Reducing Avoidable Transfer Delays in the Pediatric Intensive Care Unit for Status Asthmaticus Patients.

INTRODUCTION: Status asthmaticus (acute severe asthma) is one of the most common reasons for Pediatric Intensive Care Unit (PICU) admission. Accordingly, ensuring optimal throughput for patients admitted with status asthmaticus is essential for optimizing PICU capacity. Few studies specifically address effective methods to reduce delays related to PICU discharge. This project aimed to identify and reduce avoidable delays in PICU discharge for status asthmaticus patients. METHODS: This quality improvement project focused on reducing transfer delays for status asthmaticus patients admitted to the PICU at a freestanding academic children's hospital. We standardized the transfer criteria, identified barriers to an efficient transfer, and implemented multidisciplinary interventions. The primary aim was to decrease the average duration from fulfilling the transfer criteria to PICU discharge by 15% from the baseline within 8 months of implementation. The balancing measure was readmissions to the PICU for asthma exacerbations within 24 hours from PICU discharge. RESULTS: The analysis included 623 patients. Following interventions, the time from fulfilling transfer criteria to PICU discharge decreased from 9.8 hours to 6.8 hours, a 30.6% reduction from baseline. Improvements were sustained for 6 months. In the preintervention group, three patients were readmitted to the PICU within 24 hours of transferring out of the PICU, but no patient was readmitted during the postintervention period. CONCLUSIONS: Standardizing transfer criteria and implementing multidisciplinary strategies can reduce avoidable PICU discharge delays for patients with status asthmaticus. The application of a similar approach could potentially reduce avoidable delays for other conditions in the PICU.

Comparison of Interleukin-6 Plasma Concentration in Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 and Pediatric Sepsis.

Importance: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection is thought to be driven by a post-viral dysregulated immune response, where interleukin 6 (IL-6) might have a central role. In this setting, IL-6 inhibitors are prescribed as immunomodulation in cases refractory to standard therapy. Objective: To compare plasma IL-6 concentration between critically ill children with MIS-C and sepsis. Design: A retrospective cohort study from previously collected data. Setting: Individual patient data were gathered from three different international datasets. Participants: Critically ill children between 1 month-old and 18 years old, with an IL-6 level measured within 48 h of admission to intensive care. Septic patients were diagnosed according to Surviving Sepsis Campaign definition and MIS-C cases by CDC criteria. We excluded children with immunodeficiency or immunosuppressive therapy. Exposure: None. Main Outcome(s) and Measure(s): The primary outcome was IL-6 plasma concentration in MIS-C and sepsis group at admission to the intensive care unit. We described demographics, inflammatory biomarkers, and clinical outcomes for both groups. A subgroup analysis for shock in each group was done. Results: We analyzed 66 patients with MIS-C and 44 patients with sepsis. MIS-C cases were older [96 (48, 144) vs. 20 (5, 132) months old, p < 0.01], but no differences in sex (41 vs. 43% female, p = 0.8) compared to septic group. Mechanical ventilation use was 48.5 vs. 93% (p < 0.001), vasoactive drug use 79 vs. 66% (p = 0.13), and mortality 4.6 vs. 34.1% (p < 0.01) in MIS-C group compared to sepsis. IL-6 was 156 (36, 579) ng/dl in MIS-C and 1,432 (122, 6,886) ng/dl in sepsis (p < 0.01), while no significant differences were observed in procalcitonin (PCT) and c-reactive protein (CRP). 52/66 (78.8%) patients had shock in MIS-C group, and 29/44 (65.9%) had septic shock in sepsis group. Septic shock had a significantly higher plasma IL-6 concentration than the three other sub-groups. Differences in IL-6, CRP, and PCT were not statistically different between MIS-C with and without shock. Conclusions and Relevance: IL-6 plasma concentration was elevated in critically ill MIS-C patients but at levels much lower than those of sepsis. Furthermore, IL-6 levels don't discriminate between MIS-C cases with and without shock. These results lead us to question the role of IL-6 in the pathobiology of MIS-C, its diagnosis, clinical outcomes, and, more importantly, the off-label use of IL-6 inhibitors for these cases.

Creation of a Combination Antibiogram for Pseudomonas aeruginosa in a Pediatric Intensive Care Unit.

OBJECTIVE: This study describes the creation of a combination antibiogram directed toward Pseudomonas aeruginosa to determine the most appropriate empiric antimicrobial regimen(s). METHODS: P aeruginosa isolates were collected from all sites between January 2013 and December 2017 for patients admitted to the PICU. Patients with cystic fibrosis and isolates from the same site and susceptibility pattern obtained within 30 days were excluded. ß-Lactam susceptibilities were determined and compared with the addition of an aminoglycoside or fluroquinolone and summarized in a combination antibiogram. RESULTS: One hundred ninety-nine P aeruginosa isolates were included for analysis. The addition of a second agent to piperacillin-tazobactam was shown to have the most significant improvement among the ß-lactams, with 70% susceptibility as monotherapy and increases to above 90% with the addition of an aminoglycoside or fluroquinolone. The addition of an aminoglycoside or fluroquinolone to cefepime and meropenem increased coverage to above 95%. The addition of a second agent was likely to increase susceptibility of a monotherapy backbone; however, as the susceptibility of the first-line agent decreased, the susceptibility of the second agent needed to be higher to achieve a 95% coverage threshold. CONCLUSIONS: Our results support use of a second agent to significantly improve the likelihood of appropriate empiric coverage of P aeruginosa. Use of a combination antibiogram may be more beneficial than a simple antibiogram for units with increasing resistance rates, or for coverage of specific resistant organisms.

Relationship of Viral Detection with Duration of Ventilation in Critically Ill Infants with Lower Respiratory Tract Infection.

Rationale: Although respiratory virus testing is frequently done for critically ill infants with bronchiolitis, the prognostic value of this testing is unknown for those requiring positive-pressure ventilation (PPV). Objectives: To determine the differences in PPV use according to viral detection and to explore the association between viral detection and duration of PPV in critically ill children with presumed respiratory infection. Methods: This is a retrospective cohort study in a quaternary pediatric intensive care unit from February 2014 until February 2017. We evaluated 984 children less than 1 year of age who received PPV for presumed respiratory infection without significant congenital heart disease, care limitations, baseline PPV usage, or tracheostomy. Respiratory viruses were identified using a PCR panel. Analyses of duration of PPV according to viral etiology were performed using univariate and multivariable logistic regression and truncated negative binomial regression with calculated mean marginal effects (MME). Results: Overall, 85 (9%) infants had no viruses identified, 629 (64%) had a single virus detected, most commonly respiratory syncytial virus (417, 42%) followed by rhinovirus/enterovirus (145, 15%), 230 (23%) had two viruses detected, and 40 (4%) had three viruses detected. Compared with those with one or no virus detected, infants with ⩾2 viruses received longer total PPV duration in adjusted analysis (relative risk [RR], 1.4; 95% confidence interval [CI], 1.2-1.6; P < 0.001; MME = 29 h). Detection of rhinovirus/enterovirus alone, compared with respiratory syncytial virus alone, was associated with significantly shorter duration of total PPV (RR, 0.7; 95% CI, 0.62-0.87; P = <0.001; MME = -23 h), noninvasive PPV (RR, 0.7; 95% CI, 0.60-0.85; P < 0.001; MME = -15 h), and invasive PPV (RR, 0.7; 95% CI, 0.54-0.83; P < 0.001; MME = -54 h) when adjusted for weight, prematurity, and administration of early antibiotic therapy. Conclusions: Identification of viral type and number in severe bronchiolitis is an important predictor of duration of PPV.

Comparison of two continuous nebulized albuterol doses in critically ill children with status asthmaticus.

Objectives: Continuous nebulized albuterol is frequently used to treat children with status asthmaticus in the pediatric intensive care unit (PICU) but can have cardiovascular side effects. Limited data exist comparing different dosages. The purpose of this study was to compare hemodynamic side effects of two continuous albuterol doses (10 vs. 25 mg/h). Our hypothesis was that lower dose albuterol would be associated with lower toxicity without increased need for adjunctive therapies.Methods: We conducted a retrospective cohort study of all children over 2 years old receiving continuous nebulized albuterol for status asthmaticus in our PICU from 2011 to 2013. Standard initial therapy was intravenous steroids and continuous nebulized albuterol. Patients receiving 10 mg/h albuterol were compared to those receiving 25 mg/h. Clinical outcomes, including the need for additional asthma therapies as well as hypotension requiring fluid resuscitation, were evaluated.Results: About 632 patients were studied (342 received 10 mg/h, 290 received 25 mg/h). Children in the lower-dose group received less fluid resuscitation without increased adjunctive therapies when adjusted for confounders. Those in the 25 mg/h group receiving 17% higher bolus volume. Those receiving lower-dose albuterol had shorter adjusted PICU and hospital lengths of stay.Conclusions: In our PICU cohort of children with status asthmaticus, use of 10 mg/h continuous albuterol was associated with lower fluid bolus resuscitation without more adjunctive therapies. These findings support the safety of lower doses in this population. Prospective studies evaluating the efficacy and toxicity of specific continuous albuterol dosages in critically ill children with status asthmaticus are warranted.

Validity and Reliability of a New Tool to Evaluate Impaired Airway Clearance in Hospitalized Pediatric Subjects With Respiratory Distress.

BACKGROUND: Chest physiotherapy has been reported to be beneficial in specific clinical contexts, yet it carries a risk of potential serious adverse events with little benefit in other patients. Therefore, identifying and limiting airway clearance therapies to patients with the greatest potential benefit and least risk is clinically relevant and important. This study aims to validate the Airway Clearance and Expansion Index (ACE-I) for the serial assessment of hospitalized pediatric patients with impaired airway clearance and to establish reliability in score acquisition across a range of pediatric respiratory disease states. METHODS: Content validity of the category importance and category choices was assessed via a survey of well-established pediatric pulmonary and critical care physicians, as well as respiratory therapists (RTs). Inter-rater reliability testing was performed on hospitalized children from October 2016 through April 2017 and analyzed using a one-way random effects intraclass correlation. RESULTS: 51 providers (24 of 37 physicians and 27 of 92 RTs) responded to the survey. Agreement was defined as any score of 6 or greater out of 10 on a scale of 1-10. The total ACE-I scale content validity index (S-CVI) scores for category importance and category choices for physicians were 1 and 0.75, respectively, and for RTs the scores were 0.75 and 0.75, respectively. 172 subjects were scored by multiple raters, resulting in an excellent overall intraclass correlation coefficient of 0.77 (95% CI 0.71-0.83) and the following component scores: cough, 0.72 (95% CI 0.64-0.79); breath sounds, 0.54 (95% CI 0.43-0.64); chest radiograph findings, 0.84 (95% CI 0.79-0.88); and secretions 0.85, (95% CI 0.81-0.89). CONCLUSIONS: The ACE-I score addresses and quantifies 4 components of the respiratory assessment that RTs and pediatric physicians deem important in identifying patients who have impaired airway clearance and might benefit from airway clearance and expansion therapies. In addition, the ACE-I score had excellent inter-rater reliability and clinical feasibility within our single institution.

A Quality Improvement Initiative to Standardize Use of Inhaled Nitric Oxide in the PICU.

BACKGROUND: Inhaled nitric oxide (iNO) is a potent pulmonary vasodilator used off-label to treat refractory hypoxemia in the pediatric intensive care unit (PICU). However, clinical practice varies widely, and there is limited evidence to support this expensive therapy. Our objective was to test whether implementation of a clinical guideline for iNO therapy would decrease practice variability, reduce ineffective iNO utilization, and control iNO-related costs. METHODS: We used quality improvement (QI) methodology to standardize the use of iNO in a single quaternary care PICU (noncardiac). All PICU patients receiving iNO therapy between January 1, 2010, and December 31, 2013, were included. The QI intervention was the development and implementation of a clinical guideline for iNO initiation, continuation, and weaning. iNO use was monitored using statistical process control charts. RESULTS: We derived baseline data from 30 preguideline patients (35 separate iNO courses) compared with 33 postguideline patients (36 separate iNO courses). Despite similar baseline characteristics, disease severity, and degree of hypoxemia, postguideline patients had a shorter median [interquartile range (IQR)] duration of iNO therapy than preguideline patients [76 (48-124) hours versus 162 (87-290) hours; P < 0.0001]. We have sustained the reduced iNO usage throughout the postguideline period. Postguideline patients also had improved provider documentation and a median iNO cost savings of $4,600. CONCLUSIONS: Implementation of iNO usage guidelines was associated with decreased iNO usage and cost of iNO therapy in the PICU.

An 11-Year-Old Girl with Life-threatening Pneumonia. Independent Lung Ventilation as a Means to Facilitate Extracorporeal Membrane Oxygenation Decannulation.

Independent lung ventilation is an infrequently used ventilation strategy in the pediatric intensive care unit but can be beneficial in unique patient subsets, such as patients who have asymmetric pulmonary pathology. Independent lung ventilation allows for the independent delivery of the appropriate effective tidal volume to each lung on the basis of individual compliance and pathology. In theory, it may help avoid alveolar overdistension and ventilator-induced lung injury in the nondiseased lung. In addition, it allows for targeted interventions. Here, we describe a child with unilateral lung disease requiring veno-venous extracorporeal membrane oxygenation who rapidly improved, allowing decannulation within 24 hours, after the application of independent lung ventilation and unilateral surfactant administration.

Listeria meningitis-associated bradyarrhythmia treated with isoproterenol.

In the setting of increased intracranial pressure (ICP), various rhythm disturbances have been associated, ranging from tachyarrhythmias to bradyarrhythmias with atrioventricular dissociation. Although most of these observations have been in patients with traumatic brain injuries, it is known that children with acute bacterial meningitis may also have severe intracranial hypertension. We present the case of a previously healthy 2-year-old boy diagnosed with listeria meningitis. Along with clinical signs suggestive of increased ICP and brainstem involvement, our patient had persistent bradyarrhythmia with hemodynamic compromise that was refractory to epinephrine and successfully managed with isoproterenol.

An empiric antibiotic protocol using risk stratification improves antibiotic selection and timing in critically ill children.

RATIONALE: Timely and appropriate empiric antibiotics can improve outcomes in critically ill patients with infection. Evidence and guidelines to guide empiric antibiotic decisions are lacking for critically ill children. OBJECTIVES: To evaluate the impact of an empiric antibiotic protocol on appropriateness of initial antibiotics and time to appropriate antibiotics in critically ill children with suspected infection. METHODS: A computer order entry-based, pediatric intensive care unit-specific, empiric antibiotic protocol including risk stratification for healthcare-associated infections was implemented in a tertiary pediatric intensive care unit. Antibiotic and culture data were evaluated for a total of 556 infectious episodes in 491 patients from 2004 (preprotocol, n = 252) and 2007 (protocol, n = 304) with suspected infection. Antibiotics appropriateness based on risk factors and culture results was assessed, as was time from initial culture to appropriate antibiotics. MEASUREMENTS AND MAIN RESULTS: Patients treated using the protocols were more likely to receive appropriate empiric antibiotics based on risk factors (76 vs. 15%; P < 0.0001) and culture results (89 vs. 64%; P < 0.0001). Patients treated after protocol implementation had a shorter time to appropriate antibiotics (median, 5.9 vs. 9.6 h; P < 0.0001), particularly in those who grew healthcare-associated pathogens (5.8 vs. 24 h; P = 0.0001). No significant baseline characteristic differences were seen. CONCLUSIONS: An empiric antibiotic protocol in the pediatric intensive care unit incorporating risk stratification for healthcare-associated infections resulted in increased appropriateness of empiric antibiotics and in decreased time to appropriate antibiotics in critically ill children with infection.

Purulent pericarditis secondary to community-acquired, methicillin-resistant Staphylococcus aureus in previously healthy children. A sign of the times?

RATIONALE: Purulent pericarditis secondary to community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) is a potentially lethal infection that has yet to be described in the pediatric population. Only four cases of purulent pericarditis secondary to CA-MRSA have been described in the English literature, all of whom were adults. OBJECTIVES: We report on the first two pediatric cases of purulent pericarditis secondary to CA-MRSA to increase awareness of this potentially fatal condition. METHODS: Clinical data were obtained from an 8-year-old male patient and a 7-month-old female patient, both previously healthy, who presented to our hospital for treatment of severe shock and multiorgan failure. Literature review was performed using MEDLINE and Cochrane databases. Pulsed-field gel electrophoresis was performed to confirm the organism type. MEASUREMENTS AND MAIN RESULTS: Our previously healthy patients presented with refractory shock and were found to have purulent pericarditis with tamponade secondary to CA-MRSA. Both patients required emergent pericardiocentesis and surgical pericardial debridement. Isolates from both patients were found to be MRSA USA type 300, a common type of CA-MRSA that has become the most frequent cause of skin and soft tissue infections in the United States. CONCLUSIONS: Purulent pericarditis survival hinges upon early empiric antibiotic therapy targeting resistant Staphylococcus, rapid diagnostic efforts, and expeditious pericardial drainage when diagnosed. An aggressive multidisciplinary approach provided for complete recovery in both cases, and both children were discharged with normal cardiac function. These two cases emphasize the need for consideration of CA-MRSA presenting with purulent pericarditis as an etiology for refractory shock.

Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor.

Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m(3), for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the alpha-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500-1000 mg/m(3)) than at low vapor phase exposure (250 mg/m(3)) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

Thrombotic risk of recombinant factor seven in pediatric cardiac surgery: a single institution experience.

BACKGROUND: Recombinant activated factor seven (rFVIIa) is increasingly being used as a hemostatic adjunct in pediatric cardiac surgery. We evaluated the thrombotic safety profile of rFVIIa in pediatric congenital heart disease (CHD) surgery. METHODS: This was a retrospective matched case-control study over six years at a single institution. Patients who received rFVIIa after CHD surgery were matched to controls based on age, diagnosis, and procedure. We compared thrombosis, hemorrhage, transfusions, length of stay, and repeat procedures between groups. RESULTS: Twenty-five patients received rFVIIa (mean dose: 70 mcg/kg); 50 controls were matched. There was no significant difference in the rate of thrombosis between patients who received rFVIIa and controls (8% vs 4%). After rFVIIa, there was a significant reduction in transfusion volume (median 77.1 mL/kg vs 14.6 mL/kg; p < 0.001) as well as a significant decrease in hemorrhagic chest tube output (8.3 +/- 1.6 mL/kg/hour vs 1.4 +/- 0.3 mL/kg/hour; mean +/- standard error of the mean; p < 0.001). No difference was seen in intensive care unit or hospital length of stay or mortality between patients receiving rFVIIa and controls. CONCLUSIONS: The rFVIIa therapy did not increase thrombotic complications when used as rescue therapy after CHD surgery but did appear to decrease bleeding complications in this small cohort.