Effect of enhanced ultraviolet germicidal irradiation in the heating ventilation and air conditioning system on ventilator-associated pneumonia in a neonatal intensive care unit.

OBJECTIVE: The objective of this study was to test the hypothesis that enhanced ultraviolet germicidal irradiation (eUVGI) installed in our neonatal intensive care unit (NICU) heating ventilation and air conditioning system (HVAC) would decrease HVAC and NICU environment microbes, tracheal colonization and ventilator-associated pneumonia (VAP). STUDY DESIGN: The study was designed as a prospective interventional pre- and post-single-center study. University-affiliated Regional Perinatal Center NICU. Intubated patients in the NICU were evaluated for colonization, and a high-risk sub-population of infants <30 weeks gestation ventilated for ≥ 14 days was studied for VAP. eUVGI was installed in the NICU's remote HVACs. The HVACs, NICU environment and intubated patients' tracheas were cultured pre- and post-eUVGI for 12 months. The high-risk patients were studied for VAP (positive bacterial tracheal culture, increased ventilator support, worsening chest radiograph and ≥ 7 days of antibiotics). RESULT: Pseudomonas, Klebsiella, Serratia, Acinetobacter, Staphylococcus aureus and Coagulase-negative Staphylococcus species were cultured from all sites. eUVGI significantly decreased HVAC organisms (baseline 500,000 CFU cm(-2); P=0.015) and NICU environmental microbes (P<0.0001). Tracheal microbial loads decreased 45% (P=0.004), and fewer patients became colonized. VAP in the high-risk cohort fell from 74% (n=31) to 39% (n=18), P=0.04. VAP episodes per patient decreased (Control: 1.2 to eUVGI: 0.4; P=0.004), and antibiotic usage was 62% less (P=0.013). CONCLUSION: eUVGI decreased HVAC microbial colonization and was associated with reduced NICU environment and tracheal microbial colonization. Significant reductions in VAP and antibiotic use were also associated with eUVGI in this single-center study. Large randomized multicenter trials are needed.

Spacer inhalation technique and deposition of extrafine aerosol in asthmatic children.

The aim of the present study was to measure airway, oropharyngeal and gastrointestinal deposition of (99m)Tc-labelled hydrofluoroalkane-beclomethasone dipropionate after inhalation via a pressurised metered-dose inhaler and spacer (Aerochamber Plus) in asthmatic children. A group of 24 children (aged 5-17 yrs) with mild asthma inhaled the labelled drug. A total of 12 children took five tidal breaths after each actuation (tidal group). The other 12 children used a slow maximal inhalation followed by a 5 - 10-s breath-hold (breath-hold group). Simultaneous anterior and posterior planar gamma-scintigraphic scans (120-s acquisition) were recorded. For the tidal group, mean+/-sd lung deposition (% ex-actuator, attenuation corrected) was 35.4+/-18.3, 47.5+/-13.0 and 54.9+/-11.2 in patients aged 5-7 (n = 4), 8-10 (n = 4) and 11-17 yrs (n = 4), respectively. Oropharyngeal and gastrointestinal deposition was 24.0+/-10.5, 10.3+/-4.4 and 10.1+/-6.2. With the breath-hold technique, lung deposition was 58.1+/-6.7, 56.6+/-5.2 and 58.4+/-9.2. Oropharyngeal and gastrointestinal deposition was 12.9+/-3.2, 20.1+/-9.5 and 20.8+/-8.8. Inhalation of the extrafine formulation with the breath-hold technique showed significantly improved lung deposition compared with tidal breathing across all ages. Oropharyngeal and gastrointestinal deposition was markedly decreased, regardless of which inhalation technique was applied, compared with a previous paediatric study using the same formulation delivered via a breath-actuated metered-dose inhaler.

Ductus venosus flow velocity in newborn lambs during increased pulmonary artery pressure.

The aim of the present study was to assess with ultrasound the ductus venosus flow velocity in newborn lambs with increasing pulmonary artery pressures and to evaluate whether this is a useful method to detect elevated pulmonary artery pressure. The ductus venosus flow velocity was studied with pulsed-wave Doppler echocardiography in nine newborn lambs < or = 30 h old. The lambs were anesthetized, mechanically ventilated, and instrumented to measure mean airway pressure and pulmonary artery and arterial blood pressures. A vascular occluder was placed around the main pulmonary artery. With mean pressures ranging from 20 to 50 mm Hg in the pulmonary artery, the ductus venosus flow velocity was examined. In seven lambs, the mean portal pressure and central venous pressure were also measured. With a stepwise increase in the pulmonary artery pressure, the minimum ductus venosus flow velocity during atrial systole decreased to a reversed flow, and the duration of this reversed flow component increased. The systolic forward peak flow velocity signal also gradually decreased. No changes were detected in the mean central venous or in the portal pressure with increasing pulmonary artery pressure or changes in ductus venosus flow. The flow velocity in the ductus venosus, which is higher than in other precordial veins, shows a reduction and even reversal of the nadir and an increase of the duration of reversed flow during atrial systole as a response to increased pulmonary artery pressure. Thus, Doppler ultrasound of the ductus venosus flow velocity may be a useful noninvasive diagnostic supplement to detect pulmonary hypertension of the newborn.

Regional pulmonary blood flow during partial liquid ventilation in normal and acute oleic acid-induced lung-injured piglets.

OBJECTIVE: To determine the spatial distribution of pulmonary blood flow in three groups of piglets: partial liquid ventilation in normal piglets, partial liquid ventilation during acute lung injury, and conventional gas ventilation during acute lung injury. DESIGN: Prospective randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Regional pulmonary blood flow was studied in 21 piglets in the supine position randomized to three different groups: a normal group that received partial liquid ventilation (Normal-PLV) and two acute lung injury groups that received an oleic acid-induced lung injury: partial liquid ventilation during acute lung injury (OA-PLV) and conventional gas ventilation during acute lung injury (OA-Control). Acute lung injury was induced by infusing oleic acid (0.15 mL/kg iv) over 30 mins. Partial liquid ventilation was instituted with perflubron (LiquiVent, 30 mL/kg) after 30 mins in the Normal-PLV and OA-PLV groups. MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and pulmonary mechanics were measured every 15 mins throughout the hour-long study. Pulmonary blood flow was assessed by fluorescent microsphere technique at baseline and after 30, 45, and 60 mins. In the Normal-PLV piglets, pulmonary blood flow decreased from baseline (before injury or partial liquid ventilation) in the most dependent areas of the lung (F ratio = 3.227; p < .001). In the OA-PLV piglets, pulmonary blood flow was preserved over time throughout the lung (F ratio = 1.079; p = .38). In the OA-Control piglets, pulmonary blood flow decreased in the most dependent areas of the lung and increased from baseline in less dependent slices over time (F ratio = 2.48; p = .003). CONCLUSIONS: The spatial distribution of regional pulmonary blood flow is preserved during partial liquid ventilation compared with gas ventilation in oleic acid-induced lung injury.

Improved delivery of inhaled steroids to the large and small airways.

The reformulation of asthma medications with non-ozone depleting propellants such as hydrofluoroalkane-134a (HFA) has provided the opportunity to apply new knowledge and inhaler technology to improve significantly the delivery of aerosol drugs to the respiratory tract. Beclomethasone dipropionate (BDP), the most commonly prescribed inhaled corticosteroid for asthma therapy, is effective therapy; however currently available chlorofluorocarbon (CFC)-BDP metered dose inhalers typically deliver no more than 10% of the inhaled drug to the lungs with the remainder deposited in the oropharynx. Compared with an average particle size of 3.5-4.0 microns for CFC-BDP, the new HFA-BDP formulation has an average particle size of 1.1 microns and a respirable fraction of approximately 60%. The lung deposition of 99mTc-radiolabelled HFA-BDP has been investigated in healthy volunteers and patients with asthma. Results showed that the HFA-BDP formulation reverses the pattern of distribution seen with CFC-BDP products, delivering most of the dose of inhaled steroid directly to the lungs rather than to the oropharynx and gut where it may lead to unwanted side-effects. As such, HFA-BDP is likely to achieve equivalent efficacy to existing CFC-BDP formulations with lower doses and with reduced potential for local adverse effects.

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange.

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.

Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone.

Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.

Partial liquid ventilation with perflubron in premature infants with severe respiratory distress syndrome. The LiquiVent Study Group.

BACKGROUND: The intratracheal administration of a perfluorocarbon liquid during continuous positive-pressure ventilation (partial liquid ventilation) improves lung function in animals with surfactant deficiency. Whether partial liquid ventilation is effective in the treatment of infants with severe respiratory distress syndrome is not known. METHODS: We studied the efficacy of partial liquid ventilation with perflubron in 13 premature infants with severe respiratory distress syndrome in whom conventional treatment, including surfactant therapy, had failed. Partial liquid ventilation was initiated by instilling perflubron during conventional mechanical ventilation to a volume approximating the functional residual capacity. Infants were considered to have completed the study if they received partial liquid ventilation for at least 24 hours. RESULTS: Ten infants received partial liquid ventilation for 24 to 76 hours. In the other three infants, partial liquid ventilation was discontinued within four hours in favor of high-frequency ventilation, which was not permitted by the protocol, and the data from these infants were excluded from the analysis. Within one hour after the instillation of perflubron, the arterial oxygen tension increased by 138 percent and the dynamic compliance increased by 61 percent; the mean (+/- SD) oxygenation index was reduced from 49 +/- 60 to 17 +/- 16. Chest radiographs showed symmetric filling, with patchy clearing during the return from partial liquid to gas ventilation. There were no adverse events clearly attributable to partial liquid ventilation. Infants were weaned from partial liquid to gas ventilation without complications. Eight infants survived to 36 weeks' corrected gestational age. CONCLUSIONS: Partial liquid ventilation leads to clinical improvement and survival in some infants with severe respiratory distress syndrome who are not predicted to survive.

Partial liquid ventilation enhances surfactant phospholipid production.

OBJECTIVE: To study the effect of partial liquid ventilation on phospholipid metabolism. DESIGN: Prospective, controlled laboratory study. SETTING: University-affiliated animal research facility. SUBJECTS: Mature New Zealand white rabbits (n = 17). INTERVENTIONS: The rabbits were sedated, anesthetized, and instrumented with tracheostomy and the insertion of an arterial catheter. The rabbits were sequentially assigned to receive conventional mechanical ventilation or partial liquid ventilation with Perflubron (18 mL/kg by bolus fill). Ventilator strategies were identical in both groups and consisted of an FiO2 of 0.5, positive end-expiratory pressure of 4 cm H2O, effective tidal volume of 8 to 13 mL/kg, and rate to maintain Pco2 of 30 to 40 torr (4.0 to 5.3 kPa). Phosphatidylcholine was labeled in vivo by injection of 3H-methylcholine (25 microCi/kg iv). Ventilation was continued for 5.5 hrs. MEASUREMENTS AND MAIN RESULTS: When animals were killed, phosphatidylcholine was extracted from the total lung lavage and from the pulmonary parenchyma. After the separation of phospholipids by thin-layer chromatography, the 3H activity was determined by liquid scintillation counting. Inorganic phosphorus was also determined to assess the enrichment of the phosphatidylcholine. The 3H-phosphatidylcholine activity in the partial liquid ventilation treated- vs. control rabbits demonstrated a 53% increase (p = .051) in the lavage and a 48% increase (p = .013) in the parenchyma for a net 50% (p = .012) total pulmonary increase. The phospholipid content of the partial liquid ventilation treated- vs. the control rabbits demonstrated a 78% increase (p = .046). CONCLUSIONS: We conclude that partial liquid ventilation with Perflubron appears to have no negative impact on phospholipid metabolism but rather enhances surfactant phospholipid synthesis and secretion.

Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome.

OBJECTIVE: To compare the effectiveness of perfluorocarbon-associated gas exchange to volume controlled positive pressure breathing in supporting gas exchange, lung mechanics, and survival in an acute lung injury model. DESIGN: A prospective, randomized study. SETTING: A university medical school laboratory approved for animal research. SUBJECTS: Neonatal piglets. INTERVENTIONS: Eighteen piglets were randomized to receive perfluorcarbon-associated gas exchange with perflubron (n=10) or volume controlled continuous positive pressure breathing (n=8) after acute lung injury was induced by oleic acid infusion (0.15 mL/kg iv). MEASUREMENTS AND MAIN RESULTS: Arterial and venous blood gases, hemodynamics, and lung mechanics were measured every 15 mins during a 3-hr study period. All animals developed a metabolic and a respiratory acidosis during the infusion of oleic acid. Following randomization, the volume controlled positive pressure breathing group developed a profound acidosis (p<.05), while pH did not change in the perfluorocarbon-associated gas exchange group. Within 15 mins of initiating perfluorocarbon-associated gas exchange, oxygenation increased from a PaO2 of 52 +/- 12 torr (6.92 +/- 1.60 kPa) to 151 +/- 93 torr (20.0 +/- 12.4 kPa) and continued to improve throughout the study (p<.05). Animals that received volume controlled positive pressure breathing remained hypoxic with no appreciable change in PaO2. Although both groups developed hypercarbia during oleic acid infusion, PaCO2, steadily increased over time in the control group (p<.01). Static lung compliance significantly increased postrandomization (60 mins) in the animals supported by perflurocarbon-associated gas exchange (p<.05), whereas it remained unchanged over time in the volume controlled positive pressure breathing group. However, survival was significantly higher in the perfluorocarbon-associated gas exchange group with eight (80%) of ten animals surviving the entire study period. Only two (25%) of the eight animals in the volume controlled positive pressure breathing group were alive at the end of the study period (log-rank statistic, p=.013). CONCLUSIONS: Perflurocarbon-associated gas exchange enhanced gas exchange, pulmonary mechanics, and survival in this model of acute lung injury.

Perfluorocarbon-associated gas exchange in normal and acid-injured large sheep.

OBJECTIVES: We hypothesized that a) perfluorocarbon-associated gas exchange could be accomplished in normal large sheep; b) the determinants of gas exchange would be similar during perfluorocarbon-associated gas exchange and conventional gas ventilation; c)in large animals with lung injury, perfluorocarbon-associated gas exchange could be used to enhance gas exchange without adverse effects on hemodynamics; and d) the large animal with lung injury could be supported with an FIO2 of <1.0 during perfluorocarbon-associated gas exchange. DESIGN: Prospective, observational animal study and prospective randomized, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Thirty adult ewes. MEASUREMENT AND MAIN RESULTS: Five normal ewes (61.0 +/- 4.0 kg) underwent perfluorocarbon-associated gas exchange to ascertain the effects of tidal volume, end-inspiratory pressure, and positive end-expiratory pressure (PEEP) on oxygenation. Respiratory rate, tidal volume, and minute ventilation were studied to determine their effects on CO2 clearance. Sheep, weighing 58.9 +/- 8.3 kg, had lung injury induced by instilling 2 mL/kg of 0.05 Normal hydrochloric acid into the trachea. Five minutes after injury, PEEP was increased to 10 cm H2O. Ten minutes after injury, sheep with Pao2 values of <100 torr (<13.3 kPa) were randomized to continue gas ventilation (control, n=9) or to institute perfluorocarbon-associated gas exchange (n=9) by instilling 1.6 L of unoxygenated perflubron into the trachea and resuming gas ventilation. Blood gas and hemodynamic measurements were obtained throughout the 4-hr study. Both tidal volume and end-inspiratory pressure influenced oxygenation in normal sheep during perfluorocarbon-associated gas exchange. Minute ventilation determined CO2 clearance during perfluorocarbon-associated gas exchange in normal sheep. After acid aspiration lung injury, perfluorocarbon-associated gas exchange increased PaO2 and reduced intrapulmonary shunt fraction. Hypoxia and intrapulmonary shunting were unabated after injury in control animals. Hemodynamics were not influenced by the institution of perfluorocarbon-associated gas exchange. CONCLUSIONS: Tidal volume and end-inspiratory pressure directly influence oxygenation during perfluorocarbon-associated gas exchange in large animals. Minute ventilation influences clearance of CO2. In adult sheep with acid aspiration lung injury, perfluorocarbon-associated gas exchange at an FIO2 of <1.0 supports oxygenation and improves intrapulmonary shunting, without adverse hemodynamic effects, when compared with conventional gas ventilation.

Prolonged studies of perfluorocarbon associated gas exchange and of the resumption of conventional mechanical ventilation.

OBJECTIVE: To determine whether oxygenation and lung mechanics are preserved during perfluorocarbon associated gas exchange of 24 hrs duration and after evaporation of perfluorocarbon. DESIGN: Prospective, experimental animal trials. SETTING: Animal laboratory in a university setting. SUBJECTS: Ten normal, neonatal piglets weighing 2.5 to 4.5 kg. INTERVENTIONS: Ten piglets were anesthetized with fentanyl (25 micrograms/kg/hr), paralyzed with metocurine iodide (0.3 mg/kg) and placed on volume regulated continuous positive pressure breathing instituted at an FIO2 setting of 1.0, tidal volume of 15 mL/kg, respiratory rate of 25 breaths/min and positive end-expiratory pressure of 4 cm H2O. Perfluorocarbon associated gas exchange was initiated by intratracheal instillation of perflouorooctylbromide (30 mL/kg) followed by gas ventilation at the same settings. Evaporative losses were replaced by intratracheal instillation of 2.5 mL/kg/hr of perfluorocarbon. In one group of five piglets, evaporative losses were replaced for 24 hrs until the end of the study. In the other group of five piglets, replacement of perfluorocarbon was discontinued after 2 hrs, although gas ventilation was continued for 24 hrs. Blood gases and lung mechanics were measured in both groups. Histologic evaluation of lungs from both groups of animals was performed. MEASUREMENTS AND MAIN RESULTS: Airway pressures and blood gases were stable throughout the 24-hr study period in both groups. Airway pressures in the evaporative group increased as evaporation of perfluorocarbon neared completion. There was no hemodynamic deterioration during the 24-hr study period. Histology showed good preservation of lung architecture in both groups. CONCLUSIONS: Perfluorocarbon associated gas exchange was safe and effective in normal piglets for a period of 24 hrs. Evaporation of perfluorocarbon and resumption of continuous positive pressure breathing was well tolerated.

Partial liquid ventilation in premature lambs with respiratory distress syndrome: efficacy and compatibility with exogenous surfactant.

OBJECTIVE: To determine the efficacy of partial liquid ventilation (PLV) by means of a medical-grade perfluorochemical liquid, perflubron (LiquiVent), in premature lambs with respiratory distress syndrome (RDS). Further, to determine the compatibility of perflubron with exogenous surfactant both in vitro and in vivo during PLV. DESIGN: Prospective, randomized, controlled study, with in vitro open comparison. SUBJECTS: Twenty-two premature lambs with RDS. INTERVENTIONS: In vitro assays were conducted on three exogenous surfactants before and after combination with perflubron. We studied four groups of lambs, which received one of the following treatment strategies: conventional mechanical ventilation (CMV); surfactant (Exosurf) plus CMV; PLV; or surfactant plus PLV. MEASUREMENTS AND MAIN RESULTS: In vitro surface tension, measured for three exogenous surfactants, was unchanged in each animal after exposure to perflubron. Lung mechanics and arterial blood gases were serially measured. All animals treated with PLV survived the 5 hours of experiment without complication; several animals treated with CMV died. During CMV, all animals had marked hypoxemia and hypercapnia. During PLV, arterial oxygen tension increased sixfold to sevenfold within minutes of initiation, and this increase was sustained; arterial carbon dioxide tension decreased to within the normal range. Compliance increased fourfold to fivefold during PLV compared with CMV. Tidal volumes were increased during PLV, with lower mean airway pressure. Resistance was similar for both CMV and PLV; there was no difference with surfactant treatment. CONCLUSIONS: We conclude that PLV with perflubron improves lung mechanics and gas exchange in premature lambs with RDS, that PLV is compatible with exogenous surfactant therapy, and that, as a treatment for RDS in this model, PLV is superior to the surfactant studied.

Cardiorespiratory effects of perfluorocarbon-associated gas exchange at reduced oxygen concentrations.

OBJECTIVE: To determine whether reducing FIO2 during perfluorocarbon-associated gas exchange would cause deterioration of hemodynamics, lung mechanics, or gas exchange in normal piglets. DESIGN: A prospective, controlled animal trial. SETTING: Experimental animal laboratory in a university setting. SUBJECTS: Twelve normal, anesthetized piglets, 7 to 14 days old, and weighing 3.31 +/- 0.75 kg. INTERVENTIONS: After the induction of anesthesia, tracheostomy and catheterization, piglets were stabilized. They were mechanically ventilated with a tidal volume of 15 mL/kg, inspiratory time of 25%, positive end-expiratory pressure of 4 cm H2O, and a respiratory rate of 20 to 28 breaths/min to obtain a baseline PaCO2 between 34 and 45 torr (4.7 and 6.0 kPa). Each animal was studied during continuous positive-pressure breathing, and during perfluorocarbon-associated gas exchange. They were ventilated at an FIO2 of 1.0 for 15 mins. FIO2 was randomly varied among 0.75, 0.5, and 0.3 every 15 mins, then returned to 1.0. At each FIO2, measurements of gas exchange, lung mechanics, and hemodynamics were made. After continuous positive-pressure breathing, perfluorocarbon-associated gas exchange was instituted by replacing the gaseous functional residual capacity of the lungs with perfluorooctylbromide. Animals were then ventilated and measurements were taken. MEASUREMENTS AND MAIN RESULTS: At each FIO2, measurements of gas exchange (arterial blood gases and saturation), lung mechanics (mean airway pressure, static end-inspiratory pressure, and peak inspiratory pressure), and hemodynamics (heart rate, and mean arterial, right atrial, pulmonary artery occlusion, and pulmonary arterial pressures) were recorded. In six piglets, cardiac output was measured at each FIO2 by thermodilution. Cardiac index, indexed oxygen delivery and consumption, and indexed pulmonary vascular resistance were derived using standard formulas. Piglets were well saturated at all FIO2 settings during continuous positive-pressure breathing. However, during perfluorocarbon-associated gas exchange, arterial saturation decreased to 72% at an FIO2 of 0.3. Cardiac index and oxygen consumption were not affected by reducing FIO2 during perfluorocarbon-associated gas exchange, and were not significantly different than during continuous positive-pressure breathing. Oxygen delivery was reduced at an FIO2 of 0.3 during perfluorocarbon-associated gas exchange, but oxygen consumption remained in the flow independent portion of the curve despite arterial desaturation. Pulmonary arterial pressure was higher during perfluorocarbon-associated gas exchange than during continuous positive-pressure breathing. Pulmonary arterial pressure and indexed pulmonary vascular resistance were significantly higher during perfluorocarbon-associated gas exchange at an FIO2 of 0.3 than at any other FIO2 settings. CONCLUSIONS: Piglets showed no adverse effects on lung mechanics during perfluorocarbon-associated gas exchange. Hemodynamics were well supported at all FIO2 settings, and arterial blood was fully oxygenated during perfluorocarbon-associated gas exchange at an FIO2 of > or = 0.5.

A novel breath actuated device (Autohaler) consistently actuates during the early phase of inspiration.

OBJECTIVE: To establish and quantify the point during inspiration that the Autohaler (AH) inhalation system releases a metered dose of aerosol (placebo). The second objective was to determine if the Autohaler system actuates consistently, regardless of the canister life. DESIGN: Double-blind, randomized, two-period crossover, one-day trial. SETTING: Community based allergy and asthma clinic. PARTICIPANTS: Twelve patients with mild to moderate asthma. RESULTS: Mean verbal training time for the AH which included the patient demonstrating their ability to correctly use the AH was approximately 6 minutes. The mean time for actuation for the AH early in its canister life ("new canister") was 195 msec compared to 205 msec for the AH late in its canister life ("old canister") (p = 0.589). This represented the early part of inspiration as patients had a mean inspiratory duration of 2231 msec for the "new" AH and 2343 msec for the "old" AH. The mean percentage of inspiration time required to actuate the "new" AH was 8.92% compared to 8.82% for the "old" AH. Patients rated the system as easier to much easier to use compared with their current standard press and breathe inhaler. CONCLUSIONS: The AH consistently actuates early during inspiration, which is considered the optimal time for drug delivery, regardless of the canister life.

Perfluorocarbon-associated gas exchange in gastric aspiration.

OBJECTIVES: To test whether perfluorocarbon-associated gas exchange (gas ventilation of the perfluorocarbon-liquid filled lung) could support oxygenation better than conventional positive pressure breathing in a piglet model of gastric aspiration-induced adult respiratory distress syndrome (ARDS). DESIGN: Prospective, randomized, blinded, controlled study. SETTING: A critical care research laboratory in a university medical school. SUBJECTS: Fourteen healthy piglets. INTERVENTIONS: Under alpha-chloralose anesthesia and metocurine iodide neuromuscular blockade, 14 piglets underwent tracheostomy; central venous, systemic and pulmonary arterial catheterizations; and volume-regulated continuous positive-pressure breathing. Homogenized gastric aspirate (1 mL/kg) titrated to pH of 1.0 was instilled into the tracheostomy tube of each subject at 0 min to induce ARDS. Hemodynamics, lung mechanics, and gas exchange were evaluated every 30 mins for 6 hrs. Seven piglets were treated at 60 mins by tracheal instillation of perflubron, a volume selected to approximate normal functional residual capacity, and were supported by perfluorocarbon-associated gas exchange without modifying ventilatory settings. Perflubron was added to the trachea every hour to replace evaporative losses. MEASUREMENTS AND MAIN RESULTS: There was a significant difference in oxygenation over time when tested by repeated-measures analysis of variance (F test = 8.78, p < .01). On further analysis, the differences were not significant from baseline to 2.5 hrs but became increasingly significant from 2.5 to 6 hrs after injury (p < .05) in the inflammatory phase of gastric aspiration-induced ARDS. Histologic evidence for ARDS in the treated group 6 hrs after injury was lacking. CONCLUSIONS: In the piglet model, perfluorocarbon-associated gas exchange with perflubron facilitates oxygenation in the acute phase of gastric aspiration-induced inflammatory ARDS when compared with conventional positive-pressure breathing. Histologic and physiologic data suggest that perfluorocarbon-associated gas exchange with perflubron might prevent ARDS if instituted after aspiration in the time window before the acute inflammatory process is manifest.

Liquid ventilation: it's not science fiction anymore.

Liquid ventilation is, by all initial considerations, an unconventional concept. Decades of research, however, have found that by using perfluorocarbons, which are capable of holding high concentrations of critical gases such as oxygen and carbon dioxide, gas exchange optimal enough to support life is possible with no known toxic effects. The earliest method of liquid ventilation, tidal liquid breathing, involved infusion and active removal of tidal volumes of perfluorocarbons by a liquid ventilator for gas exchange. Recently, a new method of partial liquid breathing, called perfluorocarbon-associated gas exchange, makes the process of liquid ventilation simpler by using conventional gas ventilators. Current research is showing great promise in the use of liquid ventilation for patients with pulmonary pathology. Critical care nurses should become knowledgeable of this new mode of ventilation and be prepared to meet the special needs of this unique population.

Perfluorocarbon associated gas exchange (PAGE): gas ventilation of the perfluorocarbon filled lung.

BACKGROUND: Throughout most of the second half of this century, progress in respiratory life support was dominated by modernization of the mechanical ventilator. We have now entered an era in which the fundamental physiology of lung function can be manipulated to improve lung performance in hope of reducing morbidity and mortality and thereby decreasing the cost of intensive care. MAIN FINDINGS: Despite its almost alien technology, perfluorocarbon tidal liquid breathing is an effective means to support respiration in normal and surfactant deficient lungs. A second, technique, perfluorocarbon associated gas exchange (PAGE), has recently been shown effective in normal lungs and in several animal models of lung disease. Both techniques appear to improve pulmonary function when pulmonary surface tension is elevated. CONCLUSIONS: PAGE improves lung function and poses opportunities to reduce pulmonary morbidity and diminish the cost of intensive care.

Oxygenation during perfluorocarbon associated gas exchange in normal and abnormal lungs.

Perfluorocarbon-associated gas exchange (PAGE) has been proposed for the treatment of lung diseases characterized by high alveolar surface tension. Perflubron (perfluorooctyl bromide, LiquiVent, Alliance Pharmaceutical Corp.) is a high purity medical grade perfluorocarbon suitable for PAGE. We studied PAGE using perflubron in normal piglets and in animal models of pulmonary disease (meconium aspiration syndrome, oleic acid infusion and gastric acid aspiration as models of ARDS, and neonatal respiratory distress syndrome). All animals were studied under anesthesia. PAGE was instituted by intratracheal instillation of a volume of perflubron (generally 30 ml/kg) that approximates a normal functional residual capacity of the lung. Arterial blood gases were measured at 15 minute intervals. FiO2 during PAGE was 1.0. In normal piglets, PaO2 fell from 543 torr (during conventional gas breathing) to 363 torr (during PAGE). However, in models of lung disease, PAGE significantly enhanced PaO2.