Editorials
Functional Outcomes for Children With Severe Sepsis: Is a “Good Save” Good Enough?* Mary Hartman, MD, MPH John C. Lin, MD Department of Pediatrics Division of Pediatric Critical Care Medicine Washington University in St. Louis St. Louis, MO
R
ecent estimates indicate that approximately 75,000 U.S. children acquire severe sepsis each year, and this number is likely to continue to climb in the next few years (1). The overwhelming majority of these children will survive and return home to reintegrate into their families, schools, and communities. Although research on the early recognition (2, 3), treatment (4–6), and pathophysiologic basis (7, 8) for severe sepsis has made tremendous advances in the past decade, outcome studies evaluating the developmental, physical, and mental health consequences of severe infection in childhood are lacking. In this issue of Pediatric Critical Care Medicine, Farris et al (9) present the first description of 28-day functional outcome in 363 survivors of severe sepsis in childhood. This patient cohort from 18 countries ranging in age from newborn to 18 years old originated from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective (RESOLVE) trial, in which activated protein C was tested as a therapeutic agent for children with severe sepsis. RESOLVE, terminated early because of increased mortality in the therapy arm, also collected outcome data on all enrolled participants. Functional performance, as measured by the Pediatric Overall Performance Category (POPC), was identified at baseline by parent proxy report and then recorded by study personnel for all surviving subjects at 28 days post enrollment. Analyzing the RESOLVE data, Farris et al (9) found that the majority of pediatric severe sepsis patients (77%) were initially healthy, 10% had died by the time of follow-up, and 25% met the criteria for poor functional outcome at 28 days, defined as an increase in POPC score by at least 1 point and an absolute POPC score *See also p. 835. Key Words: critical care; outcomes; pediatric critical care; sepsis; severe sepsis The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0b013e3182a551e9
Pediatric Critical Care Medicine
more than 3. In total, one third of patients (34%) had a worse POPC score compared with baseline. Despite limitations with the POPC scoring tool and potential of recall bias in baseline proxy measurements, these data are certainly compelling. Gone are the days when sepsis could be thought of as an acute self-limited condition, regardless of preillness health status. In fact, despite using a conservative definition, Farris et al (9) found that 5% of previously healthy children who had returned to home by 28 days after admission had poor outcome. For the children who were still hospitalized at 28 days, nearly one in two had a poor outcome. Unanswered questions include the impact of other, more subtle neuropsychological and medical sequelae, and the natural history of the deficits identified. How long did these abnormalities last, and perhaps even more importantly, were there any therapeutic strategies that mitigated their effects and improved recovery? Considering what is known about recovery from critical illness in general, these findings likely represent only the tip of the proverbial iceberg. As the number of childhood survivors of critical illness has grown, so have the number of reports demonstrating persistent mental and physical health sequelae in children and their families (10–18). Although some studies suggest that age (19) and severity of illness at presentation (20) may predispose children to worse outcome, there are conflicting data (11), and the risk factors for developing these sequelae are still very poorly understood. As a dependent population, children (21–24), and especially premature infants (25, 26), have also been found to have adverse neurodevelopmental outcomes in the setting of parental mental health problems. These may be worsened by the multitude of sequelae following an episode of severe sepsis. Compounding this potential for long-term impact on future function, low-birth-weight premature infants represent the fastest growing population of children with severe sepsis. What all these findings indicate is that critical care providers must begin to consider themselves as part of a continuum of recovery that only begins in the PICU. The idea of a “good save” that leads to survivorship through PICU and hospital discharge, at which point the child becomes some other physician’s responsibility, should now be considered obsolete. Delivering a plenary session during the Society of Critical Care Medicine Annual Congress in 2012, Cheryl Misak, MA, DPhil, provided the critical care community with a challenge born from her personal experience as a septic shock and ICU survivor: “The provision of information and varied supports are vital if survivors of critical illness are to have good outcomes. This involves making available the expertise that resides in www.pccmjournal.org
893
Editorials
critical care medicine; putting in place physical and cognitive rehabilitation; and encouraging patients [and families] to push themselves without setting them up for failure.” Longitudinal assessment of function and recovery performed throughout the hospital stay and after the child returns home must become a standard component of ICU discharge planning and coordinated multidisciplinary follow-up. The accompanying research imperative is to collect longitudinal data to understand the natural history of ICU sequelae and the factors associated with an improved recovery trajectory. We acknowledge that this mandate is neither simple nor inexpensive. It is further hampered by the currently fragmented nature of healthcare delivery in the United States. As training for outpatient providers becomes increasingly streamlined, their ability to confidently manage children with complex multisystem medical problems and/or technology dependence will decline. Mental health services, particularly for children, are already at critical shortages in many places across the country. At the time of writing this editorial, we both acknowledge that we have very little first-hand knowledge of rehabilitative medicine tools, strategies, and the types and availability of rehabilitative services for children in the United States. And yet, the children who have survived critical illness clearly need our ongoing commitment to their recovery. Although a good save can only exist if a child survives to hospital discharge, it is obvious that survival to discharge can no longer be the measure of success. Coordinated multidisciplinary care models, such as spina bifida clinics, cystic fibrosis centers, and longitudinal follow-up programs that follow infants after discharge from the neonatal ICU, can all serve as a reference to guide us as we build our expertise in the study and care of children who have lasting medical and psychological problems after critical illness. Having saved them in the ICU, these children remain our responsibility. And what a tremendous accomplishment it will be when a good save means not just being alive but rather living life.
REFERENCES
1. Hartman ME, Linde-Zwirble WT, Angus DC: Trends in the Epidemiology of Pediatric Severe Sepsis. Pediatr Crit Care Med 2013; 14:686–693 2. Carcillo JA, Fields AI; American College of Critical Care Medicine Task Force Committee Members: Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 2002; 30:1365–1378 3. Han YY, Carcillo JA, Dragotta MA, et al: Early reversal of pediatricneonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003; 112:793–799 4. Carcillo JA, Kellum JA: Is there a role for plasmapheresis/plasma exchange therapy in septic shock, MODS, and thrombocytopeniaassociated multiple organ failure? We still do not know–but perhaps we are closer. Intensive Care Med 2002; 28:1373–1375 5. Kissoon N, Carcillo JA, Espinosa V, et al; Global Sepsis Initiative Vanguard Center Contributors: World Federation of Pediatric Intensive Care and Critical Care Societies: Global sepsis initiative. Pediatr Crit Care Med 2011; 12:494–503
894
www.pccmjournal.org
6. Nguyen TC, Han YY, Kiss JE, et al: Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure. Crit Care Med 2008; 36:2878–2887 7. Hall MW, Knatz NL, Vetterly C, et al: Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med 2011; 37:525–532 8. Wong HR: Genetics and genomics in pediatric septic shock. Crit Care Med 2012; 40:1618–1626 9. Farris RWD, Weiss NS, Zimmerman JJ: Functional Outcomes in Pediatric Severe Sepsis: Further Analysis of the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective Trial. Pediatr Crit Care Med 2013; 41:835–842 10. Bronner MB, Knoester H, Bos AP, et al: Posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment compared to children who survived a major fire disaster. Child Adolesc Psychiatry Ment Health 2008; 2:9 11. Bronner MB, Knoester H, Bos AP, et al: Follow-up after paediatric intensive care treatment: Parental posttraumatic stress. Acta Paediatr 2008; 97:181–186 12. Colville G: The psychologic impact on children of admission to intensive care. Pediatr Clin North Am 2008; 55:605–616, x 13. Conlon NP, Breatnach C, O’Hare BP, et al: Health-related quality of life after prolonged pediatric intensive care unit stay. Pediatr Crit Care Med 2009; 10:41–44 14. Davydow DS, Richardson LP, Zatzick DF, et al: Psychiatric morbidity in pediatric critical illness survivors: A comprehensive review of the literature. Arch Pediatr Adolesc Med 2010; 164:377–385 15. Fiser DH, Tilford JM, Roberson PK: Relationship of illness severity and length of stay to functional outcomes in the pediatric intensive care unit: A multi-institutional study. Crit Care Med 2000; 28:1173–1179 16. Knoester H, Bronner MB, Bos AP, et al: Quality of life in children three and nine months after discharge from a paediatric intensive care unit: A prospective cohort study. Health Qual Life Outcomes 2008; 6:21 17. Rees G, Gledhill J, Garralda ME, et al: Psychiatric outcome following paediatric intensive care unit (PICU) admission: A cohort study. Intensive Care Med 2004; 30:1607–1614 18. Rennick JE, Rashotte J: Psychological outcomes in children following pediatric intensive care unit hospitalization: A systematic review of the research. J Child Health Care 2009; 13:128–149 19. Buysse CM, Raat H, Hazelzet JA, et al: Long-term health-related quality of life in survivors of meningococcal septic shock in childhood and their parents. Qual Life Res 2007; 16:1567–1576 20. Rennick JE, Morin I, Kim D, et al: Identifying children at high risk for psychological sequelae after pediatric intensive care unit hospitalization. Pediatr Crit Care Med 2004; 5:358–363 21. Elison S, Shears D, Nadel S, et al: Neuropsychological function in children following admission to paediatric intensive care: A pilot investigation. Intensive Care Med 2008; 34:1289–1293 22. Patel SK, Wong AL, Cuevas M, et al: Parenting stress and neurocognitive late effects in childhood cancer survivors. Psychooncology 2013; 22:1774–1782 23. Gunlicks ML, Weissman MM: Change in child psychopathology with improvement in parental depression: A systematic review. J Am Acad Child Adolesc Psychiatry 2008; 47:379–389 24. Landry SH, Smith KE, Swank PR: The importance of parenting during early childhood for school-age development. Dev Neuropsychol 2003; 24:559–591 25. Huhtala M, Korja R, Lehtonen L, et al; PIPARI Study Group: Parental psychological well-being and cognitive development of very low birth weight infants at 2 years. Acta Paediatr 2011; 100:1555–1560 26. Huhtala M, Korja R, Lehtonen L, et al; PIPARI Study Group: Parental psychological well-being and behavioral outcome of very low birth weight infants at 3 years. Pediatrics 2012; 129:e937–e944
November 2013 • Volume 14 • Number 9
Functional Outcomes for Children With Severe Sepsis: Is a “Good Save” Good Enough?* Mary Hartman, MD, MPH John C. Lin, MD Department of Pediatrics Division of Pediatric Critical Care Medicine Washington University in St. Louis St. Louis, MO
R
ecent estimates indicate that approximately 75,000 U.S. children acquire severe sepsis each year, and this number is likely to continue to climb in the next few years (1). The overwhelming majority of these children will survive and return home to reintegrate into their families, schools, and communities. Although research on the early recognition (2, 3), treatment (4–6), and pathophysiologic basis (7, 8) for severe sepsis has made tremendous advances in the past decade, outcome studies evaluating the developmental, physical, and mental health consequences of severe infection in childhood are lacking. In this issue of Pediatric Critical Care Medicine, Farris et al (9) present the first description of 28-day functional outcome in 363 survivors of severe sepsis in childhood. This patient cohort from 18 countries ranging in age from newborn to 18 years old originated from the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective (RESOLVE) trial, in which activated protein C was tested as a therapeutic agent for children with severe sepsis. RESOLVE, terminated early because of increased mortality in the therapy arm, also collected outcome data on all enrolled participants. Functional performance, as measured by the Pediatric Overall Performance Category (POPC), was identified at baseline by parent proxy report and then recorded by study personnel for all surviving subjects at 28 days post enrollment. Analyzing the RESOLVE data, Farris et al (9) found that the majority of pediatric severe sepsis patients (77%) were initially healthy, 10% had died by the time of follow-up, and 25% met the criteria for poor functional outcome at 28 days, defined as an increase in POPC score by at least 1 point and an absolute POPC score *See also p. 835. Key Words: critical care; outcomes; pediatric critical care; sepsis; severe sepsis The authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies DOI: 10.1097/PCC.0b013e3182a551e9
Pediatric Critical Care Medicine
more than 3. In total, one third of patients (34%) had a worse POPC score compared with baseline. Despite limitations with the POPC scoring tool and potential of recall bias in baseline proxy measurements, these data are certainly compelling. Gone are the days when sepsis could be thought of as an acute self-limited condition, regardless of preillness health status. In fact, despite using a conservative definition, Farris et al (9) found that 5% of previously healthy children who had returned to home by 28 days after admission had poor outcome. For the children who were still hospitalized at 28 days, nearly one in two had a poor outcome. Unanswered questions include the impact of other, more subtle neuropsychological and medical sequelae, and the natural history of the deficits identified. How long did these abnormalities last, and perhaps even more importantly, were there any therapeutic strategies that mitigated their effects and improved recovery? Considering what is known about recovery from critical illness in general, these findings likely represent only the tip of the proverbial iceberg. As the number of childhood survivors of critical illness has grown, so have the number of reports demonstrating persistent mental and physical health sequelae in children and their families (10–18). Although some studies suggest that age (19) and severity of illness at presentation (20) may predispose children to worse outcome, there are conflicting data (11), and the risk factors for developing these sequelae are still very poorly understood. As a dependent population, children (21–24), and especially premature infants (25, 26), have also been found to have adverse neurodevelopmental outcomes in the setting of parental mental health problems. These may be worsened by the multitude of sequelae following an episode of severe sepsis. Compounding this potential for long-term impact on future function, low-birth-weight premature infants represent the fastest growing population of children with severe sepsis. What all these findings indicate is that critical care providers must begin to consider themselves as part of a continuum of recovery that only begins in the PICU. The idea of a “good save” that leads to survivorship through PICU and hospital discharge, at which point the child becomes some other physician’s responsibility, should now be considered obsolete. Delivering a plenary session during the Society of Critical Care Medicine Annual Congress in 2012, Cheryl Misak, MA, DPhil, provided the critical care community with a challenge born from her personal experience as a septic shock and ICU survivor: “The provision of information and varied supports are vital if survivors of critical illness are to have good outcomes. This involves making available the expertise that resides in www.pccmjournal.org
893
Editorials
critical care medicine; putting in place physical and cognitive rehabilitation; and encouraging patients [and families] to push themselves without setting them up for failure.” Longitudinal assessment of function and recovery performed throughout the hospital stay and after the child returns home must become a standard component of ICU discharge planning and coordinated multidisciplinary follow-up. The accompanying research imperative is to collect longitudinal data to understand the natural history of ICU sequelae and the factors associated with an improved recovery trajectory. We acknowledge that this mandate is neither simple nor inexpensive. It is further hampered by the currently fragmented nature of healthcare delivery in the United States. As training for outpatient providers becomes increasingly streamlined, their ability to confidently manage children with complex multisystem medical problems and/or technology dependence will decline. Mental health services, particularly for children, are already at critical shortages in many places across the country. At the time of writing this editorial, we both acknowledge that we have very little first-hand knowledge of rehabilitative medicine tools, strategies, and the types and availability of rehabilitative services for children in the United States. And yet, the children who have survived critical illness clearly need our ongoing commitment to their recovery. Although a good save can only exist if a child survives to hospital discharge, it is obvious that survival to discharge can no longer be the measure of success. Coordinated multidisciplinary care models, such as spina bifida clinics, cystic fibrosis centers, and longitudinal follow-up programs that follow infants after discharge from the neonatal ICU, can all serve as a reference to guide us as we build our expertise in the study and care of children who have lasting medical and psychological problems after critical illness. Having saved them in the ICU, these children remain our responsibility. And what a tremendous accomplishment it will be when a good save means not just being alive but rather living life.
REFERENCES
1. Hartman ME, Linde-Zwirble WT, Angus DC: Trends in the Epidemiology of Pediatric Severe Sepsis. Pediatr Crit Care Med 2013; 14:686–693 2. Carcillo JA, Fields AI; American College of Critical Care Medicine Task Force Committee Members: Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 2002; 30:1365–1378 3. Han YY, Carcillo JA, Dragotta MA, et al: Early reversal of pediatricneonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003; 112:793–799 4. Carcillo JA, Kellum JA: Is there a role for plasmapheresis/plasma exchange therapy in septic shock, MODS, and thrombocytopeniaassociated multiple organ failure? We still do not know–but perhaps we are closer. Intensive Care Med 2002; 28:1373–1375 5. Kissoon N, Carcillo JA, Espinosa V, et al; Global Sepsis Initiative Vanguard Center Contributors: World Federation of Pediatric Intensive Care and Critical Care Societies: Global sepsis initiative. Pediatr Crit Care Med 2011; 12:494–503
894
www.pccmjournal.org
6. Nguyen TC, Han YY, Kiss JE, et al: Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure. Crit Care Med 2008; 36:2878–2887 7. Hall MW, Knatz NL, Vetterly C, et al: Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med 2011; 37:525–532 8. Wong HR: Genetics and genomics in pediatric septic shock. Crit Care Med 2012; 40:1618–1626 9. Farris RWD, Weiss NS, Zimmerman JJ: Functional Outcomes in Pediatric Severe Sepsis: Further Analysis of the Researching Severe Sepsis and Organ Dysfunction in Children: A Global Perspective Trial. Pediatr Crit Care Med 2013; 41:835–842 10. Bronner MB, Knoester H, Bos AP, et al: Posttraumatic stress disorder (PTSD) in children after paediatric intensive care treatment compared to children who survived a major fire disaster. Child Adolesc Psychiatry Ment Health 2008; 2:9 11. Bronner MB, Knoester H, Bos AP, et al: Follow-up after paediatric intensive care treatment: Parental posttraumatic stress. Acta Paediatr 2008; 97:181–186 12. Colville G: The psychologic impact on children of admission to intensive care. Pediatr Clin North Am 2008; 55:605–616, x 13. Conlon NP, Breatnach C, O’Hare BP, et al: Health-related quality of life after prolonged pediatric intensive care unit stay. Pediatr Crit Care Med 2009; 10:41–44 14. Davydow DS, Richardson LP, Zatzick DF, et al: Psychiatric morbidity in pediatric critical illness survivors: A comprehensive review of the literature. Arch Pediatr Adolesc Med 2010; 164:377–385 15. Fiser DH, Tilford JM, Roberson PK: Relationship of illness severity and length of stay to functional outcomes in the pediatric intensive care unit: A multi-institutional study. Crit Care Med 2000; 28:1173–1179 16. Knoester H, Bronner MB, Bos AP, et al: Quality of life in children three and nine months after discharge from a paediatric intensive care unit: A prospective cohort study. Health Qual Life Outcomes 2008; 6:21 17. Rees G, Gledhill J, Garralda ME, et al: Psychiatric outcome following paediatric intensive care unit (PICU) admission: A cohort study. Intensive Care Med 2004; 30:1607–1614 18. Rennick JE, Rashotte J: Psychological outcomes in children following pediatric intensive care unit hospitalization: A systematic review of the research. J Child Health Care 2009; 13:128–149 19. Buysse CM, Raat H, Hazelzet JA, et al: Long-term health-related quality of life in survivors of meningococcal septic shock in childhood and their parents. Qual Life Res 2007; 16:1567–1576 20. Rennick JE, Morin I, Kim D, et al: Identifying children at high risk for psychological sequelae after pediatric intensive care unit hospitalization. Pediatr Crit Care Med 2004; 5:358–363 21. Elison S, Shears D, Nadel S, et al: Neuropsychological function in children following admission to paediatric intensive care: A pilot investigation. Intensive Care Med 2008; 34:1289–1293 22. Patel SK, Wong AL, Cuevas M, et al: Parenting stress and neurocognitive late effects in childhood cancer survivors. Psychooncology 2013; 22:1774–1782 23. Gunlicks ML, Weissman MM: Change in child psychopathology with improvement in parental depression: A systematic review. J Am Acad Child Adolesc Psychiatry 2008; 47:379–389 24. Landry SH, Smith KE, Swank PR: The importance of parenting during early childhood for school-age development. Dev Neuropsychol 2003; 24:559–591 25. Huhtala M, Korja R, Lehtonen L, et al; PIPARI Study Group: Parental psychological well-being and cognitive development of very low birth weight infants at 2 years. Acta Paediatr 2011; 100:1555–1560 26. Huhtala M, Korja R, Lehtonen L, et al; PIPARI Study Group: Parental psychological well-being and behavioral outcome of very low birth weight infants at 3 years. Pediatrics 2012; 129:e937–e944
November 2013 • Volume 14 • Number 9
