In this multicenter randomized, controlled trial, withholding parenteral nutrition from critically ill children in the pediatric intensive care unit for 1 week was clinically superior to providing ...early parenteral nutrition. Fluid loading was provided in both groups.
Critically ill children cannot normally be fed by mouth, and as a result a pronounced macronutrient deficit often develops after a few days. This macronutrient deficit has been associated with infections, weakness, prolonged mechanical ventilation, and delayed recovery.
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In order to prevent or limit the development of this macronutrient deficit, current guidelines, which are based largely on small studies with surrogate end points and on expert opinion, advise care providers to initiate nutritional support soon after a child’s admission to the pediatric intensive care unit (ICU).
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The preferred route for the administration of nutritional support in the pediatric . . .
Background
This position statement provides clinical recommendations for the assessment of pain, level of sedation, iatrogenic withdrawal syndrome and delirium in critically ill infants and children. ...Admission to a neonatal or paediatric intensive care unit (NICU, PICU) exposes a child to a series of painful and stressful events. Accurate assessment of the presence of pain and non-pain-related distress (adequacy of sedation, iatrogenic withdrawal syndrome and delirium) is essential to good clinical management and to monitoring the effectiveness of interventions to relieve or prevent pain and distress in the individual patient.
Methods
A multidisciplinary group of experts was recruited from the members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). The group formulated clinical questions regarding assessment of pain and non-pain-related distress in critically ill and nonverbal children, and searched the PubMed/Medline, CINAHL and Embase databases for studies describing the psychometric properties of assessment instruments. Furthermore, level of evidence of selected studies was assigned and recommendations were formulated, and grade or recommendations were added on the basis of the level of evidence.
Results
An ESPNIC position statement was drafted which provides clinical recommendations on assessment of pain (
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= 5), distress and/or level of sedation (
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= 4), iatrogenic withdrawal syndrome (
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= 3) and delirium (
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= 3). These recommendations were based on the available evidence and consensus amongst the experts and other members of ESPNIC.
Conclusions
This multidisciplinary ESPNIC position statement guides professionals in the assessment and reassessment of the effectiveness of treatment interventions for pain, distress, inadequate sedation, withdrawal syndrome and delirium.
Congenital diaphragmatic hernia (CDH) is a condition with a highly variable outcome. Some infants have a relatively mild disease process, whereas others have significant pulmonary hypoplasia and ...hypertension. Identifying high-risk infants postnatally may allow for targeted therapy.
Data were obtained on 2202 infants from the Congenital Diaphragmatic Hernia Study Group database from January 2007 to October 2011. Using binary baseline predictors generated from birth weight, 5-minute Apgar score, congenital heart anomalies, and chromosome anomalies, as well as echocardiographic evidence of pulmonary hypertension, a clinical prediction rule was developed on a randomly selected subset of the data by using a backward selection algorithm. An integer-based clinical prediction rule was created. The performance of the model was validated by using the remaining data in terms of calibration and discrimination.
The final model included the following predictors: very low birth weight, absent or low 5-minute Apgar score, presence of chromosomal or major cardiac anomaly, and suprasystemic pulmonary hypertension. This model discriminated between a population at high risk of death (∼50%) intermediate risk (∼20%), or low risk (<10%). The model performed well, with a C statistic of 0.806 in the derivation set and 0.769 in the validation set and good calibration (Hosmer-Lemeshow test, P = .2).
A simple, generalizable scoring system was developed for CDH that can be calculated rapidly at the bedside. Using this model, intermediate- and high-risk infants could be selected for transfer to high-volume centers while infants at highest risk could be considered for advanced medical therapies.
The primary lung bud originates from the foregut and develops into the bronchial tree by repetitive branching and outgrowing of the airway. The Sry related HMG box protein Sox2 is expressed in a ...cyclic manner during initiation and branching morphogenesis of the lung. It is highly expressed in non-branching regions and absent from branching regions, suggesting that downregulation of Sox2 is mandatory for airway epithelium to respond to branch inducing signals. Therefore, we developed transgenic mice that express a doxycycline inducible Sox2 in the airway epithelium. Continuous expression of Sox2 hampers the branching process resulting in a severe reduction of the number of airways. In addition, the bronchioli transiently go over into enlarged, alveolar-like airspaces, a pathology described as bronchiolization of alveoli. Furthermore, a substantial increase was observed of cGRP positive neuroendocrine cells and ΔNp63 isoform expressing (pre-) basal cells, which are both committed precursor-like cells. Thus, Sox2 prevents airways from branching and prematurely drives cells into committed progenitors, apparently rendering these committed progenitors unresponsive to branch inducing signals. However, Sox2 overexpression does not lead to a complete abrogation of the epithelial differentiation program.
Abstract Background/purpose Congenital diaphragmatic hernia (CDH) remains a significant cause of neonatal death. A wide spectrum of disease severity and treatment strategies makes comparisons ...challenging. The objective of this study was to create a standardized reporting system for CDH. Methods Data were prospectively collected on all live born infants with CDH from 51 centers in 9 countries. Patients who underwent surgical correction had the diaphragmatic defect size graded (A–D) using a standardized system. Other data known to affect outcome were combined to create a usable staging system. The primary outcome was death or hospital discharge. Results A total of 1,975 infants were evaluated. A total of 326 infants were not repaired, and all died. Of the remaining 1,649, the defect was scored in 1,638 patients. A small defect (A) had a high survival, while a large defect was much worse. Cardiac defects significantly worsened outcome. We grouped patients into 6 categories based on defect size with an isolated A defect as stage I. A major cardiac anomaly (+) placed the patient in the next higher stage. Applying this, patient survival is 99% for stage I, 96% stage II, 78% stage III, 58% stage IV, 39% stage V, and 0% for non-repair. Conclusions The size of the diaphragmatic defect and a severe cardiac anomaly are strongly associated with outcome. Standardizing reporting is imperative in determining optimal outcomes and effective therapies for CDH and could serve as a benchmark for prospective trials.
Purpose
Sedatives administered to critically ill children should be titrated to effect, because both under- and oversedation may have negative effects. We conducted a systematic review to examine ...reported incidences of under-, optimal, and oversedation in critically ill children receiving intensive care.
Methods
A systematic literature search using predefined criteria was performed in PubMed and Embase to identify all articles evaluating level of sedation in PICU patients receiving continuous sedation. Two authors independently recorded: study objective, study design, sample size, age range, details of study intervention (if applicable), sedatives used, length of sedation, sedation scale used, and incidences of optimal, under-, and oversedation as defined in the studies.
Results
Twenty-five studies were included. Two studies evaluated sedation level as primary study outcome; the other 23 as secondary outcomes. Together, these studies investigated 1,163 children; age range, 0–18 years. Across studies, children received many different sedative agents and sedation level was assessed with 12 different sedation scales. Optimal sedation was ascertained in 57.6 % of the observations, under sedation in 10.6 %, and oversedation in 31.8 %.
Conclusions
This study suggests that sedation in the PICU is often suboptimal and seldom systematically evaluated. Oversedation is more common than undersedation. As oversedation may lead to longer hospitalization, tolerance, and withdrawal, preventing oversedation in pediatric intensive care deserves greater attention.
To study whether new pharmacological and nonpharmacological guidelines lowered numbers of painful procedures in neonates and changed the amount and frequency of analgesic therapy as compared to the ...results of our previous study in 2001.
A prospective observational study.
Level III NICU of the Erasmus MC-Sophia Children's Hospital, Rotterdam.
Neonates admitted at postnatal ages less than 3 days with length of stay at least 72 h.
Number of all potentially painful procedures and analgesic therapy recorded at the bedside during the first 14 days of NICU stay.
A total number of 21,076 procedures were performed in the 175 neonates studied during 1,730 patient-days (mean 12.2). The mean number of painful procedures per neonate per day was 11.4 (SD 5.7), significantly lower than the number of 14.3 (SD 4.0) in 2001 (p < 0.001). The use of analgesics was 36.6% compared to 60.3% in 2001. Sixty-three percent of all peripheral arterial line insertions failed versus 37.5% in 2001 and 9.1% venipunctures failed versus 21% in 2001.
The mean number of painful procedures per NICU patient per day declined. Nonpharmacological pain- or stress-reducing strategies like NIDCAP and sucrose were fully embedded in our pain management. As further reduction of the number of painful procedures is unlikely, we should apply more nonpharmacological interventions and explore newer pharmacological agents.
SOX2 expression levels are crucial for the balance between maintenance and differentiation of airway progenitor cells during development and regeneration. Here, we describe patterning of the mouse ...proximal airway epithelium by SOX21, which coincides with high levels of SOX2 during development. Airway progenitor cells in this SOX2+/SOX21+ zone show differentiation to basal cells, specifying cells for the extrapulmonary airways. Loss of SOX21 showed an increased differentiation of SOX2+ progenitor cells to basal and ciliated cells during mouse lung development. We propose a mechanism where SOX21 inhibits differentiation of airway progenitors by antagonizing SOX2-induced expression of specific genes involved in airway differentiation. Additionally, in the adult tracheal epithelium, SOX21 inhibits basal to ciliated cell differentiation. This suppressing function of SOX21 on differentiation contrasts SOX2, which mainly drives differentiation of epithelial cells during development and regeneration after injury. Furthermore, using human fetal lung organoids and adult bronchial epithelial cells, we show that SOX2+/SOX21+ regionalization is conserved. Lastly, we show that the interplay between SOX2 and SOX21 is context and concentration dependent leading to regulation of differentiation of the airway epithelium.
Painful procedures in early life cause acute pain and can alter pain processing at a spinal level lasting into adulthood. Current methods of analgesia seem unable to prevent both acute and long-term ...hypersensitivity associated with neonatal pain. The current study aims to prevent acute and long-term hypersensitivity associated with neonatal procedural pain using methadone analgesia in rat pups.
Sprague-Dawley rat pups received either methadone (1 mg/kg) or saline prior to repetitive needle pricks into the left hind paw from the day of birth (postnatal day (P)0) to P7. Control littermates received a tactile stimulus. Mechanical sensitivity was assessed during the neonatal period (P0-P7), from weaning to adulthood (3-7 weeks) and following surgical re-injury of the same dermatome in adulthood.
Methadone administration completely reversed acute hypersensitivity from P0 to P7. In addition, neonatal methadone analgesia prevented prolonged hypersensitivity after re-injury in adulthood, without affecting sensitivity from weaning to adulthood.
The current study shows that neonatal methadone analgesia can attenuate acute as well as long-term hypersensitivity associated with neonatal procedural pain in a rat model.
Methadone treatment attenuates acute and long-term hypersensitivity associated with neonatal pain in a rat model. Clinical effectiveness studies are urgently warranted to assess acute and long-term analgesic effectivity of methadone.
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