Conventional vs high-frequency jet ventilation in a piglet model of meconium aspiration: comparison of pulmonary and hemodynamic effects

The pulmonary and cardiovascular effects of high-frequency jet (HFJV) and conventional (CV) ventilation were evaluated in a piglet model of meconium aspiration. A mixture of 20% human meconium and 0.9% saline solution was instilled deep into the trachea of 10 piglets, after which either HFJV or CV was administered for 4 hours. Arterial blood gases, cardiac output, mean pulmonary and systemic arterial pressures, pulmonary and systemic vascular resistances, and pulmonary mechanics were compared between groups. During the 4 hours of ventilation, PaO2 and PaCO2 were not statistically different between groups. The peak inspiratory pressure necessary to maintain PaCO2 in the preset range was approximately half as much in the HFJV group as in the CV group (P less than 0.002). Mean airway pressure was lower in the HFJV group only during the second hour (P less than 0.03). Cardiac output, mean aortic and pulmonary artery pressures, systemic and pulmonary vascular resistance, dynamic lung compliance, and pulmonary resistance were not statistically different between groups. Our results suggest that HFJV may be more effective than CV in the early stages of meconium aspiration syndrome because HFJV allows more efficient ventilation and adequate oxygenation at lower peak inspiratory pressures.     

Comparison of high-frequency jet ventilation and conventional mechanical ventilation in a meconium aspiration model

Ten adult cats received alternately high-frequency jet ventilation and conventional mechanical ventilation after aspirating 2 ml/kg 25% human meconium in saline. Equivalent mean airway pressures were maintained during the hourly ventilator changes. Aortic pressures, pulmonary artery pressures, and central venous pressures were continuously monitored. Cardiac outputs were measured, and pulmonary and systemic vascular resistances, intrapulmonary shunts, and alveolar arterial oxygen gradients were determined at regular intervals. During the first hour after aspiration, AaDO2 and Qs/Qt were lower during HFJV (P less than 0.05); PVR and Pa were always higher during HFJV (P less than 0.05). Overall, PVR, Pa, AaDO2, and Qs/Qt rose during HFJV; these changes occurred at equivalent Paw within 15 minutes of each ventilator change (P less than 0.05). In this meconium aspiration model, conventional mechanical ventilation was the superior form of ventilatory therapy.     

Relationship between mean airway pressure, cardiac output, and organ blood flow with normal and decreased respiratory compliance

We investigated the relation between blood flow and mean airway pressure in two groups of anesthetized newborn piglets. The first group had normal respiratory compliance; the second group had pulmonary surfactant depleted by repeated saline lavage, which decreased static respiratory compliance by 42%. In the normal group, cardiac output decreased linearly from 292 +/- 43 mL/min/kg at 5 cm H2O airway pressure to 134 +/- 37 ml/min/kg at 20 cm H2O airway pressure, a drop of 43% (r2 = 0.79). Blood flow to the heart, kidney, and intestines had a similar decline, but brain, hepatic artery, and adrenal flow were constant. Mean arterial blood pressure did not decrease significantly until the highest airway pressure was reached, whereas sagittal sinus pressure increased as mean airway pressure increased. In contrast, the surfactant-depleted group maintained cardiac output up to a mean airway pressure of 15 cm H2O. At 20 cm H2O, cardiac output fell to 40% of the original value. Blood flow to the heart and kidneys fell at a mean airway pressure of 20 cm H2O; intestinal blood flow decreased beginning at 10 cm H2O. As in the normal piglets, brain, hepatic arterial, and adrenal blood flow were not affected by increasing ventilation pressure. Our data show that positive pressure ventilation in the neonate has important cardiovascular effects that are blunted when respiratory compliance is decreased. More important, because cardiac output decreased prior to a significant decline in arterial blood pressure, these data suggest that in a clinical setting considerable cardiovascular alterations can occur before a decline in arterial blood pressure is detected.     

Randomized trial of high-frequency jet ventilation versus conventional ventilation in respiratory distress syndrome

To compare high-frequency jet ventilation (HFJV) with pressure-limited time-cycled conventional ventilation (CV), we randomized 41 infants with clinical and radiographic evidence of respiratory distress syndrome during the first day of life to receive either HFJV or CV. Standardized ventilatory protocols were used for 48 hours, after which CV was administered to both groups. Despite comparable oxygenation (arterial/alveolar oxygen tension ratio), mean airway pressure was lower in the HFJV group (9 +/- 2 vs 13 +/- 2 cm H2O, P less than 0.001), and thus the arterial/alveolar oxygen tension ratio corrected for mean airway pressure was improved in the HFJV group (P less than 0.05). PaCO2 was lower during HFJV (37 +/- 3 vs 42 +/- 3 mm Hg, P less than 0.05) despite a comparable peak inspiratory pressure. The incidence of air leaks, progression of intraventricular hemorrhage, and mortality during the 48-hour period did not differ between the two groups. Bronchoscopies in eight infants given HFJV and five given CV revealed no microscopic evidence of necrotizing tracheobronchitis, but one infant given HFJV had evidence of necrotizing tracheitis at autopsy. We conclude that for 48 hours during the acute stage of respiratory distress syndrome, HFJV can maintain adequate gas exchange at lower mean airway pressure than during CV, without an increase in the incidence of side effects.     

Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome

OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome. DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol. SETTING: Eight tertiary neonatal intensive care units. PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications. RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.     

Early pulmonary changes associated with high-frequency jet ventilation in newborn piglets

To assess the short-term effects of high-frequency jet ventilation (HFJV) on the neonatal lung, 28 newborn piglets were studied. Nine piglets were unventilated except during brief pulmonary measurements, nine animals were conventionally ventilated (arterial CO2 tension 35-45 torr, arterial O2 tension 70-80 torr) for 4 h, and 10 piglets were ventilated with HFJV for the same period. Pulmonary function was analyzed using a computerized technique and tracheobronchial aspirates were examined for biochemical indicators of lung injury; after 4 h, bronchoalveolar lavage was obtained for surfactant composition and activity, and lung sections were examined by light and electron microscopy. Results showed that HFJV provided adequate ventilation at lower inspiratory pressure compared with conventional ventilation (8.6 +/- 0.3 versus 13.8 +/- 1.3 cm H2O; p less than 0.01), while pulmonary mechanics did not vary significantly among the three animal groups. Tracheobronchial aspirates from HFJV animals had higher elastase activity versus unventilated piglets (118.5 +/- 14.1 versus 57.7 +/- 8.4 micrograms/mL; p less than 0.01), as well as higher albumin concentration versus unventilated animals (94.2 +/- 18.7 versus 23.2 +/- 6.5 micrograms/mL; p less than 0.01). In addition, there were small but statistically significant differences between all three groups in the distribution of surfactant phospholipids in bronchoalveolar lavage, although biophysical activity was normal. Scanning electron microscopy revealed flattening of Clara cells in the terminal bronchioles of HFJV animals due to loss of glycogen and secretory granules. These data indicate that despite lower peak inspiratory pressures, HFJV can cause subtle biochemical changes in lungs. Further studies are indicated to determine if these changes precede significant lung injury.     

Influence of an antagonist of slow-reacting substance of anaphylaxis on the cardiovascular manifestations of hypoxia in piglets

Leukotrienes have been implicated in the pathogenesis of hypoxic pulmonary hypertension in adult animals and in persistent pulmonary hypertension with accompanying hypoxemia in the neonate. In order to elucidate the role of leukotrienes in hypoxic pulmonary hypertension in a young animal model, the effects of a leukotriene antagonist, FPL 57231, were evaluated in anesthetized piglets. Cardiac output and vascular pressures were measured and pulmonary and systemic vascular resistances calculated prior to and during hypoxia. These measurements were compared during continued hypoxia between a control and treatment group which received FPL 57231. FPL 57231 infusion resulted in significant decreases in mean pulmonary artery pressure (p less than 0.04), pulmonary vascular resistance (p less than 0.01) and the ratio of pulmonary/systemic vascular resistance (p less than 0.01). Systemic vascular resistance fell approximately 25% from hypoxic baseline (p less than 0.01) while PVR decreased 54%. There were no differences between groups in mean systemic arterial pressure, cardiac output, pH, or PaCO2. In addition, pretreatment with FPL 57231 attenuated the hemodynamic response to hypoxia. These data suggest that leukotrienes may, in part, mediate hypoxic pulmonary vasoconstriction in piglets.     

Ventilation in special situations. Mechanical ventilation in congenital cardiopathies and pulmonary hypertension

The cardiovascular and respiratory systems act as a functional unit. Mechanical ventilation modifies pulmonary volumes, which generates changes in autonomic nervous system reactivity and provokes tachy- or brady-cardia (depending on the tidal volume used). Mechanical ventilation also decreases cardiac filling volumes (pre-load) and alters pulmonary vascular resistances. In addition, intrathoracic pressures are enlarged, which usually produces a decrease in right atrium filling and an increase in right ventricle afterload. If coronary flow is impaired, myocardial contractility is reduced. However, if cardiac failure is present, mechanical ventilation is especially beneficial because it corrects hypoxia and respiratory acidosis, decreases the work of breathing, and improves stroke volume. Mechanical ventilation in congenital heart diseases is indicated either as lifesaving support or as physiopathological treatment to modify the ratio between pulmonary and systemic flow. As a general rule, if excessive pulmonary blood flow is present, the aim of respiratory support is to increase pulmonary vascular resistance by using high levels of airway pressure and even by delivering FiO2<21%. When there is low pulmonary flow, the lowest possible intrathoracic pressures should be used, especially in cases of pulmonary hypertension, which will also require high FiO2. However, mechanical ventilation has adverse effects and consequently it must be stopped as early as possible, once the child is stable and requires minimal cardiopulmonary support. Weaning can even be performed in the operating room, when the surgical procedure is finished. When this is not possible, weaning should be performed in the pediatric intensive care unit. Because there are no criteria for successful withdrawal of mechanical support in congenital heart disease, general pediatric criteria should be used.     

Lung lavage using high-frequency jet ventilation in rabbits with meconium aspiration

AIM: To determine the efficacy of the expulsion effect of high-frequency jet ventilation (HFJV) on meconium clearance from the airways in comparison with conventional suctioning in adult rabbits with meconium aspiration. METHODS: Experiments were carried out on tracheotomized, anaesthetized and paralysed adult rabbits. A suspension of human meconium in saline (25 mg ml(-1), 4 ml kg(-1)) was instilled into the tracheal cannula. When respiratory failure developed, saline lavage (10 ml kg(-1) in 3 portions) was performed during conventional ventilation or by means of the inpulsion and expulsion regime of HFJV. Animals were further ventilated for 2 h with either conventional ventilation or HFJV. RESULTS: There was no significant difference between groups in the amount of meconium recovered by lavage. Compared to conventional ventilation, the application of HFJV enhanced the elimination of carbon dioxide, increased lung compliance and diminished right-to-left shunts after 30 min of ventilatory treatment. Oxygenation also improved during HFJV, although this was not a consistent finding during the ventilation period. CONCLUSION: HFJV improved gas exchange, lung compliance and reduced right-to-left pulmonary shunts, but saline lung lavage by HFJV was not found to be more efficient than lavage during conventional ventilation in rabbits with meconium aspiration.     

Hemodynamic response to high-frequency ventilation in infants following cardiac surgery

The hemodynamic response to high-frequency ventilation was compared with conventional ventilation in six infants following cardiac surgery. While undergoing high-frequency ventilation, adequate gas exchange was maintained in all infants. High frequency ventilation allowed a reduction of peak ventilatory pressure at the airway opening by 19%, and peak tracheal pressure by 42%. No clinically important changes in heart rate, systemic and pulmonary arterial pressure, cardiac index, or systemic and pulmonary vascular resistance were noted when high-frequency ventilation was compared with conventional ventilation.     

Effects of dopamine and nifedipine infusions on the pulmonary circulation of the lamb

The purpose of this study was to test the hypothesis that nifedipine when given with dopamine will lower pulmonary vascular resistance in hypoxic lambs without altering systemic vascular resistance. We studied six unanesthetized lambs (ranging in age from 13 to 35 days) as they breathed air or on a separate day as they breathed 10% O2 and 3% CO2 in nitrogen. First, we infused dopamine at progressively higher rates (10, 20, 40, 80, and 160 micrograms/kg/min) while measuring mean aortic, pulmonary arterial, and left atrial pressures and heart rate continuously and cardiac output and arterial blood gas tensions at frequent intervals. Then, while maintaining the dopamine infusion at 160 micrograms/kg/min, we infused boluses of nifedipine intravenously (10 micrograms/kg) every 5 min until a cumulative dose of 50 micrograms/kg had been administered. In both groups of lambs, cardiac output increased with increasing rates of dopamine infusion (baseline to maximum dopamine: 260 +/- 20 ml/kg/min to 420 +/- 60 ml/kg/min for normoxic lambs and 400 +/- 50 ml/kg/min to 560 +/- 80 ml/kg/min for hypoxic lambs). While systemic vascular resistance and pulmonary vascular resistance did not change significantly in either group during dopamine infusion, the ratio of pulmonary vascular resistance to systemic vascular resistance increased at low rates of infusion and decreased at high rates. The peak in this ratio occurred at a rate of infusion of 20-40 micrograms/kg/min in normoxic lambs and 40-80 micrograms/kg/min in hypoxic lambs. Infusion of nifedipine did not affect cardiac output in normoxic lambs but decreased it significantly in hypoxic lambs. Nifedipine infusion did not affect pulmonary vascular resistance in the normoxic lambs and increased pulmonary vascular resistance in the hypoxic lambs. We conclude that nifedipine, even when given with high doses of dopamine, is not a specific pulmonary vasodilator.     

Chloralose alters both basal hemodynamics and cardiovascular responses to alveolar hypoxia in chronically instrumented, spontaneously breathing lambs

We studied the effects of chloralose anesthesia on the basal hemodynamic state and on the cardiovascular response to alveolar hypoxia in chronically instrumented, spontaneously breathing lambs, compared with responses to the saline vehicle. Chloralose significantly increased heart rate (23%), mean systemic arterial pressure (11%), systemic vascular resistance (21%), mean pulmonary arterial pressure (23%), and pulmonary vascular resistance (46%) (n = 30, p less than 0.05, ANOVA). These changes were unrelated to baseline tone of the circulation, cardiac output, mean left atrial pressure, or physiologically important changes in arterial blood gas tensions. In addition, chloralose-treated lambs had increased heart rate, systemic vascular resistance, and pulmonary vascular resistance compared to controls during alveolar hypoxia (13-15% FiO2). Importantly, chloralose-treated lambs did not increase their cardiac output during alveolar hypoxia as did control lambs. During hypoxia, systemic vascular resistance remained elevated in chloralose-treated lambs, but declined in control lambs. Chloralose has been recommended as an ideal anesthetic agent for cardiovascular experimentation. Our data suggest that chloralose-induced alterations in basal hemodynamics and in cardiovascular responses to alveolar hypoxia represent an uncontrolled variable in acute experimental studies. Complex cardiovascular alterations caused by anesthesia should be considered in experimental design.     

Effects of anti-CD18 monoclonal antibody, R15.7, on the cardiopulmonary manifestations of group B streptococcal sepsis in piglets

We hypothesized that anti-CD18 monoclonal antibody, R15.7, a murine IgG(1) antibody which blocks leukocyte-endothelial cell adherence, might ameliorate the cardiopulmonary manifestations of sepsis secondary to group B streptococci (GBS). Twenty-six anesthetized, mechanically ventilated newborn piglets received a continuous infusion of GBS (7.5 x 10(9) cfu/kg/min) and were randomly assigned to a treatment group receiving R15.7 (1 mg/kg i.v.) 15 min prior to GBS infusion or to a control group. Cardiopulmonary measurements, arterial blood gases and peripheral blood leukocytes were obtained over 120 min of R15.7 infusion. GBS infusion caused significant increases in pulmonary artery and systemic arterial blood (Psa) pressures, pulmonary vascular (PVR) and systemic vascular (SVR) resistances, and PVR/SVR ratio with decreases in cardiac output and stroke volume. R15.7-treated piglets maintained significantly higher Psa (p < 0.003), dynamic lung compliance (p < 0.04), PaO2 and pH (p < 0.05), and lower total lung resistance (p < 0.01) and PaCO2 (p < 0.04). A longer median survival time was observed in the treatment group (p < 0.01). These data suggest that administration of a CD18-blocking agent prolongs survival in a young animal model of GBS sepsis, possibly secondary to improved tissue perfusion, lung mechanics and acid-base status.     

The effect of a nebulized NO donor, DPTA/NO, on acute hypoxic pulmonary hypertension in newborn piglets

NONOates, novel NO donors, are complexes of NO with nucleophiles which spontaneously and nonenzymatically release NO in aqueous solution. This study sought to determine the cardiopulmonary effects of the nebulized NONOate dipropylenetriamine (DPTA)/NO in newborn piglets with acute hypoxia-induced pulmonary hypertension. Twenty sedated and mechanically ventilated piglets (4-10 days old) exposed to hypoxia (Fi(O2) = 0.14) were randomly assigned to receive nebulized saline as placebo (PL) or DPTA/NO (75 mg) after 30 min of hypoxia. Pulmonary artery (P(pa)) and wedge pressures, systemic (P(sa)) and right atrial pressures, cardiac output (CO) and arterial blood gas were measured at baseline and every 15 min for 2 h. Methemoglobin levels were measured at baseline and 1 h after drug nebulization. Data (means +/- SD) were analyzed by repeated-measures analysis of variance. Acute hypoxia resulted in an increase in P(pa) and pulmonary vascular resistance (PVR), which was significantly attenuated by DPTA/NO nebulization as compared to the PL group (p < 0.0001). Changes in P(sa), CO, systemic vascular resistance (SVR), arterial blood gas and methemoglobin levels were not different between groups. In contrast to the increase in PVR/SVR observed during hypoxia in the PL group, there was a significant decrease in this ratio after NONOate administration (p < 0.0001). These data show that acute hypoxic pulmonary hypertension in newborn piglets is markedly attenuated by NONOate nebulization. This response is predominantly in the pulmonary vasculature as the PVR/SVR was significantly lower in the treated group. We speculate that NONOates may have clinical application in the treatment of persistent pulmonary hypertension of the newborn.     

Hemodynamic effects of dobutamine in children with cardiovascular failure

The effect of dobutamine, a synthetic catecholamine, was studied in 12 patients aged one day to 14 years with low cardiac output syndromes.After initial stabilization of the patients dobutamine was administered by continuous infusion in a dosage of 7.5 or 10 g/kg/min.Heart rate, cardiac output (using thermodilution technique and/or pulse contour method), mean systemic and mean pulmonary artery pressures were determined before and after the dobutamine infusion. Systemic and pulmonary vascular resistances, cardiac index and stroke volume index were calculated.Cardiac output and cardiac index increased significantly in every patient, whereas the heart rate changed only slightly, suggesting that the increase in cardiac output was mainly due to the alteration of stroke volume. The mean arterial pressure increased significantly, but the mean pulmonary artery pressure was unchanged. No side effects were observed during the dobutamine infusion. Dobutamine is a potent inotropic drug with limited chronotropic and peripheral vascular effects in newborns, infants and chidren.     

Impairment of hemodynamics with increasing mean airway pressure during high-frequency oscillatory ventilation

We investigated the effects of changes in mean airway pressure (Paw), oscillatory frequency and lung compliance on cardiac output (CO) and pulmonary vascular resistance in seven adult cats (3.0 +/- 0.6 kg) during high-frequency oscillatory ventilation (HFOV). The cats were anesthetized with chloralose and urethane and ventilated with a high-frequency oscillator at Paw of 4, 8, 12, and 16 cm H2O and frequencies of 3, 6, 12, 16, and 20 Hz. Saline lavage was used to reduce lung compliance. CO was continuously recorded with an electromagnetic flow probe placed around the aorta and pulmonary vascular resistance was calculated from left atrial and pulmonary artery pressures. Lung lavage reduced static compliance of the respiratory system but did not change CO during pressure-limited ventilation. During HFOV, CO was higher in animals after lung lavage at each Paw. As Paw was raised from 4 to 16 cm H2O during HFOV, CO decreased from 133 +/- 36 to 87 +/- 31 ml/min kg in animals with normal lungs and decreased from 153 +/- 33 to 107 +/- 19 ml/min kg after lung lavage (both p less than 0.001). Increasing Paw was also associated with an increase in pulmonary vascular resistance both before and after lung lavage (both p less than 0.005). Changes in frequency did not significantly alter CO or pulmonary vascular resistance. We conclude that the interaction between the heart and lungs during HFOV is largely mediated by Paw and compliance of the respiratory system. Furthermore, regardless of the degree of lung compliance, cardiac function may be impaired during HFOV as Paw is elevated.     

Partial liquid ventilation versus conventional mechanical ventilation with high PEEP and moderate tidal volume in acute respiratory failure in piglets

This prospective randomized pilot study aimed to test the hypotheses that partial liquid ventilation combined with a high positive end-expiratory pressure (PEEP) and a moderate tidal volume results in improved gas exchange and lung mechanics without negative hemodynamic influences compared with conventional mechanical ventilation in acute lung injury in piglets. Acute lung injury was induced in 12 piglets weighing 9.0 +/- 2.4 kg by repeated i.v. injections of oleic acid and repeated lung lavages. Thereafter, the animals were randomly assigned either to partial liquid ventilation (n = 6) or conventional mechanical ventilation (n = 6) at a fractional concentration of inspired O(2) of 1.0, a PEEP of 1.2 kPa, a tidal volume < 10 mL/kg body weight (bw), a respiratory rate of 24 breaths/min, and an inspiratory/expiratory ratio of 1:2. Perfluorocarbon liquid 30 mL/kg bw was instilled into the endotracheal tube over 10 min followed by 5 mL/kg bw/h. Continuous monitoring included ECG, mean right atrial, pulmonary artery, pulmonary capillary, and arterial pressures, arterial blood gas, and partial pressure of end-tidal CO(2) measurements. When compared with control animals, partial liquid ventilation resulted in significantly better oxygenation with improved cardiac output and oxygen delivery. Dead space ventilation appeared to be lower during partial liquid ventilation compared with conventional mechanical ventilation. No significant differences were observed in airway pressures, pulmonary compliance, and airway resistance between both groups. The results of this pilot study suggest that partial liquid ventilation combined with high PEEP and moderate tidal volume improves oxygenation, dead space ventilation, cardiac output, and oxygen delivery compared with conventional mechanical ventilation in acute lung injury in piglets but has no significant influence on lung mechanics.     

Pressure-Regulated Volume Control vs Volume Control Ventilation in Infants After Surgery for Congenital Heart Disease

The objective of this investigation was to compare how two modes of positive pressure ventilation affect cardiac output, airway pressures, oxygenation, and carbon dioxide removal in children with congenital heart disease in the immediate postoperative period. The investigation used a one group pretest–post-test study design and was performed in the pediatric cardiac intensive care unit in a university-affiliated children's hospital. Nine infants were enrolled immediately after repair of tetralogy of Fallot (2) or atrioventricular septal defects (7) with mean weight = 5.5 kg (4.2–7.3 kg). Children were admitted to the pediatric cardiothoracic intensive care unit after complete surgical repair of their cardiac defect and stabilized on a Siemen's Servo 300 ventilator in volume control mode (VCV1) (volume-targeted ventilation with a square flow wave pattern). Tidal volume was set at 15 cc/kg (total). Hemodynamic parameters, airway pressures and ventilator settings, and an arterial blood gas were measured. Patients were then changed to pressure-regulated volume control mode (PRVC) (volume-targeted ventilation with decelerating flow wave pattern) with the tidal volume set as before. Measurements were repeated after 30 minutes. Patients were then returned to volume control mode (VCV2) and final measurements made after 30 minutes. The measurements and results are as follows: After correction of congenital heart defects in infants, mechanical ventilation using a decelerating flow wave pattern resulted in a 19% decrease in peak inspiratory pressure without affecting hemodynamics, arterial oxygenation, or carbon dioxide removal.     

Effects of a nebulized NONOate, DPTA/NO, on group B streptococcus-induced pulmonary hypertension in newborn piglets

NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions. When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury. To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4-10 d). They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension. Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 x 10(8) CFU/min). Methemoglobin levels were measured at baseline and 60 min. A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p <0.001). Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p <0.01). Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups. These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization. The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature. Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates.     

Central hemodynamic and regional blood flow changes in the newborn with right ventricular hypertension

To evaluate the central hemodynamic and regional blood flow changes associated with right ventricular hypertension in the newborn, 13 anesthetized, mechanically ventilated piglets less than 3 d old were acutely instrumented to permit measurements of central vascular pressures, cardiac output, and regional blood flow (radio-labeled microsphere technique). After initial measurements, right ventricular afterload was progressively increased by means of a pulmonary arterial mechanical occluder until right-to-left foramen ovale shunt was observed. An increase in pulmonary arterial pressure from 32 +/- 2 to 55 +/- 3 mm Hg was associated with a decrease in PaO2 from 364 +/- 16 to 88 +/- 9 mm Hg and an increase in the shunt fraction from 13 +/- 1 to 28 +/- 1% (p less than 0.01) during ventilation with oxygen. Right ventricular hypertension induced a significant decrease in systemic arterial pressure from 79 +/- 3 to 63 +/- 4 mm Hg, and left ventricular cardiac output from 156 +/- 10 to 112 +/- 11 mL.min-1.kg-1 (p less than 0.01), likely secondary to a reduction in left ventricular compliance. Oxygen delivery to the brain and heart were unaffected, due to a substantial increase in regional blood flow, but a significant reduction in delivery to the bowel and kidneys were observed. Contrary to what has been reported in the adult, myocardial blood flow to the right ventricle increased during hypertension. Metabolic acidosis was seen in all animals and the changes in serum bicarbonate and whole body oxygen consumption were directly related to the magnitude of decline in systemic O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)