The Science Journal of the American Association for Respiratory Care

1998 OPEN FORUM Abstracts

Submersion in the ICU: Partial Liquid Ventilation

Jana Stockwell

Perfluorocarbons are colorless, odorless and inert liquids. Perflubron (LiquiVent(tm), Alliance Pharmaceutical Corp., San Diego, CA) is a perfluorocarbon which is denser than water, evaporates quickly and is radio-opaque. Though liquids do not mix with perflubron, it is unique in its ability to dissolve gases, such as oxygen and carbon dioxide. Medical application of perfluorocarbons was reported in 1966 by Clark & Gollan. In 1990, Greenspan reported the first human application of this technology when 3 preterm, moribund neonates had gas exchange supported by tidal ventilation using a warmed, preoxygenated perfluorocarbon. Subsequently, Fuhrman reported an alternative method of supporting gas exchange utilizing partial liquid ventilation.

Total liquid ventilation (TLV) involves completely filling the lungs with a tidal volume of LiquiVent(tm), then allowing the fluid to drain out by gravity before the next "breath" is instilled. This method, although effective in terms of gas exchange, is quite labor intensive and requires specially designed experimental ventilators. In contrast, partial liquid ventilation (PLV) involves filling the lungs to FRC (~15-30 cc/kg), then ventilating the patient conventionally, using standard ventilators and common modes of gas ventilation.

Preliminary data utilizing PLV in patients revealed that lung-injured animals had improved oxygenation and A-aDO_{2} gradients, without compromising hemodynamic function or suffering exposure effects. Early human studies involved patients already on ECMO for life support. Patients received LiquiVent(tm) for 3-7 days. These patients demonstrated improvement in PaO_{2}, A-aDO_{2} and static lung compliance.

During PLV, the patient's lungs are filled to Functional Residual Capacity (FRC). This is accomplished by dribbling the LiquiVent(tm) down the endotracheal tube (ETT) passively while the patient continues being conventionally ventilated. FRC is reached when, at end-expiration, a meniscus (air-fluid level) is observed in the ETT. When a mechanical breath is given, the meniscus disappears, as fluid is pushed into the expanding lungs, then reappears as gas is exhaled. Every few hours, ~2mL/kg of LiquiVent(tm) is added, as the liquid rapidly evaporates. Radiographically, the lungs appear opaque. Defects in filling are related to plugged airways.

In 1995, Alliance Pharmaceutical established a Phase 2/3, randomized, controlled trial of PLV in children with ARDS or acute lung injury. To qualify, a child had to have bilateral pulmonary infiltrates, be mechanically ventilated, with FiO_{2} >0.50 and PEEP >6 x 12 hours. Patients exited the protocol based upon changes in the A-aDO_{2} gradient, and could then proceed to other therapies (ECMO, surfactant, iNO, etc.). Patients in both groups were ventilated using pressure control mode and permissive hypercapnia was allowed. Endpoints included: PaO_{2}/FiO_{2} ratio, A-aDO_{2} gradient and Oxygenation Index (OI). After interim study evaluation, the primary endpoint was changed to "ventilator-free days". Another interim analysis led to a change in the primary endpoint to 28-day all-case mortality.

In 1997, mortality in the conventionally ventilated group was 14% and 22% in the PLV group. Due to this unexpected improvement in control group mortality, the study was suspended after enrollment of 182 subjects (91 in each group). With a lower than expected mortality rate in the conventional group, the study would need to enroll vastly more patients to demonstrate a significant effect. No deaths were related to LiquiVent(tm). Adverse events were similar in both groups. PLV is safe in children with acute lung disease. LiquiVent(tm) will be utilized in several upcoming studies involving adults, term infants, and children on high frequency oscillatory ventilation.

(See Original for Figure)

The 44th International Respiratory Congress Abstracts-On-DiskĀ®, November 7 - 10, 1998, Atlanta, Georgia.

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