Trends in Pediatric Patient-Ventilator Asynchrony During Invasive Mechanical Ventilation

OBJECTIVES: To explore the level and time course of patient-ventilator asynchrony in mechanically ventilated children and the effects on duration of mechanical ventilation, PICU stay, and Comfort Behavior Score as indicator for patient comfort.DESIGN: Secondary analysis of physiology data from mechanically ventilated children.SETTING: Mixed medical-surgical tertiary PICU in a university hospital.PATIENTS: Mechanically ventilated children 0-18 years old were eligible for inclusion. Excluded were patients who were unable to initiate and maintain spontaneous breathing from any cause.MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients were studied with a total duration of 109 days. Twenty-two study days (20%) were excluded because patients were on neuromuscular blockade or high-frequency oscillatory ventilation, yielding 87 days (80%) for analysis. Patient-ventilator asynchrony was detected through analysis of daily recorded ventilator airway pressure, flow, and volume versus time scalars. Approximately one of every three breaths was asynchronous. The percentage of asynchronous breaths significantly increased over time, with the highest prevalence on the day of extubation. There was no correlation with the Comfort Behavior score. The percentage of asynchronous breaths during the first 24 hours was inversely correlated with the duration of mechanical ventilation. Patients with severe patient-ventilator asynchrony (asynchrony index &gt; 10% or &gt; 75th percentile of the calculated asynchrony index) did not have a prolonged duration of ventilation.CONCLUSIONS: The level of patient-ventilator asynchrony increased over time was not related to patient discomfort and inversely related to the duration of mechanical ventilation.</p

Prevalence and Prognostic Significance of Extramural Venous Invasion in Patients with Locally Advanced Esophageal Cancer

BACKGROUND: Extramural venous invasion (EMVI) is a known adverse prognostic factor in patients with colorectal carcinoma. The prevalence and significance of EMVI in esophageal cancer (EC) patients is still unclear. METHODS: From a prospectively maintained database, we retrospectively reviewed the resection specimens of patients with pathologic locally advanced (pT3/T4/N0-3) EC who were treated with curative intent between 2000 and 2015. Patients with previous malignancies and gastroesophageal junction (type II/III) tumors were excluded. Included were 81 patients who underwent surgery alone and 37 patients who underwent neoadjuvant chemoradiotherapy (nCRT). EMVI was assessed on hematoxylin and eosin slides and confirmed or excluded by additional Elastica van Gieson staining. Survival was analyzed using a multivariable Cox regression. RESULTS: EMVI was present in 23.5% (n = 19) of patients in the surgery-alone group and 21.6% (n = 8) of patients in the nCRT group. The prevalence of EMVI after surgery alone was significantly high in squamous cell carcinomas and among tumors located in the mid-esophagus, as well as those with lymphovascular invasion (p  pT3/N0-3 EC patients, EMVI was present in 23.5% of patients in the surgery-alone group and in 21.6% of patients after nCRT. EMVI was an independent adverse prognostic factor in patients after surgery alone

Eating and feeding problems in children with cancer:Prevalence, related factors, and consequences

Background & aims: During treatment for cancer, children experience many side effects such as lack of appetite, nausea, and vomiting. As a result, ensuring adequate intake puts pressure on both the child and the parent. This study aims to determine the prevalence, causes and consequences of eating and feeding problems in children treated for cancer. Methods: Parents of 85 children with cancer completed the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and symptoms, BMI, energy intake, feeding style, and parental distress were measured at 0, 3, 6 and 12 months after diagnosis. Results: Parent-reports revealed that almost a quarter of the children experienced eating disorder: 15.7% experienced problems related to diminished intake and 8.6% related to excessive intake. Prevalence of feeding disorders related to parents’ behavior was 21.1%. In children <8 years prevalence of eating and feeding disorders was significantly higher: 31% and 36% for child and parent behavior respectively. Younger age, poor pre-illness eating behavior, increase in symptoms and a demanding feeding style were associated with more eating problems. Excessive eating resulted in higher energy intake, however, no association was found between eating problems and nutritional status. Food refusal resulted in more parental distress. Conclusions: Especially younger children with cancer are at risk for eating and feeding problems. In addition, poor pre-illness eating behavior, symptoms and a demanding feeding style aggravate eating problems. Therefore, interventions should focus at diminishing side effects of treatment and instructing parents to be less demanding regarding their child's eating behavior

Driving Pressure Is Associated With Outcome in Pediatric Acute Respiratory Failure

OBJECTIVES: Driving pressure (ratio of tidal volume over respiratory system compliance) is associated with mortality in acute respiratory distress syndrome. We sought to evaluate if such association could be identified in critically ill children. DESIGN: We studied the association between driving pressure on day 1 of mechanical ventilation and ventilator-free days at day 28 through secondary analyses of prospectively collected physiology data. SETTING: Medical-surgical university hospital PICU. PATIENTS: Children younger than 18 years (stratified by Pediatric Mechanical Ventilation Consensus Conference clinical phenotype definitions) without evidence of spontaneous respiration. INTERVENTIONS: Inspiratory hold maneuvers. MEASUREMENTS AND MAIN RESULTS: Data of 222 patients with median age 11 months (2-51 mo) were analyzed. Sixty-five patients (29.3%) met Pediatric Mechanical Ventilation Consensus Conference criteria for restrictive and 78 patients (35.1%) for mixed lung disease, and 10.4% of all patients had acute respiratory distress syndrome. Driving pressure calculated by the ratio of tidal volume over respiratory system compliance for the whole cohort was 16 cm H2O (12-21 cm H2O) and correlated with the static airway pressure gradient (plateau pressure minus positive end-expiratory pressure) (Spearman correlation coefficient = 0.797; p < 0.001). Bland-Altman analysis showed that the dynamic pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) overestimated driving pressure (levels of agreement -2.295 to 7.268). Rematching the cohort through a double stratification procedure (obtaining subgroups of patients with matched mean levels for one variable but different mean levels for another ranking variable) showed a reduction in ventilator-free days at day 28 with increasing driving pressure in patients ventilated for a direct pulmonary indication. Competing risk regression analysis showed that increasing driving pressure remained independently associated with increased time to extubation (p < 0.001) after adjusting for Pediatric Risk of Mortality III 24-hour score, presence of direct pulmonary indication jury, and oxygenation index. CONCLUSIONS: Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic assessments of driving pressure should be cautiously interpreted

The effect of pressure support on imposed work of breathing during paediatric extubation readiness testing

BACKGROUND: Paediatric critical care practitioners often make use of pressure support (PS) to overcome the perceived imposed work of breathing (WOBimp) during an extubation readiness test (ERT). However, no paediatric data are available that shows the necessity of adding of pressure support during such tests. We sought to measure the WOBimp during an ERT with and without added pressure support and to study its clinical correlate. This was a prospective study in spontaneously breathing ventilated children < 18 years undergoing ERT. Using tracheal manometry, WOBimp was calculated by integrating the difference between positive end-expiratory pressure (PEEP) and tracheal pressure (Ptrach) over the measured expiratory tidal volume (VTe) under two paired conditions: continuous positive airway pressure (CPAP) with and without PS. Patients with post-extubation upper airway obstruction were excluded. RESULTS: A total of 112 patients were studied. Median PS during the ERT was 10 cmH2O. WOBimp was significantly higher without PS (median 0.27, IQR 0.20-0.50 J/L) than with added PS (median 0.00, IQR 0.00-0.11 J/L). Although there were statistically significant changes in spontaneous breath rate [32 (23-42) vs. 37 (27-46) breaths/min, p < 0.001] and higher ET-CO2 [5.90 (5.38-6.65) vs. 6.23 (5.55-6.94) kPa, p < 0.001] and expiratory Vt decreased [7.72 (6.66-8.97) vs. 7.08 (5.82-8.08) mL/kg, p < 0.001] in the absence of PS, these changes appeared clinically irrelevant since the Comfort B score remained unaffected [12 (10-13) vs. 12 (10-13), P = 0.987]. Multivariable analysis showed that changes in WOBimp occurred independent of endotracheal tube size. CONCLUSIONS: Withholding PS during ERT does not lead to clinically relevant increases in WOBimp, irrespective of endotracheal tube size

Effect of Extending the Original Eligibility Criteria for the CROSS Neoadjuvant Chemoradiotherapy on Toxicity and Survival in Esophageal Cancer

Patients with curable esophageal cancer (EC) who proceed beyond the original Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) eligibility criteria are also treated with neoadjuvant chemoradiotherapy (nCRT). This study assessed the effect that extending the CROSS eligibility criteria for nCRT has on treatment-related toxicity and overall survival (OS) in EC. The study enrolled 161 patients with locally advanced EC (T1N1-3/T2-4aN0-3/M0) treated with the CROSS schedule followed by esophagectomy. Group 1 consisted of 89 patients who met the CROSS criteria, and group 2 consisted of 72 patients who met the extended eligibility criteria, i.e. a tumor length greater than 8 cm (n = 24), more than 10% weight loss (n = 35), more than 2-4 cm extension in the stomach (n = 21), celiac lymph node metastasis (n = 13), and/or age over 75 years (n = 2). The study assessed the differences in nCRT-associated toxicity [National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) grade3] and 90-day postoperative mortality. Moreover, the prognostic value for OS was assessed with multivariate Cox regression analysis. No difference was found in nCRT-associated toxicity (P = 0.117), postoperative complications (P = 0.783), and 90-day mortality (P = 0.492). The OS differed significantly (P = 0.004), with a median of 37.3 months [95% confidence interval (CI), 10.4-64.2 months] for group 1 and 17.2 months (95% CI 13.8-20.7 months) for group 2. Pathologic N stage (P = 0.023), pathologic T stage (P = 0.043), and group 2 (P = 0.008) were independent prognostic factors for OS. Extension of the CROSS study eligibility criteria for nCRT did not affect nCRT-associated toxicity, postoperative complications, and postoperative mortality, but was prognostic for OS

Application of the Scale for Assessment and Rating of Ataxia in toddlers

Introduction: In young children with early onset ataxia (EOA), quantitative rating of ataxia by the Scale for Assessment and Rating of Ataxia (SARA) is longitudinally influenced by the physiological age effect on motor coordination. To enable longitudinal quantitative interpretation of ataxia by SARA in children with EOA, the EPNS ataxia working group has previously determined SARA-scores in typically developing children (4-16 years of age). In toddlers, this information is still lacking. We therefore aimed to investigate the feasibility and reliability of SARA-scores in typically developing toddlers. Methods: In 57 typically developing toddlers (2-4 years), we aimed to determine the: 1. feasibility of SARA -scores, 2. age-related pre-requisites to obtain SARA-scores in toddlers over all domains, 3. SARA-score reliability, 4. mathematical age connection of SARA-scores in toddlers and older children. Results: In typically developing toddlers, the feasibility of SARA is strongly age-dependent (p < .000). After computing compensations for two age-related, unfeasible and therefore un-assessable kinetic subtasks and after allowing the videotaping of non-kinetic SARA sub-task performances at home, the SARA was fully reliably assessable in all (n = 57) toddlers (ICC = 0.732). From two to 16 years of age, SARA-scores were mathematically represented by one continuous, exponentially decreasing trend line approaching the adult-optimum at 16 years of age. Conclusion: In toddlers, SARA-scores are reliably assessable, by using two age-compensations and allowing the videotaping of SARA-performances partly at home. In children with EOA, these data enable longitudinal quantification and interpretation of quantitative ataxia-scores by SARA from 2 years of age throughout childhood

The long-term safety of chronic azithromycin use in adult patients with cystic fibrosis, evaluating biomarkers for renal function, hepatic function and electrical properties of the heart

Background: Azithromycin maintenance therapy is widely used in cystic fibrosis (CF), but little is known about its long-term safety. We investigated whether chronic azithromycin use is safe regarding renal function, hepatic cell toxicity and QTc-interval prolongation. Methods: Adult CF patients (72 patients using azithromycin for a cumulative period of 364.8 years and 19 controls, 108.8 years) from two CF-centers in the Netherlands with azithromycin (non)-use for at least three uninterrupted years were studied retrospectively. Results: There was no difference in mean decline of estimated glomerular filtration rate (eGFR), nor in occurrence of eGFR-events. No drug-induced liver injury could be attributed to azithromycin. Of the 39 azithromycin users of whom an ECG was available, 4/39 (10.3%) had borderline and 4/39 (10.3%) prolonged QTc-intervals, with 7/8 patients using other QTc-prolonging medication. Of the control patients 1/6 (16.7%) had a borderline QTc-interval, without using other QTc-prolonging medication. No cardiac arrhythmias were observed. Conclusion: We observed no renal or hepatic toxicity, nor cardiac arrythmias during azithromycin use in CF patients for a mean study duration of more than 5 years. One should be aware of possible QTc-interval prolongation, in particular in patients using other QTc-interval prolonging medication