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For the last thirty years, oral chloral hydrate has been used for sedation of infants for lung function testing. Recently, however, availability of chloral hydrate became severely limited in the United States after two manufacturers discontinued manufacturing in 2012. Due to these limitations and the recent and ongoing shortage of chloral hydrate, other medications have been proposed for lung function testing, including midazolam and propofol. Herein, we describe our limited experience using intravenous dexmedetomedine (DMED), a medication thus far described as having minimal effect on pulmonary function or respiratory drive., (© 2014 Wiley Periodicals, Inc.)

Background: VEPTR (vertical expandable prosthetic titanium rib) expansion thoracoplasty is used to manage thoracic insufficiency syndrome in early-onset scoliosis. Literature regarding the effects of this technique on pulmonary function is scarce. The aim of this study was to report the intermediate-term results of VEPTR expansion thoracoplasty., Methods: Twenty-one children with thoracic insufficiency syndrome underwent VEPTR expansion thoracoplasty from 2002 to 2012 and had complete chart data, preoperative and follow-up radiographs, and pulmonary function tests performed at the index implantation, first expansion, and last expansion. Pulmonary function tests with forced and passive deflation techniques developed for children under general anesthesia were performed prior to the index implantation and each expansion surgery under the same anesthetic conditions. Pulmonary and radiographic parameters were analyzed longitudinally., Results: Mean follow-up was six years, and mean age at implantation was 4.8 years. The mean number of expansion procedures per patient was eleven, and the mean number of pulmonary function tests was ten. The mean interval between surgical procedures was 6.4 months. Mean forced vital capacity (FVC) increased from 0.65 to 0.96 L (p < 0.0001). However, the percentage of the predicted FVC decreased from 77% to 58%. Respiratory system compliance normalized on the basis of body weight, Crs/kg, decreased by 39%, from 1.4 to 0.86 mL/cm H 2 O/kg. The mean Cobb angle before treatment was 80°, and the mean maximum thoracic kyphosis angle was 57° (range, 7° to 107°). The initial coronal correction was maintained at the time of final follow-up (67°); however, there was a trend toward a decrease in the maximum thoracic kyphosis angle (to 66°, p = 0.08). Clinically apparent proximal thoracic kyphosis occurred in four patients, and spinal imbalance occurred in seven. The mean gain in T1-T12 height during the treatment period was 18 mm (2.9 mm/year)., Conclusions: FVC improved over time; however, this increase in lung volume did not keep up with the growth of the child, as the percentage of the predicted FVC decreased, and the chest wall stiffness increased. Coronal correction was maintained, but the increase in proximal thoracic kyphosis is concerning., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Neuromuscular blocking drugs have been implicated in intraoperative bronchoconstrictive episodes. We examined the effects of clinically relevant doses of cisatracurium and rocuronium on the lung mechanics of pediatric subjects. We hypothesized that cisatracurium and rocuronium would have bronchoconstrictive effects., Methods: We studied ASA physical status I and II pediatric subjects having elective dental or urological procedures, requiring general anesthesia with endotracheal intubations with either cisatracurium or rocuronium. Pulmonary function tests were performed before and after neuromuscular blocking drug dosing and again after albuterol administration. Using forced deflation and passive deflation techniques, forced vital capacity (FVC) and maximum expiratory flow rate at 10% (MEF10) of FVC were obtained. Fractional changes from the baseline were used to compare subjects. Changes in MEF10 of >30% were considered clinically significant. A Shapiro-Wilk test, paired t test, and Wilcoxon rank sum test were used to analyze the data., Results: Twenty-five subjects (median age = 5.25 years; range = 9 months-9.9 years) were studied; 12 subjects received cisatracurium and 13 subjects received rocuronium. Data are shown as mean proportional change ± SD or, in the case of not normally distributed, median proportional change (first, third quartile) with P values. In the cisatracurium group, there were no differences between baseline and postneuromuscular blocker administration in the fractional change from the baselines of FVC (1.00 ± 0.04, P = 0.5), but there was a significant decrease in MEF10 (0.80 ± 0.18, P = 0.002). In the rocuronium group, there were small yet significant decreases of FVC (0.99 [first quartile 0.97, third quartile 1], P = 0.02) and significant decreases in MEF10 (0.78 ± 0.26, P = 0.008). After administration of albuterol in the cisatracurium group, FVC increased slightly but significantly from baseline values (1.02 ± 0.02, P = 0.005). MEF10 increased significantly beyond baseline values (1.24 ± 0.43, P =0.04). In the rocuronium group, there were also significant differences between baseline and postalbuterol administration from the baseline value of FVC (1.02 ± 0.02, P = 0.004) and MEF10 (1.23 ± 0.29, P = 0.01)., Conclusions: At clinically relevant doses, both cisatracurium and rocuronium caused changes in lung function, indicating constriction of smaller airways. In general, these changes were mild and not clinically detectable. However, in the rocuronium group, 3 of 13 patients showed more noticeable decreases in MEF10 (≤50%), demonstrating the potential for significant broncho-bronchiolar constriction in susceptible patients.

The effect on pulmonary function of serial VEPTR expansion thoracoplasty was studied longitudinally in anesthetized children with spondylothoracic dysplasia using a special mobile unit. The median age of 24 children at the start of surgery was 4.6 years (1.8-10.8) and most exhibited a moderate-to-severe restrictive lung defect. After a median of 3.2 years (1.0-6.5), their forced vital capacity (FVC) was found to have increased by an average of 11.1%/year. The rate of increase was greater in children who were younger than 6 years at the start of the study than in older children (14.5% versus 6.5%, p<0.01). The average specific respiratory system compliance (C(rs)) was mildly-to-moderately decreased at the start, and over the study it decreased on average to 56% of the initial value in spite of clinically successful expansion thoracoplasty and lung growth, indicating increasing stiffness of the thorax with growth.

Background: Imaging studies have shown that general anesthesia in children results in atelectasis. Lung recruitment total lung capacity (TLC) maneuvers plus positive end-expiratory pressure (PEEP) are effective in preventing atelectasis. However, physiological changes in children during general anesthesia have not been elucidated., Methods: In eight anesthetized and mechanically ventilated children (median age: 3.5 years; range: 2.3-6.5), we measured static respiratory system elastance (E(st)), flow resistance (R(int)), and elastance and resistance components resulting from tissue viscoelasticity (deltaE and deltaR, respectively) using the constant inflow, end-inspiratory occlusion method preceded by TLC maneuvers, both with zero PEEP (ZEEP) and PEEP (5 cm H2O) for comparison., Results: With constant inspiratory flow V(I) and ZEEP, increases in end-inspiratory lung volume above relaxation volume (tidal volume, V(T)) from 8 to 20 mL x kg(-1) resulted in decreases in E(st) from 1.06 to 0.82 cm H2O x mL(-1) x kg, deltaE from 0.16 to 0.09, and R(int) from 0.13 to 0.11 cm H2O x mL(-1) x s x kg, whereas deltaR increased from 0.08 to 0.12 (P < 0.05). Similar relationships were found with PEEP. Increases in V(I) (8 to 26 mL x s(-1) x kg) with constant V(T) and ZEEP resulted in decreases in E(st) from 1.09 to 0.9 and deltaR from 0.17 to 0.06 (P < 0.01), whereas deltaE and R(int) did not change. There was a similar flow and volume dependence of elastance and resistance with PEEP., Conclusions: The observed steady decreases in E(st) with increasing V(T) (up to 16 mL/kg with PEEP) indicate marked reductions in end-expiratory relaxation volume (functional residual capacity) even with PEEP. Similarity in results with ZEEP and PEEP suggests that TLC-maneuvers and O2-N2 ventilation prevented airway closure throughout the study.

This statement on the management of patients with Duchenne muscular dystrophy (DMD) undergoing procedural sedation or general anesthesia represents the consensus opinion of a multidisciplinary panel convened under the auspices of the American College of Chest Physicians. Expert recommendations on this subject are needed for several reasons. First, patients with DMD have an increased risk of complications when they undergo sedation or general anesthesia. In addition, due to improved cardiopulmonary therapies, patients with DMD are experiencing an unprecedented duration of survival. As a result, it is more common for them to require procedures involving sedation or general anesthesia. The risks related to anesthesia and sedation for DMD patients include potentially fatal reactions to inhaled anesthetics and certain muscle relaxants, upper airway obstruction, hypoventilation, atelectasis, congestive heart failure, cardiac dysrhythmias, respiratory failure, and difficulty weaning from mechanical ventilation. This statement includes advice regarding the highly interrelated areas of respiratory, cardiac, GI, and anesthetic management of patients with DMD undergoing general anesthesia or procedural sedation. The statement is intended to aid clinicians involved in the care of patients with DMD and to be a resource for other stakeholders in this field, including patients and their families. It is an up-to-date summary of medical literature regarding this topic and identifies areas in need of future research.

Study Design: Longitudinal study of intraoperative pulmonary function in young children with thoracic hypoplasia and scoliosis undergoing multiple expansion thoracoplasty using the vertical expandable prosthetic titanium ribs (VEPTRs)., Objective: To test the long-term efficacy of VEPTR multiple expansion thoracoplasty., Summary of Background Data: To our knowledge, no direct measurements of pulmonary function have been reported with VEPTR expansion thoracoplasty., Methods: There were 10 children with thoracic insufficiency syndrome, secondary to thoracic hypoplasia with progressive scoliosis, studied. A mobile pulmonary function laboratory unit was used to study forced vital capacity (FVC), maximum expiratory flow volume curves, and respiratory system compliance (Crs) with the patient under general anesthesia immediately before and after expansion thoracoplasty. Studies were repeated every 6 months at each subsequent operation for expansion thoracoplasty for the duration up to 33 months., Results: At the baseline studies, FVC showed a moderate-to-severe decrease (69% of predicted values), indicating the presence of significant restrictive lung defect. Only 1 of 10 children had severe airway obstruction. The baseline Crs was markedly decreased in part because of the presence of significant atelectasis. Crs increased with an average of 42% after repeated hyperinflation (deep sighs). There was no change in lung volume or function immediately before versus after completion of expansion thoracoplasty. FVC increased significantly over time, with an average rate of 26.8% per year, the rate of increase similar to that of healthy children of comparative ages. In terms of percent-predicted values, FVC did not change significantly between the baseline and last test, indicating that in most children studied, lung growth kept up with body growth., Conclusion: Although it is difficult to assess the extent of the efficacy without a proper or historical control group for comparison, the present study indicates that in children with severe thoracic insufficiency syndrome, the insertion of VEPTRs with multiple expansion thoracoplasties is beneficial over time, by allowing the lungs to expand with body growth without further deterioration in lung function.

Unlabelled: The administration of rapacuronium increases the risk of severe bronchospasm. There have been no studies of pulmonary function directly demonstrating airway constriction with rapacuronium in children. In this study, 10 ASA physical status I or II patients (aged 2-6 yr) were randomly divided into 2 equal groups, receiving either rapacuronium or mivacurium. Anesthesia was induced with sevoflurane and maintained with remifentanil (0.2-0.3 microg. kg(-1). min(-1)) and propofol (200-250 microg. kg(-1). min(-1)) infusions. We performed three sets of pulmonary function tests: baseline, after the administration of muscle relaxant, and after the administration of a beta(2) agonist. In both groups, there were no changes in static respiratory compliance. The increase in total respiratory system resistance after the administration of rapacuronium did not reach statistical significance (214.4% +/- 122.65% of baseline, P approximately 0.1), whereas maximal expiratory flow at 10% of forced vital capacity (MEF)(10) and MEF(functional residual capacity) on partial flow-volume curves by the forced deflation technique decreased markedly (53.4% +/- 18.49%, P < 0.01 and 41.3% +/- 27.42%, P < 0.001, respectively). With the administration of mivacurium, no changes were observed in respiratory system resistance (109.5% +/- 30.28%). MEF(10) decreased slightly (77.0% +/- 9.03%, P < 0.005) whereas MEF(FRC) did not (81.2% +/- 29.85%, not significant). After the administration of a beta(2) agonist, all measurements returned to baseline. Thus, the administration of rapacuronium consistently results in lower airway obstruction with minimal changes in static respiratory compliance when compared with mivacurium., Implications: Pulmonary function tests in the present study showed that rapacuronium consistently causes severe bronchoconstriction, confirming clinical case reports of bronchospasm. The bronchoconstriction is reversible with albuterol. Mivacurium also causes very mild subclinical bronchoconstriction.

Work of breathing (WOB) increases during general anesthesia in adults, but such information has been limited in pediatric patients. We studied WOB in 24 healthy children (mean age 2+/-1.9 yrs), during elective urogenital surgery under 1 minimum alveolar anesthetic concentration halothane-nitrous oxide anesthesia with a caudal block while breathing spontaneously. WOB was measured with an esophageal balloon, miniature flowmeter, and a computerized (Bicore) system. In each patient, WOB was computed under four conditions: a mask without oral airway (-AW), a mask with oral airway (+AW), a laryngeal mask airway (LMA), and an endotracheal tube (ETT). With each apparatus WOB was studied both with continuous positive airway pressure (CPAP) (5-6 cm H(2)O) and without CPAP (or zero end-expiratory pressure [ZEEP]). Under ZEEP, WOB (g x cm/kg) among the four apparatus were (mean +/- SEM): mask (-AW) (64 +/-19.2) > mask (+AW) (44+/-17.2), LMA (42+/-15.6) > ETT (25.4+/- 12.4) (P<0.05). WOB with CPAP significantly (P<0.05) decreased from WOB with ZEEP in three groups (mask [-AW], mask [+AW], and LMA), but not in the ETT group. Tidal volume (both ZEEP and CPAP) and end-tidal PCO(2) (with CPAP only) were significantly (P<0.05) decreased only in the ETT group, whereas no significant difference was found in respiratory rate or minute volume among the four airway apparatus groups, either with or without CPAP. The reduction in WOB, when breathing through ETT was primarily attributable to decreases in tidal volume and volume work. The finding that WOB decreases with CPAP in all groups except for the ETT group suggests that the decrease is a result of improved patency of the upper airway rather than of increases in functional residual capacity and lung compliance.

With the use of constant flow, end-inspiratory airway occlusion, respiratory system resistance (Rrs) can be partitioned into a flow resistive component (Rint) and an additional component (deltaR), reflecting viscoelasticity and time constant inequality. Similarly, respiratory system elastance (Edyn) can be partitioned into static elastance (Est) and elastance due to viscoelasticity and time constant inequality (deltaE). We measured Rrs and Edyn and their subdivisions (Rint and deltaR, Est and deltaE, respectively) and studied their flow and volume dependence in eight otherwise healthy children (median age 3.6 y; range 1.9-5.2 y) undergoing general anesthesia for oral rehabilitation. With a constant inspiratory flow (VI) of approximately 15 mL/s/kg and tidal volume of 12 mL/kg, the mean values of Rrs, Rint, and deltaR were: 0.20, 0.11, and 0.10 cmH2O/mL/s.kg. Under the same conditions, the mean Est and deltaE were: 1.04 and 0.12 cmH2O/mL/kg. With increasing VI and under constant VT, deltaR decreased (p < 0.001) progressively. Rint also decreased paradoxically (p < 0.001). Hence, Rrs decreased (p < 0.001) with increasing VI. Est decreased (p < 0.001) with increasing VI, whereas delta E increased (p < 0.005). With increasing VT and under constant VI, Rint decreased (p < 0.001) and deltaR tended to increase (p = 0.058); Rrs did not change. With increasing VT under constant VI, both Est and deltaE decreased (p < 0.001 and p = 0.001, respectively). Thus, in contrast to the findings in adults, Rint and Est decreased in children with increasing flow and under constant tidal volume, probably reflecting decreased functional residual capacity in anesthetized children, compared with adults. The flow and volume dependence of deltaR and deltaE were similar to those in adults, whereas Rrs did not necessarily follow the direction of changes of deltaR.

Using end-inspiratory airway occlusion, respiratory system resistance (Rrs) can be partitioned into a flow-resistive component (Rint), and an additional component (DeltaR), reflecting viscoelasticity and time constant inequalities. We studied flow and volume dependence of Rrs and its subdivisions (Rint and DeltaR) in 13 children, seven mechanically ventilated for pulmonary insufficiency (Group 1; six with parenchymal lung disease; one with lower airway obstruction) and six without primary lung disorder (Group 2). In comparison with healthy children, Rint was increased in the patient with lower airway obstruction and five of six patients without primary lung disorder but in only one of six with parenchymal lung disease. DeltaR was increased in all seven patients in Group 1 and in four of six patients in Group 2. The directions of changes in Rint and Rrs with increasing flow (isovolume conditions) and with increasing volume (isoflow conditions) were variable. DeltaR decreased exponentially (p < 0.05) with increasing flow in 11 of 13 subjects and increased with increasing tidal volume (VT) in 12 of 13. Thus, DeltaR was increased in most children on mechanical ventilation with or without primary lung disease; its volume and flow dependence were opposite to that of airway resistance.

We postulated that prolonged exposure to intermittent positive-pressure ventilation (IPPV) with high pressure (HIPPV) alone without hyperoxia promotes the development of airway hyperresponsiveness and remodeling. To test this hypothesis, young rats were ventilated under halothane anesthesia with HIPPV (maximum inspiratory pressure at 32-35 cmH2O in 70% nitrous oxide and 30% O2) for 3.5-4 h daily for 6 days. Control rats were ventilated with low IPPV (maximum inspiratory pressure < 13 cmH2O) during the same time period with the same gas mixture. With the use of tracheal rings isolated from these rats and a setup in tissue baths, contractile responses to carbachol (10(-6) to 10(-2) mM), 5-hydroxytryptamine (5-HT; 10(-9) to 10(-5) mM) and KCl (1-100 mM) were examined isometrically. In tracheal rings from HIPPV rats compared with low-pressure IPPV rats, the concentration tension curves showed a significantly enhanced response to all agonists (P < 0.005). Sensitivity to carbachol, 5-HT, and KCl was also significantly increased (P < 0.05) compared with control rats as evidenced by decreases in EC50. Maximum tension (reactivity) to 5-HT and KCl in the HIPPV group increased significantly (P < 0.05), and there was a trend (P = 0.07) toward increased reactivity to carbachol in this group as well. Histological examinations of tracheal rings demonstrated epithelial squamous metaplasia in the HIPPV group. Morphometric studies demonstrated tracheal smooth muscle thickening (P < 0.05) without changes in the thickness of the mucosa or the lamina propria. When contractile responses were normalized for the smooth muscle cross-sectional area (i.e., stress), reactivity to all contractile agents was reduced, whereas reactivity to 5-HT still demonstrated significant increase (P < 0.005). Sensitivity of tracheal segments to all three agents was not affected by this normalization. These findings suggest that prolonged exposure to HIPPV without hyperoxia and the resultant overdistension of lung tissues (volutrauma) induced airway remodeling and airway hyperreactivity.

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.

Objective: To assess the efficacy of inhaled nitric oxide in improving pulmonary hypertension and gas exchange following oleic acid-induced acute lung injury., Design: Prospective, pharmacologic study., Setting: Surgical research laboratory at the University of Pittsburgh, Pittsburgh, PA., Subjects: Instrumented, intubated pigs weighing 16 to 27 kg., Interventions: Intravenous oleic acid and inhaled nitric oxide., Measurements and Main Results: All pigs treated with intravenous oleic acid (0.11 mL/kg) developed a severe lung injury with pulmonary hypertension, accompanied by impaired oxygenation, intrapulmonary shunting, and increased extravascular lung water (p < .05 compared with baseline). Following nitric oxide inhalation, although pulmonary hypertension decreased in a dose-dependent fashion, no amelioration in pulmonary gas exchange was observed, as reflected by PaO2 and intrapulmonary shunt. Plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, did not increase following nitric oxide exposure in this model of severe lung injury., Conclusions: The effect of inhaled nitric oxide, restricted to relieving pulmonary vasoconstriction in this model of lung injury, may have limited benefit in improving pulmonary gas exchange when diffusion is impaired by severe lung injury and inflammatory thickening of the alveolar-capillary barrier. Nitric oxide inhalation may have better results when used at an earlier, less severe stage of acute lung injury.

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.

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.

Objective: To determine whether airway hyperresponsiveness contributes to the development of lower airway obstruction in infants recovering from severe meconium aspiration syndrome treated with extracorporeal membrane oxygenation (ECMO)., Design: Prospective comparison study of the response to bronchodilator during the acute and convalescent phase of severe meconium aspiration., Setting: Pediatric/neonatal intensive care unit in a tertiary care hospital., Patients: Seven neonates with severe meconium aspiration syndrome that was refractory to conventional mechanical ventilation, requiring ECMO treatment., Interventions: Evaluation of the effect of bronchodilator treatment on the airway function at a postnatal age of 14 +/- 2.7 (SEM) days, after the patients had been off ECMO for 4.6 +/- 1.4 days, and comparison with the response the same patients had shown at a postnatal age of 2.7 +/- 0.6 days, when they had been on ECMO for 1.3 +/- 0.6 days. Lung mechanics and lower airway function were measured and compared before and after administration of aerosolized isoetharine early in the course of ECMO and again several days after ECMO. Maximum expiratory flow-volume curves produced by the deflation flow-volume curve technique were used for evaluating the lower airway function, and partial passive flow-volume curves were used for measuring respiratory system compliance and resistance., Measurements and Main Results: During the first test, isoetharine produced a mild increase in maximum expiratory flows at 25% (MEF25) of forced vital capacity (FVC) (48 +/- 27% compared with baseline values), without significant change in the MEF25 to FVC ratio. During the second test approximately 2 wks later (post-ECMO), isoetharine increased MEF25 by 123 +/- 29% and increased the MEF25/FVC by 40 +/- 13% compared with baseline values. The percent change in both indices was significantly higher during the second test (p < .05) than in the first test., Conclusions: Airway obstruction in infants recovering from severe meconium aspiration syndrome is partially reversible with aerosolized isoetharine, indicating that airway hyperresponsiveness contributes to the pathogenesis of airway obstruction.

Background: For pediatric patients, sevoflurane may be an alternative to halothane, the anesthetic agent used most commonly for inhalational induction. The induction, maintenance, and emergence characteristics were studied in 120 unpremedicated children 1-12 yr of age randomly assigned to receive one of three anesthesia regimens: sevoflurane with oxygen (group S), sevoflurane with nitrous oxide and oxygen (group SN), or halothane with nitrous oxide and oxygen (group HN)., Methods: Anesthetic was administered (via a Mapleson D, F or Bain circuit) beginning with face mask application in incremental doses to deliver maximum inspired concentrations of 4.5% halothane or 7% sevoflurane. End-tidal concentrations of anesthetic agents and vocal cord position were noted at the time of intubation. Elapsed time intervals from face mask application to loss of the eyelash reflex, intubation, surgical incision, and discontinuation of the anesthetic were measured. Heart rate, systolic, diastolic, and mean blood pressures, and end-tidal anesthetic concentrations were measured at fixed intervals. Anesthetic MAC-hour durations were calculated. The end-tidal concentration of anesthetic was adjusted to 1 MAC (0.9% halothane, 2.5% sevoflurane) for at least the last 10 min of surgery. Intervals from discontinuation of anesthetic to hip flexion or bucking, extubation, administration of first postoperative analgesic, and attaining discharge criteria from recovery room were measured. Venous blood was sampled at anesthetic induction, at the end of anesthesia, and 1, 4, 6, 12, and 18-24 h after discontinuation of the anesthetic for determination of plasma inorganic fluoride content., Results: Induction of anesthesia was satisfactory in groups SN and HN. Induction in group S was associated with a significantly greater incidence of excitement (35%) than in the other groups (5%), resulting in a longer time to intubation. The end-tidal minimum alveolar concentration multiple of potent inhalational anesthetic at the time of intubation was significantly greater in patients receiving halothane than in patients receiving sevoflurane. Induction time, vocal cord position at intubation, time to incision, duration of anesthesia, and MAC-hour duration were similar in the three groups. During emergence, the time to hip flexion was similar among the three groups, whereas the time to extubation, time to first analgesic, and time to attaining discharge criteria were significantly greater in group HN than in groups S and SN. Mean heart rate and systolic blood pressure decreased during induction in group HN but not in groups S and SN. The maximum serum fluoride concentration among all patients was 28 microM., Conclusions: Sevoflurane with nitrous oxide provides satisfactory anesthetic induction and intubating conditions; however, induction using sevoflurane without nitrous oxide is associated with a high incidence of patient excitement and prolonged time to intubation. There were greater decreases in heart rate and systolic blood pressure during induction with halothane than with sevoflurane; however, these differences may be dose-related. The more rapid emergence with sevoflurane when compared with halothane is consistent with the low solubility of sevoflurane in blood and tissues. Children receiving sevoflurane for up to 9.6 MAC-hours did not develop high serum fluoride concentrations.

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.

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.

Pulmonary hypertension is a major source of morbidity and mortality in infants born with congenital diaphragmatic hernia (CDH). Increased pulmonary vascular resistance leads to right-to-left shunting, which is evident as decreases in the PaO2 measured in postductal arterial blood. Thromboxane A2 (TXA2), a vasoconstrictor, and prostacyclin (prostaglandin I2, PGI2), a vasodilator, have been studied as possible mediators of pulmonary hypertension in certain conditions of the newborn, including congenital diaphragmatic hernia (CDH). The goal of our study was to determine the association of TXA2 and PGI2 levels with hypoxemia in infants born with CDH. Eleven newborn infants with severe respiratory insufficiency (birth weight 2.0-4.1 kg; gestational age 32-42 weeks) were studied 0-5 days after surgical repair of CDH. Umbilical artery samples were collected for arterial blood gas determinations and radioimmunoassay of thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of TXA2 and PGI2, respectively. Postductal arterial hypoxemia (reflected by a low a-A ratio, the ratio of oxygen tension in arterial blood to that in the alveolus) was associated with increases in TXB2 (r = -0.71, P = 0.004) and 6-keto-PGF1 (r = -0.65, P = 0.017). The a-A ratio also correlated inversely with TXB2/6-keto-PGF1 alpha (r = -0.50, P = 0.01), suggesting an increased influence of the vasoconstrictor TXA2.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine whether abnormalities in lung mechanics detected in infants during the acute phase of meconium aspiration syndrome persist after treatment with extracorporeal membrane oxygenation (EMCO)., Design: Prospective, descriptive study. Prospective evaluation of airway function and lung mechanics during and after ECMO by pulmonary function testing at 1.8 +/- 0.5 days of EMCO (period 1), follow-up at 1.4 +/- 0.2 days (period 2), and 7.0 +/- 0.9 days (period 3) after decannulation from ECMO., Setting: Tertiary care neonatal/pediatric ICU., Patients: Twelve neonates undergoing ECMO treatment for severe meconium aspiration syndrome that was refractory to conventional mechanical ventilation., Interventions: Maximum expiratory flow-volume curves were studied with the deflation flow-volume curve technique, and compliance and resistance of the respiratory system were studied with partial passive flow-volume curves., Measurements and Main Results: Respiratory system compliance was the only index of respiratory mechanics that was significantly (p less than .05) improved (0.96 +/- 0.1 vs. 0.61 +/- 0.1 mL/cm H2O/kg) immediately after decannulation from ECMO compared with period 1. Clinically important (p less than .05) improvement in forced vital capacity (28.0 +/- 5.5 vs. 16.1 +/- 1.9 mL/kg), respiratory system compliance (1.01 +/- 0.2 vs. 0.61 +/- 0.1 mL/cm H2O/kg), and maximum expiratory flow at 25%/forced vital capacity (1.0 +/- 0.3 vs. 2.2 +/- 0.3) was evident only during period 3 compared with period 1., Conclusions: We conclude that improvements in the clinical condition and oxygenation, permitting successful decannulation from ECMO, are achieved before clinically important improvements in lung mechanics.

Recent studies in humans and animals have indicated that different inspiratory muscles have different sensitivities to respiratory depressants. The sensitivity of inspiratory muscles during early growth and development relative to that in adults of the same species, however, has not been studied. We therefore studied the activity of the diaphragm, the external intercostals, and the genioglossus by means of electromyography and its moving time average with different concentrations of halothane in seven 2-mo-old kittens. The kittens spontaneously breathed 1.0%-2.0% halothane in oxygen while PaCO2 was maintained at about 60 mm Hg by adding CO2 to the inspired gas as needed. Muscle activity was evaluated in terms of the peak height of the moving time average. Activity at 1% halothane was used as the control measurement because measurements at zero inspired concentrations of halothane could not be obtained without sedation, which is known to depress respiratory muscle activity. Halothane anesthesia significantly (P less than 0.01) decreased phasic inspiratory activity of the inspiratory muscles in a dose-dependent fashion. Genioglossal activity was completely abolished at 1.5% and 2.0% halothane. By contrast, in our previous study in adult cats under nearly identical experimental conditions, the phasic genioglossal activity was depressed but present even at 3.0% halothane. The degree of depression at 1.5% and 2.0% halothane was least in the crural diaphragm (71.8% +/- 5.8%, 66.6% +/- 4.5% of control, respectively), intermediate in the intercostals (68.9% +/- 9.6%, 35.4% +/- 8.8%), and greatest in the genioglossus (0.0%, 0.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Objective: To describe the pathophysiology of surgical conditions that are associated with respiratory insufficiency in the newborn infant., Design: Survey., Setting: Newborn ICU in a children's hospital., Patients: Twenty-four newborn infants (1 to 28 days old) who required endotracheal intubation and mechanical ventilation for operative procedures or postoperative ventilatory support., Interventions: Flow-volume curves obtained by manual inflation of the lungs, followed by forced deflation by negative pressure, and by passive expiration, under sedation and pharmacologic paralysis., Measurements: Deflation flow-volume curves and passive expiratory curves were measured. Pulmonary function testing before and after bronchodilator administration (n = 11) began midway during the study period. Term and preterm groups served as controls., Main Results: Forced vital capacity (FVC) was decreased in all groups with surgical disease as follows: abdominal wall defects and necrotizing enterocolitis groups to 48.3% and 62.1% that of preterm, respectively; pulmonary hypoplasia group to 55.5% that of term (p less than .05). Maximal expiratory flow at 25% of FVC decreased in all groups: abdominal wall defects and necrotizing enterocolitis group, to 36.8% and 37.9% that of preterm, respectively (p less than .05); pulmonary hypoplasia group, 20.0% that of term (p less than .05). The ratio of maximal expiratory flow at 25% of FVC divided by FVC was significantly decreased in necrotizing enterocolitis and pulmonary hypoplasia groups compared with that of preterm and term groups, respectively, but not in the abdominal wall defects group. Maximal expiratory flow at 25% of FVC, but not FVC, increased significantly (36%, p less than .05) after bronchodilator nebulization, indicating the presence of airway reactivity. Respiratory system compliance was decreased significantly (p less than .05) in all surgical disease groups compared with the term group., Conclusions: Bronchial reactivity contributes to decreased maximal expiratory flow at 25% of FVC, a feature also seen in premature infants with respiratory distress syndrome who later develop bronchopulmonary dysplasia. Babies who require chronic ventilatory support after operation and who have developed reactive airways may benefit from the administration of bronchodilators during postoperative ventilatory management.

To determine whether preoperative stabilization and delay of operative repair of congenital diaphragmatic hernia (CDH) may decrease operative risk, we performed serial pulmonary function tests on 22 newborn infants with CDH and on four infants without pulmonary hypoplasia (two with ileal atresia and two with tracheoesophageal anomalies) who served as control subjects. We used 2 passive respiratory mechanics technique to measure respiratory system compliance. All patients with CDH had respiratory distress immediately after birth, and required mechanical ventilation. Thirteen babies underwent emergency repair (six survived, seven died); nine of them received extracorporeal membrane oxygenation (ECMO) after the operation (two survived, seven died). Operative repair was delayed deliberately for 2 to 11 days in nine infants with severe hypoxemia. Six immediately received ECMO for 4 to 10 days; one died of intraventricular hemorrhage, and five survived and later underwent surgical repair. The seventh patient did not receive ECMO but appeared to have respiratory distress syndrome of infancy and improved after administration of synthetic surfactant. Improvement was seen in two additional infants who received conventional assisted ventilation during a 48-hour delay before surgery, and survived. In all, eight of nine infants who underwent preoperative stabilization survived (p less than 0.05 compared with survival after emergency surgery). Following surgical repair immediately after birth, respiratory system compliance improved only slightly during the first week of life, a time when control infants had a rapid increase in respiratory system compliance (p less than 0.001). In contrast, respiratory system compliance increased nearly twofold in the nine patients undergoing preoperative stabilization (p less than 0.02). Preoperative ECMO was associated with an increase in respiratory system compliance of more than 60% for 1 week, a significant difference from respiratory system compliance among patients undergoing emergency CDH repair (p less than 0.05). These observations provide physiologic evidence of possible benefits of preoperative stabilization before repair of CDH.

Background and Methods: Liquid ventilation using perfluorocarbons is a new technique for ventilation of infants with restrictive lung disease. However, this method of ventilation has been shown to impair cardiac output (Qt) in several animal species, casting doubt as to its feasibility. This study tested whether Qt could be maintained during liquid breathing by intravascular volume expansion. Seven piglets were carefully hydrated, instrumented for continuous Qt measurement, and subjected to 2 hr of liquid breathing. PaCO2 was maintained at 40 to 50 torr (5.3 to 6.7 kPa), and PaO2 greater than 80 torr (greater than 10.7 kPa). Additional colloid was given during liquid breathing if Qt decreased to less than 90% of preliquid breathing values., Results: Four piglets maintained Qt throughout the liquid breathing trial with maintenance fluids only. Three piglets each required one 10 mL/kg fluid bolus for Qt 82% to 89% of the baseline value, after which Qt rapidly increased to greater than 90% of baseline. Oxygen consumption and serum lactate levels remained normal throughout liquid breathing., Conclusion: Qt is readily maintained during liquid breathing in properly hydrated animals.

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.

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.

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.

The effect of a standardized intramuscular premedication (morphine, 0.1 mg/kg, scopolamine, 13 micrograms/kg, and secobarbital, 2.5 mg/kg) on the arterial oxygen saturation of hemoglobin was evaluated in 33 patients with congenital heart disease by use of the Nellcor pulse oximeter. Sixteen patients had noncyanotic congenital heart disease and 17 patients had cyanotic congenital heart disease. In the noncyanotic congenital heart disease group, pulse oximeter saturations decreased from 98.1% +/- 1.5% (mean +/- SD), before premedication, to 96.5% +/- 1.5% following premedication. Although this decrease was statistically significant (P less than 0.05), it was determined to not be clinically meaningful. In the patients with cyanotic congenital heart disease, oxygen saturation increased from 73.5% +/- 11.8 to 74.7% +/- 10.2 following premedication, but this change was not statistically significant. The effect of premedication on SaO2 was highly variable in patients with cyanotic heart disease; although the group mean appeared to increase, 6 of the 17 patients had decreases in saturation and the decrease exceeded 10% in saturation in 3 of them. Therefore, oxygen saturation should be monitored following premedication in patients with cyanotic heart disease and oxygen administered as needed.

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.

In children with obstructive lung disease, the determination of functional resident capacity by the conventional helium dilution method [FRC(He)] often results in gross underestimations. This is due to exceptionally poor He mixing in children, which may be related to characteristics of the developing lung. We added a low level (2.5 cmH2O) of continuous positive pressure to the airway (CPAP) for 2 min beyond the end of conventional He rebreathing to evaluate its effect on gas mixing. The FRC was determined again from He concentration 1 min after CPAP was stopped. We recorded the results as an increase in measured FRC after CPAP (delta FRC) as percent of FRC(He). A total of 46 children (mean age: 13.5 yr) were studied, including those with normal lung function, those with central airway disease, and those with peripheral airway obstruction. With CPAP, delta FRC increased markedly in those with peripheral airway obstruction and was significantly correlated with volume of isoflow and the volume of trapped gas. Thus, the measurement of delta FRC is simple yet useful in detecting peripheral airway obstruction and air trapping.

To evaluate the role of genetic and environmental factors in the genesis of large lungs in high-altitude natives, we measured forced vital capacity (FVC), static lung pressure-volume characteristics and maximum expiratory flow-volume loops in 17- to 20-yr-old Peruvian natives to 3,850 m (highlanders) and 800 m (lowlanders). Forced vital capacity was 5.11 +/- 0.64 liters in highlanders, 116 +/- 11% of predicted; and 3.73 +/- 0.32 liters in lowlanders, 84 +/- 7% of predicted. Lung elastic recoil at functional residual capacity and at total lung capacity, and size-corrected pressure volume curves were similar in the two groups. Despite the larger volumes in highlanders, density-corrected maximum flow rates were similar in highlanders and lowlanders, and flow expressed in FVC'S-S-1 was less in highlanders. Upstream conductance at 50% FVC expressed in fvc's-s-1-cmH2O was 0.094 +/- 0.023 in highlanders vs. 0.147 +/- 0.050 in lowlanders. Flow rates did not change in sojourners to altitude, suggesting that the lower values of highlanders were due to anatomic factors. These findings suggest that airways, which form in fetal life, do not participate in adaptation to altitude, and that the large lungs of highlanders result from postnatal environmental hypoxic stimulation of lung growth. Our results illustrate the importance of "dysynaptic" lung growth in determining patterns of adult lung function.

Four volunteers judged eight levels of thermal stimuli induced by a Hardy dolorimeter, varying in intensity from extremely painful to a low level seldom even perceived. Half of the 406 stimuli were applied during acupuncture and half either before insertion or after removal of the needles. The experimental design minimized or eliminated factors other than the needles themselves, i.e., no medication was given, the subjects were scientists accustomed to objectivity and, on a preceding day or days, all had become experienced in assigning numbers (individually chosen) to the sensations produced by the different stimuli. Galvanic skin resistance was also tested. The results did not show any influence of acupuncture on perception of pain or on galvanic skin resistance.

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.