OBJECTIVES:To describe medical management surrounding withdrawal of life-sustaining therapy (WLST) in nine U.S. PICUs. DESIGN:Retrospective, secondary analysis of the "Death One Hour After Terminal Extubation" (DONATE) cohort (2009-2021) assessing usage patterns of: 1) analgesics and sedatives; 2) vasoactive infusions; 3) neuromuscular blockade; and 4) post-extubation respiratory support. SETTING:Nine U.S. PICUs. PATIENTS:Children and adolescents 0-21 years old, who had died after WLST (discontinuation of invasive mechanical ventilation). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Of 905 patients, 680 (75.1%) died within 1 hour of WLST. Opioids were administered in 721 of 905 patients (79.7%); across sites the range was 68-89% ( p < 0.001). We did not observe a temporal trend. Benzodiazepines were used in 507 of 905 patients (56.0%; site range, 41-66%; p < 0.001), with lower odds of usage per year (odds ratio [OR], 0.95 per year; 95% CI, 0.90-0.99 per year; p = 0.04). Dexmedetomidine was used in 140 of 905 patients (15.5%; sites range, 4-21%; p = 0.002), with greater odds of usage per year (OR, 1.16 per year; 95% CI, 1.05-1.27 per year; p = 0.004). Vasoactive infusions were discontinued in 458 of 520 patients (88.1%) receiving this medication (site range, 59-100%; p < 0.001), with greater odds of discontinuation per year (OR, 1.15 per year; 95% CI, 1.04-1.26 per year; p = 0.007). Neuromuscular blockade was used in 46 of 905 patients (5.1%; sites range, 0-13%; p < 0.001), with greater odds of usage per year (OR, 1.23 per year; 95% CI, 1.08-1.40 per year; p = 0.002). Use of any post-extubation respiratory support occurred in 50 of 905 patients (5.5%), and we did not identify an association with site or year-on-year trend. CONCLUSIONS:The 2009-2021 DONATE dataset shows substantial institutional and temporal variability in WLST practices across our nine collaborating PICUs in the United States. Future studies should focus on understanding the drivers of variability to improve the consistency and quality of end-of-life management.

OBJECTIVES:In the PICU, predicting death within 1 hour after terminal extubation (TE) is valuable in augmenting family counseling and in identifying suitable candidates for organ donation after circulatory determination of death (DCDD). The objective of this study was to train and validate a machine learning model to predict death within 1 hour after TE. DESIGN:The Death One Hour After Terminal Extubation (DONATE) database was generated using multicenter retrospective data from 2009 to 2021. Data covering demographics, clinical features, vital signs, laboratory values, ventilator settings, medications, and procedures were collected. Machine learning models were trained to predict whether a pediatric patient would die within 1 hour after TE and evaluated on a holdout set. SETTING:Ten U.S. PICUs. PATIENTS:Children and adolescents, 0-21 years old, who died after TE ( n = 957). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:The final model was a parsimonious extra-trees model with 21 input features. It was trained on the 2009-2018 data from eight sites ( n = 634) and evaluated on a holdout set comprised of the 2019-2021 data of all ten sites ( n = 323), representing temporal and external validation. The area under the receiver operating characteristic curve and 95% CI was 0.84 (95% CI, 0.81-0.87). At a sensitivity of 90%, the positive predictive value (PPV) was 88%, the negative predictive value (NPV) was 70%, and the number needed to alert (NNA) was 1.14. Among potential organ donors, at the same sensitivity level, the PPV was 86%, the NPV was 74%, and the NNA was 1.17. CONCLUSIONS:Our model, trained and validated on multisite data, predicted whether a child will die within 1 hour of TE with high discrimination and a low false alarm rate. This finding has important applications to end-of-life counseling and institutional resource utilization when families wish to attempt DCDD.

Introduction: The doctrine of double effect provides an ethical framework for providers to titrate medications to patient comfort at the end-of-life even if doing so hastens death, but moral distress may result from perceived under- or over- treatment. Objective of this study was to describe the doses of opioids and benzodiazepines (BZD) administered to children around the time of Terminal Extubation (TE) and to identify their association with the time to death (TTD). Methods: Secondary analysis of data collected for the Death One Hour After Terminal Extubation (DONATE) study, which included retrospective data from 9 U.S. hospitals. Medications included total doses of opioids and BZD 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression was performed to determine their association with TTD after adjusting for age, sex, last Saturation/FiO2 (SF) ratio, inotrope requirement in last 24 hours, and last recorded Glasgow Coma Scale (GCS) score. Results: Analysis cohort included 680 patients between 0-21 years who died within 1 hour in ICU after TE (2010-2021). Median age of the study population was 2.1 (IQR 0.4, 11) years. The median TTD was 15 (IQR 8, 23) minutes. 40% (278/680) of patients received either opioids or BZD within one hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent (eq) within 1 hour after TE was 0.75 (IQR 0 .3, 1.8) mg/kg/hr (n=263), and median lorazepam eq was 0.22 (IQR 0.11, 0.44) mg/kg/hr (n=118). The median morphine eq and lorazepam eq rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or BZD doses before or after TE and TTD. After adjusting for confounding variables regression analysis also failed to show any association between drug dose and TTD. Conclusions: Children after TE are often prescribed opioids and BZD. Time to death after TE is not associated with the dose of medication administered as part of comfort care. Providers should titrate analgesic and sedative/anxiolytic medications to patient comfort after terminal extubation.

Objectives:To describe the doses of opioids and benzodiazepines administered around the time of terminal extubation (TE) to children who died within 1 hour of TE and to identify their association with the time to death (TTD). Design:Secondary analysis of data collected for the Death One Hour After Terminal Extubation study. Setting:Nine U.S. hospitals. Patients:Six hundred eighty patients between 0 and 21 years who died within 1 hour after TE (2010-2021). Measurements and Main Results:Medications included total doses of opioids and benzodiazepines 24 hours before and 1 hour after TE. Correlations between drug doses and TTD in minutes were calculated, and multivariable linear regression performed to determine their association with TTD after adjusting for age, sex, last recorded oxygen saturation/Fio(2) ratio and Glasgow Coma Scale score, inotrope requirement in the last 24 hours, and use of muscle relaxants within 1 hour of TE. Median age of the study population was 2.1 years (interquartile range [IQR], 0.4-11.0 yr). The median TTD was 15 minutes (IQR, 8-23 min). Forty percent patients (278/680) received either opioids or benzodiazepines within 1 hour after TE, with the largest proportion receiving opioids only (23%, 159/680). Among patients who received medications, the median IV morphine equivalent within 1 hour after TE was 0.75 mg/kg/hr (IQR, 0.3-1.8 mg/kg/hr) (n = 263), and median lorazepam equivalent was 0.22 mg/kg/hr (IQR, 0.11-0.44 mg/kg/hr) (n = 118). The median morphine equivalent and lorazepam equivalent rates after TE were 7.5-fold and 22-fold greater than the median pre-extubation rates, respectively. No significant direct correlation was observed between either opioid or benzodiazepine doses before or after TE and TTD. After adjusting for confounding variables, regression analysis also failed to show any association between drug dose and TTD. Conclusions:Children after TE are often prescribed opioids and benzodiazepines. For patients dying within 1 hour of TE, TTD is not associated with the dose of medication administered as part of comfort care.

OBJECTIVE:Terminal extubation (TE) and terminal weaning (TW) during withdrawal of life-sustaining therapies (WLSTs) have been described and defined in adults. The recent Death One Hour After Terminal Extubation study aimed to validate a model developed to predict whether a child would die within 1 hour after discontinuation of mechanical ventilation for WLST. Although TW has not been described in children, pre-extubation weaning has been known to occur before WLST, though to what extent is unknown. In this preplanned secondary analysis, we aim to describe/define TE and pre-extubation weaning (PW) in children and compare characteristics of patients who had ventilatory support decreased before WLST with those who did not.DESIGN:Secondary analysis of multicenter retrospective cohort study.SETTING:Ten PICUs in the United States between 2009 and 2021.PATIENTS:Nine hundred thirteen patients 0-21 years old who died after WLST.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:71.4% ( n = 652) had TE without decrease in ventilatory support in the 6 hours prior. TE without decrease in ventilatory support in the 6 hours prior = 71.4% ( n = 652) of our sample. Clinically relevant decrease in ventilatory support before WLST = 11% ( n = 100), and 17.6% ( n = 161) had likely incidental decrease in ventilatory support before WLST. Relevant ventilator parameters decreased were F io2 and/or ventilator set rates. There were no significant differences in any of the other evaluated patient characteristics between groups (weight, body mass index, unit type, primary diagnostic category, presence of coma, time to death after WLST, analgosedative requirements, postextubation respiratory support modality).CONCLUSIONS:Decreasing ventilatory support before WLST with extubation in children does occur. This practice was not associated with significant differences in palliative analgosedation doses or time to death after extubation.

OBJECTIVES:Rudeness exposure has been shown to inhibit diagnostic performance. The effects of rudeness on challenging a handed-off diagnostic error has not been studied. METHODS:This was a randomized controlled study of attending, fellow, and resident physicians in a tertiary care pediatric ICU. Participants underwent a standardized simulation that started with the wrong diagnosis in hand-off. The hand-off was randomized to neutral vs. rude. Participants were not informed of the randomization nor diagnostic error prior to the simulation. Perspective taking questionnaires were administrated for each participant. Primary outcome was challenging diagnostic error post-simulation. Secondary outcomes included rate and frequency of diagnostic error challenge during simulation. RESULTS:Among 41 simulations (16 residents, 14 fellows, and 11 attendings), the neutral group challenged the diagnostic error more than the rude group (neutral: 71%, rude: 55%, p=0.28). The magnitude of this trend was larger among resident physicians only, although not statistically significant (neutral: 50%, rude: 12.5%, p=0.11). Experience was associated with a higher percentage of challenging diagnostic error (residents: 31%, fellows: 86%, attendings: 82%, p=0.003). Experienced physicians were faster to challenge diagnostic error (p<0.0003), and experience was associated with a greater frequency of diagnostic error challenges (p<0.0001). High perspective taking scores were also associated with 1.63 times more diagnostic error challenges (p=0.007). CONCLUSIONS:Experience was strongly associated with likelihood to challenge diagnostic error. Rudeness may disproportionally hinder diagnostic performance among less experienced physicians. Perspective taking merits further research in possibly reducing diagnostic error momentum.

The impact of noninvasive ventilation (NIV) on local and systemic inflammation is poorly characterized, particularly when compared with invasive mechanical ventilation (IMV). We sought to quantify the local and systemic inflammatory response of these 2 respiratory treatments in rats with lipopolysaccharide (LPS)-induced lung injury (LPS-injured) and healthy rats. Animals were subjected to 4 h of NIV or IMV treatments at noninjurious settings, or 4 h of control treatment in which healthy or LPS-injured animals remained spontaneously breathing under isoflurane anesthesia with no respiratory support. Cytokines were then quantified in the serum and lung tissue by multiplex enzyme-linked immunosorbent assay. Contrary to our hypothesis, there were no significant differences in cytokine levels in serum or lung when comparing the NIV- and IMV-treated groups; this was true in both LPS-injured and healthy rats. However, within the LPS-injured group, pulmonary levels of interleukin (IL)-1α, IL-6, and tumor necrosis factor α were significantly lower in the NIV-treated group than in control but not in the IMV-treated group compared with control. We conclude that NIV, unlike IMV, could attenuate local inflammation.

The novel coronavirus (severe acute respiratory syndrome coronavirus-2) has led to a global pandemic. In the adult population, coronavirus disease 2019 (COVID-19) has been found to cause multiorgan system damage with predicted long-term sequelae. We present a case of a 10-year-old boy with a history of ROHHAD (rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation) who presented with hypoxia, emesis, and abdominal pain. Imaging found bilateral ground glass opacities in the lungs and a pericardial effusion. Laboratory evaluation was concerning for elevated inflammatory markers. Remdesivir, hydroxychloroquine, and anticoagulation (heparin and enoxaparin) were utilized. The patient's severe respiratory failure was managed with conventional mechanical ventilation, inhaled nitric oxide, and airway pressure release ventilation. We hope that this report provides insight into the course and management of the severe acute pediatric COVID-19 patient, specifically with underlying comorbidities such as ROHHAD. Clinical trial registration is none.