Pediatric Acute Lung Injury and Sepsis Investigators (PALISI): Evolution of an Investigator-Initiated Research Network.

The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network originated over 20 years ago to foster research to optimize the care of critically ill infants and children. Over this period, PALISI has seen two major evolutions: formalization of our network infrastructure and a broadening of our clinical research focus. First, the network is unique in that its activities and meetings are funded by subscriptions from members who now comprise a multidisciplinary group of investigators from over 90 PICUs all over the United States (US) and Canada, with collaborations across the globe. In 2020, the network converted into a standalone, nonprofit organizational structure (501c3), making the PALISI Network formally independent of academic and clinical institutions or professional societies. Such an approach allows us to invest in infrastructure and future initiatives with broader opportunities for fund raising. Second, our research investigations have expanded beyond the original focus on sepsis and acute lung injury, to incorporate the whole field of pediatric critical care, for example, efficient liberation from mechanical ventilator support, prudent use of blood products, improved safety of intubation practices, optimal sedation practices and glucose control, and pandemic research on influenza and COVID-19. Our network approach in each field follows, where necessary, the full spectrum of clinical and translational research, including: immunobiology studies for understanding basic pathologic mechanisms; surveys to explore contemporary clinical practice; consensus conferences to establish agreement about literature evidence; observational prevalence and incidence studies to measure scale of a clinical issue or question; case control studies as preliminary best evidence for design of definitive prospective studies; and, randomized controlled trials for informing clinical care. As a research network, PALISI and its related subgroups have published over 350 peer-reviewed publications from 2002 through September 2022.

Rehabilitation in critically ill children: Findings from the Korean National Health Insurance database.

PURPOSE: Intensive care unit (ICU) survivors suffer from physical weakness and challenges returning to daily life. With the importance of rehabilitating patients in the pediatric intensive care unit being increasingly recognized, we evaluated the prevalence of physical and occupational therapy (PT/OT)-provided rehabilitation and factors affecting its use. METHODS: We conducted a retrospective cohort analysis of rehabilitation between 2013 and 2019 using the Korean National Health Insurance database. All patients aged 28 days to 18 years who had been admitted to 245 ICUs for more than 2 days were included. Neonatal ICUs were excluded. RESULTS: Of 13,276 patients, 2,447 (18%) received PT/OT-provided rehabilitation during their hospitalization; prevalence was lowest for patients younger than 3 years (11%). Neurologic patients were most likely to receive rehabilitation (adjusted odds ratio [aOR], 6.47; 95% confidence interval [CI], 5.11-8.20). Longer ICU stay (versus ≤ 1 week) was associated with rehabilitation (aOR for 1-2 weeks, 3.50 [95% CI, 3.04-4.03]; 2-3 weeks, 6.60 [95% CI, 5.45-8.00]; >3 weeks, 13.69 [95% CI, 11.46-16.35]). Mechanical ventilation >2 days (aOR, 0.78; 95% CI, 0.67-0.91) and hemodialysis (aOR, 0.50; 95% CI, 0.41-0.52) were negatively affecting factors. CONCLUSION: Prevalence of rehabilitation for critically ill children was low and concentrated on patients with a prolonged ICU stay. The finding that mechanical ventilation, a risk factor for ICU-acquired weakness, was an obstacle to rehabilitation highlights the need for studies on early preventive rehabilitation based on individual patient needs.

Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

Mobilization and Rehabilitation Practice in ICUs During the COVID-19 Pandemic.

BACKGROUND: Mobilization and acute rehabilitation are essential in the intensive care unit (ICU), with substantial evidence supporting their benefits. This study aimed to characterize ICU mobilization practices during the COVID-19 pandemic for patients with and without COVID-19. METHODS: This was a secondary analysis of an international point prevalence study. All ICUs across the world were eligible to participate and were required to enroll all patients in each ICU on the survey date, 27 January 2021. The primary outcome was the achievement of mobilization at the level of sitting over the edge of the bed. Independent factors associated with mobilization, including COVID-19 infection, were analyzed by multivariable analysis. RESULTS: A total of 135 ICUs in 33 countries participated, for inclusion of 1229 patients. Among patients who were not receiving mechanical ventilation (MV), those with COVID-19 infection were mobilized more than those without COVID-19 (60% vs. 34%, p < 0.001). Among patients who were receiving MV, mobilization was low in both groups (7% vs. 9%, p = .56). These findings were consistent irrespective of ICU length of stay. Multivariable analysis showed that COVID-19 infection was associated with achievement of mobilization in patients without (adjusted odds ratio [aOR] = 4.48, 95% confidence interval [CI] = 2.71-7.42) and with MV (aOR = 2.13, 95% CI = 1.00-4.51). Factors that prevented mobilization were prone positioning in patients without MV and continuous use of neuromuscular blockade and sedation agents in patients with MV, whereas facilitating factors were the presence of targets/goals in both groups. CONCLUSION: Mobilization rates for ICU patients across the globe are severely low, with the greatest immobility observed in mechanically ventilated patients. Although COVID-19 is not an independent barrier to the mobilization of patients with or without MV, this study has highlighted the current lack of mobility practice for all ICU patients during the COVID-19 pandemic.(299 words).

Implementation of the ABCDEF Bundle for Critically Ill ICU Patients During the COVID-19 Pandemic: A Multi-National 1-Day Point Prevalence Study.

Background: Data regarding delivery of evidence-based care to critically ill patients in Intensive Care Units (ICU) during the COVID-19 pandemic is crucial but lacking. This study aimed to evaluate the implementation rate of the ABCDEF bundle, which is a collection of six evidence-based ICU care initiatives which are strongly recommended to be incorporated into clinical practice, and ICU diaries for patients with and without COVID-19 infections in ICUs, and to analyze the impact of COVID-19 on implementation of each element of the bundle and independent associated factors. Methods: A world-wide 1-day point prevalence study investigated the delivery of the ABCDEF bundle and ICU diary to patients without or with COVID-19 infections on 27 January 2021 via an online questionnaire. Multivariable logistic regression analysis with adjustment for patient demographics evaluated the impact of COVID-19 and identified factors in ICU administrative structures and policies independently associated with delivery. Results: From 54 countries and 135 ICUs, 1,229 patients were eligible, and 607 (49%) had COVID-19 infections. Implementation rates were: entire bundle (without COVID-19: 0% and with COVID-19: 1%), Element A (regular pain assessment: 64 and 55%), Element B (both spontaneous awakening and breathing trials: 17 and 10%), Element C (regular sedation assessment: 45 and 61%), Element D (regular delirium assessment: 39 and 35%), Element E (exercise: 22 and 25%), Element F (family engagement/empowerment: 16 and 30%), and ICU diary (17 and 21%). The presence of COVID-19 was not associated with failure to implement individual elements. Independently associated factors for each element in common between the two groups included presence of a specific written protocol, application of a target/goal, and tele-ICU management. A lower income status country and a 3:1 nurse-patient ratio were significantly associated with non-implementation of elements A, C, and D, while a lower income status country was also associated with implementation of element F. Conclusions: Regardless of COVID-19 infection status, implementation rates for the ABCDEF bundle, for each element individually and an ICU diary were extremely low for patients without and with COVID-19 infections during the pandemic. Strategies to facilitate implementation of and adherence to the complete ABCDEF bundle should be optimized and addressed based on unit-specific barriers and facilitators.

Nutrition therapy in the intensive care unit during the COVID-19 pandemic: Findings from the ISIIC point prevalence study.

BACKGROUND & AIMS: Nutrition therapy for Intensive Care Unit (ICU) patients involves complex decision-making, especially during the COVID-19 pandemic. We investigated the use of nutrition therapy in ICU patients with and without COVID-19 infections. METHODS: Nutrition therapy was evaluated during a world-wide one-day prevalence study focused on implementation of the ABCDEF bundle (A: regular pain assessment, B: both spontaneous awakening and breathing trials, C: regular sedation assessment, D: regular delirium assessment, E: early mobility and exercise, and F: family engagement and empowerment) during the COVID-19 pandemic. Basic ICU and patient demographics including nutrition therapy delivery were collected on the survey day. Physical activity for patients with and without COVID infections was categorized using the ICU mobility scale (IMS). Multivariable regression analysis of nutrition was conducted using ICU parameters. RESULTS: The survey included 627 non-COVID and 602 COVID patients. A higher proportion of COVID-19 patients received energy ≥20 kcal/kg/day (55% vs. 45%; p = 0.0007) and protein ≥1.2 g/kg/day (45% vs. 35%; p = 0.0011) compared to non-COVID patients. Enteral nutrition was provided to most COVID patients even with prone positioning (91%). Despite nutrition therapy, IMS was extremely low in both groups; median IMS was 1 in non-COVID patients and 0 in COVID patients. The rate of energy delivery ≥20 kcal/kg/day was significantly higher in patients with COVID-19 infections in the subgroup of ICU days ≤5 days and IMS ≤2. Having a dedicated ICU nutritionist/dietitian was significantly associated with appropriate energy delivery in patients both with and without COVID-19 infections, but not with protein delivery. CONCLUSION: During the COVID-19 pandemic, patients with COVID-19 infections received higher energy and protein delivery. Generally low mobility levels highlight the need to optimize early mobilization with nutrition therapy in all ICU patients.

ABCDEF Bundle and Supportive ICU Practices for Patients With Coronavirus Disease 2019 Infection: An International Point Prevalence Study.

OBJECTIVES: To investigate implementation of evidence-based and supportive cares in ICUs, such as the ABCDEF, nutrition therapy, and ICU diary, for patients with coronavirus disease 2019 infection in ICUs and their association with ICU clinical practice and setting. DESIGN: A worldwide, 2-day point prevalence study. SETTING: The study was carried out on June 3, 2020, and July 1, 2020. A total of 212 ICUs in 38 countries participated. Clinicians in each participating ICU completed web-based online surveys. PATIENTS: The ICU patients with coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The implementation rate for the elements of the ABCDEF bundle, other supportive ICU care measures, and implementation-associated structures were investigated. Data were collected for 262 patients, of whom 47.3% underwent mechanical ventilation and 4.6% were treated with extracorporeal membrane oxygenation. Each element was implemented for the following percentages of patients: elements A (regular pain assessment), 45%; B (both spontaneous awakening and breathing trials), 28%; C (regular sedation assessment), 52%; D (regular delirium assessment), 35%; E (early mobility and exercise), 47%; and F (family engagement and empowerment), 16%. The implementation of element E was 4% for patients on mechanical ventilation and 8% for patients on extracorporeal membrane oxygenation. Supportive care, such as protein provision throughout the ICU stay (under 1.2 g/kg for more than 50% of the patients) and introduction of ICU diary (25%), was infrequent. Implementation rates of elements A and D were higher in ICUs with specific protocols and fewer ICU beds exclusively for patients with coronavirus disease 2019 infection. Element E was implemented at a higher rate in ICUs that had more ICU beds assigned for them. CONCLUSIONS: This point prevalence study showed low implementation of the ABCDEF bundle. Specific protocols and the number of ICU beds reserved for patients with coronavirus disease 2019 infection might be key factors for delivering appropriate supportive care.

Using Social Media for Rapid Information Dissemination in a Pandemic: #PedsICU and Coronavirus Disease 2019.

OBJECTIVE: To describe the impact of a strategy for international collaboration and rapid information dissemination on Twitter among the pediatric critical care community during a global pandemic. DESIGN: Analysis of #PedsICU and coronavirus disease 2019 Twitter data in the Symplur Signals Database between February 1, 2020, and May 1, 2020. SETTING: Social media platform Twitter. PATIENTS: None. INTERVENTIONS: Promotion of the joint usage of #PedsICU and #COVID19 throughout the international pediatric critical care community in tweets relevant to the coronavirus disease 2019 pandemic and pediatric critical care. MEASUREMENTS AND MAIN RESULTS: We collected data on all tweets containing the hashtag #PedsICU in addition to those containing both #PedsICU and coronavirus disease 2019 hashtags. Tweets including #PedsICU were shared 49,865 times on six continents between February 1, 2020, and May 1, 2020; between February 1 and March 13, only 8% of #PedsICU tweets included a coronavirus disease 2019 hashtag. After a sharp rise during the week of March 14, 2020, coronavirus disease 2019 content has dominated the #PedsICU conversation on Twitter, comprising 69% of both #PedsICU tweets and impressions (p < 0.001). The most commonly used coronavirus disease 2019 hashtag over the study period was #COVID19 (69%). Proportionately, a greater percentage of #PedsICU tweets including the coronavirus disease 2019 hashtag (vs not) had images or videos (45% vs 41%; p < 0.001). In addition, non-physician healthcare providers were the largest group of users (46%) of the combination of #PedsICU and coronavirus disease 2019 hashtags. The most popular tweets shared on Twitter were open-access resources, including links for updated literature, narrative reviews, and educational videos relevant to coronavirus disease 2019 clinical care. Concurrent hashtags and words in tweets containing #PedsICU and coronavirus disease 2019 hashtags spanned several different disciplines and topics in pediatric critical care. CONCLUSION: Twitter has been used widely for real-time information sharing and collaboration among the international pediatric critical care community during the coronavirus disease 2019 pandemic. Targeted use of #PedsICU and #COVID19 for engagement on Twitter is a conduit to combat misinformation and optimize reach to pediatric critical care stakeholders across the globe when rapid dissemination is needed.