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Background The physiological benefit of parent-infant skin-to-skin contact (SSC) is uncertain for preterm infants with ventilatory support. We aimed to investigate whether SSC stabilizes the respiration compared to incubator care in mechanically ventilated preterm infants. Methods The prospective observational study was performed in Turku University Hospital, Finland. Preterm infants were eligible if they were born before 36 weeks gestation and received respiratory support with either invasive or non-invasive neurally adjusted ventilatory assist (NAVA). SSC was applied as soon as possible after birth. Respiratory variables were collected from the ventilator log data, and SSC episodes were compared with matched control periods during incubator care. Results A total of 167 episodes of SSC were recorded from 17 preterm infants: 138 episodes during invasive NAVA and 29 episodes during non-invasive NAVA. During invasive NAVA, peak electrical activity of the diaphragm (Edi), minimum Edi, respiratory rate, time on backup ventilation, peak inspiratory pressure, and mean airway pressure were significantly lower in SSC than in incubator care. During non-invasive NAVA, peak Edi, minimum Edi, time on backup ventilation, and peak inspiratory pressure were significantly lower in SSC than in incubator care. Conclusions SSC stabilized and improved the respiratory physiology in mechanically ventilated preterm infants. Impact Skin-to-skin contact reduced work of breathing compared to incubator care in mechanically ventilated preterm infants. Skin-to-skin contact reduced the need for backup ventilation during neurally adjusted ventilatory assist in preterm infants. Skin-to-skin contact among ventilated preterm infants was not only safe but also stabilized and improved their respiratory physiology.

Background Noninvasive 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. Methods The 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. Results The 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. Conclusion NIV-NAVA was a safe, alternative mode of noninvasive support that produced beneficial short-term physiological effects, especially compared with NIMV.

Hyaluronan (HA), an ionic polymer, is normally present in the alveolar subphase and is known to decrease lung surfactant inactivation caused by serum in vitro. In this study, we examined whether HA can ameliorate the inactivating effects of meconium in vitro and in vivo. Surface activities of various mixtures of Survanta, HA, and meconium were measured using a modified pulsating bubble surfactometer. With meconium, almost all surface activity measures were improved by the addition of HA of several molecular weights at a concentration of 0.25%. Anesthetized, paralyzed rats were maintained on positive-pressure ventilation. After lung injury by instillation of meconium, they were treated with Survanta, Survanta with HA, or control mixtures. Serial measures of blood gases and peak inspiratory pressure were recorded for the duration of the experiment. When the Survanta plus HA group was compared with the Survanta alone group, arterial oxygen tension averaged 117% higher, peak inspiratory pressure was 27% lower at the end of the experiment, and lung compliance also showed significant improvement. These results indicate that HA added to Survanta decreases inactivation caused by meconium in vitro and improves gas exchange and pulmonary mechanics of animals with meconium-induced acute lung injury.

Surfactant instillation may affect systemic and pulmonary hemodynamics. The aim of this study was to investigate whether this effect is specific to surfactant or if it can be triggered by instillation of the same volume of saline. Piglets 3-5-d-old were subjected to repeated lung lavage using 20 mL/kg 0.9% saline until the partial pressure of arterial O2 was < 10 kPa and partial pressure of arterial CO2 was between 4.0 and 6.0 kPa with fraction of inspired oxygen (FiO2) 1.0 and peak inspiratory pressure 25 cm H2O. Porcine surfactant 200 mg/kg (80 mg/mL) or the same volume of 0.9% saline was instilled into the lungs through a feeding catheter entered through the endotracheal tube. Mean arterial blood pressure, pulmonary artery pressure, and cardiac output were measured continuously. There was a significant decrease in mean arterial blood pressure from 67 (+/- 13) mm Hg to 52 (+/- 18) mm Hg (p < 0.05) 210 s after instillation of surfactant. Systemic vascular resistance decreased from 0.42 (+/- 0.18) to 0.34 (+/- 0.18) mm Hg x mL-1 x min x kg (p < 0.05) from 0 min to 180 s after instillation of surfactant. In the group receiving saline instillations there were no significant changes in mean arterial blood pressure or systemic vascular resistance. A transient but significant increase in mean pulmonary artery pressure was seen 120 s after instillation in both groups with a return to presurfactant level 240 s after instillation. Pulmonary vascular resistance increased transiently and significantly only in the group receiving surfactant. We conclude that porcine surfactant causes a decrease in systemic vascular resistance, resulting in a decrease in mean arterial blood pressure in newborn lung-lavaged piglets not seen after instillation of the same volume of saline.

Tracheostomized cats and piglets demonstrate respiratory stimulation during experimental seizures, whereas airway intact piglets demonstrate hypoventilation and increased subglottic resistances. The purpose of this study was to characterize the role of the vocal folds in contributing to these increased subglottic resistances during experimental seizures. A controlled animal study was performed in six anesthetized, spontaneously breathing, hyperoxic piglets who had subglottic pressure and airflow measured. A fiberoptic video scope directed into the cephalad trachea recorded subglottic images of the vocal folds. Glottal area patency (GAP) was evaluated at inspiratory onset (Io), peak inspiratory pressure (Ip), and expiratory onset (Eo) for four to five consecutive breaths under baseline control, ictal, interictal, and anticonvulsant conditions. Seizures were induced with i.v. pentylenetetrazol or bicuculline. Normalized GAP was greatest at Ip under all conditions, except anticonvulsant. During ictal periods, piglets demonstrated significant reductions in mean GAP throughout the respiratory cycle (Io, 98%; Ip, 78%; Eo, 98%), compared with baseline (p < 0.001, repeat measures analysis of variance). During ictel discharges, hypoventilation and glottal obstruction resulted in significant reductions in mean arterial pH (–0.35) and Pao2 (–39 kPa) and elevations in Paco2 (+8.1 kPa), compared with baseline conditions. During interictal conditions mean GAP at Ip was increased, whereas at Eo (–66%) GAP was reduced, compared with control. These data demonstrate that the vocal folds are tonically adducted throughout the respiratory cycle during ictal phases and have increased expiratory adduction during interictal phases of seizures induced with standard i.v. convulsants in hyperoxic piglets.

We wished to determine in a laboratory animal model how much residual lung was needed to sustain total gas exchange. In a series of young, healthy lambs weighing approximately 10 kg that were sedated and paralyzed, we progressively excluded from gas exchange all the left lung (a total of 43%), plus the right lower and cardiac lobes (81%), plus the right middle lobe (87.5%). In some studies, the respective lobes were surgically removed; in others, the bronchi and the pulmonary arteries to the respective lobes were ligated. We provided pulmonary ventilation using the pressure control mode (Servo 900 C) at a tidal volume of 20 mL/kg multiplied by the fraction of the remaining lungs, a respiratory rate up to 120/min, a peak inspiratory pressure of 12–15 cm H2O, and a positive end-expiratory pressure of 3 cm H2O. Those lambs with at least both the right upper lobe (RUL) and right middle lobe remaining (19% of total lungs) were weaned to room air on mechanical ventilation within 48 h. Ventilating RUL (12.5% of remaining lung) with the same ventilator required a substantially higher tidal volume and peak inspiratory pressure to result in adequate alveolar ventilation but led to respiratory failure and death within 8 h. We then applied a newly developed system of intratracheal pulmonary ventilation to ventilate the RUL (12.5% of remaining lung) alone. A continuous flow of humidified mixture of air and oxygen was directly passed into the trachea at the level of the carina through a diffuser at a tidal volume of 2.5 mL/kg. A single valve controlled expiration and respiratory rate. Lambs with only RUL remaining were weaned to room air within 2 h, at a respiratory rate of 60–120/min and peak inspiratory pressure of 14–9 cm H2O, inspiration to expiration ratio of 1:1, and positive end-expiratory pressure of 3 cm H2O. Initial mean pulmonary artery pressure progressively decreased from 40 ± 5 to 25 ± 7 mm Hg within 6 h after surgery.

In newborn infants, closed endotracheal tube (ETT) suction may reduce associated adverse effects, but it is not clear whether ventilation is maintained during the procedure. We aimed to determine the effect of ETT size, catheter size, and suction pressure on ventilation parameters measured distal to the ETT. Suction was performed on a test lung, ventilated with conventional (CMV) and high-frequency oscillatory ventilation (HFOV) using ETT sizes 2.5-4.0 mm, catheter sizes 5-8 French gauge (Fr), and suction pressures 80-200 mm Hg. Tracheal and circuit peak inspiratory pressure, positive end-expiratory pressure, and tracheal tidal volume (VT) were recorded for each suction episode. During both CMV and HFOV, tracheal pressures and VT were considerably reduced by suctioning; this reduction was dependent on the combination of ETT, catheter, and suction pressure. Loss of VT, inflation pressure (CMV), and pressure amplitude (HFOV) occurred primarily with insertion of the catheter, and loss of end-expiratory pressure (CMV) and mean tracheal pressure (HFOV) occurred with the application of suction. Circuit pressures were reduced to lesser degree. We conclude that airway pressures and VT are not maintained during closed endotracheal suction with either CMV or HFOV, and choice of equipment and settings will affect the degree of interruption to ventilation.

Lung deposition of inhaled drugs in ventilated neonates has been studied in models of questionable relevance. With conventional nebulizers, pulmonary deposition has been limited to 1% of the total dose. The objective of this study was to assess lung delivery of aerosols in a model of neonatal ventilation using a conventional and novel electronic micropump nebulizer. Aerosol deposition studies with 99mTc diethylenetriamine pentaacetate (99mTc-DTPA) were performed in four macaques (2.6 kg) that were ventilated through a 3.0-mm endotracheal tube (with neonatal settings (peak inspiratory pressure 12-14 mbar, positive end-expiratory pressure 2 mbar, I/E ratio 1/2, respiratory rate 40/min), comparing a jet-nebulizer MistyNeb (3-mL charge, 4.8 microm), an electronic micropump nebulizer operating continuously [Aeroneb Professional Nebulizer (APN-C); 0.5-mL charge, 4.6 microm], and another synchronized with inspiration [Aeroneb Professional Nebulizer Synchronized (APN-S); 0.5-mL charge, 2.8 microm]. The amount of radioactivity deposited into lungs and connections and remaining in the nebulizer was measured by a gamma counter. Despite similar amounts of 99mTc-DTPA in the respiratory circuit with all nebulizers, both APN-S and APN-C delivered more drug to the lungs than MistyNeb (14.0, 12.6, and 0.5% in terms of percentage of nebulizer charge, respectively; p = 0.006). Duration of delivery was shorter with APN-C than with the two other nebulizers (2 versus 6 and 10 min for the APN-S and the MistyNeb, respectively; p < 0.001). Electronic micropump nebulizers are more efficient to administer aerosols in an animal model of ventilated neonates. Availability of Aerogen's electronic micropump nebulizers offers new opportunities to study clinical efficacy and risks of aerosol therapy in ventilated neonates.

Positive end expiratory pressure (PEEP) is important for neonatal ventilation but is not considered in guidelines for resuscitation. Our aim was to investigate the effects of PEEP on cardiorespiratory parameters during resuscitation of very premature lambs delivered by hysterotomy at approximately 125 d gestation (term approximately 147 d). Before delivery, they were intubated and lung fluid was drained. Immediately after delivery, they were ventilated with a Drager Babylog plus ventilator in volume guarantee mode with a tidal volume of 5 mL/kg. Lambs were randomized to receive 0, 4, 8, or 12 cm H(2)O of PEEP. They were ventilated for a 15-min resuscitation period followed by 2 h of stabilization at the same PEEP. Tidal volume, peak inspiratory pressure, PEEP, arterial pressure, oxygen saturation, and blood gases were measured regularly, and respiratory system compliance and alveolar/arterial oxygen differences were calculated. Lambs that received 12 cm H(2)O of PEEP died from pneumothoraces; all others survived without pneumothoraces. Oxygenation was significantly improved by 8 and 12 cm H(2)O of PEEP compared with 0 and 4 cm H(2)O of PEEP. Lambs with 0 PEEP did not oxygenate adequately. The compliance of the respiratory system was significantly higher at 4 and 8 cm H(2)O of PEEP than at 0 PEEP. There were no significant differences in partial pressure of carbon dioxide in arterial blood between groups. Arterial pressure was highest with 8 cm H(2)O of PEEP, and there was no cardiorespiratory compromise at any level of PEEP. Applying PEEP during resuscitation of very premature infants might be advantageous and merits further investigation.

Energy expenditure measurements in ventilated preterm infants are difficult because indirect calorimetry underestimates energy expenditure during gas leaks around uncuffed endotracheal tubes routinely used in preterm infants or during nasal continuous positive airway pressure (CPAP). We, therefore, developed a breath collector that simultaneously sampled expired air expelled at the ventilator outlet and escaping via the tube leak from the infant's mouth and nose. Our breath collector was combined with a proprietary calorimeter (Deltatrac II). In vitro validation was done by methanol burning (VO(2), 13.8 mL/min; VCO(2), 9.2 mL/min) during intermittent positive pressure ventilation (IPPV) with two commonly used ventilators (Sechrist IV-100B and Infant Star). Measurement error was determined at different ventilator flows, peak inspiratory pressures of 12-24 cm H(2)O, and during a complete tube leak. The mean measurement error with both ventilators was low (VO(2) +/- 3 %, VCO(2) +/- 2 %) even during a complete tube leak and did not increase with peak inspiratory pressure. The system response time was 2 min. In vivo measurements at the bedside were performed in 25 preterm infants (body weight, 537-1402 g). Energy expenditure during IPPV was 40 +/- 9 kcal/kg per day and 46 +/- 15 kcal/kg per day during nasal CPAP. The tube leak in the preterm infants studied during IPPV was 0 to 47 %, and during nasal CPAP 84 to 97 %. In conclusion, indirect calorimetry performed with our breath collector was accurate during IPPV and nasal CPAP and was unaffected by tube leaks.

Intratracheal pulmonary ventilation (ITPV) enhances the clearance of CO2 from dead space and lungs by a bias flow of gas administered in the distal trachea. ITPV flow is continuously administered through a separate catheter placed within an endotracheal tube (ETT). After exiting from catheter's tip in the distal trachea, the flow of gas is redirected outward away from the lungs. We hypothesized that, compared with conventional mechanical ventilation (CMV), ITPV may increase minute CO2 clearance (VCO2), reduce the partial pressure of CO2 dioxide in arterial gas (PaCO2), and reduce distal tracheal peak inspiratory pressure (dPIP). We induced surfactant deficiency in 15 adult rabbits by lung lavage with 10 mL/kg normal saline. Animals were ventilated through a double-lumen 4.0 ETT, inserted through a tracheotomy incision. dPIP, distal positive end expiratory pressure, and distal mean airway pressure were monitored, and the mean exhaled CO2 concentration was measured. For ventilator rates (respiratory rate) of 30, 45, and 70 breaths/min, the study included two phases: phase I compared CO2 clearance and PaCO2 between ITPV and CMV using similar ventilatory pressures; phase II evaluated the effectiveness of ITPV in reducing dPIP and tidal volume (Vt), compared with CMV, while maintaining eucapnea. When comparing ITPV and CMV, the following results (mean +/- SD) were achieved at respiratory rate of 30, 45, and 70 breaths/min, respectively. Phase I ITPV resulted in mean percent reduction of PaCO2 by 31.4 +/- 10%, 37.1 +/- 9.7% and 38.3 +/- 9%; mean percent increase in VCO2 by 61.3 +/- 29%, 56 +/- 23, and 98 +/- 40%, compared with CMV. Phase II ITPV resulted in mean percent reduction of dPIP by 35.5 +/- 14%, 38 +/- 10.8%, and 37.2 +/- 13.7%, and mean percent reduction in Vt by 34.7 +/- 12.9%, 36.4 +/- 15%, and 52.7 +/- 10.7%, compared with CMV. The changes in PaCO2, VCO2 (phase I), and dPIP and Vt (phase II) were all significantly more than 25% (p0.05). Oxygenation and pH were not significantly different between ITPV and CMV. We conclude that, in a surfactant deficiency rabbit model, ITPV is an efficient mode of assisted ventilation that increases CO2 clearance and reduces ventilator pressures required for adequate ventilation. We speculate that ITPV can minimize lung barotrauma associated with mechanical ventilation.

Treatment of nonhuman primate fetuses with epidermal growth factor (EGF) results in histologic and biochemical maturation of their lungs. To determine whether these effects improve lung function postnatally, we studied premature rhesus infants delivered at 78% of gestation after in utero treatment with EGF (n = 5) or placebo (n = 5). Indices of lung function during the 4 d of postnatal care included fractional concentration of inspired oxygen, peak inspiratory pressure, ventilator rate, mean airway pressure, arterial to alveolar oxygen tension ratio, and ventilation index. Statistically significant differences were noted in the time courses of these variables between EGF- and placebo-treated infants. The direction of the differences indicated that the EGF-treated infants had less severe lung disease. Surfactant apoprotein A concentration and lecithin to sphingomyelin ratio were both significantly higher in the amniotic fluid of the EGF-treated group, indicating advanced biochemical maturation in this group of animals. Whereas birth weight was not affected by EGF exposure, adrenal and gut weights, standardized for body weight, were increased significantly. Histologic studies showed advanced cellular maturation with increased parenchymal airspace and decreased parenchymal tissue space in the EGF-treated group compared with the control group. We conclude that prenatal exposure to EGF stimulates biochemical and histologic maturation of the lung and markedly attenuates the clinical severity of respiratory disease in this model of simian respiratory distress syndrome.

Promotion of lung volume recruitment in atelectatic lung and maintenance of existing recruited lung are vital goals of contemporary ventilatory support. In the mature adult lung, the recruitment of terminal airspaces are governed by power-law distributions, arising from avalanches associated with threshold pressure phenomena propagating down a branching tree structure. Superimposition of noise on the pressure waveform during conventional can promote recruitment of collapsed lung zones when the peak inspiratory pressure is at or around the lower inflexure and that this approach may also promote increased secretion of endogenous surfactant. The mechanism involves the phenomenon of stochastic resonance, which is most simply described as the addition of noise to a weak input signal to enhance output in a nonlinear dynamic system. It is a widespread, naturally occurring phenomenon that can be seen reflected in the patterns of world weather, fluctuations on the stock market, population biology, and optimal functioning of neural networks, to name but a few. Recent studies in newborn lambs show that incorporating variability in the breathing pattern enhances gas exchange, lung mechanics and regional ventilation distribution, indicating that these same stochastic principles apply to the immature lung. Further, increased expression of endogenous surfactant protein mRNA in lambs receiving variable volume ventilation compared to controlled mechanical ventilation suggests the fetus is programmed to respond to variable input signals.

Potential beneficial and/or detrimental effects of inhaled NO on oxidant-induced lung injury have not been fully investigated in newborn infants. The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter pulmonary vascular permeability and respiratory function in mechanically ventilated newborn piglets -1 to 2 days old-, exposed to 100% O2 for 76 hours. They were randomly assigned to treatment with 20 ppm inhaled NO (n=5) from the onset of ventilation or control (n=6). Peak inspiratory pressure was set to maintain PaCO2 between 35 and 45 mmHg. The other ventilator parameters were not changed during the course of the study (FiO2=1; PEEP=5cmH2O; RR=25/min). The main studied parameters were gas exchange (PaO2/FiO2 ratio, lung diffusing capacity=DLCO), respiratory mechanics (static compliance of the respiratory system=Crs,stat measured at 5, 10, 15, and 20 ml/kg during inspiration and expiration, quasi-static hysteresis area, functional residual capacity=FRC) and pulmonary vascular permeability assessed by simultaneous intravenous administration of 125I-labeled albumin and 51Cr-labeled red blood cells. PaO2/FiO2 decreased significantly between 2 and 76 hours of 100% O2 exposure in the control and the NO groups (from 388±63 to 225±63 and from 375±84 to 200±64 mmHg respectively). The extravascular albumin space of the lung and the dry lung weight were significantly higher in the NO group versus control group (Alb space: 1.08 ± 0.16 ml / kg body weight versus 0.70 ±0.26 ml / kg body weight and dry lung weight: 3.20 ± 0.34 g / kg body weight versus 2.66 ± 0.14 g / kg body weight respectively). Moreover, hysteresis area was higher from 24 hours of NO exposure. Conversely, NO inhalation did alter neither the extravascular lung water content (12.98 ± 2.79 ml / kg body weight in the NO group versus 12.18 ± 2.26 ml / kg body weight in the control group; NS), nor the main respiratory mechanic parameters (Crs,stat, FRC) and gas exchange (DLCO, PaO2/FiO2 ratio). In conclusion, our results do not support the hypothesis that NO inhalation combined with hyperoxia may alter the main lung function parameters in neonates. However, it may induce an increase in lung vascular protein leakage. Pathophysiological consequences of this finding remain to be elucidated.

It has previously been established that only 1% to 3% of albuterol placed in a small volume nebulizer (SVN) is delivered to an intubated infant receiving conventional mechanical ventilation (CMV). We hypothesized that in high frequency oscillation (HFO) even less drug would be delivered due the very small tidal volumes. To demonstrate this we nebulized green food coloring in an HFO circuit attached via an endotracheal tube (ETT) to a test lung with a white filter at the opening. However, the filter quickly turned green, se we formed a new hypothesis to the effect that the ouput of an SVN was as likely to reach an intubated lung when used with HFO as it was in CMV. To test this a cotton ball was placed in an adapter at the opening of a neonatal test lung. A 3.0 mm ETT was attached to the adapter containing the cotton ball, and placed in brackets which held it in a curved shape. This ETT was in turn attached to the circuit of an actively cycling ventilator in which a nebulizer containing 2.5 mg of albuterol in 3 mL of solution was driven with 8 L/min flow until the nebulizer was exhausted. The cotton ball was then removed, placed in a cup, washed with 20 mL of saline solution, and agitated for one minute. The concentration of albuterol present in the resulting solutions was determined by spectrophotometry. Five repetitions of three different ventilator configurations were performed. In trial A HFO was performed using a Sensormedics 3100a operated at a rate of 15 Hz, a mean airway pressure of 15 cm H2O, a ΔP of 33 cm H2O, and the SVN placed on the inspiratory side of the patient circuit in the temperature monitoring port. In trial B HFO was performed in the same way but the SVN was placed directly on the ETT. In trial C the SVN was placed in the inspiratory side of the patient circuit in the temperature monitoring port with a Sechrist 1000 IV providing CMV at a rate of 60, a peak inspiratory pressure of 30 cm H2O, a continuous positive airway pressure of 4 cm H2O, and an inspiratory time of 0.40 seconds. Results: Trial A- 0.18 mg ± 0.059; Trial B- 0.225 mg ± 0.107; Trial C- 0.172 mg±0.009. Results for all three trials were not significantly different from one another (P-value >.4 by both Kruskal-Wallis H and ANOVA.) We therefore have concluded that an SVN is not more inefficient in albuterol delivery to the lung in HFO that it is in CMV. As a result, we are now investigating particle size and dose effect when the SVN is used in HFO.

Retrospective studies suggest that ventilatory strategies that tolerate mild hypercapnia and/or prevent hypocapnia during the first days of life may reduce chronic lung disease (CLD). We performed a randomized trial to compare the effects of permissive hypercapnia (H, PaCO245-55 torr) versus normocapnia (N, PaCO235-45 torr) during the first 96 hours of life in neonates weighing 601 to 1250 gm who received mechanical ventilation (MV) and surfactant. The primary outcome measure was total days on MV. Extubation criteria were pH ≥ 7.25, ventilator rate ≤ 10/min, and peak inspiratory pressure (PIP) ≤ 19 cm H2O. All patients received aminophylline prior to extubation. Ventilator-dependent infants at 10 days received 7 days of dexamethasone. Reintubation was performed for a pH < 7.20. Patients(n=49) were randomized at a mean age of 10 hours of life (H=24, N=25). The groups were comparable for gestational age (26 ± 1 weeks), birth weight(H 852 ± 156 gm, N 856 ± 173 gm), gender, race, prenatal steroid use, and blood gas values, oxygenation index, and ventilator settings prior to randomization. The total number of days on MV (median, 25-75 quartiles) was 2.5, 1.5-11.2 in the H group and 9.2, 1.5-22.5 in the N group (p=0.17, Mann-Whitney). The number of patients on MV throughout the 96 hours after randomization was lower in the H group (figure). During that time, the ventilated patients in the H group had a higher PaCO2 and lower PIP, mean airway pressure, and ventilator rate than those in the N group (repeated measures ANOVA, all p

Historically, pressure limited, time cycled ventilation has been the cornerstone of neonatal ventilation. The advent of sensitive flow sensors now allows rapid, continuous measurement of Vt in small neonates. We hypothesized that an algorithm combining Vt measurements with maximal use of noninvasive monitoring would allow safe, uniform weaning of infants with RDS from mechanical ventilation with a minimum of blood draws. The primary premise of the algorithm: using Vt to modify peak inspiratory pressure (PIP) to keep Vt 5-7 ml/kg; modify rate to keep pH 7.27-7.33; modify FiO2 to maintain SaO2 89-94%. Tidal volumes were measured with the Bicore CP-100 Neonatal monitor. This uses a self calibrated transducer to measure air flow. Flow is then integrated to give the infant's tidal volume. CO2 was monitored with transcutaneous CO2 (Novametrix), SaO2 with the Nellcor pulse oximeter. Arterial blood gases were drawn from the umbilical arterial line when available, or peripheral capillary blood gases were followed. Data from 33 infants (mean BW=1326g, GA=29.5 wks, 54% male, 50% Caucasian, initial mean airway pressure (MAP)=8.5 cmH2O, initial FIO2= 0.62) intubated secondary to RDS and managed as per the WP were evaluated. This was compared with data from 33 matched retrospective controls (mean BW=1274 g, GA=29.2 wks, 57% male, 66% Caucasian, initial MAP=8.7 cm H2O, FIO2=0.63). Primary outcome variables included: initial PIP (IPIP) and maximum PIP (MPIP), total blood gases (BG) for initial 72 hours of management and for first 7 days of hospitalization, and duration of mechanical ventilation. No patient managed per the weaning protocol had a pH value of

Surfactant protein B (SP-B) is critical to surfactant function. Survanta®, a modified bovine lung extract, contains less SP-B than surfactants derived from lung lavage (Seeger et al., Eur Resp J 1993;6:971). Supplementation of Survanta with native SP-B increases dynamic compliance and deflation lung volume in preterm rabbits (Mizuno et al., Pediatr Res 1995;37:271). We hypothesized that the in vivo function of Survanta can be improved by supplementation with synthetic SP-B and SP-C and tested this hypothesis in a surfactant-deficient rat model. Full length SP-B1-78 and palmitoylated SP-C1-34 were synthesized, purified, derivatized, and analyzed by mass spectrometry and amino acid analysis. Survanta was extracted, unmodified (Surv-1) or enriched with 1% SP-B (Surv-2), 2% SP-B (Surv-3), or 2% SP-B + 1% SP-C (Surv-4), and resuspended. In vitro surface activity was tested on a modified Langmuir/Wilhelmy balance and SP-B and SP-C content were measured by Fourier transform infrared spectroscopy. Adult rats were anesthetized, tracheotomized, had an arterial line placed, and were ventilated with 100% oxygen, a peak inspiratory pressure of 30 cm H2O and a rate of 40/min. The lungs were lavaged with warmed normal saline until the PaO2 dropped below 60 torr, at which time 100 mg/kg of one of the four surfactant preparations was instilled. After 15 min of ventilation, the rats were killed and pressure-volume curves performedin situ. The mean arterial/Alveolar PO2 ratio was 0.08 post-lavage and increased by 74% after treatment with Surv-1 (n=5), by 92% after treatment with Surv-2 (n=6), by 257% after treatment with Surv-3 (n=5), and by 202% after treatment with Surv-4 (n=6). Surv-4 not only improved PaO2, but also reduced PaCO2 values. These data suggest that the addition of 2% synthetic SP-B to Survanta improves its short-term positive effects on oxygenation in this surfactant-deficient rat model.

Monitoring of respiratory mechanics is not a well developed technique in neonatal intensive care units. The aim of this report was to describe an automated system that could be routinely used at bedside in neonatal and pediatric intensive care units. This system is composed of a microcomputer IBM 486 PC equipped with an analog-to-digital data acquisition board (12 bits resolution). Flow was measured by a Fleisch pneumotachometer n°00 inserted between the endotracheal tube and the breathing circuit and connected to a pressure transducer (± 2 cmH2O). Pressure variations were measured at airway opening. Signals were sampled at 256 Hz. Data processing includes “time fi notion” and “loop function”. Time function provides data processing (low pass and high pass filtering, gain and sweep frequency tuning, numeric integration) and real time computing of several parameters (tidal volume, respiratory frequency, inspiratory time, peak inspiratory pressure, mean pressure, positive end expiratory pressure and air leak ratio). With Loop function, flow/volume, volume/pressure and pressure/flow loops are displayed in real time at each ventilatory cycle. At any time, the operator can freeze the display and calculate respiratory mechanic parameters (resistances, compliance, time constant, trapped volume and intrinsic positive end expiratory pressure) by using the passive inflation method. This system provides qualitative informations by displaying loops and quantitative data. The use of microcomputer makes this technique attractive and highly suitable for understanding the pathophysiology of the underlying disease, for optimizing ventilator settings and/or for evaluating drug efficiency.

We studied the possibility to improve lung distensibility by SI during the first hours of age. Preterm newborn lambs (123-133 days of gestational age, n=70) were used. Initially all lambs were mechanically ventilated with 100% O2, peak inspiratory pressure (PIP) was adjusted for paCO2. For SI the ventilator was disconnected and the lungs were inflated during five seconds at a PIP of 25 or 35 cmH2O with a mixture of 5% CO2 and 95% O2. Each inflation was followed by positive end expiratory pressure of 5 cmH2O for 5 seconds. This procedure was repeated three times. SI was applied in three groups: 1) within 15 minutes after birth, 2) within 15 minutes after birth and repeated each hour for 3 hours 3) at 4 hours of age. Two control groups (4 and 5) were formed, 4) as group 1, except that during disconnection the lungs were inflated at the same pressure as for SI, but with short inspiratory time, 5) lambs were ventilated without any manipulation. Blood gas samples were taken every 30 minutes. Compliance (Cl) was calculated from the injected volume of air per kg wet body weight needed to obtain a pressure of 20 cmH2O. Results (mean±SEM) at 3 hours after birth: In summary, SI as used here showed no significant changes in compliance or blood gas exchange at 3 hours of age.

Summary: After delivery by cesarean section at 133–136 days gestational age, 18 lambs were supported with infant ventilators. Peak inspiratory pressure was the only ventilator setting that was changed in an attempt to normalize PCO2. The lambs were retrospectively divided into two groups based on their respiratory status before treatment. Ten lambs with PCO2 values of 38 ± 2 mmHg (mean ± S.E.) at 5 h of age were treated with a 15-ml suspension containing 50 mg natural sheep surfactant lipid/kg body weight. After surfactant instillation, pH fell, PCO2 increased and compliance/kg decreased transiently. Surfactant treatment did not reduce the respiratory support that these lambs required. Eight lambs with PCO2 values of 68 ± 3 mmHg at 3 ± 0.8 h of age responded to surfactant instillation with a decrease in PCO2 and an increase in PO2 and pH. In both groups of lambs heart rates, mean aortic pressures, and mean pulmonary artery pressures changed little after surfactant instillation. Cardiac outputs and regional blood flows measured before and after surfactant treatment were unchanged. Instillation of surfactant suspensions to premature lambs did not adversely affect cardiovascular status; however, some lambs did have a transient deterioration of lung function after surfactant instillation.

Summary: The pressure-volume (PV) characteristics of 21 adult rat lungs were examined before and after lung washing after which natural or synthetic (dipalmitoyl lecithin (DPL)) surfactant was administered by either an ultrasonic nebulizer or instilled directly into the trachea. Lungs receiving surfactant by nebulization were ventilated at a rate of 40/min at 20 cm H2O peak inspiratory pressure and with 7 cm H2O positive end expiratory pressure (PEEP) for 2 hr. Lungs receiving surfactant by instillation were ventilated for 5 min in a fashion similar to the nebulization study; then a final PV curve was obtained. Results from the deflation limb of the PV curves at 5 and 10 cm H2O were analyzed and expressed as a percentage of the original total lung capacity obtained at 30 cm H2O (percentage of TLC). The control values of percentage of TLC were 52.8 ± 6.4 at 5 cm H2O and 73.9 ± 3.9 at 10 cm H2O. Neither nebulization nor instillation of DPL produced a significant increase in percentage of TLC. Nebulization of natural surfactant produced only a slight increase in percentage of TLC from 4.8 ± 2.4 to 6.7 ± 2.1 (not significant) at 5 cm H2O and from 21.1 ± 6.1 to 27.8 ± 5.4 (P < 0.05) at 10 cm H2O. Instillation of natural surfactant produced a very striking increase of percentage of TLC from 13.2 ± 8.0 to 55.6 ± 4.3 (P < 0.01) at 5 cm H2O and from 47.9 ± 6.1 to 78.6 ± 4.2 (P < 0.01) at 10 cm H2O. Speculation: From these studies, it appears that nebulization is not an effective method for depositing surfactant into the alveoli. On the other hand, direct instillation of the material into the tracheal bronchial tree seems to be a promising method worthy of further study as a method for treatment of the respiratory distress syndrome.

The mechanical work of breathing (WOB), can be determined from the simultaneous measurement of changes in volume displacement and pressure (WOB=ΔV·ΔP). We designed a lung simulator device which typifies a breathing, intubated neonate in compliance, frequency, inspiratory flowrate, resistance and tidal volume (2cc/cmH2O, 50/minute, 80cc/second, 3.0 ET tube, 10cc respectively). All measurements were at the airway opening via a calibrated transducer/recorder system with a frequency response flat to >50 Hz. We evaluated the performance of the BABYbird 1R, BABYbird 2R Bear BP-200R, Bear-2001 ‘Cub’R, Healthdyne 105R, Healthdyne 200R and Sechrist IV-100BR. All units were stock and represented a wide sampling of current continuos flow, pressure limited, time cycled neonatal ventilators. Excluding the exhalation valve, the ventilator circuits were identical (TYGONR tubing, 0.3cc/cmH2O, compliance). The following settings were used during the test period: inspiratory time= 1.0 second, peak inspiratory pressure= 25 cmH2O, and PEEP= 5 cmH2O. Mechanical WOB ranged from 140 to 240 cc·cmH2O during the IMV breaths and 110 to 200 in the PEEP interval. The Healthdyne 105R had the lowest WOB in both periods whereas the greatest WOB occurred with the Sechrist in IMV and Bear Cub in PEEP. We have used clinically all of the ventilators tested and have not noted any deleterious results secondary to the diversity in mechanical WOB. However, the WOB difference is broad and may have subtle and/or patient compensated effects on the spontaneously breathing infant being exposed to mechanical ventilation.

To evaluate the subjective impression of improved gas exchange with muscle paralysis in some infants on mechanical ventilation, we observed 35 infants who received pancuronium while on Baby Bird ventilators. Pancuronium (0.1 mg/kg I.V.) was repeated until spontaneous respirations ceased in infants who had inadequate gas exchange with FIO2 > 0.60, peak inspiratory pressure >30cm H2O or who were “fighting” the ventilator. 27 infants received pancuronium within the first 48 hours of life, 15 within the first 24 hours. Infants remained paralyzed for a median of 36 hours. 27 infants had ≥ torr before paralysis. ≥ improved by >100 torr within one hour of paralysis in only 2 of the 27 infants; it worsened in 2 infants within the same period. By 6 hours post-paralysis, 12 infants had improved, 5 of whom had had a worsening ≥ before administration of pancuronium. ≥ decreased in 5 infants by > 10 torr within 1 hour of paralysis and increased in 8 infants with either unchanged ventilator settings or changes expected to improve ventilation. No significant changes were observed in blood pressure or heart rate. Only 4 of the 35 infants developed a pneumothorax while paralyzed. Since birthweight, gestational age, or diagnosis could not distinguish those who would respond, one can determine efficacy in a particular patient only by trial. Improvement, when it occurs, is most likely related to changes in right-to-left shunting or V/Q abnormality.

High frequency jet ventilation (HFJV) represents a radically different management approach to severe neonatal respiratory disease. In order to determine if HFJV could be augmented by the use of intermittent mandatory ventilation (IMV), two groups of infants were prospectively evaluated. Both groups consisted of 3 infants, two with severe RDS, one with pulmonary hypertension. Mean BW was similar (2.0 ± .6 SEM kg vs. 2.1 ± .7 SEM kg) as were GA (32.7 ± 3.4 wks vs. 24 ± 3.1 SEM wks). One group (HFJV-IMV) received HFJV (Bunnell Life Systems Inc.) (rate 400-500 bpm) and IMV (5 bpm). The other group received HFJV alone (rate 400-600 bpm). The HFJV-IMV group was treated for a mean of 112 ± 40.6 SEM hrs., the HFJV group was treated for a mean of 24.3 ± 13.6 SEM hrs. The HFJV-IMV group demonstrated a 13.3 ± 2.3 SEM cmH2O decrease in peak inspiratory pressure (PIP) and a 5.0 ± 1.1 SEM cmH2O decrease in mean airway pressure (MAP). PaO2 increased a mean of 66.0 ± 11.5 SEM torr, while PaCO2 decreased 13.6 ± 7.1 SEM torr. In the HFJV group there was a 9.6 ± 4.9 cmH2O decrease in PIP and a 3.3 ± 1.2 cmH2O decrease in MAP. PaO2 increased 31.3 ± 17.6 SEM torr, while CO2 showed a 4.3 ± 11.6 SEM torr decrease. Infants in both groups took 2.2 ± 0.4 SEM hours to stabilize on HFJV. One infant in each group survived and is entirely well at present. These preliminary data suggest that HFJV may be an effective therapy in severe neonatal respiratory disease. Augmentation of HFJV by IMV may be a valuable approach in some infants.

Few studies have determined if severity of RDS is influenced by the affected infant being born at a tertiary level center as opposed to being transported from an outlying hospital to the ICU. To evalute this problem, we followed 10 inborn(I), infants and 20 outborn(O) infants. All had RDS by standard criteria. Inborn infants were slightly less mature (I = 31.1±.7 wks. SEM; 0 = 31.6±.6 wks. SEM) and weighed less (I = 1490±109 gms. SEM; 0 = 1620±76 gms. SEM), but the difference was not statistically significant. The inborn group had a lower mean maximum FiO2 (I = 0.63±.03 SEM; 0 = 0.73±.03 SEM) to maintain paO2 at 50-75 torr and required oxygen for a significantly shorter period (I = 135.3 ±27.5 SEM hrs; 0 = 247.7±46.0 SEM hrs.) to resolution of their disease (p < .05). While maximum ventilator rate was similar in each group (I = 50±2.8 SEM breaths/min.; 0=48.5±4.05 SEM breaths/min), peak inspiratory pressure was significantly higher in the outborn babies (I = 16.8±0.7 SEM cm H20; 0 = 24.4±1.7 SEM cm H20) (p < .025). Infants in the inborn group also required mechanical ventilation for a shorter duration (I = 68.3±13.8 SEM hrs.; 0 = 138.1±36.7 SEM hrs.), but this difference was not significant (p=.09). Results of this study suggest that the course of RDS in the perinatal center is significantly milder than that seen in infants requiring transport. Avoidance of perinatal asphyxia and early intervention may be the critical factors.

HFJV has been reported to reduce airway pressures during assisted ventilation in preterm infants. Nonetheless, augmented pressure transmission to alveoli has been observed at frequencies near resonance. We determined the effect of surfactant deficiency on airway to alveolar pressure transmission in 6 postmortem adult rabbit lungs (3 normal and 3 surfactant-deficient by multiple saline lavage) during both conventional ventilation (CV, f=30/min, rectangular wave) and HFJV (f=200/min, triangular wave). Alveolar pressure was measured via a piezoelectric transducer on the visceral pleura and communicating with the alveoli. Airway pressure was measured with a similar transducer and/or catheter, both inside the distal endotracheal tube. With each ventilator, measurements were obtained maintaining either peak inspiratory pressure(PIP 20-30cmH2O), positive end expiratory pressure(PEEP 3-13cmH2O) or ΔP(PIP-PEEP 7-27cmH2O) constant. During CV the ratios of alveolar to airway PIP, PEEP and ΔP were always 1.0, while during HFJV they ranged from 0.9 to 1.1. Alveolar to airway pressure ratios were not affected by saline lavage and were independent of magnitude or combination of pressures used. We conclude that in this rabbit model of normal and surfactant-deficient lungs, airway pressures are transmitted to the alveoli with little distortion during HFJV at the frequencies employed. Thus, the previously reported reduction in airway pressures during HFJV may in fact portend decreased barotrauma at the alveolar level. Supported by ALA-Ohio

PS can lower surface tension (ST) to

RDS is characterized by an inadequate surfactant system which, in the untreated course, leads to progressive atelectasis and decreased FRC. PEEP is used to counter atelectasis and reduce intrapulmonary shunting. FRC is controlled by PEEP yet PEEP is selected primarily on the basis of blood gases and not FRC. We were concerned that these empirical methods of selecting PEEP for RDS infants frequently result in FRC levels well above or below normal. Therefore, we measured the FRC of 14 prematurely born infants in their second day of life. The infants' mean (± SD) gestational age was 31.5 ± 2.2 wk; birth wt 1.6 ± 0.5 kg; Apgar score (1 min) 4.4 ± 2.2. All infants had clinically diagnosed RDS and were ventilated with the following mean settings: peak inspiratory pressure 23.3 (range 14-34) cm H2O; PEEP 4.4 (3-8) cm H2O; rate 42 (20-60) BPM. Computerized N2 washout methods, similar to those used in this study, show the FRC of healthy infants this postnatal age to be 17 ± 2 ml/kg body wt (Hansen et al, Ped 1970). In our study on RDS infants the FRC ranged from 3 to 33 ml/kg with a mean of 14.5 ml/kg. Only 3 infants (21%) had volumes within one SD of normal. In 5 infants, FRC was greater than one SD above normal and in 6 infants, FRC was greater than one SD below normal. Six infants (43%) had FRC values outside of 2 SD of normal. These results suggest that conventional methods of selecting PEEP do not result in the maintenance of normal FRC levels in infants with RDS.

We examined the effect of progressive increases in ventilator rate on delivered tidal (VT) and minute volumes (V), and the effect of changing peak inspiratory pressure (PIP), PEEP, and I:E at different ventilator rates. Five different pressure preset infant ventilators were studied using a pneumotachograph, airway pressure monitor, and lung simulator. As rates increased from 10 to 150 bpm, VT stayed constant until 25-30 bpm; then progressively decreased. In all, VT began to decrease when proximal airway pressure waves lost inspiratory pressure plateaus. As rates increased, V increased until 75 bpm; then leveled off; then decreased. Substituting Helium for Oxygen increased the ventilator rate at which this V plateau effect occurred. Increasing PIP consistently increased VT. Increasing PEEP decreased VT. At rates less than 75 bpm, I:E (inspiratory time) had little effect on VT or V. At rates above 75 bpm, inspiratory time became a prime determinant of delivered V.

Although selective paralysis significantly reduces the incidence of pneumothoraces, initiation of paralysis with pancuronium has been associated with transient hypoxia and catecholamine surge, both of which could hazardously affect cerebral blood flow. This study investigated the effectiveness of increasing ventilator settings 1 immediately prior to paralysis to try and prevent transient hypoxia and consequent rise in catecholamine levels resulting from hypo- ventilation (associated with the first dose of pancuronium). 18 infants GA 30 wks (range 26-34)

RRV has been used to reduce PaCO2 in infants with persistent fetal circulation. RRV produces AO in the rabbit lung (time constant (τ) similar to infants). We hypothesized that AO could be reduced if the PEEP in the trachea (PEEPT) was controlled during RRV. We studied 10 rabbits measuring tracheal airway pressure, functional residual capacity (FRC) PaO2 and PaCO2 at ventilator (Baby Bird®) rates of 30, 60, 90 and 120 BPM white: 1) controlling ventilator PEEP (PEEPV) at 2 cm H2O then 2) controlling PEEPT at 2 cm H2O. Peak inspiratory pressure was held constant (15 cm H2O) as was inspiratory:expiratory time (1:2) at rates of 60, 90 ahd 120 BPM. To control PEEPT we lowered PEEPv to 1.2, 1.1 and 0.5 cm H2O. As rates were increased, controlling PEEPT resulted in significant decreases in mean airway pressure (Paw) (by 0.0±.0(SE), 0.4±.1, 0.5±.1 and 1.0±.2 cm H2O) and FRC (14±1, 15±1, 17±2, 21±2 ml/kg when PEEPV was 2 cm H2O vs. 14±1, 14±1, 15±1, 16±2 ml/kg when PEEPT was 2 cm H2O) (p

We have used a pulsed bidirectional doppler ultrasound system to study the possible effects that IPPV may have on cerebral arterial and venous blood velocities in the newborn. The signal obtained from these vessels (usually the superior sagittal sinus and an intra-cerebral artery) is analysed by computer and the results are presented as velocity per consecutive heartbeat. 26 babies have been studied, several on more than one occasion and they represent a broad spectrum of babies requiring IPPV. The results indicate that the babies fall into 3 main groups:1.those in whom we could find no effect on cerebral blood velocities related either to the rate of ventilation or the peak inspiratory pressure(PIP),2.those in whom venous velocities diminished intermittantly in time with the rate of ventilation and 3.those in whom both arterial and venous velocties were influenced by the rate and the PIP. Most babies were in group 2 but a few showed large swings in arterial velocities related to IPPV and in general the higher the PIP the greater the beat to beat variation in the velocities. By lowering the PIP even by 1-3cm H2O the effect on venous velocities lessened and disappeared at a certain critical pressure. These findings could vary from day to day depending on lung disease and spontaneous respiratory effort. We have been able to show that it is possible to avoid some of the largest fluctuations in cerebral velocities by only small reductions in PIP whilst still adequately ventilating the infant.

Because of high airway resistance and low lung compliance in severe RDS, it has been suggested that a respirator able to produce a square pressure waveform may provide better oxygenation & ventilation. To test this hypothesis we made a study of 15 neonates with severe RDS. Two most commonly used infant respirators, one a time-cycled, continuous flow, generating modified sine ware with slow ascending inspiratory limb and slow descending expiratory limb (I), and a second, generating a square wave with rapid inspiratory and expiratory limb (II) were used. Neonates were stabilized for a period of 6-8 hrs on respirator I when pH, PaO2 and PaCO2 were determined before switching to respirator II. Respirators were matched for FiO2, Peak Inspiratory Pressure, End Expiratory Pressure, I:E ratio and Duration of Positive Pressure (DPP) or the area under the curve of respiratory waveform. After 20 minutes on respirator II pH and blood gases were done before switching back to respirator I, and again, after 20 min, pH and blood gases were obtained. Values were compared for the two variables of equal DPP and equal area under the curve. Statistically significant differences were found for PaO2 (71±16vs62±16 Torr, p

In 3 Infants with BPD, aged 35 to 90 days, dramatic ventilatory improvement began within the first 24 hours of I.M. dexamethasone, 0.8 mg every 8 hours. This improvement made it possible to decrease peak inspiratory pressure an average of 9.5 cm H2O (range 7-12) within 72 hours. In 2 infants an L/S ratio was performed on tracheal aspirate obtained prior to therapy and 24, and 72 hours post-medication. The values remained essentially unchanged. One infant regressed after dexamethasone was discontinued and again improved after therapy was restarted. Two infants were successfully extubated while on dexamethasone. All 3 infants eventually succumbed, 2 to their disease and 1 to complications of dexamethasone therapy. Two additional infants with BPD also demonstrated significant improvement in ventilatory function associated with an episode of bacterial sepsis. It is hypothesized that an endogenous steroid surge may have been responsible. Both of these infants survived. The mechanism of steroid action in BPD is unknown. Induction of enzymes, other than those involved in lecithin synthesis, or a shift in fluid compartments is a theoretical possibility. Steroid therapy may be considered as a final alternative in those infants with chronic BPD who show no natural trend toward improvement.

Mean airway pressure (MAP) directly relates to oxygenation in neonates with respiratory distress syndrome (RDS). Variations in the Positive End Expiratory Pressure(PEEP)with concomitant changes of the Duration of Positive Pressure (DPP) while MAP, Peak Inspiratory Pressure, flow, FiO2 and rate remained constant, were investigated in 9 neonates with RDS during the 1st and 2nd day of life. After stabilization on baseline ventilator settings, PEEP was increased by an average of 60% and the DPP was decreased (about 0.3 sec)in order to maintain baseline MAP. Following a return to baseline,a second experimental condition consisted of decreasing PEEP by 60%, increasing DPP accordingly to maintain constant MAP. Arterial BP, heart rate, paO2, paCO2, pH and arterial/Alveolar pO2 ratios (a/APO2) were measured before, during, between and after the experimental conditions. Analysis of the data revealed no significant changes in BP, paO2, a/APO2, heart rate during baseline or experimental conditions. PaCO2 decreased significantly when PEEP was decreased and DPP increased, both on Day 1(37.2 ± 6.6 vs 41.4 ± 6.4 Torr; p

We examined the performance of 4 infant ventilators (Bourns BP 200, Healthdyne 105, Sechrist IV-100B, Infrasonic Infant Star) during a simulated expiration. A test lung was connected via a conventional circuit to the ventilator which was set to deliver a PIP of 20 cm H2O. A Statham pressure transducer was placed proximal to the test lung. During the inspiratory phase of the ventilator, an expiratory flow was introduced. This varied from +4 to +12 L/min. We had previously recorded such peak crying expiratory flow rates on intubated infants (birthweight 0.5 to 2.5 kg). Three ventilators of each type were tested at all 5 expiratory flow rates and each ventilator was examined twice. Increments of PIP above the set value of 20 cm H2O are tabulated below. Values represent X ± S.D. of 6 records. Because these findings were consistent over a range of tidal volumes of 10 to 30 ml, we conclude that expiration during the inspiratory cycle of some ventilators considerably increases PIP in a flow dependent manner. This PIP overshoot is remarkably different in currently used infant ventilators. It is speculated that this PIP overshoot contributes to the development of air leaks in actively expiring ventilated infants.

Eight ventilator-dependent infants with clinical and radiographic BPD (birth weight 924 ± 118 grams; age 22 ± 7 days) were treated with IV dexamethasone (Dex), 0.5 mg/kg/day, for 7 days. Dex was then tapered over 2 weeks and discontinued. These infants were compared to 8 controls (birth weight 986 ± 138 grams) with improving lung disease. At study entry, treated infants had significantly increased ventilator requirements compared to controls at 14 days. Controls were extubated at age 13.3 ± 14 days. FiO2, rate, peak inspiratory pressure (PIP), and alveolar arterial oxygen differences (AaDO2) were compared before and after 7 days of Dex and to controls at age 28 days, using two-tailed Student-t test. All infants were extubated 6.1 ± 2 days after Dex treatment. Compared to 28 day controls, treated infants had higher AaDO2 (P

Twenty-two neonates with pulmonary interstitial emphysema (PIE) unresponsive to conventional forms of treatment, were ventilated with a high frequency jet ventilator (HFJV). Sixteen of 22 developed PIE subsequent to severe hyaline membrane disease (HMD), 5 were in association with bacterial pneumonia-septicemia, and 1 was associated with meconium aspiration syndrome. All but 1 patient (septicemia) showed temporary or permanent resolution of the PIE; however only 11 (50%) survived. The 16 patients with HMD-associated PIE had the most favorable outcome. In that group, switching from intermittent mandatory ventilation (IMV) to HFJV resulted in a mean drop in PaCO2 from 60 mmHg (range 29-192) to 37 mmHg (range 13-53) while operating at an intratracheal mean airway pressure (MAP) of 3.1 cm H2O less (0.3-7.6) and a peak inspiratory pressure (PIP) of 9 cmH2O less (2-15) than on IMV. Of the 11 patients who died, 7 (64%) had pulmonary bacterial infection, either during life (n=3) or at postmortem (n=4). Factors significantly favoring survival included (1) lack of bacterial infection, (2) development of PIE after 48 hours of age, and (3) a drop of PaCO2 of over 30 mmHg on HFJV while maintaining a constant PaO2 using lower PIP and MAP than was required on IMV. We conclude that HFJV is effective in resolving PIE and improving survival in neonates with HMD-associated PIE.

In order to assess the effects of high frequency jet ventilation (HFJV) on pulmonary and hemodynamic parameters, 10 anesthetized adult rabbits (1.8-2.2 kg) were studied while receiving HFJV and conventional mechanical ventilation (CMV). Each rabbit received two hours of one ventilatory mode, then two hours of the other. HFJV was delivered by a Sechrist 990 HFJ ventilator while CMV was delivered by a Sechrist IV-100 B infant ventilator. Prior to data collection ventilation in both modes was adjusted to maintain the PaCO2 between 35 and 45 Torr. CMV was accomplished using a peak inspiratory pressure of 12 cm H2O and 4 cm H2O end expiratory pressure. Ventilatory rates of 300 (six rabbits) and 600 (four rabbits) breaths per minute were used during HFJV. In both modes FiO2 was 0.5 and flow rate was 10 L/min. Pulmonary gas exchange (A-a DO2), venous saturation (SvO2), mean airway pressure (MAP), heart rate (HR), mean arterial blood pressure (BP), and central venous pressure (CVP) were recorded every 30 minutes (Table). The results suggest no impedance to pulmonary gas exchange, a lower MAP, and improved hemodynamic stability with HFJV compared to CMV in the adult rabbit.

Goldberg recently reported an increased incidence of intraventricular hemorrhage(IVH) in infants receiving muscle relaxants(MR). The mechanism is unknown. We studied 11 infants (BW 850-2800gm) before and during administration of curare or pancuronium. The effects of an increase of 4cm. peak inspiratory pressure (↑PIP) and of leg raising(LR) were tested. Intracranial pressure(ICP) was measured. Cerebral blood flow (CBF) was assessed by a doppler technique and expressed as pulsatility index (PI=systolic-diastolic/systolic) (Bada). Our results (Mean±SD): During MR, PI decreased, consistent with an increase in apparent CBF. There was no significant change in ICP due to MR alone. However, there was a significantly greater increase in ICP during ↑PIP and LR. Both observations suggest a loss of autoregulation during MR. We conclude, muscle relaxants affect cerebrovascular dqnamics and may be dangerous in infants at risk for IVH, particularly when high PIP is required.

The pathogenesis of neonatal periventricular-intraventricular hemorrhage (PVH-IVH) remains unclear, although an aberration in cerebral hemodynamics imposed upon prematurity appears fundamental. Microthermistors were implanted in the cerebral cortex of 17 adult greyhounds. An analog-digital hybrid system developed using the IBM PC computer to provide simultaneous continuous 1CBF data at four discrete sites. Variables of peak inspiratory pressure (PIP), positive and expiratory pressure (PEEP), total minute ventilation and pulse pressure were investigated through a 1 mm burr hole as well as 2 cm craniotomy to compare cranial compliance effects. Positive pressure ventilation induces a fluctuating pattern of 1CBF with blood flow lowest during peak inspiration. A large craniotomy defect (simulating the open fontanel), high PIP or high PEEP accentuate this effect. The use of a small burr hole to simulate a closed fontanel results in the obliteration of the fluctuating pattern and the enhancement of beat-to-beat changes in 1CBF that were directly proportional to pulse pressure. These data suggest that hemodynamic changes produce fluctuations in local tissue perfusion which are dependent upon cranial compliance. The exact relation of such changes to the pathogenesis of PVH-IVH requires continuous 1CBF measurement in the subependymal zone in the human newborn or an animal model.

In order to evaluate the cardiorespiratory effects of changes in the duration of the positive-pressure (DPP) on the neonates requiring mechanical ventilation, 6 infants (2 with meconium aspiration and 4 with bronchopulmonary dysplasia) were studied. Their (mean ± S.E.) B.wt.= 1985 ± 352 gms. and GA =33 ± 1.8 wks. Arterial blood pressure (ABP), central venous pressure (CVP), blood gases and M-mode echocardiograms were obtained prior to and 10 minutes after changing DPP by 200 milliseconds while maintaining the same mean airway pressure. This was achieved by adjusting the respirator rate and the peak inspiratory pressure. There were no significant changes in ABP, CVP, PaO2, pH, LA/AA, LVIDd and LPEP/LVET, whereas, the RPEP/RVET increased in every instance after an increase in DPP (0.31 ± 0.04 versus 0.37 ± 0.05. P

Do airway pressures effect intracranial and intravascular pressures? If so, does one component of the respiratory cycle have more of an effect than another? The cerebral and vascular effects of changes in I:E ratio, peak inspiratory pressure, and PEEP were examined in 11 paralyzed, anesthetized cats. While oxygen saturation, end tidal CO2, and mean airway pressures were held constant, I:E ratios, peak inspiratory pressures, and PEEP were individually varied. Intracranial pressure (ICP), central venous pressure (CVP), and aortic pressures were continuously recorded and cerebral tissue perfusion pressures were calculated. Two animals developed fatal cerebral hemorrhages when I:E ratios were reversed (2:1). In the 9 surviving animals, ICP, CVP, aortic pressure, and cerebral tissue perfusion pressures varied directly with mean airway pressures. As mean airway pressures increased, ICP and CVP increased; aortic pressure and cerebral tissue perfusion pressures decreased. Equivalent changes in I:E ratio and peak inspiratory pressures appeared to have a greater effect on the vascular pressures than did changes in PEEP. (Supported by a grant from the Hennepin County Lung Association, Minneapolis, MN.)