Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units.

IMPORTANCE: The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs). OBJECTIVE: To provide an early description and characterization of COVID-19 infection in North American PICUs, focusing on mode of presentation, presence of comorbidities, severity of disease, therapeutic interventions, clinical trajectory, and early outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included children positive for COVID-19 admitted to 46 North American PICUs between March 14 and April 3, 2020. with follow-up to April 10, 2020. MAIN OUTCOMES AND MEASURES: Prehospital characteristics, clinical trajectory, and hospital outcomes of children admitted to PICUs with confirmed COVID-19 infection. RESULTS: Of the 48 children with COVID-19 admitted to participating PICUs, 25 (52%) were male, and the median (range) age was 13 (4.2-16.6) years. Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation. Eleven patients (23%) had failure of 2 or more organ systems. Extracorporeal membrane oxygenation was required for 1 patient (2%). Targeted therapies were used in 28 patients (61%), with hydroxychloroquine being the most commonly used agent either alone (11 patients) or in combination (10 patients). At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively. CONCLUSIONS AND RELEVANCE: This early report describes the burden of COVID-19 infection in North American PICUs and confirms that severe illness in children is significant but far less frequent than in adults. Prehospital comorbidities appear to be an important factor in children. These preliminary observations provide an important platform for larger and more extensive studies of children with COVID-19 infection.

Providing Early Attending Physician Expertise via Telemedicine to Improve Rapid Response Team Evaluations.

OBJECTIVES: To evaluate the effect of providing early attending physician involvement via telemedicine to improve the decision process of rapid response teams. DESIGN: Quasi-experimental; three pairs of control/intervention months: June/July; August/October; November/December. SETTING: Single-center, urban, quaternary academic children's hospital with three-member rapid response team: critical care fellow or nurse practitioner, nurse, respiratory therapist. Baseline practice: rapid response team leader reviewed each evaluation with an ICU attending physician within 2 hours after return to ICU. SUBJECTS: 1) Patients evaluated by rapid response team, 2) rapid response team members. INTERVENTIONS: Implementation of a smartphone-based telemedicine platform to facilitate early co-assessment and disposition planning between the rapid response team at the patient's bedside and the attending in the ICU. MEASUREMENTS AND MAIN RESULTS: As a marker of efficiency, the primary provider outcome was time the rapid response team spent per patient encounter outside the ICU prior to disposition determination. The primary patient outcome was percentage of patients requiring intubation or vasopressors within 60 minutes of ICU transfer. There were three pairs of intervention/removal months. In the first 2 pairs, the intervention was associated with the rapid response team spending less time on rapid response team calls (June/July: point estimate -5.24 min per call; p < 0.01; August/October: point estimate -3.34 min per call; p < 0.01). During the first of the three pairs, patients were significantly less likely to require intubation or vasopressors within 60 minutes of ICU transfer (adjusted odds ratio, 0.66; 95 CI, 0.51-0.84; p < 0.01). CONCLUSIONS: Early in the study, more rapid ICU attending involvement via telemedicine was associated with rapid response team providers spending less time outside the ICU, and among patients transferred to the ICU, a significant decrease in likelihood of patients requiring vasopressors or intubation within the first 60 minutes of transfer. These findings provide evidence that early ICU attending involvement via telemedicine can improve efficiency of rapid response team evaluations.

Preventing Catheter-Associated Urinary Tract Infections in the Pediatric Intensive Care Unit.

BACKGROUND: Catheter-associated urinary tract infections are common health care-associated infections and have been associated with increased mortality, morbidity, length of stay, and cost. Prevention strategies are grouped into bundles focused on reducing unnecessary catheter use and promptly removing urinary catheters. Before intervention in the study institution, no urinary catheters were unnecessarily used and compliance with the catheter-associated urinary tract infection bundle was 84%. OBJECTIVE: To increase bundle compliance by using targeted rounds specifically focused on eliminating dependent loops in drainage tubing and ensuring appropriate catheter use to reduce the incidence of catheter-associated urinary tract infections. METHODS: A multidisciplinary team was formed to identify misperceptions, highlight best practices, and eliminate barriers to success over 1 year in a single pediatric intensive care unit. The team completed a quality improvement project of daily targeted rounding for patients with an indwelling urinary catheter. The goals were to assess appropriateness of catheterization, increase bundle compliance, and decrease catheter-associated urinary tract infection risk. Targeted rounds were conducted in addition to the medical team rounds. RESULTS: Bundle compliance supported by targeted rounding increased from 84% to 93% and helped reduce the overall catheter-associated urinary tract infection rate from 2.7 infections per 1000 catheter-days at baseline to 0. This change was sustained for 1 year. CONCLUSION: Targeted rounding for pediatric patients with an indwelling urinary catheter is an effective and sustainable strategy to reduce catheter-associated urinary tract infections. The ease of implementation for this intervention lends itself to generalizability to other patient populations.

Structured Chart Review: Assessment of a Structured Chart Review Methodology.

BACKGROUND AND OBJECTIVES: Chart reviews are frequently used for research, care assessments, and quality improvement activities despite an absence of data on reliability and validity. We aim to describe a structured chart review methodology and to establish its validity and reliability. METHODS: A generalizable structured chart review methodology was designed to evaluate causes of morbidity or mortality and to identify potential therapeutic advances. The review process consisted of a 2-tiered approach with a primary review completed by a site physician and a short secondary review completed by a central physician. A total of 327 randomly selected cases of known mortality or new morbidities were reviewed. Validity was assessed by using postreview surveys with a Likert scale. Reliability was assessed by percent agreement and interrater reliability. RESULTS: The primary reviewers agreed or strongly agreed in 94.9% of reviews that the information to form a conclusion about pathophysiological processes and therapeutic advances could be adequately found. They agreed or strongly agreed in 93.2% of the reviews that conclusions were easy to make, and confidence in the process was 94.2%. Secondary reviewers made modifications to 36.6% of cases. Duplicate reviews (n = 41) revealed excellent percent agreement for the causes (80.5%-100%) and therapeutic advances (68.3%-100%). κ statistics were strong for the pathophysiological categories but weaker for the therapeutic categories. CONCLUSIONS: A structured chart review by knowledgeable primary reviewers, followed by a brief secondary review, can be valid and reliable.

Hyperglycemia at the Time of Acquiring Central Catheter-Associated Bloodstream Infections Is Associated With Mortality in Critically Ill Children.

OBJECTIVES: Hyperglycemia is common and may be a risk factor for nosocomial infections, including central catheter-associated bloodstream infections in critically ill children. It is unknown whether hyperglycemia at the time of acquiring central catheter-associated bloodstream infections in pediatric critical illness is associated with worse outcomes. We hypothesized that hyperglycemia (blood glucose concentration > 126 mg/dL [> 7 mmol/L]) at the time of acquiring central catheter-associated bloodstream infections (from 4 d prior to the day of first positive blood culture, i.e., central catheter-associated bloodstream infections) in critically ill children is common and associated with ICU mortality. DESIGN: Retrospective observational cohort study. SETTING: Fifty-five-bed PICU and 26-bed cardiac ICU at an academic freestanding children's hospital. PATIENTS: One hundred sixteen consecutively admitted critically ill children from January 1, 2008, to June 30, 2012, who were 0-21 years with central catheter-associated bloodstream infections were included. We excluded children with diabetes mellitus, metabolic disorders, and those with a "do not attempt resuscitation" order. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study cohort had an overall ICU mortality of 23%, with 48% of subjects developing hyperglycemia at the time of acquiring central catheter-associated bloodstream infections. Compared with survivors, nonsurvivors experienced more hyperglycemia both at the time of acquiring central catheter-associated bloodstream infections and subsequently. Median blood glucose at the time of acquiring central catheter-associated bloodstream infections was higher in nonsurvivors compared with survivors (139.5 mg/dL [7.7 mmol/L] vs 111 mg/dL [6.2 mmol/L]; p < 0.001) with 70% of nonsurvivors experiencing blood glucose greater than 126 mg/dL (> 7 mmol/L) during the 7 days following central catheter-associated bloodstream infections (in comparison to 45% of survivors; p = 0.03). After controlling for severity of illness and interventions, hyperglycemia at the time of acquiring central catheter-associated bloodstream infections was independently associated with ICU mortality (adjusted odds ratio, 1.9; 95% CI, 1.1-6.4; p = 0.03), in addition to other risk factors for ICU mortality (vasopressor use and severity of organ dysfunction). CONCLUSIONS: Hyperglycemia at the time of acquiring central catheter-associated bloodstream infections is common and associated with ICU mortality in critically ill children. Strategies to monitor and control blood glucose to avoid hyperglycemia may improve outcomes in critically ill children experiencing central catheter-associated bloodstream infections.

Development of a pragmatic measure for evaluating and optimizing rapid response systems.

OBJECTIVES: Standard metrics for evaluating rapid response systems (RRSs) include cardiac and respiratory arrest rates. These events are rare in children; therefore, years of data are needed to evaluate the impact of RRSs with sufficient statistical power. We aimed to develop a valid, pragmatic measure for evaluating and optimizing RRSs over shorter periods of time. METHODS: We reviewed 724 medical emergency team and 56 code-blue team activations in a children's hospital between February 2010 and February 2011. We defined events resulting in ICU transfer and noninvasive ventilation, intubation, or vasopressor infusion within 12 hours as "critical deterioration." By using in-hospital mortality as the gold standard, we evaluated the test characteristics and validity of this proximate outcome metric compared with a national benchmark for cardiac and respiratory arrest rates, the Child Health Corporation of America Codes Outside the ICU Whole System Measure. RESULTS: Critical deterioration (1.52 per 1000 non-ICU patient-days) was more than eightfold more common than the Child Health Corporation of America measure of cardiac and respiratory arrests (0.18 per 1000 non-ICU patient-days) and was associated with >13-fold increased risk of in-hospital death. The critical deterioration metric demonstrated both criterion and construct validity. CONCLUSIONS: The critical deterioration rate is a valid, pragmatic proximate outcome associated with in-hospital mortality. It has great potential for complementing existing patient safety measures for evaluating RRS performance.

Extracorporeal membrane oxygenation after stage I reconstruction for hypoplastic left heart syndrome.

OBJECTIVE: Although extracorporeal membrane oxygenation (ECMO) is an acceptable strategy for children with refractory cardiac dysfunction after cardiac surgery, its role after stage I reconstruction for hypoplastic left heart syndrome and its variants is controversial. Our objective is to describe the outcome of "nonelective" ECMO after stage I reconstruction. DESIGN: Retrospective case series. SETTING: Pediatric cardiac intensive care unit. PATIENTS: Infants placed on ECMO after stage I reconstruction from January 1998 to May 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 382 infants who underwent stage I reconstruction during the study period, 36 (9.4%) required ECMO in the postoperative period. There were 22 infants with hypoplastic left heart syndrome. Indications for ECMO included inability to separate from cardiopulmonary bypass in 14 and cardiac arrest in 22. Fourteen infants (38.8%) survived to hospital discharge. Nonsurvivors had longer cardiopulmonary bypass time (150.1 +/- 70.0 mins vs. 103.9 +/- 30.0 mins, p =. 01). 9/14 infants (64%) supported with ECMO> than 24 hrs after stage I reconstruction survived while only 5/22 infants (22%) requiring ECMO< 24 hrs of stage I reconstruction survived (p =. 02). Of note, all five infants diagnosed with an acute shunt thrombosis were early survivors. Mean duration of ECMO was 50.1 +/- 12.5 hrs for survivors and 125.2 +/- 25.0 for nonsurvivors (p =. 01). 7/14 early survivors are alive at a median follow-up of 20 months (2-78 months). CONCLUSIONS: In our experience, ECMO after stage I reconstruction can be life saving in about a third of infants with otherwise fatal conditions. It is particularly useful in potentially reversible conditions such as acute shunt thrombosis and transient depression of ventricular function.

The plasma pharmacokinetics and cerebral spinal fluid penetration of intravenous topiramate in newborn pigs.

INTRODUCTION: Pre-clinical studies suggest that the anticonvulsant topiramate confers neurologic protection against ischemia. An intravenous formulation of topiramate has been developed for administration during conditions such as hypoxia-ischemia when enteral absorption may be unpredictable. The plasma pharmacokinetics, cerebrospinal fluid (CSF) penetration and pharmacodynamics of intravenous topiramate were studied in an established piglet model of hypoxia-ischemia. METHODS: The plasma pharmacokinetics of topiramate were studied in a group of chronically instrumented conscious piglets (n = 8), and in a group of piglets following an episode of hypoxia-ischemia (n = 8). These groups were divided into equal dose cohorts in which two doses of intravenously administered topiramate, 5 and 40 mg/kg, were studied. The animals' heart rate, arterial pressure and EEG were monitored. Plasma for topiramate concentration was sampled for up to 26 h. A single CSF topiramate concentration was determined 1 h following drug administration. Topiramate was quantified using a specific LC/MS assay. RESULTS: The animals tolerated intravenous topiramate well, with no significant changes in physiologic and neurologic parameters. Plasma topiramate concentrations following an intravenous dose were best described by a bi-exponential equation, with a mean clearance of 39+/-18 ml/h/kg, and a terminal half-life of 14.3 (range 7.5-48.1) h. A dose of 5 mg/kg was sufficient to maintain plasma drug concentrations greater than 10 micro M for 24 h. CSF topiramate concentration at 1 h was 12+/-1 micro M and 109+/-26 micro M at the 5 and 40 mg/kg doses, respectively. CONCLUSION: Topiramate administered intravenously was well tolerated. Slow clearance of the drug allowed for maintenance of potential neuroprotective concentrations following a single dose of drug for 24 h. High drug penetration into the CSF is an ideal pharmacologic characteristic of any potential neuroprotective agent. The pharmacokinetic profile of intravenously administered topiramate, including its penetration into the CSF, appears to achieve this goal.

Approaches in the management of acute respiratory failure in children.

PURPOSE OF REVIEW: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are conditions that are associated with significant morbidity and mortality in children. There have been no advances in preventing ARDS, but this review highlights strategies directed at minimizing ventilator-induced lung injury and other new adjunctive therapies in the care of these patients. RECENT FINDINGS: High-frequency oscillatory ventilation, airway pressure release ventilation, and partial liquid ventilation are potential protective ventilatory modes for children with ALI or ARDS. Recruitment maneuvers, prone positioning, and kinetic therapy are all reported to improve oxygenation by opening the lung while positive end-expiratory pressure maintains functional residual capacity. Inhaled nitric oxide and surfactant are used to reduce inspired oxygen concentration and facilitate gas exchange, but their efficacy in ARDS continues to be investigated. Also, early investigations suggest that a specialized enteral formula can be a useful adjunctive therapy by reducing lung inflammation and improving oxygenation. When mechanical ventilation and adjunctive therapies fail, extracorporeal life support continues to be used as a rescue therapy. SUMMARY: It is likely that a combination of these therapies will maximize treatment and clinical outcomes in the future, but the only way that will be proven is through large controlled clinical trials in pediatric patients.

Apoptotic neuronal death following deep hypothermic circulatory arrest in piglets.

BACKGROUND: Deep hypothermic circulatory arrest (DHCA), as used in infant heart surgery, carries a risk of brain injury. In a piglet DHCA model, neocortical neurons appear to undergo apoptotic death. Caspases, cytochrome c, tumor necrosis factor (TNF), and Fas play a role in apoptosis in many ischemic models. This study examined the expression of these factors in a DHCA piglet model. METHODS: Thirty-nine anesthetized piglets were studied. After cardiopulmonary bypass (CPB) cooling of the brain temperature to 19 degrees C, DHCA was induced for 90 min, followed by CPB rewarming. After separation from CPB, piglets were killed at 1, 4, 8, 24, and 72 h and 1 week. Caspase-8 and -3 activity, and concentrations of TNF-alpha, Fas, Fas-ligand, cytochrome c, and adenosine triphosphate (ATP) were measured in the neocortex by enzymatic assay and Western blot analysis. Caspase-8 and -3 activity and cell death were examined histologically. Significance was set at P < 0.05. RESULTS: In neocortex, damaged neurons were not observed in control (no CPB), rarely observed in CPB (no DHCA), and rarely observed in the DHCA 1-h, 4-h, and 1-week reperfusion groups. However, they were seen frequently in the DHCA 8-, 24-, and 72-h reperfusion groups. Although neuronal death was widespread 8-72 h after DHCA, cortical ATP concentrations remained unchanged from control. Both caspase-3 and -8 activities were significantly increased at 8 h after DHCA, and caspase-3 concentration remained elevated for as long as 72 h. Caspase-3 and -8 activity was also observed in damaged neocortical neurons. Cytosolic cytochrome c and Fas were significantly expressed at 1 h and 4 h after DHCA, respectively. Fas-ligand and TNF-alpha were not observed in any group. CONCLUSION: After DHCA, induction of apoptosis in the neocortex occurs within a few hours of reperfusion and continues for several days. Increased Fas, cytochrome c, and caspase concentrations, coupled with normal brain ATP concentrations and apoptotic histologic appearance, are consistent with the occurrence of apoptotic cell death.

Desflurane improves neurologic outcome after low-flow cardiopulmonary bypass in newborn pigs.

BACKGROUND: Despite improvements in neonatal heart surgery, neurologic complications continue to occur from low-flow cardiopulmonary bypass (LF-CPB) and deep hypothermic circulatory arrest (DHCA). Desflurane confers neuroprotection against ischemia at normothermia and for DHCA. This study compared neurologic outcome of a desflurane-based with a fentanyl-based anesthetic for LF-CPB. METHODS: Thirty piglets aged 1 week received either fentanyl-droperidol (F/D), desflurane 4.5% (Des4.5), or desflurane 9% (Des9) during surgical preparation and CPB. Arterial blood gases, glucose, heart rate, arterial pressure, brain temperature, and cerebral blood flow (laser Doppler flowmetry) were recorded. After CPB cooling (22 degrees C brain) using pH-stat strategy, LF-CPB was performed for 150 min followed by CPB rewarming, separation from CPB, and extubation. On postoperative day 2, functional and histologic outcomes were assessed. RESULTS: Cardiovascular variables were physiologically similar between groups before, during, and after LF-CPB. Cerebral blood flow during LF-CPB (13% of pre-CPB value) did not differ significantly between the groups. Functional disability was worse in F/D than in Des9 (P = 0.04) but not Des4.5 (P = 0.1). In neocortex, histopathologic damage was greater in F/D than in Des4.5 (P = 0.03) and Des9 (P = 0.009). In hippocampus, damage was worse in F/D than in Des9 (P = 0.01) but not Des4.5 (P = 0.08). The incidences of ventricular fibrillation during LF-CPB were 90, 60, and 10% for F/D, Des4.5 (P = 0.06), and Des9 (P = 0.0002), respectively. CONCLUSIONS: Desflurane improved neurologic outcome following LF-CPB compared with F/D in piglets, indicated by less functional disability and less histologic damage, especially with Des9. Desflurane may have produced cardiac protection, suggested by a lower incidence of ventricular fibrillation.