Stimualtion of glycerolphosphate phosphatidyltransferase activity in fetal rabbit lung by cortisol administration.

Phosphatidylglycerol is an important component of pulmonary surfactant. Previous studies have shown that direct administration of corticosteroids of thyroxine to the fetus during the latter part of gestation results in accelerated lung maturation with increased surfactant production. We have shown that administration of cortisol to fetal rabbits at 24 days' gestation results 3 days later in a significant increase in the activity of pulmonary glycerolphosphate phosphatidyltransferase, an enzyme involved in the synthesis of phosphatidylglycerol. The activity of the liver enzyme was not affected. Choline phosphotransferase, CDPdiglyceride-inositol phosphatidyltransferase, lysophosphatidic acid acyltransferase and lysolecithin acyltransferase activities were not altered significantly by cortisol treatment. Thyroxine treatment had no effect on any of the enzymes of phospholipid or fatty acid biosynthesis studied.

Phospholipid content, composition and biosynthesis during fetal lung development in the rabbit.

The phospholipid content and composition of lung wash and lung tissue as well as the activities of the enzymes involved in the synthesis of phosphatidylcholine and phosphatidylglycerol (the major surface active components of pulmonary surfactant) were studied in the rabbit during fetal lung development. In lung wash the amount of phospholipid increased four-fold during the period 27-31 day's gestation. There was a further ten-fold increase following the onset breathing. During the same period the amount of phosphatidylcholine in lung wash increased from 29% of the total phospholipid to 80% while the amount of sphingomyelin decreased from 38% to 2%. The amount of phosphatidylcholine in lung tissue also increased during development but to a much lesser extent. During fetal lung development the activities of choline kinase and cholinephosphate cytidyltransferase changed little, cholinephosphotranserase decreased while lysophosphatidic acid acyltransferase and lysolecithin acyltransferase increased. There was a postnatal increase in the activities of cholinephosphate cytidyltransferase, cholinephosphotransferase and both acyltransferases. The amount of phosphatidylglycerol, as a percentage of the total phospholipid, in lung wash and lung tissue as well as the activity of pulmonary glycerolphosphate phosphatidyltransferase did not change appreciably during development.

Studies on pulmonary surfactant. Effects of cortisol administration to fetal rabbits on lung phospholipid content, composition and biosynthesis.

Corticosteroids are known to accelerate maturation of the fetal lung and production of surfactant. We examined the effect of cortisol administration to fetal rabbits on the phospholipid content and composition of lung lavage and lung tissue, as well as on the activities of enzymes involved in the synthesis of phosphatidylcholine and phosphatidylglycerol, the major surface-active components of surfactant. Cortisol was administered by intrauterine injection at 25 days' gestation and the fetuses were delivered at 27 days (full term, 31 days). Saline-injected fetuses, littermates of the cortisol-treated as well as non-littermates, were used as controls. The amount of phospholipid in lung lavage from the hormone-treated fetuses was almost double that of the saline-injected controls and was similar to that of an untreated fetus of more than 30 days' gestation. Similarly, the phospholipid composition of lung lavage from the hormone-treated fetuses was similar to that of an untreated fetus at a greater gestational age. These data, therefore, suggest that cortisol acts by accelerating physiological development. Cortisol administratration stimulated the activity of cholinephosphate cytidylyltransferase and lysolecithin acyltransferase to a small, but statistically significant extent. This is also consistent with an acceleration of normal development. The stimulation of lysolecithin acyltransferase is of interest, since this enzyme is believed to be involved in the synthesis of dipalmitoylglycerophosphocholine, the major surface-active species of phosphatidylcholine. Cortisol administration had no effect on the activities of pulmonary choline kinase, cholinephosphotransferase, lysophosphatidic acid acyltransferase and glycerolphosphate phosphatidyltranferase, although we have previously shown the latter enzyme to be stimulated following a longer period of exposure to the hormone. Saline injection produced some maturational effects presumably as a result of stress, which may be mediated by corticosteroids or other hormones.

Phospholipid biosynthesis and secretion by a cell line (A549) which resembles type II aleveolar epithelial cells.

The A549 cell line is a continuous cell line derived from a human adenocarcinoma of the lung. At low cell population density the cells contain relatively few lamellar bodies, but in mature cells in very confluent cultures lamellar bodies are abundant. The lamellar bodies from these cells are enriched for phosphatidylcholine and disaturated phosphatidylcholine. In mature cells, 45% of newly synthesized phosphatidylcholine is disaturated. Stimulation with the calcium ionophore A23187 produces exocytosis of phosphatidylcholine (46% disaturated). The A549 cell synthesizes, stores in lamellar bodies, and secretes phosphatidylcholine, and thus has many important biological properties of the alveolar epithelial type II cell.

Cardiopulmonary bypass significantly reduces surfactant activity in children.

Lung injury remains an important problem after cardiopulmonary bypass. The contribution of altered surfactant concentration or activity to pulmonary dysfunction after cardiopulmonary bypass is unclear. Recent evidence indicates that alveolar surfactant exists in specific aggregate forms that differ with respect to density, phospholipid composition, and function. A transition from surface active, higher density, large aggregates of surfactant to lower density, small aggregates that possess reduced surface activity has been demonstrated after experimental lung injury. The purpose of the present study was to examine surfactant aggregate fractions before and after bypass in children. Twelve acyanotic patients, aged 2 to 12 years, underwent intraoperative pulmonary function testing followed by bronchoalveolar lavage before incision and approximately 1 hour after termination of cardiopulmonary bypass. Saturated phosphatidylcholine pool sizes and total protein content of the small- and large-aggregate fractions of bronchoalveolar lavage fluid were determined. One hour after termination of cardiopulmonary bypass, the ratio of saturated phosphatidylcholine in small-aggregate as compared with that in large-aggregate fractions increased (mean +/- standard error) from 0.19 +/- 0.03 to 0.37 +/- 0.07 (p < 0.02), as did the ratio of saturated phosphatidylcholine to protein in the small-aggregate fraction (from 0.04 +/- 0.01 to 0.08 +/- 0.02, p < 0.05). Reductions in forced vital capacity (-19% +/- 5%), inspiratory capacity (-15% +/- 3%), and small airway flow rates (-32% +/- 6%) were also observed after bypass. These changes were accompanied by a fivefold increase in alveolar polymorphonuclear leukocyte content. The present study suggests that cardiopulmonary bypass of moderate duration in relatively healthy children is associated with surfactant changes that are similar in type and magnitude to those observed in experimental lung injury.

Efficacy of inhaled nitric oxide in a porcine model of adult respiratory distress syndrome.

OBJECTIVE: To assess the efficacy of inhaled nitric oxide (NO) in reducing pulmonary hypertension in a porcine model of adult respiratory distress syndrome. DESIGN: Nonrandomized, controlled experiment without blinding. SETTING: Surgical research laboratory. PARTICIPANTS: Twelve pigs, matched equally for body weight. INTERVENTION: Acute lung injury was induced by intravenous injection of oleic acid. Animals were then divided into either a control group, for monitoring without any further intervention, or a NO-treatment group, in which NO was administered at concentrations of 10 to 80 ppm, with each step separated by a NO-free interval to assess duration of effect. MAIN OUTCOME MEASURES: Pulmonary artery pressure, systemic blood pressure, PaO2, intrapulmonary shunt fraction, and extravascular lung water. Nitrosylated hemoglobin, arterial methemoglobin, and plasma nitrite and nitrate concentrations. RESULTS: All animals responded to oleic acid injection with rapid development of pulmonary hypertension and deterioration of PaO2 and intrapulmonary shunt fraction. Inhaled NO reversed these changes in a concentration-dependent manner. Cessation of NO administration led to a prompt return of pulmonary hypertension. A small but significant drop in systemic blood pressure was observed only at the highest concentration of NO administered (80 ppm). Extravascular lung water almost doubled following oleic acid injury. This increase was sustained in all animals for the remainder of the experiment. Significant increases in circulating methemoglobin and plasma nitrite and nitrate concentrations were measured during NO inhalation. CONCLUSION: Inhaled NO appears to be a selective pulmonary vasodilator and may prove to be useful in improving gas exchange in adult respiratory distress syndrome.

Studies on the biosynthesis of pulmonary surfactant. The role of the methylation pathway of phosphatidylcholine biosynthesis in primate and non-primate lung.

The relative importance of the choline incorporation and methylation pathways of phosphatidylcholine biosynthesis was studied in the rat, rabbit, rhesus monkey and human lung. In vitro studies showed that phosphatidylethanolamine methyltransferase activity in the lungs of all species was only a fraction of that in rat liver. In vivo experiments were carried out to study the incorporation of an intravenously administered equimolar mixture of L-[methyl-14C]-methionine and [methyl-3H] choline into lipid inthe lung and liver of the rabbit and monkey. Over 90% of the total radioactivity incorporated into lipid was found in phosphatidylcholine. In the liver, methionine incorporation was 40--71% of that of choline in the rabbit and 99--120% in the monkey while in the lungs of both species it was less than 3%. On a weight basis, choline incorporation in the lung was 2--4 times that in the liver. These findings suggest that the methylation pathway is of little quantitative significance in the biosynthesis of phosphatidylcholine in primate and non-primate lung.

Phosphatidylcholine content and fatty acid composition of tracheal and gastric liquids from premature and full-term newborn infants.

The phosphatidylcholine content and fatty acid composition of tracheal and gastric liquids from newborn full-term and premature (30-36 weeks) infants were studied. Phosphatidylcholine accounted for about 70% of the total phospholipids in both liquids from the full-term infants but only 55-57% of those from the prematures. There was a significant correlation between tracheal and gastric liquids in the fatty acid composition of phosphatidylcholine. There were significant differences in fatty acid composition between the full-term and premature liquids. These differenences were most apparent in the gastric liquid. It is suggested that phospholipid or fatty acid analysis of tracheal or gastric liquids from newborn infants can be used in the assessment of pulmonary maturity.

Pulmonary dysfunction after primary closure of an abdominal wall defect and its improvement with bronchodilators.

To determine the extent of pulmonary dysfunction following primary closure of an abdominal wall defect, we obtained pulmonary function tests (PFT) in 11 newborn infants with gastroschisis and 6 with large omphaloceles admitted to a newborn ICU in a children's hospital. Patients were 1 to 30 days of age at the time of the PFT; all required endotracheal intubation and mechanical ventilation for operative procedures or for postoperative ventilatory support. Full-term infants (n = 21) undergoing minor surgical procedures provided comparative measurements. Flow-volume curves were obtained with manual inflation of the lungs followed by forced deflation using negative pressure, or by passive expiration, under sedation and pharmacologic paralysis. Deflation flow-volume curves gave measurements of forced vital capacity (FVC) and maximal expiratory flow at 25% of vital capacity from residual volume (MEF25). Modified passive mechanics technique gave passive expiratory curves that provided measurements of respiratory system compliance (Crs) and resistance (Rrs). Tests were done: within 48 h (period A), 3-7 days (period B), and 8-30 days after surgical repair (period C). Pulmonary function testing after nebulized 0.1% isoetharine (a bronchodilator), to test for bronchial reactivity, began midway during the study period in 15 patients. Preoperative and postoperative tests were obtained in 5 patients. Closure of an abdominal wall defect decreased FVC, Crs, and MEF25 by up to 50% of normal, reference values after surgery (P less than 0.05). FVC and MEF25 approached values of normal infants by 4 weeks, whereas Crs remained 50% lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal changes in lung function during the first three years of premature infants with moderate to severe bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic obstructive pulmonary disease of prematurely born infants following prolonged mechanical ventilation and oxygen therapy. Developmental changes in pulmonary function of children with BPD during their early years have been difficult to study. We longitudinally studied maximal expiratory flow-volume curves by the forced deflation technique in 11 infants who had previous tracheostomy with moderate to severe BPD. Patients were classified into: those who were mechanically ventilated for less than 5 months (Group A), and those who were ventilated for 10 or more months (Group B). At 6 months of age, forced vital capacity (FVC) was 28.1 and 25.5 mL/kg in Group A and B, respectively, significantly less than normal (41.8 mL/kg). The maximum expiratory flow at 25% FVC (MEF25) at 6 months of age was 6.9 and 8.1 mL.kg-1.s-1 in Group A and B, respectively, (predicted value, 39.2 mL.kg-1.s-1). FVC reached the normal range by 12 months of age in Group A, but remained lower until 36 months of age in Group B. MEF25 gradually increased in Group A, reaching 18.0 mL.kg-1.s-1 at 36 months of age, whereas in Group B it was severely decreased at the same age (3.5 mL.kg-1.s-1). More than 75% of the patients had airway hyperreactivity at all ages. We have demonstrated that in patients with moderate to severe BPD, vital capacity is moderately decreased, but catches up to normal levels by 36 months of age. In contrast, severe lower airway obstruction persists in all infants, although in those with moderate BPD gradual improvement is seen. These findings suggest that in BPD neither obstruction of the smaller intrathoracic airways nor bronchial hyperreactivity resolves during the first 3 years of life.

Evolution of airway hyperresponsiveness in infants with severe congenital diaphragmatic hernia.

Infants born with severe congenital diaphragmatic hernia (DH) characteristically have pulmonary hypoplasia. Airway hyperresponsiveness during the first 4 weeks of life can be demonstrated in most of these neonates. Early postnatal pulmonary development in infants with severe DH has not been well characterized. We examined lung growth in patients with congenital DH by using the forced deflation method to study pulmonary function in 18 infants on mechanical ventilation who survived neonatal repair of their congenital DH. Thirteen infants without primary pulmonary pathology who required general anesthesia for other surgery served as controls. Infants were further divided according to age at the time of testing into early (age < or = 7 days at time of testing) and late (age > or = 29 days) groups, yielding four groups of subjects: early diaphragmatic hernia (EDH): n = 9; mean age, 4.2 days; range, 1-7 days; early controls (EC): n = 8; mean age, 3.1 days; range, 1-6 days; late diaphragmatic hernia (LDH): n = 11; mean age, 57.7 days, range, 28-120 days; and late controls (LC); n = 5; mean age, 52.2 days; range 32-90 days. All infants were studied once, with the exception of two infants with DH who were studied on two occasions at EDH and LDH stages. A marked reduction in weight-corrected forced vital capacity (FVC) was seen in the EDH group (13.9 +/- 3.9 ml/kg) as compared to the EC group (44.4 +/- 4.9 ml/kg). During the ensuing 4 months of life, FVC in patients with LDH (24.5 +/- 1.9 ml/kg) was much higher than FVC in patients with EDH (P < 0.05). These findings demonstrate the presence of pulmonary hypoplasia in the EDH group and suggest subsequent rapid postnatal lung growth. An index of rate constant, MEF25/FVC, as compared with control groups was abnormally elevated in EDH subjects (1.87 +/- 0.30/second vs 1.16 +/- 0.32/ second, P < 0.05), indicating significantly increased lower airway caliber relative to lung volume. The severe reduction of the rate constant in the LDH group (0.36 +/- 0.05/second vs 0.73 +/- 0.07/second, P < 0.05) suggests the development of lower airway obstruction. After the administration of a nebulized bronchodilator (BD), an increase in MEF25 (32.9%) in the EDH group was not significant, but an increase of 134.7% in the LDH group was significant (P < 0.05). Although the study utilized a cross-sectional design with most of the infants in either the early or late group, present findings suggest that infants with EDH have lung restriction reflecting pulmonary hypoplasia. These infants developed lower airway obstruction and airway hyperresponsiveness with only mild fixed obstruction over the first 4 months of life.

Pulmonary function in newborns after repair of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia that limits survival, but the nature and extent of pulmonary dysfunction in neonates with CDH have not been studied. We performed pulmonary function tests (PFTs) in eight intubated infants who survived neonatal repair of CDH (wt, 3.33 +/- 0.15 kg; age, 20.1 +/- 2.7 d; mean +/- S.E.M.). PFTs obtained from six full-term infants (wt, 3.56 +/- 0.15 kg; age, 25.0 +/- 3.3 d) with no respiratory illness served as controls. The deflation flow-volume curve technique produced maximum expiratory flow-volume (MEFV) curves, giving reproducible measurements of forced vital capacity (FVC) and maximal expiratory flow at 25% of FVC (MEF25). Respiratory system compliance (Crs) and resistance (Rrs) were obtained with a modified passive mechanics technique. In seven of eight infants PFTs were repeated after nebulized bronchodilator (0.1% isoetharine). In neonates surviving CDH repair, as compared to those with normal lung function, FVC was significantly reduced (20.78 +/- 3.32 vs. 39.83 +/- 3.30 mL.kg-1, P less than 0.05). MEF25 was also markedly reduced (20.78 +/- 3.32 vs. 39.83 +/- 3.30 mL.kg-1.s-1, P less than 0.05), indicating lower airway obstruction. After administration of nebulized bronchodilator, PFTs showed significant increases from control values in both FVC (15.9%) and MEF25 (200%) without changes in Crs and Rrs. These findings indicate that neonates with CDH have restrictive lung defects, reflecting hypoplasia. After surgical repair and mechanical ventilation airway reactivity develops, primarily in smaller airways, and this may complicate the postoperative course.

Bronchial reactivity in infants in acute respiratory failure with viral bronchiolitis.

Airway reactivity and the effects of bronchodilators in infants are controversial. We studied the response to bronchodilator treatment in 14 mechanically ventilated infants (mean age, 2.74 months; range, 0.6-5.9) in respiratory failure caused by respiratory syncytial virus (RSV)-associated bronchiolitis. Sixteen infants without lung disease, undergoing elective surgery, provided normal values. Maximum expiratory deflation flow-volume (DFV) curves were produced by manual inflation of the lungs with an anesthesia bag to a predetermined static airway pressure followed by rapid deflation with a negative airway pressure before and after administration of bronchodilator. At baseline, the bronchiolitis group had a forced vital capacity (FVC) of 34.5 +/- 3.6 ml/kg compared with 41.8 +/- 1.5 ml/kg in the normal group; maximum expiratory flow rate at 25% of FVC (MEF25) was 10.2 +/- 2.0 ml/kg/s compared with 27.3 +/- 2.0 ml/kg/s in the normal group. The clinical and radiologic impression was severe lower airway obstruction and air trapping. After administration of bronchodilator, FVC did not increase significantly, but MEF25isov increased by over 30% in 13 of 14 infants. Mean MEF25 increased by 148 +/- 43.2% to 21.7 +/- 3.9 ml/kg/s (P less than 0.02). These findings indicate that during the acute phase of severe RSV-positive bronchiolitis most infants have airway reactivity that responds positively to bronchodilator treatment.

Longitudinal follow-up of lung function from childhood to adolescence in prematurely born patients with neonatal chronic lung disease.

We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean +/- SD) of 8.2 +/- 1.2 years to the age of 15.1 +/- 1.6 years. They had been born at 29.1 +/- 1.9 weeks of gestation, with a birthweight of 1120 +/- 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 +/- 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV1), and the ratio FEV1/FVC remained at or above the predicted normal range in all patients. FEF25-75, FEF50, and FEF75 were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. in contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity.

The phospholipids of rabbit type II alveolar epithelial cells: comparison with lung lavage, lung tissue, alveolar macrophages, and a human alveolar tumor cell line.

The phospholipid composition of type II alveolar epithelial cells from the rabbit was compared with that of alveolar macrophages, lung lavage and lung tissue. In addition, the phospholipid composition of a human alveolar tumor cell line, which is morphologically similar to type II cells, was examined. Phosphatidylcholine accounted for 48% of the total phospholipid in the type II cells, 41% in the tumor cells, and 30% in the macrophages. Phosphatidylcholine was 51% disaturated in the type II cells, 54% in lung lavage, 39% in whole lung, 29% in lavaged lung and macrophages, and 16% in the tumor cells. Palmitic acid was the major fatty acid in phosphatidylcholine from all samples with the exception of the tumor cells in which almost half of the fatty acids were accounted for by oleic acid. The phospholipids of the type II cells were more similar to those of lung lavage, and thus surfactant, than to lung tissue and macrophages. This is consistent with their supposed role in surfactant production. The tumor cells, although morphologically similar to type II cells, were quite different with respect to phospholipid composition.

Pulmonary function studies in a newborn with congenital laryngeal atresia.

Congenital laryngeal atresia is a rare cause of upper airway obstruction that leads to death unless a surgical airway is immediately established. We were able to resuscitate a baby boy with laryngeal atresia by the placement of an 18-gauge plastic intravenous cannula into the trachea, connected in turn to a 3-mL syringe without the plunger, and then to the connector to a 7.0-mm endotracheal tube. This arrangement allowed hand ventilation and sufficient gas exchange until a formal tracheotomy was established minutes later. The baby boy had deficient abdominal musculature (without cryptorchidism or obstructive uropathy), bilateral inguinal hernias, and idiopathic hypercalcemia (since spontaneously resolved), but no other major anomalies. His survival allowed measurements of pulmonary function in lungs distal to an obstructed upper airway, an arrangement that mimics experiments that examine the influence of lung fluid volume and pressure on developing lungs. The baby's lungs had a forced vital capacity (FVC) in the upper limits of normal (not grossly enlarged lungs seen in newborn animals undergoing ligation of the trachea in utero). Maximal expiratory flow at 25% of FVC from residual volume (MEF25) was decreased, indicating airway obstruction involving smaller airways. Although direct laryngoscopy failed to find a opening in the larynx, some communication probably existed during development to allow some drainage of lung fluid. This opening, in the form of a persistent pharyngoglottic duct, prevented gross distention of the developing lung, but provided an insufficient airway at birth.

Tidal flow measurement in the decision to decannulate the pediatric patient.

Measurements of peak inspiratory flow obtained through the tracheostomy cannula (MIFT) during tidal breathing were compared to peak inspiratory flow measurements obtained through the mouth (MIFM) in 40 children to assess physiologic readiness to decannulate the tracheostomized pediatric patient. Ratio of peak flow MIFM/MIFT was 1.40 for 34 successfully decannulated children compared to 0.83 for 22 unsuccessful attempts (p less than 0.01). Tidal flow measurements are highly predictive (84%) in identifying children who are unlikely to be ready for decannulation. A schema is proposed to utilize tidal flow measurements as the first step in the decannulation process.

Pulmonary aspiration in pediatric patients during general anesthesia: incidence and outcome.

STUDY OBJECTIVES: To determine the incidence of, outcome of, and risk factors for anesthesia-related pulmonary aspiration in the predominantly pediatric population receiving anesthesia care. DESIGN: Using a clinical concurrent quality assessment system we developed, we used data stored in a custom-designed computerized database to initiate a retrospective review. Statistical relationships were analyzed by Fisher's exact test and binary logistic regression with commercially available software. SETTING: University-affiliated pediatric hospital. PATIENTS: All patients receiving anesthesia (n = 50,880) between April 1, 1988, and March 31, 1993. MEASUREMENTS AND MAIN RESULTS: Aspiration occurred in 52 (0.10% or 10.2 per 10,000) of the 50,880 general anesthesia cases. Aspirate was food or gastric contents in 25 cases (0.049% or 4.9 per 10,000), blood in 13 (0.026% or 2.6 per 10,000), and unknown material in 14 (0.0275% or 2.76 per 10,000). There were no deaths attributable to aspiration. Morbidity was confined to unanticipated hospital admission (n = 12), cancellation of the surgical procedure (n = 4), and intubation, with or without ventilation (n = 15). Aspiration occurred significantly more often in patients with greater severity of underlying illness (ASA physical status III or IV) (p = 0.0015), intravenous induction (p = 0.0054), and age equal to or greater than 6.0 years and less than 11.0 years (p = 0.0029). Emergency procedures had a marginally significant increased aspiration risk (p = 0.0527). CONCLUSIONS: The overall incidence of anesthesia-related aspiration in our series (0.10%) was twice that reported in studies of adults, and four times (0.25%) higher for those at highest risk (ASA physical status III or IV vs. physical status I or II). Anesthesia-related pulmonary aspiration was proven to be a rare event in this tertiary pediatric center and its consequences relatively mild. Because of the very low frequency and the lack of serious outcome after aspiration in ASA physical status I and II pediatric patients, it appears that routine prophylactic administration of histamine blockers or propulsive drugs in healthy pediatric patients is unwarranted.

Bioimpedance measurement with respect to pulsatile pulmonary blood flow.

We used four-electrode electrical impedance plethysmography (IPG) to estimate regional pulmonary perfusion at three lung volumes, RV, FRC, and TLC. To define the region, the upright lung was divided into four equal sampling areas dorsally along the paravertebral space. The Kubicek formula was used to calculate pulmonary perfusion. Regional base resistance (Ro) decreased from the top to about 3/4 down the lung and then leveled off. The regional perfusion (Qz) showed an increase from the apex to about 3/4 down the lung and thereafter decreased toward the base, except at TLC. The regional distribution of the electrical derivative of resistance (dR/dt) resembled that of Qz because there was no statistically significant difference in ventricular ejection time or heart rate among studies. The value of the arithmetic sum of regional Ro was significantly larger than that of Ro for the total sampling field while the reverse was true for Qz. These discrepancies can be explained on the basis of the lead field theory applied to IPG. The regional perfusion gradient determined by IPG represents the pulsatile perfusion gradient in vivo because the outputs from the impedance analyzer are intimately linked to the pulse-synchronous pulsatile nature of pulmonary blood flow. Safe, simple, and noninvasive IPG can be used to study regional pulmonary perfusion in clinical situations, high altitude, or unusual environments.