Association of Postarrest Hypotension Burden With Unfavorable Neurologic Outcome After Pediatric Cardiac Arrest.

OBJECTIVE: Quantify hypotension burden using high-resolution continuous arterial blood pressure (ABP) data and determine its association with outcome after pediatric cardiac arrest. DESIGN: Retrospective observational study. SETTING: Academic PICU. PATIENTS: Children 18 years old or younger admitted with in-of-hospital or out-of-hospital cardiac arrest who had invasive ABP monitoring during postcardiac arrest care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: High-resolution continuous ABP was analyzed up to 24 hours after the return of circulation (ROC). Hypotension burden was the time-normalized integral area between mean arterial pressure (MAP) and fifth percentile MAP for age. The primary outcome was unfavorable neurologic status (pediatric cerebral performance category ≥ 3 with change from baseline) at hospital discharge. Mann-Whitney U tests compared hypotension burden, duration, and magnitude between favorable and unfavorable patients. Multivariable logistic regression determined the association of unfavorable outcomes with hypotension burden, duration, and magnitude at various percentile thresholds from the 5th through 50th percentile for age. Of 140 patients (median age 53 [interquartile range 11-146] mo, 61% male); 63% had unfavorable outcomes. Monitoring duration was 21 (7-24) hours. Using a MAP threshold at the fifth percentile for age, the median hypotension burden was 0.01 (0-0.11) mm Hg-hours per hour, greater for patients with unfavorable compared with favorable outcomes (0 [0-0.02] vs. 0.02 [0-0.27] mm Hg-hr per hour, p < 0.001). Hypotension duration and magnitude were greater for unfavorable compared with favorable patients (0.03 [0-0.77] vs. 0.71 [0-5.01]%, p = 0.003; and 0.16 [0-1.99] vs. 2 [0-4.02] mm Hg, p = 0.001). On logistic regression, a 1-point increase in hypotension burden below the fifth percentile for age (equivalent to 1 mm Hg-hr of burden per hour of recording) was associated with increased odds of unfavorable outcome (adjusted odds ratio [aOR] 14.8; 95% CI, 1.1-200; p = 0.040). At MAP thresholds of 10th-50th percentiles for age, MAP burden below the threshold was greater in unfavorable compared with favorable patients in a dose-dependent manner. CONCLUSIONS: High-resolution continuous ABP data can be used to quantify hypotension burden after pediatric cardiac arrest. The burden, duration, and magnitude of hypotension are associated with unfavorable neurologic outcomes.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

OBJECTIVES: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING: Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

Venovenous Extracorporeal Membrane Oxygenation Initiation for Pediatric Acute Respiratory Distress Syndrome With Cardiovascular Instability is Associated With an Immediate and Sustained Decrease in Vasoactive-Inotropic Scores.

OBJECTIVE: To determine the association of venovenous extracorporeal membrane oxygenation (VV-ECMO) initiation with changes in vasoactive-inotropic scores (VISs) in children with pediatric acute respiratory distress syndrome (PARDS) and cardiovascular instability. DESIGN: Retrospective cohort study. SETTING: Single academic pediatric ECMO center. PATIENTS: Children (1 mo to 18 yr) treated with VV-ECMO (2009-2019) for PARDS with need for vasopressor or inotropic support at ECMO initiation. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas values, VIS, mean airway pressure (mPaw), and oxygen saturation (Sp o2 ) values were recorded hourly relative to the start of ECMO flow for 24 hours pre-VV-ECMO and post-VV-ECMO cannulation. A sharp kink discontinuity regression analysis clustered by patient tested the difference in VISs and regression line slopes immediately surrounding cannulation. Thirty-two patients met inclusion criteria: median age 6.6 years (interquartile range [IQR] 1.5-11.7), 22% immunocompromised, and 75% had pneumonia or sepsis as the cause of PARDS. Pre-ECMO characteristics included: median oxygenation index 45 (IQR 35-58), mPaw 32 cm H 2o (IQR 30-34), 97% on inhaled nitric oxide, and 81% on an advanced mode of ventilation. Median VIS immediately before VV-ECMO cannulation was 13 (IQR 8-25) with an overall increasing VIS trajectory over the hours before cannulation. VISs decreased and the slope of the regression line reversed immediately surrounding the time of cannulation (robust p < 0.0001). There were pre-ECMO to post-ECMO cannulation decreases in mPaw (32 vs 20 cm H 2o , p < 0.001) and arterial P co2 (64.1 vs 50.1 mm Hg, p = 0.007) and increases in arterial pH (7.26 vs 7.38, p = 0.001), arterial base excess (2.5 vs 5.2, p = 0.013), and SpO 2 (91% vs 95%, p = 0.013). CONCLUSIONS: Initiation of VV-ECMO was associated with an immediate and sustained reduction in VIS in PARDS patients with cardiovascular instability. This VIS reduction was associated with decreased mPaw and reduced respiratory and/or metabolic acidosis as well as improved oxygenation.

Early, Persistent Lymphopenia Is Associated With Prolonged Multiple Organ Failure and Mortality in Septic Children.

OBJECTIVES: Sepsis-associated immune suppression correlates with poor outcomes. Adult trials are evaluating immune support therapies. Limited data exist to support consideration of immunomodulation in pediatric sepsis. We tested the hypothesis that early, persistent lymphopenia predicts worse outcomes in pediatric severe sepsis. DESIGN: Observational cohort comparing children with severe sepsis and early, persistent lymphopenia (absolute lymphocyte count < 1,000 cells/µL on 2 d between study days 0-5) to children without. The composite outcome was prolonged multiple organ dysfunction syndrome (MODS, organ dysfunction beyond day 7) or PICU mortality. SETTING: Nine PICUs in the National Institutes of Health Collaborative Pediatric Critical Care Research Network between 2015 and 2017. PATIENTS: Children with severe sepsis and indwelling arterial and/or central venous catheters. INTERVENTIONS: Blood sampling and clinical data analysis. MEASUREMENTS AND MAIN RESULTS: Among 401 pediatric patients with severe sepsis, 152 (38%) had persistent lymphopenia. These patients were older, had higher illness severity, and were more likely to have underlying comorbidities including solid organ transplant or malignancy. Persistent lymphopenia was associated with the composite outcome prolonged MODS or PICU mortality (66/152, 43% vs 45/249, 18%; p < 0.01) and its components prolonged MODS (59/152 [39%] vs 43/249 [17%]), and PICU mortality (32/152, 21% vs 12/249, 5%; p < 0.01) versus children without. After adjusting for baseline factors at enrollment, the presence of persistent lymphopenia was associated with an odds ratio of 2.98 (95% CI [1.85-4.02]; p < 0.01) for the composite outcome. Lymphocyte count trajectories showed that patients with persistent lymphopenia generally did not recover lymphocyte counts during the study, had lower nadir whole blood tumor necrosis factor-α response to lipopolysaccharide stimulation, and higher maximal inflammatory markers (C-reactive protein and ferritin) during days 0-3 ( p < 0.01). CONCLUSIONS: Children with severe sepsis and persistent lymphopenia are at risk of prolonged MODS or PICU mortality. This evidence supports testing therapies for pediatric severe sepsis patients risk-stratified by early, persistent lymphopenia.

Acute Disorders of Consciousness in Pediatric Severe Sepsis and Organ Failure: Secondary Analysis of the Multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study.

OBJECTIVES: Acute disorders of consciousness (DoC) in pediatric severe sepsis are associated with increased risk of morbidity and mortality. We sought to examine the frequency of and factors associated with DoC in children with sepsis-induced organ failure. DESIGN: Secondary analysis of the multicenter Phenotyping Sepsis-Induced Multiple Organ Failure Study (PHENOMS). SETTING: Nine tertiary care PICUs in the United States. PATIENTS: Children less than 18 years old admitted to a PICU with severe sepsis and at least one organ failure during a PICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was frequency of DoC, defined as Glasgow Coma Scale (GCS) less than 12 in the absence of sedatives during an ICU stay, among children with severe sepsis and the following: single organ failure, nonphenotypeable multiple organ failure (MOF), MOF with one of the PHENOMS phenotypes (immunoparalysis-associated MOF [IPMOF], sequential liver failure-associated MOF, thrombocytopenia-associated MOF), or MOF with multiple phenotypes. A multivariable logistic regression analysis was performed to evaluate the association between clinical variables and organ failure groups with DoC. Of 401 children studied, 71 (18%) presented with DoC. Children presenting with DoC were older (median 8 vs 5 yr; p = 0.023), had increased hospital mortality (21% vs 10%; p = 0.011), and more frequently presented with both any MOF (93% vs 71%; p < 0.001) and macrophage activation syndrome (14% vs 4%; p = 0.004). Among children with any MOF, those presenting with DoC most frequently had nonphenotypeable MOF and IPMOF (52% and 34%, respectively). In the multivariable analysis, older age (odds ratio, 1.07; 95% CI, 1.01-1.12) and any MOF (3.22 [1.19-8.70]) were associated with DoC. CONCLUSIONS: One of every five children with severe sepsis and organ failure experienced acute DoC during their PICU stay. Preliminary findings suggest the need for prospective evaluation of DoC in children with sepsis and MOF.

Diastolic Blood Pressure Threshold During Pediatric Cardiopulmonary Resuscitation and Survival Outcomes: A Multicenter Validation Study.

OBJECTIVES: Arterial diastolic blood pressure (DBP) greater than 25 mm Hg in infants and greater than 30 mm Hg in children greater than 1 year old during cardiopulmonary resuscitation (CPR) was associated with survival to hospital discharge in one prospective study. We sought to validate these potential hemodynamic targets in a larger multicenter cohort. DESIGN: Prospective observational study. SETTING: Eighteen PICUs in the ICU-RESUScitation prospective trial from October 2016 to March 2020. PATIENTS: Children less than or equal to 18 years old with CPR greater than 30 seconds and invasive blood pressure (BP) monitoring during CPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Invasive BP waveform data and Utstein-style CPR data were collected, including prearrest patient characteristics, intra-arrest interventions, and outcomes. Primary outcome was survival to hospital discharge, and secondary outcomes were return of spontaneous circulation (ROSC) and survival to hospital discharge with favorable neurologic outcome. Multivariable Poisson regression models with robust error estimates evaluated the association of DBP greater than 25 mm Hg in infants and greater than 30 mm Hg in older children with these outcomes. Among 1,129 children with inhospital cardiac arrests, 413 had evaluable DBP data. Overall, 85.5% of the patients attained thresholds of mean DBP greater than or equal to 25 mm Hg in infants and greater than or equal to 30 mm Hg in older children. Initial return of circulation occurred in 91.5% and 25% by placement on extracorporeal membrane oxygenator. Survival to hospital discharge occurred in 58.6%, and survival with favorable neurologic outcome in 55.4% (i.e. 94.6% of survivors had favorable neurologic outcomes). Mean DBP greater than 25 mm Hg for infants and greater than 30 mm Hg for older children was significantly associated with survival to discharge (adjusted relative risk [aRR], 1.32; 1.01-1.74; p = 0.03) and ROSC (aRR, 1.49; 1.12-1.97; p = 0.002) but did not reach significance for survival to hospital discharge with favorable neurologic outcome (aRR, 1.30; 0.98-1.72; p = 0.051). CONCLUSIONS: These validation data demonstrate that achieving mean DBP during CPR greater than 25 mm Hg for infants and greater than 30 mm Hg for older children is associated with higher rates of survival to hospital discharge, providing potential targets for DBP during CPR.

The Temporal Association of the COVID-19 Pandemic and Pediatric Cardiopulmonary Resuscitation Quality and Outcomes.

OBJECTIVES: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes. DESIGN: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021). SETTING: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial. PATIENTS: Children (≤ 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic ( p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2]; p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points; p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46]; p = 0.04). CONCLUSIONS: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels.

OBJECTIVES: Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks. DATA SOURCES: A prospective, observational cohort study. STUDY SELECTION: Children with sepsis and organ failure in nine pediatric intensive care units in the United States. DATA EXTRACTION: Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin. DATA SYNTHESIS: Group 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines. CONCLUSIONS: Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.

Association Between Quantitative Diffusion Weighted Magnetic Resonance Neuroimaging and Outcome After Pediatric Cardiac Arrest.

BACKGROUND AND OBJECTIVES: Diffusion magnetic resonance imaging (MRI) can quantify extent of hypoxic-ischemic brain injury after cardiac arrest. Our objective was to determine the association between adult-derived threshold of apparent diffusion coefficient (ADC) <650x10-6mm2/s in >10% of brain tissue and unfavorable outcome after pediatric cardiac arrest. Since ADC decreases exponentially as a function of increasing age, we determined association 1) having >10% of brain tissue below a novel age-dependent ADC threshold, and 2) age-normalized whole brain mean ADC and unfavorable outcome. METHODS: Retrospective study of patients ≤18 years old who had cardiac arrest and a clinically obtained brain MRI within 7 days. Primary outcome was unfavorable neurologic status at hospital discharge based on Pediatric Cerebral Performance Category (PCPC) score. ADC images were extracted from three-direction diffusion imaging. We determined whether each patient had >10% of voxels with ADC below prespecified thresholds. We computed whole brain mean ADC for each patient. RESULTS: One-hundred-thirty-four patients were analyzed. Patients with ADC <650x10-6mm2/s in >10% of voxels had 15 times higher odds (95%CI 5, 65) of unfavorable outcome compared to patients with ADC <650x10-6mm2/s (AUROC 0.72 [95%CI 0.63, 0.80]). This ADC criteria had a sensitivity and specificity of 0.49 and 0.94, and positive and negative predictive values of 0.93 and 0.52 for unfavorable outcome. The age-dependent ADC threshold that yielded optimal sensitivity and specificity for unfavorable outcome was <300x10-6mm2/s below each patient's predicted whole brain mean ADC. The sensitivity, specificity, positive and negative predictive values for this ADC threshold were 0.53, 0.96, 0.96, and 0.54, respectively (OR: 26.4 [95%CI 7.5, 168.3]; AUROC 0.74 [95%CI 0.66, 0.83]). Lower age-normalized whole brain mean ADC was also associated with unfavorable outcome (OR 0.42 [0.24, 0.64], AUROC 0.76 [95%CI 0.66, 0.82]). DISCUSSION: Quantitative diffusion thresholds on MRI within 7 days after cardiac arrest were associated with unfavorable outcome in children. Age-independent ADC threshold was highly specific for predicting unfavorable outcome. However, specificity and sensitivity increased when using age-dependent ADC thresholds. Age-dependent ADC thresholds may improve prognostic accuracy and require further investigation in larger cohorts. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that quantitative diffusion-weighted imaging (DWI) within 7 days post-arrest can predict an unfavorable clinical outcome in children.

Health Resource Use in Survivors of Pediatric Septic Shock in the United States.

OBJECTIVES: To evaluate postdischarge health resource use in pediatric survivors of septic shock and determine patient and hospitalization factors associated with health resource use. DESIGN: Secondary analyses of a multicenter prospective observational cohort study. SETTING: Twelve academic PICUs. PATIENTS: Children greater than or equal to 1 month and less than 18 years old hospitalized for community-acquired septic shock who survived to 1 year. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 308/338 patients (91%) with baseline and greater than or equal to one postdischarge survey, we evaluated readmission, emergency department (ED) visits, new medication class, and new device class use during the year after sepsis. Using negative binomial regression with bidirectional stepwise selection, we identified factors associated with each outcome. Median age was 7 years (interquartile range, 2-13), 157 (51%) had a chronic condition, and nearly all patients had insurance (private [n = 135; 44%] or government [n = 157; 51%]). During the year after sepsis, 128 patients (42%) were readmitted, 145 (47%) had an ED visit, 156 (51%) started a new medication class, and 102 (33%) instituted a new device class. Having a complex chronic condition was independently associated with readmission and ED visit. Documented infection and higher sum of Pediatric Logistic Organ Dysfunction--2 hematologic score were associated with readmission, whereas younger age and having a noncomplex chronic condition were associated with ED visit. Factors associated with new medication class use were private insurance, neurologic insult, and longer PICU stays. Factors associated with new device class use were preadmission chemotherapy or radiotherapy, presepsis Functional Status Scale score, and ventilation duration greater than or equal to 10 days. Of patients who had a new medication or device class, most had a readmission (56% and 61%) or ED visit (62% and 67%). CONCLUSIONS: Children with septic shock represent a high-risk cohort with high-resource needs after discharge. Interventions and targeted outcomes to mitigate postdischarge resource use may differ based on patients' preexisting conditions.

Validity Evidence for a Novel, Comprehensive Bag-Mask Ventilation Assessment Tool.

OBJECTIVE: To develop a comprehensive competency assessment tool for pediatric bag-mask ventilation (pBMV) and demonstrate multidimensional validity evidence for this tool. STUDY DESIGN: A novel pBMV assessment tool was developed consisting of 3 components: a 22-item-based checklist (trichotomized response), global rating scale (GRS, 5-point), and entrustment assessment (4-point). Participants' performance in a realistic simulation scenario was video-recorded and assessed by blinded raters. Multidimensional validity evidence for procedural assessment, including evidence for content, response-process, internal structure, and relation to other variables, was assessed. The scores of each scale were compared with training level. Item-based checklist scores also were correlated with GRS and entrustment scores. RESULTS: Fifty-eight participants (9 medical students, 10 pediatric residents, 18 critical care/neonatology fellows, 21 critical care/neonatology attendings) were evaluated. The pBMV tool was supported by high internal consistency (Cronbach α = 0.867). Inter-rater reliability for the item-based checklist component was acceptable (r = 0.65, P < .0001). The item-based checklist scores differentiated between medical students and other providers (P < .0001), but not by other trainee level. GRS and entrustment scores significantly differentiated between training levels (P < .001). Correlation between skill item-based checklist and GRS was r = 0.489 (P = .0001) and between item-based checklist and entrustment score was r = 0.52 (P < .001). This moderate correlation suggested each component measures pBMV skills differently. The GRS and entrustment scores demonstrated moderate inter-rater reliability (0.42 and 0.46). CONCLUSIONS: We established evidence of multidimensional validity for a novel entrustment-based pBMV competence assessment tool, incorporating global and entrustment-based assessments. This comprehensive tool can provide learner feedback and aid in entrustment decisions as learners progress through training.

Serial Neurologic Assessment in Pediatrics (SNAP): A New Tool for Bedside Neurologic Assessment of Critically Ill Children.

OBJECTIVES: We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN: Mixed-methods, observational cohort. SETTING: Pediatric and neonatal ICUs. SUBJECTS: Critical care nurses and patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS: When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

A Core Outcome Set for Pediatric Critical Care.

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Deployment of a Clinical Pathway to Improve Postcardiac Arrest Care: A Before-After Study.

OBJECTIVES: Postcardiac arrest care bundles following adult cardiac arrest are associated with improved survival to discharge. We aimed to evaluate whether a clinical pathway and computerized order entry were associated with improved pediatric postcardiac arrest care and discharge outcomes. DESIGN: Single-center retrospective before-after study. SETTING: Academic PICU. PATIENTS: Patients who suffered an in- or out-of-hospital cardiac arrest from January 2008 to December 2015 cared for in the PICU within 12 hours of sustained return of circulation. INTERVENTION: Deployment of a postcardiac arrest clinical pathway and computerized order entry system. MEASUREMENTS AND MAIN RESULTS: There were 380 patients included-163 in the pre-pathway period and 217 in the post-pathway period. Primary outcome was percent adherence to pathway clinical goals at 0-6 and 6-24 hours post-return of circulation and to diagnostics (continuous electroencephalogram monitoring, head CT for out-of-hospital cardiac arrests, echocardiogram). Secondary outcomes included survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). The pre-pathway and post-pathway groups differed in their baseline Pediatric Cerebral Performance Category scores and the following causes of arrest: airway obstruction, arrhythmias, and electrolyte abnormalities. Pathway adherence was not significantly different between the pre-pathway and post-pathway groups, with the exception of higher rates of continuous electroencephalogram monitoring (45% vs 64%; p < 0.001). There was no difference in survival to hospital discharge between the two groups (56% vs 67%; adjusted odds ratio, 1.68; 95% CI, 0.95-2.84; p = 0.05). Survival to discharge was higher in the post-pathway group for the in-hospital cardiac arrest cohort (55% vs 76%; adjusted odds ratio, 3.06; 95% CI, 1.44-6.51; p < 0.01). There was no difference in favorable neurologic outcome between all patients (adjusted odds ratio, 1.21; 95% CI, 0.72-2.04) or among survivors (adjusted odds ratio, 0.72; 95% CI, 0.27-1.43). CONCLUSIONS: After controlling for known potential confounders, the creation and deployment of a postcardiac arrest care pathway and computerized order entry set were not associated with improvement in pathway adherence or overall outcomes, but was associated with increased survival to hospital discharge for children with in-hospital cardiac arrests.

Pediatric Resuscitation Practices During the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: While most pediatric coronavirus disease 2019 cases are not life threatening, some children have severe disease requiring emergent resuscitative interventions. Resuscitation events present risks to healthcare provider safety and the potential for compromised patient care. Current resuscitation practices and policies for children with suspected/confirmed coronavirus disease 2019 are unknown. DESIGN: Multi-institutional survey regarding inpatient resuscitation practices during the coronavirus disease 2019 pandemic. SETTING: Internet-based survey. SUBJECTS: U.S. PICU representatives (one per institution) involved in resuscitation system planning and oversight. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 130 institutions surveyed, 78 (60%) responded. Forty-eight centers (62%) had admitted coronavirus disease 2019 patients; 26 (33%) reported code team activation for patients with suspected/confirmed coronavirus disease 2019. Sixty-seven respondents (86%) implemented changes to inpatient emergency response systems. The most common changes were as follows: limited number of personnel entering patient rooms (75; 96%), limited resident involvement (71; 91%), and new or refined team roles (74; 95%). New or adapted technology is being used for coronavirus disease 2019 resuscitations in 58 centers (74%). Most institutions (57; 73%) are using enhanced personal protective equipment for all coronavirus disease 2019 resuscitation events; 18 (23%) have personal protective equipment policies dependent on the performance of aerosol generating procedures. Due to coronavirus disease 2019, most respondents are intubating earlier during cardiopulmonary resuscitation (56; 72%), utilizing video laryngoscopy (67; 86%), pausing chest compressions during laryngoscopy (56; 72%), and leaving patients connected to the ventilator during cardiopulmonary resuscitation (56; 72%). Responses were varied regarding airway personnel, prone cardiopulmonary resuscitation, ventilation strategy during cardiopulmonary resuscitation without an airway in place, and extracorporeal cardiopulmonary resuscitation. Most institutions (46; 59%) do not have policies regarding limitations of resuscitation efforts in coronavirus disease 2019 patients. CONCLUSIONS: Most U.S. pediatric institutions rapidly adapted their resuscitation systems and practices in response to the coronavirus disease 2019 pandemic. Changes were commonly related to team members and roles, personal protective equipment, and airway and breathing management, reflecting attempts to balance quality resuscitation with healthcare provider safety.

Diaphragm Atrophy During Pediatric Acute Respiratory Failure Is Associated With Prolonged Noninvasive Ventilation Requirement Following Extubation.

OBJECTIVES: Diaphragm atrophy is evident during invasive ventilation for pediatric acute respiratory failure, but with unknown significance. We hypothesized that diaphragm atrophy in pediatric acute respiratory failure is associated with prolonged noninvasive positive pressure ventilation following extubation. DESIGN: Prospective observational study. SETTING: Single-center academic PICU. PATIENTS: Invasively ventilated children with acute respiratory failure. INTERVENTIONS: Diaphragm ultrasound was performed within 36 hours after intubation and repeated within 48 hours preceding extubation. Rapid shallow breathing index at 15 and 30 minutes of a spontaneous breathing trial and negative inspiratory force were collected in a subset of patients concurrently with the ultrasound measurements. MEASUREMENTS AND MAIN RESULTS: Diaphragm thickness at end-expiration was measured to assess for diaphragm atrophy during mechanical ventilation. Percentage change in diaphragm thickness at end-expiration was defined as baseline diaphragm thickness at end-expiration minus final, preextubation diaphragm thickness at end-expiration divided by baseline diaphragm thickness at end-expiration. The primary outcome measure was duration of noninvasive positive pressure ventilation following extubation with prolonged use defined as noninvasive positive pressure ventilation use for greater than 24 hours postextubation. Among 56 children, 47 (median age, 15.5 mo; interquartile range, 6-53 mo) had diaphragm thickness at end-expiration measured within 48 hours prior to extubation. Fourteen (30%) had prolonged noninvasive positive pressure ventilation use with median duration 110 hours (interquartile range, 52-130 hr). The median percentage change of diaphragm thickness at end-expiration from baseline among those with and without prolonged noninvasive positive pressure ventilation use was -20% (interquartile range, -32% to -10%) versus -7% (interquartile range, -21% to 0%) (p = 0.04). CONCLUSIONS: Diaphragm atrophy is associated with prolonged postextubation noninvasive positive pressure ventilation in children with acute respiratory failure. Serial bedside diaphragm ultrasound may identify children at risk for prolonged noninvasive positive pressure ventilation use after extubation.

Circulating Neurofilament Light Chain Is Associated With Survival After Pediatric Cardiac Arrest.

OBJECTIVES: To characterize neurofilament light levels in children who achieved return of spontaneous circulation following cardiac arrest compared with healthy controls and determine an association between neurofilament light levels and clinical outcomes. DESIGN: Retrospective cohort study. SETTING: Academic quaternary PICU. PATIENTS: Children with banked plasma samples from an acute respiratory distress syndrome biomarker study who achieved return of spontaneous circulation after a cardiac arrest and healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Neurofilament light levels were determined with a highly sensitive single molecule array digital immunoassay. Patients were categorized into survivors and nonsurvivors and into favorable (Pediatric Cerebral Performance Category score of 1-2 or unchanged from baseline) or unfavorable (Pediatric Cerebral Performance Category score of 3-6 or Pediatric Cerebral Performance Category score change ≥1 from baseline). Associations between neurofilament light level and outcomes were determined using Wilcoxon rank-sum test. We enrolled 32 patients with cardiac arrest and 18 healthy controls. Demographics, severity of illness, and baseline Pediatric Cerebral Performance Category scores were similar between survivors and nonsurvivors. Healthy controls had lower median neurofilament light levels than patients after cardiac arrest (5.5 [interquartile range 5.0-8.2] vs 31.0 [12.0-338.6]; p < 0.001). Neurofilament light levels were higher in nonsurvivors than survivors (78.5 [26.2-509.1] vs 12.4 [10.3-28.2]; p = 0.012) and higher in survivors than healthy controls (p = 0.009). The four patients who survived with a favorable outcome had neurofilament light levels that were not different from patients with unfavorable outcomes (21.9 [8.5--35.7] vs 37.2 [15.4-419.1]; p = 0.60) although two of the four patients who survived with favorable outcomes had progressive encephalopathies with both baseline and postcardiac arrest Pediatric Cerebral Performance Category scores of 4. CONCLUSIONS: Neurofilament light is a blood biomarker of hypoxic-ischemic brain injury and may help predict survival and neurologic outcome after pediatric cardiac arrest. Further study in a larger, dedicated cardiac arrest cohort with serial longitudinal measurements is warranted.

Survival and Hemodynamics During Pediatric Cardiopulmonary Resuscitation for Bradycardia and Poor Perfusion Versus Pulseless Cardiac Arrest.

OBJECTIVES: The objective of this study was to compare survival outcomes and intra-arrest arterial blood pressures between children receiving cardiopulmonary resuscitation for bradycardia and poor perfusion and those with pulseless cardiac arrests. DESIGN: Prospective, multicenter observational study. SETTING: PICUs and cardiac ICUs of the Collaborative Pediatric Critical Care Research Network. PATIENTS: Children (< 19 yr old) who received greater than or equal to 1 minute of cardiopulmonary resuscitation with invasive arterial blood pressure monitoring in place. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 164 patients, 96 (59%) had bradycardia and poor perfusion as the initial cardiopulmonary resuscitation rhythm. Compared to those with initial pulseless rhythms, these children were younger (0.4 vs 1.4 yr; p = 0.005) and more likely to have a respiratory etiology of arrest (p < 0.001). Children with bradycardia and poor perfusion were more likely to survive to hospital discharge (adjusted odds ratio, 2.31; 95% CI, 1.10-4.83; p = 0.025) and survive with favorable neurologic outcome (adjusted odds ratio, 2.21; 95% CI, 1.04-4.67; p = 0.036). There were no differences in diastolic or systolic blood pressures or event survival (return of spontaneous circulation or return of circulation via extracorporeal cardiopulmonary resuscitation). Among patients with bradycardia and poor perfusion, 49 of 96 (51%) had subsequent pulselessness during the cardiopulmonary resuscitation event. During cardiopulmonary resuscitation, these patients had lower diastolic blood pressure (point estimate, -6.68 mm Hg [-10.92 to -2.44 mm Hg]; p = 0.003) and systolic blood pressure (point estimate, -12.36 mm Hg [-23.52 to -1.21 mm Hg]; p = 0.032) and lower rates of return of spontaneous circulation (26/49 vs 42/47; p < 0.001) than those who were never pulseless. CONCLUSIONS: Most children receiving cardiopulmonary resuscitation in ICUs had an initial rhythm of bradycardia and poor perfusion. They were more likely to survive to hospital discharge and survive with favorable neurologic outcomes than patients with pulseless arrests, although there were no differences in immediate event outcomes or intra-arrest hemodynamics. Patients who progressed to pulselessness after cardiopulmonary resuscitation initiation had lower intra-arrest hemodynamics and worse event outcomes than those who were never pulseless.