Child Opportunity Index and Pediatric Intensive Care Outcomes: A Multicenter Retrospective Study in the United States.

OBJECTIVES: To evaluate for associations between a child's neighborhood, as categorized by Child Opportunity Index (COI 2.0), and 1) PICU mortality, 2) severity of illness at PICU admission, and 3) PICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Fifteen PICUs in the United States. PATIENTS: Children younger than 18 years admitted from 2019 to 2020, excluding those after cardiac procedures. Nationally-normed COI category (very low, low, moderate, high, very high) was determined for each admission by census tract, and clinical features were obtained from the Virtual Pediatric Systems LLC (Los Angeles, CA) data from each site. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 33,901 index PICU admissions during the time period, median patient age was 4.9 years and PICU mortality was 2.1%. There was a higher percentage of admissions from the very low COI category (27.3%) than other COI categories (17.2-19.5%, p < 0.0001). Patient admissions from the high and very high COI categories had a lower median Pediatric Index of Mortality 3 risk of mortality (0.70) than those from the very low, low, and moderate COI groups (0.71) ( p < 0.001). PICU mortality was lowest in the very high (1.7%) and high (1.9%) COI groups and highest in the moderate group (2.5%), followed by very low (2.3%) and low (2.2%) ( p = 0.001 across categories). Median PICU LOS was between 1.37 and 1.50 days in all COI categories. Multivariable regression revealed adjusted odds of PICU mortality of 1.30 (95% CI, 0.94-1.79; p = 0.11) for children from a very low versus very high COI neighborhood, with an odds ratio [OR] of 0.996 (95% CI, 0.993-1.00; p = 0.05) for mortality for COI as an ordinal value from 0 to 100. Children without insurance coverage had an OR for mortality of 3.58 (95% CI, 2.46-5.20; p < 0.0001) as compared with those with commercial insurance. CONCLUSIONS: Children admitted to a cohort of U.S. PICUs were often from very low COI neighborhoods. Children from very high COI neighborhoods had the lowest risk of mortality and observed mortality; however, odds of mortality were not statistically different by COI category in a multivariable model. Children without insurance coverage had significantly higher odds of PICU mortality regardless of neighborhood.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Nonadherence to appropriate tidal volume and PEEP in children with pARDS at a single center.

BACKGROUND: Low tidal volume and adequate positive end-expiratory pressure (PEEP) are evidence-based approaches for pediatric acute respiratory distress syndrome (pARDS), however, data are limited regarding their use since pARDS guidelines were revised in 2015. OBJECTIVE: To identify prevalence of, and factors associated with, nonadherence to appropriate tidal volume and PEEP in children with pARDS. METHODS: Retrospective cohort study of children 1 month to <18 years with pARDS who received invasive mechanical ventilation from 2016 to 2018 in a single pediatric intensive care unit (PICU). RESULTS: At 24 h after meeting pARDS criteria, 48/86 (56%) patients received tidal volume ≤8 ml/kg of ideal body weight and 45/86 (52%) received appropriate PEEP, with 22/86 (26%) receiving both. Among patients ≥2 years of age, a lower proportion of patients with overweight/obesity (9/25, 36%) had appropriate tidal volume versus those in the normal or underweight category (16/22, 73%, p = 0.02). When FIO2 was ≥50%, PEEP was appropriate in 19/60 (32%) cases versus 26/26 (100%) with FIO2 < 50% (p < 0.0001). pARDS was documented in the progress note in 7/86 (8%) patients at 24 h. Severity of pARDS, documentation in the progress note, and other clinical factors were not significantly associated with use of appropriate tidal volume and PEEP, however pARDS was documented more commonly in patients with severe pARDS. CONCLUSIONS: In a single PICU in the United States, children with pARDS did not receive appropriate tidal volume for ideal body weight nor PEEP. Targets for improving tidal volume and PEEP adherence may include overweight patients and those receiving FIO2 ≥ 50%, respectively.

The Impact of Strict Public Health Restrictions on Pediatric Critical Illness.

OBJECTIVES: To characterize the impact of public health interventions on the volume and characteristics of admissions to the PICU. DESIGN: Multicenter retrospective cohort study. SETTING: Six U.S. referral PICUs during February 15, 2020-May 14, 2020, compared with the same months during 2017-2019 (baseline). PATIENTS: PICU admissions excluding admissions for illnesses due to severe acute respiratory syndrome coronavirus 2 and readmissions during the same hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was admission volumes during the period of stay-at-home orders (March 15, 2020-May 14, 2020) compared with baseline. Secondary outcomes were hospitalization characteristics including advanced support (e.g., invasive mechanical ventilation), PICU and hospital lengths of stay, and mortality. We used generalized linear mixed modeling to compare patient and admission characteristics during the stay-at-home orders period to baseline. We evaluated 7,960 admissions including 1,327 during March 15, 2020-May 14, 2020. Daily admissions and patients days were lower during the period of stay-at-home orders compared with baseline: median admissions 21 (interquartile range, 17-25) versus 36 (interquartile range, 30-42) (p < 0.001) and median patient days 93.0 (interquartile range, 55.9-136.7) versus 143.6 (interquartile range, 108.5-189.2) (p < 0.001). Admissions during the period of stay-at-home orders were less common in young children and for respiratory and infectious illnesses and more common for poisonings, endocrinopathies and for children with race/ethnicity categorized as other/unspecified. There were no differences in hospitalization characteristics except fewer patients received noninvasive ventilation during the period of stay-at-home orders. CONCLUSIONS: Reductions in PICU admissions suggest that much of pediatric critical illness in younger children and for respiratory and infectious illnesses may be preventable through targeted public health strategies.

Long-Term Outcomes and the Post-Intensive Care Syndrome in Critically Ill Children: A North American Perspective.

Advances in medical and surgical care for children in the pediatric intensive care unit (PICU) have led to vast reductions in mortality, but survivors often leave with newly acquired or worsened morbidity. Emerging evidence reveals that survivors of pediatric critical illness may experience a constellation of physical, emotional, cognitive, and social impairments, collectively known as the "post-intensive care syndrome in pediatrics" (PICs-P). The spectrum of PICs-P manifestations within each domain are heterogeneous. This is attributed to the wide age and developmental diversity of children admitted to PICUs and the high prevalence of chronic complex conditions. PICs-P recovery follows variable trajectories based on numerous patient, family, and environmental factors. Those who improve tend to do so within less than a year of discharge. A small proportion, however, may actually worsen over time. There are many gaps in our current understanding of PICs-P. A unified approach to screening, preventing, and treating PICs-P-related morbidity has been hindered by disparate research methodology. Initiatives are underway to harmonize clinical and research priorities, validate new and existing epidemiologic and patient-specific tools for the prediction or monitoring of outcomes, and define research priorities for investigators interested in long-term outcomes.

Characteristics of Burn-Injured Children in 117 U.S. PICUs (2009-2017): A Retrospective Virtual Pediatric Systems Database Study.

OBJECTIVES: To describe characteristics and outcomes of children with burn injury treated in U.S. PICUs. DESIGN: Retrospective study of admissions in the Virtual Pediatric Systems, LLC, database from 2009 to 2017. SETTING: One hundred and seventeen PICUs in the United States. PATIENTS: Patients less than 18 years old admitted with an active diagnosis of burn at admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,056 patients were included. They were predominantly male (62.6%) and less than 6 years old (66.7%). Cutaneous burns were recorded in 92.1% of patients, mouth/pharynx burns in 5.8%, inhalation injury in 5.1%, and larynx/trachea/lung burns in 4.5%. Among those with an etiology recorded (n = 861), scald was most common (38.6%), particularly in children less than 2 years old (67.8%). Fire/flame burns were most common (46.6%) in children greater than or equal to 2 years. Multiple organ failure was present in 26.2% of patients. Most patients (89%) were at facilities without American Burn Association pediatric verification. PICU mortality occurred in 4.5% of patients. On multivariable analysis using Pediatric Index of Mortality 2, greater than or equal to 30% total body surface area burned was significantly associated with mortality (odds ratio, 5.40; 95% CI, 2.16-13.51; p = 0.0003). When Pediatric Risk of Mortality III was used, greater than or equal to 30% total body surface area burned (odds ratio, 5.45; 95% CI, 1.95-15.26; p = 0.001) and inhalation injury (odds ratio, 5.39; 95% CI, 1.58-18.42; p = 0.007) were significantly associated with mortality. Among 366 survivors (18.6%) with Pediatric Cerebral Performance Category or Pediatric Overall Performance Category data, 190 (51.9%) had a greater than or equal to 1 point increase in Pediatric Cerebral Performance Category or Pediatric Overall Performance Category disability category and 80 (21.9%) had a new designation of moderate or severe disability, or persistent vegetative state. CONCLUSIONS: Burn-injured patients in U.S. PICUs have a substantial burden of organ failure, morbidity, and mortality. Coordination among specialized facilities may be particularly important in this population, especially for those with higher % total body surface area burned or inhalation injury.

A Framework for Pediatric Intensivists Providing Compassionate Extubation at Home.

For families facing end-of-life decisions for their critically ill children, compassionate extubation at home is a valuable service that pediatric intensivists can provide. Compassionate extubation at home is resource intensive and can be logistically challenging. Discouragingly, guidance on compassionate extubation at home in the literature is limited. We developed an evidence- and experience-based framework for compassionate extubation at home addressing common planning challenges and resource management. Our objective is to share this framework and an accompanying checklist, so that pediatric intensivists in other institutions can adapt these tools for their use, reducing barriers to providing compassionate extubation at home for critically ill children at the end of life.

Prolonged Duration Topical Corneal Anesthesia With the Cationic Lidocaine Derivative QX-314.

PURPOSE: Topical corneal local anesthetics are short acting and may impair corneal healing. In this study we compared corneal anesthesia and toxicity of topically applied N-ethyl lidocaine (QX-314) versus the conventional local anesthetic, proparacaine (PPC). METHODS: Various concentrations of QX-314 and 15 mM (0.5%) PPC were topically applied to rat corneas. Corneal anesthesia was assessed with a Cochet-Bonnet esthesiometer at predetermined time points. PC12 cells were exposed to the same solutions to assess cytotoxicity. Repeated topical corneal administration in rats was then used to assess for histologic evidence of toxicity. Finally, we created uniform corneal epithelial defects in rats and assessed the effect of repeated administration of these compounds on the defect healing rate. RESULTS: QX-314 (15 mM) and PPC (15 mM) caused similar total duration (114 ± 17 and 87 ± 16 minutes, respectively; P = 0.06) of anesthesia. The depth of anesthesia was similar between these low-dose groups at 15 minutes after application (1.8 ± 0.3- and 2.0 ± 0.8-cm filament lengths). QX-314 (100 mM) provided more prolonged corneal anesthesia (174 ± 13 minutes; P < 0.0001), with improved depth at 15 minutes (0.7 ± 0.3-cm filament length; P = 0.007). All tested concentrations of QX-314 demonstrated similar or less toxicity than 0.5% PPC. CONCLUSIONS: Topical administration of QX-314 is effective for corneal anesthesia and demonstrates no histologic signs of local toxicity in a rodent model. In higher concentrations, QX-314 provides more than twofold the duration of anesthetic effect than does 0.5% PPC. TRANSLATIONAL RELEVANCE: Our study reveals a clinically relevant compound providing prolonged duration topical corneal anesthesia.

Sirtuins and Immuno-Metabolism of Sepsis.

Sepsis and septic shock are the leading causes of death in non-coronary intensive care units worldwide. During sepsis-associated immune dysfunction, the early/hyper-inflammatory phase transitions to a late/hypo-inflammatory phase as sepsis progresses. The majority of sepsis-related deaths occur during the hypo-inflammatory phase. There are no phase-specific therapies currently available for clinical use in sepsis. Metabolic rewiring directs the transition from hyper-inflammatory to hypo-inflammatory immune responses to protect homeostasis during sepsis inflammation, but the mechanisms underlying this immuno-metabolic network are unclear. Here, we review the roles of NAD+ sensing Sirtuin (SIRT) family members in controlling immunometabolic rewiring during the acute systemic inflammatory response associated with sepsis. We discuss individual contributions among family members SIRT 1, 2, 3, 4 and 6 in regulating the metabolic switch between carbohydrate-fueled hyper-inflammation to lipid-fueled hypo-inflammation. We further highlight the role of SIRT1 and SIRT2 as potential "druggable" targets for promoting immunometabolic homeostasis and increasing sepsis survival.