Prevalence of Bacterial Codetection and Outcomes for Infants Intubated for Respiratory Infections.

OBJECTIVES: To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration. DESIGN: Prospective observational study evaluating the prevalence of bacterial codetection (moderate/heavy growth of pathogenic bacterial plus moderate/many polymorphonuclear neutrophils) and the impact of codetection on invasive mechanical ventilation (IMV) duration. SETTING: PICUs in 12 high and low/middle-income countries. PATIENTS: Children younger than 2 years old requiring intubation and ICU admission for LRTI and who had a lower respiratory tract culture obtained at the time of intubation between December 1, 2019, and November 30, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% ( n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684-1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value. CONCLUSIONS: Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.

CALIPSO: A Randomized Controlled Trial of Calfactant for Acute Lung Injury in Pediatric Stem Cell and Oncology Patients.

To assess if calfactant reduces mortality among children with leukemia/lymphoma or after hematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS), we conducted a multicenter, randomized, placebo-controlled, double-blinded trial in 17 pediatric intensive care units (PICUs) of tertiary care children's hospitals. Patients ages 18 months to 25 years with leukemia/lymphoma or having undergone HCT who required invasive mechanical ventilation for bilateral lung disease with an oxygenation index (OI) > 10 and <37 were studied. Interventions used were intratracheal instillation of either calfactant or air placebo (1 or 2 doses). Forty-three subjects were enrolled between November 2010 and June 2015: 26 assigned to calfactant and 17 to placebo. There were no significant differences in the primary outcome, which was survival to PICU discharge (adjusted hazard ratio of mortality for calfactant versus placebo, 1.78; 95% confidence interval, .53 to 6.05; P = .35), OI, functional outcomes, or ventilator-free days, adjusting for risk strata and Pediatric Risk of Mortality (PRISM) score. Despite the risk-stratified randomization, more allogeneic HCT patients received calfactant (76% and 39%, respectively) due to low recruitment at various sites. This imbalance is important because independent of treatment arm and while adjusting for PRISM score, those with allogeneic HCT had a nonsignificant higher likelihood of death at PICU discharge (adjusted odds ratio, 3.02; 95% confidence interval, .76 to 12.06; P = .12). Overall, 86% of the patients who survived to PICU discharge also were successfully discharged from the hospital. These data do not support the use of calfactant among this high mortality group of pediatric leukemia/lymphoma and/or HCT patients with PARDS to increase survival. In spite of poor enrollment, allogeneic HCT patients with PARDS appeared to be characterized by higher mortality than even other high-risk immunosuppressed groups. Conducting research among these children is challenging but necessary, because survival to PICU discharge usually results in successful discharge to home.

The Diagnostic Accuracy of Serum Procalcitonin for Bacteremia in Critically Ill Children.

BACKGROUND: Bacterial sepsis is frequently encountered in children admitted to the Pediatric Intensive Care Unit (PICU) and requires early recognition and treatment. Procalcitonin (PCT) is a serum biomarker with a high sensitivity to predict bacteremia in critically-ill adults. This study sought to evaluate the diagnostic accuracy of PCT for bacteremia in febrile children in the PICU. METHODS: This retrospective observational study used data from children admitted to the PICU from October 2010 to October 2012. Patients up to 21 years of age were included if they had an abnormal temperature, serum PCT and blood culture assayed, and were not receiving empiric antibiotics at the time. RESULTS: There were 202 PCT values that met inclusion criteria. The prevalence of positive blood cultures was 13.2% (27 total positive blood cultures). The area under the curve (AUC) for PCT was 0.79 (95% CI, 0.70-0.89), the AUC for lactate was 0.76 (95% CI, 0.65-0.87), and the AUC for C-reactive protein was 0.68 (95% CI, 0.57-0.80). The optimal threshold of PCT for accuracy was determined to be 2 ng/mL (sensitivity = 69.2%, specificity = 74.4%, positive predictive value = 28.6%, negative predictive value = 94.2%). The combination of an abnormal lactate (> 2.0mmol/L) increased the specificity of PCT for diagnosing bacteremia. CONCLUSIONS: PCT has a good diagnostic accuracy to rule-out bacteremia in critically-ill, febrile children. The combination of PCT and an abnormal lactate value increases the specificity and may improve the ability to diagnose bacteremia.

Intensivists' Reported Management of Critical Bronchiolitis: More Data and New Guidelines Needed.

OBJECTIVES: Existing bronchiolitis guidelines do not reflect the needs of infants admitted to the PICU. This study aimed to identify PICU providers' reported practice variations and explore the need for critical bronchiolitis clinical guidelines. METHODS: Cross-sectional electronic survey available in English, Spanish, and Portuguese between November 2020 and March 2021, distributed via research networks from North and Latin America, Asia, and Australia/New Zealand. RESULTS: A total of 657 PICU providers responded, including 344 English, 204 Spanish, and 109 Portuguese. PICU providers indicated frequently using (≥25% of time) diagnostic modalities for nonintubated and intubated patients on PICU admission (complete blood count [75%-97%], basic metabolic panel [64%-92%], respiratory viral panel [90%-95%], chest x-ray [83%-98%]). Respondents also reported regularly (≥25% of time) prescribing ß-2 agonists (43%-50%), systemic corticosteroids (23%-33%), antibiotics (24%-41%), and diuretics (13%-41%). Although work of breathing was the most common variable affecting providers' decision to initiate enteral feeds for nonintubated infants, hemodynamic status was the most common variable for intubated infants (82% of providers). Most respondents agreed it would be beneficial to have specific guidelines for infants with critical bronchiolitis who are requiring both noninvasive (91% agreement) and invasive (89% agreement) respiratory support. CONCLUSIONS: PICU providers report performing diagnostic and therapeutic interventions for infants with bronchiolitis more frequently than recommended by current clinical guidelines, with interventions occurring more frequently for infants requiring invasive support. More clinical research is needed to inform the creation of evidence-based guidelines specifically for infants with critical bronchiolitis.

Outcomes following thoracoabdominal resection of neuroblastoma.

OBJECTIVE: To evaluate the intraoperative and postoperative care of children following thoracoabdominal resection of neuroblastoma. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit (PICU) of major pediatric cancer center. PATIENTS: Eighty-eight patients undergoing thoracoabdominal resection of neuroblastoma over a 6-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected, including: length of PICU stay (LOS-P), duration of mechanical ventilation (MVD), mean arterial blood pressure, central venous pressure (CVP), fluid management, pressor use, and mortality. Twenty-one patients required inotropic/vasopressors support pressors following surgery. Patients who received pressors had longer operative times (p < .05) and received less intraoperative fluid (p < .05), but had the same estimated blood loss and urine output as nonpressor (NP) patients. Among the patients who received pressors, the MVD was 57 hrs, compared with 24 hrs in the NP group (p < .01). The LOS-P was 118 hours in the pressors group, vs. 69 hrs in the NP group (p < .01). The mean arterial blood pressure was lower and the CVP was higher in the pressors group compared with the NP group, and pressors patients received significantly more fluid postoperatively (p < .01). When pressors were initiated at a low CVP (<8), MVD was 39 hrs compared with 71 hrs when pressors were started at a higher CVP (p = .08). LOS-P was only slightly shorter in the low CVP group, 112 hrs vs. 123 hours (p = NS). The PICU mortality rate was 0%. CONCLUSIONS: Patients who received pressors had longer operative times and received less intraoperative fluid. Subsequently, they required more postoperative fluid, which is likely the result of hemodynamic instability leading to longer MVD and LOS-P. A prospective study evaluating operative fluid management and optimal time for initiation of pressors, in addition to the role of catecholamines and cytokines in this unique postoperative patient population is indicated.

Extended-release glipizide overdose presenting with delayed hypoglycemia and treated with subcutaneous octreotide.

The onset of symptomatic hypoglycemia in children with ingestions of second-generation sulfonylureas has never been documented to be later than 21 hours post-ingestion. We report a case with the longest known interval, 45 hours, between ingestion of a sulfonylurea and the onset of hypoglycemia requiring medical intervention. The hypoglycemia was severe and required multiple dextrose boluses in addition to continuous dextrose infusion for 36 hours. This patient was also treated with multiple doses of subcutaneous octreotide because of persistent hypoglycemia despite the above management. This case represents the first report of subcutaneous octreotide used as a treatment for pediatric hypoglycemia secondary to sulfonylurea exposure.

Post hoc analysis of calfactant use in immunocompromised children with acute lung injury: Impact and feasibility of further clinical trials.

OBJECTIVE: To assess the impact of calfactant (a modified natural bovine lung surfactant) in immunocompromised children with acute lung injury and to determine the number of patients required for a definitive clinical trial of calfactant in this population. DESIGN: Post hoc analysis of data from a previous randomized, control trial. SETTING: Tertiary care pediatric intensive care units. PATIENTS: All children, defined as immunocompromised, enrolled in a multicenter, masked, randomized, control trial of calfactant for acute lung injury conducted between July 2000 and July 2003. INTERVENTIONS: Patients received either an intratracheal instillation of calfactant or an equal volume of air placebo in a protocolized manner. MEASUREMENTS AND MAIN RESULTS: Eleven of 22 (50%) calfactant-treated patients died when compared with 18 of 30 (60%) placebo patients (absolute risk reduction 10.0%, 95% confidence interval [CI] -17.3, 37.3). Among the 23 patients with an initial oxygen index (OI) >/=13 and

Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols.

Guiding Principles for a Pediatric Neurology ICU (neuroPICU) Bedside Multimodal Monitor: Findings from an International Working Group.

BACKGROUND: Physicians caring for children with serious acute neurologic disease must process overwhelming amounts of physiological and medical information. Strategies to optimize real time display of this information are understudied. OBJECTIVES: Our goal was to engage clinical and engineering experts to develop guiding principles for creating a pediatric neurology intensive care unit (neuroPICU) monitor that integrates and displays data from multiple sources in an intuitive and informative manner. METHODS: To accomplish this goal, an international group of physicians and engineers communicated regularly for one year. We integrated findings from clinical observations, interviews, a survey, signal processing, and visualization exercises to develop a concept for a neuroPICU display. RESULTS: Key conclusions from our efforts include: (1) A neuroPICU display should support (a) rapid review of retrospective time series (i.e. cardiac, pulmonary, and neurologic physiology data), (b) rapidly modifiable formats for viewing that data according to the specialty of the reviewer, and (c) communication of the degree of risk of clinical decline. (2) Specialized visualizations of physiologic parameters can highlight abnormalities in multivariable temporal data. Examples include 3-D stacked spider plots and color coded time series plots. (3) Visual summaries of EEG with spectral tools (i.e. hemispheric asymmetry and median power) can highlight seizures via patient-specific "fingerprints." (4) Intuitive displays should emphasize subsets of physiology and processed EEG data to provide a rapid gestalt of the current status and medical stability of a patient. CONCLUSIONS: A well-designed neuroPICU display must present multiple datasets in dynamic, flexible, and informative views to accommodate clinicians from multiple disciplines in a variety of clinical scenarios.

Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial.

CONTEXT: Despite evidence that patients with acute lung injury (ALI) have pulmonary surfactant dysfunction, trials of several surfactant preparations to treat adults with ALI have not been successful. Preliminary studies in children with ALI have shown that instillation of a natural lung surfactant (calfactant) containing high levels of surfactant-specific protein B may be beneficial. OBJECTIVE: To determine if endotracheal instillation of calfactant in infants, children, and adolescents with ALI would shorten the course of respiratory failure. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, blinded trial of calfactant compared with placebo in 153 infants, children, and adolescents with respiratory failure from ALI conducted from July 2000 to July 2003. Twenty-one tertiary care pediatric intensive care units participated. Entry criteria included age 1 week to 21 years, enrollment within 48 hours of endotracheal intubation, radiological evidence of bilateral lung disease, and an oxygenation index higher than 7. Premature infants and children with preexisting lung, cardiac, or central nervous system disease were excluded. INTERVENTION: Treatment with intratracheal instillation of 2 doses of 80 mL/m2 calfactant or an equal volume of air placebo administered 12 hours apart. MAIN OUTCOME MEASURES: Ventilator-free days and mortality; secondary outcome measures were hospital course, adverse events, and failure of conventional mechanical ventilation. RESULTS: The calfactant group experienced an acute mean (SD) decrease in oxygenation index from 20 (12.9) to 13.9 (9.6) after 12 hours compared with the placebo group's decrease from 20.5 (14.7) to 15.1 (9.0) (P = .01). Mortality was significantly greater in the placebo group compared with the calfactant group (27/75 vs 15/77; odds ratio, 2.32; 95% confidence interval, 1.15-4.85), although ventilator-free days were not different. More patients in the placebo group did not respond to conventional mechanical ventilation. There were no differences in long-term complications. CONCLUSIONS: Calfactant acutely improved oxygenation and significantly decreased mortality in infants, children, and adolescents with ALI although no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was observed.

Mortality rates in pediatric septic shock with and without multiple organ system failure.

OBJECTIVES: To determine the current mortality rates for pediatric patients with septic shock and the frequency and outcome of associated multiple organ system failure. DESIGN: Retrospective chart review. SETTING: Multidisciplinary pediatric intensive care unit. PATIENTS: Children age 1 month to 21 yrs admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 1999, with a diagnosis of septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A database of all admissions to the pediatric intensive care unit was queried, and cases with diagnoses of sepsis and septic shock were reviewed. The final study cohort consisted of 96 episodes of septic shock in 80 patients. Septic shock was defined as a clinical suspicion of sepsis manifested by hyperthermia or hypothermia accompanied by hypotension and/or alteration in perfusion. Multiple organ system failure was defined by established criteria. Data were analyzed by using Fisher's exact test. The overall mortality rate for the study cohort was 13.5%. There were differences in case mortality rates between patients requiring one inotropic agent (0%) and patients requiring multiple inotropic agents (42.9%), between oncology patients who had undergone bone marrow transplantation (38.5%) and oncology patients without bone marrow transplantation (5.5%), and between patients with multiple organ system failure (18.6%) and those without multiple organ system failure (0%); p <.05. There did not appear to be differences in the case mortality rates between oncology and nononcology patients or among patients with varying degrees of neutropenia. CONCLUSIONS: The mortality rate in pediatric septic shock is lower than has been previously reported. Oncologic illness in the absence of bone marrow transplantation does not appear to be associated with an increased mortality rate in children with septic shock. Bone marrow transplantation patients have an increased mortality rate compared with other patients with septic shock. Mortality from septic shock occurs most frequently in the context of multiple organ system failure.

Multimodal monitoring in the pediatric intensive care unit: new modalities and informatics challenges.

We review several newer modalities to monitor the brain in children with acute neurologic disease in the pediatric intensive care unit, such as partial brain tissue oxygen tension (PbtO2), jugular venous oxygen saturation (SjvO2), near infrared spectroscopy (NIRS), thermal diffusion measurement of cerebral blood flow, cerebral microdialysis, and EEG. We then discuss the informatics challenges to acquire, consolidate, analyze, and display the data. Acquisition includes multiple data types: discrete, waveform, and continuous. Consolidation requires device interoperability and time synchronization. Analysis could include pressure reactivity index and quantitative EEG. Displays should communicate the patient's current status, longitudinal and trend information, and critical alarms.

Quality: performance improvement, teamwork, information technology and protocols.

Using the Institute of Medicine framework that outlines the domains of quality, this article considers four key aspects of health care delivery which have the potential to significantly affect the quality of health care within the pediatric intensive care unit. The discussion covers: performance improvement and how existing methods for reporting, review, and analysis of medical error relate to patient care; team composition and workflow; and the impact of information technologies on clinical practice. Also considered is how protocol-driven and standardized practice affects both patients and the fiscal interests of the health care system.

Alteplase in the treatment of complicated parapneumonic effusion: a case report.

The treatment of complex parapneumonic effusions in children remains controversial, with some advocating less invasive, strictly medical management and others supporting a more aggressive approach of thoracotomy with or without decortication. Recent advances, including video-assisted thoracoscopic surgery and intrapleural fibrinolytic therapy, offer new options for effective treatment. We report the first case of successful resolution of a complex parapneumonic effusion in a 16-month-old girl with the use of tissue plasminogen activator (alteplase), infused via a catheter in the pleural space.