354 research outputs found
Gastroschisis and omphalocele
It has been widely acknowledged that exomphalos and gastroschisis are two different clinical entities. Their etiology and pathogenesis, however, remain controversial. Several techniques are available for making a prenatal diagnosis of these as well as many other malformations. Some prenatal treatment is possible, but operative management is the more usual course. In most cases, of omphalocele and gastroschisis, treated either conservatively or by any kind of surgery, intensive care is mandatory to support nutrition and often ventilation as well. Enterai nutrition at an early stage during the postoperative period might lead to bouts of necrotizing enterocolitis requiring aggressive medical treatment and sometimes even operative treatment
Neurocognitive Outcome After Treatment With(out) ECMO for Neonatal Critical Respiratory or Cardiac Failure
Over the years, it has become clear that children growing up after neonatal critical illness
are at high risk of long-term neurocognitive deficits that impact their school performance
and daily life activities. Although the pathophysiological mechanisms remain largely
unknown, emerging evidence seems to suggest that long-term neuropsychological
deficits following neonatal critical illness are not associated with the type of treatment,
such as extracorporeal membrane oxygenation (ECMO), but rather with underlying
disease processes. In this review, neurocognitive outcome and brain pathology
following neonatal critical respiratory and cardiac illness, either treated with or
without ECMO, are described and compared in order to gain insight into potential
underlying pathophysiological mechanisms. Putting these findings together, it becomes
apparent that both children with complex congenital heart disease and children who
survived severe respiratory failure are at risk of neurocognitive deficits later in life.
Neurorehabilitation strategies, such as Cogmed working-memory training, are discussed.
While prevention of neurocognitive deficits altogether should be strived for in the future,
this is not realistic at this moment. It is therefore of great importance that children growing
up after neonatal critical illness receive long-term care that includes psychoeducation and
personalized practical tools that can be used to improve their daily life activities
Developmental pharmacokinetics of morphine and its metabolites in neonates, infants and young children
BACKGROUND: Descriptions of the pharmacokinetics and metabolism of
morphine and its metabolites in young children are scant. Previous studies
have not differentiated the effects of size from those related to age
during infancy. METHODS: Postoperative children 0-3 yr old were given an
intravenous loading dose of morphine hydrochloride (100 micro g kg(-1) in
2 min) followed by either an intravenous morphine infusion of 10 micro g
h(-1) kg(-1) (n=92) or 3-hourly intravenous morphine boluses of 30 micro g
kg(-1) (n=92). Additional morphine (5 micro g kg(-1)) every 10 min was
given if the visual analogue (VAS, 0-10) pain score was >/=4. Arterial
blood (1.4 ml) was sampled within 5 min of the loading dose and at 6, 12
and 24 h for morphine, morphine-3-glucuronide (M3G) and
morphine-6-glucuronide (M6G). The disposition of morphine and formation
clearances of morphine base to its glucuronide metabolites and their
elimination clearances were estimated using non-linear mixed effects
models. RESULTS: The analysis used 1856 concentration observations from
184 subjects. Population parameter estimates and their variability (%) for
a one-compartment, first-order elimination model were as follows: volume
of distribution 136 (59.3) litres, formation clearance to M3G 64.3 (58.8)
litres h(-1), formation clearance to M6G 3.63 (82.2) litres h(-1),
morphine clearance by other routes 3.12 litres h(-1) per 70 kg,
elimination clearance of M3G 17.4 (43.0) litres h(-1), elimination
clearance of M6G 5.8 (73.8) litres h(-1). All parameters are standardized
to a 70 kg person using allometric 3/4 power models and reflect fully
mature adult values. The volume of distribution increased exponentially
with a maturation half-life of 26 days from 83 litres per 70 kg at birth;
formation clearance to M3G and M6G increased with a maturation half-life
of 88.3 days from 10.8 and 0.61 litres h(-1) per 70 kg respectively at
birth. Metabolite formation decreased with increased serum bilirubin
concentration. Metabolite clearance increased with age (maturation
half-life 129 days), and appeared to be similar to that described for
glomerular filtration rate maturation in infants. CONCLUSION: M3G is the
predominant metabolite of morphine in young children and total body
morphine clearance is 80% that of adult values by 6 months. A mean
steady-state serum concentration of 10 ng ml(-1) can be achieved in
children after non-cardiac surgery in an intensive care unit with a
morphine hydrochloride infusion of 5 micro g h(-1) kg(-1) at birth (term
neonates), 8.5 micro g h(-1) kg(-1) at 1 month, 13.5 micro g h(-1) kg(-1)
at 3 months and 18 micro g h(-1) kg(-1) at 1 year and 16 micro g h(-1)
kg(-1) for 1- to 3-yr-old children
The vulnerable microcirculation in the critically ill pediatric patient
In neonates, cardiovascular system development does not stop after the transition from intra-uterine to extra-uterine life and is not limited to the macrocirculation. The microcirculation (MC), which is essential for oxygen, nutrient, and drug delivery to tissues and cells, also develops. Developmental changes in the microcirculatory structure continue to occur during the initial weeks of life in healthy neonates. The physiologic hallmarks of neonates and developing children make them particularly vulnerable during critical illness; however, the cardiovascular monitoring possibilities are limited compared with critically ill adult patients. Therefore, the development of non-invasive methods for monitoring the MC is necessary in pediatric critical care for early identification of impending deterioration and to enable the initiation and titration of therapy to ensure cell survival. To date, the MC may be non-invasively monitored at the bedside using hand-held videomicroscopy, which provides useful information regarding the microcirculation. There is an increasing number of studies on the MC in neonates and pediatric patients; however, additional steps are necessary to transition MC monitoring from bench to bedside. The recently introduced concept of hemodynamic coherence describes the relationship between changes in the MC and macrocirculation. The loss of hemodynamic coherence may result in a depressed MC despite an improvement in the macrocirculation, which represents a condition associated with adverse outcomes. In the pediatric intensive care unit, the concept of hemodynamic coherence may function as a framework to develop microcirculatory measurements towards implementation in daily clinical practice
Assessment and significance of long-term outcomes in pediatric surgery
Treatment modalities for newborns with anatomical congenital anomalies have greatly improved over the past decades, with a concomitant increase in survival. This review will briefly discuss specific long-term outcomes to illustrate, which domains deserve to be considered in long-term follow-up of patients with anatomical congenital anomalies. Apart from having disease-specific morbidities these children are at risk for impaired neurodevelopmental problems and school failure, which may affect participation in society in later life. There is every reason to offer them long-term multidisciplinary follow-up programs. We further provide an overview of the methodology of long-term follow-up, its significance and discuss ways to improve care for newborns with anatomical congenital anomalies from childhood into adulthood. Future initiatives should focus on transition of care, risk stratification, and multicenter collaboration
Congenital diaphragmatic hernia: Comparison of animal models and relevance to the human situation
Congenital diaphragmatic hernia (CDH) occurs in 1 in 3,000 newborns. Mortality and morbidity are due to the amount of pulmonary hypoplasia (PH), the response on artificial ventilation and the presence of therapy-resistant pulmonary hypertension. The pathogenesis and etiology of CDH and its associated anomalies are still largely unknown despite all research efforts over the past years. Several animal models have been proposed to study CDH. In this review we compare surgical, pharmacological and transgenic models, and discuss their strengths and limitations to study PH
Pulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia
Lung hypoplasia and persistent pulmonary hypertension are the principal causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Amine-and peptide-producing pulmonary neuroendocrine cells (PNEC), widely distributed throughout the airway mucosa, are thought to play an important role in both pulmonary development and regulation of pulmonary vascular tone. Furthermore, recent studies show increased levels of calcitonin gene-related peptide (CGRP), a pulmonary vasodilator produced by PNEC, during chronic hypoxia. The article reports data on morphometric analysis of CGRP immunoreactive PNEC clusters (neuroepithelial bodies, NEB) in a rat model of CDH. CDH was induced in neonatal Sprague Dawley rats by oral administration of 2,4-dichloro-phenyl- p-nitro-phenylether (Nitrofen; Rohm Haas, Philadelphia, PA) to the mother at 10 days of gestation. Sections of lungs from term neonatal rats with and without CDH and controls were immunostained for CGRP (marker of NEB) with specific antibody against rat CGRP. NEB size and number of NEB/area of lung were assessed using a semiautomatic image analysis system. In lungs of neonatal rats with CDH, the number of NEB per surface area of lung parenchyma was significantly increased compared with the age-matched controls. Although the mean size of NEB was larger in CDH, the differences were not significant. This is the first study of PNEC in CDH. Whether the phenomenon observed in this study results in altered NEB function including imbalance in vasoactive mediators requires further studies, especially in the human being
Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia
Congenital diaphragmatic hernia (CDH) is associated with high neonatal
mortality from lung hypoplasia and persistent pulmonary hypertension.
Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related
peptide (CGRP), a potent vasodilator. We previously reported altered
distribution of CGRP-positive PNEC in full-term rats with CDH, that may
lead to an imbalance in vasoactive mediators. In the present study we
examined the expression of CGRP-positive PNEC during lung development in
rats with CDH induced by 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen).
Cesarean sections were performed on Days 16, 18, 20, or 22, and the lungs
were immunostained for CGRP and immunoreactive cells were quantitated
through image analysis. On Day 16, CGRP-immunoreactive staining was
negative; on Day 18, CGRP-immunoreactive cells were found in all controls
(not exposed to Nitrofen), whereas in CDH pups, CGRP-positive cells were
present in only four of six cases. On Day 20, CGRP immunoreactivity was
similar in CDH pups, Nitrofen-exposed pups without CDH, and controls. On
Day 22 (term), significantly more CGRP-positive cells (i.e., number of
positive cells per surface area [mm2] or lung volume [mm3]) were found in
ipsilateral lungs of CDH pups than in controls (P < 0.05). The difference
was even more striking in contralateral lungs of CDH pups (P < 0.001),
ruling out nonspecific effects of Nitrofen. In CDH lungs, the proportion
of immunostained epithelium and the size of the neuroendocrine cell
clusters (neuroepithelial bodies [NEB]) were not significantly different
from those of controls. On Day 22, supraoptimal dilution
immunocytochemistry yielded similar results in CDH pups and controls. We
conclude that in CDH, CGRP expression in PNEC and NEB is delayed during
early stages of lung development. Because CGRP also exhibits growth
factor-like properties for endothelium and epithelial cells, the lack of
this factor during a crucial developmental stage (canalicular period) may
be causally related to lung hypoplasia
Striving for an effective but parsimonious use of sedation in pediatric intensive care
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Pain in Intellectually Disabled Children: Towards Evidence-Based Pharmacotherapy?
This critical opinion article deals with the challenges of finding the most effective pharmacotherapeutic options for the management of pain in intellectually disabled children and provides recommendations for clinical practice and research. Intellectual disability can be caused by a wide variety of underlying diseases and may be associated with congenital anomalies such as cardiac defects, small-bowel obstructions or limb abnormalities as well as with comorbidities such as scoliosis, gastro-esophageal reflux disease, spasticity, and epilepsy. These conditions themselves or any necessary surgical interventions are sources of pain. Epilepsy often requires chronic pharmacological treatment with antiepileptic drugs. These antiepileptic drugs can potentially cause drug–drug interactions with analgesic drugs. It is unfortunate that children with intellectual disabilities often cannot communicate pain to caregivers. Although these children are at high risk of experiencing pain, researchers nevertheless often have to exclude them from trials on pain management because of ethical considerations. We therefore make a plea for prescribers, researchers, patient organizations, pharmaceutical companies, and policy makers to study evidence-based, safe and effective pharmacotherapy in these children through properly designed studies. In the meantime, parents and clinicians must resort to validated pain assessment tools such as the revised FLACC scale
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