Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Database
Language
Publication year range
1.
Article in English | MEDLINE | ID: mdl-38833575

ABSTRACT

BACKGROUND: Gastric tube insertion is necessary to support early enteral feeding of newborns during their neonatal intensive care stay. This frequent and invasive procedure is known to be painful. Very few analgesic techniques (sweet solutions, sucking, swaddling, and skin-to-skin contact) are available to reduce the pain caused by orogastric tube insertion procedure. OBJECTIVE: To determine whether a new orogastric tube insertion technique modifies the pain response in newborns, we hypothesize that inserting an orogastric tube through the nipple of a bottle reduces pain caused by this procedure. DESIGN: Prospective, controlled, randomized, multicentered and open label study. SETTINGS: Three neonatal intensive care units in France (2 level 3 units and 1 level 2B). PARTICIPANTS: Full-term or premature newborns at 32 weeks of gestation or more, postnatal age between 48 hours and 21 days, not ventilated and requiring enteral feeding, were randomized into 2 groups: usual technique (n = 36) and experimental technique (n = 35). METHODS: Our experimental technique was to insert the orogastric tube through a modified nipple of a bottle. This method was compared with the usual technique of inserting the tube directly into the newborn's mouth without a support to guide it accompanied by a nipple encouraging sucking with a nonnutritive solution. An association of nonnutritive sucking and orally administered 30% glucose was given to all children for analgesic purposes. Pain during the orogastric tube insertion was assessed on video recordings by 2 independent experts, using a heteroassessment behavioral scale for pain (DAN-Douleur Aiguë du Nouveau-né; APN-Acute Pain in Newborns). The primary outcome was an Acute Pain in Newborns score of less than 3 at the time of the procedure. Comparisons were made using Fisher exact test or Mann-Whitney U test. Factors associated with an Acute Pain in Newborns score of 3 and greater were explored using univariable and multivariable regression models. RESULTS: All but 1 video recording in each group were analyzed. Among the 34 neonates in the experimental group, 71.4% (95% CI: [53.7-85.4]) had an Acute Pain in Newborns score of less than 3 during orogastric tube insertion versus 41% (95% CI: [27.9-61.9]) in the control group (P = .031). Gagging was frequent and nonsignificantly different between the 2 groups (69% in the control group, 51% in the experimental group, P = .13). In multivariable analysis, the experimental technique was an independent factor of pain prevention compared with the usual technique (odds ratio = 0.21 [0.06-0.71], P = .015). CONCLUSIONS: This study suggests that a simple, inexpensive, and feasible technique of orogastric tube insertion through the nipple of a bottle limits pain associated with this procedure in newborns.

2.
Paediatr Neonatal Pain ; 3(2): 46-58, 2021 Jun.
Article in English | MEDLINE | ID: mdl-35547594

ABSTRACT

To describe the frequency and nature of premedication practices for neonatal tracheal intubation (TI) in 2011; to identify independent risk factors for the absence of premedication; to compare data with those from 2005 and to confront observed practices with current recommendations. Data concerning TI performed in neonates during the first 14 days of their admission to participating neonatal/pediatric intensive care units were prospectively collected at the bedside. This study was part of the Epidemiology of Procedural Pain in Neonates study (EPIPPAIN 2) conducted in 16 tertiary care units in the region of Paris, France, in 2011. Multivariate analysis was used to identify factors associated with premedication use and multilevel analysis to identify center effect. Results were compared with those of the EPIPPAIN 1 study, conducted in 2005 with a similar design, and to a current guidance for the clinician for this procedure. One hundred and twenty-one intubations carried out in 121 patients were analyzed. The specific premedication rate was 47% and drugs used included mainly propofol (26%), sufentanil (24%), and ketamine (12%). Three factors were associated with the use of a specific premedication: nonemergent TI (Odds ratio (OR) [95% CI]: 5.3 [1.49-20.80]), existence of a specific written protocol in the ward (OR [95% CI]:4.80 [2.12-11.57]), and the absence of a nonspecific concurrent analgesia infusion before TI (OR [95% CI]: 3.41 [1.46-8.45]). No center effect was observed. The specific premedication rate was lower than the 56% rate observed in 2005. The drugs used were more homogenous and consistent with the current recommendations than in 2005, especially in centers with a specific written protocol. Premedication use prior to neonatal TI was low, even for nonemergent procedures. Scientific consensus, implementation of international or national recommendations, and local written protocols are urgently needed to improve premedication practices for neonatal intubation.

3.
BMC Pediatr ; 20(1): 144, 2020 04 01.
Article in English | MEDLINE | ID: mdl-32238150

ABSTRACT

BACKGROUND: Lung recruitment at birth has been advocated as an effective method of improving the respiratory transition at birth. Sustained inflations (SI) and dynamic positive end-expiratory pressure (PEEP) were assessed in clinical and animal studies to define the optimal level. Our working hypothesis was that very low gestational age infants (VLGAI) < 32 weeks' gestation require an individualized lung recruitment based on combining both manoeuvers. METHODS: Between 2014 and 2016, 91 and 72 inborn VLGAI, requiring a respiratory support beyond a continuous positive airway pressure (CPAP) = 5 cmH2O, were enrolled before and after introducing these manoeuvers based on progressive increase in SI up to 15 s, with simultaneous gradual increase in PEEP up to 15 cmH2O, according to the cardiorespiratory response. Retrospective comparisons of the incidence of mechanical ventilation (MV) < 72 h of life, short-term and before discharge morbidity were then performed. RESULTS: Among extremely low gestational age infants (ELGAI) < 29 weeks' gestation, the following outcomes decreased significantly: intubation (90 to 55%) and surfactant administration (54 to 12%) in the delivery room, MV (92 to 71%) and its mean duration < 72 h of life (45 h to 13 h), administration of a 2nd dose of surfactant (35 to 12%) and postnatal corticosteroids (52 to 19%), and the rate of bronchopulmonary dysplasia (23 to 5%). Among VLGAI, all of these results were also significant. Neonatal mortality and morbidity were not different. CONCLUSIONS: In our setting, combining two individualized lung recruitment maneuvers at birth was feasible and may be beneficial on short-term and before discharge pulmonary outcomes. A randomized controlled trial is needed to confirm these results.


Subject(s)
Bronchopulmonary Dysplasia , Respiratory Distress Syndrome, Newborn , Bronchopulmonary Dysplasia/epidemiology , Bronchopulmonary Dysplasia/prevention & control , Cesarean Section , Feasibility Studies , Female , Gestational Age , Humans , Infant, Newborn , Lung , Male , Pregnancy , Respiration, Artificial , Respiratory Distress Syndrome, Newborn/therapy , Retrospective Studies
4.
Stem Cells Dev ; 21(15): 2789-97, 2012 Oct 10.
Article in English | MEDLINE | ID: mdl-22533467

ABSTRACT

Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity. Bone marrow derived-mesenchymal stem cells (BM-MSC) prevent lung injury in an O(2)-induced model of BPD. The low level of lung BM-MSC engraftment suggests alternate mechanisms-beyond cell replacement-to account for their therapeutic benefit. We hypothesized that BM-MSC prevent O(2)-induced BPD through a paracrine-mediated mechanism and that preconditioning of BM-MSC would further enhance this paracrine effect. To this end, conditioned medium (CM) from BM-MSC (MSCcm) or preconditioned CM harvested after 24 h of BM-MSC exposure to 95% O(2) (MSC-O2cm) were administrated for 21 days to newborn rats exposed to 95% O(2) from birth until postnatal day (P)14. Rat pups exposed to hyperoxia had fewer and enlarged air spaces and exhibited signs of pulmonary hypertension (PH), assessed by echo-Doppler, right ventricular hypertrophy, and pulmonary artery medial wall thickness. Daily intraperitoneal administration of both CM preserved alveolar growth. MSC-O2cm exerted the most potent therapeutic benefit and also prevented PH. CM of lung fibroblasts (control cells) had no effect. MSCcm had higher antioxidant capacity than control fibroblast CM. Preconditioning did not increase the antioxidant capacity in MSC-O2cm but produced higher levels of the naturally occurring antioxidant stanniocalcin-1 in MSC-O2cm. Ex vivo preconditioning enhances the paracrine effect of BM-MSC and opens new therapeutic options for cell-based therapies. Ex vivo preconditioning may also facilitate the discovery of MSC-derived repair molecules.


Subject(s)
Bronchopulmonary Dysplasia/prevention & control , Hyperoxia/complications , Mesenchymal Stem Cells/physiology , Oxygen/pharmacology , Paracrine Communication , Animals , Animals, Newborn , Antioxidants/metabolism , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Bone Marrow Cells/physiology , Bronchopulmonary Dysplasia/diagnostic imaging , Bronchopulmonary Dysplasia/etiology , Cells, Cultured , Culture Media, Conditioned/pharmacology , Gene Expression , Glycoproteins/genetics , Glycoproteins/metabolism , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/prevention & control , Infant, Newborn , Lung/pathology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Pulmonary Artery/pathology , Rats , Rats, Sprague-Dawley , Ultrasonography
5.
Mol Ther ; 15(11): 2008-16, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17653105

ABSTRACT

Transient overexpression of genes involved in lung regulation might prevent alveolar developmental disorders (ADDs) in premature neonates. However, adenovirus 5 (Ad5) vectors per se, and not isolated capsid proteins, induce ADDs after tracheal administration to newborn rats. To test the hypothesis that Ad5 capsid components are mainly responsible for ADDs, we evaluated newborn rats' lung development by morphometry after tracheal administration of a panel of Ad5 vectors with mutations in the fiber or penton base. Three distinct patterns of lung response were observed on postnatal day (PD) 21: (i) emphysematous-like lesions, common to Ad5 overexposing RGD motifs; (ii) altered septation, representative of the wild-type capsid Ad5 lesion; (iii) absence of lung toxicity, shown by Ad5 vectors with fibers shortened to seven repeats. None of these patterns correlated with the degree of lung inflammation or gene transduction. In contrast, a more impaired elastogenesis associated with emphysema was preceded by a significantly increased level of activated caspase 3 on PD11. Moreover, the altered septation was associated with a persistent and significant increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive alveolar septal cells on PD21. Our results underline the deleterious effects of Ad-induced apoptosis, which is not only responsible for limited transgene expression but also involved in lung development disorders.


Subject(s)
Adenoviridae/genetics , Capsid Proteins/metabolism , Genetic Vectors/genetics , Genetic Vectors/toxicity , Lung/cytology , Lung/growth & development , Animals , Capsid Proteins/genetics , Caspase 3/metabolism , Cell Line , Cell Shape , Humans , Infant, Newborn , Pneumonia/enzymology , Pneumonia/pathology , Rats , Rats, Sprague-Dawley , Transduction, Genetic
6.
Hum Gene Ther ; 16(11): 1298-306, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16259563

ABSTRACT

Transient local overexpression of genes that promote lung defense or repair may help to protect or promote alveolar development in premature neonates. We showed that the use of adenoviral vectors in neonates was limited by the induction of lung growth disorders. In the present work we compare the efficiency of gene transfer to the neonatal lung by three adeno-associated viral vectors: rAAV1, rAAV2, and rAAV5. Transduction efficiency was first measured in vitro, by infecting A549 immortalized human lung epithelial cells, and primary epithelial and mesenchymal cells isolated from human fetal lung. AAV vectors yielded similar low levels of luciferase gene expression in the different cell types. In vivo transduction efficiency was evaluated in newborn rats, with AAV-LacZ vectors being intratracheally instilled at 3 days of age. Both rAAV5 and rAAV1, but not rAAV2, induced significant lung beta-galactosidase expression, which persisted on day 35. Highest beta- galactosidase levels were measured with rAAV5, but remained far lower than those obtained with adenoviral vectors. A transient increase in alveolar macrophages was observed on day 6, but not on day 8, after rAAV5-LacZ instillation. Morphometric evaluation of lung structures was performed on day 21, and showed no altered lung growth. We conclude that rAAV1 or rAAV5 was more efficient at mediating gene transfer in the neonatal lung than was rAAV2, without adversely affecting lung development. However, in vivo transgene expression was relatively low, and needs to be improved for future therapeutic use of these adeno-associated vectors.


Subject(s)
Dependovirus/genetics , Genetic Vectors/administration & dosage , Animals , Animals, Newborn , Cell Line, Tumor , Humans , Lac Operon , Lung/growth & development , Rats , Rats, Sprague-Dawley , Recombination, Genetic
7.
Hum Gene Ther ; 13(15): 1873-85, 2002 Oct 10.
Article in English | MEDLINE | ID: mdl-12396619

ABSTRACT

Local overexpression of genes that promote lung defense or repair may be helpful in protecting the immature neonatal lung from injuries, but whether the vectors used to administer these genes affect physiological postnatal lung growth has not been investigated. We explored the effect on alveolarization of E1-deleted Adnull vector (Ad5-LMP-null) given intratracheally to 3-day-old rats. Three Adnull doses were evaluated 10(8), 5 x 10(8), and 10(9) TCID(50). Lung morphometry on day 21 showed significant growth disorders with the two higher doses. With 5 x 10(8) TCID(50), absolute lung volume increased significantly (+16%), as did absolute (+20%) and specific (+32%) alveolar airspace volumes, whereas alveolar surface density decreased by 13% (p < 0.009 for all parameters). Lung inflammation was mild, nonsignificant, and occurred mainly with the highest Adnull dose, indicating that it was unlikely to contribute to our results. Adnull instillation induced a significant#10; decrease in terminal bronchiolar cell proliferation as evaluated by proliferating cell nuclear antigen immunostaining (p = 0.02), as well as a 23% decrease in absolute parenchyma elastic fiber length (p = 0.02). Furthermore, lung tropoelastin mRNA content decreased by 25% (p < 0.02). In conclusion, E1-deleted adenoviral vectors can induce lung growth disorders when instilled into the airways of neonatal rats. Interactions with lung matrix turnover may be the main explanation to these deleterious effects.


Subject(s)
Adenoviruses, Human/physiology , Genetic Vectors/toxicity , Lung/virology , Adenovirus E1A Proteins/deficiency , Adenovirus E1A Proteins/physiology , Adenoviruses, Human/genetics , Animals , Animals, Newborn , Bronchi/pathology , Bronchi/virology , Bronchoalveolar Lavage Fluid , Cell Division , Defective Viruses/genetics , Defective Viruses/physiology , Dose-Response Relationship, Drug , Elastic Tissue/pathology , Elastin/metabolism , Epithelial Cells/pathology , Gene Expression Regulation, Viral , Genes, Reporter , Genetic Vectors/pharmacology , Inflammation , Instillation, Drug , Lung/metabolism , Lung/pathology , Lung Volume Measurements , RNA, Messenger/biosynthesis , Rats , Recombinant Fusion Proteins/biosynthesis , Trachea , Transfection , Tropoelastin/biosynthesis , Tropoelastin/genetics , beta-Galactosidase/biosynthesis , beta-Galactosidase/genetics
8.
Am J Physiol Lung Cell Mol Physiol ; 282(3): L491-500, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11839543

ABSTRACT

Postnatal lung growth disorders may involve imbalance between metalloproteinases and their inhibitors. Inflammatory cell 92-kDa gelatinase overactivity has been reported in adults with lung injury but has not been looked for in neonates. We compared gelatinase activity in neonatal and adult rats and evaluated postnatal lung growth after lipopolysaccharide (LPS)-induced lung injury. Significant intra-alveolar inflammatory cell recruitment occurred in adults and neonates; cell counts increased 16-fold in adults and 2.7-fold in neonates. Total 92-kDa gelatinase activity was increased in neonates and adults and was significantly correlated to inflammatory cell counts. For a given cell count, 92-kDa gelatinase increased more in neonates than in adults. Morphometric neonatal lung analysis showed that LPS-injured lungs had decreases in absolute values of lung volume (P < 0.03), alveolar surface (P < 0.004), and air space volume (P < 0.03). Doxycycline, a nonspecific metalloproteinase inhibitor, partly inhibited LPS-induced 92-kDa gelatinase overactivity but did not improve LPS-induced alveolar growth disorders. LPS-mediated lung injury in neonatal rats induced both gelatinase B overactivity and alveolar growth disorders, although no causal link between these two effects was demonstrated.


Subject(s)
Animals, Newborn/physiology , Lipopolysaccharides , Pneumonia/chemically induced , Animals , Dose-Response Relationship, Drug , Doxycycline/adverse effects , Doxycycline/pharmacology , Drug Synergism , Gelatinases/antagonists & inhibitors , Gelatinases/metabolism , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/pharmacology , Lung/drug effects , Lung/growth & development , Metalloendopeptidases/antagonists & inhibitors , Pneumonia/physiopathology , Rats , Rats, Sprague-Dawley , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL