Clinical response to inhaled nitric oxide in persistent pulmonary hypertension of the newborn

We observed clinical response to inhaled nitric oxide (iNO) in 12 neonates with persistent pulmonary hypertension of the newborn (PPHN). Clinical response was defined as a decrease in oxygenation index (OI) by 40%. Ten of 12 neonates had response to iNO showing decrease OI from 46.1+/-7.6 to 14.4+/-6.8 at 1 hour after inhalation. Sustained improvement of OI was achieved in 8 neonates and two neonates were relapsed. In the group of neonates who had OI above 40 (n=7), 6 of them showed the decrease of OI from 66.1+/-4.8 to 18.3+/-8.0 at 1 hour. In two groups, one had OI of 40 or greater, and the other OI of 40 or less, there were no differences in pattern of response and early death rate. The response rates according to underlying diseases were as follows; idiopathic PPHN 100%, respiratory distress syndrome 100%, and diaphragmatic hernia 66.7%. Relapse was observed in one neonate with sepsis caused by pneumonia and in one infant with meconium aspiration syndrome. Two infants showed no response to iNO (one diaphragmatic hernia and one suspected pulmonary hypoplasia). We conclude that iNO therapy could improve oxygenation in high percentage of newborn infants with severe PPHN of various underlying conditions except pulmonary hypoplasia.     

Early response to inhaled nitric oxide and its relationship to outcome in children with severe hypoxemic respiratory failure

OBJECTIVE: To examine whether the early response to inhaled nitric oxide (iNO) is a measure of reversibility of lung injury and patient outcome in children with acute hypoxemic respiratory failure (AHRF). DESIGN: Retrospective review study. SETTING: Pediatric ICUs. PATIENTS: Thirty infants and children, aged 1 month to 13 years (median, 7 months) with severe AHRF (mean alveolar arterial oxygen gradient of 568+/-9.3 mm Hg, PaO2/fraction of inspired oxygen of 56+/-2.3, oxygenation index [OI] of 41+/-3.8, and acute lung injury score of 2.8+/-0.1). Eighteen patients had ARDS. INTERVENTIONS: The magnitude of the early response to iNO was quantified as the percentage change in OI occurring within 60 min of initiating 20 ppm iNO therapy. This response was compared to patient outcome data. MEASUREMENTS AND RESULTS: There was a significant association between early response to iNO and patient outcome (Kendall tau B r=0.43, p < 0.02). All six patients who showed < 15% improvement in OI died; 4 of the 11 patients (36%) who had a 15 to 30% improvement in OI survived, while 8 of 13 (61%) who had a > 30% improvement in OI survived. Overall, 12 patients (40%) survived, 9 with ongoing conventional treatment including iNO, and 3 with extracorporeal support. CONCLUSIONS: In AHRF in children, greater early response to iNO appears to be associated with improved outcome. This may reflect reversibility of pulmonary pathophysiologic condition and serve as a bedside marker of disease stage.     

Range of echocardiographic findings in term neonates with high oxygen requirements

AIMS: To examine the hypothesis that right to left shunting occurs mainly in the lungs rather than through the fetal channels in neonates. METHODS: Thirty two term babies requiring over 70% oxygen had daily colour Doppler echocardiograms until recovery. Measurements included left ventricular fractional shortening, right and left ventricular outputs, colour and pulsed Doppler ductal and atrial shunting and systolic pulmonary artery pressure (SPAP) derived from ductal shunt or tricuspid incompetence velocities. RESULTS: The babies were retrospectively classified into a respiratory group (n = 19) and a persistent pulmonary hypertension (PPHN) group (n = 13) on the basis of clinical history and radiology. At the initial echocardiogram, just 50% of babies had suprasystemic SPAP. Despite better oxygenation, more of the PPHN group had suprasystemic PAP (85% vs 26%). A correlation between SPAP and Oxygen index (OI) was present only in the respiratory group (r = 0.7). Low ventricular outputs (< 150 ml/kg/min) were common in both groups (53% and 79%). The respiratory group had more closed ducts (47% vs 0%) and those ducts which were patient were more constricted (1.75 mm vs 2.6 mm). Pure right to left ductal shunts were seen in just 15% and pure right to left atrial shunts in just 6% of all babies. The serial echocardiograms showed that SPAP fell and ducts closed well before oxygenation improved. Ventricular outputs increased with age in both groups. CONCLUSIONS: Apart from early on in the sickest babies with a primarily respiratory diagnosis and the babies with primary PPHN, most right to left shunting occurred at an intrapulmonary level.     

Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios

OBJECTIVE: We determined whether inhaled nitric oxide (NO) could improve systemic oxygenation in human neonates with hypoplastic lungs. METHODS: A multicenter nonrandomized investigation was performed to study the efficacy of short-term NO inhalation. Inhaled NO was administered at 80 ppm to nine neonates without evidence of structural cardiac disease by echocardiography. Lung hypoplasia was due to congenital diaphragmatic hernia (CDH) in eight patients and to oligohydramnios in one patient. A total of 15 trials of NO inhalation were performed in these nine patients. Eight trials in seven patients were performed before extracorporeal membrane oxygenation ((ECMO); one patient had two trials) and seven trials were performed in five patients after decannulation from ECMO (two patients had two trials each). RESULTS: NO inhalation before ECMO did not change postductal PaO2 (42 +/- 3 mmHg vs 42 +/- 4 mmHg), oxygen saturation (SpO2; 89% vs 88%) or oxygenation index (31 +/- 4 cm H2O/torr vs 31 +/- 4 cm H2O/torr) for the group. All patients required ECMO support, which lasted from 5 to 17 days (mean 9). After decannulation from ECMO, NO inhalation increased postductal PaO2 from a median of 56 mm Hg (range 41 to 94) to a median of 113 mm Hg (range 77 to 326), P < .05. It decreased the oxygenation index from a median of 23 cm H2O/torr (range 11 to 7) to a median of 11 cm H2O/torr (range 4 to 21), P < .05. It increased SpO2 from 91% to 96% (P < .05) and pH from 7.48 +/- .03 to 7.50 +/- .03. CONCLUSION: In our patients with hypoplastic lungs, inhaled NO was effective only after ECMO. This could be due to maturational changes such as activating the endogenous surfactant system. Inhaled NO may be effective in neonates with hypoplastic lungs who have recurrent episodes of pulmonary hypertension after ECMO, even if they were previously unresponsive.     

Response to inhaled nitric oxide in acute lung injury depends on distribution of pulmonary blood flow prior to its administration

Responses to inhaled nitric oxide (iNO) in acute lung injury (ALI), as evidenced by improvements in oxygenation, are variable. We hypothesized that the effect of iNO may be related to the pre-iNO distribution of pulmonary blood flow (PBF). In the present study we evaluated the effect of iNO on PBF in normal healthy dogs and in a canine model of ALI induced by oleic acid (OA). In Group "OA only" (n = 5), ALI was induced by central venous injection of 0.08 ml/kg OA. In Group "E+OA" (n = 5), hypoxic pulmonary vasoconstriction after ALI was blocked with low-dose endotoxin (15 microg/kg of Escherichia coli endotoxin) administered 30 min before giving the same dose of OA. Measurements of regional PBF and lung water concentration (LWC) using positron emission tomography (PET) and H215O were performed before and after OA or placebo, and then again at concentrations of 10, 40, and 0 ppm iNO. One hundred twenty minutes after OA injury, PaO2/FIO2 fell significantly in Group OA only, from 567 +/- 32 to 437 +/- 67 mm Hg. In these animals, PBF redistributed from the dorsal edematous regions of the lungs to the nondependent zones, thus partially preserving normal ventilation/ perfusion relationships. As in the normal animals, in Group OA only, iNO did not significantly change either PBF or oxygenation. In Group E+OA, the administration of low-dose endotoxin eliminated perfusion redistribution from the dorsal edematous lung regions. As a result, PaO2/FIO2 fell from 558 +/- 70 to 119 +/- 53 mm Hg, a decrease that was significantly greater than that in Group OA only. In Group E+OA, administration of iNO restored perfusion redistribution to a similar level as in Group OA only, which was associated with a significant improvement in PaO2/FIO2, from 119 +/- 53 to 251 +/- 159 (10 ppm iNO), and 259 +/- 165 mm Hg (40 ppm iNO). We conclude that the effect of iNO on oxygenation after ALI depends on the pre-iNO perfusion pattern, which may help explain the variable response to iNO often observed in patients with acute respiratory distress syndrome.     

Plasma immunoreactive endothelin-1 concentrations in infants with persistent pulmonary hypertension of the newborn

Plasma concentrations of endothelin-1 (ET-1) have been reported to be elevated in children and adults with pulmonary hypertension. We hypothesized that infants with persistent pulmonary hypertension of the newborn (PPHN) have elevated plasma concentrations of ET-1. Plasma concentrations of immunoreactive-endothelin-1 (ir-ET-1) were measured using a radioimmunoassay in 20 infants with PPHN and 20 normal term infants. Mean birthweight and gestational age of the infants were comparable in the two groups. The mean plasma ir-ET-1 concentrations were significantly elevated in neonates with PPHN compared to those of normal term infants (2.04 +/- 0.30 versus 1.04 +/- 0.29 pg/mL, p = 0.02). A linear regression analysis demonstrated a significant relationship between ir-ET-1 concentrations and alveolar-arterial oxygen gradient (r = 0.49, p = 0.02) and mean airway pressure (r = 0.49, p = 0.02). There was also a significant correlation between ir-ET-1 concentrations and duration of extracorporeal membrane oxygenation among infants with PPHN (r = 0.44, p = 0.05). We conclude that plasma ir-ET-1 concentrations are elevated in infants with PPHN. The presence of elevated ir-ET-1 concentrations and their positive correlation with disease severity suggests that ET-1 may serve as a marker of the disease severity in these infants. However, further studies are needed to elucidate the role of ET-1 in the pathophysiology of PPHN.     

Suicidal behavior in bipolar and unipolar affective disorders: a meta-analysis

Manual ventilation (MAV) or handbagging is a frequent and often life-saving procedure for neonates; however, few studies allow for an objective evaluation of techniques or possible risks. We compared parameters of ventilation and pulmonary mechanics obtained during routine pressure-limited MAV to those obtained during spontaneous breathing (SPB) in the same infant at approximately the same time. We selected 20 preterm neonates in the recovery phase of respiratory distress syndrome who received periodic MAV and were capable of optimum spontaneous minute ventilation (> 300 mL/kg/min). During MAV compared to SPB we measured higher tidal volume (8.1 +/- 0.5 SE vs. 5.4 +/- 0.4 SE mL/kg, P < 0.001), lower total pulmonary compliance (0.65 +/- 0.05 vs. 1.16 +/- 0.11 SE mL/cmH2O, P < 0.001), end-inspiratory compliance, higher pulmonary resistance (121 +/- 11 vs. 61 +/- 7 SE cmH2O/L/s, P < 0.001) and higher peak inspiratory airflow (2.8 +/- 0.2 vs. 1.6 +/- 0.1 L/s, P < 0.001). Inspiratory time (Ti) was consistently longer during MAV (0.49 +/- 0.02 vs. 0.36 +/- 0.02 SE, P < 0.001) such that during MAV the difference between actual Ti and minimal effective Ti (fivefold inspiratory time constant) was larger (0.29 +/- 0.03 vs. 0.13 +/- 0.03 s, P < 0.05). Our study suggests that operator-dependent ventilatory variables such as tidal volume, inspiratory time, frequency, and airflow need to be further evaluated in order to develop standardized guidelines for the safe administration of MAV. Until then the ventilator used for brief or augmented ventilatory support is a reasonable alternative to administering MAV by inconsistent standards.     

The antibody response to 27-, 17-, and 15-kDa Cryptosporidium antigens following experimental infection in humans

STUDY OBJECTIVE: Data concerning inhaled nitric oxide (iNO) on pediatric ARDS is rare. We investigated the effects of iNO on pediatric ARDS in order to examine the ability to predict a response to iNO, the optimal concentration of iNO, the effects of < or = 1 ppm nitric oxide (NO), and the effect of iNO on PaCO2. SETTING: ICU at Kumamoto (Japan) University Hospital. PATIENTS AND INTERVENTIONS: Seven children with ARDS. The initial responses to 16 ppm NO and the dose-response effects of 0.13 to 16 ppm NO were assessed. MEASUREMENTS AND RESULTS: Sixteen ppm of iNO improved oxygenation in all seven children. The use of iNO significantly increased the ratio of arterial oxygen tension to the fraction of inspired oxygen (PaO2/FIO2). A correlation between the NO-induced increase in PaO2/FIO2 and the baseline PaO2/FIO2 was observed (r=0.93, p<0.01). Dose-response tests showed that the optimal concentration of iNO was < or = 4 ppm, improvements in PaO2/FIO2 could be observed with concentrations of < or = 1 ppm NO, and iNO induced a slight decrease in PaCO2. CONCLUSIONS: In children with ARDS, iNO frequently improves oxygenation and induces a slight decrease in PaCO2, with the baseline PaO2/FIO2 functioning as a predictor of all NO response. Improvements of PaO2 and PaCO2 were observed with concentrations of iNO of < or = 1 ppm, a level in which the risk of a toxic reaction in children is minimal. Effects on outcome need verification in larger controlled trials.     

Getting at the management of care within managed care

Although inhaled nitric oxide (INO) improves oxygenation in critically ill neonates, the neurodevelopmental outcome of premature neonates with severe hypoxemic respiratory failure treated with INO has not been reported. Mortality and prospective neurodevelopmental assessment in early childhood were studied in a cohort of 24 very low birth weight neonates (相似文献   

Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.     

Phosphate metabolism in the red cell of sick prematures

The effect of different amounts of phosphorus supplementation on phosphate metabolism was studied in two groups of sick preterms (B and C) during the first week of life. Group B included prematures that started formula milk feeding from day 3 and group C neonates on total parenteral nutrition with phosphate supplementation for 7 days. Twelve healthy preterm neonates on formula milk feeding from day 2 (group A) were used as controls. On the 7th day of life all phosphate parameters measured in group C (plasma and red cell inorganic phosphate and erythrocyte ATP and 2,3-diphosphoglycerate) were found significantly lower than in the controls (1.60 +/- 0.07; 0.60 +/- 0.08; 1.45 +/- 0.09 and 4.42 +/- 0.18 vs. 2.05 +/- 0.10; 0.94 +/- 0.11; 1.69 +/- 0.07 and 6.24 +/- 0.42 mmol/l, respectively). The renal tubular reabsorption of phosphate was also lower in this group (86.8 +/- 3.2 vs. 97.3 +/- 1.0%). No significant differences were observed between groups B and A. Higher phosphorus intake that was better achieved through early milk feeding prevented phosphate depletion and the decline of 2,3-diphosphoglycerate in the erythrocytes even of sick neonates which in turn might help to improve tissue oxygenation. The amount of parenteral phosphate supplementation that could have beneficial effects on red cell phosphate parameters needs further investigation.     

Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results

OBJECTIVE: Instrumental dead space wash-out can be used to improve carbon dioxide clearance. The aim of this study was to define, using a bench test, an optimal protocol for long-term use, and to assess the efficacy of this technique in neonates. DESIGN: A bench test with an artificial lung model, and an observational prospective study. Dead space wash-out was performed by continuous tracheal gas insufflation (CTGI), via six capillaries molded in the wall of a specially designed endotracheal tube, in 30 preterm neonates with hyaline membrane disease. SETTING: Neonatal intensive care unit of a regional hospital. RESULTS: The bench test study showed that a CTGI flow of 0.5 l/ min had the optimal efficacy-to-side-effect ratio, resulting in a maximal or submaximal efficacy (93 to 100%) without a marked increase in tracheal and CTGI circuit pressures. In the 30 newborns, 15 min of CTGI induced a significant fall in arterial carbon dioxide tension (PaCO2), from 45 +/- 7 to 35 +/- 5 mmHg (p = 0.0001), and in 14 patients allowed a reduction in the gradient between Peack inspirating pressure and positive end-expiratory pressure from 20.8 +/- 4.6 to 14.4 +/- 3.7 cmH2O (p < 0.0001) while keeping the transcutaneous partial pressure of carbon dioxide constant. As predicted by the bench test, the decrease in PaCO2 induced by CTGI correlated well with PaCO2 values before CTGI (r = 0.58, p < 0.002) and with instrumental dead space-to-tidal volume ratio (r = 0.54, p < 0.005). CONCLUSION: CTGI may be a useful adjunct to conventional ventilation in preterm neonates with respiratory disease, enabling an increase in CO2 clearance or a reduction in ventilatory pressure.     

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.     

Bone mineral density in pediatric patients with idiopathic hypercalciuria

Between October 1993 and April 1995, a total of 77 neonates requiring mechanical ventilation were enrolled in this study and were randomly divided into two groups. Group A consisted of 31 premature infants (mean birthweight 1.36 +/- 0.29 kg) with respiratory distress syndrome (RDS) and seven neonates (mean birthweight 3.2 +/- 0.5 kg) with meconium aspiration syndrome (MAS). Group B consisted of 31 premature infants (mean birthweight 1.31 +/- 0.3 kg) with RDS and eight neonates (mean birthweight 3.3 +/- 0.5 kg) with MAS. Infants in group A received synchronized intermittent mandatory ventilation (SIMV) and infants in group B received conventional intermittent mandatory ventilation (CIMV) therapy. In premature infants with RDS, our data showed: (i) the duration of ventilation was significantly shorter (P < 0.05) in the synchronized group (156 +/- 122 h) compared to the conventional group (242 +/- 175 h); (ii) significantly fewer (P < 0.05) patients required reintubation in the synchronized group than in the conventional group (three vs 11 patients); (iii) incidence of severe intraventricular hemorrhage (grades 3 and 4) was significantly lower (P < 0.05) in the synchronized group compared to the conventional group (one vs seven patients); (iv) incidence of bronchopulmonary dysplasia was significantly lower (P < 0.05) in the synchronized group than in the control group (one vs seven patients). In neonates with MAS, our data showed no significant difference (P < 0.05) on duration of ventilation, incidence of reintubation, incidence of pneumothorax or mortality rate between synchronized and control groups.     

Sudden cardiac death in hypertrophic cardiomyopathy: risk evaluation

The pathophysiology of the lamb model of congenital diaphragmatic hernia (CDH) involves pulmonary hypoplasia, pulmonary hypertension, and surfactant deficiency. Inhaled nitric oxide (NO) is a highly selective pulmonary vasodilator. The aim of this study was to determine the effects of inhaled NO on pulmonary gas exchange, acid-base balance, and pulmonary pressures in a lamb model of CDH with or without exogenous surfactant therapy. At the gestational age of 78 days (full term, 145 days) 11 lamb fetuses had a diaphragmatic hernia created via a left thoracotomy and then were allowed to continue development in utero. After cesarean section, performed at term, six lambs received exogenous surfactant therapy (50 mg/kg, Infasurf) and five served as controls. All animals were pressure-ventilated for 30 minutes and then received 80 ppm of inhaled NO at an F1O2 of .9 for a 10-minute interval. Compared with the control lambs, the lambs with exogenous surfactant therapy had higher pH (7.17 +/- .06 v 6.96 +/- .07; P < .05), lower PCO2 (73 +/- 8 v 122 +/- 20, p < .05), and higher PO2 (153 +/- 38 v 50 +/- 23; P < .05). In control CDH lambs (without surfactant), inhaled NO did not improve pH, PCO2, or PO2, or decrease pulmonary artery pressure. In CDH lambs given exogenous surfactant, NO decreased pulmonary artery pressures (42 +/- 4 v 53 +/- 5; P < .005) and further improved PCO2 and PO2. NO also made the difference between pulmonary and systemic artery pressures more negative in the surfactant-treated lambs (-15 +/- 4 v -2.3 +/- 2.4; P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional hemodynamic effects of dopamine in the sick preterm neonate

OBJECTIVE: To study the effects of dopamine on renal, mesenteric, and cerebral blood flow in sick preterm neonates. Study design: The pulsatility index was used to assess the dopamine-induced changes in renal, mesenteric, and cerebral blood flow by means of color Doppler ultrasonography in 23 nonhypotensive preterm neonates (birth weight: 981 +/- 314 g; postnatal age: <2 days). Dopamine was given at a dose of 6.1 +/- 3.0 microgram/kg per minute to combat oliguria, impaired peripheral perfusion, or both. Blood flow velocity measurements were made before and during dopamine administration, with each patient serving as his or her own control subject. RESULTS: Dopamine significantly increased blood pressure and urine output. Dopamine decreased the pulsatility index in the renal artery (2.98 +/- 1.18 vs 1.68 +/- 0.45; P <.05) while the pulsatility index in the superior mesenteric and medial cerebral artery was not affected. Thus renal blood flow increased while mesenteric and cerebral blood flow remained unchanged during dopamine treatment. The increase in renal blood flow was independent of the blood pressure changes. CONCLUSIONS: These findings suggest a functionally mature renal, but not mesenteric, vasodilatory dopaminergic response in the preterm neonate. The observations also indicate the lack of an effect of low- to medium-dose dopamine on cerebral hemodynamics in the nonhypotensive preterm neonate.     

Same-day pediatric surgery

HL surfactant was used for vital indications in 12 newborns with respiratory distress syndrome born at 28-36 weeks weighing 1000-2500 g at birth and postgestation age of up to 48 h, without apparent congenital diseases and evident signs of intrauterine infection and with intraventricular hemorrhages no more severe than of the second degree. Control group consisted of 12 babies with similar condition treated similarly but without surfactant. Surfactant HL was administered endotracheally in a dose of 50 mg/kg twice at 12-h interval. Good effect was attained in 4 newborns, stable deterioration in 2, and no effect in 6 children. The majority of artificial ventilation values were virtually the same in both groups, but 2 days after surfactant, FiO2 was significantly lower in the controls than in experimental group (0.37 +/- 0.05 vs. 0.64 +/- 0.4, p < 0.01), and VEI was higher in the controls (0.33 +/- 0.05 vs. 0.18 +/- 0.03, p < 0.05). VR, MAP, FiO2, and oxygenation index decreased slower in the test group than in the controls. The mean duration of treatment with hypoxic gaseous mixtures and artificial ventilation of the lungs in the test vs. control group were 143 +/- 60 and 288 +/- 45 h vs. 45.5 +/- 8.3 and 200.8 +/- 28.5 h, respectively. The incidence of air leakage syndrome was 83% (10 cases) in the test group and 17% (2 cases) in the control group, chronic pulmonary diseases developed in 3 (25%) babies in the test and in 1 (8.3%) in the control group. Seven (67%) children in the test group developed obstructive changes in the lungs vs. 1 child in the control group. One child (test group) died from causes other than pulmonary. Hospital stay was longer in the test group than in control (14.8 +/- 1.7 vs. 8.3 +/- 1.3 days, p < 0.01).     

Mid-trimester emergent cerclage: a ten year single institution review

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine inhalation challenge. Twelve infants with CLD and 22 age-matched children without respiratory diseases were enrolled in this study (ages--5 to 36 months; mean age--16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO2 had been reached (Dmin-PO2) was considered to represent the dose at which reactivity to methacholine (RO2meth) had occurred. In the CLD group, Dmin-PO2 (3.50 +/- 0.1 log x milli-units) was significantly lower than in the preterm control infant group (4.31 +/- 0.2 log x milli-units) and the term infant group (4.21 +/- 0.1 log x milli-units) (P = 0.004, P < 0.001). Dmin-PO2 in the preterm control infant group was not significantly different than in the term infant group (P > 0.5). These results suggest that infants who require additional therapeutic oxygen and mechanical ventilation during the early months of life are at risk of developing early-onset, long-lasting respiratory disease that is related to an acquired BHR.     

alpha-Melanocyte-stimulating hormone during human perinatal life

To obtain information on human pituitary intermediate lobe activity throughout the perinatal period, plasma alpha MSH immunoreactivity (IR) was measured in 106 newborns at delivery and during the first week of postnatal life. Subjects were divided into groups according to gestational age at birth, mode of parturition, and antenatal state of health. Plasma alpha MSH IR decreased progressively from severe preterm to fullterm neonates born by vaginal delivery (VD; P < 0.001) or cesarean section (CS) with and without prenatal distress (P < or = 0.001 in both cases). alpha MSH IR was due, in all studied conditions, to three major forms: desacetyl alpha MSH, alpha MSH, and diacetyl alpha MSH. Desacetyl alpha MSH was always the most represented form, but it decreased from 75-80% of the total in severe premature to 40-45% in mature infants. In term neonates, total alpha MSH IR values were higher in subjects born by normal VD than by elective CS (P < or = 0.05), in complicated than in normal VD (P < or = 0.01), and in CS performed because of fetal distress than in elective CS (P < or = 0.01). No significant difference was detectable in mature subjects in the percentages of the three alpha MSH forms in relation to the mode of delivery and fetal state during antenatal life or at parturition. Twelve hours after birth, total alpha MSH IR significantly decreased in all groups of term newborns, reaching a plateau of 0.8-1.4 pmol/L. In premature infants, similar concentrations were detectable by the fourth postnatal day. We conclude that 1) alpha MSH IR intermediate lobe secretion progressively decreases throughout the third trimester of pregnancy; 2) stress, including that pertinent to parturition, stimulates alpha MSH IR release; and 3) pituitary intermediate lobe activity declines shortly after birth independently of the maturity reached by the fetus, the mode of parturition, and the presence of antenatal chronic distress, although the process is slightly retarded in premature newborns.     

One-sample pregnancy diagnosis in elk using fecal steroid metabolites

In utero hypoxia may affect the development of the brain and result in altered respiratory responses postnatally. Using a barometric plethysmograph, we examined the effects of exposing pregnant guinea pigs to 200 ppm carbon monoxide (CO) for 10 h/d from d 23-25 of gestation until term (approximately 68 d) on the ventilatory responses of their 4-5-d-old neonates at rest, and during progressive asphyxia and steady state hypercapnia. Exposure to this concentration of CO produced significantly higher levels of carboxyhemoglobin (COHb) in maternal (8.53 +/- 0.6% versus 0.25 +/- 0.1%) and fetal blood (13.0 +/- 0.4% versus 1.6 +/- 0.1%) from CO-treated animals when compared with controls. Hematocrit was significantly higher in the CO-treated neonates (46.3 +/- 1.0% versus 41.3 +/- 0.9%) at 5-6 d of age, although no difference existed between the groups for COHb at this time. There was no difference between the groups for length of gestation, litter size, or birth weight, but CO-treated neonates were significantly smaller at 4 d of age (102.4 +/- 3.7 g) compared with controls (132.0 +/- 5.0 g). At 4-5 d of age there was no difference between the groups for either tidal volume (VT), respiratory frequency (f), or minute ventilation (VE) at rest, but during steady state hypercapnia (4 and 6% CO2) the CO-treated neonates had a significantly greater VT and VE (but not f) than did controls. During progressive asphyxia, CO-treated animals had a significantly greater VT than did controls from 1-8% CO2. There was a significant fall in f at 1 and 3% CO2 in CO-treated animals; however, this effect did not persist, resulting in a significantly increased VE from 3 to 8% CO2. The inspiratory flow rate (VT/expiratory time) was significantly increased in the CO-treated neonates during progressive asphyxia; this occurred in the absence of a difference in inspiratory time between the groups. These results indicate that prenatal exposure to CO increases CO2 sensitivity in 4-5-d-old guinea pigs. This may be due to developmental alterations in the areas of the brainstem responsible for respiratory control.