Care of critically ill children includes sedation but current therapies are suboptimal. To describe dexmedetomidine use in children supported on mechanical ventilation for acute respiratory failure.
...Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial.
Thirty-one PICUs.
Data from 2,449 children; 2 weeks to 17 years old.
Sedation practices were unrestrained in the usual care arm. Patients were categorized as receiving dexmedetomidine as a primary sedative, secondary sedative, periextubation agent, or never prescribed. Dexmedetomidine exposure and sedation and clinical profiles are described.
Of 1,224 usual care patients, 596 (49%) received dexmedetomidine. Dexmedetomidine as a primary sedative patients (n = 138; 11%) were less critically ill (Pediatric Risk of Mortality III-12 score median, 6 interquartile range, 3-11) and when compared with all other cohorts, experienced more episodic agitation. In the intervention group, time in sedation target improved from 28% to 50% within 1 day of initiating dexmedetomidine as a primary sedative. Dexmedetomidine as a secondary sedative usual care patients (n = 280; 23%) included more children with severe pediatric acute respiratory distress syndrome or organ failure. Dexmedetomidine as a secondary sedative patients experienced more inadequate pain (22% vs 11%) and sedation (31% vs 16%) events. Dexmedetomidine as a periextubation agent patients (n = 178; 15%) were those known to not tolerate an awake, intubated state and experienced a shorter ventilator weaning process (2.1 vs 2.3 d).
Our data support the use of dexmedetomidine as a primary agent in low criticality patients offering the benefit of rapid achievement of targeted sedation levels. Dexmedetomidine as a secondary agent does not appear to add benefit. The use of dexmedetomidine to facilitate extubation in children intolerant of an awake, intubated state may abbreviate ventilator weaning. These data support a broader armamentarium of pediatric critical care sedation.
Previous latent class analysis of adults with acute respiratory distress syndrome (ARDS) identified two phenotypes, distinguished by the degree of inflammation. We aimed to identify phenotypes in ...children with ARDS in whom developmental differences might be important, using a latent class analysis approach similar to that used in adults.
This study was a secondary analysis of data aggregated from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial and the Genetic Variation and Biomarkers in Children with Acute Lung Injury (BALI) ancillary study. We used latent class analysis, which included demographic, clinical, and plasma biomarker variables, to identify paediatric ARDS (PARDS) phenotypes within a cohort of children included in the RESTORE and BALI studies. The association of phenotypes with clinically relevant outcomes and the performance of paediatric data in adult ARDS classification algorithms were also assessed.
304 children with PARDS were included in this secondary analysis. Using latent class analysis, a two-class model was a better fit for the cohort than a one-class model (p<0·001). Latent class analysis identified two classes: class 1 (181 60% of 304 patients with PARDS) and class 2 (123 40% of 304 patients with PARDS), referred to as phenotype 1 and 2 hereafter. Phenotype 2 was characterised by higher concentrations of inflammatory biomarkers, a higher incidence of vasopressor use, and more frequent diagnosis of sepsis, consistent with the adult hyperinflammatory phenotype. All levels of severity of PARDS were observed across both phenotypes. Children with the hyperinflammatory phenotype (phenotype 2) had worse clinical outcomes than those with the hypoinflammatory phenotype (phenotype 1), with a longer duration of mechanical ventilation (median 10·0 days IQR 6·3-21·0 for phenotype 2 vs 6·6 days 4·1-10·8 for phenotype 1, p<0·0001), and higher incidence of mortality (17 13·8% of 123 patients vs four 2·2% of 181 patients, p=0·0001). When using adult phenotype classification algorithms in children, the soluble tumour necrosis factor receptor-1 (sTNFr1), vasopressor use, and interleukin (IL)-6 variables gave an area under the curve (AUC) of 0·956, and the sTNFr1, vasopressor use, and IL-8 variables gave an AUC of 0·954, compared with the gold standard of latent class analysis.
Latent class analysis identified two phenotypes in children with ARDS with characteristics similar to those in adults, including worse outcomes among patients with the hyperinflammatory phenotype. PARDS phenotypes should be considered in design and analysis of future clinical trials in children.
US National Institutes of Health.
To determine the frequency of respiratory complications in children admitted to the ICU after adenotonsillectomy and to identify factors associated with the risk of respiratory complications in this ...cohort.
Retrospective observational study.
PICU.
All children admitted to the ICU following adenotonsillectomy from September 30, 2009, to March 30, 2014.
Of the 165 children included in the study, 150 (91%) received no respiratory support other than oxygen in the first 2 hours postoperatively. Of the 15 who required support following 2 hours, 14 required nasopharyngeal airways, one required invasive mechanical ventilation, and seven required supplemental oxygen for more than 2 hours. None of the children who received respiratory support for less than 2 hours required subsequent ICU level care. When comparing those who received support for more than 2 hours to those who did not, there were no differences in clinical characteristics except that those who received support were more likely to have chronic neurologic disease including autism, seizures, or cerebral palsy (odds ratio, 3.7; 95% CI, 1.1-11.9; p = 0.04). Intraoperative events were not predictive of need for respiratory support. Most of the children (n = 117/165 or 71%) had sleep studies preoperatively. Abnormal sleep studies (apnea-hypopnea index > 20 n = 68 or oxygen saturation nadir < 80% n = 48) were not associated with need for postoperative respiratory support.
Most children admitted to the ICU following adenotonsillectomy in this population required no support after 2 hours. Preoperative factors such as obesity and abnormal sleep studies were not predictive of need for postoperative respiratory support. Need for respiratory support at 2 hours may be a useful criterion for need for ICU level care in this population.
To assess how a change in practice to more frequent use of high-flow nasal cannula for the treatment of bronchiolitis would affect the use of invasive devices in children.
Retrospective cohort study ...of children under 2 years old admitted to the ICU with respiratory failure secondary to bronchiolitis. Outcomes and invasive device use were compared between two time periods, before and after the practice change.
Eighteen bed tertiary care PICU.
A total of 325 children: 146 from 2010 to 2012 and 179 from 2015 to 2016.
None.
There were no significant differences between the two time periods regarding gender, race/ethnicity, medical history, and viral profile, although children were younger in the earlier cohort (median age of 1.9 mo interquartile range, 1.2-3.5 vs 3.3 mo 1.7-8.6;
< 0.001). There was an increased use of noninvasive ventilation in the second time period (94% from 69%;
< 0.001), as well as a decreased frequency of intubation (13% from 42%;
< 0.001) and reduced central venous catheter placement (7% from 37%;
< 0.001). There was no significant difference in mortality between the two groups. A logistic regression analysis was conducted, which found that time period, intubation, and hospital length of stay were all independently associated with central venous catheter placement.
A practice change toward managing patients with bronchiolitis in respiratory failure with less invasive means was associated with a reduction in the use of other invasive devices. In our cohort, minimizing the use of invasive ventilation and devices was not associated with an increase in mortality and could potentially have additional benefits.
Background:
Use of dexmedetomidine in pediatric critical care is common, despite lack of prospective studies on its hemodynamic effects.
Objective:
To describe cardiovascular effects in critically ...ill children treated with a constant continuous infusion of dexmedetomidine without a loading dose at highest Food and Drug Administration-approved adult dose.
Methods:
Prospective, pilot study of 17 patients with dexmedetomidine infused at a rate of 0.7 μg/kg/h for 6 to 24 hours. Heart rate (HR) and blood pressure (BP) values over time were analyzed by a random effects mixed model.
Results:
Patients with median age of 1.6 years (1 month to 17 years) and median weight of 11.8 kg (2.8-84 kg) received an infusion for a mean of 16 ± 7.2 hours. There were no cardiac conduction abnormalities. One patient required discontinuation of infusion for predetermined low HR termination criteria at hour 13 of infusion; there was no clinical compromise and it coincided with planned extubation. Decreased HR of 20% from baseline was found in 35% of patients. The mean HR reduction was largest at hour 13 of infusion with a decrease of 13 ± 17 bpm from baseline, but HR changes over time were not statistically significant. Blood pressure effects included a decrease in 12% and an increase in 29%. There was a small but statistically significant increase in systolic BP of 0.4 mm Hg/h of infusion, P < .001.
Conclusion:
A continuous infusion of 0.7 μg/kg/h of dexmedetomidine without a loading dose for up to 24 hours in critically ill children had tolerable effects on HR and BP.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Organ donation after cardiac death is increasingly implemented, with outcomes similar to those of organ donation after brain death. Many hospitals hesitate to implement a protocol for donation after ...cardiac death because of the potential negative reactions among health care providers.
To determine the acceptance of a protocol for donation after cardiac death among multidisciplinary staff in a pediatric intensive care unit.
An anonymous, 15-question, Likert-scale questionnaire (scores 1-5) was used to determine the opinions of staff about donation after brain death and after cardiac death in a pediatric intensive care unit of a tertiary-care university hospital.
Survey response rate was 67% (n = 60). All physicians, 89% of nurses, and 82% of the remaining staff members stated that they understood the difference between donation after brain death and donation after cardiac death; staff supported both types of donation, at rates of 90% and 85%, respectively. Staff perception was the same for each type of donation (ρ = 0.82; r = 0.92; P < .001). The 20 staff members who provided care directly to patients who were donors after cardiac death considered such donation worthwhile. However, 60% of those providers offered suggestions to improve the established protocol for donation.
The multidisciplinary staff has accepted organ donation after cardiac death and has fully integrated this kind of donation without reported differences from their acceptance of donation after brain death.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Elevated surfactant protein D (SP-D) is a relatively specific indicator of lung injury and is associated with both acute and chronic lung disease in adults and respiratory distress syndrome in ...premature infants. The relationship between plasma SP-D and lung injury in children with acute respiratory failure is unclear.
Is plasma SP-D associated with lung injury or outcome in children with acute respiratory failure?
This was a prospective cohort study in children 2 weeks to 17 years of age with acute respiratory failure who participated in the BALI multi-center study. Analyses were done using SP-D levels in plasma from the first sample taken on either the day of intubation or one of the following 2 days. SP-D level was measured by enzyme-linked immunosorbent assay.
Plasma samples from 350 patients were used in the analysis; 233 had pediatric ARDS (PARDS). SP-D levels varied across primary diagnoses (P < .001). Elevated SP-D levels were associated with severe PARDS after adjusting for age, pediatric risk of mortality III (PRISM-III), and primary diagnosis (OR = 1.02; CI = 1.01-1.04; P = .011). Multivariable analyses also indicated that elevated SP-D levels were associated with death (OR = 1.02; CI = 1.01-1.04; P = .004), duration of mechanical ventilation (P = .012), PICU length of stay (P = .019), and highest oxygenation index (P = .040). SP-D levels also correlated with age (rs = 0.16, P = .002).
Elevated plasma SP-D levels are associated with severe PARDS and poor outcomes in children with acute respiratory failure. Future studies will determine whether SP-D can be used to predict the degree of lung injury or response to treatment and whether SP-D is useful in identifying PARDS endotypes.
The association of plasma interleukin-8 (IL-8), or IL-8 genetic variants, with pediatric acute respiratory distress syndrome (PARDS) in children with acute respiratory failure at risk for PARDS has ...not been examined. The purpose of this study was to examine the association of early and sequential measurement of plasma IL-8 and/or its genetic variants with development of PARDS and other clinical outcomes in mechanically ventilated children with acute respiratory failure.
This was a prospective cohort study of children 2 weeks to 17 years of age with acute airways and/or parenchymal lung disease done in 22 pediatric intensive care units participating in the multi-center clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). Plasma IL-8 levels were measured within 24 h of consent and 24 and 48 h later. DNA was purified from whole blood, and IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, were genotyped.
Five hundred forty-nine patients were enrolled; 480 had blood sampling. Plasma IL-8 levels ranged widely from 4 to 7373 pg/mL. Highest IL-8 levels were observed on the day of intubation with subsequent tapering. Levels of IL-8 varied significantly across primary diagnoses with the highest levels occurring in patients with sepsis and the lowest levels in those with asthma. Plasma IL-8 was strongly correlated with oxygenation defect and severity of illness. IL-8 was consistently higher in PARDS patients compared to those without PARDS; levels were 4-12 fold higher in non-survivors compared to survivors. On multivariable analysis, IL-8 was independently associated with death, duration of mechanical ventilation, and PICU length of stay on all days measured, but was not associated with PARDS development. There was no association between the IL-8 single nucleotide polymorphisms, rs4073, rs2227306, and rs2227307, and PARDS development or plasma IL-8 level.
When measured sequentially, plasma IL-8 was robustly associated with multiple, relevant clinical outcomes including mortality, but was not associated with PARDS development. The wide range of plasma IL-8 levels exhibited in this cohort suggests that further study into the heterogeneity of this patient population and its impact on individual responses to PARDS treatment is warranted.
Abstract
Background
Acute respiratory failure (ARF) can progress to acute respiratory distress syndrome and death. Biomarkers may allow for risk stratification and prognostic enrichment in ARF. ...Thrombomodulin (TM) is a transmembrane antithrombotic mediator expressed in endothelial cells. It is cleaved into its soluble form (sTM) during inflammation and vascular injury. Levels of sTM correlate with inflammation and end organ dysfunction.
Methods
This was a prospective observational study of 432 patients aged 2 weeks—17 years requiring invasive mechanical ventilation. It was ancillary to the multicenter clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). After consent, patients had up to 3 plasma samples collected at 24-h intervals within 5 days after intubation. sTM was assayed by ELISA. The Hazard ratio (HR) for 90-day mortality was determined by Cox regression. Mixed effect models (MEM) were used to test for association with extrapulmonary multiorgan failure (MOF) and oxygenation index (OI). Age, race, sex and PRISM-III scores were used as confounding variables for multivariable analyses.
Results
sTM values ranged from 16.6 to 670.9 ng/ml within 5 days after intubation. Higher sTM was associated with increased 90-day mortality (
n
= 432, adjusted HR = 1.003,
p
= 0.02) and worse OI in the first 5 days after intubation (
n
= 252, Estimate = 0.02,
p
< 0.01). Both initial and slope of sTM were associated with increased extrapulmonary MOF in unadjusted and adjusted analyses (Intercept, Estimate = 0.003,
p
< 0.0001; and slope, Estimate = 0.01,
p
= 0.0009,
n
= 386).
Conclusions
Plasma sTM is associated with mortality, severity of hypoxic respiratory failure and worsening extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in the pathogenesis of ARF and provides potential applicability towards targeted therapies.
Trial registration
:
https://clinicaltrials.gov/ct2/show/NCT00814099
.
In healthy lung endothelium, thrombomodulin (TM) recruits thrombin to activate Protein-C (PC/APC), that inhibits plasminogen activator-1 (PAI-1) and thrombosis. In inflamed and damaged endothelium, TM is cleaved into its soluble form (sTM), precluding its usual regulation of thrombosis. In this study, we measured plasma sTM levels in pediatric patients with respiratory failure and found that sTM correlated with mortality and other clinical markers of poor outcomes.
Objective To evaluate whether race or ethnicity was independently associated with parental refusal of consent for their child's participation in a multisite pediatric critical care clinical trial. ...Study design We performed a secondary analyses of data from Randomized Evaluation of Sedation Titration for Respiratory Failur e (RESTORE), a 31-center cluster randomized trial of sedation management in critically ill children with acute respiratory failure supported on mechanical ventilation. Multivariable logistic regression modeling estimated associations between patient race and ethnicity and parental refusal of study consent. Result Among the 3438 children meeting enrollment criteria and approached for consent, 2954 had documented race/ethnicity of non-Hispanic White (White), non-Hispanic Black (Black), or Hispanic of any race. Inability to approach for consent was more common for parents of Black (19.5%) compared with White (11.7%) or Hispanic children (13.2%). Among those offered consent, parents of Black (29.5%) and Hispanic children (25.9%) more frequently refused consent than parents of White children (18.2%, P < .0167 for each). Compared with parents of White children, parents of Black (OR 2.15, 95% CI 1.56-2.95, P < .001) and Hispanic (OR 1.44, 95% CI 1.10-1.88, P = .01) children were more likely to refuse consent. Parents of children offered participation in the intervention arm were more likely to refuse consent than parents in the control arm (OR 2.15, 95% CI 1.37-3.36, P < .001). Conclusions Parents of Black and Hispanic children were less likely to be approached for, and more frequently declined consent for, their child's participation in a multisite critical care clinical trial. Ameliorating this racial disparity may improve the validity and generalizability of study findings. Trial registration ClinicalTrials.gov : NCT00814099.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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