Christopher M. Horvat

Evaluation of Electronic Medical Record Vital Sign Data Versus a Commercially Available Acuity Score in Predicting Need for Critical Intervention at a Tertiary Children's Hospital.

Objectives: Evaluate the ability of vital sign data versus a commercially available acuity score adapted for children (pediatric Rothman Index) to predict need for critical intervention in hospitalized pediatric patients to form the foundation for an automated early warning system. Design: Retrospective review of electronic medical record data. Setting: Academic children’s hospital. Patients: A total of 220 hospitalized children 6.7 ± 6.7 years old experiencing a cardiopulmonary arrest (condition A) and/or requiring urgent intervention with transfer (condition C) to the ICU between January 2006 and July 2011. Interventions: None. Measurements and Main Results: Physiologic data 24 hours preceding the event were extracted from the electronic medical record. Vital sign predictors were constructed using combinations of age-adjusted abnormalities in heart rate, systolic and diastolic blood pressures, respiratory rate, and peripheral oxygen saturation to predict impending deterioration. Sensitivity and specificity were determined for vital sign–based predictors by using 1:1 age-matched and sex-matched non-ICU control patients. Sensitivity and specificity for a model consisting of any two vital sign measurements simultaneously outside of age-adjusted normal ranges for condition A, condition C, and condition A or C were 64% and 54%, 57% and 53%, and 59% and 54%, respectively. The pediatric Rothman Index (added to the electronic medical record in April 2009) was evaluated in a subset of these patients (n = 131) and 16,138 hospitalized unmatched non-ICU control patients for the ability to predict condition A or C, and receiver operating characteristic curves were generated. Sensitivity and specificity for a pediatric Rothman Index cutoff of 40 for condition A, condition C, and condition A or C were 56% and 99%, 13% and 99%, and 28% and 99%, respectively. Conclusions: A model consisting of simultaneous vital sign abnormalities and the pediatric Rothman Index predict condition A or C in the 24-hour period prior to the event. Vital sign only prediction models have higher sensitivity than the pediatric Rothman Index but are associated with a high false-positive rate. The high specificity of the pediatric Rothman Index merits prospective evaluation as an electronic adjunct to human-triggered early warning systems.

ABCB1 genotype is associated with fentanyl requirements in critically Ill children

BackgroundThe gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has been previously associated with patient opioid requirements and may influence fentanyl dosing requirements in critically ill children.MethodsA diagnostically diverse cohort of 61 children who received a fentanyl infusion while admitted to the pediatric intensive care unit (PICU) were included in this study. We examined associations between fentanyl requirements, pain and sedation scores, serum fentanyl levels, and ABCB1 genotype.ResultsPatients with the AA allele at ABCB1 locus rs1045642 received less fentanyl compared with patients with the AG or GG allele. A multivariable model demonstrated that patients with the AA allele received 18.6 mcg/kg/day less fentanyl than patients with either the AG or GG allele (95% confidence interval −33.4 to −3.8 mcg/kg/day; P=0.014). Incorporating race in this model demonstrated a similar association, but did not reach the threshold for multiple testing.ConclusionABCB1 genotype rs1045642 AA is associated with fentanyl administration in this cohort of children admitted to the PICU, likely because of decreased expression and activity of p-glycoprotein. Prospective evaluation of the influence of ABCB1 in sedative–analgesia administration in critically ill children is warranted.

Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children

Background There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. Methods IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1–96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. Results There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. Conclusions Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. Trial registration ClinicalTrials.gov NCT01322009

Thiamin Deficiency as a Cause of Persistent Hyperlactatemia in a Parenteral Nutrition-Dependent Patient.

BACKGROUND Despite the demonstrated dangers of inadequate supplies of injectable multivitamins, periodic shortages of these crucial pharmaceuticals continue to occur in the developed world. This case report provides a recent example of the potential danger of rationing parenteral multivitamins in chronically parenteral nutrition (PN)-dependent patients in the setting of national supply shortages. METHOD AND RESULTS Case report describing a chronically PN-dependent 21-year-old man who presented with signs and symptoms of septic shock to a pediatric intensive care unit at a university hospital. The patient demonstrated hyperlactatemia that persisted following hemodynamic stabilization, and he was determined to be severely deficient in thiamin despite thrice-weekly home multivitamin infusions, instead of daily due to national supply shortages. The patients hyperlactatemia rapidly resolved following thiamine supplementation. CONCLUSION Physicians must be vigilant for potentially life-threatening nutrition deficiencies, as illustrated in this case of thiamine insufficiency, in PN-dependent children and adults in the setting of nationwide limitations in multivitamin supply.

Presenting predictors and temporal trends of treatment-related outcomes in diabetic ketoacidosis

This study examines temporal trends in treatment‐related outcomes surrounding a diabetic ketoacidosis (DKA) performance improvement intervention consisting of mandated intensive care unit admission and implementation of a standardized management pathway, and identifies physical and biochemical characteristics associated with outcomes in this population.

Contrast-Enhanced Ultrasonography During Extracorporeal Membrane Oxygenation: Clinical Letter

A 5-year-old male with pulmonary hypoplasia and stage IV chronic kidney disease secondary to reflux nephropathy was being supported for progressive severe acute respiratory distress syndrome secondary to human metapneumovirus infection with bacterial and fungal coinfection, with right internal jugular vein approach venovenous extracorporeal membrane oxygenation (ECMO) using a 19 French Maquet Avalon Elite Bi-Caval Dual Lumen Catheter (Gettinge Group, Rastatt, Germany). The clinical course was complicated by pulmonary hemorrhage and poor lung expansion, with areas of shifting atelectasis. On chest radiographs, there was a persistent round opacity in the inferolateral left lower lobe that appeared as a subpleural multiloculated complex mass or collection on gray scale ultrasound imaging (Figure 1A), and no flow could be seen within the collection on color or power Doppler imaging. The lung parenchyma surrounding this collection was not aerated but rather was heterogeneously echogenic. Before possible sampling or drainage to guide clinical management, the care team wished to evaluate the likelihood that fluid could be aspirated from the abnormal parenchymal focus, as the patient was anticoagulated for ECMO. The patient underwent computed tomography (CT) without intravenous (IV) contrast to further evaluate this round focus, with very poor detail of the masslike collection compared to adjacent consolidated lung (Figure 1B). Iodinated IV CT contrast was undesirable due to persistent renal failure. Major barriers existed to obtaining magnetic resonance imaging (MRI), including several components of the ECMO circuit being unsafe for use in the MRI suite, as well as the extended duration required to obtain adequate imaging. Additionally, use of gadolinium was undesirable in this patient with persistent renal failure. Therefore, contrast-enhanced ultrasonography (CEUS) was attempted, with attention to the left lower lobe lung parenchyma and collection, which is an off-label indication. One milliliter (0.03 mL/kg) of sulfur hexafluoride lipid-type A microspheres (Lumason, Bracco Diagnostics, Monroe Township, NJ) was administered via a right common femoral vein 5 French, 12-cm triple-lumen central venous catheter, which was already in place for care purposes. A LOGIQ E9 ultrasonography system (GE Healthcare, Milwaukee, WI) and 2–8-MHz linear transducer were utilized, with a low mechanical index of 0.13. There was enhancement of the abnormal heterogeneous, nonaerated lung surrounding the collection. No enhancement of the heterogeneous collection or internal septations occurred during the arterial or later phases of enhancement, confirming that this was a fluid collection amenable to possible sampling and drainage (Figure 1C). Additionally, numerous smaller areas of nonenhancing lung parenchyma elsewhere were much more apparent at CEUS than initial gray scale ultrasonography (Figure 1D, Video 1). There were no changes in patient vital signs during or 30 minutes after microbubble contrast administration, and no allergic reactions occurred. There was no further deterioration in the patient’s already marked respiratory failure over the next 24 hours. No adverse effects on the ECMO equipment were observed during or after microbubble contrast administration. Extracorporeal membrane oxygenation is a form of prolonged cardiopulmonary bypass used in patients with severe but potentially reversible or treatable cardiac or respiratory failure who are undergoing medical therapy and/or awaiting surgical treatment. For example, many pediatric patients with congenital heart disease or congenital diaphragmatic hernias are placed on ECMO until medical management is optimized and corrective surgery can be performed, whereas other patients are temporarily supported with ECMO while organ function is recovering or severe infection is clearing. Patients on ECMO cannot be transported easily to the imaging suite to undergo CT, and many components of the ECMO circuit are incompatible with MRI. Additionally, these critically ill patients frequently have multisystem organ failure, including renal failure, increasing the risks for adverse reactions to gadolinium-based agents used for MRI or iodinated agents used for CT. Microbubble ultrasonographic contrast, on the other hand, can be safely given to patients with renal insufficiency. Microbubble contrast is a wellestablished, safe, low-cost, and efficient imaging modality. These IV enhancing agents are exhaled via the lungs with no renal excretion, which eliminates the concern for possible contrast-induced renal injury or nephrogenic system fibrosis. In fact, no functioning

The STELAR ICU: Leveraging Electronic Health Record Data to Foster Research and Optimize Patient Care

Electronic health records (EHR) combined with robust data collection systems can be used to simultaneously drive research and performance improvement initiatives. Our Smart, Transformative, EHR-based Approaches to Revolutionizing the Intensive Care Unit (STELAR ICU) consists of a framework of five best practices that make optimal use of objective data to guide clinicians caring for the sickest patients in our quaternary center. Our strategy has relied on an accessible data infrastructure, standardizing without protocolizing care, using technology to increase patient contact and time spent at the bedside, continuously re-evaluating performance in real-time, and acknowledging uncertainty by using electronic data to provide probabilistic weight to clinical decision-making. These strategies blur the lines between research and quality improvement, with the aim of achieving truly stellar patient outcomes.

Bringing attention into higher focus within the traumatic brain injury research agenda

Traumatic brain injury (TBI) holds a unique position within children’s health. It has been clear for decades that TBI is the leading cause of death and disability of children (1,2). However, only recently has the impact of TBI on developing brain gained the attention of the public and lay press due to the attention paid toward injuries in sports such as football, boxing and others. Guidelines for caring for children with mild (3-5) and severe (6) injuries have been assiduously developed from the available literature, yet the proven therapies have remained elusive. Recently, the National Institute of Neurological Disorders and Stroke (NINDS), the European Commission and the Canadian Institutes of Health Research have led (and funded) efforts to address the burden of TBI with the International Initiative for Traumatic Brain Injury Research (InTBIR) with the goal of “working together to improve outcomes and lessen the global burden of TBI by 2020” (7).

Liquid fluorocarbon lavage to clear thrombus from the distal airways after severe pulmonary hemorrhage requiring extracorporeal life support (ECLS)

Massive pulmonary hemorrhage can pose a significant therapeutic challenge. Traditional methods of airway clearance using saline lavage and direct thrombus removal via bronchoscopy have limited ability to retrieve thrombi from deep airways. We report a patient on extracorporeal life support with massive pulmonary hemorrhage resulting in extensive alveolar and airway thrombus extending well beyond the proximal airways and the novel use of perfluorodecalin lavage to facilitate airway clearance and lung recruitment. Clinical trial registration None.