant born with low weight. Cardiol Young 2010; 20: 8–17 11. Chai PJ, Jacob JP, Dalton HJ, et al: Extracorporeal cardiopulmonary resuscitation for post-operative cardiac arrest: Indications, techniques, controversies, and early results—What is known (and unknown). Cardiol Young 2011; 21(Suppl 2):109–117 12. Raymond TT, Cunnygham CB, Thompson MT, et al: Outcomes among neonates, infants, and children after extracorporeal cardiopulmonary resuscitation for refractory inhospital pediatric cardiac arrest: A report from the National Registry of Cardiopulmonary Resuscitation. Pediatr Crit Care Med 2010; 11:362–371 13. Undar A, McKenzie DE, McGarry MC, et al: Outcomes of congenital heart surgery patients after extracorporeal life support at Texas Children’s Hospital. Artif Organs 2004; 28:963–966 14. McMullan DM, Thiagarajan RR, Smith KM, et al: Extracorporeal Cardiopulmonary Resuscitation Outcomes in Term and Premature Neonates. Pediatr Crit Care Med 2014; 15:e9–e16 15. Rozmiarek AJ, Qureshi FG, Cassidy L, et al: How low can you go? Effectiveness and safety of extracorporeal membrane oxygenation in low-birth-weight neonates. J Pediatr Surg 2004; 39:845–847 16. Berg RA, Bobrow BJ: Cardiac resuscitation: Is an advanced airway harmful during out-of-hospital CPR? Nat Rev Cardiol 2013; 10:188–189 17. Doski JJ, Butler TJ, Louder DS, et al: Outcome of infants requiring cardiopulmonary resuscitation before extracorporeal membrane oxygenation. J Pediatr Surg 1997; 32:1318–1321 18. Moler FW, Meert K, Donaldson AE, et al: In-hospital versus out-ofhospital pediatric cardiac arrest: A multicenter cohort study. Crit Care Med 2009; 37:2259–2267 19. Becker C: Consumers are king. From IT projects to quality initiatives to improved transparency, in ‘07 it’s all about making the healthcare experience better, safer. Mod Health 2007; 37:24–28 20. Craven, Ober: Transparency in reimbursement policy rewards clinical excellence: The pay-for-performance era means quality and revenue are no longer separate issues for healthcare providers. J Infus Nurs 2007; 30:18–19 21. Russell TR: Nothing to hide: Transparency in healthcare. MedGenMed 2006; 8:83 22. Shuhaiber JH, Moore J, Dyke DB: The effect of transplant center volume on survival after heart transplantation: A multicenter study. J Thorac Cardiovasc Surg 2010; 139:1064–1069 23. Checchia PA, McCollegan J, Daher N, et al: The effect of surgical case volume on outcome after the Norwood procedure. J Thorac Cardiovasc Surg 2005; 129:754–759 24. Birkmeyer JD: Relation of surgical volume to outcome. Ann Surg 2000; 232:724–725 25. Karamlou T, Vafaeezadeh M, Parrish AM, et al: Increased extracorporeal membrane oxygenation center case volume is associated with improved extracorporeal membrane oxygenation survival among pediatric patients. J Thorac Cardiovasc Surg 2013; 145:470–475 www.pccmjournal.org
89
