Association of Fluid Overload with Escalation of Respiratory Support and Endotracheal Intubation in Acute Bronchiolitis Patients.

Fluid overload has been associated with increased oxygen requirement, prolonged duration of mechanical ventilation, and longer length of hospital stay in children hospitalized with pulmonary diseases. Critically ill infants with bronchiolitis admitted to the pediatric intensive care unit (PICU) also tend to develop fluid overload and there is limited information of its role on noninvasive respiratory support. Thus, our primary objective was to study the association of fluid overload in patients with bronchiolitis admitted to the PICU with respiratory support escalation (RSE) and need for endotracheal intubation (ETI). Infants ≤24 months of age with bronchiolitis and admitted to the PICU between 9/2009 and 6/2015 were retrospectively studied. Demographic variables, clinical characteristics including type of respiratory support and need for ETI were evaluated. Fluid overload as assessed by net fluid intake and output (net fluid balance), cumulative fluid balance (CFB) (mL/kg), and percentage fluid overload (FO%), was compared between patients requiring and not requiring RSE and among patients requiring ETI and not requiring ETI at 0 (PICU admission), 12, 24, 36, 48, 72, 96, and 120 hours. One-hundred sixty four of 283 patients with bronchiolitis admitted to the PICU qualified for our study. Thirty-four of 164 (21%) patients required escalation of respiratory support within 5 days of PICU admission and of these 34 patients, 11 patients required ETI. Univariate analysis by Kruskal-Wallis test of fluid overload as assessed by net fluid balance, CFB, and FO% between 34 patients requiring and 130 patients not requiring RSE and among 11 patients requiring ETI and 153 patients not requiring ETI, at 0, 12, 24, 36, 48, 72, 96 and 120 hours did not reveal any significant difference ( p >0.05) at any time interval. Multivariable logistic regression analysis revealed higher PRISM score (odds ratio [OR]: 4.95, 95% confidence interval [95% CI]: 1.79-13.66; p = 0.002), longer hours on high flow nasal cannula (OR: 4.86, 95% CI: 1.68-14.03; p = 0.003) and longer hours on noninvasive ventilation (OR: 11.16, 95% CI: 3.36-36.98; p < 0.001) were associated with RSE. Fluid overload as assessed by net fluid balance, CFB, and FO% was not associated with RSE or need for ETI in critically ill bronchiolitis patients admitted to the PICU. Further prospective studies involving larger number of patients with bronchiolitis are needed to corroborate our findings.

Association of enteral feeds in critically ill bronchiolitis patients supported by high-flow nasal cannula with adverse events and outcomes.

To study association of enteral feeds in bronchiolitis patients supported by different levels of high flow nasal cannula (HFNC) with adverse events, nutritional goals, and clinical outcomes. Bronchiolitis patients ≤ 24 months of age treated with < 1 L/kg/min, 1-2 L/kg/min and > 2 L/kg/min of HFNC between January 2014 and December 2021 were studied retrospectively at a tertiary care children's hospital. Adverse events (aspiration pneumonia, emesis, and respiratory support escalation), nutritional goals (initiation of enteral feeds, achievement of nutritional goal volume and goal calories, percentage weight change during hospital stay) and clinical outcomes (HFNC duration, oxygen supplementation duration after HFNC, length of hospital stay following HFNC support, total length of hospital stay and follow-up for 1 month after hospital discharge) were compared between fed and non-fed patients on HFNC. Six hundred thirty-six (489 fed and 147 not-fed) bronchiolitis patients on HFNC studied. 260 patients, 317 patients and 59 patients were supported by < 1 L/kg/min, 1-2 L/kg/min and > 2 L/kg/min of HFNC, respectively. Enterally fed patients had significantly less adverse events (OR = 0.14, 95% CI 0.083 - 0.23, p < 0.001), significantly better nutritional goals: earlier initiation of enteral feeds by 65% in time (mean ratio = 0.35, 95% CI 0.28 - 0.43, p < 0.001), earlier achievement of goal volume and goal calorie needs by 14% in time (mean ratio = 0.86, 95% CI 0.78 to 0.96, p = 0.005) and significantly better clinical outcomes: shorter HFNC duration by 29.75 h (95% CI 20.19 -39.31, p < 0.001), shorter oxygen supplementation duration after HFNC by 12.14 h (95% CI 6.70 -17.59, p < 0.001), shorter length of hospital stay after HFNC support by 21.35 h (95% CI 14.71-27.98, p < 0.001) and shorter total length of hospital stay by 51.10 h (95% CI 38.65 -63.55, p < 0.001), as compared to non-fed patients, after adjusting for age, weight, prematurity, comorbidities, admission time, admission bronchiolitis score, admission respiratory rate, and HFNC levels. The number of revisits and readmissions at 7 and 30 days after hospital discharge were not significantly different (p > 0.05) between the fed and non-fed groups.    Conclusion: Enteral feeding of bronchiolitis patients supported by different levels of HFNC is associated with less adverse events and better nutrition goals and clinical outcomes. What is Known: •There is general apprehension to feed critically ill bronchiolitis patients supported by high flow nasal cannula. What is New: •Our study reveals that enteral feeding of critically ill bronchiolitis patients supported by different levels of high flow nasal cannula is associated with minimal adverse events, better nutritional goals and improved clinical outcomes as compared to non-fed patients.

Inhaled nitric oxide therapy for severe hypoxemia in hyperinflated mechanically ventilated bronchiolitis patient.

Management of hospitalized bronchiolitis patients comprises supportive care including non-invasive and invasive mechanical ventilation. Inhaled nitric oxide (iNO) therapy has been used in bronchiolitis patients to manage pulmonary hypertension, acute respiratory distress syndrome, bronchoconstriction or inflammation. We report the role of iNO in management of severe hypoxemia in a 7-month-old mechanically ventilated bronchiolitis patient on 100% oxygen and high ventilator settings who had hyperinflation on chest x-ray, and diffuse bronchospasm on clinical assessment. We believe iNO improved hypoxemia in our patient by optimizing the ventilation/perfusion mismatch, decreasing dead space ventilation and relieving elevated pulmonary vascular resistance associated with alveolar overdistention. Inhaled nitric oxide therapy for severe hypoxemia in hyperinflated mechanically ventilated bronchiolitis patient.

Dead space ratio as a tool in nitric oxide weaning: a study in pulmonary hypertensive disease.

OBJECTIVES: To describe the association between successful weaning of inhaled nitric oxide and trends in dead space ratio during such weans in patients empirically initiated on nitric oxide therapy out of concern of pulmonary hypertensive crisis. PATIENTS: Children in a cardiac intensive care unit initiated on inhaled nitric oxide out of clinical concern for pulmonary hypertensive crisis retrospectively over 2 years. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients were included, and nitric oxide was successfully discontinued in 23/27. These patients exhibited decreases in dead space ratio (0.18 versus 0.11, p = 0.047) during nitric oxide weaning, and with no changes in dead space ratio between pre- and post-nitric oxide initiation (p = 0.88) and discontinuation (p = 0.63) phases. These successful patients had a median age of 10 months [4.0, 57.0] and had a pre-existent diagnosis of CHD in 6/23 and pulmonary hypertension in 2/23. Those who failed nitric oxide discontinuation trended with a higher dead space ratio at presentation (0.24 versus 0.10), were more likely to carry a prior diagnosis of pulmonary hypertension (50% versus 8.7%), and had longer mechanical ventilation days (5 versus 12). CONCLUSIONS: Patients empirically placed on nitric oxide out of concern of pulmonary hypertensive crisis and successfully weaned off showed unchanged or decreased dead space ratio throughout the initiation to discontinuation phases of nitric oxide therapy. Trends in dead space ratio may aid in determining true need for nitric oxide and facilitate effective weaning. Further studies are needed to directly compare trends between success and failure groups.

Streptococcus Pneumoniae-Associated Hemolytic Uremic Syndrome in the Era of Pneumococcal Vaccine.

Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) is a serious complication of invasive pneumococcal disease that is associated with increased mortality in the acute phase and morbidity in the long term. Recently, Sp-HUS definition has undergone revision and cases are categorized as definite, probable, and possible, based on less invasive serological investigations that evaluate Thomsen-Friedenreich crypt antigen (T-antigen) activation. In comparison to the pre-vaccine era, Sp-HUS incidence seems to be decreasing after the introduction of 7-serotype valence and 13-serotype valence pneumococcal vaccines in 2000 and 2010, respectively. However, Sp-HUS cases continue to occur secondary to vaccine failure and emergence of non-vaccine/replacement serotypes. No single hypothesis elucidates the molecular basis for Sp-HUS occurrence, although pneumococcal neuraminidase production and formation of T-antigen antibody complexes on susceptible endothelial and red blood cells continues to remain the most acceptable explanation. Management of Sp-HUS patients remains supportive in nature and better outcomes are being reported secondary to earlier recognition, better diagnostic tools and improved medical care. Recently, the addition of eculizumab therapy in the management of Sp-HUS for control of dysregulated complement activity has demonstrated good outcomes, although randomized clinical trials are awaited. A sustained pneumococcal vaccination program and vigilance for replacement serotypes will be the key for persistent reduction in Sp-HUS cases worldwide.

Acute Tracheal Necrosis After Intubation in a Childhood Onset Systemic Lupus Erythematosus.

Upper airway involvement in systemic lupus erythematosus (SLE) disease process is uncommon. A 15-year-old girl, a known patient with class IVA lupus nephritis, presented in acute renal failure due to flare-up of SLE. She underwent an uneventful elective intubation procedure for placement of a hemodialysis catheter. After 36 hours of extubation, she developed biphasic stridor and severe shortness of breath that was unresponsive to multiple medications. Prompt airway evaluation by laryngoscopy and confirmation of acute tracheal necrosis by histopathology along with reintubation and high-dose steroid therapy resulted in good outcome and recovery.

Gestational Exposure to Cigarette Smoke Suppresses the Gasotransmitter H2S Biogenesis and the Effects Are Transmitted Transgenerationally.

Rationale: Gestational cigarette smoke (CS) impairs lung angiogenesis and alveolarization, promoting transgenerational development of asthma and bronchopulmonary dysplasia (BPD). Hydrogen sulfide (H2S), a proangiogenic, pro-alveolarization, and anti-asthmatic gasotransmitter is synthesized by cystathionine-γ-lyase (CSE), cystathionine-ß-synthase (CBS), and 3-mercaptopyruvate sulfur transferase (3MST). Objective: Determine if gestational CS exposure affected the expression of H2S synthesizing enzymes in the mouse lung and human placenta. Methods: Mice were exposed throughout gestational period to secondhand CS (SS) at approximating the dose of CS received by a pregnant woman sitting in a smoking bar for 3 h/days during pregnancy. Lungs from 7-days old control and SS-exposed pups and human placenta from mothers who were either non-smokers or smokers during pregnancy were analyzed for expression of the enzymes. Measurements: Mouse lungs and human placentas were examined for the expression of CSE, CBS, and 3MST by immunohistochemical staining, qRT-PCR and/or Western blot (WB) analyses. Results: Compared to controls, mouse lung exposed gestationally to SS had significantly lower levels of CSE, CBS, and 3MST. Moreover, the SS-induced suppression of CSE and CBS in F1 lungs was transmitted to the F2 generation without significant change in the magnitude of the suppression. These changes were associated with impaired epithelial-mesenchymal transition (EMT)-a process required for normal lung angiogenesis and alveolarization. Additionally, the placentas from mothers who smoked during pregnancy, expressed significantly lower levels of CSE, CBS, and 3MST, and the effects were partially moderated by quitting smoking during the first trimester. Conclusions: Lung H2S synthesizing enzymes are downregulated by gestational CS and the effects are transmitted to F2 progeny. Smoking during pregnancy decreases H2S synthesizing enzymes is human placentas, which may correlate with the increased risk of asthma/BPD in children.

Fever without a source in children with congenital heart disease.

Two paediatric congenital heart disease patients presented with a brief history of low-grade fever without any focal symptoms. Their clinical features and laboratory tests were unremarkable; however, their blood cultures were positive that prompted further work-up. Infective endocarditis should be considered in any paediatric congenital heart disease patient who presents with fever without any other associated clinical features.

Clinical Outcomes and Risk Factors for In-Hospital Mortality in Neonates with Hypoplastic Left Heart Syndrome.

The objective of this study was to identify patient and hospitalization characteristics associated with in-hospital mortality in infants with hypoplastic left heart syndrome (HLHS). We conducted a retrospective analysis of a large administrative database, the National Inpatient Sample dataset of the Healthcare Cost and Utilization Project for the years 2002-2016. Neonates with HLHS were identified by ICD-9 and ICD-10 codes. Hospital and patient factors associated with inpatient mortality were analyzed. Overall, 18,867 neonates met the criteria of inclusion; a total of 3813 patients died during the hospitalization (20.2%). In-hospital mortality decreased over the years of the study (27.0% in 2002 vs. 18.3% in 2016). Extracorporeal membrane oxygenation utilization was 8.1%. Univariate and multivariate logistic regression analyses were used to identify risk factors for in-hospital mortality in infants with hypoplastic left heart syndrome. Independent non-modifiable risk factors for mortality were birth weight < 2500 g (Adjusted odds ratio (aOR) 2.16 [1.74-2.69]), gestational age < 37 weeks (aOR 1.73 [1.42-2.10]), chromosomal abnormalities (aOR 3.07 [2.60-3.64]) and renal anomalies (aOR 1.34 [1.10-1.61]). Independent modifiable risk factors for mortality were being transferred-in from another hospital (aOR 1.15 [1.03-1.29]), use of extracorporeal membrane oxygenation (aOR 12.74 [10.91-14.88]). Receiving care in a teaching hospital is a modifiable variable, and it decreased the odds of mortality (aOR 0. 78 [0.64-0.95]). In conclusion, chromosomal anomalies, Extra Corporeal Membrane Oxygenation, gestational age < 37 weeks or birth weight < 2500 g were associated with increased odds of mortality. Modifiable variables as receiving care at birth center and in a hospital designated as a teaching hospital decreased the odds of mortality.

Acetylcholinesterase Inhibitor Pyridostigmine Bromide Attenuates Gut Pathology and Bacterial Dysbiosis in a Murine Model of Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a Th2 inflammatory bowel disease characterized by increased IL-5 and IL-13 expression, eosinophilic/neutrophilic infiltration, decreased mucus production, impaired epithelial barrier, and bacterial dysbiosis of the colon. Acetylcholine and nicotine stimulate mucus production and suppress Th2 inflammation through nicotinic receptors in lungs but UC is rarely observed in smokers and the mechanism of the protection is unclear. METHODS: In order to evaluate whether acetylcholine can ameliorate UC-associated pathologies, we employed a mouse model of dextran sodium sulfate (DSS)-induced UC-like conditions, and a group of mice were treated with Pyridostigmine bromide (PB) to increase acetylcholine availability. The effects on colonic tissue morphology, Th2 inflammatory factors, MUC2 mucin, and gut microbiota were analyzed. RESULTS: DSS challenge damaged the murine colonic architecture, reduced the MUC2 mucin and the tight-junction protein ZO-1. The PB treatment significantly attenuated these DSS-induced responses along with the eosinophilic infiltration and the pro-Th2 inflammatory factors. Moreover, PB inhibited the DSS-induced loss of commensal Clostridia and Flavobacteria, and the gain of pathogenic Erysipelotrichia and Fusobacteria. CONCLUSIONS: Together, these data suggest that in colons of a murine model, PB promotes MUC2 synthesis, suppresses Th2 inflammation and attenuates bacterial dysbiosis therefore, PB has a therapeutic potential in UC.

Eutectic mixture of lidocaine and prilocaine versus 1% lidocaine injection for lumbar punctures in pediatric oncology patients.

BACKGROUND: The role of local analgesics for lumbar punctures (LPs) in pediatric oncology patients has not been specifically studied. AIM: To compare the efficacy of eutectic mixture of local anesthetics (EMLA) cream to 1% lidocaine injection for LPs. METHOD: This was a retrospective observational study of all patients receiving either EMLA cream (EMLA group) or 1% lidocaine subcutaneous injection (lidocaine group) in addition to fentanyl and propofol for LPs over 18 months. Demographics, vital parameters, procedural and recovery times, propofol and fentanyl doses, and adverse events were studied. RESULTS: Two hundred ninety LPs in 49 children were studied: 148 in the EMLA group and 142 in the lidocaine group. There was no difference in demographics or preprocedural parameters between the two groups. LPs in the EMLA group were completed in a shorter time (7.5 minutes [CI 7.0-8.1] vs 9.4 minutes [CI 8.9-9.9]) with a faster recovery time (38.7 minutes [CI 36.9-40.9] vs 43.9 minutes. [CI 41.9-45.9]) as compared with the lidocaine group (P < 0.001). The EMLA group required less maintenance doses (0.54 mg/kg [CI 0.47-0.62] vs 1.14 mg/kg [CI 1.06-1.21]) and total doses (2.58 mg/kg [CI 2.42-2.75] vs 3.12 mg/kg [CI 2.95-3.29]) of propofol as compared with the lidocaine group (P < 0.0001). Adverse events in the EMLA group were less (19% vs 41%) as compared with the lidocaine group (P < 0.0001). CONCLUSION: The addition of EMLA cream for procedural sedation for LPs in pediatric oncology patients significantly improves pain management in comparison with 1% lidocaine injection.

Conversion Disorder Manifesting as Functional Visual Loss.

BACKGROUND: Children with conversion disorder experience neurological symptoms without a definable organic cause. Clinical presentation of conversion disorders is uncommon in the emergency department (ED). CASE REPORT: An 11-year-old previously healthy girl presented to the ED for management of lobar pneumonia. She developed acute visual loss subsequent to accidental placement of an intra-arterial cannula in her arm. Clinical assessments by the emergency physician, neurology, ophthalmology, and psychiatry services, and negative neuroimaging studies established the diagnosis of functional visual loss as a manifestation of conversion disorder. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Conversion disorder symptoms are often without any specific markers and do not fit standard clinical guidelines. A comprehensive and step-wise evaluation of unusual clinical presentation by multiple specialties and ancillary test results should be considered to rule out organic causes and establish the diagnosis of conversion disorder, as seen in our patient.

Effects of zolpidem on sleep parameters in patients with cirrhosis and sleep disturbances: A randomized, placebo-controlled trial.

BACKGROUND/AIMS: The aim of this study was to study the efficacy and safety of zolpidem for sleep disturbances in patients with cirrhosis. METHODS: Fifty-two Child-Turcotte-Pugh (CTP) class A or B cirrhotics with Pittsburgh Sleep Quality Index >5 were randomized to either zolpidem 5 mg daily (n=26) or placebo (n=26) for 4 weeks. RESULTS: The therapy of 4 weeks was completed by 23 patients receiving zolpidem (3 stopped treatment due to excessive daytime drowsiness) and 24 receiving placebo (2 refused to continue the study). In the zolpidem group, after 4 weeks of therapy, there was significant increase in total sleep time (TST) and sleep efficiency compared to baseline and improvement in polysomnographic parameters of sleep initiation and maintenance (i.e., decrease in sleep latency time, decrease in wake time, and decreases in number of arousals and periodic limbs movements per hour of sleep), without any significant change in sleep architecture. CONCLUSION: Four weeks of 5 mg daily zolpidem in CTP class A or B cirrhosis patients with insomnia led to significant increases in TST and sleep efficiency and improvement in polysomnographic parameters of sleep initiation and maintenance without any significant change in sleep architecture.

Subclinical cerebral edema in diabetic ketoacidosis in children.

Subclinical cerebral edema in diabetic ketoacidosis tends to manifest with subtle neurological symptoms including headache, lethargy, or disorientation and a Glasgow Coma Scale of 14-15. Treatment of subclinical cerebral edema with hyperosmolar therapy for persistent symptoms is associated with good outcomes.

Early Testing of Serum Ferritin Facilitates Hemophagocytic Lymphohistiocytosis Diagnosis in Children.

The clinical and laboratory features of hemophagocytic lymphohistiocytosis (HLH) are nonspecific that makes the definitive diagnosis of HLH very challenging. The disease is almost universally fatal in the absence of early recognition and appropriate therapy. Elevated serum ferritin level is one of the diagnostic markers of HLH disease. We report the value of testing serum ferritin level early in the disease process in 3 pediatric patients who presented with persistent fever and sepsis-like features. Detection of elevated serum ferritin levels facilitated further testing to confirm the diagnosis of HLH and initiate early therapy with good outcomes.

Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques.

In the era of combined antiretroviral therapy (cART), lung diseases such as chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) are common among persons living with HIV (PLWH), particularly smokers. Although smoking is highly prevalent among PLWH, HIV may be an independent risk factor for lung diseases; however, the role of HIV and cigarette smoke (CS) and their potential interaction in the development of chronic lung diseases among PLWH has not been delineated. To investigate this interaction, cynomolgus macaques were exposed to CS and/or simian-adapted human immunodeficiency virus (SHIV) and treated with cART. The development of CB and the lung functions were evaluated following CS±SHIV treatment. The results showed that in the lung, SHIV was a strong independent risk factor for goblet cell metaplasia/hyperplasia and mucus formation, MUC5AC synthesis, loss of tight junction proteins, and increased expression of Th2 cytokines/transcription factors. In addition, SHIV and CS synergistically reduced lung function and increased extrathoracic tracheal ring thickness. Interestingly, SHIV infection generated significant numbers of HIV-gp120+ epithelial cells (HGECs) in small airways and alveoli, and their numbers doubled in CS+SHIV-infected lungs. We conclude that even with cART, SHIV independently induces CB and pro-COPD changes in the lung, and the effects are exacerbated by CS.

Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia.

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.