Why Partial Liquid Ventilation Did Not Fulfill Its Promise

With regard to the recent article byKacmarek and colleagues, we are in complete agreement on the absolute necessity of making public the results of negative trials (1). Discovering the reason(s) why randomized controlled trials did not confirm the information on which they were based can be highly instructive. Partial liquid ventilation (PLV), once introduced in the clinical arena, failed to live up to expectations. These disappointing results of a highly promising technique occurred in the context of major improvements in the outcome of control patients treated with conventional mechanical ventilation (CMV) utilizing a lung-protective strategy. Others have speculated that high-dose perfluorocarbon administration in the LiquiVent trial may have resulted in the socalled baby lung effect (2). We believe that the initial enthusiasm about PLV was based on a too hasty extrapolation from total liquid ventilation (TLV) data and on a poorly adapted study design used to investigate the effectiveness of PLV. In 1991, the scientific community welcomed PLV as a major technical simplification of TLV, and it was assumed that the new hybrid method would preserve all the obvious benefits of TLV. Gradually, however, we learned that the physiology of PLV is fairly complicated and definitely different from that of TLV. The lung-protective effect of PLV turned out to be less important than that associated with TLV. It took several years before the effect of perfluorocarbon liquid volume and the gas ventilation strategy to be used during PLV were investigated in depth. Strange to say, initially, most investigators used a study design adopted from surfactant research to assess PLV efficacy. In animals with respiratory failure, no attempt was made to adjust or optimize the ventilation settings. In a Medline (1966–December 2001) and personal file search, we identified 50 animal studies likely overestimating the benefits of PLV because the control groups were ventilated inadequately in terms of modern standards (3). As a consequence of inappropriate study design, much effort, time, and money have been wasted. When PLV was compared with other recruitment strategies, perfluorocarbons did not prove to be the golden bullet (4, 5), even after optimizing the gas ventilation strategy (6). We hope that PLV researchwill not be perceived as a frustrating misadventure to be forgotten as soon as possible, but rather as an instructive experience not bearing repetition.

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