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1.
Arch Pediatr ; 17(4): 399-406, 2010 Apr.
Article in French | MEDLINE | ID: mdl-20219332

ABSTRACT

The process of weaning from mechanical ventilation (WMV) is the same in children as in adults. In the pediatric literature, weaning failure rate ranges from 1.4 to 34%. So far, no indices of weaning success have been demonstrated to be sufficiently accurate. The criteria for assessing readiness to wean, which must be screened daily, have neither been validated nor adapted to the pediatric population. The spontaneous breathing test (SBT), the reference screening test for weaning, precedes extubation; it can be achieved with pressure support ventilation or spontaneous breathing (T piece or canopy or flow-inflating bag). A standardized weaning protocol (which can be computer driven) was used in only three pediatric studies and the impact on shortening the duration of mechanical ventilation has not yet been demonstrated. It should be paired with a sedative interruption protocol. Weaning criteria, SBT criteria, and/or protocol tolerance are guides, but clinicians must individualize decisions to use these criteria. The use of noninvasive ventilation is increasing and its place in weaning protocols for children needs to be determined; it might modify the definitions of weaning failure and weaning success in the future.


Subject(s)
Respiratory Insufficiency/therapy , Ventilator Weaning/methods , Adult , Child , Child, Preschool , Humans , Hypoxia/physiopathology , Hypoxia/therapy , Infant , Oxygen/blood , Oxygen Inhalation Therapy , Prognosis , Respiration, Artificial/methods , Respiratory Insufficiency/physiopathology , Therapy, Computer-Assisted , Work of Breathing/physiology
3.
Biol Neonate ; 88(2): 73-8, 2005.
Article in English | MEDLINE | ID: mdl-15785018

ABSTRACT

OBJECTIVE: Adaptation to extra-uterine life requires dramatic increase in pulmonary blood flow. Mechanisms that induce pulmonary vasodilatation at birth are incompletely understood but include alveolar ventilation, increase in PaO2, and production of vasoactive mediators. We hypothesized that antenatal glucocorticoids (GC) increase pulmonary vasodilatation to birth-related stimuli. STUDY DESIGN: To test this hypothesis, we studied the pulmonary hemodynamic response at birth to mechanical ventilation with low (<10%) and then with high (100%) FiO2 in chronically prepared late-gestation fetal lambs treated or not by antenatal maternal steroids. RESULTS: Basal mean aortic and pulmonary artery pressure (PAP), left pulmonary blood flow, pulmonary vascular resistance (PVR), and blood gas were similar between control and dexamethasone-treated animals (GC group). During mechanical ventilation with low FiO2, mean PVR decreased by 40% in the control group (from 0.44 +/- 0.01 to 0.25 +/- 0.01 mm Hg/ml/min) and by 60% in the GC group (from 0.44 +/- 0.02 to 0.19 +/- 0.02 mm Hg/ml/min) (p < 0.01). When subsequently ventilated with 100% O2, there was no difference in PVR decrease between groups (0.15 +/- 0.02 mm Hg/ml/min in the GC group vs. 0.14 +/- 0.01 mm Hg/ml/min in the control group). CONCLUSION: Antenatal GC enhance pulmonary vasodilatation induced by alveolar ventilation at birth but do not alter the pulmonary vascular response to O2. We speculate that antenatal steroids exposure improve adaptation at birth through acceleration of both parenchymal and vascular lung maturation.


Subject(s)
Adaptation, Physiological/drug effects , Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Pulmonary Circulation/drug effects , Animals , Animals, Newborn , Female , Fetus/drug effects , Hemodynamics , Oxygen/analysis , Pregnancy , Pregnancy, Animal , Sheep , Vasodilation/drug effects
4.
Br J Anaesth ; 93(6): 818-24, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15465842

ABSTRACT

BACKGROUND: This experimental study was performed to determine the effects of norepinephrine on: (i) the pulmonary vascular tone during the development of pulmonary hypertension (PH) in the fetus and (ii) the circulatory adaptation at birth after chronic intrauterine PH. METHODS: Chronically instrumented fetal lambs were randomized into two groups: (i) a group with PH obtained by antenatal partial ligation of the ductus arteriosus (DA) (n=9) and (ii) a control group without DA ligation (n=6). Pulmonary vascular responses to norepinephrine (1.5 microg min(-1)) were measured in utero 7 days after surgery. At day 8 post-surgery, after delivery, animals were ventilated for 3 h with oxygen 100%. The group with PH was randomly assigned to receive norepinephrine or saline. RESULTS: Mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were higher in the PH group (P<0.01). Norepinephrine-induced decrease in PVR was more pronounced in the PH group than in the control group (63 vs 35%, respectively; P<0.01). In the PH group, the decrease in PVR during mechanical ventilation was greater in the animals receiving norepinephrine than in the animal receiving saline (from 1.05 (0.12) to 0.1 (0.02) vs from 1.04 (0.1) to 0.2 (0.04) mm Hg ml(-1) min(-1), respectively; P<0.01). After 3 h of ventilation, mean PVR in the PH lambs treated by norepinephrine was similar to those measured in the control lambs. Aortic pressure was higher in the group treated with norepinephrine. CONCLUSION: The data suggest that norepinephrine may improve post-natal pulmonary adaptation in the newborn with persistent PH both by increasing systemic vascular pressure and by increasing pulmonary blood flow.


Subject(s)
Fetal Diseases/drug therapy , Hypertension, Pulmonary/drug therapy , Lung/drug effects , Norepinephrine/therapeutic use , Vasodilator Agents/therapeutic use , Adaptation, Physiological/drug effects , Animals , Animals, Newborn , Fetal Diseases/physiopathology , Hemodynamics/drug effects , Hypertension, Pulmonary/physiopathology , Lung/blood supply , Pulmonary Circulation/drug effects , Sheep, Domestic , Statistics, Nonparametric , Vascular Resistance/drug effects
5.
Intensive Care Med ; 30(7): 1461-7, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15138670

ABSTRACT

OBJECTIVES: To assess the reproducibility of respiratory dead space measurements in ventilated children. DESIGN: Prospective study. SETTING: University pediatric intensive care unit. PATIENTS: Thirty-two mechanically ventilated children (0.13-15.4 years) who were clinically stable. METHODS: The single-breath CO(2) test (SBT-CO(2)) was recorded using the CO(2)SMO Plus from the mean of 30 ventilatory cycles during 1 h (at T0, T15, T30, T45, and T60). Airway dead space was determined automatically (Novametrix Medical Systems, USA), and manually by Bohr- Enghoff equations using data obtained by SBT-CO(2). At the end of the study period, arterial blood gas was sampled in order to calculate alveolar and physiologic dead space. Intrasubject reproducibility of measurements was evaluated by the intraclass correlation coefficient. Two-way analysis of variance was used to evaluate the relationships between time and measurements. The two methods for calculating airway dead space were compared by using two-tailed Student's t-test and Bland-Altman analysis. RESULTS: Airway dead space measurement had a good reproducibility during the 1-h period, whatever the method used (intraclass correlation coefficient: 0.84 to 0.87). No significant difference was observed with time. Airway dead space values from the SBT-CO(2) method were smaller than those from Bohr-Enghoff equations. Physiologic dead space values from the SBT-CO2 method were similar to those from Bohr-Enghoff equations. CONCLUSION: The measurement of airway dead space by the CO(2)SMO Plus was reproducible over a 1-h period in children requiring mechanical ventilation, provided ventilatory parameters were constant throughout the study. SBT-CO(2) analysis may provide a bedside non-invasive monitoring of volumetric capnography.


Subject(s)
Carbon Dioxide/analysis , Respiration, Artificial/methods , Respiratory Dead Space/physiology , Adolescent , Blood Gas Analysis , Child , Child, Preschool , Humans , Infant , Lung Diseases/physiopathology , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Prospective Studies , Reproducibility of Results
6.
Pediatr Pulmonol ; 37(6): 485-91, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15114548

ABSTRACT

The end-expiratory lung-volume level of premature newborn infants is maintained above passive resting volume during active breathing, through the combination of reduced time constant and high respiratory rate. To determine whether nasal continuous positive airway pressure (NCPAP) alters this characteristic dynamic breathing pattern, we studied the effects of various NCPAP levels on the dynamic elevation of end-expiratory lung volume level (DeltaEELV) in spontaneously breathing premature newborn infants, using respiratory inductive plethysmography (RIP). Eleven premature newborn infants with moderate respiratory failure were included. NCPAP levels were set in a random order to 0, 2, 4, and 6 cm H2O. Tidal volume (Vt), rib-cage contribution to Vt (%RC), phase angle between abdominal and thoracic motions (theta), respiratory rate (RR), and inspiratory and expiratory times (Ti and Te) were continuously recorded by RIP. The slope of the linear part of the expiratory flow-volume relation was extrapolated up to zero flow level to evaluate the dynamic elevation of the functional residual capacity (FRC) (DeltaEELV). The time-constant of the respiratory system (tauRS) was calculated as the slope of the linear part of the expiratory flow-volume loop. At NCPAP = 6 cm H2O, DeltaEELV reached 0.6 +/- 0.2 times the Vt at NCPAP = 0 cm H2O. An increase in NCPAP level resulted in a significant decrease in DeltaEELV (P < 0.01). A decrease in DeltaEELV during NCPAP was associated with a significant increase in Te from 0.62 +/- 0.13 sec at NCPAP = 0 cm H2O to 0.80 +/- 0.07 sec at NCPAP = 6 cm H2O (P < 0.05), and a decrease in tauRS from 0.4 +/- 0.1 sec at NCPAP = 0 cm H2O to 0.24 +/- 0.04 sec at NCPAP = 6 cm H2O (P < 0.01). These results indicate that the characteristic spontaneous breathing pattern causing a dynamic elevation of FRC is abolished by NCPAP. We speculate that the dynamic volume-preserving mechanisms resulting from expiratory flow braking are no longer required during NCPAP, as the constant pressure may passively elevate FRC.


Subject(s)
Infant, Premature , Positive-Pressure Respiration , Respiration , Female , Functional Residual Capacity , Humans , Infant, Newborn , Lung Volume Measurements , Male , Nasal Cavity
7.
Am J Obstet Gynecol ; 189(1): 208-15, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12861164

ABSTRACT

OBJECTIVES: Although mechanisms of glucocorticoids-induced parenchymal lung maturation have been largely studied, little is known about the pulmonary vascular effects of antenatal glucocorticoids (GCs). We therefore hypothesized that antenatal GCs may alter the hemodynamic response to vasodilatory agents in the fetal lung. STUDY DESIGN: We tested the hemodynamic response to acetylcholine, increased PaO(2), and norepinephrine infusion before and after maternal GC administration in chronically prepared, late-gestation fetal lambs (135-137 days of gestational age, term = 147 days). RESULTS: We found that antenatal GCs (1). do not change the basal pulmonary vascular tone and (2). do not alter the vasodilatory response to acetylcholine and increased PaO (2) but enhanced the norepinephrine-mediated pulmonary vasodilation. CONCLUSION: Our results indicate that antenatal GCs alter the pulmonary vascular reactivity to catecholamines. We speculate that the benefits of antenatal GCs on the cardiovascular adaptation at birth may be related to potentiation of catecholamines vascular effects.


Subject(s)
Glucocorticoids/administration & dosage , Lung/blood supply , Lung/embryology , Acetylcholine/pharmacology , Animals , Blood Flow Velocity/drug effects , Blood Pressure/drug effects , Female , Gestational Age , Heart Rate/drug effects , Hemodynamics/drug effects , Hydrogen-Ion Concentration , Norepinephrine/pharmacology , Oxygen/administration & dosage , Pregnancy , Pulmonary Artery/drug effects , Pulmonary Artery/embryology , Pulmonary Artery/physiology , Sheep , Vasodilation/drug effects
8.
Rev Mal Respir ; 19(1): 53-61, 2002 Feb.
Article in French | MEDLINE | ID: mdl-17546814

ABSTRACT

UNLABELLED: Simple clinical markers have poor sensitivity; specificity and predictive value in both infants and adults when predicting the success of weaning from mechanical ventilation. Recently, multi-parametric indices, such as the CROP (Compliance-Respiratory Rate-Oxygenation-Pressure) and the RSB (Rapid-Shallow-Breathing) have been used in adults and subsequently in children. The aim of this study was to test the value of the pediatric CROP and RSB (CROPp, RSBp) and the accuracy of a simplified pediatric CROP (CROPpS) that does not require an arterial blood gas sample. MATERIALS AND METHODS: This prospective study was conducted in a pediatric ICU which does not admit neonates. All infants were intubated and ventilated at the time of entry. Spontaneous tidal volume and maximal negative inspiratory pressure, that are required to assess and calculate the indices, were measured using a Fleish pneumotachograph and a unidirectional valve. The other parameters were recorded or calculated. A maximum 4 hour-duration trial of spontaneous ventilation was then performed. Weaning failure was defined as the requirement of re-ventilation within 48 hours of extubation. The discriminant power of CROPp and RSBp was determined by calculating the area under the receiver operating characteristic (ROC) curve. The best cut-off value of the CROPpS was determined by chi2 optimisation. RESULTS: 39 children (20 males) were included in the trial. They had a median age of 3.2 years and a median duration of mechanical ventilation of 1.3 days. 89.7% of children were successfully weaned of mechanical ventilation. Sensitivity of CROP, and RSB, was 97% and 94%, specificity was 0% and 0%, positive predictive value was 89% and 89%, and negative predictive value was 0% and 0% respectively; the area under the ROC curve was 0.57 and 0.74. The CROP,S was found to be as accurate as the CROP, index using the same cut-off value. Comparison of the 2 groups (success, failure) revealed a significant difference in duration of ventilation (longer in the failure group). CONCLUSION: Even though they correctly classified 87% and 85% of patients respectively, the CROPp and RSBp are not good predictors of weaning from mechanical ventilation as the area under the ROC curve is less than 0.80. Other indices need to be evaluated.


Subject(s)
Severity of Illness Index , Ventilator Weaning , Child, Preschool , Female , Humans , Intensive Care Units, Pediatric , Male , Prospective Studies , Respiratory Function Tests , Respiratory Insufficiency/therapy
9.
Ann Chir ; 126(7): 659-65, 2001 Sep.
Article in French | MEDLINE | ID: mdl-11676238

ABSTRACT

STUDY AIM: Mechanisms that modulate fetal pulmonary circulation and transitional circulation at birth are incompletely understood. The aim of this experimental study was to describe an animal model in order to study the perinatal pulmonary circulation. MATERIAL AND METHODS: Pregnant ewes were operated on between 126 and 128 days gestation (term = 145 days). A skin incision was performed to the fetal lambs in utero and catheters were placed into the ascending aorta and the superior vena cava after insertion in the axillary artery and vein. Then, catheters were inserted into the left pulmonary artery (LPA), main pulmonary artery, and left atrium via a thoracotomy. Moreover, an ultrasonic flow transducer, and an inflatable vascular occluder were placed around the LPA and around the ductus arteriosus. During 10 days, studies were performed in utero (possibly continued when fetal lambs were delivered by caesarean section). This chronically prepared animal may be used to perform hemodynamic studies according to different protocols (drugs injection to the fetus or to the ewes, ductus arteriosus compression, oxygen test). The main pulmonary artery, aortic, left atrial and amniotic pressures, heart rhythm, and flow signal were continuously recorded. RESULTS: Eighteen pregnant ewes were operated on and nine only could be used for experimentation. This ovine model permitted several studies, particularly about effects of catecholamines on the pulmonary circulation, and about effects of ductus arteriosus compression on the pulmonary circulation. CONCLUSION: Chronically instrumented fetal lambs are an excellent model in order to study the perinatal pulmonary circulation.


Subject(s)
Disease Models, Animal , Lung/blood supply , Sheep/physiology , Animals , Aorta/physiology , Catheterization/veterinary , Female , Hemodynamics , Humans , Infant, Newborn , Lung/diagnostic imaging , Lung/embryology , Pregnancy , Pulmonary Artery/physiology , Regional Blood Flow , Ultrasonography, Prenatal/methods , Ultrasonography, Prenatal/veterinary , Vena Cava, Superior/physiology
10.
Crit Care ; 5(4): 196-203, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11511332

ABSTRACT

Ventilating patients with acute respiratory failure according to standardized recommendations can lead to varying volume-pressure (V-P) relationships and overdistension. Young children may be more susceptible than adults to overdistension, and individual evaluation of the effects of ventilator settings is therefore required. Three studies have applied indices for the detection of overdistension to dynamic V-P curves in ventilated children. Two of those studies compared these indices to those obtained using a reference technique ([quasi]-static V-P curves), and suggested that the c coefficient of a second order polynomial equation (SOPE) and the ratio of the volume-dependent elastance to total dynamic elastance (%E2) were suitable indices for estimating overdistension.


Subject(s)
Lung/physiopathology , Pulmonary Ventilation , Respiration, Artificial/adverse effects , Respiratory Insufficiency/physiopathology , Animals , Child , Forced Expiratory Flow Rates , Humans , Respiratory Insufficiency/therapy , Respiratory Physiological Phenomena
11.
Am J Physiol Regul Integr Comp Physiol ; 281(2): R607-14, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11448866

ABSTRACT

High levels of circulating catecholamines are found in the fetus, and fetal stress and birth induce a marked surge in catecholamine secretion. Little is known about the role of catecholamines on the fetal pulmonary circulation. To determine the effects of catecholamines on the pulmonary vascular tone, we tested the hemodynamic response to norepinephrine and dopamine infusion in chronically prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5 microg. kg(-1). min(-1)) increased pulmonary artery pressure (PAP) by 10 +/- 1% (P < 0.01), left pulmonary artery blood flow by 73 +/- 14% (P < 0.01), and decreased pulmonary vascular resistance (PVR) by 33 +/- 6% (P < 0.01). The pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide synthase inhibition. Dopamine infusion at 5 microg. kg(-1). min(-1) did not significantly change PVR. Conversely, dopamine infusion at 10 microg. kg(-1). min(-1) increased PAP (P < 0.01) and progressively increased PVR by 30 +/- 14% (P < 0.01). These results indicate that catecholamines may modulate basal pulmonary vascular tone in the ovine fetus. We speculate that catecholamines may play a significant role in the maintenance of the fetal pulmonary circulation and in mediating changes in the transitional pulmonary circulation.


Subject(s)
Blood Pressure/drug effects , Dopamine/pharmacology , Fetus/physiology , Norepinephrine/pharmacology , Pulmonary Circulation/physiology , Adrenergic alpha-Agonists/pharmacology , Animals , Enzyme Inhibitors/pharmacology , Female , Nitroarginine/pharmacology , Pregnancy , Pulmonary Circulation/drug effects , Sheep , Vascular Resistance/drug effects
12.
Arch Pediatr ; 8(4): 368-73, 2001 Apr.
Article in French | MEDLINE | ID: mdl-11339127

ABSTRACT

UNLABELLED: Discrepancies exist in the recommendations about the oxygen flow to deliver during manual ventilation. The aim of the present study was to determine the effects of ventilatory frequency (FR), inspiratory pressure (P) and oxygen flow on the concentration of the delivered oxygen (FiO2) to obtain FiO2 near 1. MATERIAL AND METHODS: Experimental study with self-inflating resuscitation bag (Ambu with oxygen reservoir) tested on a mono-compartmental test lung (resistant tube and elastic bag [Draeger]; characteristics: compliance = 0.6 mL/cmH2O; resistance = 85 cmH2O.L-1.s-1). Protocol 1: six neonatologists ventilated this model as if they were ventilating premature newborn infants with RDS at various ventilatory rates from 30 to 120 bpm and at various oxygen flows (from 2 to 12 L/min). Tidal volumes (Vt), inspiratory times (Ti), P and FiO2 were recorded continuously during the study. Protocol 2: a graduated manometer was added to visualize pressure. The same protocol was then applied. RESULTS: Protocol 1 (without visual control of the pressure): increase in oxygen flow delivered with the Ambu increases the FiO2 values (P < 0.0001); the higher the ventilatory frequency, the lower the FiO2 (P < 0.0001). The mean value of delivered FiO2 was related to the operator (extreme: 47-86%) (P < 0.001). Multivariate statistical analysis showed that O2 flow, ventilator rate and operator modulated independently the FiO2. Ti and Vt did not change the FiO2. Protocol 2 (with visual control of the pressure: the mean inflating pressures were less than those obtained without visual control of the pressure (26 vs 40 cmH2O respectively; P < 0.05). FiO2 was independent of O2 flow and ventilatory rate. CONCLUSIONS: A special device for continuous visual control of airway pressure is recommended during neonatal manual ventilation. It prevents ventilatory rate-induced FiO2 fluctuations and overdistention.


Subject(s)
Oxygen/administration & dosage , Respiration, Artificial/methods , Equipment Design , Humans , Infant, Newborn , Pressure , Respiratory Function Tests
13.
Intensive Care Med ; 27(11): 1782-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11810123

ABSTRACT

OBJECTIVE: The aim of the study was to assess the influence of nasal continuous positive airway pressure (NCPAP) on breathing pattern in preterm newborns. DESIGN: Prospective study. SETTING: Neonatal intensive care unit. PATIENTS: Ten premature newborn infants on NCPAP (gestational age range from 27 to 32 weeks, mean birth weight 1300+/-460 g) admitted in our neonatal intensive care unit (NICU) for respiratory distress syndrome. METHODS: Breathing patterns and changes in lung volumes level were obtained using respiratory inductive plethysmography (RIP), at random CPAP levels (0, 2, 4, 6 and 8 cmH2O). Raw data were analysed for end-expiratory lung volume level (EELV-level), tidal volume (Vt), respiratory rate, phase angle and labour breathing index (LBI). RESULTS: CPAP increased EELV-level by 2.1+/-0.3xVt from 0 to 8 cmH2O ( p<0.01). Vt increased by 43% from CPAP of 0 cmH2O to CPAP of 8 cmH2O ( p<0.01). We also found that CPAP lowered the phase angle (from 76+/-21 degrees at CPAP of 0 cmH2O to 30+/-15 degrees at CPAP of 8 cmH2O; p<0.01 ) and LBI (from 1.7+/-0.8 at CPAP of 0 cmH2O to 1.2+/-0.3 at CPAP of 8 cmH2O; p<0.05). CONCLUSION: NCPAP improves the breathing strategy of premature infants with respiratory failure, as reflected by improved thoraco-abdominal synchrony, increased Vt and reduction of the LBI. This effect is associated with an increase in EELV-level with CPAP level. However, further investigations are necessary to establish the best CPAP level that ensures both safety and efficiency.


Subject(s)
Infant, Premature, Diseases/therapy , Lung Diseases/therapy , Positive-Pressure Respiration/methods , Analysis of Variance , Humans , Infant, Newborn , Infant, Premature , Intensive Care Units, Neonatal , Plethysmography , Prospective Studies , Respiratory Mechanics , Treatment Outcome
14.
Eur J Cardiothorac Surg ; 18(3): 328-33, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10973543

ABSTRACT

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a technique of extracorporeal oxygenation used in newborn infants with refractory hypoxemia after failure of maximal conventional medical management, when mortality risk is higher than 80%. We retrospectively reviewed all the neonates treated by ECMO between October 1991 and September 1997 in our newborn intensive care unit. METHODS: Fifty-seven patients were treated with ECMO for severe respiratory failure: congenital diaphragmatic hernia (CDH) (n=23), neonatal sepsis (NS) (n=14), meconium aspiration syndrome (MAS) (n=12), and others (n=8). Mean gestational age and birth weight were 38+/-2 weeks and 3200+/-500 g, respectively. Oxygenation index was 61+/-8. Both venovenous (n=28) or venoarterial ECMO (n=29) were used. The mean time at ECMO initiation was 47 h (range 8 h-2 months). The mean duration was 134+/-68 h. In each case of VA ECMO, carotid reconstruction was performed. Survival at 2 years was 40/57 (70%) (CDH 12/23 (52%), NS 11/14 (79%), MAS 12/12 (100%), others 5/8). Follow-up at 2 years was available in 36 survivors. RESULTS: Neurodevelopmental outcome was not related to the initial diagnosis: normal neurologic development (n=30), cerebral palsy (n=5), and neurologic developmental delay (n=1). Two patients remained oxygen dependant at 2 years, and four required surgical treatment for severe gastroesophageal reflux. Respiratory and digestive sequelae were more frequent in the CDH group (P<0.01). Patency and flow of the repaired carotid artery was assessed in 20 infants at 1 year of age using Doppler ultrasonography: normal (n=10), <50% stenosis (n=9), and >50% stenosis (n=1). CONCLUSION: ECMO increased survival of newborn infants with refractory hypoxemia. However, higher a survival rate and lower morbidity were found in non-CDH infants than in congenital diaphragmatic hernia.


Subject(s)
Extracorporeal Membrane Oxygenation , Respiratory Insufficiency/therapy , Brain Ischemia/diagnostic imaging , Brain Ischemia/etiology , Brain Ischemia/physiopathology , Brain Ischemia/prevention & control , Cerebrovascular Circulation , Extracorporeal Membrane Oxygenation/methods , Follow-Up Studies , Gestational Age , Humans , Hypoxia/complications , Hypoxia/mortality , Hypoxia/therapy , Infant, Newborn , Prospective Studies , Respiratory Insufficiency/complications , Respiratory Insufficiency/mortality , Survival Rate , Ultrasonography, Doppler, Transcranial
15.
Eur J Cardiothorac Surg ; 18(3): 334-41, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10973544

ABSTRACT

OBJECTIVE: The purpose of this study was to examine whether inhaled nitric oxide (iNO) may change lung injury in moderate hyaline membrane disease (HMD). METHODS: Fifteen moderately premature lambs (128 days gestation, term=147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n=7) from the onset of ventilation or control (n=8). Except for inhaled NO, treatments were intentionally similar to those applied in clinical situations. After porcine surfactant administration (Curosurf, 100 mg/kg), mechanical ventilator settings were modified during the course of the study to maintain PaCO(2) between 40 and 50 mmHg and post-ductal SpO(2) between 90 and 95%. The main studied parameters were gas exchanges parameters, respiratory mechanics (static compliance and functional residual capacity) and pulmonary vascular permeability and/or filtration rate indices. RESULTS: We found that 20 ppm of inhaled NO for 5 h significantly reduce ventilatory and oxygen requirements, but only during the first hour of mechanical ventilation. No increase in extravascular lung water content (5.41+/-0.96 vs. 5.46+/-1.09 ml/g bloodless dry lung in the control group and in the NO group, respectively) and no impairment of the respiratory mechanics could be found in the NO-treated group. However, inhaled NO increased the albumin lung leak index in this model (6.09+/-1.51 in the NO-treated group vs. 4.08+/-1.93 in the control group; P<0.05). CONCLUSIONS: Our results do not therefore support a detrimental effect of short-term exposure to low doses of NO inhalation in moderate HMD. However, it may induce an increase in lung vascular protein leakage. The pathophysiological consequences of this finding remain to be elucidated.


Subject(s)
Free Radical Scavengers/administration & dosage , Hyaline Membrane Disease/physiopathology , Lung/physiopathology , Nitric Oxide/administration & dosage , Pulmonary Gas Exchange/drug effects , Administration, Inhalation , Animals , Animals, Newborn , Blood Gas Analysis , Capillary Permeability/drug effects , Disease Models, Animal , Extravascular Lung Water/drug effects , Female , Humans , Infant, Newborn , Lung/blood supply , Pulmonary Circulation/physiology , Pulmonary Edema/physiopathology , Random Allocation , Respiration, Artificial , Respiratory Mechanics/drug effects , Sheep
16.
Crit Care Med ; 28(4): 1068-71, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10809284

ABSTRACT

OBJECTIVE: To investigate the effects of the association of inhaled nitric oxide (iNO) and oxidant drugs (acetaminophen, phytomenadione, and EMLA cream) on methemoglobinemia during the neonatal period. DESIGN: Prospective, randomized, experimental study. SETTING: University Experimental Pharmacology laboratory. SUBJECTS: Sixty newborn piglets weighing 1.5-2.0 Kg. INTERVENTIONS: Twelve groups of five piglets were anaesthetized, mechanically ventilated, and studied for 3 hrs. Eight groups received iNO (40 ppm or 80 ppm) alone or in association with a single intravenous dose of acetaminophen (120 mg/kg propacetamol), phytomenadione (5 mg vitamin K1) or EMLA cream (2.5 g) applied to the ventral lower abdomen for 3 hrs. Three other groups received, respectively, acetaminophen, phytomenadione, or EMLA cream without iNO. The last group (control group) received neither drugs nor iNO. MEASUREMENTS AND MAIN RESULTS: Methemoglobinemia was measured before the beginning of each experiment, 30 mins later, and every hour for 3 hrs. There was no significant difference in methemoglobinemia at any time between groups receiving acetaminophen (0.90%+/-0.12%), phytomenadione (0.88%+/-0.11%), or EMLA cream alone (0.97%+/-0.11%) and the control group (0.92%+/-0.12%). At 3 hrs, methemoglobinemia was slightly but significantly increased in group receiving iNO alone (1.04%+/-0.17% at 40 ppm iNO and 1.14%+/-0.16% at 80 ppm iNO; p < .05). Conversely, methemoglobinemia increased as a function of time in groups in which iNO was associated to drug administration and was significantly greater than the control group at 3 hrs (80 ppm iNO + acetaminophen, 2.80%+/-0.47%; 80 ppm iNO + phytomenadione, 2.38%+/-0.45%; 80 ppm iNO + EMLA cream, 2.33%+/-046%; p < .001). CONCLUSIONS: These results demonstrate that if oxidant drugs (acetaminophen, phytomenadione, or EMLA cream) did not increase blood methemoglobinemia in neonatal piglets, their association with iNO caused an increase in methemoglobin. Special care should be taken to monitor methemoglobinemia when iNO is combined to such drugs in newborn infants.


Subject(s)
Acetaminophen/administration & dosage , Lidocaine/administration & dosage , Methemoglobinemia/chemically induced , Nitric Oxide/administration & dosage , Oxidants/administration & dosage , Prilocaine/administration & dosage , Vasodilator Agents/administration & dosage , Vitamin K 1/administration & dosage , Acetaminophen/adverse effects , Administration, Inhalation , Animals , Animals, Newborn , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Lidocaine/adverse effects , Lidocaine, Prilocaine Drug Combination , Methemoglobin/analysis , Methemoglobin/drug effects , Methemoglobinemia/blood , Nitric Oxide/adverse effects , Ointments , Oxidants/adverse effects , Prilocaine/adverse effects , Prospective Studies , Random Allocation , Swine , Time Factors , Vasodilator Agents/adverse effects , Vitamin K 1/adverse effects
17.
Arch Pediatr ; 7(2): 132-42, 2000 Feb.
Article in French | MEDLINE | ID: mdl-10701057

ABSTRACT

BACKGROUND: During the last ten years, new therapeutic strategies have been used in order to improve the management of congenital diaphragmatic hernia (CDH). CDH is associated with pulmonary hypoplasia, abnormal pulmonary vascular reactivity and pulmonary immaturity. Between 1985 and 1990, mechanical hyperventilation and early surgery were provided systematically. Since 1991, the management of CDH in our institution has involved a preoperative stabilization with exogenous surfactant replacement, gentle ventilation, high-frequency oscillation, nitric oxide or extracorporeal membrane oxygenation. PURPOSE: To analyse the impact of the new therapeutic strategy on the survival and outcome of newborns with CDH. METHODS: Retrospective review of all infants with CDH admitted to our institution from 1985 through 1996. Mortality and morbidity were compared between period I (1985-1990) and period II (1991-1996). RESULTS: Between 1985 and 1996, 123 neonates were admitted to our Neonatal Department. Nine of them had another severe congenital malformation and were excluded from the study. Survival was 23% (12/52) in period I and 56% (35/62) in period II (p < 0.001). In period II, complications were more frequent among survivors in whom an extracorporeal membrane oxygenation was required (13 infants): bronchopulmonary dysplasia 77% (10/13), gastroesophageal reflux 61% (8/13), and hypotrophy 61% (8/13). CONCLUSION: These data demonstrate a significant improvement in survival in CDH since the implementation of new therapeutic modalities. Nevertheless, a significant morbidity exists among the infants who survive a severe respiratory failure.


Subject(s)
Hernias, Diaphragmatic, Congenital , Bronchopulmonary Dysplasia/complications , Extracorporeal Membrane Oxygenation , Fetal Organ Maturity , France , Gastroesophageal Reflux/congenital , Hernia, Diaphragmatic/surgery , Hernia, Diaphragmatic/therapy , High-Frequency Jet Ventilation , Humans , Infant, Newborn , Lung/abnormalities , Lung/blood supply , Lung/embryology , Muscle Hypotonia/congenital , Nitric Oxide/therapeutic use , Pulmonary Surfactants/therapeutic use , Respiration, Artificial/methods , Respiratory Insufficiency/complications , Retrospective Studies , Survival Rate , Treatment Outcome , Vasodilator Agents/therapeutic use
18.
FEBS Lett ; 487(2): 213-8, 2000 Dec 29.
Article in English | MEDLINE | ID: mdl-11150512

ABSTRACT

Direct electrometric measurements of membrane potential changes are a valuable tool for study of vectorial transfer of electrons, protons, and ions. Commonly model membrane systems are created by fusion of lipid/protein vesicles with lipid-coated thin films. We characterized the electric units resulting from this process using chromatophores from the purple bacterium Rhodobacter sphaeroides and either a Mylar film or a planar modified gold electrode as support. Investigation of the shunting activity of the ionophore gramicidin on the flash-induced potential change demonstrates fusion of individual chromatophores to form independent 'blisters', which preserve an interior aqueous compartment. Under current-clamp conditions the photovoltage follows the change of the membrane potential of the individual blisters.


Subject(s)
Bacterial Chromatophores/physiology , Rhodobacter sphaeroides/physiology , Bacterial Chromatophores/ultrastructure , Electrophysiology/methods , Intracellular Membranes/physiology , Light , Membrane Fusion , Membrane Potentials , Patch-Clamp Techniques/instrumentation , Photosynthesis
19.
Intensive Care Med ; 25(10): 1118-25, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10551968

ABSTRACT

The aim of the study was to compare measurements of the elevation of functional residual capacity (FRC) above the relaxation volume obtained in 34 mechanically ventilated infants (median weight 2.6 kg, range 1.2-9) from four different methods: (1) direct measurement of the complete exhalation volume after brief disconnection from the ventilator, (2) calculated measurement from total positive end-expiratory pressure (PEEP) measured by end-expiratory occlusion of the breathing circuit, (3) extrapolated evaluation from the mathematical model of Brody, (4) extrapolated evaluation from the passive expiration method. We considered the direct measurement (1) as the "gold standard". Measurements obtained by total PEEP (2) and by the Brody's mathematical model (3) provided similar results than the direct measurement. Conversely, graphical extrapolation from the passive expiration method (4) underestimated the elevation of FRC. In conclusion, we suggest using the mathematical extrapolation from the Brody's model to evaluate the elevation of FRC in mechanically ventilated infants: this method is non-invasive, does not require disruption of gas flow, can be easily performed with all the neonatal ventilators, and allows continuous breath-by-breath measurements.


Subject(s)
Functional Residual Capacity , Monitoring, Physiologic/methods , Positive-Pressure Respiration, Intrinsic/diagnosis , Respiration, Artificial/methods , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Airway Resistance , Blood Gas Analysis , Bronchiolitis/complications , Bronchopulmonary Dysplasia/complications , Humans , Hyaline Membrane Disease/complications , Infant , Infant, Newborn , Lung Compliance , Mathematics , Models, Statistical , Positive-Pressure Respiration, Intrinsic/etiology , Positive-Pressure Respiration, Intrinsic/metabolism , Positive-Pressure Respiration, Intrinsic/physiopathology , Reproducibility of Results , Respiration, Artificial/adverse effects , Respiratory Insufficiency/etiology , Respiratory Insufficiency/metabolism
20.
Crit Care Med ; 27(6): 1168-74, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10397224

ABSTRACT

OBJECTIVE: To determine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in an in vivo model. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: University experimental pharmacology laboratory. SUBJECTS: Mechanically ventilated newborn piglets, 1 to 2 days old, exposed to 100% oxygen for 76 hrs. INTERVENTIONS: The piglets were randomly assigned either to a treatment group receiving 20 ppm inhaled NO from the onset of ventilation (n = 5) or to a control group (n = 6) receiving no treatment. MEASUREMENTS AND MAIN RESULTS: The main variables studied were gas exchange (PaO2/F(IO2) ratio, lung diffusing capacity), respiratory mechanics (static compliance of the respiratory system, stat, quasi-static hysteresis area, functional residual capacity), and pulmonary vascular permeability assessed by simultaneous intravenous administration of iodine-125-labeled albumin and chromium-51-labeled red blood cells. Extravascular albumin space of the lung and dry lung weight were significantly higher in the NO group vs. the control group (albumin space, 1.08+/-0.16 vs. 0.70+/-0.26 [SD] mL/kg body weight [p < .05]; dry lung weight, 3.20+/-0.34 vs. 2.66+/-0.14 g/kg body weight [p < .05]). Moreover, the hysteresis area was higher from 24 hrs of NO exposure. Conversely, NO inhalation altered neither the extravascular lung water content (12.98+/-2.79 mL/kg body weight in the NO group vs. 12.18+/-2.26 mL/kg body weight in the control group [not significant]) nor the main respiratory mechanical variables (static compliance, functional residual capacity) and gas exchange (lung diffusing capacity, PaO2/F(IO2) ratio). CONCLUSION: These results do not support the hypothesis that NO inhalation combined with hyperoxia can alter the main lung-function variables in neonates. However, it may induce an increase in lung vascular protein leakage. The pathophysiologic consequences of this finding remain to be elucidated.


Subject(s)
Capillary Permeability/drug effects , Hyperoxia/metabolism , Nitric Oxide/pharmacology , Respiratory Mechanics/drug effects , Vasodilator Agents/pharmacology , Administration, Inhalation , Animals , Animals, Newborn , Disease Models, Animal , Extravascular Lung Water/drug effects , Hemodynamics , Nitric Oxide/administration & dosage , Pulmonary Gas Exchange/drug effects , Random Allocation , Swine , Vasodilator Agents/administration & dosage
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