Feasibility and physiological effects of noninvasive neurally adjusted ventilatory assist in preterm infants.

BackgroundNoninvasive neurally adjusted ventilator assist (NIV-NAVA) was introduced to our clinical practice via a pilot and a randomized observational study to assess its safety, feasibility, and short-term physiological effects.MethodsThe pilot protocol applied NIV-NAVA to 11 infants on nasal CPAP, high-flow nasal cannula, or nasal intermittent mandatory ventilation (NIMV), in multiple 2- to 4-h periods of NIV-NAVA for comparison. This provided the necessary data to design a randomized, controlled observational crossover study in eight additional infants to compare the physiological effects of NIV-NAVA with NIMV during 2-h steady-state conditions. We recorded the peak inspiratory pressure (PIP), FiO2, Edi, oxygen saturations (histogram analysis), transcutaneous PCO2, and movement with an Acoustic Respiratory Movement Sensor.ResultsThe NAVA catheter was used for 81 patient days without complications. NIV-NAVA produced significant reductions (as a percentage of measurements on NIMV) in the following: PIP, 13%; FiO2, 13%; frequency of desaturations, 42%; length of desaturations, 32%; and phasic Edi, 19%. Infant movement and caretaker movement were reduced by 42% and 27%, respectively. Neural inspiratory time was increased by 39 ms on NIV-NAVA, possibly due to Head's paradoxical reflex.ConclusionNIV-NAVA was a safe, alternative mode of noninvasive support that produced beneficial short-term physiological effects, especially compared with NIMV.

Impulse oscillometry versus spirometry in a long-term study of controller therapy for pediatric asthma.

BACKGROUND: Determination of the benefits and limitations of specific physiologic tests has not been well studied in long-term clinical pediatric trials. OBJECTIVE: We sought to determine the utility of impulse oscillometry in a long-term comparison of 3 controller regimens in children with persistent asthma. METHODS: Children 6 to 14 years of age with mild-to-moderate persistent asthma were characterized with oscillometry and spirometry before entry into a clinical trial and then serially during 48 weeks of therapy with either an inhaled corticosteroid, a combination inhaled corticosteroid with a long-acting beta-agonist, or a leukotriene receptor antagonist. RESULTS: The FEV(1)/forced vital capacity ratio, as well as the forced expiratory flow from 25% to 75% of forced vital capacity in terms of spirometric parameters and the reactance area (XA) from impulse oscillometry, appeared to complement information provided by FEV(1) when comparing the tests and factors that appeared to predict a response to treatment. XA was unique in that it, as distinct from spirometric variables, reflected ongoing improvement during the latter part of the trial. In general, improvements in XA during the latter part of the study occurred independently of indices of atopy and the level of airway responsiveness. CONCLUSION: Assessment of respiratory mechanics over time with oscillometry might offer additional insights into the response of asthmatic patients to therapy. In particular, the pattern of improvement seen in XA over the course of therapy suggests this test might detect alterations in airway mechanics not reflected by spirometry. The possibility that changes in XA reflect ongoing improvement in small airway function deserves additional study.

Evaluation of Ultrasound-Based Sensor to Monitor Respiratory and Nonrespiratory Movement and Timing in Infants.

GOAL: To describe and validate a noncontacting sensor that used reflected ultrasound to separately monitor respiratory, nonrespiratory, and caretaker movements of infants. METHODS: An in-phase and quadrature (I & Q) detection scheme provided adequate bandwidth, in conjunction with postdetection filtering, to separate the three types of movement. The respiratory output was validated by comparing it to the electrical activity of the diaphragm (Edi) obtained from an infant ventilator in 11 infants. The nonrespiratory movement output was compared to movement detected by miniature accelerometers attached to the wrists, ankles, and heads of seven additional infants. Caretaker movement was compared to visual observations annotated in the recordings. RESULTS: The respiratory rate determined by the sensor was equivalent to that from the Edi signal. The sensor could detect the onset of inspiration significantly earlier than the Edi signal (23+/-69 ms). Nonrespiratory movement was identified with an agreement of 0.9 with the accelerometers. It potentially interfered with the respiratory output an average of 4.7+/-4.5% and 14.9+/15% of the time in infants not requiring or on ventilatory support, respectively. Caretaker movements were identified with 98% sensitivity and specificity. The sensor outputs were independent of body coverings or position. CONCLUSION: This single, noncontacting sensor can independently quantify these three types of movement. SIGNIFICANCE: It is feasible to use the sensor as trigger for synchronizing mechanical ventilators to spontaneous breathing, to quantify overall movement, to determine sleep state, to detect seizures, and to document the amount and effects of caretaker activity in infants.

Chronic hypercapnia alters lung matrix composition in mouse pups.

RATIONALE: permissive hypercapnia, a stretch-limiting ventilation strategy, often results in high Pa(CO(2)). This strategy is associated with reduced morbidity and mortality in premature infants and its benefits have been attributed to diminished barotrauma. However, little is known about the independent effect of high CO(2) levels during the lung development. METHODS: mice were exposed to 8% CO(2) or room air for 2 wk either from postnatal day 2 through 17 or as adults (approximately 2 mo of age). Lungs were excised and processed for protein, RNA, histology, and total lung volumes. RESULTS: histologic analysis demonstrated that alveolar walls of CO(2)-exposed mouse pups were thinner than those of controls and had twice the total lung volume. Molecular analysis revealed that several matrix proteins in the lung were downregulated in mouse pups exposed to hypercapnia. Interstitial collagen type I alpha1, type III alpha1, elastin and fibronectin protein, and mRNA levels were less than half of controls while collagen IV alpha 5 was unaffected. This decrease in interstitial collagen could thus account for the thinning of the interstitial matrix and the altered lung biomechanics. Matrix metalloproteinase (MMP)-8, a collagenase that has specificity for collagen types I and III, increased in hypercapnic mouse pups, suggesting increased collagen degradation. Moreover, tissue inhibitor of MMP (TIMP)-1, a potent inhibitor of MMP-8, was significantly decreased. However, unlike pups, adult mice exposed to hypercapnia demonstrated only a mild increase in total lung volumes and did not exhibit similar molecular or histologic changes. CONCLUSIONS: although permissive hypercapnia may prevent lung injury from barotrauma, our study revealed that exposure to hypercapnia may be an important factor in lung remodeling and function, especially in early life.

Virulence role of group B Streptococcus beta-hemolysin/cytolysin in a neonatal rabbit model of early-onset pulmonary infection.

We examined the virulence role of group B Streptococcus (GBS) beta-hemolysin/cytolysin (beta h/c) in a neonatal-rabbit model of GBS pulmonary infection. Rabbits infected intratracheally with wild-type (wt) GBS developed focal pneumonia and, by 18 h after infection, had 100-fold more bacteria in lung tissue than did rabbits infected with a delta beta h/c mutant. Mortality (40% vs. 0%), development of bacteremia, and mean bacterial blood counts were all significantly higher in the rabbits challenged with wt GBS than in those challenged with the delta beta h/c mutant. Lung compliance during mechanical ventilation was impaired after injection of wt GBS but not after injection of the Delta beta h/c mutant strain. This work, to our knowledge, provides the first in vivo evidence for a critical role of the beta h/c toxin in GBS neonatal pneumonia and in the breakdown of the pulmonary barrier to systemic infection.

Thickness of the blood-gas barrier in premature and 1-day-old newborn rabbit lungs.

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We studied the ultrastructure of the blood-gas barrier (BGB) in premature and 1-day-old rabbit lungs and compared it with the ultrastructure of adult lungs. Normal gestation of rabbits is 30 days. After extensive pilot measurements, three premature (27 days gestation) and three newborn (1 day old) rabbit lungs were perfusion-fixed at arterial, venous, and airway pressures of 25, 0, and 10 cmH2O, respectively, and the measurements were compared with those of three adult lungs. The thickness of the capillary endothelium, alveolar epithelium, and interstitium of the BGB was measured at right angles to the barrier at random points. A striking finding was the large number of measurements of the interstitial thickness in 1-day-old lungs that were very thin (0-0.1 microm). The percentages of occurrence of very thin interstitium in premature, 1-day-old, and adult lungs were 35.3 +/- 9.4, 71.7 +/- 5.2, and 43.0 +/- 2.6, respectively (P < 0.02 for 1 day old vs. premature and adult). Given the previously found relationship between stress failure and interstitial thickness, this large proportion of very thin interstitial layers in the capillaries of 1-day-old lungs is a reasonable explanation for their previously demonstrated vulnerability to stress failure.

Increased fragility of pulmonary capillaries in newborn rabbit.

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We perfusion fixed the lungs from nine anesthetized newborn rabbits at capillary transmural pressures (P(tm)) of 5 +/- 5, 10 +/- 5, and 15 +/- 5 cmH(2)O. Normal microscopic appearances were seen at P(tm) values of 5 +/- 5 and 10 +/- 5 cmH(2)O, but massive airway edema was observed in lungs perfused at a P(tm) of 15 +/- 5 cmH(2)O. Consistent with this, no disruptions of the alveolar epithelium were observed at P(tm) values of 5 +/- 5 cmH(2)O, but mean values of 0.11 and 1.22 breaks/mm epithelium were found at P(tm) of 10 +/- 5 and 15 +/- 5 cmH(2)O, respectively (P < 0.05 for 5 +/- 5 vs. 15 +/- 5 cmH(2)O). These pressures are in striking contrast to those in the adult rabbit in which, by a similar procedure, a P(tm) of 52.5 cmH(2)O, is required before stress failure is consistently seen. We conclude that stress failure of pulmonary capillaries in newborn rabbit lungs can occur at P(tm) values of less than one-third of those that are required in adult lungs.