Education in the Pediatric Intensive Care Unit.

This article addresses the latest data and ideas related to education in the pediatric intensive care unit, including traditional education methods with newer and technology-based methods. A review of adult learning theory is included with discussions regarding medical decision making and error prevention, bedside teaching, medical simulation, and electronic methods of education.

Barriers to Aging in Place for Rural, Institutionalized Older Adults: A Qualitative Exploration.

OBJECTIVES: Although the majority of older adults wish to "age in place" in their communities, rural contexts pose challenges to maintaining long-term independence. The purpose of this study was to develop an understanding of the experiences of rural older adults who live in Skilled Nursing Facilities (SNFs) and thus have not aged in place. By retrospectively analyzing their pre-institution care situation, we aim to generate foundational knowledge on the barriers to aging in place in rural settings. METHODS: A series of individual and group interviews was conducted in SNFs across seven rural communities. A grounded, thematic analysis was used to interpret interview findings, and coding was informed by the socio-ecological model (SEM). RESULTS: Participants were 32 adults with a mean age of 72 years (SD = 5.7 years) and an average SNF residence of 3.9 years. Two themes emerged as primary barriers to successful aging in place: (1) Caregiver-related support issues and (2) Present focus, or lack of advanced care-planning. CONCLUSIONS: Findings suggest the importance of specifically supporting caregivers, to ease burden and allow for increased agency for rural older adults. A lack of access to caregiver supports and other services limits the ability of community-dwelling rural older adults to age in place or plan for the future. CLINICAL IMPLICATIONS: Existing networks of rural community resources and innovative solutions should be leveraged to improve access to services for older adults and their informal caregivers.

A 17-Year-Old Girl with a Recent History of Marijuana Use Presented with Pneumomediastinum and Pneumopericardium and Tested Positive for SARS-CoV-2 Infection on Hospital Admission.

BACKGROUND Pneumomediastinum and pneumopericardium have been reported to occur in people who regularly smoke marijuana and have also been reported in patients with COVID-19 pneumonia due to infection with SARS-CoV-2. This report is of a 17-year-old girl with a history of marijuana use who presented with pneumomediastinum and pneumopericardium and was found to be positive for SARS-CoV-2 infection on hospital admission by Abbott ID NOW testing. CASE REPORT A 17-year-old girl presented to the emergency room with a 3-day history of abdominal pain, nausea, and vomiting and a 1-day history of diarrhea. She had a history of daily marijuana use and lived with her grandmother who was presumed to be positive for COVID-19, based on symptoms. Her admission laboratory results were unremarkable except for pyuria, which was suspicious for urinary tract infection. The patient's nasopharyngeal swab was positive for SARS-CoV-2 infection. Owing to abdominal pain, a computed tomography (CT) scan of the abdomen and pelvis was obtained, which was concerning for pneumomediastinum and pneumopericardium. A CT scan of the thorax confirmed the findings. A contrast-enhanced barium esophagogram was performed and was unremarkable. The patient was admitted to the pediatric intensive care unit for observation and supportive care. CONCLUSIONS This report shows the importance of current testing for SARS-CoV-2 infection in patients of all ages who present acutely to the hospital. It also highlights the importance of obtaining a full social and medical history so that symptoms and signs from causes other than SARS-CoV-2 infection are not missed.

Noninvasive Determination of Blood Pressure by Heart Sound Analysis Compared With Intra-Arterial Monitoring in Critically Ill Children-A Pilot Study of a Novel Approach.

OBJECTIVES: To develop a novel device to predict systolic and diastolic blood pressure based on measured heart sound signals and evaluate its accuracy in comparison to intra-arterial blood pressure readings. STUDY DESIGN: Prospective, observational pilot study. SETTING: PICU. PATIENTS: Critically ill children (0-18 yr) undergoing continuous blood pressure monitoring via radial artery intra-arterial catheters were enrolled in the study after informed consent. The study included medical, cardiac, and surgical PICU patients. INTERVENTIONS: Along with intra-arterial blood pressure, patient's heart sounds were recorded simultaneously by a highly sensitive sensor taped to the chest. Additional hardware included a data acquisition unit and laptop computer. Subsequently, advanced signal processing technologies were used to minimize random interfering signals and extract and separate S1 and S2 signals. A computerized model was then developed using artificial neural network systems to estimate blood pressure from the extracted heart sound analysis. MEASUREMENTS AND MAIN OUTCOMES: We found a statistically significant correlation for systolic (r = 0.964; R = 0.928) and diastolic (r = 0.935; R = 0.868) blood pressure readings (n = 491) estimated by the novel heart-sound signal-based method and those recorded by intra-arterial catheters. The mean difference of the individually paired determinations of the blood pressure between the heart-sound-based method and intra-arterial catheters was 0.6 ± 7 mm Hg for systolic blood pressure and -0.06 ± 5 mm Hg for diastolic blood pressure, which was within the recommended range of 5 ± 8 mm Hg for any new blood pressure devices. CONCLUSIONS: Our findings provide proof of concept that the heart-sound signal-based method can provide accurate, noninvasive blood pressure monitoring.

Analysis of DNA Damage Response Gene Alterations and Tumor Mutational Burden Across 17,486 Tubular Gastrointestinal Carcinomas: Implications for Therapy.

BACKGROUND: Alterations in the DNA damage response (DDR) pathway confer sensitivity to certain chemotherapies, radiation, and other DNA damage repair targeted therapies. BRCA1/2 are the most well-studied DDR genes, but recurrent alterations are described in other DDR pathway members across cancers. Deleterious DDR alterations may sensitize tumor cells to poly (ADP-ribose) polymerase inhibition, but there are also increasing data suggesting that there may also be synergy with immune checkpoint inhibitors. The relevance of DDR defects in gastrointestinal (GI) cancers is understudied. We sought to characterize DDR-defective GI malignancies and to explore genomic context and tumor mutational burden (TMB) to provide a platform for future rational investigations. MATERIALS AND METHODS: Tumor samples from 17,486 unique patients with advanced colorectal, gastroesophageal, or small bowel carcinomas were assayed using hybrid-capture-based comprehensive genomic profiling including sequencing of 10 predefined DDR genes: ARID1A, ATM, ATR, BRCA1, BRCA2, CDK12, CHEK1, CHEK2, PALB2, and RAD51. TMB (mutations per megabase [mut/Mb]) was calculated from up to 1.14 Mb of sequenced DNA. Clinicopathologic features were extracted and descriptive statistics were used to explore genomic relationships among identified subgroups. RESULTS: DDR alterations were found in 17% of cases: gastric adenocarcinoma 475/1,750 (27%), small bowel adenocarcinoma 148/666 (22%), esophageal adenocarcinoma 467/2,501 (19%), and colorectal cancer 1,824/12,569 (15%). ARID1A (9.2%) and ATM (4.7%) were the most commonly altered DDR genes in this series, followed by BRCA2 (2.3%), BRCA1 (1.1%), CHEK2 (1.0%), ATR (0.8%), CDK12 (0.7%), PALB2 (0.6%), CHEK1 (0.1%) and RAD51 (0.1%). More than one DDR gene alteration was found in 24% of cases. High microsatellite instability (MSI-H) and high TMB (TMB-H, ≥20 mut/Mb) were found in 19% and 21% of DDR-altered cases, respectively. Of DDR-altered/TMB-H cases, 87% were also MSI-H. However, even in the microsatellite stable (MSS)/DDR-wild-type (WT) versus MSS/DDR-altered, TMB-high was seen more frequently (0.4% vs. 3.3%, P < .00001.) Median TMB was 5.4 mut/Mb in the MSS/DDR-altered subset versus 3.8 mut/Mb in the MSS/DDR-WT subset (P ≤ .00001), and ATR alterations were enriched in the MSS/TMB-high cases. CONCLUSION: This is the largest study to examine selected DDR defects in tubular GI cancers and confirms that DDR defects are relatively common and that there is an association between the selected DDR defects and a high TMB in more than 20% of cases. Microsatellite stable DDR-defective tumors with elevated TMB warrant further exploration. IMPLICATIONS FOR PRACTICE: Deleterious DNA damage response (DDR) alterations may sensitize tumor cells to poly (ADP-ribose) polymerase inhibition, but also potentially to immune checkpoint inhibitors, owing to accumulation of mutations in DDR-defective tumors. The relevance of DDR defects in gastrointestinal (GI) cancers is understudied. This article characterizes DDR-defective GI malignancies and explores genomic context and tumor mutational burden to provide a platform for future rational investigations.

Low thiamine levels in children with type 1 diabetes and diabetic ketoacidosis: a pilot study.

OBJECTIVE: Thiamine deficiency has been documented in adults with diabetes and in a single report of reversible encephalopathy in a child with diabetic ketoacidosis. In children who present with severe diabetic ketoacidosis, one of the most serious complications is cerebral edema of which the primary symptom may be encephalopathy. Thiamine deficiency in other disease states has been clearly linked with acute encephalopathy, but there are no data on thiamine status in children with diabetic ketoacidosis. This study describes the prevalence of thiamine deficiency in children with type 1 diabetes mellitus who present with diabetic ketoacidosis and are admitted to the ICU. DESIGN: A prospective observational pilot study. SETTING: PICU in a tertiary care children's hospital. PATIENTS: Children 2-18 years admitted to the ICU for treatment of diabetic ketoacidosis. INTERVENTIONS: Treatment of diabetic ketoacidosis. MEASUREMENTS AND MAIN RESULTS: Twenty-two patients were enrolled. The mean age was 13.7 ± 3.6 years. Five of 21 patients (23.8%) had thiamine deficiency prior to insulin administration. After 8 hours of insulin therapy, seven of 20 patients (35%) had thiamine deficiency, and four of these seven patients also had thiamine deficiency at presentation. Sixty-eight percent of patients had a decrease in thiamine levels after 8 hours of insulin therapy, with a mean fall of 20 ± 31.4 nmol/L. CONCLUSIONS: Thiamine deficiency is common in children with diabetic ketoacidosis, and this deficiency may be worsened by treatment. When metabolic acidosis persists despite appropriate treatment of diabetic ketoacidosis, other factors such as thiamine deficiency should be considered.

Views of pediatric intensive care physicians on the ethics of organ donation after cardiac death.

OBJECTIVE: Donation after cardiac death has been endorsed by professional organizations, including the American Academy of Pediatrics as a means of increasing the supply of transplantable organs. However, ethical concerns have been raised about donation after cardiac death, especially in children. This study explores the views of pediatric intensive care physicians on the ethics of pediatric donation after cardiac death. DESIGN: Internet survey. SUBJECTS: Physician members of the American Academy of Pediatrics Section of Critical Care. INTERVENTIONS: Physicians were emailed an anonymous survey consisting of four demographic items and 16 items designed to assess their views on the ethics of pediatric donation after cardiac death. Responses to ethics items were rated on a 5-point scale ranging from strongly disagree to strongly agree. Physicians were also given the opportunity to provide free-text comments regarding their views. MEASUREMENTS AND MAIN RESULTS: Of the 598 eligible physicians, 264 (44.1%) responded to the survey. Of these, 193 (73.4%) were practicing in a transplant center and 160 (60.6%) participated in at least one donation after cardiac death procedure at the time of survey completion. Two hundred twenty (83.4%) agreed or strongly agreed that regarding donation after cardiac death, parents should be able to make decisions based on the best interests of their child. Two hundred twenty-two (84.1%) agreed or strongly agreed that it is not acceptable to harvest organs from a child before the declaration of death, consistent with the Dead Donor Rule. However, only 155 (59.1%) agreed or strongly agreed that the time of death in donation after cardiac death can be conclusively determined. Twenty-nine (11.0%) agreed or strongly agreed that the pediatric donation after cardiac death donor may feel pain or suffering during the harvest procedure. CONCLUSIONS: Most pediatric intensive care physicians agree that the Dead Donor Rule should be applied for donation after cardiac death and that donation after cardiac death can be consistent with the best interest standard. However, concerns about the ability to determine time of death for the purpose of organ donation and the possibility of increasing donor pain and suffering exist.

Family-centered care in the pediatric intensive care unit.

Patient-centered and family-centered care (PFCC) has been endorsed by many professional health care organizations. Although variably defined, PFCC is an approach to care that is respectful of and responsive to the preferences, needs, and values of individual patients and their families. Research regarding PFCC in the pediatric intensive care unit has focused on 4 areas including (1) family visitation; (2) family-centered rounding; (3) family presence during invasive procedures and cardiopulmonary resuscitation; and (4) family conferences. Although challenges to successful implementation exist, the growing body of evidence suggests that PFCC is beneficial to patients, families, and staff.

Copeptin as a marker of relative arginine vasopressin deficiency after pediatric cardiac surgery.

PURPOSE: Relative arginine vasopressin (AVP) deficiency after pediatric cardiac surgery has recently been described. Copeptin, a more stable and easily measured product of pro-AVP processing, may be a means of identifying these patients. We aimed to determine if copeptin was correlated with AVP in these children and whether it can be a surrogate marker of relative AVP deficiency. METHODS: Patients <6 years of age with basic Aristotle scores ≥7 requiring surgery with cardiopulmonary bypass were prospectively enrolled. Plasma AVP and copeptin concentrations were measured pre-cardiopulmonary bypass and 4 and 24 h post-cardiopulmonary bypass. Relative AVP deficiency was defined a priori based on our previous work as AVP <9.2 pg/ml at 4 h post-cardiopulmonary bypass. RESULTS: Of 41 children enrolled, relative AVP deficiency was present in 13 (32 %). AVP and copeptin concentrations were significantly lower in these 13 children at 4 h post-cardiopulmonary bypass as compared to the other 28 patients. A significant positive association between plasma AVP and copeptin concentrations over time was determined. Based on log-transformed analyses, a 1 % increase in plasma AVP led to a 0.19 % increase in copeptin. Further, copeptin <1.12 ng/ml at 4 h post-cardiopulmonary bypass had a sensitivity of 92 % and a negative predictive value of 95 % for relative AVP deficiency. CONCLUSIONS: Plasma AVP and copeptin are positively associated in children undergoing cardiac surgery. Copeptin may represent a useful means of identifying relative AVP deficiency in these patients.

Relative deficiency of arginine vasopressin in children after cardiopulmonary bypass.

OBJECTIVE: To describe changes in plasma arginine vasopress in concentration in children following cardiopulmonary bypass and determine whether, in some patients, plasma arginine vasopressin remains relatively low despite hemodynamic instability. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit at a tertiary care university hospital. PATIENTS: One hundred twenty patients ≤ 18 yrs of age undergoing open heart surgery requiring cardiopulmonary bypass at Children's Hospital of Michigan between January 2008 and January 2009. INTERVENTIONS: Blood samples were collected before cardiopulmonary bypass and 4, 24, and 48 hrs after cardiopulmonary bypass for measurement of plasma arginine vasopressin concentration. MEASUREMENTS AND MAIN RESULTS: Mean plasma arginine vasopressin (pg/mL) for all patients was 21 ± 63 before cardiopulmonary bypass and 80 ± 145, 43 ± 79, and 19 ± 25 at 4, 24, and 48 hrs, respectively, after cardiopulmonary bypass. Patients with plasma arginine vasopressin below the lower quartile (< 9.2 pg/mL) at 4 hrs after cardiopulmonary bypass (n = 29), labeled group A, were examined separately and compared with the rest of the study population, labeled group B. Mean plasma arginine vasopressin was 4.9 ± 2.6 in group A at 4 hrs after cardiopulmonary bypass, statistically unchanged from its baseline mean plasma arginine vasopressin of 5.0 ± 10.4 (p = .977). Mean plasma arginine vasopressin in group B was 104 ± 160 at 4 hrs after cardiopulmonary bypass. Mean plasma arginine vasopressin of group A was also significantly lower as compared with group B before and 24 and 48 hrs after cardiopulmonary bypass. Hemodynamics, inotrope score, and serum sodium did not differ between groups at any time point. Plasma arginine vasopressin was measured immediately before exogenous arginine vasopressin administration in 10 patients; only those (n = 3) with hemodynamic instability and relatively low plasma arginine vasopressin concentration (< 9.2 pg/mL) had notable hemodynamic improvement. CONCLUSIONS: In some children undergoing open heart surgery, plasma arginine vasopressin concentration is relatively low at baseline and remains low after cardiopulmonary bypass regardless of hemodynamic stability and serum osmolality. These children are likely the optimal candidates for exogenous arginine vasopressin should hemodynamic compromise occur.

Integrative basic sciences: change in mental status.

This case discussion is part of the Integrating Basic Science Into Clinical Teaching Initiative. It examines the presentation of altered mental status and describes the underlying physiology, which explains the basic laboratory findings in an attempt to reach a diagnosis. This article describes a 13-year-old boy who presented to the emergency department with altered mental status after being found unconscious and alone in an abandoned building. He was unresponsive to painful and verbal stimuli, with otherwise normal findings on physical examination. Basic laboratory studies, including arterial blood gas, electrolytes, and serum osmolality, were obtained. The case discussion uses fundamentals of anatomy to build a focused differential diagnosis. The laboratory studies are interpreted using basic physiologic principles, including acid-base balance, anion gap, and osmolar gap, to determine the most likely cause of this patient's altered mental status. Subsequent investigation confirms a diagnosis of ethanol toxic effects. An understanding of electrolyte and acid-base physiology allows the clinician to use basic laboratory studies to build a focused differential diagnosis for altered mental status. This case discussion demonstrates how basic science principles of anatomy and physiology can be applied in clinical settings.

Arginine vasopressin to manage hypoxemic infants after stage I palliation of single ventricle lesions.

OBJECTIVE: Management of patients with single ventricle physiology following stage I palliation procedures is often challenging, with optimization of the ratio of pulmonary-to-systemic blood flow as an important goal. Persistent hypoxemia may be a manifestation of elevated pulmonary vascular resistance and therefore decreased blood flow to the lungs. In such situations, the use of arginine vasopressin to increase systemic vascular resistance may be an effective strategy to improve pulmonary blood flow and maintain adequate pulmonary-to-systemic blood flow ratio. We describe three infants in whom persistent hypoxemia improved after institution of arginine vasopressin. DESIGN: Retrospective chart review. SETTING: Twenty-four bed medical-surgical pediatric intensive care unit at a large tertiary care academic hospital. PATIENTS: Three neonates with single ventricle physiology who received arginine vasopressin in the setting of hypoxemia following stage I palliation. RESULTS: Arginine vasopressin was initiated in all three patients for hypoxemia with a goal to increase systemic vascular resistance and generate a higher driving pressure for pulmonary blood flow. Twelve hours after arginine vasopressin initiation, systemic arterial saturation as determined by pulse oximetry and blood pressure increased, whereas heart rate, inotrope score, and Fio2 decreased in all three patients. Urine output was maintained and arterial lactate decreased during this time. Pulmonary-to-systemic flow ratio increased in one patient in whom it could be determined. CONCLUSION: In patients with single ventricle physiology and persistent hypoxemia following stage I palliation, administration of arginine vasopressin could improve oxygenation possibly by increasing systemic vascular resistance and therefore the pulmonary blood flow.

Wheezing child.

This case discussion is part of the Integrating Basic Science into Clinical Teaching Initiative. It is intended to examine wheezing as a symptom and to describe the underlying physiology that explains the physical findings and blood gas features in an attempt to localize the site of obstruction. The information contained in this case is a compilation and derived from 2 similar patients. This case discussion describes a 13-month-old girl who presents with wheezing and respiratory distress. A close examination of her physical findings and blood gas analysis indicate that she is experiencing overall alveolar hypoventilation without significant hypoxemia, suggesting her airway obstruction is located above the carina. Subsequent investigations reveal a right aortic arch and vascular ring as the cause of her symptoms. An understanding of the physiology of airway obstruction and pulmonary gas exchange allows for better localization of sites of airway obstruction and the institution of appropriate diagnostic tests and therapy.