Carla M. Weis

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.

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 (ρ) and viscosity (μ) of these fluids. Knowledge of the effect of ρ, μ, 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.

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.

SELECTIVE PULMONARY VASODILATION AND PULMONARY DISTRIBUTION OF RADIOLABELED HISTAMINE DURING LIQUID VENTILATION (LV) IN HYPOXIC NEWBORN (NB) LAMBS|[dagger]| 2336

Histamine (H) is a selective pulmonary vasodilator in the fetus and NB. During total LV (TLV), significant decreases in pulmonary artery pressure(Ppa) without systemic effects have been reported during hypoxia-induced pulmonary hypertension following intravenous (IV) and pulmonary administration of drug (PAD) delivering equal doses of H, however during partial liquid ventilation (PLV) there were no PAD effects. To test the hypothesis that differences in the homogeneity of drug distribution within the lung contribute to the differences in PAD effects of H during PLV compared to TLV, we compared both the pulmonary and systemic vascular effects and the pulmonary distribution of H following PAD delivery of 0.05 μg/kg as 0.5cc/kg bolus at the beginning of inspiration during PLV and TLV. NB lambs (n=14) were studied(2.5-5.0 kg) during hypoxia (PaO2:20-35 mm Hg) during both PLV and TLV, using a perfluorochemical (PFC) (LiquiVent®). Ppa and systemic arterial pressure (SAP) were continuously monitored; physiologic pH and normocarbia were maintained. Radiolabeled (3H) histamine was delivered to randomly selected animals in a supine position using PAD delivery during TLV and PLV. Lungs were hung and dried with continuous distending pressure of 30 cm H2O and sectioned using a standardized matrix method; samples were weighed, digested and radioactivity counted. Pulmonary distribution was assessed by normalizing the radioactivity of each piece (per dry weight) to the average radioactivity of all pieces in ratio form (uniform distribution resulting in a value of one for each piece) and all ratios were expressed in histogram form. During TLV, PAD H decreased Ppa significantly (p<0.02) and SAP did not change. During PLV, PAD H did not change Ppa or SAP. Representative distribution data using PAD during TLV resulted in 48% of pieces having ratio values between 0.8-1.2. Using PAD during PLV resulted in 14% of samples having ratio values between 0.8-1.2. We conclude that PAD delivery of H during TLV is an effective way of achieving pulmonary selective decreases in vascular pressure, due in part to more homogeneous distribution within the lung. We speculate that alternative techniques for drug delivery with liquid ventilation, such as creating a suitable emulsion of drug in PFC liquid for delivery with the initial fill of the lung, may allow improved pulmonary distribution of drug during both PLV and TLV. (Supp in part by Alliance Pharm Comp and Wyeth Pharm)

Does Dead Space Increase During Perfluorochemical (PFC) Partial Liquid Ventilation (PLV)? 1975

Does Dead Space Increase During Perfluorochemical (PFC) Partial Liquid Ventilation (PLV)? 1975