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.

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.

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.

Current status of liquid ventilation.

Perfluorochemical liquid has been used experimentally to enhance mechanical ventilation for the past 30 years. Liquid ventilation is one of the most extensively studied revolutionary medical therapies being considered for use in practice. Since 1989, when the first human neonates were treated with perfluorochemical liquid, more than 500 human patients--neonate, pediatric, and adult--have been treated with liquid ventilation as part of clinical trials. However, most of the clinically relevant information known to the medical field about liquid ventilation still comes from the laboratory. This paper seeks to briefly present current information available from studies involving liquid ventilation, both laboratory-based and clinical trials, as well as to inform the reader on patient management. In addition, we attempt to elucidate future directions.

Comparison of perfluorochemical fluids used for liquid ventilation: effect of endotracheal tube flow resistance.

Neonatal endotracheal tubes with small inner diameters are associated with increased resistance regardless of the medium used for assisted ventilation. During liquid ventilation (LV) reduced interfacial tension and pressure drop along the airways result in lower alveolar inflation pressure compared with gas ventilation (GV). This is possible by optimizing liquid ventilation strategies to overcome the resistive forces associated with liquid density (rho) and viscosity (mu) of these fluids. Knowledge of the effect of rho, mu, and endotracheal tube (ETT) size on resistance is essential to optimize LV strategies. To evaluate these physical properties, three perfluorochemical (PFC) fluids with a range of kinematic viscosities (FC-75 = 0.82, LiquiVent = 1.10, APF-140 = 2.90) and four different neonatal ETT tubes (Mallincrokdt Hi-Lo Jet ID 2.5, 3.0, 3.5, and 4.0 mm) were studied. Under steady-state flow, flow and pressure drop across the ETTs were measured simultaneously. Resistance was calculated by dividing pressure drop by flow, and both pressure-flow and resistance-flow relationships were plotted. Also, pressure drop and resistance were each plotted as a function of kinematic viscosity at flows of 0.01 L.s-1 for all four ETT sizes. Data demonstrated a quadratic relationship with respect to pressure drop versus flow, and a linear relationship with resistance versus flow: both were significantly correlated (R = 0.92; P < 0.01) and were inversely related to ETT size. Additionally, there was a significant correlation between pressure drop or resistance and kinematic viscosity (R = 0.99; P < 0.01). For LV in neonates these data can be used to select the optimum ETT size and PFC liquid depending OR the chosen ventilation strategy.

Pulmonary administration of gentamicin during liquid ventilation in a newborn lamb lung injury model.

OBJECTIVES: Newborns with pulmonary infection frequently present with acute lung injury leading to ventilation/perfusion abnormalities in which intravenous delivery of antibiotics to the lung can be suboptimal. Tidal liquid ventilation (TLV) has been shown to be an effective means for delivering drugs directly to the pulmonary system. The objective of this study was to compare, with lung injury, antibiotic delivery achieved by conventional techniques (gas ventilation and intravenous gentamicin) with that using pulmonary administration of drug (PAD) during TLV. METHODS: Twelve newborn lambs with an acid lung injury were randomized to receive gentamicin either intravenously during gas ventilation or via PAD during TLV using LiquiVent (Alliance Pharmaceutical Corporation, San Diego, CA, and Hoechst-Marion Roussel, Bridgewater, NJ) perfluorochemical. Gentamicin (5 mg/kg) was administered over 1 minute, and serum levels were obtained at 15-minute intervals. Arterial blood gases and pulmonary mechanics were measured. Ventilation efficiency index and arterial/alveolar oxygen ratio were calculated. Lung-tissue gentamicin levels were measured 4 hours after administration and corrected to dry weight. RESULTS: Serum gentamicin levels were similar in both groups. Lung gentamicin levels (micrograms/g) were significantly higher for TLV. Also, TLV resulted in significantly more of the total delivered dose in the lung after 4 hours. Ventilation efficiency index and arterial/alveolar oxygen ratios were significantly higher for TLV. CONCLUSIONS: In this lung injury model, both methods achieved equivalent serum gentamicin levels with higher lung levels using PAD during TLV. This study suggests that TLV may provide an effective vehicle for gentamicin delivery in infants with severe pulmonary infection and ventilation/perfusion abnormalities.

Liquid-assisted ventilation: physiology and clinical application.

Liquid-assisted ventilation, as an alternative ventilation strategy for respiratory distress, is progressing from theory and basic science research to clinical application. Biochemically inert perfluorochemical liquids have low surface tension and high solubility for respiratory gases. From early immersion experiments, two primary techniques for liquid-assisted ventilation have emerged: total liquid ventilation and partial liquid ventilation. While computer-controlled, time-cycled, pressure/volume-limited total liquid ventilators can take maximum advantage of these liquids by completely eliminating the gas phase in the distressed lung, partial liquid ventilation takes advantage of having these liquids in the lung while maintaining gas ventilation. The benefits of both partial and total techniques have been demonstrated in animal models of neonatal and adult respiratory distress syndrome, aspiration syndromes and congenital diaphragmatic hernia and also in combination with other therapeutic modalities including extracorporeal membrane oxygenation, high-frequency ventilation and nitric oxide. Additionally, nonrespiratory applications have expanding potential including pulmonary drug delivery and radiographic imaging. Since its use in neonates in 1989, liquid-assisted ventilation in humans has progressed to a variety of clinical experiences with different aetiologies of respiratory distress. The future holds the opportunity to clarify and optimize the potential of multiple clinical applications for liquid-assisted ventilation.