Deep Sedation in Pediatric Patients With Single Ventricle Physiology Outside of the Operating Room.

Background: Advancements in palliative surgery of patients with single ventricle physiology have led to an increase in the need for deep sedation protocols for painful procedures. However, positive pressure ventilation during anesthesia can result in unfavorable cardiopulmonary interactions. This patient population may benefit from sedation from these painful procedures. Methods: This study aims to demonstrate the safety and efficacy of deep sedation by pediatric intensivists outside the operating room for children with single ventricle physiology. This is a single-center, retrospective chart review on consecutive pediatric patients with single ventricle physiology who received deep sedation performed by pediatric intensivists between 2013 and 2020. Results: Thirty-three sedations were performed on 27 unique patients. The median age was 3.7 years (25th%-75th%: 2.1-15.6). The majority of the sedations, 88% (29/33), were done on children with Fontan physiology and 12% (4/33) were status-post superior cavopulmonary anastomosis. The primary cardiac defect was hypoplastic left heart in 63% (17/27) of all sedation procedures. There were 24 chest tube placements and 9 cardioversions. Ketamine alone [median dose 1.5 mg/kg (range 0.8-3.7)], ketamine [median dose 1 mg/kg (range 0.1-2.1)] with propofol [median dose 2.3 mg/kg (range 0.7-3.8)], and ketamine [median dose 1.5 mg/kg (range 0.4-3.0)] with morphine [median dose 0.06 mg/kg (range 0.03-0.20)] were the most common sedation regimens used. Adverse events (AEs) occurred in 4 patients (15%), three of which were transient AEs. All sedation encounters were successfully completed. Conclusion: Procedural deep sedation can be safely and effectively administered to single ventricle patients by intensivist-led sedation teams in selective case.

Unplanned Extubation During Pediatric Cardiac Intensive Care: U.S. Multicenter Registry Study of Prevalence and Outcomes.

OBJECTIVES: The epidemiology of unplanned extubations (UEs) and associated adverse outcomes in pediatric cardiac ICUs (CICU). DESIGN: Registry data (August 2014 to October 2020). SETTING: Forty-five Pediatric Cardiac Critical Care Consortium hospitals. PATIENTS: Patients receiving mechanical ventilation (MV) via endotracheal tube (ETT). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-six thousand five hundred eight MV courses occurred in 36,696 patients, with a crude UE rate of 2.8%. In cardiac surgical patients, UE was associated with longer duration of MV, but we failed to find such association in medical patients. In both cohorts, UE was associated with younger age, being underweight, and airway anomaly. In multivariable logistic regression, airway anomaly was associated with UE in all patients. Younger age, higher Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery score category, longer duration of MV, and initial oral rather than nasal ETT are associated with UE in the surgical group, but we failed to find such associations in the medical group. UE was associated with a higher reintubation rate compared with elective extubation (26.8 vs 4.8%; odds ratio [OR], 7.35; 95% CI, 6.44-8.39; p < 0.0001) within 1 day of event. After excluding patients having redirection of care, UE was associated with at least three-fold greater odds for each of ventilator-associated pneumonia (VAP), cardiac arrest, and use of mechanical circulatory support (MCS). However, we failed to identify an association between UE and greater odds of mortality (1.2 vs 0.8%; OR, 1.48; 95% CI, 0.86-2.54; p = 0.15), but uncertainty remains. CONCLUSIONS: UE in CICU patients is associated with greater odds of cardiac arrest, VAP, and MCS. Cardiac medical and surgical patients in the CICU appear to have different explanatory factors associated with UE, and perhaps these may be modifiable and tested in future collaborative population research.

High variability in cardiac education and experiences during United States paediatric critical care fellowships.

BACKGROUND: Paediatric cardiac critical care continues to become more sub-specialised, and many institutions have transitioned to dedicated cardiac ICUs. Literature regarding the effects of these changes on paediatric critical care medicine fellowship training is limited. OBJECTIVE: To describe the current landscape of cardiac critical care education during paediatric critical care medicine fellowship in the United States and demonstrate its variability. METHODS: A review of publicly available information in 2021 was completed. A supplemental REDCap survey focusing on cardiac ICU experiences during paediatric critical care medicine fellowships was e-mailed to all United States Accreditation Council of Graduate Medical Education-accredited paediatric critical care medicine fellowship programme coordinators/directors. Results are reported using inferential statistics. RESULTS: Data from 71 paediatric critical care medicine fellowship programme websites and 41 leadership responses were included. Median fellow complement was 8 (interquartile range: 6, 12). The majority (76%, 31/41) of programmes had a designated cardiac ICU. Median percentage of paediatric critical care medicine attending physicians with cardiac training was 25% (interquartile range: 0%, 69%). Mandatory cardiac ICU time was 16 weeks (interquartile range: 13, 20) with variability in night coverage and number of other learners present. A minority of programmes (29%, 12/41) mandated other cardiac experiences. Median CHD surgical cases per year were 215 (interquartile range: 132, 338). When considering the number of annual cases per fellow, programmes with higher case volume were not always associated with the highest case number per fellow. CONCLUSIONS: There is a continued trend toward dedicated cardiac ICUs in the United States, with significant variability in cardiac training during paediatric critical care medicine fellowship. As the trend toward dedicated cardiac ICUs continues and practices become more standardised, so should the education.

Cardiac Arrest in Children Following Cardiac Surgery: A Scoping Review of Contributing Factors.

Nearly half of children experiencing cardiac arrest following cardiac surgery do not survive hospital discharge and patients who survive often experience significant neurological impairment. Additionally, increased resource utilization following cardiac arrest translates into adverse logistical and financial consequences. Although some studies have identified patient characteristics that increase the risk of cardiac arrest after pediatric cardiac surgery, modifiable risk factors, which could provide a foundation for effective prevention strategies, have been elusive. This scoping review explores the current knowledge surrounding risk factors associated with cardiac arrest in children following cardiac surgery and provides recommendations for future research.

Meningitis and high-grade, second-degree atrioventricular block in an adolescent: causal effect or coincidence?

We describe an adolescent with Streptococcus pneumoniae meningitis and symptomatic high-grade, second-degree atrioventricular block requiring permanent pacemaker placement. It is difficult to ascertain if these two diagnoses were independent or had a causal relationship though ongoing symptoms were not present prior to the infection. Because of this uncertainty, awareness that rhythm disturbances can be cardiac in origin but also secondary to other aetiologies, such as infection, is warranted.

Analysis of Patient Characteristics and Risk Factors for Thrombosis After Surgery for Congenital Heart Disease.

OBJECTIVES: Thrombosis is a cause of morbidity in 4-15% of children who undergo pediatric cardiac surgery. Data on how to prevent this complication are sorely needed. We aimed to identify risk factors for thrombosis following pediatric cardiac surgery and determine if use of low molecular weight heparin prophylaxis is associated with a reduction in thrombosis risk. DESIGN: Retrospective cohort study. SETTING: Tertiary pediatric cardiovascular ICU. PATIENTS: Patients who underwent cardiac surgery between June 2014 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from patients with venous or arterial thrombosis confirmed by radiologic studies were matched two-to-one to controls based on age, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category, and gender. Thrombosis was detected in 33 patients (6.2%): 25 patients (76%) had venous thromboses, five patients (15%) had arterial thromboses, and three patients (9%) had both. Median time to thrombosis detection was 13 days (25-75%; 7-31 d). On multivariate analysis, which included adjustment for postoperative disease severity, fresh frozen plasma exposure was independently associated with thrombosis (odds ratio, 3.7; 95% CI, 1.4-9.4). Twenty-eight patients (85%) had central venous catheter-related thromboses. Low molecular weight heparin prophylaxis use in this subset of patients was not statistically different from controls (50% vs 45%, respectively; p = 0.47). On multivariable analysis, fresh frozen plasma exposure was also independently associated with central venous catheter-related thrombosis (odds ratio, 3.6; 95% CI, 1.2-10.6). CONCLUSIONS: The occurrence of thrombosis after pediatric cardiac surgery at our institution was 6.2%, similar to what has been reported in other studies, despite frequent use of low molecular weight heparin. Further study is needed to determine the role of low molecular weight heparin for thromboprophylaxis and the relationship between fresh frozen plasma and thrombosis risk in children who undergo cardiac surgery.

Fat Embolism Syndrome in Duchenne Muscular Dystrophy Patients: Early Recognition and Aggressive Therapy.

We describe two pediatric patients with Duchenne muscular dystrophy that presented with acute neurologic deterioration and hypoxic respiratory failure requiring mechanical ventilation. These cases fulfill the clinical criteria for Fat Embolism Syndrome. Early recognition and aggressive supportive therapy with mechanical ventilation, right ventricular afterload reduction, and blood transfusion led to survival without any residual effects from the event. Fat Embolism Syndrome needs to be considered early in the course of patients with Duchenne muscular dystrophy who present with respiratory and neurological symptoms.

Disparities in Adherence to Pediatric Diabetic Ketoacidosis Management Guidelines Across a Spectrum of Emergency Departments in the State of Indiana: An Observational In Situ Simulation-Based Study.

BACKGROUND: Diabetic ketoacidosis (DKA) is a common presentation to an emergency department (ED), with the majority presenting to community EDs. Adherence to clinical guidelines in these EDs can reduce morbidity and mortality. Few methods to describe practice gaps for DKA management have been reported. OBJECTIVES: We hypothesized that high-fidelity in situ simulation can be used to measure and compare the quality of the care provided to pediatric patients with DKA presenting to community EDs in the state of Indiana. METHODS: This observational study examined multiprofessional teams caring for a simulated pediatric patient who presented with DKA to community EDs. The primary outcome was overall adherence to pediatric DKA guidelines as measured by a validated performance checklist. A composite adherence score (CAS) was calculated using the sum of 9 checklist performance parameters. Multivariable logistic regression was used to examine the impact of ED volume and characteristics on the scores. RESULTS: A 49 multiprofessional teams from 13 sites were enrolled. Of the 252 participants, 26 (10.3%) were physicians, 143 (56.7%) registered nurses, 25 (9.9%) respiratory therapists, and 58 (23.0%) were other. The overall CAS for all sites was 55.6% (25th, 75th interquartile range, 44.4%, 66.7%). Excessive intravenous fluid boluses were given by 53.1%, whereas 30.6% and 26.5% incorrectly administered insulin and sodium bicarbonate boluses, respectively. Only 10.2% used an appropriate intravenous fluid rate, and 57.1% performed an hourly glucose. No significant difference in the CAS was found due to pediatric ED volume or presence of an inpatient pediatric service. CONCLUSIONS: Using validated in situ simulation; we revealed high variability in adherence to the pediatric DKA management guidelines at a wide range of community EDs. A statewide education initiative focused on decreasing variation and improving adherence to pediatric DKA guidelines is necessary for patient safety.

Evidence for a dispersed Hox gene cluster in the platyhelminth parasite Schistosoma mansoni.

In most bilaterian organisms so far studied, Hox genes are organized in genomic clusters and determine development along the anteroposterior axis. It has been suggested that this clustering, together with spatial and temporal colinearity of gene expression, represents the ancestral condition. However, in organisms with derived modes of embryogenesis and lineage-dependent mechanisms for the determination of cell fate, temporal colinearity of expression can be lost and Hox cluster organization disrupted, as is the case for the ecdysozoans Drosophila melanogaster and Caenorhabditis elegans and the urochordates Ciona intestinalis and Oikopleura dioica. We sought to determine whether a lophotrochozoan, the platyhelminth parasite Schistosoma mansoni, possesses a conserved or disrupted Hox cluster. Using a polymerase chain reaction (PCR)-based strategy, we have cloned and characterized three novel S. mansoni genes encoding orthologues of Drosophila labial (SmHox1), deformed (SmHox4), and abdominal A (SmHox8), as well as the full-length coding sequence of the previously described Smox1, which we identify as an orthologue of fushi tarazu. Quantitative reverse transcriptase-PCR showed that the four genes were expressed at all life-cycle stages but that levels of expression were differentially regulated. Phylogenetic analysis and the conservation of "parapeptide" sequences C-terminal to the homeodomains of SmHox8 and Smox1 support the grouping of platyhelminths within the lophotrochozoan clade. However, Bacterial Artificial Chromosome (BAC) library screening followed by genome walking failed to reconstitute a cluster. The BAC clones containing Hox genes were sequenced, and in no case were other Hox genes found on the same clone. Moreover, the SmHox4 and SmHox8 genes contained single very large introns (>40 kbp) further indicating that the schistosome Hox cluster is highly extended. Localization of the Hox genes to chromosomes using fluorescence in situ hybridization showed that SmHox4 and SmHox8 are on the long arm of chromosome 4, whereas SmHox1 and Smox1 are on chromosome 3. In silico screening of the available genome sequences corroborated results of Southern blotting and BAC library screening that indicate that there are no paralogues of SmHox1, SmHox4, or SmHox8. The schistosome Hox cluster is therefore not duplicated, but is both dispersed and disintegrated in the genome.

Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica.

Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions.

Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei.

BACKGROUND: Whipple's disease is a rare multisystem chronic infection, involving the intestinal tract as well as various other organs. The causative agent, Tropheryma whipplei, is a Gram-positive bacterium about which little is known. Our aim was to investigate the biology of this organism by generating and analysing the complete DNA sequence of its genome. METHODS: We isolated and propagated T whipplei strain TW08/27 from the cerebrospinal fluid of a patient diagnosed with Whipple's disease. We generated the complete sequence of the genome by the whole genome shotgun method, and analysed it with a combination of automatic and manual bioinformatic techniques. FINDINGS: Sequencing revealed a condensed 925938 bp genome with a lack of key biosynthetic pathways and a reduced capacity for energy metabolism. A family of large surface proteins was identified, some associated with large amounts of non-coding repetitive DNA, and an unexpected degree of sequence variation. INTERPRETATION: The genome reduction and lack of metabolic capabilities point to a host-restricted lifestyle for the organism. The sequence variation indicates both known and novel mechanisms for the elaboration and variation of surface structures, and suggests that immune evasion and host interaction play an important part in the lifestyle of this persistent bacterial pathogen.