The impact of estradiol on serotonin, glutamate, and dopamine systems.

Estradiol, the most potent and prevalent member of the estrogen class of steroid hormones and is expressed in both sexes. Functioning as a neuroactive steroid, it plays a crucial role in modulating neurotransmitter systems affecting neuronal circuits and brain functions including learning and memory, reward and sexual behaviors. These neurotransmitter systems encompass the serotonergic, dopaminergic, and glutamatergic signaling pathways. Consequently, this review examines the pivotal role of estradiol and its receptors in the regulation of these neurotransmitter systems in the brain. Through a comprehensive analysis of current literature, we investigate the multifaceted effects of estradiol on key neurotransmitter signaling systems, namely serotonin, dopamine, and glutamate. Findings from rodent models illuminate the impact of hormone manipulations, such as gonadectomy, on the regulation of neuronal brain circuits, providing valuable insights into the connection between hormonal fluctuations and neurotransmitter regulation. Estradiol exerts its effects by binding to three estrogen receptors: estrogen receptor alpha (ERα), estrogen receptor beta (ERß), and G protein-coupled receptor (GPER). Thus, this review explores the promising outcomes observed with estradiol and estrogen receptor agonists administration in both gonadectomized and/or genetically knockout rodents, suggesting potential therapeutic avenues. Despite limited human studies on this topic, the findings underscore the significance of translational research in bridging the gap between preclinical findings and clinical applications. This approach offers valuable insights into the complex relationship between estradiol and neurotransmitter systems. The integration of evidence from neurotransmitter systems and receptor-specific effects not only enhances our understanding of the neurobiological basis of physiological brain functioning but also provides a comprehensive framework for the understanding of possible pathophysiological mechanisms resulting to disease states. By unraveling the complexities of estradiol's impact on neurotransmitter regulation, this review contributes to advancing the field and lays the groundwork for future research aimed at refining understanding of the relationship between estradiol and neuronal circuits as well as their involvement in brain disorders.

Palliative Care Across the Life Span for Children With Heart Disease: A Scientific Statement From the American Heart Association.

AIM: This summary from the American Heart Association provides guidance for the provision of primary and subspecialty palliative care in pediatric congenital and acquired heart disease. METHODS: A comprehensive literature search was conducted from January 2010 to December 2021. Seminal articles published before January 2010 were also included in the review. Human subject studies and systematic reviews published in English in PubMed, ClinicalTrials.gov, and the Cochrane Collaboration were included. Structure: Although survival for pediatric congenital and acquired heart disease has tremendously improved in recent decades, morbidity and mortality risks remain for a subset of young people with heart disease, necessitating a role for palliative care. This scientific statement provides an evidence-based approach to the provision of primary and specialty palliative care for children with heart disease. Primary and specialty palliative care specific to pediatric heart disease is defined, and triggers for palliative care are outlined. Palliative care training in pediatric cardiology; diversity, equity, and inclusion considerations; and future research directions are discussed.

Comparison of electromagnetic guided imagery to standard confirmatory methods for ascertaining nasogastric tube placement in children.

PURPOSE: Evaluate the accuracy of an electromagnetic device (EMD) guided nasogastric tube (NGT) placement compared with standard confirmation methods. A secondary aim was to determine if EMD guided NGT placement would avert potential pulmonary misplacements of the tube. DESIGN AND METHODS: Pediatric Intensive Care Unit (PICU) patients were enrolled if they had an NGT order during the study period of April 2014 through December 2016. Patients were included if they were one through 18 years of age. An EMD trained nurse inserted the NGT using EMD guidance. An insertion questionnaire, confirming if the nurse determined the NGT to be gastric per EMD, was completed immediately after NGT placement and before confirmation via either pH testing or radiographic imaging. RESULTS: Forty-five patients were enrolled in the study. Nurses reported, based on EMD, that 86.7% (n = 39) of placements were gastric. Overall agreement between EMD guided tube placement and pH testing was 58% (n = 26). The marginal distribution was significantly different between the two methods (p = .0029). When compared to radiographic confirmation, sensitivity of the pH method was 32% (95% confidence interval [CI]: 17%-51%) compared with 85% (95% CI 69%-95%) for the EMD method. CONCLUSIONS: EMD guidance was superior to pH testing when compared with radiographic confirmation of nasogastric tube placement in children. PRACTICE IMPLICATIONS: EMD guided NGT placement is a potentially viable method for confirming nasogastric tube placement in children when done by appropriately trained clinicians. More research on EMD guided NGT placement in children is needed before any practice recommendation can be made.

Prevalence of ICU Delirium in Postoperative Pediatric Cardiac Surgery Patients.

OBJECTIVES: The objective of this study was to determine the prevalence of ICU delirium in children less than 18 years old that underwent cardiac surgery within the last 30 days. The secondary aim of the study was to identify risk factors associated with ICU delirium in postoperative pediatric cardiac surgical patients. DESIGN: A 1-day, multicenter point-prevalence study of delirium in pediatric postoperative cardiac surgery patients. SETTING: Twenty-seven pediatric cardiac and general critical care units caring for postoperative pediatric cardiac surgery patients in North America. PATIENTS: All children less than 18 years old hospitalized in the cardiac critical care units at 06:00 on a randomly selected, study day. INTERVENTIONS: Eligible children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the study team in collaboration with the bedside nurse. MEASUREMENT AND MAIN RESULTS: Overall, 181 patients were enrolled and 40% (n = 73) screened positive for delirium. There were no statistically significant differences in patient demographic information, severity of defect or surgical procedure, past medical history, or postoperative day between patients screening positive or negative for delirium. Our bivariate analysis found those patients screening positive had a longer duration of mechanical ventilation (12.8 vs 5.1 d; p = 0.02); required more vasoactive support (55% vs 26%; p = 0.0009); and had a higher number of invasive catheters (4 vs 3 catheters; p = 0.001). Delirium-positive patients received more total opioid exposure (1.80 vs 0.36 mg/kg/d of morphine equivalents; p < 0.001), did not have an ambulation or physical therapy schedule (p = 0.02), had not been out of bed in the previous 24 hours (p < 0.0002), and parents were not at the bedside at time of data collection (p = 0.008). In the mixed-effects logistic regression analysis of modifiable risk factors, the following variables were associated with a positive delirium screen: 1) pain score, per point increase (odds ratio, 1.3; 1.06-1.60); 2) total opioid exposure, per mg/kg/d increase (odds ratio, 1.35; 1.06-1.73); 3) SBS less than 0 (odds ratio, 4.01; 1.21-13.27); 4) pain medication or sedative administered in the previous 4 hours (odds ratio, 3.49; 1.32-9.28); 5) no progressive physical therapy or ambulation schedule in their medical record (odds ratio, 4.40; 1.41-13.68); and 6) parents not at bedside at time of data collection (odds ratio, 2.31; 1.01-5.31). CONCLUSIONS: We found delirium to be a common problem after cardiac surgery with several important modifiable risk factors.

Protein-Losing Enteropathy and Plastic Bronchitis After the Fontan Operation.

Protein-losing enteropathy and plastic bronchitis remain challenging to treat despite recent treatment advances. Protein-losing enteropathy and plastic bronchitis have been diagnosed in patients with cardiomyopathy, constrictive pericarditis, and congestive heart failure. This article focuses on patients with protein-losing enteropathy or plastic bronchitis following the Fontan procedure. Patients with single-ventricle physiology who have undergone the Fontan procedure are at risk for these conditions. Fontan physiology predisposes patients to chronically low cardiac output, increased central venous pressure, and congestive heart failure. These altered hemodynamics lead to increased mesenteric vascular resistance, resulting in venous hypertension and congestion in protein-losing enteropathy. Plastic bronchitis is a complex disease in which chronic high lymphatic pressures from Fontan physiology cause acellular bronchial casts to develop. These entities may also occur in patients with normal Fontan hemodynamics. This article also covers medical and surgical interventions for protein-losing enteropathy and plastic bronchitis. (Critical Care Nurse 2018;38[6]:e5-e12).

Adverse events in children implanted with ventricular assist devices in the United States: Data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).

BACKGROUND: Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) METHODS: PediMACS is a national registry that contains clinical data on patients who are <19 years of age at the time of VAD implantation. Data collection concludes at the time of VAD explantation. All FDA-approved devices are included. PediMACS was launched on September 1, 2012, and this report includes all data from launch until August 2014. Adverse events were coded with a uniform, pre-specified set of definitions. RESULTS: This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy (n = 146, 73%), myocarditis (n = 17, 9%), congenital heart disease (n = 35, 18%) and other (n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 81% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction (n = 79), infection (n = 78), neurologic dysfunction (n = 52) and bleeding (n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population. CONCLUSIONS: In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.

Improved nutrition delivery and nutrition status in critically ill children with heart disease.

BACKGROUND: This initiative sought to improve nutrition delivery in critically ill children with heart disease admitted to the cardiac ICU (CICU) and neonates undergoing stage 1 palliation (S1P) for single-ventricle physiology through interdisciplinary team interventions. Specific goals were increased caloric and protein delivery for all patients and a more nourished state for infants with single ventricles at the time of discharge. METHODS: We developed a nutrition flow sheet in the electronic health record to track whether daily nutrition goals were met. Interventions included nurses reporting daily whether caloric and protein goals were met, mandatory involvement of feeding specialists, and introduction of an enteral nutrition guideline. For infants undergoing S1P, weight-for-age z score (as an indicator for assessing malnutrition) was calculated at admission and discharge. RESULTS: The percentage of patient days per month when daily caloric goals were met increased from 50.1% to 60.7%, and protein goals met increased from 51.6% to 72.7%. Hospital length of stay, need for ventilation, and mortality did not differ. Patients undergoing S1P demonstrated a statistically significant improvement in weight-for-age z score compared with the preintervention group (P = .003). Thirteen S1P patients were discharged undernourished in the preintervention group; 5 were severely undernourished. In the intervention group, 4 patients were discharged undernourished, and none were severely undernourished. CONCLUSIONS: This initiative resulted in improved nutrition delivery for a heterogeneous population of cardiac patients in the CICU as well as significant improvements in weight gain and nourishment status at discharge in infants undergoing S1P.

A handoff protocol from the cardiovascular operating room to cardiac ICU is associated with improvements in care beyond the immediate postoperative period.

BACKGROUND: Handoff protocols from the cardiovascular operating room (CVOR) to the cardiac intensive care unit (CICU) can improve patient outcomes and delivery of care beyond the immediate postoperative period. In a prospective quality improvement study, a structured CVOR-to-CICU handoff protocol was implemented at a university-affiliated children's hospital. As a parallel project, an initiative to reduce unplanned extubations in the CICU was implemented. METHODS: In a 41-month period, 1,507 neonates, infants, children, and adults were admitted to the CICU from the CVOR after undergoing a surgical procedure. The study was divided into a 17-month prehandoff-protocol period (January 2009-May 2010) and a 24-month posthandoff-protocol period (June 2010-May 2012). The handoff protocol was intended to streamline the handoff process from the CVOR and throughout the transition to the CICU. The specifics of the handoff, as outlined in a bedside laminated flowchart, included patient transport from the CVOR, the cardiovascular surgeon's report, the anesthesiologist's report, and the patient status summary and care plan. RESULTS: After introduction of the handoff protocol, there was a statistically significant and sustained reduction in the mean rate of unplanned extubations from 0.62 to 0.24 per 100 ventilator-days (p = .03). There was a statistically significant reduction in median ventilator time per patient--from 17 hours (interquartile range [IQR]: 5.3 to 57.7) to 12.8 hours (IQR: 4.8 to 31.8); p = .02). The mean rate of unplanned extubations was 0.26 in 2011 and 0.30 in 2012. CONCLUSIONS: Implementation of a handoff protocol from the CVOR to the CICU was associated with sustained decrease in unplanned extubations and in mean ventilator times.

Predicting recovery: successful explant of a ventricular assist device in a child with dilated cardiomyopathy.

A previously healthy, 13-year-old girl presented with new-onset dilated cardiomyopathy, and is placed on a left ventricular assist device (VAD). Herein we describe a unique VAD weaning protocol used to determine the timing and feasibility of a VAD explant.