Cost analysis of hospitals performing continuous albuterol in non-intensive care settings.

OBJECTIVE: To compare hospital costs and resource utilization for pediatric asthma admissions based on the hospitals' availability of continuous albuterol aerosolization administration (CAA) in non-intensive care unit (ICU) settings. METHODS: We conducted a retrospective cohort study of children ages 2-17 years admitted in 2019 with a principal diagnosis of asthma using the Pediatric Health Information System. Hospitals and hospitalizations were categorized based on location of CAA administration, ICU-only versus general inpatient floors. Hospitals preforming CAA in an intermediate care unit were excluded. We calculated total cost, standardized unit costs and rates of interventions. Groups were compared using Chi-Square, t-test and Wilcoxon rank-sum test as indicated. A log linear mixed model was created to evaluate potential confounders. RESULTS: Twenty-one hospitals (7084 hospitalizations) allowed CAA on the floor.Twenty-four hospitals (6100 hospitalizations) allowed CAA in the ICU-only. Median total cost was $4639 (Interquartile Range (IQR) $3060-$7512) for the floor group and $5478 (IQR $3444-$8539) for the ICU-only group (p < 0.001) (mean cost difference of $775 per patient). Hospitalization costs were $4,726,829 (95% CI $3,459,920-$5,993,860) greater for the children treated at hospitals restricting CAA to the ICU. We observed higher standardized laboratory, imaging, clinical and other unit costs, along with higher use of interventions in the ICU-only group. After adjustment, we found that ICU stay and hospital LOS were the main drivers of cost difference between the groups. CONCLUSIONS: There was cost savings and decreased resource utilization for hospitals that performed CAA on the floor. Further studies exploring variations in asthma management are warranted.

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.

Sugammadex to Reverse Neuromuscular Blockade Prior to Withdrawal of Life Support.

In certain end-of-life scenarios, pharmacologic reversal of neuromuscular blockade may be indicated. However, given the depth of blockade frequently necessitated in the ICU setting, rapid reversal of neuromuscular blockade is generally not feasible with conventional reversal agents such as neostigmine that inhibit acetylcholinesterase. Sugammadex is a novel pharmacologic agent for the reversal of neuromuscular blockade that acts by directly encapsulating steroidal neuromuscular blocking agents and providing effective 1:1 binding of rocuronium or vecuronium. This unique mechanism of action is rapid and allows for complete reversal and recovery of neuromuscular function. We report the use of sugammadex to reverse neuromuscular blockade prior to compassionate extubation in three pediatric patients. Its clinical use in children is reviewed, potential applications in the palliative care arena discussed, and dosing algorithms presented.

Elevated endotracheal tube cuff pressure in the pediatric emergency department.

OBJECTIVE: The objective of this study was to evaluate endotracheal tube cuff pressure after emergency intubation and identify variables associated with an elevated cuff pressure. METHODS: This was a prospective cohort study of intubated patients in the emergency department of Nationwide Children's Hospital. The primary study outcome, cuff pressure, was measured via manometer. Clinical details related to the intubation were collected and analyzed as secondary outcomes. RESULTS: Of the 104 patients enrolled, cuff pressure was 30 cmH2O in 59 (57%); exceeding the recommended safe upper limit. The average cuff pressure was 38 cmH2O for the entire cohort. Patients who had their endotracheal tube cuff inflated by a respiratory therapist tended to be exposed to a lower cuff pressure. CONCLUSIONS: More than half of patients in this study were exposed to a cuff pressure greater than the safe upper limit. Our analysis of secondary outcomes suggests that patient care could be improved by having certified respiratory therapists inflate the endotracheal tube cuffs of intubated children.

Safe Interfacility Transport of Pediatric Patients: Medical Control Training, an Interdisciplinary Approach.

INTRODUCTION: Critically ill children who require transfer to tertiary care centers often require transport by specialized transport teams (TT). These interfacility transports require a medical control physician (MCP). Traditionally this role is assigned to fellows who are taught "on-the-job", but achieving competency in communication for those trained this way may not be optimal. We sought to close this curriculum gap by developing a MCP training program immersing emergency medicine (EM) and critical care (CC) fellows together with TT members to manage a simulated patient. METHODS: Pilot curriculum from 2014-2016 involving 1st year fellows. A case is presented initially with a referral call. By phone the fellow is to communicate with and guide the TT, who is in a separate room managing the "sick" patient using high-fidelity simulation. Each MCP and TT communication is evaluated by faculty and peers. An immediate debriefing session provided formative feedback. RESULTS: 11 fellows participated and 10 completed a post-simulation survey (91%). The fellows and TT members rated the curriculum as "highly important" and positively viewed the interprofessional collaboration. Respondents were neutral when asked if communication skills improved. CONCLUSION: The MCP training curriculum was viewed favorably and participants reported that this formalized training is needed.

Dexmedetomidine as Single Continuous Sedative During Noninvasive Ventilation: Typical Usage, Hemodynamic Effects, and Withdrawal.

OBJECTIVES: Dexmedetomidine use in pediatric critical care is increasing. Its prolonged effects as a single continuous agent for sedation are not well described. The aim of the current study was to describe prolonged dexmedetomidine therapy without other continuous sedation, specifically the hemodynamic effects, discontinuation strategies, and risk factors for withdrawal. DESIGN: Retrospective chart review. SETTING: Large, single-center, quaternary care pediatric academic institution. PATIENTS: Data from 382 children, less than 18 years old admitted to the PICU who received dexmedetomidine for more than 24 hours without other infusions for sedation during noninvasive positive pressure ventilation. INTERVENTIONS: Usual care practices for dexmedetomidine use were described. Discontinuation strategies were categorized as abrupt discontinuation, wean from dexmedetomidine infusion, and transition to enteral clonidine. MEASUREMENTS AND MAIN RESULTS: Median peak and cumulative doses with interquartile range were 1 µg/kg/hr (0.6-1.2 µg/kg/hr) and 30 µg/kg (20-50 µg/kg), respectively, and median duration was 45 hours (34-66 hr). Four hours after reaching peak dose, we observed a decrease in heart rate (p < 0.01) with 28% prevalence of bradycardia and an increase in systolic blood pressure (p < 0.01) with 33% prevalence of hypertension and 2% hypotension. During the escalation phase, the prevalence of bradycardia and hypotension were 75% and a 30%, respectively. Three-hundred thirty-six patients (88%) had abrupt discontinuation, 37 (10%) were weaned, and nine (2%) were transitioned to clonidine. Nineteen patients (5%) experienced withdrawal. Univariate risk of withdrawal was most associated with duration: odds ratio equal to 1.5 (1.3-1.7) for each 12-hour period (p < 0.01). By multivariate analysis including age, discontinuation group, dexmedetomidine cumulative dose, and peak dose, only cumulative dose remained significant with an odds ratio equal to 1.3 (1.1-1.5) for each 10 µg/kg (p < 0.01). CONCLUSIONS: Dexmedetomidine use for noninvasive positive pressure ventilation sedation in pediatric critical care has predictable hemodynamic effects including bradycardia and hypertension. Although withdrawal was associated with higher cumulative dose, these symptoms were effectively managed with short-term enteral clonidine.

Development of a new interfacility extracorporeal membrane oxygenation transport program for pediatric lung transplantation evaluation.

Pediatric lung transplantation is a life-saving intervention for children with irreversible end-stage lung disease. Access to transplant can be limited by geographic isolation from a center or the presence of comorbidities affecting transplant eligibility. Extracorporeal membrane oxygenation (ECMO)-supported patients are an uncommon but historically high-risk cohort of patients considered for lung transplant. We report the development of a service at our center to provide transport services to our hospital for patients unable to wean from ECMO support at their local institution for the purpose of evaluation for lung transplantation by our program. We developed a process for pre-transport consultation by the lung transplant physician team, standardized hand-off tools and equipment lists, and procedures for transitioning patients to transport ECMO machinery. Four patients have been transported to date including fixed wing (FW) and helicopter transports. All patients were successfully transported with either none or minor complications. Transport of ECMO-supported patients is a feasible method to increase access of patients with irreversible lung injured patients to evaluation for lung transplant.

Pediatric Extracorporeal Membrane Oxygenation Transport by EC-145 With a Custom-Built Sled.

Indications for the use of extracorporeal membrane oxygenation (ECMO) in pediatrics has expanded beyond the initial historic treatment of neonates with respiratory failure. Patients with severe refractory cardiopulmonary failure may benefit from ECMO support until the primary insult has subsided or been treated. More recently, ECMO has been used by some centers as a bridge to transplant for irreversible organ failure. Nationwide Children's Hospital is a referral center that supports the use of ECMO as a bridge to transplant and is able to provide transport services for ECMO patients referred for transplant evaluation. In this report, we describe our design of a unique, custom-built sled designed specifically for the EC-145 helicopter to transport pediatric ECMO patients to our institution. This report is the first, to our knowledge, to describe the safe and successful transport of a pediatric ECMO patient in an EC-145 helicopter.

Baclofen Toxicity Responsive to Hemodialysis in a Pediatric Patient with Acute Kidney Injury.

Background Baclofen (para-chlorophenyl-gamma-aminobutyric acid) is widely used for its therapeutic effect of providing muscle relaxation from the persistent muscle spasms and posturing often related to spinal and central nervous system injuries. However, baclofen is also a potent neuronal depressant which is most evident in cases of toxicity. In severe toxicity, respiratory failure and obtundation may occur. Case-diagnosis/treatment We present the case of a neurologically devastated 16-year-old on chronic baclofen therapy for bilateral spastic cerebral palsy (Gross Motor Function Classification System level V) who presented with fever, leukocytosis, and hypotension. Initial management with fluid resuscitation and antimicrobials for presumed infection did initially improve the patient's mental status; however, he subsequently became comatose later during the same hospitalization. Comprehensive diagnostic studies and infectious work-up did not reveal an etiology. Upon further examination of history, acute kidney injury from chronic nonsteroidal use and complicated by vancomycin toxicity was suspected to cause acute baclofen toxicity. The patient underwent a single run of hemodialysis with resultant neurologic improvement and later laboratory-confirmed toxic baclofen levels. Conclusion Clinicians should consider possible acute baclofen toxicity in patients with impaired renal function who present with neurologic depression. Respiratory failure and mechanical ventilation, with its associated intensive care costs and complications, may be avoided with prompt treatment using hemodialysis.

Dexmedetomidine Infusion to Control Agitation due to Anticholinergic Toxidromes in Adolescents, a Case Series.

Dexmedetomidine is an α2-adrenergic agonist approved by the US Food and Drug Administration for the sedation of adults who are intubated on mechanical ventilation and in non-intubated adults who are undergoing surgical procedures. However, it has also recently become a commonly used sedative agent in varied clinical settings for the pediatric patient as well. We present the use of dexmedetomidine for sedation in a unique clinical scenario, the severely agitated and combative patient following the intentional misuse of anticholinergic drugs. Its applications in this situation are discussed, and previous reports in the literature are reviewed.

The lethargic diabetic: cerebral edema in pediatric patients in diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is the leading cause of hospitalizations for pediatric patients with diabetes mellitus. The most severe complication of DKA is cerebral edema that may lead to brain herniation. We present a case report that highlights the subclinical presentation of DKA-related cerebral edema in a pediatric patient and review the acute care management of suspected cerebral edema during transport.

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.

High-efficiency transduction of liver cancer cells by recombinant adeno-associated virus serotype 3 vectors.

Recombinant vectors based on a non-pathogenic human parvovirus, the adeno-associated virus 2 (AAV2) have been developed, and are currently in use in a number of gene therapy clinical trials. More recently, a number of additional AAV serotypes have also been isolated, which have been shown to exhibit selective tissue-tropism in various small and large animal models. Of the 10 most commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells and tissues in vitro as well as in vivo. However, in our recently published studies, we have documented that AAV3 vectors transduce human liver cancer - hepatoblastoma (HB) and hepatocellular carcinoma (HCC) - cell lines extremely efficiently because AAV3 utilizes human hepatocyte growth factor receptor as a cellular co-receptor for binding and entry in these cells. In this article, we describe the steps required to achieve high-efficiency transduction of human liver cancer cells by recombinant AAV3 vectors carrying a reporter gene. The use of recombinant AAV3 vectors carrying a therapeutic gene may eventually lead to the potential gene therapy of liver cancers in humans.

Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3.

Adeno-associated viruses (AAVs) use a variety of cellular receptors/coreceptors to gain entry into cells. A number of AAV serotypes are now available, and the cognate receptors/coreceptors for only a handful of those have been identified thus far. Of the 10 commonly used AAV serotypes, AAV3 is by far the least efficient in transducing cells in general. However, in our more recent studies, we observed that AAV3 vectors transduced human liver cancer cells remarkably well, which led to the hypothesis that AAV3 uses hepatocyte growth factor receptor (HGFR) as a cellular coreceptor for viral entry. AAV3 infection of human liver cancer cell lines was strongly inhibited by hepatocyte growth factor, HGFR-specific small interfering RNA, and anti-HGFR antibody, which corroborated this hypothesis. However, AAV3 vectors failed to transduce murine hepatocytes, both in vitro and in vivo, suggesting that AAV3 specifically uses human HGFR, but not murine HGFR, as a cellular coreceptor for transduction. AAV3 may prove to be a useful vector for targeting human liver cancers for the potential gene therapy.