Intrauterine exposure to SARS-CoV-2 infection and early newborn brain development.

Epidemiologic studies suggest that prenatal exposures to certain viruses may influence early neurodevelopment, predisposing offspring to neuropsychiatric conditions later in life. The long-term effects of maternal COVID-19 infection in pregnancy on early brain development, however, remain largely unknown. We prospectively enrolled infants in an observational cohort study for a single-site study in the Washington, DC Metropolitan Area from June 2020 to November 2021 and compared these infants to pre-pandemic controls (studied March 2014-February 2020). The primary outcomes are measures of cortical morphometry (tissue-specific volumes), along with global and regional measures of local gyrification index, and sulcal depth. We studied 210 infants (55 infants of COVID-19 unexposed mothers, 47 infants of COVID-19-positive mothers, and 108 pre-pandemic healthy controls). We found increased cortical gray matter volume (182.45 ± 4.81 vs. 167.29 ± 2.92) and accelerated sulcal depth of the frontal lobe (5.01 ± 0.19 vs. 4.40 ± 0.13) in infants of COVID-19-positive mothers compared to controls. We found additional differences in infants of COVID-19 unexposed mothers, suggesting both maternal viral exposures, as well as non-viral stressors associated with the pandemic, may influence early development and warrant ongoing follow-up.

Characterization of Inhaled Nitric Oxide Use for Cardiac Indications in Pediatric Patients.

OBJECTIVES: Characterize the use of inhaled nitric oxide (iNO) for pediatric cardiac patients and assess the relationship between patient characteristics before iNO initiation and outcomes following cardiac surgery. DESIGN: Observational cohort study. SETTING: PICU and cardiac ICUs in seven Collaborative Pediatric Critical Care Research Network hospitals. PATIENTS: Consecutive patients, less than 18 years old, mechanically ventilated before or within 24 hours of iNO initiation. iNO was started for a cardiac indication and excluded newborns with congenital diaphragmatic hernia, meconium aspiration syndrome, and persistent pulmonary hypertension, or when iNO started at an outside institution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred seven patients with iNO initiation based on cardiac dysfunction. Cardiac dysfunction patients were administered iNO for a median of 4 days (2-7 d). There was significant morbidity with 51 of 407 (13%) requiring extracorporeal membrane oxygenation and 27 of 407 (7%) requiring renal replacement therapy after iNO initiation, and a 28-day mortality of 46 of 407 (11%). Of the 366 (90%) survivors, 64 of 366 patients (17%) had new morbidity as assessed by Functional Status Scale. Among the postoperative cardiac surgical group (n = 301), 37 of 301 (12%) had a superior cavopulmonary connection and nine of 301 (3%) had a Fontan procedure. Based on echocardiographic variables prior to iNO (n = 160) in the postoperative surgical group, right ventricle dysfunction was associated with 28-day and hospital mortalities (both, p < 0.001) and ventilator-free days (p = 0.003); tricuspid valve regurgitation was only associated with ventilator-free days (p < 0.001), whereas pulmonary hypertension was not associated with mortality or ventilator-free days. CONCLUSIONS: Pediatric patients in whom iNO was initiated for a cardiac indication had a high mortality rate and significant morbidity. Right ventricular dysfunction, but not the presence of pulmonary hypertension on echocardiogram, was associated with ventilator-free days and mortality.

Inhaled Nitric Oxide Use in Pediatric Hypoxemic Respiratory Failure.

OBJECTIVES: To characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes. DESIGN: An observational cohort study. SETTING: Eight sites of the Collaborative Pediatric Critical Care Research Network. PATIENTS: One hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication. MEASUREMENTS AND MAIN RESULTS: Clinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity. CONCLUSIONS: Clinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.

Association Between Diastolic Blood Pressure During Pediatric In-Hospital Cardiopulmonary Resuscitation and Survival.

BACKGROUND: On the basis of laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data demonstrating that survival depends on attaining adequate arterial diastolic blood pressure (DBP) during CPR, the American Heart Association recommends using blood pressure to guide pediatric CPR. However, evidence-based blood pressure targets during pediatric CPR remain an important knowledge gap for CPR guidelines. METHODS: All children ≥37 weeks' gestation and <19 years old in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ≥1 minute and invasive arterial blood pressure monitoring before and during CPR between July 1, 2013, and June 31, 2016, were included. Mean DBP during CPR and Utstein-style standardized cardiac arrest data were collected. The hypothesis was that DBP ≥25 mm Hg during CPR in infants and ≥30 mm Hg in children ≥1 year old would be associated with survival. Primary outcome was survival to hospital discharge. Secondary outcome was survival to hospital discharge with favorable neurological outcome, defined as Pediatric Cerebral Performance Categories 1 to 3 or no worse than prearrest baseline. Multivariable Poisson regression models with robust error estimates were used to estimate the relative risk of outcomes. RESULTS: Blinded investigators analyzed blood pressure waveforms during CPR from 164 children, including 60% <1 year old, 60% with congenital heart disease, and 54% after cardiac surgery. The immediate cause of arrest was hypotension in 67%, respiratory decompensation in 44%, and arrhythmia in 19%. Median duration of CPR was 8 minutes (quartiles, 3 and 27 minutes). Ninety percent survived the event, 68% with return of spontaneous circulation and 22% by extracorporeal life support. Forty-seven percent survived to hospital discharge, and 43% survived to discharge with favorable neurological outcome. Maintaining mean DBP ≥25 mm Hg in infants and ≥30 mm Hg in children ≥1 year old occurred in 101 of 164 children (62%) and was associated with survival (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.6; P=0.007) and survival with favorable neurological outcome (adjusted relative risk, 1.6; 95% confidence interval, 1.1-2.5; P=0.02). CONCLUSIONS: These data demonstrate that mean DBP ≥25 mm Hg during CPR in infants and ≥30 mm Hg in children ≥1 year old was associated with greater likelihood of survival to hospital discharge and survival with favorable neurological outcome.

PICU Length of Stay: Factors Associated With Bed Utilization and Development of a Benchmarking Model.

OBJECTIVES: ICU length of stay is an important measure of resource use and economic performance. Our primary aims were to characterize the utilization of PICU beds and to develop a new model for PICU length of stay. DESIGN: Prospective cohort. The main outcomes were factors associated with PICU length of stay and the performance of a regression model for length of stay. SETTING: Eight PICUs. PATIENTS: Randomly selected patients (newborn to 18 yr) from eight PICUs were enrolled from December 4, 2011, to April 7, 2013. Data consisted of descriptive, diagnostic, physiologic, and therapeutic information. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean length of stay for was 5.0 days (SD, 11.1), with a median of 2.0 days. The 50.6% of patients with length of stay less than 2 days consumed only 11.1% of the days of care, whereas the 19.6% of patients with length of stay 4.9-19 days and the 4.6% with length of stay greater than or equal to 19 days consumed 35.7% and 37.6% of the days of care, respectively. Longer length of stay was observed in younger children, those with cardiorespiratory disease, postintervention cardiac patients, and those who were sicker assessed by Pediatric Risk of Mortality scores receiving more intensive therapies. Patients in the cardiac ICU stayed longer than those in the medical ICU. The length of stay model using descriptive, diagnostic, severity, and therapeutic factors performed well (patient-level R-squared of 0.42 and institution-level R-squared of 0.76). Standardized (observed divided by expected) length of stay ratios at the individual sites ranged from 0.87 to 1.09. CONCLUSIONS: PICU bed utilization was dominated by a minority of patients. The 5% of patients staying the longest used almost 40% of the bed days. The multivariate length of stay model used descriptive, diagnostic, therapeutic, and severity factors and has potential applicability for internal and external benchmarking.

Cognitive Development One Year After Infantile Critical Pertussis.

OBJECTIVES: Pertussis can cause life-threatening illness in infants. Data regarding neurodevelopment after pertussis remain scant. The aim of this study was to assess cognitive development of infants with critical pertussis 1 year after PICU discharge. DESIGN: Prospective cohort study. SETTING: Eight hospitals comprising the Eunice Kennedy Shriver National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network and 18 additional sites across the United States. PATIENTS: Eligible patients had laboratory confirmation of pertussis infection, were less than 1 year old, and were admitted to the PICU for at least 24 hours. INTERVENTIONS: The Mullen Scales of Early Learning was administered at a 1-year follow-up visit. Functional status was determined by examination and parental interview. MEASUREMENTS AND MAIN RESULTS: Of 196 eligible patients, 111 (57%) completed the Mullen Scales of Early Learning. The mean scores for visual reception, receptive language, and expressive language domains were significantly lower than the norms (p < 0.001), but not fine and gross motor domains. Forty-one patients (37%) had abnormal scores in at least one domain and 10 (9%) had an Early Learning Composite score 2 or more SDs below the population norms. Older age (p < 0.003) and Hispanic ethnicity (p < 0.008) were associated with lower mean Early Learning Composite score, but presenting symptoms and PICU course were not. CONCLUSIONS: Infants who survive critical pertussis often have neurodevelopmental deficits. These infants may benefit from routine neurodevelopmental screening.

Variability in Usual Care Mechanical Ventilation for Pediatric Acute Respiratory Distress Syndrome: Time for a Decision Support Protocol?

OBJECTIVES: Although pediatric intensivists philosophically embrace lung protective ventilation for acute lung injury and acute respiratory distress syndrome, we hypothesized that ventilator management varies. We assessed ventilator management by evaluating changes to ventilator settings in response to blood gases, pulse oximetry, or end-tidal CO2. We also assessed the potential impact that a pediatric mechanical ventilation protocol adapted from National Heart Lung and Blood Institute acute respiratory distress syndrome network protocols could have on reducing variability by comparing actual changes in ventilator settings to those recommended by the protocol. DESIGN: Prospective observational study. SETTING: Eight tertiary care U.S. PICUs, October 2011 to April 2012. PATIENTS: One hundred twenty patients (age range 17 d to 18 yr) with acute lung injury/acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Two thousand hundred arterial and capillary blood gases, 3,964 oxygen saturation by pulse oximetry, and 2,757 end-tidal CO2 values were associated with 3,983 ventilator settings. Ventilation mode at study onset was pressure control 60%, volume control 19%, pressure-regulated volume control 18%, and high-frequency oscillatory ventilation 3%. Clinicians changed FIO2 by ±5 or ±10% increments every 8 hours. Positive end-expiratory pressure was limited at ~10 cm H2O as oxygenation worsened, lower than would have been recommended by the protocol. In the first 72 hours of mechanical ventilation, maximum tidal volume/kg using predicted versus actual body weight was 10.3 (8.5-12.9) (median [interquartile range]) versus 9.2 mL/kg (7.6-12.0) (p < 0.001). Intensivists made changes similar to protocol recommendations 29% of the time, opposite to the protocol's recommendation 12% of the time and no changes 56% of the time. CONCLUSIONS: Ventilator management varies substantially in children with acute respiratory distress syndrome. Opportunities exist to minimize variability and potentially injurious ventilator settings by using a pediatric mechanical ventilation protocol offering adequately explicit instructions for given clinical situations. An accepted protocol could also reduce confounding by mechanical ventilation management in a clinical trial.

Potential Acceptability of a Pediatric Ventilator Management Computer Protocol.

OBJECTIVES: To examine issues regarding the granularity (size/scale) and potential acceptability of recommendations in a ventilator management protocol for children with pediatric acute respiratory distress syndrome. DESIGN: Survey/questionnaire. SETTING: The eight PICUs in the Collaborative Pediatric Critical Care Research Network. PARTICIPANTS: One hundred twenty-two physicians (attendings and fellows). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used an online questionnaire to examine attitudes and assessed recommendations with 50 clinical scenarios. Overall 80% of scenario recommendations were accepted. Acceptance did not vary by provider characteristics but did vary by ventilator mode (high-frequency oscillatory ventilation 83%, pressure-regulated volume control 82%, pressure control 75%; p = 0.002) and variable adjusted (ranging from 88% for peak inspiratory pressure and 86% for FIO2 changes to 69% for positive end-expiratory pressure changes). Acceptance did not vary based on child size/age. There was a preference for smaller positive end-expiratory pressure changes but no clear granularity preference for other variables. CONCLUSIONS: Although overall acceptance rate for scenarios was good, there was little consensus regarding the size/scale of ventilator setting changes for children with pediatric acute respiratory distress syndrome. An acceptable protocol could support robust evaluation of ventilator management strategies. Further studies are needed to determine if adherence to an explicit protocol leads to better outcomes.

Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society.

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Clopidogrel in infants with systemic-to-pulmonary-artery shunts.

BACKGROUND: Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. METHODS: In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pulmonary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. RESULTS: The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P=0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). CONCLUSIONS: Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.).

Incidence and Outcomes of Cardiopulmonary Resuscitation in PICUs.

OBJECTIVES: To determine the incidence of cardiopulmonary resuscitation in PICUs and subsequent outcomes. DESIGN, SETTING, AND PATIENTS: Multicenter prospective observational study of children younger than 18 years old randomly selected and intensively followed from PICU admission to hospital discharge in the Collaborative Pediatric Critical Care Research Network December 2011 to April 2013. RESULTS: Among 10,078 children enrolled, 139 (1.4%) received cardiopulmonary resuscitation for more than or equal to 1 minute and/or defibrillation. Of these children, 78% attained return of circulation, 45% survived to hospital discharge, and 89% of survivors had favorable neurologic outcomes. The relative incidence of cardiopulmonary resuscitation events was higher for cardiac patients compared with non-cardiac patients (3.4% vs 0.8%, p <0.001), but survival rate to hospital discharge with favorable neurologic outcome was not statistically different (41% vs 39%, respectively). Shorter duration of cardiopulmonary resuscitation was associated with higher survival rates: 66% (29/44) survived to hospital discharge after 1-3 minutes of cardiopulmonary resuscitation versus 28% (9/32) after more than 30 minutes (p < 0.001). Among survivors, 90% (26/29) had a favorable neurologic outcome after 1-3 minutes versus 89% (8/9) after more than 30 minutes of cardiopulmonary resuscitation. CONCLUSIONS: These data establish that contemporary PICU cardiopulmonary resuscitation, including long durations of cardiopulmonary resuscitation, results in high rates of survival-to-hospital discharge (45%) and favorable neurologic outcomes among survivors (89%). Rates of survival with favorable neurologic outcomes were similar among cardiac and noncardiac patients. The rigorous prospective, observational study design avoided the limitations of missing data and potential selection biases inherent in registry and administrative data.

The Pediatric Risk of Mortality Score: Update 2015.

OBJECTIVES: Severity of illness measures have long been used in pediatric critical care. The Pediatric Risk of Mortality is a physiologically based score used to quantify physiologic status, and when combined with other independent variables, it can compute expected mortality risk and expected morbidity risk. Although the physiologic ranges for the Pediatric Risk of Mortality variables have not changed, recent Pediatric Risk of Mortality data collection improvements have been made to adapt to new practice patterns, minimize bias, and reduce potential sources of error. These include changing the outcome to hospital survival/death for the first PICU admission only, shortening the data collection period and altering the Pediatric Risk of Mortality data collection period for patients admitted for "optimizing" care before cardiac surgery or interventional catheterization. This analysis incorporates those changes, assesses the potential for Pediatric Risk of Mortality physiologic variable subcategories to improve score performance, and recalibrates the Pediatric Risk of Mortality score, placing the algorithms (Pediatric Risk of Mortality IV) in the public domain. DESIGN: Prospective cohort study from December 4, 2011, to April 7, 2013. MEASUREMENTS AND MAIN RESULTS: Among 10,078 admissions, the unadjusted mortality rate was 2.7% (site range, 1.3-5.0%). Data were divided into derivation (75%) and validation (25%) sets. The new Pediatric Risk of Mortality prediction algorithm (Pediatric Risk of Mortality IV) includes the same Pediatric Risk of Mortality physiologic variable ranges with the subcategories of neurologic and nonneurologic Pediatric Risk of Mortality scores, age, admission source, cardiopulmonary arrest within 24 hours before admission, cancer, and low-risk systems of primary dysfunction. The area under the receiver operating characteristic curve for the development and validation sets was 0.88 ± 0.013 and 0.90 ± 0.018, respectively. The Hosmer-Lemeshow goodness of fit statistics indicated adequate model fit for both the development (p = 0.39) and validation (p = 0.50) sets. CONCLUSIONS: The new Pediatric Risk of Mortality data collection methods include significant improvements that minimize the potential for bias and errors, and the new Pediatric Risk of Mortality IV algorithm for survival and death has excellent prediction performance.

Limiting and Withdrawing Life Support in the PICU: For Whom Are These Options Discussed?

OBJECTIVES: Most deaths in U.S. PICUs occur after a decision has been made to limitation or withdrawal of life support. The objective of this study was to describe the clinical characteristics and outcomes of children whose families discussed limitation or withdrawal of life support with clinicians during their child's PICU stay and to determine the factors associated with limitation or withdrawal of life support discussions. DESIGN: Secondary analysis of data prospectively collected from a random sample of children admitted to PICUs affiliated with the Collaborative Pediatric Critical Care Research Network between December 4, 2011, and April 7, 2013. SETTING: Seven clinical sites affiliated with the Collaborative Pediatric Critical Care Research Network. PATIENTS: Ten thousand seventy-eight children less than 18 years old, admitted to a PICU, and not moribund at admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Families of 248 children (2.5%) discussed limitation or withdrawal of life support with clinicians. By using a multivariate logistic model, we found that PICU admission age less than 14 days, reduced functional status prior to hospital admission, primary diagnosis of cancer, recent catastrophic event, emergent PICU admission, greater physiologic instability, and government insurance were independently associated with higher likelihood of discussing limitation or withdrawal of life support. Black race, primary diagnosis of neurologic illness, and postoperative status were independently associated with lower likelihood of discussing limitation or withdrawal of life support. Clinical site was also independently associated with likelihood of limitation or withdrawal of life support discussions. One hundred seventy-three children (69.8%) whose families discussed limitation or withdrawal of life support died during their hospitalization; of these, 166 (96.0%) died in the PICU and 149 (86.1%) after limitation or withdrawal of life support was performed. Of those who survived, 40 children (53.4%) were discharged with severe or very severe functional abnormalities, and 15 (20%) with coma/vegetative state. CONCLUSIONS: Clinical factors reflecting type and severity of illness, sociodemographics, and institutional practices may influence whether limitation or withdrawal of life support is discussed with families of PICU patients. Most children whose families discuss limitation or withdrawal of life support die during their PICU stay; survivors often have substantial disabilities.

Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment.

OBJECTIVES: Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality. DESIGN: Prospective cohort study from December 4, 2011, to April 7, 2013. SETTING: General and cardiac/cardiovascular PICUs at seven sites. PATIENTS: Randomly selected PICU patients from their first PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p < 0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p > 0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. CONCLUSIONS: New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.

Cardiac resuscitation events: one eyewitness is not enough.

OBJECTIVE: To determine the accuracy of paper cardiopulmonary resuscitation records. DESIGN: Case series. SETTING: Twenty-six-bed video-monitored pediatric cardiac ICU. PATIENTS: All patients who had a resuscitation event with available video and electronically stored vital sign and waveform data from May 2012 to February 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 41 cardiopulmonary resuscitation events during the study period. Fifteen had complete and valid data from the paper cardiopulmonary resuscitation forms, the retrieved monitor data, and the continuous bedside video monitoring. These 15 events occurred in 12 individual patients, and there was 100% agreement of data in the documentation of interventions in place (ventilation, arterial catheter, pulse oximetry, and vascular access) and in the presence of a witness at the onset of the arrest. All events were witnessed. Of the 15 events, video and monitor review revealed that 14 used waveform and numeric capnometry to confirm endotracheal tube/tracheostomy placement, but this section was only completed on the paper cardiopulmonary resuscitation record in three of the 14 cases. All records showed no discrepancies in the time of return of spontaneous circulation. The video and monitor review revealed delay in initiating cardiopulmonary resuscitation (mode, 2 min; two cases ≥ 7 min) and shockable rhythms (ventricular arrhythmia) in two cases. A sign of pulseless state was discovered in seven cases classified on the paper record as "always with a pulse." Those include sudden loss of consciousness, flat arterial line tracing, and abrupt drop in the partial pressure of exhaled carbon dioxide tracing (< 10 mm Hg). CONCLUSIONS: Eyewitness accounts of cardiopulmonary resuscitation are often inaccurate and incomplete. Review of information from video and electronically stored vital sign and waveform data provides more accurate information than review of paper-based cardiopulmonary resuscitation records and may provide the insight necessary to improving cardiopulmonary resuscitation.

End-of-Life Practices Among Tertiary Care PICUs in the United States: A Multicenter Study.

OBJECTIVE: To describe variability in end-of-life practices among tertiary care PICUs in the United States. DESIGN: Secondary analysis of data prospectively collected from a random sample of patients (n = 10,078) admitted to PICUs affiliated with the Collaborative Pediatric Critical Care Research Network between December 4, 2011, and April 7, 2013. SETTING: Seven clinical centers affiliated with the Collaborative Pediatric Critical Care Research Network. PATIENTS: Patients included in the primary study were less than 18 years old, admitted to a PICU, and not moribund on PICU admission. Patients included in the secondary analysis were those who died during their hospital stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred and seventy-five (2.7%; range across sites, 1.3-5.0%) patients died during their hospital stay; of these, 252 (92%; 76-100%) died in a PICU. Discussions with families about limitation or withdrawal of support occurred during the initial PICU stay for 173 patients (63%; 47-76%; p = 0.27) who died. Of these, palliative care was consulted for 67 (39%; 12-46%); pain service for 11 (6%; 10 of which were at a single site); and ethics committee for six (3%, from three sites). Mode of death was withdrawal of support for 141 (51%; 42-59%), failed cardiopulmonary resuscitation for 53 (19%; 12-28%), limitation of support for 46 (17%; 7-24%), and brain death for 35 (13%; 8-20%); mode of death did not differ across sites (p = 0.58). Organ donation was requested from 101 families (37%; 17-88%; p < 0.001). Of these, 20 donated (20%; 0-64%). Sixty-two deaths (23%; 10-53%; p < 0.001) were medical examiner cases. Of nonmedical examiner cases (n = 213), autopsy was requested for 79 (37%; 17-75%; p < 0.001). Of autopsies requested, 53 (67%; 50-100%) were performed. CONCLUSIONS: Most deaths in Collaborative Pediatric Critical Care Research Network-affiliated PICUs occur after life support has been limited or withdrawn. Wide practice variation exists in requests for organ donation and autopsy.

Language Analysis as a Window to Bereaved Parents' Emotions During a Parent-Physician Bereavement Meeting.

Parent-physician bereavement meetings may benefit parents by facilitating sense making, which is associated with healthy adjustment after a traumatic event. Prior research suggests a reciprocal relationship between sense making and positive emotions. We analyzed parents' use of emotion words during bereavement meetings to better understand parents' emotional reactions during the meeting and how their emotional reactions related to their appraisals of the meeting. Parents' use of positive emotion words increased, suggesting the meetings help parents make sense of the death. Parents' use of positive emotion words was negatively related to their own and/or their spouse's appraisals of the meeting, suggesting that parents who have a positive emotional experience during the meeting may also have a short-term negative reaction. Language analysis can be an effective tool to understand individuals' ongoing emotions and meaning making processes during interventions to reduce adverse consequences of a traumatic event, such as a child's death.

Feasibility and perceived benefits of a framework for physician-parent follow-up meetings after a child's death in the PICU.

OBJECTIVE: To evaluate the feasibility and perceived benefits of conducting physician-parent follow-up meetings after a child's death in the PICU according to a framework developed by the Collaborative Pediatric Critical Care Research Network. DESIGN: Prospective observational study. SETTING: Seven Collaborative Pediatric Critical Care Research Network-affiliated children's hospitals. SUBJECTS: Critical care attending physicians, bereaved parents, and meeting guests (i.e., parent support persons, other health professionals). INTERVENTIONS: Physician-parent follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework. MEASUREMENTS AND MAIN RESULTS: Forty-six critical care physicians were trained to conduct follow-up meetings using the framework. All meetings were video recorded. Videos were evaluated for the presence or absence of physician behaviors consistent with the framework. Present behaviors were evaluated for performance quality using a 5-point scale (1 = low, 5 = high). Participants completed meeting evaluation surveys. Parents of 194 deceased children were mailed an invitation to a follow-up meeting. Of these, one or both parents from 39 families (20%) agreed to participate, 80 (41%) refused, and 75 (39%) could not be contacted. Of 39 who initially agreed, three meetings were canceled due to conflicting schedules. Thirty-six meetings were conducted including 54 bereaved parents, 17 parent support persons, 23 critical care physicians, and 47 other health professionals. Physician adherence to the framework was high; 79% of behaviors consistent with the framework were rated as present with a quality score of 4.3 ± 0.2. Of 50 evaluation surveys completed by parents, 46 (92%) agreed or strongly agreed the meeting was helpful to them and 40 (89%) to others they brought with them. Of 36 evaluation surveys completed by critical care physicians (i.e., one per meeting), 33 (92%) agreed or strongly agreed the meeting was beneficial to parents and 31 (89%) to them. CONCLUSIONS: Follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework are feasible and viewed as beneficial by meeting participants. Future research should evaluate the effects of follow-up meetings on bereaved parents' health outcomes.

Pediatric intensive care outcomes: development of new morbidities during pediatric critical care.

OBJECTIVE: To investigate significant new morbidities associated with pediatric critical care. DESIGN: Randomly selected, prospective cohort. SETTING: PICU patients from eight medical and cardiac PICUs. PATIENTS: This was a randomly selected, prospective cohort of PICU patients from eight medical and cardiac PICUs. MEASUREMENTS AND MAIN RESULTS: The main outcomes measures were hospital discharge functional status measured by Functional Status Scale scores and new morbidity defined as an increase in the Functional Status Scale of more than or equal to 3. Of the 5,017 patients, there were 242 new morbidities (4.8%), 99 PICU deaths (2.0%), and 120 hospital deaths (2.4%). Both morbidity and mortality rates differed (p < 0.001) among the sites. The worst functional status profile was on PICU discharge and improved on hospital discharge. On hospital discharge, the good category decreased from a baseline of 72% to 63%, mild abnormality increased from 10% to 15%, moderate abnormality status increased from 13% to 14%, severe status increased from 4% to 5%, and very severe was unchanged at 1%. The highest new morbidity rates were in the neurological diagnoses (7.3%), acquired cardiovascular disease (5.9%), cancer (5.3%), and congenital cardiovascular disease (4.9%). New morbidities occurred in all ages with more in those under 12 months. New morbidities involved all Functional Status Scale domains with the highest proportions involving respiratory, motor, and feeding dysfunction. CONCLUSIONS: The prevalence of new morbidity was 4.8%, twice the mortality rate, and occurred in essentially all types of patients, in relatively equal proportions, and involved all aspects of function. Compared with historical data, it is possible that pediatric critical care has exchanged improved mortality rates for increased morbidity rates.

Implications of the U.S. Food and Drug Administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension.

Pulmonary arterial hypertension (PAH) contributes to disability and death in children with diverse cardiac, pulmonary, or systemic diseases, and therapeutic options are currently limited. Data from adult studies provide the basis for most PAH-specific therapies; however, many of these medications are commonly used in children on an off-label basis due to the life-threatening nature of PAH. Although currently approved for use in adult PAH, sildenafil is used extensively off-label for the treatment of neonates, infants, and children with PAH. Past studies have generally suggested favorable effects and outcomes in infants and young children with PAH, but these reports are generally uncontrolled observations, except for one single-center trial for persistent pulmonary hypertension of the newborn. Despite extensive clinical experience with sildenafil therapy in children and approval by the European Medicines Agency for its pediatric use in Europe, the U.S. Food and Drug Administration recently issued a warning against the use of sildenafil for pediatric PAH between 1 and 17 years of age due to an apparent increase in mortality during long-term therapy. Although these data are extremely limited, this U.S. Food and Drug Administration review challenges the pediatric PAH community to further assess the efficacy and safety of sildenafil, especially with chronic treatment. Although low doses of sildenafil are likely safe in pediatric PAH, further studies should carefully examine its role in the long-term therapy of children, especially with diverse causes of PAH. Pediatric patients with PAH require close surveillance and frequent monitoring, and persistent sildenafil monotherapy is likely insufficient with disease progression.