Gregory P Heldt

Improved oxygenation during synchronized intermittent mandatory ventilation in neonates with respiratory distress syndrome: A randomized, crossover study

In a randomized, crossover study, we compared arterial partial pressure of oxygen and of carbon dioxide between consecutive periods of conventional and synchronized intermittent mandatory ventilation (SIMV). We studied spontaneously breathing infants with an endotracheal tube in place. The infants were < 12 hours of age, had a diagnosis of respiratory distress syndrome, and had an arterial/alveolar oxygen ratio of < 0.25. The infants had a mean birth weight of 1077 gm and gestational age of 28 weeks. The mean rate of asynchrony on intermittent mandatory ventilation (IMV) was 52% (range, 36% to 76%), and on SIMV was < 1%. Infants were randomly assigned to IMV or SIMV as their initial ventilator mode and underwent ventilation for four 15-minute periods, and crossed over to the alternate mode after each period. Ventilator settings and the fraction of inspired oxygen were not changed between modes. At the end of each period, arterial blood gas measurements were obtained; 26 paired comparisons were made between modes. The mean arterial partial pressure of oxygen was significantly higher during SIMV than during IMV (mean, 61.5 vs 53.3 mmHg; p < 0.01). The mean arterial partial pressure of carbon dioxide was slightly lower during SIMV than during IMV (mean, 42.7 vs 41.3 mm Hg; p < 0.05). The improvement in oxygenation demonstrated with SIMV may allow a reduction in ventilator pressure or oxygen exposure in this group of infants, who are at risk of having complications of ventilation.

The Use of Synthetic Peptides in the Formation of Biophysically and Biologically Active Pulmonary Surfactants

ABSTRACT: Synthetic pulmonary surfactants consisting of mixtures of phospholipids with synthetic peptides based on the amino acid sequence of human surfactant apoprotein SP-B were prepared. These surfactants were analyzed for their ability to lower surface tension on a pulsating bubble surfactometer and for their capacity to improve lung compliance and increase alveolar expansion in a fetal rabbit model of surfactant deficiency. The data demonstrate that several peptides, ranging from 17 to 45 residues in length, matching the carboxy-terminal sequence of the SP-B protein, when appropriately recombined with the phospholipids dipalmitoylphosphatidycholine and phosphatidylglycerol (3:1), are capable of producing a synthetic surfactant with biophysical and biologic activity approaching that of human surfactant derived from amniotic fluid.

Airway leak size in neonates and autocycling of three flow-triggered ventilators.

OBJECTIVES To define the spectrum of airway leak in the neonatal population and examine the occurrence rate of autocycling of three flow-triggered ventilators within the defined spectrum of airleak. DESIGN Prospective study of pulmonary function tests of intubated infants and performance of ventilators on a mechanical lung model under simulated clinical conditions. SETTING An intensive care nursery and research laboratory at a university medical center. INTERVENTIONS Analysis of pulmonary function tests of 50 infants from our intensive care nursery, selected at random, to determine size of airleak around the endotracheal tube. The rate of autocycling of ventilators due to airleak of variable size, while connected to a test lung was subsequently studied. Ventilators were set on the assist-control mode with the control rate set at 0 breath/min. Each ventilator was studied at the maximum sensitivity setting, which was 1, 2.5, and 3.3 mL/sec for each ventilator, respectively, and also at decreased sensitivity settings to 10 mL/sec. Airleak size was varied (10% to 45%) by increasing the orifice size within the endotracheal tube adapter/connector sideport and/or the positive end-expiratory pressure level (2 to 8 cm H2O). MEASUREMENTS AND MAIN RESULTS In the infants, airleak size was calculated during synchronous ventilator breaths as (inspiratory minus expiratory) tidal volume/expiratory tidal volume x 100% (n = 25 +/- 11 breaths/patient). Mean +/- SD leak size in the infants was 15.6 +/- 11%. A minimal leak size of 0 to 10% was present in 15 (30%) infants, leak size of 10% to 20% in 24 (48%), leak size of 20% to 30% in seven (14%), and leak size > 30% in four (8%) infants. The relative tendency of the three ventilators to autocycle is a function of the maximum sensitivity setting, which varies with each ventilator. The ventilator with the maximum sensitivity set at 1 mL/sec autocycled rapidly (> or = 40 breaths/min) at leak size of > 10%; the ventilator set at 2.5 mL/sec autocycled rapidly at leak size of > or = 20%; and the ventilator set at 3.3 mL/sec autocycled rapidly at leak size of > or = 30%. In all ventilators, the rate of autocycling increased with increased leak size, and decreased with decreased sensitivity setting. CONCLUSIONS Flow-triggered ventilators are susceptible to autocycling due to flow compensation to maintain positive end-expiratory pressure levels in the presence of an airway leak. The difference in autocycling is due to the maximum sensitivity setting of each ventilator, and not to intrinsic ventilator flowsensing or other software mechanisms. The 3.3-mL/sec setting was the least prone to autocycling and seems appropriate. The ventilator set at 2.5 mL/sec at the time of this study has been released instead at 4 mL/sec, due to these findings. The ventilator with the maximum setting at 1 mL/sec autocycled readily at leak size of > or = 10%. Since such a leak size was present in 70% of infants, this setting should be used with caution. Using these guidelines, autocycling of all three ventilators is likely to occur mainly in 8% of infants with leak size of > 30%. In these cases, lowering the sensitivity setting and/or positive end-expiratory pressure level may decrease autocycling, or may necessitate reintubation with a larger endotracheal tube.

Tidal Volume Threshold for Colorimetric Carbon Dioxide Detectors Available for Use in Neonates

OBJECTIVE. Colorimetric carbon dioxide detectors are used for confirmation of endotracheal intubation. The colorimetric carbon dioxide detectors that are used for neonates are labeled for use with infants and small children >1 and <15 kg. The objective of this study was to determine the minimal tidal volume that causes a breath-to-breath color change on 2 colorimetric carbon dioxide detectors. METHODS. Using an artificial-lung model, we determined the tidal volume threshold of 2 colorimetric carbon dioxide detectors (Pedi-Cap [Nellcor, Pleasanton, CA] or Mini StatCO2 [Mercury Medical, Clearwater, FL]) during ventilation with a T-piece resuscitator or neonatal ventilator. Digital video recordings of the colorimetric carbon dioxide detectors were made during 20 seconds of ventilation at each tidal volume. Seven clinicians who were blinded to the tidal volume reviewed the videos in random order and graded the color change to determine adequacy for clinical application. RESULTS. The Mini StatCO2 tidal volume threshold was 0.83 mL, and the Pedi-Cap tidal volume threshold was 1.08 mL. CONCLUSIONS. The lung model revealed that the tidal volume threshold for the tested colorimetric carbon dioxide detectors is less than the expected tidal volume of a 400-g infant and suggests that these devices are appropriate for use with any neonate to confirm intubation.

Resection of distal tracheal stenosis in a baby with agenesis of the lung

A newborn infant with agenesis of the left lung and critical distal tracheal stenosis required tracheal resection and reanastomosis. This case illustrates the combined use of flow-volume curves, radiology and endoscopy in the diagnosis and management of airway obstruction in infants. It also establishes the feasibility of complete tracheal reconstruction in small babies.

Exercise performance of the survivors of hyaline membrane disease

We measured the cardiopulmonary response of 62 school-aged survivors of hyaline membrane disease to the stress of submaximal steady-state exercise on a cycle ergometer. The children represented a 48% follow-up of infants with HMD who-survived in our hospital in the years 1968 to 1974. They had incidences of wheezing, pulmonary infections, and abnormal chest roentgenograms after discharge similar to those in groups reported by other investigators. The first group required only supplemental oxygen or continuous positive airway pressure; the second required oxygen and CPAP plus mechanical ventilation with intermittent positive pressure; and the third, half of whom had been treated with positive pressure, developed pulmonary air leaks. Children in all groups had normal heart rates and oxygen consumptions for their heights and work rates. Ventilation was normal in all but three subjects. These three patients had had air leaks and one had severe bronchopulmonary dysplasia, requiring 36 months of oxygen therapy; the other two were only 5 years of age. All three developed hypercarbia during moderate exercise. There was no difference in the tidal volumes, respiratory rates, dead space, or the distribution of ventilation between the three groups and the normal subjects. The alveolar-to-skin oxygen tension gradient decreased in all groups and the normal subjects during light exercise, implying that the match of ventilation to perfusion improved. Most survivors of HMD appear to have normal cardiopulmonary function by school age.

The effect of gavage feeding on the mechanics of the lung, chest wall, and diaphragm of preterm infants

ABSTRACT: Preterm infants when given bolus nasogas-tric (gavage) feedings have well-characterized decreases in arterial partial pressure of oxygen, increases in arterial partial pressure of carbon dioxide, a tendency to have apnea, and are reported to have no change in the mechanics of breathing. The purpose of this study was to assess the function of the lungs, chest wall, and diaphragm in preterm infants without lung disease before and after gavage feeding. Lung mechanics were measured with a pneumotacho-graph and esophageal balloon, and the mechanics of the chest wall and diaphragm were assessed by inductance plethysmography and measurement of transdiaphragmatic pressure. After feeding, there was a significant decrease in dynamic lung compliance and increase in the minute ventilation (p < 0.05). The work performed on the lungs was unchanged. The chest wall became more stable, with a significant decrease in its dynamic compliance (p < 0.05). The diaphragmatic volume displacement, expressed as a percentage of the minute ventilation, was unchanged. The diaphragmatic work increased significantly (p < 0.05), and was greater than four times the work performed on the lungs. These results are consistent with previous reports of a decrease in functional residual capacity after feeding. The mechanical stability of the chest wall may have been improved by an increase in the area of apposition of the diaphragm to it, or by an increase in the central drive to breathing after feeding. The increment in diaphragmatic work after feeding, being nearly as large as the absolute amount of work performed on the lungs, may be enough to cause muscular fatigue and resultant apnea noted in some preterm infants after gavage feeding.

Distribution of surfactant, lung compliance, and aeration of preterm rabbit lungs after surfactant therapy and conventional and high-frequency oscillatory ventilation.

ABSTRACT: Previous studies in preterm lambs have shown that exogenous surfactant is more uniformly distributed if given at birth before ventilation or if followed by high-frequency ventilation (HFV) after establishing conventional ventilation (CV). We hypothesized that the preterm rabbit pup would respond similarly and that improved respiratory system compliance (Crs) would accompany improved surfactant distribution. We randomized pups (27 d gestation) into three groups: control, surfactant at birth, and surfactant after 15 min of CV (rescue). We administered dipalmitoylphosphatidyl-[3H]choline-labe!ed natural surfactant by tracheostomy to each of the treated groups. The two treatment groups were treated for 15 min with either HFV or CV and subsequently with CV. We measured Crs at 15, 25, 35, and 45 min after surfactant. Lungs from pups treated with CV or HFV (n = 89) for 15 min, with and without 30 min of subsequent CV, were cut into 32 pieces that were counted for distribution of label or were sectioned for quantitative morphometry (n = 36). Pups receiving surfactant after 15 min of CV had higher Crs 15 min after surfactant than either pups treated with surfactant at birth or controls (p < 0.001). The Crs of pups 15 min after rescue surfactant followed by HFV was lower than that of pups treated with CV (p < 0.05) but was higher than that of either control or pups treated at birth groups (p < 0.05). Crs at 35 and 45 min after surfactant were the same in all treatment groups. Application of HFV appeared to delay the delivery of surfactant to the distal airspaces. Differences in Crs paralleled differences in the uniformity of distribution of radiolabel. Distribution was more uniform in pups treated with CV than HFV after rescue (p < 0.001) and after an additional 30 min of CV in both CV and HFV rescue groups. Aeration as judged by morphometry was similar in all treatment groups. These observations differ from previous reports and may be explained by differences in species, methods of HFV, or the use of natural surfactant containing surfactant-associated protein A versus lipid-extracted surfactant formulations containing solely lipophilic proteins.

Effects of different gain settings during assisted mechanical ventilation using respiratory unloading in rabbits

Compared with conventional modes of patient-initiated mechanical ventilation, respiratory mechanical unloading aims at improving the match between ventilator pressure profiles and the specific derangements in lung mechanics. This may reduce lung barotrauma. The ventilator pressure increases either in proportion to the volume or to the flow of spontaneous breathing(elastic or resistive unloading), thereby selectively decreasing elastic or resistive work of breathing. The clinician sets a gain of increase in pressure per unit of volume or flow. In an attempt to develop criteria for selecting an appropriate gain, we investigated the effects of unloading using increasing gains that either partially compensated or overcompensated lung elastance or resistance. We studied spontaneously breathing, anesthetized, and tracheotomized rabbits. Compared with continuous positive airway pressure, respiratory unloading decreased the electromyographic activity of the diaphragm and increased minute ventilation in normal (n = 5) and surfactant-depleted (n = 6) animals when the gain was partially compensating. Fluctuations in systemic blood pressure associated with breathing decreased. The end-expiratory lung volume remained unchanged. Overcompensation of lung elastic recoil during elastic unloading with an excessive gain caused large tidal volumes associated with a cyclic decrease in blood pressure. Overcompensation of resistance induced oscillations. Complete inhibition of spontaneous breathing occurred with a further increase in gain. We conclude that respiratory unloading with an appropriate gain enhances the effect of diaphragmatic muscle activity on ventilation. A stable breathing pattern ensues whenever a regular spontaneous effort is present. However, excessive gain causes large tidal volumes during elastic unloading or oscillations during resistive unloading.

A trial of the safety of inhaled beclomethasone in ventilator-treated neonates

Fifteen neonates were studied to determine whether beclomethasone could be safely administered with a metered-dose inhaler to subjects with an endotracheal tube in place. Oxygen saturations and transcutaneous carbon dioxide values were monitored before, during, and after administration. We found significantly more episodes of desaturation to less than 85% before administration than after administration (p < 0.05). The transcutaneous carbon dioxide values increased 4 to 10 mm Hg during delivery (p < 0.02) but returned to baseline by 30 minutes.