177 e1 eT A B LE 21 2 H ea lt h R el at ed Q u al it y o f L if e (H R Q L) A ss es sm en t T o o ls In st ru m en t Na m e/ Or ig in Ag e (y ) No I te m s No Do m ai ns Ti m e (m in ) Re po rt Re lia[.]
Name/Origin Child Health & Illness Profile—Adolescent Edition (US) Child Health & Illness Profile—Child Edition (US) Child Health Questionnaire— Child Form (US) Child Health Questionnaire— Parent Form (US) Child Health Questionnaire— Parent Form (US) Dartmouth COOP Charts (US) DISABKIDS (Europe) EuroQOL (Europe) Functional Independence Measure Functional Status II Revised (US) Health Utilities Index (Canada) Infant & Toddler QOL Questionnaire Instrument CHIP-AE CHIP-CE CHQ-CF87 CHQ-PF50 CHQ-PF28 COOP DISABKIDS EQ–5D FIM/WEEFIM FS IIR HUI ITQOL mo– 5y 2–18 0–16 0–18 5–18 4–16 8–18 5–18 5–18 10–18 6–11 11–17 Age (y) 103 45 14 18 37 28 50 87 76 (proxy) 45 (self) 183 No Items 10 8 6 13 13 13 No Domains eTABLE Health-Related Quality of Life (HRQL) Assessment Tools 21.2 ,5 10 10 5–10 20 20 20 45 Time (min) Proxy Proxy Self Proxy Proxy Proxy Self Proxy Self Self Proxy Self (51) Proxy Self (51) Proxy Self (101) Proxy Self Self Report ICC Test-retest Test-retest ICC Test-retest Test-retest Test-retest ICC Test-retest Test-retest ICC Test-retest ICC Test-retest ICC Test-retest ICC Test-retest ICC Test-retest Reliability Content Construct Criterion Construct Content Construct Content Construct Construct Content Construct Construct Content Construct Criterion Content Construct Criterion Content Construct Criterion Content Construct Criterion Content Construct Criterion Validity x x x x x x x x x x x x x x x x x x x x x x x x x Emotional Physical x Sensitivity to Change x x x x x x x x x x Social/ Behavioral x x x x x x x School 177.e1 Kidscreen (International) Kidscreen (Germany) Pediatric Evaluation & Disability Inventory Pediatric Quality of Life Inventory (US) Quality of Well-Being Scale TNO-AZL Child QOL (Netherlands) TNO-AZL Parent QOL (Netherlands) Youth Quality of Life Instrument— Research Version (US) Vecu et Sante Percue de l’Adolescent (France) KIDSCR-27 KINDL PEDI PedsQL 4.0 QWD TACQOL TA PQOL YQOL-R VSP-A ICC, internal consistency Kidscreen (International) KIDSCR-52 11–17 11–18 1–5 6–15 4–18 2–18 0–8 8–16 4–7 8–18 8–18 37 56 43 108 29 23 237 24 12 27 52 4 10 10–15 10 10 5–10 5–10 10–15 15–20 Self Self Proxy Proxy Self (81) Proxy Self (111) Proxy Self (51) Proxy Proxy Self Proxy Self Proxy Self ICC Test-retest ICC Test-retest ICC Test-retest ICC Test-retest ICC Test-retest ICC ICC Test-retest ICC Content Construct Content Construct Construct Content Construct Predictive Content Construct Criterion Content Construct Content Construct Content Construct x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x 177.e2 178 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal 100 Patient 90 Patient Population mean 80 70 Patient HRQL score 60 50 Patient 40 30 20 10 Baseline Admission Discharge months year years years Time of assessment • Fig 21.3 Hypothetical health-related quality of life (HRQL) trajectory of sample patients following critical illness compared with population mean Patient 1: Previously healthy child who sustains a traumatic brain injury and has persistent clinically significant HRQL deterioration from baseline but does not fall significantly below the population mean Patient 2: Previously healthy child admitted with sepsis who recovers to baseline within to 12 months of discharge Patient 3: Child with congenital heart disease who undergoes corrective surgery and has significant improvement in HRQL from baseline Patient 4: Child with cerebral palsy admitted with respiratory illness who recovers back to baseline but remains significantly below the population mean children experience HRQL improvement following hospitalization for sepsis, especially among those with preexisting chronic illnesses and immune compromise, possibly due to improved control of underlying conditions during hospitalization.27 Collectively, these data demonstrate the importance of assessment of baseline health status whenever possible to appropriately interpret post-hospitalization outcomes Summary of Outcomes in General Pediatric Intensive Care Unit Populations Hospital Readmission and Late Mortality Multiple studies have demonstrated that children surviving critical illness remain at high risk for hospital readmission and death in the years following their initial PICU hospitalization.43–49 Nearly one-quarter of PICU survivors are readmitted to the hospital in the year after discharge, and half of all readmissions are nonelective; one-third of nonelective admissions include a repeat PICU stay This is particularly pronounced among patients with prolonged ICU stays, with 36% of children with an index PICU stay of at least weeks being readmitted within the year Importantly, 14% of children with an index stay of only day are also readmitted.47 Mortality in the year after PICU discharge is 10 times higher than in the general US pediatric population,47 with late mortality particularly high among patients with prolonged ICU stays50 and patients with complex chronic conditions.51 Health-Related Quality of Life Impaired HRQL has been demonstrated in many children following critical illness.9,11,12,15,30,41,52–58 While estimates vary depending on the instrument used and time to follow-up, approximately one-third of PICU survivors experience significant impairments in HRQL when assessed between months and years after hospital discharge,30,41,54 and one study demonstrated that 16% had an unfavorable quality of life when assessed up to years after discharge.56 HRQL outcomes for patients who required prolonged PICU stays are worse; two separate studies both found that 43% to 47% of survivors of PICU stays longer than 28 days had impaired HRQL at least years after discharge.15,55 Higher severity of illness tends to correlate with worse HRQL after discharge,30,53,57 but this is not consistently demonstrated across all studies.52,59 Children with chronic comorbidities have been repeatedly found to have worse HRQL after critical illness.15,53,54,58 CHAPTER 21 Long-Term Outcomes Following Critical Illness in Children Functional Status Between 10% and 36% of PICU survivors experience some degree of functional impairment at discharge, with persistent functional impairment after more than years in 10% to 13%.60 New substantial functional morbidity, defined by an increase in Functional Status Scale (FSS)61 score of or greater, was present in 4.8% of PICU patients at discharge and encompassed all functional domains, with the highest proportion of new morbidity present in respiratory, motor, and feeding domains.4 Importantly, new morbidity as defined by FSS increased to 6.5% at months and 10.4% at years postdischarge.62 When measured by Pediatric Overall Performance Category (POPC) score, 37% of survivors of urgent PICU admissions reported a score of or worse (at least moderated disability) month after discharge, with mean POPC scores significantly worse than baseline, especially among patients with prolonged ICU stays and oncologic diagnoses.53 While over 80% of patients with organ dysfunction in the ICU were found to experience functional deterioration with critical illness, two-thirds demonstrated recovery at 6-month follow-up, with faster recovery among younger children.63 Among patients with prolonged PICU stays (i.e., 28 days), however, over half had moderate to severe disability at a median of years after discharge.55 Neurocognitive Status Decline in neurocognitive status occurs in up to one-quarter of PICU patients.64 PICU survivors had significantly lower neurocognitive scores than the general population 18 months after discharge, with lower scores associated with longer PICU stays; lower global cognitive function was associated with increased behavioral problems and worse executive functioning.65 Among patients urgently admitted to the PICU, 28% had poor adaptive behavior functioning after discharge.53 Mental Health Children surviving an ICU stay are at high risk for impaired mental health and development of posttraumatic stress disorder (PTSD) following their hospitalization Multiple studies identified an inverse relationship between PTSD and HRQL following critical illness.18,52,66–77 One study found that at a median of months after discharge, 20% of PICU survivors were at risk for psychiatric disorders, 34% were at risk for PTSD, 38% were at risk for fatigue disorder, and 80% were at risk for a sleep disorder.78 Children admitted to the PICU were significantly more likely to develop PTSD than children admitted to the general hospital ward.74 Younger children and those who were more severely ill and endured more invasive procedures had significantly more medical fears, a lower sense of control of their health, and ongoing posttraumatic stress responses for months following PICU discharge.75 Family Functioning Families of critically ill children may experience high levels of stress and uncertainty, relationship conflict, and financial burdens during and following their child’s hospitalization.79,80 Parents of PICU survivors may also have psychologic sequelae affecting their own quality of life.12 Several studies found that over one-quarter of parents of PICU patients screened positive for PTSD to 12 months after discharge.68,74 Importantly, PTSD in families is not well correlated with objective factors 179 such as severity of illness but rather is correlated to subjective experiences; many families experience delayed reactions, with PTSD scores increasing over time.68 Outcomes for Common Pediatric Intensive Care Unit Illness Categories Respiratory Failure The Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of long-term outcomes among mechanically ventilated pediatric patients found that 20% of patients experienced a decline in functional status from baseline to 6-month postdischarge follow-up and 30% were at risk for PTSD Of those with normal preadmission function, 19% had impaired HRQL.81,82 Older age, history of prematurity or cancer, inadequate pain and sedation management, use of clonidine and methadone, and ventilator duration were among the demographic and clinical factors associated with poor outcomes.81 Among children surviving acute respiratory distress syndrome (ARDS), nearly one-quarter experience substantial new morbidity as defined by an increase in FSS of or greater, and 8% die in the years following discharge.83 Among a limited sample of ARDS survivors seen in follow-up year after discharge, one-third had persistent pulmonary function deficits, and quality of life scores were significantly lower than those of a comparison group of patients with chronic asthma.84 Sepsis Sepsis and other severe infections are associated with high morbidity across multiple domains of health outcomes Children surviving hospitalization for severe sepsis have mortality rates to 50 times greater than that of the general population depending on age and gender, and high rates of hospital readmission.43 HRQL is impaired in sepsis survivors, with 38.5% of PICU patients with sepsis failing to recover to their baseline HRQL at a median of 31 days postdischarge; older age, immune compromise, septic shock, and longer length of stay were all associated with failure to recover.27 Children surviving meningococcemia also exhibit impaired HRQL up to years after discharge from a PICU.31,85 Decline in functional status is common after severe sepsis, with 34% of survivors experiencing a decline in functional status 28 days after sepsis onset Clinical factors associated with increased risk of poor outcome included central nervous system or intraabdominal infections, a history of recent trauma, requirement for cardiopulmonary resuscitation, and high PRISM III score.86 Neurocognitive status and development are also affected Children admitted to the PICU with meningoencephalitis and sepsis experience more severe deficits in neuropsychologic and school performance than other forms of critical illness.78,87 Patients with sepsisassociated encephalopathy had delayed neurodevelopment, lower IQ scores, and declines in school performance and behavior at follow-up,88 and infants surviving pertussis demonstrated neurodevelopmental deficits year after discharge.89 Trauma Traumatic injury is the leading cause of preventable morbidity in children Pediatric trauma mortality has been steadily decreasing over the past several decades, leaving an increasing number of children at risk of experiencing long-term impairments.90,91 Children surviving traumatic injury experience high 180 S E C T I O N I I I Pediatric Critical Care: Psychosocial and Societal rates of hospital readmission45,46 and ongoing healthcare use92 and are at risk for impaired HRQL,67,93–98 decreased physical functioning,93,95,98–104 PTSD,105,106 depression,107 and family strain.98,108 While patients exhibit improvements over time, some continue to have deficits across a variety of health domains up to years following injury.18 Importantly, one of the factors most strongly associated with poor HRQL after trauma is the presence of PTSD.18,105 Studies focused on patients with traumatic brain injury (TBI) have similarly demonstrated deficits across a range of health domains.109–117 New functional morbidity is present in 37% of TBI survivors at hospital discharge, including over half of patients with severe TBI.109 Functional impairments may persist for years following TBI.112,114,116 Nearly half of survivors of severe pediatric TBI with elevated intracranial pressure demonstrate residual neurologic and neurocognitive deficits more than years after injury, and 16% remained dependent on caregivers.110 Impaired HRQL occurred in 40% of TBI survivors year after injury111 and can persist for at least years.114,117 TBI survivors frequently experience family dysfunction113 and have high rates of ongoing healthcare use and unmet healthcare needs.115 Higher severity of head injury is consistently associated with worse outcome.109–111,113,114,117 Extracorporeal Life Support Several studies evaluated outcomes among populations of children requiring extracorporeal life support (ECLS) A study of neonatal and pediatric ECLS survivors found significantly lower HRQL scores compared to population norms at a median of years after discharge.118 FSS was moderately-to-severely abnormal among 29% of neonatal and pediatric ECLS survivors at hospital discharge, but one-third of survivors had a good FSS.119 At 18 months after discharge, 87% of ECLS survivors were found to have a normal neurologic status; follow-up up to 20 years later found that 90% of survivors had no disability and had normal quality of life, with only 5% demonstrating cognitive impairment.120 Cardiac ECLS survivors were found to have significantly lower HRQL scores than population norms at a median 6-year follow-up, with 18% reporting significant physical limitations or fair/poor health.121 In contrast, a study of children surviving extracorporeal CPR found good mean quality of life and family functioning scores at median 3-year follow-up.122 Examples of Postdischarge Outcomes in Pediatric Interventional Trials Survival is still the most commonly used primary outcome in pediatric critical care trials.10,123–125 After survival, families of critically ill children and critical care practitioners see long-term functional status and HRQL as the most important outcomes for an interventional trial.10 The first large pediatric investigation that included a morbidity measure as a secondary outcome was the interventional trial examining bactericidal, permeability-increasing protein (rBPI21) as adjunctive therapy for meningococcemia sepsis.126 Although mortality did not differ between children treated with placebo versus study drug, those who received rBPI21 demonstrated superior gross functional status at day 28 Subsequently, the RESOLVE trial of activated protein C as adjunctive therapy for pediatric septic shock found no differences in mortality or time to composite resolution of organ dysfunction,127 but 34% of participants experienced a decline in their functional status 28 days after enrollment and 18% demonstrated poor functional outcome.86 For the Therapeutic Hypothermia After Cardiac Arrest trials, the primary efficacy outcome was survival at 12 months with a Vineland Adaptive Behavior Scales (VABS-II) score of 70 or higher among patients with a VABS-II score of at least 70 before cardiac arrest.128,129 Of 629 total patients randomized, 517 (82%) had results for the primary outcome, which did not significantly differ between the groups In a single-center study of tight glycemic control involving 700 critically ill children, 569 (81%) subjects underwent neurocognitive testing 3.8 to 4.1 years after study randomization, with no differences found by treatment arm or associated with in-hospital hypoglycemia.130 In the RESTORE cluster-randomized trial of 2449 critically ill children that examined nurse-implemented, goal-directed sedation versus usual care for acute respiratory failure, the primary outcome measure—duration of mechanical ventilation—did not differ between groups.131 However, children randomized to the intervention arm were exposed to fewer sedative and analgesic medications; accordingly, they were generally more awake while intubated At months post-PICU discharge, a stratified, random sample of subjects was evaluated, with no significant differences found by treatment arm in HRQL, decline in functional status from baseline, or PTSD.82 An ongoing study, RESTORE-cognition, is examining the relationships between sedative exposure during pediatric critical illness with long-term neurocognitive outcomes 2.5 to years following hospital discharge among a subset of participants in the original RESTORE study.132 The Approaches and Decisions for Acute Pediatric TBI (ADAPT) trial is an international, observational comparative effectiveness study that enrolled more than 1000 children with severe TBI to examine the utility of six common interventions.133 ADAPT investigators conducted telephone surveys at months and comprehensive neuropsychologic testing at 12 months to assess HRQL, intellectual ability, speech, memory, executive function, attention/processing speed, and motor skills At this writing, two large pivotal interventional trials using nonmortality outcomes have initiated enrollment PROSPECT (Prone and Oscillation Pediatric Clinical Trial, NCT03896763) will employ a two-by-two factorial, response-adaptive design to examine combinations of supine and prone positioning and conventional and high-frequency oscillatory ventilation for supporting up to 1000 children with severe ARDS Although mechanical ventilation-free days truncated at 28 days represents the primary outcome measure, the investigators will also serially assess functional status and HRQL at 1, 3, 6, and 12 months as exploratory outcomes SHIPSS (Stress Hydrocortisone In Pediatric Septic Shock, NCT03401398) will examine hydrocortisone as adjunctive therapy for pediatric septic shock As the primary endpoint, SHIPSS investigators will employ a composite measure of death or persistent, severe HRQL disability compared to baseline Functional status and HRQL will be assessed at baseline, 28 days, and 90 days Design of SHIPPS was informed by the prospective, descriptive cohort outcome investigation, Life After Pediatric Sepsis Evaluation (LAPSE, R01HD073362), which ascertained the logistical and biological plausibility of this composite mortality/morbidity outcome.134 LAPSE reported that at 1, 3, 6, and 12 months following admission to the ICU for septic shock, 8%, 11%, 12%, and 13% of patients had died, while 50%, 37%, 30%, and 35% of surviving patients had not yet regained their baseline HRQL.135 At month, 35% of patients had died or survived with persistent, severe HRQL disability; various measures ... after discharge, and half of all readmissions are nonelective; one-third of nonelective admissions include a repeat PICU stay This is particularly pronounced among patients with prolonged ICU... population mean Patient 2: Previously healthy child admitted with sepsis who recovers to baseline within to 12 months of discharge Patient 3: Child with congenital heart disease who undergoes corrective... prolonged ICU stays, with 36% of children with an index PICU stay of at least weeks being readmitted within the year Importantly, 14% of children with an index stay of only day are also readmitted.47