Mechanics In Infants Research Articles

Thoracoabdominal Asynchrony in Infants with Airflow Obstruction

Thoracoabdominal asynchrony (TAA) has long been thought clinically useful in the assessment of airflow obstruction (AO) in infants. To test the hypothesis that the measurement of TAA is useful in the assessment of lung mechanics in infants with AO, we have used respiratory inductive plethysmography (RIP) to quantity TAA. We compared changes in TAA to changes in lung mechanics before and after aerosolized bronchodilator (BD) administration in 13 infants. Abdominal wall (AB) and rib cage (RC) motion were displayed on an X-Y recorder in a Lissajous figure. Asynchrony between RC and AB motion was quantified by comparing the width m of the Lissajous figure (difference between AB inspiratory and expiratory positions) at mid-RC excursion with the total AB excursion at its extremes (s). Phase angle phi ws computed as sin phi = m/s (or phi = 180 degrees - mu, where sin mu = m/s for phase angles greater than 90 degrees) and was taken as a measure of TAA. Lung resistance RL and elastance EL were calculated from esophageal pressure (Pes), mouth pressure, tidal volume, and tidal flow. All infants displayed TAA at baseline. After BD administration, TAA decreased in those infants in whom RL decreased. The percentage decrease in the phase angle from baseline after BD administration was significantly correlated with the decrease in peak-to-peak Pes (delta Pes) and the percentage decrease in RL and EL. We conclude that AO in infants leads to TAA through altered pleural pressure swings acting on the compliant chest wall. Changes in lung mechanics induced by bronchodilators are reflected in changes in TAA.(ABSTRACT TRUNCATED AT 250 WORDS)

Disturbance in respiratory mechanics in infants with bronchiolitis.

Disturbance in respiratory mechanics in infants with bronchiolitis.

The Effect of Reconstituted Bovine Surfactant on Pulmonary Mechanics in Infants with Respiratory Distress Syndrome

We performed sequential measurements of pulmonary mechanics following instillation of reconstituted bovine surfactant (surfactant TA) in 10 neonates with severe respiratory distress syndrome. The respiratory compliance did not increase significantly until six hours after surfactant administration, while the arterial oxygenation and radiographic appearance improved rapidly after surfactant therapy. Six infants developed clinically significant PDA between 24 hours and 48 hours after surfactant therapy, when the compliance decreased temporarily after initial improvement until the PDA was closed pharmacologically. In six cases airway resistance rose transiently following surfactant treatment, whereas PCO2 fell significantly in all cases by six hours after surfactant administration. We recommend that only inspired oxygen concentration should be adjusted without changing the pressure setting of a respirator for at least three hours after surfactant therapy.

Neck and Body Position Effects on Pulmonary Mechanics in Infants

Pulmonary mechanics and ventilatory parameters were measured in 30 former preterm infants at a postterm age of 8 to 10 months. All subjects had required assisted ventilation in the neonatal period and 16 had a history of bronchopulmonary dysplasia. Each infant was studied in both supine and semisitting positions, and in each body position the infants were studied with neutral, flexed, and extended neck positions. Baseline measurements (body supine, neck neutral) and the response to postural changes did not differ between infants who had had bronchopulmonary dysplasia and those who had not. Change in body position from supine to semisitting decreased total pulmonary resistance (P less than .05) and increased specific lung compliance (P less than .01). Neck flexion increased resistance (P less than .001) in both body positions but did not influence compliance. These postural effects are consistent with an increase in functional residual capacity in the semisitting position and a decrease in pharyngeal area during neck flexion. Thus, posture needs to be precisely controlled during pulmonary function testing in infants. Furthermore, optimal neck and body position may improve their clinical status.

Cardiopulmonary effects of the volume recruitment manoeuvre in infant swine

The volume recruitment manoeuvre is a non-invasive technique used to measure respiratory mechanics in infants. Because airway pressure increases during this manoeuvre, lung volume, compliance and cardiac output may change. In order to assess possible changes in cardiopulmonary function caused by the volume recruitment manoeuvre, we applied this technique to seven intubated infant swine breathing spontaneously during anaesthesia with halothane and N2O. Tidal volume (VT), respiratory frequency, arterial blood gases, cardiac output (CO) and total respiratory compliance were measured before and after the manoeuvre. In three swine functional residual capacity (FRC) was measured by helium dilution before the manoeuvre, and in four swine diaphragmatic EMG was recorded continuously. Finally, all swine were paralysed during volume recruitment to assess the contribution of the respiratory muscles to post-manoeuvre respiratory mechanics. VT and f increased immediately after the manoeuvre but there were no significant changes in PaCO2, or alveolar to arterial oxygen gradient. There was a small but statistically significant decrease in CO. Compliance increased by 17.8 +/- 3.6 per cent and FRC increased by a mean of 41.1 ml (or 51.9 per cent increase above the baseline FRC). The increase in FRC could not be explained by active mechanisms since the diaphragmatic EMG showed no post-inspiratory activity and neuromuscular paralysis did not decrease FRC. We conclude that the volume recruitment manoeuvre increases FRC and compliance by recruiting collapsed alveoli, and this effect must be taken into consideration when applying this test to infants.

Disturbance in respiratory mechanics in infants with bronchiolitis.

The passive flow-volume and partial forced expiratory flow-volume techniques were used to assess pulmonary function in 14 spontaneously breathing infants with acute respiratory syncytial virus bronchiolitis. Two additional infants were studied while paralysed and ventilated. During the acute stage of the illness there was a significant reduction in forced expiratory flow rates and an increase in respiratory resistance. Although the mean thoracic gas volume for the group was increased, five infants did not compensate for their airways obstruction by hyperinflation. Curvilinear passive flow-volume curves were seen in three of the 14 non-ventilated infants and in both ventilated infants. At follow up three to four months later all passive flow-volume curves were linear. There was a significant reduction in hyperinflation and an increase in forced expiratory flow rates, but values still differed significantly from those in normal infants.

Respiratory control in infants at increased risk for sudden infant death syndrome.

There is much debate relating to possible abnormalities in respiratory control mechanisms in infants considered at increased risk for sudden infant death syndrome (SIDS). The P0.1 occlusion technique was used to assess the central respiratory response to hyperoxic hypercapnia during quiet sleep in 21 normal infants, 13 siblings of SIDS victims, and 17 infants with apparent life threatening events. The slope of P0.1 plotted against carbon dioxide concentration increased exponentially with age, independent of body weight in each group. Birth weight has a significant effect on slope with a lower weight predisposing to a lower slope. Siblings as a group had a significantly lower slope at any given age than normal infants, whereas the infants who had had apparent life threatening events were not significantly different from the controls. As intragroup variation in both siblings and control groups greatly exceeded the significant intergroup differences observed, the technique cannot identify individual infants as belonging to one or other group.

Comparison of dynamic and static measurements of respiratory mechanics in infants

The objective of this study was to compare the conventional method of measuring respiratory mechanics, which requires the passage of an esophageal tube, with the occlusion technique, which is less invasive. Thirty-nine preterm infants who received mechanical ventilation on the first day were studied before discharge (mean +/- SD: postnatal age 67 +/- 23 days; weight 1790 +/- 300 gm), and 27 of them again at 1 year (weight 8.1 +/- 1.4 kg). Flows were measured through a nosepiece by pneumotachometry, tidal volume by integration of flow, esophageal pressure through a water-filled tube, and airway pressure directly at the nasal piece. Airway occlusion was performed at the end of inspiration, and the following relaxed exhalation was analyzed to give compliance (Crs) and resistance (Rrs) of the respiratory system. These values were compared with dynamic lung compliance (Cdyn) and expiratory resistance (Re) of the previous unoccluded breath. In the younger infants, dynamic and static measurements did not differ significantly and were well correlated (Cdyn/Crs, r = 0.91; Re/Rrs, r = 0.95). In the older infants, Crs was 80% of Cdyn (p less than 0.001), and Rrs was 24% higher than Re (p less than 0.001). The measurements were well correlated (Cdyn/Crs, r = 0.94; Re/Rrs, r = 0.91). The regression line Cdyn versus Crs had a slope (0.77) significantly less than 1; the regression Re versus Rrs had an intercept (13.8) significantly greater than zero. The lower Crs and higher Rrs values can be expected because the static determinations include the chest wall. In the more immature infants, the very compliant chest wall, in combination with an underestimation of Cdyn because of the higher breathing frequency of these infants, may obscure this difference. We conclude that the occlusion technique gives accurate and reproducible results, is easily applied, does not need the passage of an esophageal tube, and is well tolerated by the infants.

Evaluation of the flow-volume loop as an intra-operative monitor of respiratory mechanics in infants.

Airway pressure is currently the primary indicator of respiratory mechanics used by the anesthetist in the operating room. This quantity can signal that the mechanical properties of the respiratory system have changed. However, there is a need for more sophisticated monitors of mechanics, capable of indicating the nature of the change. We have investigated the use of the tidal flow-volume loop in differentiating between an obstruction of the endotracheal tube and changes in the distribution of regional ventilation, using a computer model. Endotracheal obstruction caused the descending limb of flow-volume loop to become convex to the volume axis, whereas ventilation inhomogeneity caused the curve to become concave to the volume axis. In contrast, examination of peak airway pressure did not allow differentiation between the two conditions. We conclude that, while the peak airway pressure is useful in signaling a change in a patient's condition, the combination of airway pressure and the flow-volume loop serves as a more comprehensive monitor of respiratory mechanics.

Sequential changes in pulmonary mechanics in the very low birth weight (≤1000 grams) infant

Pulmonary function tests were performed on 36 very low birth weight neonates (birth weight less than or equal to 1000 gm, gestational age less than or equal to 30 weeks, appropriate size for gestational age) from birth until 8 weeks of age. Tidal airflow was measured by means of a pneumotachygraph, and the transpulmonary pressure changes were determined by the esophageal balloon technique. Pulmonary mechanics and energetics were calculated by the least mean square analysis technique at 1/2, 1, 2, 4, 6, and 8 weeks of age. Compliance was lowest at 2 weeks and subsequently increased linearly (at approximately 0.1 ml/cm H2O/wk). When compliance was based on body weight, however, no change was noted with advancing age. Resistance was greatest at 2 weeks and subsequently decreased. The infants maintained a normal minute ventilation with a slightly increased resistive work of breathing. Despite our ability to wean 53% of the infants to room air by 8 weeks, none of them had pulmonary mechanics considered normal for term infants. Infants with and without bronchopulmonary dysplasia (BPD) had similar patterns of pulmonary development. At 8 weeks of age, the pulmonary mechanics in infants with BPD who had been weaned to room air were comparable to those in infants without BPD, an observation that calls into question the rationale for defining BPD at 4 weeks in this population. These data suggest that such pulmonary function profiles provide evidence of persistent lung parenchymal abnormalities.

Posterior cricoarytenoid and diaphragm activities during tidal breathing in neonates.

To investigate airflow regulation in newborn infants, we recorded airflow, volume, diaphragm (Di), and laryngeal electromyogram (EMG) during spontaneous breathing in eight supine unsedated sleeping full-term neonates. Using an esophageal catheter electrode, we recorded phasic respiratory activity consistent with that of the principal laryngeal abductors, the posterior cricoarytenoids (PCA). Sequential activation of PCA and Di preceded inspiration. PCA activity typically peaked early in inspiration followed by either a decrescendo or tonic EMG activity of variable amplitude during expiration. Expiratory airflow retardation, or braking, accompanied by expiratory prolongation and reduced ventilation, was commonly observed. In some subjects we observed a time interval between PCA onset and a sudden increase in expiratory airflow just before inspiration, suggesting that release of the brake involved an abrupt loss of antagonistic adductor activity. Our findings suggest that airflow in newborn infants is controlled throughout the breathing cycle by the coordinated action of the Di and the reciprocal action of PCA and laryngeal adductor activities. We conclude that braking mechanisms in infants interact with vagal reflex mechanisms that modulate respiratory cycle timing to influence both the dynamic maintenance of end-expiratory lung volume and ventilation.

Oral theophylline and diuretics improve pulmonary mechanics in infants with bronchopulmonary dysplasia

We studied the effects of orally administered theophylline and diuretics (chlorothiazide and spironolactone) on pulmonary mechanics in 16 infants with bronchopulmonary dysplasia. Their gestational age (mean +/- SD) was 28.5 +/- 3.4 weeks, and postnatal age at the time of study 19.5 +/- 10.7 weeks. The infants were randomized to two groups. Group 1 received successively placebo, theophylline, and theophylline plus diuretics; Group 2 received theophylline, placebo, and placebo plus diuretics on successive 4-day periods. Pulmonary function was measured before beginning the study (baseline) and at the end of each 4-day period. No significant changes in pulmonary function were noted after treatment with placebo. After treatment with theophylline, dynamic compliance (Cdyn) increased from baseline (mean +/- SD) 0.075 +/- 0.017 to 0.091 +/- 0.028 mL/cm H2O/cm (P less than 0.01), airway resistance (Raw) decreased from 67.19 +/- 36.71 to 41.44 +/- 22.50 cm H2O/L/sec (P less than 0.001), maximal expiratory flow at functional residual capacity (VmaxFRC) increased from 0.261 +/- 0.240 to 0.357 +/- 0.299 thoracic gas volume (TGV)/sec (P less than 0.01), and time constant decreased from 0.312 +/- 0.224 to 0.275 +/- 0.247 sec (P less than 0.02). After treatment with combined placebo and diuretics, Cdyn increased to 0.103 +/- 0.023 mL/cm H2O/cm (P less than 0.05), Raw decreased to 31.76 +/- 24.90 cm H2O/L/sec (P less than 0.001), VmaxFRC increased to 0.638 +/- 0.595 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.141 sec (P less than 0.05). After treatment with combined theophylline and diuretics, Cdyn increased to 0.118 +/- 0.017 mL/cm H2O/cm (P less than 0.001), Raw decreased to 35.98 +/- 25.85 cm H2O/L/sec (P less than 0.02), VmaxFRC increased to 0.479 +/- 0.377 TGV/sec (P less than 0.02), and time constant decreased to 0.180 +/- 0.137 sec (P less than 0.01). We conclude that theophylline and diuretics have additive effects on the improvement of pulmonary function in infants with bronchopulmonary dysplasia.

Effect of ipratropium bromide on respiratory mechanics in infants with acute bronchiolitis.

The effect of nebulized ipratropium bromide in 14 infants (mean age: 20 weeks, range: 4-41) with acute respiratory syncytial virus bronchiolitis was examined. A modified rapid chest compression technique was used to obtain partial expiratory flow-volume curves and maximum flow at functional residual capacity. Passive respiratory mechanics were assessed by brief occlusion at end inspiration. Thoracic gas volume was measured in a body plethysmograph. No significant difference was found in forced and passive respiratory mechanics pre- and post-ipratropium bromide. No subgroups could be identified. These results do not support the use of ipratropium bromide in acute viral bronchiolitis.

Physiology of sucking in the normal term infant using real-time US.

Our study of 16 normal term, breast-fed infants documents real-time ultrasound as a technique for evaluating the oral portion of the sucking mechanism in infants. We also describe the mechanics of sucking used by the infants during breast-feeding.

1755 WHAT IS THE OBJECTIVE OF FUROSEMIDE THERAPY IN INFANTS WITH CHRONIC LUNG DISEASE?

Although furosemide (F) improves lung mechanics in infants with chronic lung disease (CLD), this effect may not be important unless gas exchange also improves. To determine the relationship between improvement in mechanics and improvement in gas exchange, we studied the acute and chronic effects of F therapy in 10 infants with CLD aged 4–24 weeks who were both oxygen dependent and hypercarbic. Each infant was studied 3 times: before F therapy, 1 h after the first dose of F (2 mg/Kg IV), and after a 6–10 day course (2 mg/Kg/day IV or 4 mg/Kg/day po). We measured skin surface (s) pO2 and pCO2, esophageal pressure, airflow and tidal volume; and we calculated pulmonary resistance (R), lung compliance (C) and the alveolar to skin (A–s) pO2 gradient. Criteria for improvement were a fall in PsCO2 > 2 torr, a fall in the A–s gradient > 10 torr, and a > 15% rise in C or fall in R. For the latter 4 variables we compared the acute effect of F with its chronic effect. We found that after both acute and chronic F, compliance, resistance and PsCO2 improved significantly from baseline values, but A–s pO2 gradient did not. Overall, mechanics improved in 9 patients, but gas excnange improved in only 6. In individual patients, improvement in R or C was unrelated to improvement in either gas exchange variable. However, the infants whose gas exchange chronically improved could be predicted by the acute change in PsCO2 or in pO2 gradient. We conclude that 1) F improves lung mechanics but may have little effect on gas exchange and 2) skin surface monitoring of the first dose of F can accurately identify those who will respond to chronic F therapy.

Effect of Oral Diuretics on Pulmonary Mechanics in Infants with Chronic Bronchopulmonary Dysplasia: Results of a Double-Blind Crossover Sequential Trial

In a randomized double-blind crossover trial with sequential analysis, the effects of oral diuretics were compared with the effects of placebo on pulmonary mechanics in ten infants with bronchopulmonary dysplasia (BPD). Pulmonary mechanics were measured before and at the end of a week of treatment with oral diuretics (chlorothiazide, 20 mg/kg/dose and spironolactone, 1.5 mg/kg/dose) given twice daily, or placebo. Mean airway resistance decreased 35.3 cm H2O/L/s, mean specific airway conductance increased 0.095 1/L/s/cm H2O, and mean dynamic pulmonary compliance increased 1.74 mL/cm H2O during treatment with diuretics (all P less than .001), but not during treatment with placebo. The infants' rate of weight gain decreased on the first three days of diuretic treatment, but was thereafter comparable with weight gain during treatment with placebo. Fluid intake was similar in infants receiving diuretics and placebo. But, infants receiving diuretics not only had significantly increased urine output, osmolal clearance, and potassium and phosphorus excretion, but these infants also retained less fluid, and, in addition, excreted less calcium than infants receiving placebo. It is concluded that oral diuretics improve lung function in infants with chronic bronchopulmonary dysplasia; however, potassium and phosphorus depletion are potential complications of treatment.

FUROSEMIDE DECREASES VENTILATION IN NEWBORN RABBITS

Furosemide improves lung mechanics in infants with bronchopul-monary dysplasia (BPD). However, in some infants we found that even if lung mechanics improve, PaCO2 rises and ventilation falls during furosemide therapy. Is this due to a furosemide-induced metabolic alkalosis with a secondary respiratory adjustment? Because the acid-base status of BPD patients is complex, we studied normal rabbit pups. For the first 9 days of life, 10 pups received intraperitoneal injections of furosemide (2mg/kg bid) and 10 pups received saline. On day 10, we inserted a catheter into one carotid artery and placed each pup in a plethysmograph. We measured body temperature; blood pressure; arterial gases and pH; serum Na, C1, K; respiratory frequency and tidal volume. We calculated ventilation (VE/g) and base excess (BE) and measured post-mortem static lung compliance (CL). Variables which were significantly different by unpaired t-test are shown below (means only, p<.05):Furosemide treated pups developed a primary alkalosis and a secondary respiratory acidosis; in addition, lung compliance was improved. KC1 injection to alkalotic pups increased VE and decreased pH. We conclude that furosemide 1) causes a metabolic alkalosis and reduces ventilation and 2) increases the PaCO2 which reflects changes in acid-base status and not changes in lung function.

Reactivation of Infant Mechanisms

Reactivation of Infant Mechanisms

Virus excretion and neutralizing antibody response in saliva in human cytomegalovirus infection.

The local secretory immune mechanism in infants with cytomegalovirus infection was studied by a measurement of neutralizing antibody in saliva. Neutralizing antibodies were determined by the microculture plaque assay in 65 saliva specimens including 54 samples from cytomegalovirus-infected subjects and 11 from seronegative controls. In addition, cytomegalovirus isolation from saliva or urine or both and antibody determination in serum and saliva were simultaneously performed on seven infants with cytomegalovirus excretion over long periods. Results obtained were as follows. (i) Neutralizing antibodies were detected in 41 (76%) of 54 saliva specimens obtained from infected subjects but in none of the 11 seronegative controls. (ii) Neutralizing antibodies in saliva were of low titer but persistently detectable in all but one of the seven infants. No relationship was recognized between the cessation of virus excretion and the development of neutralizing antibodies in saliva. (iii) Virus-neutralizing activity was specifically found in the immunoglobulin A fraction of pooled saliva by diethylaminoethyl cellulose chromatography.

Dengue viruses and mononuclear phagocytes. I. Infection enhancement by non-neutralizing antibody

Cultured mononuclear peripheral blood leukocytes (PBL) from nonimmune human beings and monkeys are nonpermissive to dengue 2 virus (D2V) infection at multiplicities of infection of 0.001-0.1, but become permissive when non-neutralizing dengue antibody is added to medium. D2V infection occurred in PBL prepared from anti-coagulated but not from defibrinated plasma. Infection enhancement was produced by multiple lots of heterotypic anti-dengue raised in several mammalian species. Homotypic anti-dengue neutralized D2V at high concentrations but enhanced at low concentrations; enhancement end point in one serum was 1:320,000. The infection-enhancing factor was a noncytophilic antibody of the IgG class. D2V infection occurred in the absence of heat-labile complement components but did not occur when complexes were prepared with anti- dengue F(ab)(2). Treatment of PBL with several proteases increased permissiveness to D2V infection by immune complexes but not by virus alone. Two rhesus monkey serums collected 14 days after D2V infection contained an IgG antibody with high-titered enhancing activity but with no hemagglutination-inhibition or neutralizing activity. Virus-antibody complexes are irreversibly attached to PBL within 15 min and completely internalized in 60 min. There was considerable variation in cellular infection in different experiments, however, maximum virus yields usually exceeded 1,000 plaque-forming units per 1 x 10(6) PBL occurring between 2 and 4 days in culture. In vitro antibody-dependent infection of PBL provides a possible model for study of pathogenetic mechanisms in infants with dengue shock syndrome who passively acquire maternal anti-dengue IgG.