Changes In Mean Airway Pressure Research Articles

Nasal High-Flow (NHF) Improves Ventilation in Patients with Interstitial Lung Disease (ILD)-A Physiological Study.

Acute hypercapnic respiratory failure has a poor prognosis in patients with interstitial lung disease (ILD). Recent data demonstrated a positive effect of nasal high-flow (NHF) in patients with acute hypoxemic respiratory failure. Preliminary data also show benefits in several hypercapnic chronic lung diseases. The aim of this study was to characterize flow-dependent changes in mean airway pressure, breathing volumes, and breathing frequency and decreases in PCO2. Mean airway pressure was measured in the nasopharyngeal space. To evaluate breathing volumes, a polysomnographic device was used (16 patients). All subjects received 20, 30, 40, and 50 L/min and-to illustrate the effects-nCPAP and nBiPAP. Capillary blood gas analyses were performed in 25 hypercapnic ILD subjects before and 5 h after the use of NHF. Additionally, comfort and dyspnea during the use of NHF were surveyed. NHF resulted in a small flow-dependent increase in mean airway pressure. Tidal volume was unchanged and breathing rate decreased. The calculated minute volume decreased by 20 and 30 L/min NHF breathing. In spite of this fact, hypercapnia decreased at a flow rate of 24 L/min. Additionally, an improvement in dyspnea was observed. NHF leads to a reduction in paCO2. This is most likely achieved by a washout of the respiratory tract and a reduction in functional dead space. NHF enhances the effectiveness of breathing in ILD patients by the reduction in respiratory rate. In summary, NHF works as an effective ventilatory support device in hypercapnic ILD patients.

Respiratory outcomes in preterm infants following intravitreal bevacizumab for retinopathy of prematurity-a 10-year matched case study.

To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB). This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO2), and respiratory severity score (RSS, MAP x FiO2) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented. A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO2, and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW. This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge.

Role of lung ultrasound in the assessment of recruitment maneuvers in ventilated preterm neonates with respiratory distress syndrome and its correlation with tracheal IL-6 levels: A randomized controlled trial.

This study's aim is to evaluate lung ultrasound (LUS) efficacy in detecting opening and closing lung pressures and its correlation with the tracheal interleukin 6 (IL-6) level. This single-blinded randomized controlled study was done at Ain Shams University Children's Hospital neonatal intensive care units, Egypt. It consists of 44 mechanically ventilated preterm neonates with Respiratory Distress Syndrome (RDS). Initial LUS assessment was done followed by randomization to one of 2 groups; group I: 22 patients underwent LUS guided RM and group II: 22 patients underwent non-ultrasound guided RM. Tracheal IL-6 level was measured before and after RM in both groups. The LUS scores showed a sensitivity of 86.7%, specificity of 62.10% and accuracy of 70.45% at the cut-off point >B1 grade. After RM, there was a higher percentage of changes in mean airway pressure (p = 0.03), FiO2 (p = 0.01), PaO2/FiO2 ratio (p = 0.01), and IL-6 (p < 0.01) in group I. The duration of oxygen requirement (6 vs.13.5 days, p = 0.01), invasive ventilation (3 vs.5.5 days, p = 0.03), non-invasive ventilation (2.5 vs. 5 days, p = 0.02) and NICU stay (21.5 vs. 42.5 days, p = 0.03) were less in group I. A positive correlation is found between reaeration score and the duration of O2 requirement (p = 0.002), duration of invasive ventilation (p = 0.001), NICU length of stay (p = 0.002) and negative correlation with PaO2/FiO2 ratio before RM (p = 0.012). The best cut-off point for the reaeration score is >21 with a sensitivity of 75%, specificity of 71.43% and area under the curve of 78.1%. LUS-guided RM achieved earlier lowest FiO2, shorter O2 dependency, lesser NICU stay and marked decrease in lung inflammation by decreasing atelectotrauma and shortening the duration of invasive ventilation.

Effects of ventilatory strategy on arterial oxygenation and respiratory mechanics in overweight and obese patients undergoing posterior spine surgery

Prolonged inspiratory to expiratory (I:E) ratio ventilation may improve arterial oxygenation or gas exchange and respiratory mechanics in patients with obesity. We performed a randomised study to compare the effects of the conventional ratio ventilation (CRV) of 1:2 and the equal ratio ventilation (ERV) of 1:1 on arterial oxygenation and respiratory mechanics during spine surgery in overweight and obese patients. Fifty adult patients with a body mass index of ≥25 kg/m2 were randomly allocated to receive an I:E ratio either l:2 (CRV; n = 25) or 1:1 (ERV; n = 25). Arterial oxygenation and respiratory mechanics were recorded in the supine position, and at 30 minutes and 90 minutes after placement in the prone position. The changes in partial arterial oxygen pressure (PaO2) over time did not differ between the groups. The changes in partial arterial carbon dioxide pressure over time were significantly different between the two groups (P = 0.040). The changes in mean airway pressure (Pmean) over time were significantly different between the two groups (P = 0.044). Although ERV provided a significantly higher Pmean than CRV during surgery, the changes in PaO2 did not differ between the two groups.

Pressure support ventilation, sigh adjunct to pressure support ventilation, and neurally adjusted ventilatory assist in infants after cardiac surgery: A physiologic crossover randomized study.

We sought to compare gas exchange, respiratory mechanics, and asynchronies during pressure support ventilation (PSV), sigh adjunct to PSV (PSV SIGH), and neurally adjusted ventilatory assist (NAVA) in hypoxemic infants after cardiac surgery. Prospective, single-center, crossover, randomized physiologic study. Tertiary-care pediatric intensive care unit. Fourteen hypoxemic infants (median age 11.5 days [8.7-74]). The protocol begins with a 1 hour step of PSV, followed by two consecutive steps in PSV SIGH and NAVA in random order, with a washout period of 30 minutes (PSV) between them. Three infants presented an irregular Eadi signal because of diaphragmatic paralysis and were excluded from analysis. For the remaining 11 infants, PaO2 /FiO 2 and oxygenation index improved in PSV SIGH compared with PSV (P < 0.05) but not in NAVA compared with PSV. PSV SIGH showed increased tidal volumes and lower respiratory rate than PSV (P < 0.05), as well as a significant improvement in compliance with respiratory system indexed to body weight when compared with both PSV and NAVA (P < 0.01). No changes in mean airway pressure was registered among steps. Inspiratory time resulted prolonged for both PSV SIGH and NAVA than PSV (P < 0.05). NAVA showed the higher coefficient of variability in respiratory parameters and a significative decrease in asynchrony index when compared with both PSV and PSV SIGH (P < 0.01). The adjunct of one SIGH per minute to PSV improved oxygenation and lung mechanics while NAVA provided the best patient-ventilator synchrony in infants after cardiac surgery.

Tidal volume, recruitment and compliance in HFOV: same principles, different frequency: Figure 1–

The widespread clinical introduction of high-frequency oscillatory ventilation (HFOV) for the treatment of respiratory distress syndrome in neonates in the late 1980s and early 1990s heralded a new era of understanding of the optimal approach to lung volume ( V L) recruitment, which embraced the concept of open lung ventilation [1]. The promotion of HFOV as a means of independently controlling oxygenation and ventilation contributed to the ease with which it was accepted as a clinical treatment in many neonatal units. Unlike mechanical ventilation at physiological breathing rates where changes in ventilator settings on contemporary ventilators inevitably affect both oxygenation and ventilation, traditional teaching of HFOV promoted changes in mean airway pressure as the means of influencing arterial oxygen tension and alterations to proximal pressure amplitude (Δ P ) and frequency ( f ) of the oscillatory waveform as the determinants of arterial carbon dioxide tension ( P a,CO2) [2]. Like any intensive care technology, however, successful and safe application of HFOV is highly dependent on fully understanding the specific nuances of this ventilatory modality. As recognised previously, there are clear changes in compliance during recruitment of the atelectatic lung [3]. During ventilation at conventional breathing rates, as V L is recruited, lung compliance improves and this is accompanied by increased tidal volume ( V T) to which the clinical response is normally a reduction in minute volume: in synchronised modes, this is most often achieved via a reduction in Δ P or targeted V T rather than a reduction in respiratory rate. Changes in compliance [4–7] and lung tissue resistance [5] have also been widely recognised during volume recruitment achieved with HFOV. In this issue of the European Respiratory Journal , Miedema et al. [8] present an elegant study …

Design and Control of a Demand Flow System Assuring Spontaneous Breathing of a Patient Connected to an HFO Ventilator

Lung protective ventilation is intended to minimize the risk of ventilator induced lung injury and currently aimed at preservation of spontaneous breathing during mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is a lung protective ventilation strategy. Commonly used high-frequency oscillatory (HFO) ventilators, SensorMedics 3100, were not designed to tolerate spontaneous breathing. Respiratory efforts in large pediatric and adult patients impose a high workload to the patient and may cause pressure swings that impede ventilator function. A Demand Flow System (DFS) was designed to facilitate spontaneous breathing during HFOV. Using a linear quadratic Gaussian state feedback controller, the DFS alters the inflow of gas into the ventilator circuit, so that it instantaneously compensates for the changes in mean airway pressure (MAP) in the ventilator circuit caused by spontaneous breathing. The undesired swings in MAP are thus eliminated. The DFS significantly reduces the imposed work of breathing and improves ventilator function. In a bench test the performance of the DFS was evaluated using a simulator ASL 5000. With the gas inflow controlled, MAP was returned to its preset value within 115 ms after the beginning of inspiration. The DFS might help to spread the use of HFOV in clinical practice.

Total and regional lung volume changes during high-frequency oscillatory ventilation (HFOV) of the normal lung

The effect of high-frequency oscillatory ventilation (HFOV) settings on the distribution of lung volume (V(L)) with changes in mean airway pressure (Paw), frequency (f(R)) and tidal volume (V(T)) remains controversial. We used computer tomographic (CT) imaging to quantify the distribution of V(L) during HFOV compared to static continuous positive airway pressure (CPAP). In anesthetized, supine canines, CT imaging of the entire lung was performed during CPAP and HFOV at Paw of 5, 12.5 and 20 cm H(2)O, f(R)=5, 10, 15 Hz. We found small, statistically significant decreases compared with CPAP in total and regional V(L) during HFOV that were greatest at lower f(R) and Paw. Apex and base sub-volumes underwent changes comparable to the lung overall. Increases in f(R) were accompanied by increases in Pa(O)(2). These finding provide additional insight into the impact of HFOV settings on the distribution of V(L) and suggest that there is low risk of occult regional over-distention during HFOV in normal lungs.

Tidal volume delivery during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome*

a) Characterize how ventilator and patient variables affect tidal volume during high-frequency oscillatory ventilation; and b) measure tidal volumes in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation. Observational study. Research laboratory and medical intensive care unit. Test lung and patients with acute respiratory distress syndrome. Using a previously validated hot wire anemometer placed in series with a Sensormedics 3100B high-frequency ventilator, an endotracheal tube, and a test lung, tidal volume was measured at different combinations of frequency (4, 6, 8, 10, and 12 Hz), pressure amplitude (50, 60, 70, 80, and 90 cm H2O), mean airway pressure (20, 30, and 40 cm H2O), test lung compliance (10, 30, and 50 mL/cm H2O), endotracheal tube internal diameter (6, 7, and 8 mm), bias flow (20, 30, and 40 L/min), and inspiratory/expiratory ratio (1:2 and 1:1). In patients, tidal volume was measured at baseline ventilator settings and at baseline frequency +/-2 Hz and baseline pressure amplitude +/-10 cm H2O. Measured tidal volumes were 23-225 mL during high-frequency oscillatory ventilation of the test lung. A 2-Hz increase in frequency and a 10-cm H2O increase in pressure amplitude caused a 21.3% +/- 4.1% decrease and 21.4% +/- 3.4% increase in tidal volume, respectively. Decreasing endotracheal tube internal diameter from 8 mm to 7 mm and from 7 mm to 6 mm caused a 15.3% +/- 1.7% and 18.9% +/- 2.1% reduction in tidal volume, respectively. Increasing bias flow from 20 L/min to 30 L/min increased tidal volume by 11.2% +/- 3.9%. Further increases in bias flow, changes in compliance, and changes in mean airway pressure had little effect. Tidal volumes measured in acute respiratory distress syndrome patients were 44-210 mL. A 2-Hz increase in frequency was associated with a 23.1% +/- 6.3% decrease in tidal volume. In contrast to the test lung data, a 10-cm H2O increase in pressure amplitude resulted in only a 5.6% +/- 4.5% increase in tidal volume. Tidal volumes are not uniformly small during high-frequency oscillatory ventilation. The primary determinant of tidal volume in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation with the Sensormedics 3100B is frequency. Test lung findings suggest that endotracheal tube internal diameter is also an important determinant of tidal volume.

Changes in mean airway pressure during HFOV influences cardiac output in neonates and infants.

Changes in mean airway pressure affect cardiac output during conventional positive pressure ventilation. The effect of high-frequency oscillation ventilation (HFOV) on cardiac output is less studied. A prospective study in a university hospital pediatric intensive care unit. Fourteen patients aged <1 year and weighing <10 kg who were on HFOV were included. All patients had been on HFOV for >12 h and were considered to be in a stable condition. In the study group (n = 9) the mean proximal airway pressure (Paw) was increased and decreased by +5 and -3 cmH2O, respectively, from baseline in each patient. Measurements were made at each level including baseline settings between each change. In a control group (n = 5) no changes in ventilatory parameters were made. Cardiac output was assessed with echocardiography and the Doppler technique at each level of Paw and at similar intervals in the control group. Cardiac output changed significantly when Paw was changed in the study group (P = 0.02), with the greatest change at the highest Paw at -11% (range: -19 to -9) compared with baseline. We found no significant changes over time in the control group. This study shows that CO is affected by changes in mean airway pressure during HFOV in concordance with the known effects of mean airway pressure during conventional positive pressure ventilation. The mean changes are smaller than expected compared with earlier studies of conventional mechanical ventilation. Further studies are needed to better understand these relationships.

Effects of Inspiratory Flow Waveforms on Lung Mechanics, Gas Exchange, and Respiratory Metabolism in COPD Patients During Mechanical Ventilation

The clinical usefulness of varying inspiratory flow waveforms during mechanical ventilation has not been adequately studied. The aim of this study was to compare the effects of three different respiratory waveforms on the pulmonary mechanics, gas exchange, and respiratory metabolism of ventilated patients with COPD. A randomized and comparative trial of consecutive patients. Medical ICUs of a 2,000-bed university hospital. Fifty-four patients with COPD were enrolled. Constant, decelerating, and sine waveforms were applied to each patient in a random order. With tidal volume, inspiratory time, and inspiratory frequency being kept constant, the decelerating waveform produced statistically significant reductions of peak inspiratory pressure, mean airway resistance, physiologic dead space ventilation (VD/VT), PaCO(2), and symptom score. There was also a significant increase in alveolar-arterial oxygen pressure difference with the decelerating flow waveform, but there were no significant changes in mean airway pressure, arterial oxygenation, heart rate, mean BP, and other hemodynamic measurements. In addition, assessment on the work of breathing (WOB) revealed that ventilator WOB values were reduced with the decelerating waveform. Oxygen consumption and carbon dioxide output were virtually not affected by changing inspiratory flow waveforms. Except for VD/VT, the effects of constant square and sine waveforms were similar to each other and could not be separated statistically. The most favorable flow pattern for ventilated patients with COPD appeared to be the decelerating waveform. There are possibilities for the improvement of ventilation in these patients by selecting an appropriate inspiratory flow.

Identification of optimal lung volume during high-frequency oscillatory ventilation using respiratory inductive plethysmography.

First, to define the relationships between critical opening and closing pressures and oxygenating efficiency, and second, to address whether respiratory inductive plethysmography (RIP) could be used to monitor changes in thoracic volume that follow changes in mean airway pressure during high- frequency oscillatory ventilation (HFOV). Prospective, interventional animal study. University research laboratory. Five anesthetized, paralyzed, and ventilated pigs. The animals were ventilated by using HFOV after lung injury. Pre- and post-HFOV pressure-volume curves were obtained by supersyringe. A pressure-volume curve was constructed during HFOV as mean airway pressure was increased from 10 to 40 cm H(2)O and then weaned back down to the minimum sustainable. Hemodynamic and oxygenation data were obtained at each data point. RIP-derived thoracic volumes correlated with known lung volumes during supersyringe (r(2) =.78, p <.00001). During HFOV, three of five animals had an identifiable critical opening pressure of the lung, and four of five had an identifiable critical closing pressure. No consistent relationship between critical opening and critical closing pressures was observed. During the weaning phase of HFOV, a relative decrease in RIP-measured volume of >10% predicted the decrease in oxygenation associated with reaching the critical closing pressure. The ability of RIP to detect optimal lung volume during the weaning of mean airway pressure may allow clinicians to more directly monitor lung volume changes during HFOV and use the lowest possible airway pressures after lung recruitment.

Outcome in children receiving continuous venovenous hemofiltration.

Continuous venovenous hemofiltration (CVVH) alone or with dialysis (D) has become an important supportive therapy for critically ill children with acute renal failure. Previous reports of pediatric patient outcome either mix CVVH/D with other renal replacement modalities or do not examine severity of illness. The current study examines only outcomes of children receiving CVVH/D using Pediatric Risk of Mortality (PRISM) scores to control for severity of illness. Twenty-one patients (mean age: 8.8 +/- 6.3 years; mean weight: 28.3 +/- 20.8 kg) received 22 courses of CVVH/D. Nine (42.8%) of 21 patients survived. Nine (75%) of 12 deaths occurred within 25 days of pediatric intensive care unit (PICU) admission. Mean PRISM score at PICU admission and CVVH initiation were 13.1 +/- 5.8 and 15.4 +/- 8.9, respectively. Mean patient weight, age, PRISM score at PICU admission and at CVVH/D initiation, maximum pressor number, estimated glomerular filtration rate at CVVH/D initiation and change in mean airway pressure did not differ between survivors and nonsurvivors. The degree of fluid overload at CVVH/D initiation was significantly lower in survivors (16.4% +/- 13.8%) compared with nonsurvivors (34.0% +/- 21.0%), even when controlled for severity of illness by PRISM score. Mean cost of providing CVVH/D accounted for only 1% of total PICU cost per patient. The pattern of early multiorgan system failure and death, minimal relative cost of CVVH/D provision, and potential for improved outcome with initiation of CVVH/D at lesser degrees of fluid overload are factors that may support early initiation of CVVH/D in critically ill children with acute renal failure.

Lung volume recruitment in lambs during high-frequency oscillatory ventilation using respiratory inductive plethysmography.

Monitoring lung volume is important in the treatment of acute hypoxemic respiratory failure. However, there are no tools available for lung volume measurement to guide ventilator management during high-frequency oscillatory ventilation (HFOV) and during dynamic changes in conventional ventilation (CV). We studied the performance of a new respiratory inductive plethysmograph (RIP) with modified software. We measured Delta changes in lung volume above end-expiratory volume (V(RIP)) during HFOV and studied whether changes in V(RIP) parallel changes in mean airway pressure. Calibration of the plethysmograph was made by serial injections of a known gas volume in six term (140 d gestation) and eight preterm (125 d gestation) lambs. Linear regression analysis of the relationship between injected gas volume and V(RIP) showed strong correlation (r(2) = 0.93-1.00 term animals, r(2) = 0.86-1.00 preterm animals). The pressure volume curves from the calibration with the injected gas volumes also correlated well with the pressure volume curves extrapolated from changes in V(RIP). Lung hysteresis was clearly demonstrated with RIP after changes in mean airway pressure during HFOV and after changes in positive end-expiratory pressure during CV. We conclude that measurements of lung volume in term and preterm lambs by use of modified RIP correlate well with changes in mean airway pressure during HFOV, with static pressure volume curves and with changes in positive end-expiratory pressure during CV. We speculate that this technique may provide clinically useful information about changes in lung volume during HFOV and CV. However, evaluation of the precision and chronic stability of RIP measurements over prolonged periods will require further studies.

Comparison of hyperventilation and inhaled nitric oxide for pulmonary hypertension after repair of congenital heart disease

Pulmonary hypertension is associated with congenital heart lesions with increased pulmonary blood flow. Acute increases in pulmonary vascular resistance (PVR) occur in the postoperative period after repair of these defects. These increases in PVR can be ablated by inducing an alkalosis with hyperventilation (HV) or bicarbonate therapy. Studies have shown that these patients also respond to inhaled nitric oxide (iNO), but uncertainty exists over the relative merits and undesirable effects of HV and iNO. Alkalosis and iNO are equally effective in reducing PVR and pulmonary artery pressure (PAP) in children with pulmonary hypertension after open heart surgery. Critical care unit of a tertiary care pediatric hospital. Prospective, randomized, crossover design. Twelve children with a mean PAP > 25 mm Hg at normal pH after biventricular repair of congenital heart disease. Patients were assigned to receive iNO or HV (pH > 7.5) in random order, and the effect on hemodynamics was measured. Each treatment was administered for 30 mins with a 30-min washout period between treatments. Finally, both treatments were administered together to look for a possible additive effect. Cardiac output and derived hemodynamic parameters using the dye dilution technique. Hyperventilation, achieved by an increase in ventilator rate without a change in mean airway pressure, decreased Pa(CO2) from a mean (SD) of 43.7+/-5.3 to 32.3+/-5.4 mm Hg and increased pH from 7.40+/-0.04 to 7.50+/-0.03. This significantly altered both pulmonary and systemic hemodynamics with a reduction in PAP, PVR, central venous pressure, and cardiac output and an increase in systemic vascular resistance. In comparison, iNO selectively reduced PAP and PVR only. The reduction in PVR was comparable between treatments, although addition of iNO to HV resulted in a small additional reduction in PVR. An additional decrease in PAP was seen when HV was added to iNO, attributable to a reduction in cardiac output rather than a further decrease in PVR. Inhaled NO and HV are both effective at lowering PAP and PVR in children with pulmonary hypertension after repair of congenital heart disease. The selective action of iNO on the pulmonary circulation offers advantages over HV because a decrease in cardiac output and an increase in SVR are undesirable in the postoperative period.

Cerebral Blood Flow Velocity Changes After Bovine Natural Surfactant Instillation

To determine the effects of bovine natural surfactant (beractant) instillation on cerebral hemodynamics in preterm infants with respiratory distress syndrome (RDS). Preterm infants who required surfactant for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the pericallosal artery were analyzed by pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. CBFV was measured before and at 5, 10, 20, and 30 minutes after the first dose of a bolus instillation of surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and PAO2 before and at 30 minutes after surfactant administration were also determined. The 30 enrolled preterm infants had a mean birth weight of 973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks). Mean postnatal age at surfactant administration was 4.7 +/- 2.7 hours. There were no significant changes in pH and PACO2 before and at 30 minutes after surfactant (before surfactant: mean pH of 7.29 +/- 0.07 and mean PACO2 of 44.4 +/- 7.1 torr; after surfactant: mean pH of 7.31 +/- 0.07 and mean PACO2 of 42.7 +/- 8.3 torr). PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at 30 minutes after surfactant (p < 0.05), with no significant changes in mean airway pressure. There were no significant changes in MBP, heart rate, mean CBFV, peak systolic flow velocity, and diastolic flow velocity before and after surfactant instillation regardless of gestational age. Individual changes in mean CBFV were related to MBP changes (p < 0.001, linear mixed models with random effects). In low birth weight infants with RDS, bovine surfactant instillation is not associated with a significant alteration in cerebral hemodynamics. However, the direct relationship between CBFV and MBP is consistent with the reported pressure-passive cerebral circulation in sick preterm infants.

Effects of duration of positive-pressure ventilation on blood-brain barrier function in premature lambs

We have been studying the ontogeny of the blood-brain barrier function in ovine fetuses and lambs. During these studies, we have found that the duration of ventilation also influences blood-brain barrier permeability in premature lambs. Chronically instrumented hysterotomy-delivered surfactant-treated premature lambs were studied at 90% or 137 days of gestation (n = 9). Blood-brain barrier function was quantified with the blood-to-brain transfer constant K(i) to alpha-aminoisobutyric acid. Linear regression analysis was used to compare the K(i) values in the brain regions, as the dependent variable, to the duration of ventilation, as the independent variable. There were direct correlations (P < 0.05) between the K(i) values and the duration of ventilation [306 min (mean), 162-474 min (range)] in the cerebral cortex, cerebellum, medulla, caudate nucleus, hippocampus, superior colliculus, inferior colliculus, thalamus, pons, cervical spinal cord, and choroid plexus, but not in the pituitary gland. Ventilatory pressures and rates were established before the onset of the permeability studies. Calculated mean airway pressures [14 cmH(2)O (mean), 7-20 cmH(2)O (range)] from similarly studied premature lambs did not correlate with the duration of positive-pressure ventilation. We conclude that increases in the duration of positive-pressure ventilation predispose premature lambs to increases in regional blood-brain barrier permeability. These alterations in barrier function occur over relatively short time intervals (minutes to hours). In our study, these changes in permeability are most likely not attributable to changes in mean airway pressure.

Cerebral Blood Flow Velocity Changes after Bovine Natural Surfactant Instillation

OBJECTIVE: To determine the effects of bovine natural surfactant (beractant) instillation on cerebral hemodynamics in preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN: Preterm infants who required surfactant for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the pericallosal artery were analyzed by pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. CBFV was measured before and at 5, 10, 20, and 30 minutes after the first dose of a bolus instillation of surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and PAO2 before and at 30 minutes after surfactant administration were also determined. RESULTS: The 30 enrolled preterm infants had a mean birth weight of 973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks). Mean postnatal age at surfactant administration was 4.7 ± 2.7 hours. There were no significant changes in pH and PACO2 before and at 30 minutes after surfactant (before surfactant: mean pH of 7.29 ± 0.07 and mean PACO2 of 44.4 ± 7.1 torr; after surfactant: mean pH of 7.31 ± 0.07 and mean PACO2 of 42.7 ± 8.3 torr). PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at 30 minutes after surfactant (p < 0.05), with no significant changes in mean airway pressure. There were no significant changes in MBP, heart rate, mean CBFV, peak systolic flow velocity, and diastolic flow velocity before and after surfactant instillation regardless of gestational age. Individual changes in mean CBFV were related to MBP changes (p < 0.001, linear mixed models with random effects). CONCLUSION: In low birth weight infants with RDS, bovine surfactant instillation is not associated with a significant alteration in cerebral hemodynamics. However, the direct relationship between CBFV and MBP is consistent with the reported pressure-passive cerebral circulation in sick preterm infants.

Cardiopulmonary effects of permissive hypercapnia in the management of adult respiratory distress syndrome.

Despite numerous advances, the mortality from adult respiratory distress syndrome (ARDS) remains high. Traditional ventilator management in ARDS has been to maintain normal PaCO2 by positive pressure ventilation (PPV). However, high levels of PPV may worsen the lung injury by alveolar overdistension. Permissive hypercapnia (PHC) has been proposed as an alternative method of ventilation, but hypercapnia may affect the hemodynamics of a hyperdynamic, critically ill patient. The purpose of this study was to determine the effect of PHC on ventilator requirement, arterial oxygenation, and hemodynamic performance in patients with severe ARDS. Ten men and 5 women with established ARDS (mean Murray lung injury score 3.42 +/- 0.1) were prospectively studied using an established protocol when the static pulmonary plateau pressure (Pplat) exceeded 40 cm H2O. The initial tidal volume (V(t)) was decreased to achieve a Pplat < 40 cm H2O or to a lower limit of 5 cc/kg. Arterial blood gas and hemodynamic data were obtained serially. The V(t) was reduced from 9.9 +/- 0.5 mL/kg to 7.7 +/- 0.5 mL/kg at 24 hours, p < 0.05. This reduction of V(t) produced a decrease in minute ventilation (Ve: 18.0 +/- 1.6 to 11.9 +/- 0.7 L/min, p < 0.05), peak airway pressure (PAP: 55 +/- 2 vs 45 +/- 3 cm H2O, p < 0.05), and Pplat (Pplat 45.4 +/- 1.5 vs. 36.7 +/- 1.9) at 24 hours. The PaCO2 rose from 37.9 +/- 1.3 to 56.7 +/- 3.0 mm Hg (p < 0.05), and the pH decreased from 7.41 +/- 0 to 7.31 +/- 0 (p < 0.05) at 24 hours. There were no significant changes in mean airway pressure, static compliance, arterial oxygenation, pulmonary vascular resistance, systemic vascular resistance, cardiac index, or systemic oxygen delivery and consumption. Permissive hypercapnia by V(t) reduction: (1) decreased Ve, PAP, and Pplat without a change in mean airway pressure, static compliance or arterial oxygenation; (2) caused a mild partially compensated acidosis; and (3) does not adversely affect pulmonary vascular resistance, systemic vascular resistance, cardiac index, or systemic oxygen delivery and consumption.

Variability of respiratory system compliance in mechanically ventilated infants.

We measured respiratory flow, volume by integrated flow, and airway pressure in four mechanically ventilated infants. Compliance of the respiratory system (Crs) was measured by the multiple occlusion method. Airway occlusion and release were achieved by a balloon in an occlusion valve between the endotracheal tube and a pneumotachometer, all connected in series with the respirator circuit. Values of Crs varied greatly due to changes in mean airway pressure (MAP). The Crs increased with the elevation of MAP on some occasions and decreased on others. Values of Crs also varied corresponding to different occlusion pressures for individual levels of MAP. Thus Crs changed continuously, even within a single respiratory cycle. The observed variability in Crs was explained by the following mechanism: a pressure-volume (P-V) loop of tidal ventilation moves its position within the pressure-volume diagram and changes shape due to variations of the ventilator settings. In some infants the lungs were ventilated in the range of the linear portion of the P-V diagram while in others they may have been ventilated on the flattened portion. Some patients had convex expiratory P-V curves even with low pressure swings during tidal ventilation.