The impact of kangaroo mother care on work of breathing and oxygen saturation in very low birth weight infants with respiratory insufficiency.

BACKGROUND: Kangaroo mother care (KMC) is defined as prolonged skin to skin care between a mother and infant with the infant lying in prone position on mom's chest. KMC decreases morbidity and mortality and promotes physiologic stability. The aim of this study is to measure work of breathing (WOB) during KMC in very low birth weight (VLBW) infants on non-invasive respiratory support. METHODS: A prospective observational pilot study was conducted comparing WOB indices during standard care (SC) and KMC. Respiratory inductive plethysmography (RIP) measured WOB indices non-invasively: phase angle and labored breathing index. VLBW infants who were stable on non-invasive respiratory support were randomized to receive RIP measurements during KMC or during SC first. Summary statistics and mixed linear models were used to compare WOB and vital signs. RESULTS: A total of 32 infants were consented for the study, data collection and analysis was completed on 28 infants. There were no significant differences in mean phase angle during KMC or SC (73.5±4.6 SE deg vs 66.8±3.9 SE deg, p = 0.25). No differences in WOB and vital signs were detected. Controlling for respiratory support or randomization/first location did not change the results. CONCLUSION: In this pilot cohort, infants demonstrated no differences in work of breathing indices or oxygen saturation during KMC or SC while receiving non-invasive respiratory support. KMC appears to be safe and well tolerated with no worsened WOB. Larger studies should be performed to confirm our findings.

Effects of xenon gas on human airway epithelial cells during hyperoxia and hypothermia.

BACKGROUND: Hypothermia with xenon gas has been used to reduce brain injury and disability rate after perinatal hypoxia-ischemia. We evaluated xenon gas therapy effects in an in vitro model with or without hypothermia on cultured human airway epithelial cells (Calu-3). METHODS: Calu-3 monolayers were grown at an air-liquid interface and exposed to one of the following conditions: 1) 21% FiO2 at 37°C (control); 2) 45% FiO2 and 50% xenon at 37°C; 3) 21% FiO2 and 50% xenon at 32°C; 4) 45% FiO2 and 50% xenon at 32°C for 24 hours. Transepithelial resistance (TER) measurements were performed and apical surface fluids were collected and assayed for total protein, IL-6, and IL-8. Three monolayers were used for immunofluorescence localization of zonula occludens-1 (ZO-1). The data were analyzed by one-way ANOVA. RESULTS: TER decreased at 24 hours in all treatment groups. Xenon with hyperoxia and hypothermia resulted in greatest decrease in TER compared with other groups. Immunofluorescence localization of ZO-1 (XY) showed reduced density of ZO-1 rings and incomplete ring-like staining in the 45% FiO2- 50% xenon group at 32°C compared with other groups. Secretion of total protein was not different among groups. Secretion of IL-6 in 21% FiO2 with xenon group at 32°C was less than that of the control group. The secretion of IL-8 in 45% FiO2 with xenon at 32°C was greater than that of other groups. CONCLUSION: Hyperoxia and hypothermia result in detrimental epithelial cell function and inflammation over 24-hour exposure. Xenon gas did not affect cell function or reduce inflammation.

High flow nasal heliox improves work of breathing and attenuates lung injury in a newborn porcine lung injury model.

BACKGROUND: High flow nasal cannula (HFNC) has been shown to improve ventilation and oxygenation and reduce work of breathing in newborns with respiratory distress. Heliox, decreases resistance to airflow, reduces the work of breathing, facilitates the distribution of inspired gas, and has been shown to attenuate lung inflammation during the treatment of acute lung injury. HYPOTHESIS: Heliox delivered by HFNC will decrease resistive load, decrease work of breathing, improve ventilation and attenuate lung inflammation during spontaneous breathing following acute lung injury in the newborn pig. METHODS: Spontaneously breathing neonatal pigs received Nitrox or Heliox by HFNC and studied over 4 hrs following oleic acid injury. Gas exchange, pulmonary mechanics and systemic inflammation were measured serially. Lung inflammation biomarkers were assessed at termination. RESULTS: Heliox breathing animals demonstrated lower work of breathing reflected by lower tracheal pressure, phase angle and phase relationship. Ventilation efficiency index was greater compared to Nitrox. Heliox group showed less lung inflammation reflected by lower tissue interleukin-6 and 8. CONCLUSION: High flow nasal Heliox decreased respiratory load, reduced resistive work of breathing indices and attenuated lung inflammatory profile while ventilation was supported at less pressure effort in the presence of acute lung injury.

Work of breathing indices in infants with respiratory insufficiency receiving high-flow nasal cannula and nasal continuous positive airway pressure.

OBJECTIVE: To compare work of breathing (WOB) indices between two nCPAP settings and two levels of HFNC in a crossover study. STUDY DESIGN: Infants with a CGA 28-40 weeks, baseline of HFNC 3-5 lpm or nCPAP 5-6 cmH2O and fraction of inspired oxygen ≤40% were eligible. WOB was analyzed using respiratory inductive plethysmography (RIP) for each of the four modalities: HFNC 3 and 5 lpm, nCPAP 5 and 6 cmH2O. N=20; Study weight 1516 g (±40 g). RESULT: Approximately 12,000 breaths were analyzed indicating a high degree of asynchronous breathing and elevated WOB indices at all four levels of support. Phase angle values (means) (P<0.01): HFNC 3 lpm (114.7°), HFNC 5 lpm (96.7°), nCPAP 5 cmH2O (87.2°), nCPAP 6 cmH2O (80.5°). The mean phase relation of total breath (PhRTB) (means) (P<0.01): HFNC 3 lpm (63.2%), HFNC 5 lpm (55.3%), nCPAP 5 cmH2O (49.3%), nCPAP 6 cmH2O (48.0%). The relative labored breathing index (LBI) (means) (P≤0.001): HFNC 3 lpm (1.39), HFNC 5 lpm (1.31), nCPAP 5 cmH2O (1.29), nCPAP 6 cmH2O (1.26). Eighty-two percent of the study subjects-respiratory mode combinations displayed clustering, in which a proportion of breaths either occurred predominantly out-of-phase (relative asynchrony) or in-phase (relative synchrony). CONCLUSION: In this study, WOB indices were statistically different, yet clinically similar in that they were elevated with respect to normal values. These infants with mild-to-moderate respiratory insufficiency demonstrate a meaningful elevation in WOB indices and continue to require non-invasive respiratory support. Patient variability exists with regard to biphasic clustered breathing patterns and the level of supplemental fraction of inspired oxygen ≤40% alone does not provide guidance to the optimal matching of WOB indices and non-invasive respiratory support.

Cold perfluorochemical-induced hypothermia protects lung integrity in normal rabbits.

To test the hypothesis that intrapulmonary perfluorochemical (PFC) liquid may induce hypothermia, and to compare the effects of internal (IC), external (EC), and combined cooling techniques (EC + IC), 14 juvenile rabbits were randomized to EC by a cold blanket (4 degrees C, n = 5), IC by intrapulmonary cold PFC liquid lavage (4 degrees C, n = 5), or combined IC with PFC and EC (n = 4). Arterial blood gas, blood pressure, and lung mechanics were monitored, and lung histology was examined by light microscopy. The results showed that cooling rates and the time needed to be cooled down to 30 degrees C were significantly faster in EC and EC + IC than IC (p < 0.05). Blood gas analysis and cardiopulmonary function were within the normal range in all groups. Histological assessment revealed varied atelectasis in all lung regions in EC, whereas PFC-filled lungs (IC and EC + IC) demonstrated more homogenous expansion and no evidence of atelectasis. The results indicate that intrapulmonary PFC may be an effective technique to induce and/or augment hypothermia while supporting gas exchange, lung volume and pulmonary architecture.

Feasibility of lung cancer hyperthermia using breathable perfluorochemical (PFC) liquids. Part I: Convective hyperthermia.

Clinical studies have shown that hyperthermia in combination with radiotherapy and/or chemotherapy may be effective in the treatment of advanced cancer. No method of lung hyperthermia, however, has been accepted as standard or superior. This investigation sought to demonstrate in animals the thermal and physiologic feasibility of lung hyperthermia induced using heated breathable perfluorochemical (PFC) liquids, a method termed liquid-filled lung convective hyperthermia (LCHT). The ability to use LCHT is rooted in the development of both PFC liquid ventilation, now in clinical development with the PFC perflubron (LiquiVent), and a PFC blood substitute also in late Phase III trials (Oxygent). As LCHT background, the PFC technologies and biology are first reviewed. The physical properties of a variety of PFCs were evaluated for LCHT and it was concluded that more than one liquid is suitable based on such properties. Using total liquid ventilation type devices, LCHT was shown to deliver successfully localized (lobar) lung heating in sheep, and bilateral whole lung heating and whole-body hyperthermia in rabbits, cats and lambs. During LCHT, lung parenchymal temperatures were uniform (<1 degree C) across heated regions. In addition, based on patterns relating lung tissue temperatures to inspiratory and expiratory PFC liquid temperatures in the endotracheal tube, LCHT may minimize invasive thermometry requirements in the lung. Based on acute experiments, it was concluded that LCHT appears feasible and may simplify lung hyperthermia. It was recommended that potentially synergistic combinations of LCHT with other whole-body hyperthermia or local heating modalities, and with chemotherapeutic lung drug delivery, also be explored in the future.

Feasibility of lung cancer hyperthermia using breathable perfluorochemical (PFC) liquids. Part II: Ultrasound hyperthermia.

Enhanced local control of disease in lung cancer has been shown to improve survival, and controlled clinical trials of hyperthermia adjunctive to radiotherapy in other cancers have shown improved disease control and survival over radiotherapy alone. The challenge of lung hyperthermia, however, persists. This investigation sought to demonstrate the feasibility of localized lung hyperthermia at depth via therapeutic ultrasound. The method is based on using breathable perfluorochemical liquids as acoustic coupling media in the lung, liquids that have also been shown to enable controlled liquid-filled lung convective hyperthermia (LCHT). The ability to use both lung convective hyperthermia and liquid-filled lung ultrasound hyperthermia (LUHT) provides potential flexibility in heating patterns for the hyperthermic treatment of lung cancer with concurrent radiotherapy and/or chemotherapy. Using custom ultrasound transducers designed and built for these studies, the acoustic properties of three candidate perfluorochemicals were characterized over a range of temperatures, gas contents and ultrasound frequencies and acoustic intensities. Both sound speed and attenuation were measured in the neat liquids and in isolated lungs filled with the perfluorochemicals. Successful ultrasound hyperthermia at depth was demonstrated in vivo in sheep lung lobes in intraoperative conditions. In addition, the use of ultrasound diagnostic imaging was explored as a tool for use in conjunction with lung ultrasound hyperthermia.

Positive end-expiratory pressure modulates perfluorochemical evaporation from the lungs.

To study the effects of positive end-expiratory pressure (PEEP) level on perfluorochemical (PFC) elimination profiles (E(L)), 6 ml/kg of perflubron were instilled into healthy anesthetized rabbits. The ventilation strategy was to maintain constant minute ventilation (300 ml/kg/min) and mean airway pressure (7-8 cm H(2)O) while randomly changing the PEEP levels from 5 to 0, 1, 3, and 10 cm H(2)O, each for a period of 15 min. The PFC content in the expired gas was measured and the E(L) was calculated. There was a significant reduction in the E(L) when decreasing the PEEP levels from 5 to 0 cm H(2)O, but no differences were seen when the PEEP was increased from 5 to 10 cm H(2)O. The results indicate that PEEP levels influence PFC elimination profiles; therefore, the measurement of the E(L) and PEEP levels should be considered when optimizing supplemental PFCs during partial liquid ventilation.

Perfluorochemical liquids do not stimulate endothelin-1 or nitric oxide production in human blood leukocytes.

The purpose of these studies was to examine if perfluorochemical (PFC) liquids stimulate blood leukocytes to secrete nitric oxide (NO) and/or endothelin-1 (ET-1). As such, NO and ET-1 may modulate broncho- and vascular dilatation and constriction, respectively, and thereby influence the clinical condition of a patient in respiratory distress with persistent pulmonary hypertension. Blood leukocytes in their natural habitat (whole blood) were incubated in the presence of two different perfluorochemicals (perflubron and perfluorodecalin). The overall response in ET-1 or NO (indirectly measured as nitrite/nitrate) production was examined at increasing PFC percentages (wt/vol) of PFC/whole blood. The lowest proportion used, 0.001% (wt/vol), was relevant to serum concentrations of PFC observed in liquid-ventilated individuals, whereas the highest proportion PFC, 50% (wt/vol), would mimic a situation where leukocytes are presented to PFC-filled airways. Plasma levels of freshly drawn blood, similar to levels of incubated (6 h) non-PFC-supplemented cultures, were ET-1 0.59 +/- 0.07 pg/ml (6 h, mean +/- SEM) and NO(-2)/NO(-3) 50 +/- 9 microM (6 h). Perflubron or perfluorodecalin did not induce significant differences in ET-1 or NO(-2)/NO(-3) levels as function of PFC type or dose. In conclusion, PFC liquids do not stimulate production in leukocytes in vitro of substances that may modulate constriction or dilatation in the vascular and respiratory tract systems.

Temperature and heater responses during transition between radiant and incubator thermal environment in newborn preterm lambs.

OBJECTIVE: Although both incubators and radiant warmer beds can provide thermal support to infants in the neonatal intensive care unit, the transition between devices can be a stressful event. The goal of this study was to evaluate a new device that combines these methods of warming and converts between them without requiring physical movement of the infant. STUDY DESIGN: Twin preterm lambs received thermal support from a radiant warmer bed and an incubator (control), or from the Versalet 7700 Care Center (treatment) in the warmer and incubator configurations. Temperature of each lamb, as well as device heater power, were monitored every 2 min before, during, and after the transition. Physiological parameters were monitored every 15 min. RESULTS: There was a significant difference in response time between closed-open and open-closed conditions for both groups. More adverse events occurred in the control group during transfers. There were no differences in temperatures or physiological variables during transitions in either group. CONCLUSIONS: These data suggest the Versalet provides similar thermal stability to traditional devices, with fewer adverse events associated with the lack of physical movement between warming configurations. The impact of this device on the care of the preterm neonate will be evaluated in a clinical trial.

Perfluorochemical liquids modulate cell-mediated inflammatory responses.

OBJECTIVE: To examine whether chemically different perfluorochemical liquids (PFC) (perfluorodecalin [PFD]; perflubron [PFB]) induce inflammatory responses in blood leukocytes. SETTING: University research laboratory. DESIGN: Whole blood from 12 healthy adults was incubated with increasing PFC concentrations and/or bacterial lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: Adhesion molecules (CD62L, CD11b), reactive oxygen species, and cytokine responses in resting and activated leukocyte subtypes were studied. Scanning and transmission electron microscopies were performed. At the highest concentrations, PFB stimulated a significant increase in resting monocytic reactive oxygen species production; all types of blood leukocytes were unresponsive to PFD. Neither PFB nor PFD changed CD62L expression; PFB increased CD11b expression in monocytes and granulocytes. PFD induced a small though significant increase in interleukin-8 secretion. When simulating a condition in which patients with severe lung disease or sepsis would be ventilated with PFC, neither PFB nor PFD plus lipopolysaccharide stimulated tumor necrosis-alpha or interleukin-8 production above levels induced by lipopolysaccharide alone, but rather demonstrated a trend for decreased tumor necrosis factor-alpha production. Expression of CD11b and CD62L and the production of reactive oxygen species were not changed beyond the levels induced by lipopolysaccharide alone. As a morphologic correlate to the above proinflammatory changes, surface-bound blebs and intracellular vacuoles were seen by electron microscopy. CONCLUSIONS: At PFC concentrations comparable with those in blood during liquid ventilation, PFC liquids did not induce variables associated with inflammation. In the presence of high PFC concentrations, simulating the condition in which bronchoalveolar cells are exposed to PFC, monocytes may be induced by PFB to produce reactive oxygen species, and blood leukocytes induced by PFB to express CD11b and by PFD to secrete interleukin-8; the presence of either PFC attenuated tumor necrosis factor-alpha production after lipopolysaccharide stimulation.

Thermal stability and transition studies with a hybrid warming device for neonates.

OBJECTIVE: The use of both warmer beds and incubators is common in neonatal intensive care units (NICU), and transferring between these two warming devices is a routine and necessary event. This study was designed to evaluate the efficacy of a new hybrid-warming device, the Versalet, in transitioning a preterm animal from a warmer bed to an incubator mode and back. STUDY DESIGN: Nine premature lambs were randomized, following delivery, to receive thermal support from a conventional warming bed and an incubator (control group), or from the Versalet (study group) in the warmer bed and incubator modes. Core and various surface temperatures, as well as physiological parameters were measured first during warming in the radiant warmer bed mode, Versalet or Resuscitaire and then during transition to the incubator mode, Versalet or Isolette, and then back to the warmer bed mode. RESULTS: The animals remained stable during all the transitions. Despite careful planning, adverse events occurred in the control group during transfers. There were no significant differences in the temperature or physiologic profiles during any of the transitions in either group. CONCLUSION: Compared with the standard warming technique used in NICUs (separate warmer bed and incubator), the Versalet provides similar thermal and cardiovascular stability without adverse events during transition to different modes of warming. The degree to which this device would contribute to ease of management and improved outcomes in humans needs to be evaluated in a clinical trial.

A comparison of surfactant delivery with conventional mechanical ventilation and partial liquid ventilation in meconium aspiration injury.

The objective of this study was to compare surfactant (SF) distribution and physiological effects after standard SF delivery during conventional mechanical ventilation (CMV) with that using partial liquid ventilation (PLV). A model of meconium aspiration syndrome (MAS) was developed using two groups of adult rats (n = 14). After meconium instillation of 2.5 ml kg(-1) (20% v/w), SF/CMV: (n = 7) CMV and SF/PLV: (n = 7) PLV, received 14C-labeled surfactant (4 ml kg(-1)) delivered intratracheally in four aliquots over 20 min in both groups. Sequential measurements of arterial blood chemistry and lung mechanics were performed in all animals. At the conclusion of experiments, lungs were inflated (30 cmH2O), dried, sectioned and evaluated for radioactivity in disintegrations per minute (DPM). Surfactant distribution was improved (P< 0.01) with PLV as compared to CMV with 48.8% of the pieces vs. 30.9% of the pieces receiving within 25% of the mean amount of surfactant, respectively. Further, regional distribution was also significantly more uniform with PLV than CMV: left vs right (P<0.01) lung and ventral vs. dorsal (P<0.01) regions. Finally, arterial PO2 and ventilation efficiency index were significantly (P<0.01) greater post-treatment in SF/PLV than SF/CMV. These data demonstrate surfactant delivery with PLV, as compared to CMV alone, to be an improved method of delivering surfactant in MAS and suggest the possible utility of SF/PLV combination therapy for its treatment of other etiologies of neonatal respiratory distress.

Intratracheal administration of perfluorochemical-gentamicin suspension: a comparison to intravenous administration in normal and injured lungs.

Respiratory infections can lead to acute lung injury and perfusion abnormalities. We hypothesized that intratracheal (IT) administration of a perfluorochemical (PFC) gentamicin (G) suspension as compared to intravenous (IV) administration of gentamicin will result in higher lung tissue levels of gentamicin, while maintaining safe serum levels. To test this hypothesis, 21 lambs with normal and acid injured lungs were studied for 4 hr, using 2 different drug delivery methods, IT and IV. Lungs were injured with warm HCl acid in saline lavage, followed by partial liquid ventilation with perflubron (bolus FRC = 20 mL/kg). G at a dose of 5 mg/kg was delivered either IT (G-PFC; 20 mL/kg) or IV (aqueous injection with IT 20 mL/kg PFC alone). Throughout the study, serum G levels, arterial blood gases, respiratory system compliance, and mean arterial blood pressure were measured. Lung tissue G levels were measured at 4 hr and averaged across lobes. Physiologic gas exchange and pulmonary function were maintained throughout the protocol for both the normal and injured lungs. Intravenously administered G resulted in an initial 5-min serum concentration of 43 +/- 2.5 mcg/mL, followed by an exponential decline over the 4-hr protocol to a level of 2.1 +/- 0.23 mcg/mL at hr 4. The intratracheally administered G suspension resulted in a 5-min serum concentration of 1.8 +/- 0.98 mcg/mL and remained relatively constant throughout the protocol, with a 4-hr level of 1.6 +/- 0.29 mcg/mL. With respect to lung tissue G levels, IT administration was significantly more effective in delivering the drug to the normal lungs than IV (31.4 +/- 3.3 mcg/g vs. 4.0 +/- 0.7 mcg/g) 4 hr after administration. In the lung injury group, there was a small but significant difference in lung tissue G levels, with the IT-administered perfluorochemical-G suspension achieving greater levels than the IV-administered G (11.9 +/- 0.52 mcg/g vs. 10.1 +/- 0.8 mcg/g). Additionally, the drug delivered IV and IT in both the normal and injured lung models was homogeneously distributed throughout the lung. These data show that G lung tissue levels in both normal and injured lungs were higher in the IT group when compared to IV administration. The results of this study demonstrate that in normal and injured lungs, homogeneous G lung tissue levels can be more effectively achieved at lower serum levels when delivered IT in a G-PFC suspension as compared to IV administration.

Role of ventilation strategy on perfluorochemical evaporation from the lungs.

To study the effect of ventilation strategy on perfluorochemical (PFC) elimination profile (evaporative loss profile; E(L)), 6 ml/kg of perflubron were instilled into anesthetized normal rabbits. The strategy was to maintain minute ventilation (VE, in ml/min) in three groups: VE(L) (low-range VE, 208 +/- 2), VE(M) (midrange VE, 250 +/- 9), and VE(H) (high-range VE, 293 +/- 1) over 4 h. In three other groups, respiratory rate (RR, breaths/min) was controlled at 20, 30, or 50 with a constant VE and adjusted tidal volume. PFC content in the expired gas was measured, and E(L) was calculated. There was a significant VE- and time-dependent effect on E(L.) Initially, percent PFC saturation and loss rate decreased in the VE(H) > VE(M) > VE(L) groups, but by 3 h the lower percent PFC saturation resulted in a loss rate such that VE(H) < VE(M) < VE(L) at 4 h. For the groups at constant VE, there was a significant time effect on E(L) but no RR effect. In conclusion, E(L) profile is dependent on VE with little effect of the RR-tidal volume combination. Thus measurement of E(L) and VE should be considered for the replacement dosing schemes during partial liquid ventilation.

Effects of perfluorochemical distribution and elimination dynamics on cardiopulmonary function.

Based on a physicochemical property profile, we tested the hypothesis that different perfluorochemical (PFC) liquids may have distinct effects on intrapulmonary PFC distribution, lung function, and PFC elimination kinetics during partial liquid ventilation (PLV). Young rabbits were studied in five groups [healthy, PLV with perflubron (PFB) or with perfluorodecalin (DEC); saline lavage injury and conventional mechanical ventilation (CMV); saline lavage injury PLV with PFB or with DEC]. Arterial blood chemistry, respiratory compliance (Cr), quantitative computed tomography of PFC distribution, and PFC loss rate were assessed for 4 h. Initial distribution of PFB was more homogenous than that of DEC; over time, PFB redistributed to dependent regions whereas DEC distribution was relatively constant. PFC loss rate decreased over time in all groups, was higher with DEC than PFB, and was lower with injury. In healthy animals, arterial PO(2) (Pa(O(2))) and Cr decreased with either PFC; the decrease was greater and sustained with DEC. Lavaged animals treated with either PFC demonstrated increased Pa(O(2)), which was sustained with PFB but deteriorated with DEC. Lavaged animals treated with PFB demonstrated increased Cr, higher Pa(O(2)), and lower arterial PCO(2) than with CMV or PLV with DEC. The results indicate that 1) initial distribution and subsequent intrapulmonary redistribution of PFC are related to PFC properties; 2) PFC distribution influences PFC elimination, gas exchange, and Cr; and 3) PFC elimination, gas exchange, and Cr are influenced by PFC properties and lung condition.

Meconium aspiration injury: Uncoupling between the in vivo physiologic and in vitro inflammatory responses.

OBJECTIVE: To correlate the in vivo physiologic changes that occur with meconium aspiration injury to an associated in vitro cellular response to meconium. DESIGN: Experimental, prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Eighteen adult Sprague-Dawley rats with meconium aspiration injury. INTERVENTIONS: Rats were given 3 mL/kg of a 25% meconium solution and were treated with conventional gas ventilation; nine rats were given exogenous surfactant therapy (Survanta, 4 mL/kg), and nine rats were not treated (control). Bronchoalveolar lavages were collected for total cell counts. Histologic samples also were taken for analysis. In addition, the in vitro effect of meconium on granulocytic elastase release from human neutrophils was determined. MEASUREMENTS AND MAIN RESULTS: Meconium caused significant morbidity in vivo, including poor oxygenation, elevated Paco(2), diminished compliance, and elevated white cell count in the bronchial lavages. Lung white cell count was significantly less in the surfactant group (p <.01). Meconium did not cause elastase release from human neutrophils in vitro. CONCLUSIONS: This study demonstrated uncoupling between in vivo physiologic responses to meconium injury in rats and the in vitro effect of meconium on human neutrophils. Surfactant therapy alleviated some of the perturbations associated with meconium injury, including a reduction in the inflammatory cell count in lung lavages. The absence of direct neutrophil activation by meconium suggests the requirement of an intermediary in the pathogenesis of meconium aspiration injury.

A perfluorochemical loss/restoration (L/R) system for tidal liquid ventilation.

Tidal liquid ventilation is the transport of dissolved respiratory gases via volume exchange of perfluorochemical (PFC) liquid to and from the PFC-filled lung. All gas-liquid surface tension is eliminated, increasing compliance and providing lung protection due to lower inflation pressures. Tidal liquid ventilation is achieved by cycling fluid from a reservoir to and from the lung by a ventilator. Current approaches are microprocessor-based with feedback control. During inspiration, warmed oxygenated PFC liquid is pumped from a fluid reservoir/gas exchanger into the lung. PFC fluid is conserved by condensing (60-80% efficiency) vapor in the expired gas. A feedback-control system was developed to automatically replace PFC lost due to condenser inefficiency. This loss/restoration (L/R) system consists of a PFC-vapor thermal detector (+/- 2.5%), pneumatics, amplifiers, a gas flow detector (+/- 1%), a PFC pump (+/- 5%), and a controller. Gravimetric studies of perflubron loss from a flask due to evaporation were compared with experimental L/R results and found to be within +/- 1.4%. In addition, when L/R studies were conducted with a previously reported liquid ventilation system over a four-hour period, the L/R system maintained system perflubron volume to within +/- 1% of prime volume and 11.5% of replacement volume, and the difference between experimental PFC loss and that of the L/R system was 1.8 mL/hr. These studies suggest that the PFC L/R system may have significant economic (appropriate dosing for PFC loss) as well as physiologic (maintenance of PFC inventory in the lungs and liquid ventilator) impact on liquid ventilation procedures.

Perfluorochemical elimination from the lungs: effect of initial dose.

Liquid-assisted ventilation with perfluorochemical (PFC) has been beneficial in a variety of respiratory diseases in animals and humans. Although PFC evaporation from the lungs is in part dependent on ventilation strategy and positioning, guidelines for initial and replacement dosing are unclear. We hypothesized that PFC evaporative loss over time is dependent on the size of the initial dose. Juvenile rabbits (n = 18) were ventilated using constant animal position and ventilator strategy. PFC (perflubron: LiquiVent ) was instilled endotracheally, using four groups with initial doses of 2, 6, 12, and 17 mL/kg. A previously described thermal detector that measures PFC in expired gas was used to calculate loss rate, residual perflubron in the lung, and volume loss as a % of initial fill volume. There was a significant dose, time, and dose-time interaction such that evaporative loss was dependent on initial PFC volume and time after fill (P < 0.05). Evaporative loss rate decreased earlier at lower doses. The percentage of initial volume lost to evaporation over time was inversely related to dose and could not be predicted by decreasing % PFC saturations, independent of dose. Evaporative loss should be considered to optimize both the application of PFC to the lung and replacement dosing during partial liquid ventilation.

Effects of partial liquid ventilation with perfluorodecalin in the juvenile rabbit lung after saline injury.

OBJECTIVE: To evaluate the feasibility of using the perfluorochemical, perfluorodecalin, for partial liquid ventilation (PLV) with respect to gas exchange and lung mechanics in normal and saline-injured lungs of juvenile rabbits. DESIGN: Experimental, prospective, randomized, controlled study. SETTING: Physiology laboratory at a university medical school. SUBJECTS: Seventeen juvenile rabbits assigned to three groups. INTERVENTIONS: The conventional mechanical ventilation (CMV)-injury group (n = 5) was treated with CMV after establishing a lung injury; the PLV-injury group (n = 6) was treated with PLV after lung injury; and the PLV-healthy group (n = 6) was supported with PLV without lung injury. Lung injury was created by repeated saline lung lavages. PLV-treated animals received a single dose of intratracheal perfluorodecalin at a volume equal to the measured preinjury gas functional residual capacity (functional residual capacity = 18.6+/-1.5 [SEM] mL/kg). MEASUREMENTS AND MAIN RESULTS: Sequential measurements of total respiratory compliance and arterial blood chemistries were performed in all groups. Oxygenation index (OI) and ventilation efficiency index were calculated. After lung injury, there was a significant (p < .05) decrease in PaO2, total respiratory compliance, and ventilation efficiency index and an increase in OI and PaCO2. In the PLV-injury group, PLV significantly (p < .05) improved PaO2 (+60%) and OI (-33%) over time. Compliance was significantly (p < .05) higher (90%) than in the CMV-injury group over time. CONCLUSIONS: These results demonstrate that PLV with perfluorodecalin improved oxygenation and increased respiratory compliance in the saline-injured rabbit lung. In addition, similar to the effects of several other perfluorochemical liquids on normal lungs, pulmonary administration of perfluorodecalin was associated with a small impairment in gas exchange and a significant decrease in lung compliance in the juvenile rabbit model.