Pediatric calfactant in acute respiratory distress syndrome trial.

RATIONALE: Our previous studies in children with acute lung injury/acute respiratory distress syndrome demonstrated improved outcomes with exogenous surfactant (calfactant) administration. Sample sizes in those studies were small, however, and the subject populations heterogeneous, thus making recommendations tenuous. OBJECTIVE: To investigate the efficacy of surfactant administration in a larger, more homogenous population of children with lung injury/acute respiratory distress syndrome due to direct lung injury. DESIGN AND SETTING: Masked, randomized, placebo-controlled trial in 24 children's hospitals in six different countries. PATIENTS AND METHODS: Children 37 weeks postconception to 18 years old with lung injury/acute respiratory distress syndrome due to direct lung injury were randomized to receive up to three doses of 30 mg/cm height of surfactant (calfactant) versus placebo (air) within 48 hours of intubation and initiation of mechanical ventilation. The primary outcome was mortality at 90 days. Ventilator-free days, changes in oxygenation, and adverse events were also assessed. RESULTS: The study was stopped at the sponsor's request after the second interim analysis for presumed futility. A total of 110 subjects were enrolled, with consent withdrawn from one whose data are unavailable. There were no significant differences between groups except in hospital-free days (10.4 ± 7.8 placebo vs 6.4 ± 7.8 surfactant; p = 0.01). Overall 90-day mortality was 11% (seven surfactant, five placebo). No immediate improvement in oxygenation was associated with surfactant administration. CONCLUSIONS: Surfactant did not improve outcomes relative to placebo in this trial of children with direct lung injury/acute respiratory distress syndrome. Differences in concentration of the surfactant, failure to recruit the lung during surfactant administration, or using two rather than four position changes during administration are possible explanations for the difference from previous studies. Exogenous surfactant cannot be recommended at this time for children with direct lung injury/acute respiratory distress syndrome.

The relationship of fluid administration to outcome in the pediatric calfactant in acute respiratory distress syndrome trial.

OBJECTIVES: Adult studies have demonstrated the relationship between fluid overload and poor outcomes in acute lung injury/acute respiratory distress syndrome. The approach of pediatric intensivists to fluid management in acute lung injury/acute respiratory distress syndrome and its effect on outcomes is less clear. In a post hoc analysis of our Calfactant in Acute Respiratory Distress Syndrome trial, we examined the relationship of fluid balance to in-hospital outcomes in subjects with acute lung injury/acute respiratory distress syndrome. DESIGN: Calfactant in Acute Respiratory Distress Syndrome was a masked randomized controlled trial of calfactant surfactant versus placebo in pediatric patients with acute lung injury/acute respiratory distress syndrome due to direct lung injury. Caregivers were encouraged to follow a conservative fluid management guideline based on the adult Fluid and Catheter Treatment Trial. Daily fluid balance was collected for the first 7 days after trial enrollment and correlated with clinical outcomes. PATIENTS AND SETTING: Children admitted to PICUs with acute lung injury/acute respiratory distress syndrome from 24 children's hospitals in six different countries. INTERVENTION: Post hoc analysis of daily fluid balance in subjects from the Pediatric Calfactant in Acute Respiratory Distress Syndrome trial. MEASUREMENTS AND MAIN RESULTS: Despite the conservative fluid guideline, fluid management was more consistent with a "liberal" approach. On average, study subjects accumulated 1.96 ± 4.2 L/m over the first 7 days of the trial. Subjects who died accumulated on average 8.7 ± 9.5 L/m versus 1.2 ± 2.4 L/m in survivors. Increasing fluid accumulation was associated with fewer ventilator-free days and worsening oxygenation. Multivariable regression models that included age, gender, Pediatric Risk of Mortality score, initial oxygen saturation index and PaO2/FIO2 ratio, injury category, and treatment arm failed to account for the differences in fluid management. CONCLUSIONS: Pediatric intensivists generally follow a "liberal" approach to fluid management in children with acute lung injury/acute respiratory distress syndrome. Illness severity or oxygenation disturbance did not explain differences in fluid accumulation but such accumulation was associated with worsening oxygenation, a longer ventilator course, and increased mortality. A more conservative approach to fluid management may improve outcomes in children with acute lung injury/acute respiratory distress syndrome.

National survey of health services provided by pediatric post-acute care facilities in the US.

PURPOSE: The need for pediatric post-acute facility care (PAC) is growing due to technological advances that extend the lives of many children, especially those with complex medical needs. The objectives were to describe [1] the types and settings of PAC; [2] the clinical characteristics of the pediatric patients requiring PAC; and [3] perceptions of PAC care delivery by clinical staff. METHODS: An online survey was administered between 6/2018 to 12/2018 to administrative leaders in PAC facilities that have licensed beds for children and who were active members of the Pediatric Complex Care Association. Survey topics included types of health services provided; pediatric patient characteristics; clinical personnel characteristics; and perceptions of pediatric PAC health care delivery. RESULTS: Leaders from 26 (54%) PAC facilities in 16 U.S. states completed the survey. Fifty-four percent identified as skilled nursing facility/long-term care, 19% intermediate care facilities, 15% respite and medical group homes, and 12% post-acute rehabilitation facilities. Sixty-nine percent of facilities had a significant increase in the medical complexity of patients over the past 10 years. Most reported capability to care for children with tracheostomy/invasive ventilation (100%), gastrostomy tubes (96%), intrathecal baclofen pump (89%), non-invasive positive pressure ventilation (85%), and other medical technology. Most facilities (72%) turned away patients for admission due to bed unavailability occasionally or always. Most facilities (62%) reported that insurance reimbursement to cover the cost of providing PAC to children was not acceptable, and most reported that it was difficult to hire clinical staff (77%) and retain staff (58%). CONCLUSION: PAC in the U.S. is provided to an increasingly medically-complex population of children. There is a critical need to investigate financially-viable solutions for PAC facilities to meet the patient demands for their services and to sufficiently reimburse and retain staff for the challenging and important care that they provide.

Investigating Parent Needs, Participation, and Psychological Distress in the Children's Hospital.

BACKGROUND AND OBJECTIVES: Greater parent participation in a child's hospital care is associated with better child outcomes in the hospital and after discharge. This study examined the relationships between perceived need fulfillment for parents, parent participation in hospital care, and parent psychological distress. We hypothesized that greater perceived need fulfillment would be associated with greater participation in hospital care and decreased psychological distress. METHODS: In this prospective cohort study, 166 parents completed questionnaires on a pediatric (nonintensive care) floor. Eligible parents were fluent in English and had a child who was hospitalized ≥2 nights. Previously validated questionnaires were used to assess parent participation in hospital care and psychological distress (defined here as symptoms of anxiety/depression). A modified version of the Bereaved Parent Needs Assessment was used to assess perceived need fulfillment. The association between perceived need fulfillment and each outcome variable was examined using multiple linear regression analyses. RESULTS: Of 186 eligible parents, 166 were enrolled (1 declined, 19 missed/not present). In multivariable analyses, greater perceived need fulfillment was associated with greater participation in hospital care and fewer symptoms of depression, even after controlling for relevant covariates. Exploratory analyses identified needs that were differentially important within groups of parents at risk for distress. CONCLUSIONS: This study suggests that assessing and supporting parent needs during a child's hospitalization may improve parent and child outcomes by increasing parents' ability to participate in hospital care and decreasing psychological distress. Future research is needed to investigate the impact of interventions targeting specific parent needs.

Use of Post-Acute Facility Care in Children Hospitalized With Acute Respiratory Illness.

BACKGROUND: Recovery from respiratory illness (RI), a common reason for hospitalization, can be protracted for some children because of high illness severity or underlying medical complexity. OBJECTIVE: We assessed which children hospitalized with RI are the most likely to use post-acute facility care (PAC) for recovery. METHODS: Retrospective analysis of 609,800 hospitalizations for patients in 43 US children's hospitals between 2010- 2015 for RI, identified with the Agency for Healthcare Research and Quality Clinical Classification System. Discharge to PAC was identified using Centers for Medicare & Medicaid Services Discharge Status Codes. We compared patient characteristics by PAC use with generalized estimating equations. RESULTS: There were 2660 (0.4%) RI hospitalizations resulting in PAC transfer (n = 2660, 0.4%). Discharges to PAC had greater percentages of technology assistance (83.2% vs 15.1%), neuromuscular chronic condition (57.5% vs 8.9%), and mechanical ventilation (52.7% vs 9.1%), 𝑃 < 0.001 for all. The highest likelihood of PAC use occurred with ≥11 vs no chronic conditions (odds ratio [OR] 11.7 [95% CI, 8.0- 17.2]), ≥9 vs no therapeutic medication classes (OR 4.8 [95% CI, 1.8-13.0]), and existing tracheostomy (OR 3.0, 95% confidence interval [CI], 2.6-3.5). Median (interquartile range [IQR]) acute-care length of stay (LOS) for children most likely to use PAC was 19 (8-56) days; LOS remained long (median 13 [6-41] days) for children with the same attributes (n = 9448) not transferred to PAC. CONCLUSIONS: Children with RI who are most likely to use PAC have a high prevalence of multiple chronic conditions, multiple medications, and medical technology. Future investigations should assess the supply of PAC against the demand of hospitalized children with RI who might need it.

Pediatric Hospital Discharges to Home Health and Postacute Facility Care: A National Study.

IMPORTANCE: Acute care hospitals are challenged to provide efficient, high-quality care to children who have medically complex conditions and may require weeks or months for recovery. Although the use of home health care (HHC) and facility-based postacute care (PAC) after discharge is well documented for adults, to our knowledge, little is known for children. OBJECTIVE: To assess the national prevalence of, characteristics of children discharged to, and variation in use across states of HHC and PAC for children. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 2,423,031 US acute care hospital discharges in 2012 for patients ages 0 to 21 years from the nationally representative Agency for Healthcare Research and Quality Kids' Inpatient Database. MAIN OUTCOMES AND MEASURES: Discharges to HHC (eg, visiting or private-duty home nursing) and PAC (eg, rehabilitation facility) were identified from Centers for Medicare and Medicaid Services Discharge Status Codes. We compared children's characteristics (eg, race/ethnicity and number of chronic conditions) by discharge type using generalized linear regression. RESULTS: The median age of participants was 3 years (interquartile range, 0-13 years), and 45.6% were female. Of 2,423,031 US acute care hospital discharges in 2012 for patients ages 0 to 21 years, 122,673 discharges (5.1%) were to HHC and 26,282 (1.1%) were to PAC facilities. Neonatal care was the most common reason (44.5%, n = 54,589) for acute care hospitalization with discharge to HHC. Nonneonatal respiratory, musculoskeletal, and trauma-related problems, collectively, were the most common reasons for discharge to PAC (42.9%, n = 11,275). When compared with PAC, more discharges to HHC had no chronic condition (34.4% vs 18.0%, P < .001) and fewer discharges to HHC had 4 or more chronic conditions (22.5% vs 37.7%, P < .001). In multivariable analysis, Hispanic children were less likely to use PAC (0.8% vs 1.1%; odds ratio [OR], 0.9 [95% CI, 0.8-0.9]) or HHC (3.3% vs 5.5%; OR, 0.8 [95% CI, 0.7-0.8]) compared with other children. Children with 4 or more chronic conditions compared with no chronic conditions had a higher likelihood of HHC use (11.0% vs 4.4%; OR, 2.9 [95% CI, 2.8-3.0]) and PAC (3.9% vs 0.8%; OR, 4.5 [95% CI, 4.3-4.9]). After case-mix adjustment, there was significant (P < .001) variation across states in HHC (range, 0.4%-24.5%) and PAC (range, 0.4%-4.9%) use. CONCLUSIONS AND RELEVANCE: Home health care and PAC use after discharge for hospitalized children is infrequent, even for children with multiple chronic conditions. It varies significantly by race/ethnicity and across states. Further investigation is needed to assess reasons for this variation and to determine for which children HHC and PAC are most effective.

The Adult Calfactant in Acute Respiratory Distress Syndrome Trial.

BACKGROUND: Surfactant has been shown to be dysfunctional in ARDS, and exogenous surfactant has proven effective in many forms of neonatal and pediatric acute lung injury (ALI). In view of the positive results of our studies in children along with evidence that surfactant-associated protein B containing pharmaceutical surfactants might be more effective, we designed a multiinstitutional, randomized, controlled, and masked trial of calfactant, a calf lung surfactant, in adults and children with ALI/ARDS due to direct lung injury. METHODS: Adult subjects within 48 h of initiation of mechanical ventilation for direct ARDS were randomized to receive up to three interventions with instilled calfactant vs air placebo. The primary outcome was 90-day all-cause mortality. RESULTS: Three hundred seventeen subjects were enrolled, 308 of whom could be evaluated. There were no significant baseline differences between groups. Calfactant administration was not associated with improved survival, lengths of stay, or oxygenation. Calfactant instillation was frequently associated with transient hypoxia and hypotension. The study was stopped at the first interim analysis at the sponsor's request. CONCLUSIONS: Administration of calfactant was not associated with improved oxygenation or longer-term benefits relative to placebo in this randomized, controlled, and masked trial. At present, exogenous surfactant cannot be recommended for routine clinical use in ARDS. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00682500; URL: www.clinicaltrials.gov.

Pediatric post-acute care hospital transitions: an evaluation of current practice.

OBJECTIVES: After discharge from an acute care hospital, some children require ongoing care at a post-acute care hospital. Care transitions occur at both admission to the post-acute care hospital and again at discharge to the home/community. Our objective was to report the current practices used during the admission to and discharge from 7 pediatric post-acute care hospitals in the United States. METHODS: Participants from 7 pediatric post-acute care hospitals completed a survey and rated the frequency of use of 20 practices to prepare and support children and their families during both admission to the hospital and at time of discharge to the home/community. For consistency with existing literature, practices were grouped into 4 previously reported categories: assessment, communication, education, and logistics. Descriptive statistics were used to report the frequency of use within practices and between hospitals. RESULTS: Only 2 of 10 admission practices and 3 of 10 discharge practices were reportedly "always" used by all hospitals. Assessment and communication practices were reported to be more frequently used (57%-100% of the time) than education and logistic procedures. Between hospitals, only the reported frequency of use of the discharge practices was statistically significantly different (P = .03). CONCLUSIONS: Variability exists in transition practices among 7 post-acute care pediatric hospitals. This report is the first known to detail the frequency of use of admission and discharge practices for pediatric post-acute care hospitals in the United States.

Acute encephalopathy with biphasic seizures and late restricted diffusion on MRI in a Japanese child living in the USA.

We report an 18-month-old Japanese female living in the USA whose clinical course and radiographic findings were consistent with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). She was initially diagnosed with complex febrile seizures. However, on day 3 of admission, she had a cluster of complex partial seizures and the onset of a global developmental regression. In contrast to the normal magnetic resonance image of the brain obtained on admission, subsequent imaging demonstrated transient subcortical diffusion-weighted abnormalities in the white matter of the bilateral posterosuperior frontal, parietal, temporal, and occipital regions, with sparing of the perirolandic area. One year later, her developmental delay, although improved, persisted and she continued to experience sporadic seizures while being treated with topiramate monotherapy. Repeat imaging showed diffuse, poorly defined, increased T2 signals in the white matter of the posterosuperior frontal, parietal, temporal and occipital regions and diffuse cerebral volume loss. Previous reports of AESD have been limited to children aged under 4 years living in Japan. With the identification of this case, it is important that all physicians, not only those in Japan, who care for children with febrile seizures be aware of AESD and its associated neurological morbidity.