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 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.

Effects of acrolein on macrophage functions in rats.

Male Sprague-Dawley rats were exposed to 0.1, 1.0 or 3.0 ppm acrolein or filtered air 6 h/day, 5 days/week for 3 weeks. Rats were tested one day following the last exposure and exhibited no change in pulmonary clearance of inhaled 35S-labeled Klebsiella pneumoniae at any acrolein concentration. Decreased numbers of peritoneal cells were obtained from exposed rats while the number of cells lavaged from the lungs was unchanged. Macrophages of acrolein-exposed rats had altered phagocytic and enzymatic patterns as compared to macrophages from animals breathing filtered air. However, these changes had no apparent effect on macrophage killing of inhaled bacteria and were therefore probably not indicative of extreme chemical toxicity.

The pathologic and immunologic effects of inhaled acrolein in rats.

Four groups of 40 male Sprague-Dawley rats each were exposed by inhalation to target concentrations of 0, 0.1, 1.0, and 3.0 ppm of acrolein 6 h/day, 5 days/week for 3 weeks. Subsequent changes in local pulmonary immunity were determined by examining the number of antibody plaque-forming cells in the lung-associated lymph nodes following intratracheal immunization with sheep red blood cells. Separate groups of rats were evaluated for blastogenic responsiveness to phytohemagglutinin-P and Salmonella typhimurium antigen using spleen- and lung-associated lymph node cells. In vivo resistance was evaluated utilizing acrolein-exposed rats subsequently challenged with intravenous Listeria monocytogenes. Local pulmonary antibody responsiveness was not affected by acrolein exposure. Lymphocyte blastogenesis and resistance to Listeria challenge were not altered. Body weights and spleen weights were decreased in the 3 ppm-exposed group only. Microscopic examination of the nasal turbinates revealed acrolein-induced exfoliation, erosion, and necrosis of the respiratory epithelium as well as squamous metaplasia, however, lung histology was not affected. Thus at environmental concentrations, acrolein toxicity appeared to be confined to local nasal pathologic changes with no alterations in lung histology or immune function.

Local anesthesia for mediastinoscopy: experience with 450 consecutive cases.

Mediastinoscopy has been widely applied in the evaluation of patients with suspected bronchogenic carcinoma over the past decade. Though there remain those who feel that such findings should not play a significant role in determining resectability, we have found a number of patients who have been saved from exploratory thoracotomy in obviously incurable situations. We have had a relatively high degree of success in the diagnosis of benign diseases. Wtih no mortality and a morbidity of 1.1%, we feel that mediastinoscopy under local anesthesia is applicable in many clinical circumstances in which the requirement for general anesthesia would preclude such evaluation. Though it is not necessary that local anesthesia be exclusively applied, we feel that our experience with over 450 cases in the last six years has demonstrated safety and efficacy in universal application of local anesthesia for cervical mediastinal exploration.

Pathophysiology of congenital diaphragmatic hernia II: the fetal lamb CDH model is surfactant deficient.

The high mortality for congenital diaphragmatic hernia (CDH) has been attributed to a combination of pulmonary hypoplasia and pulmonary hypertension. We hypothesize that a surfactant deficiency may in part be contributing to the pathophysiology of CDH. This study documents the functional, quantitative, and qualitative aspects of the surfactant status of the alveolar air-liquid interface and the type II pneumocyte in the fetal lamb CDH model. Ten lamb fetuses (gestational age, 80 days) had a CDH created via a left thoracotomy and then were allowed to continue in utero development until term. Three litter mates and three nonoperated time-dated fetuses served as controls. At term, pressure-volume curves were performed to measure pulmonary compliance and total lung capacity. Alveolar lavage was then performed to measure the quantitative and the qualitative aspects of pulmonary surfactant. Finally, isolation of type II pneumocytes allowed quantification of phospholipid synthesis. When compared with controls (N = 6), the CDH lambs (N = 5) had significantly smaller lungs (P = .009), decreased total lung capacity (P less than .001) and compliance (P less than .001), reduced total lavaged phospholipids (P = .006), and decreased percent phosphatidylcholine (P = .02). CDH lambs also had increased total lavaged proteins (P = .05) and higher minimum dynamic surface tension (P less than .001). A surfactant deficiency may be contributing to the pathophysiology of CDH. Surfactant replacement therapy in premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Exogenous surfactant may also benefit infants with CDH.

Pathophysiology of congenital diaphragmatic hernia. III: Exogenous surfactant therapy for the high-risk neonate with CDH.

Exogenous surfactant therapy (EST) in surfactant-deficient premature infants has been shown to improve lung compliance, decrease morbidity, and improve survival. Reports have demonstrated that newborns with congenital diaphragmatic hernia (CDH) have lung compliance, pressure-volume curves, and hyaline membrane formation resembling those changes seen in surfactant deficient premature newborns. We hypothesize that EST may also benefit infants with CDH. All high risk cases of prenatally diagnosed CDH at Children's Hospital of Buffalo from November 1988 to February 1991 were prospectively evaluated for EST. In those families who chose to participate, the surfactant preparation, Infasurf (100 mg/kg), was instilled into the newborn's lungs prior to the first breath. The remainder of the perinatal, neonatal, and surgical care was performed in a routine manner. Three high-risk prenatally diagnosed newborns with left CDH were treated with EST. All showed signs of decreased pulmonary compliance, but could still be adequately oxygenated and ventilated. Surgical correction was performed after stabilization and all required patch closures. Two of the three infants suffered no life-threatening episodes of pulmonary hypertension and all survived. These infants had many known indicators for poor outcome in CDH with an expected survival of less than 20%. We believe that EST in these neonates with CDH contributed to their survival with minimum morbidity. These results suggest that surfactant replacement for the high-risk neonate with CDH warrants further consideration and a randomized clinical trial is being planned.

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.

Marfan's syndrome, pregnancy, and the cardiac surgeon.

Marfan's syndrome in a pregnant woman appears to be particularly hazardous because of the increased risk of aortic rupture. The first reported case report of replacement of the ascending aorta in a pregnant woman with a successful outcome for mother and fetus is presented. The literature is reviewed with regard to Marfan's syndrome and pregnancy as well as to open heart surgery during pregnancy.

The abused woman and her family of origin.

The abuse of women in significant heterosexual relationships is an important societal problem in the United States. Structural family therapy offers a useful perspective to nurse therapists working with abused women who have left the abusive relationship to rejoin their families of origin. Common errors are avoided if the abused woman and her family are diagnosed within the system's context of structural family therapy. Dysfunctional transactional patterns that originated in the abused woman's childhood or adolescent years can be challenged at their source.

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.

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.

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.

Immunologic tolerance in rats during 13 weeks of inhalation exposure to trimellitic anhydride.

Trimellitic anhydride (TMA) causes several immunologically based pulmonary syndromes in humans. We developed a rat model representative of some of those syndromes whereby rats exposed for 2 weeks to TMA by inhalation developed hemorrhagic lung foci and pneumonitis accompanied by the appearance of TMA-specific serum antibody. The purpose of the study reported here was to examine the long-term, low-dose effects of TMA inhalation. Rats were exposed to target concentrations of 0, 2, 15, or 50 micrograms/m3 TMA 6 hr/day, 5 days/week for 13 weeks. The study included an interim 6.5-week termination and two recovery periods of 3 and 38 weeks, each with and without a final TMA inhalation challenge. Additional rats were bled regularly throughout the study and monitored for the appearance of TMA-specific antibody; other rats were terminated periodically during the 13-week exposure and examined for lung lesions. These serially terminated rats showed that TMA-induced lung lesions reached a maximum after approximately 2 weeks of exposure, but began to diminish thereafter. Rats bled regularly showed increasing TMA-specific antibody titers through the first 6 weeks of exposure, after which antibody titers diminished. Serum antibody levels rose sharply after the 13-week exposure ended and tapered off throughout the recovery period. Rats terminated after 6.5 weeks of exposure showed a dose-dependent increase in lung lesions and serum antibody. However, rats exposed to TMA for 13 weeks showed greatly reduced lung lesions and antibody titers. Rats exposed for 13 weeks and allowed to recover for 3 weeks showed increased antibody titers but few lesions, even after a TMA challenge. Rats exposed for 13 weeks and allowed to recover 38 weeks had reduced but still significant antibody titers; however, no lung lesions were noted even after a TMA inhalation challenge prior to termination. These results indicated that rats became tolerant to TMA and that 13 weeks of exposure to TMA did not produce lesions of any type, even after 38 weeks of recovery.

Perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome: a prospective, randomized, controlled study.

OBJECTIVE: To determine the efficacy of perfluorocarbon-associated gas exchange (partial liquid ventilation) in respiratory distress syndrome. DESIGN: Prospective, randomized, controlled study. SETTING: State University of New York at Buffalo, School of Medicine and Biomedical Sciences. SUBJECTS: Eleven premature lambs with respiratory distress syndrome, delivered by cesarean section. INTERVENTIONS: Five lambs were supported by conventional mechanical ventilation alone. Six lambs were switched to perfluorocarbon-associated gas exchange after 60 to 90 mins of conventional mechanical ventilation. Perfluorocarbon-associated gas exchange was accomplished by instilling a volume of liquid perfluorocarbon equivalent to normal functional residual capacity (30 mL/kg) into the trachea, performing 3 to 4 mins of tidal liquid ventilation, and, at end-expiration, with liquid functional residual capacity of 30 mL/kg remaining in the lung, reconnecting the animal to the volume ventilator for gas tidal volumes. MEASUREMENTS AND MAIN RESULTS: Serial arterial blood gases and lung mechanics were measured. While receiving conventional ventilation, all animals developed progressive hypoxemia, hypercarbia, and acidosis. However, in the perfluorocarbon-associated gas exchange group, within 5 mins of the initiation of perfluorocarbon-associated gas exchange, mean PaO2 increased four-fold, from 59 +/- 6 torr (7.9 +/- 0.8 kPa) during conventional ventilation to 250 +/- 28 torr (33.3 +/- 3.7 kPa; p < .05) during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (268 +/- 38 torr; 35.7 +/- 5.1 kPa; p < .05). Mean PaCO2 decreased progressively from 62 +/- 4 torr (8.3 +/- 0.5 kPa) during conventional ventilation to 38 +/- 3.3 torr (5.1 +/- 0.4 kPa) at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean pH concomitantly increased. Dynamic compliance increased three-fold within 15 mins of instituting perfluorocarbon-associated gas exchange, from 0.31 +/- 0.02 mL/cm H2O during conventional ventilation to 0.90 +/- 0.11 mL/cm H2O during perfluorocarbon-associated gas exchange, and this increase was sustained at 60 mins of perfluorocarbon-associated gas exchange (p < .05). Mean peak expiratory flow and mean expiratory resistance were essentially unchanged during perfluorocarbon-associated gas exchange as compared with conventional ventilation in the same group. CONCLUSIONS: We conclude that perfluorocarbon-associated gas exchange, which employs liquid functional residual capacity and gas tidal volumes delivered by a conventional ventilator, can facilitate oxygenation and CO2 removal, and dramatically improve lung mechanics in the premature lamb with respiratory distress syndrome.

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.

Reducing the number of rabbits in the Draize eye irritancy test: a statistical analysis of 155 studies conducted over 6 years.

The Draize eye irritancy test in rabbits has been the focus of recent efforts to reduce the use of live animals in toxicity testing. A suitable alternative is not yet available; therefore, we studied the adequacy of reducing the number of rabbits used per test. Data generated from 6-rabbit eye irritation tests of 155 various materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from six rabbits. There are 930, 2325, 3100, and 2325 possible combinations of 155 studies for the 5-, 4-, 3-, and 2-rabbit subsets, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score. Comparisons indicated that 5-, 4-, 3-, and 2-rabbit scores were in 98, 96, 94, and 91% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2-rabbit scores versus the Draize score for six rabbits were 0.998, 0.996, 0.992, and 0.984, respectively. This study confirms the findings of an earlier report by De Sousa et al. (1984), and indicates that a high level of accuracy can be obtained with reduced numbers of rabbits per test.