Liquid breathing:Medical applications

Medical treatment

• The most promising area for the use of liquid ventilation is in the field of pediatric medicine. The first medical use of liquid breathing was treatment of premature babies and adults with acute respiratory distress syndrome (ARDS) in the 1990s. Liquid breathing was used in clinical trials after the development by Alliance Pharmaceuticals of the fluorochemical perfluorooctyl bromide, or perflubron for short. Current methods of positive-pressure ventilation can contribute to the development of lung disease in pre-term neonates, leading to diseases such as bronchopulmonary dysplasia. Liquid ventilation removes many of the high pressure gradients responsible for this damage. Furthermore, Perfluorocarbons have been demonstrated to reduce lung inflammation, improve ventilation-perfusion mismatch and to provide a novel route for the pulmonary administration of drugs. Clinical trials with premature infants, children and adults were conducted. Since the safety of the procedure and the effectiveness were apparent from an early stage, the US Food and Drug Administration (FDA) gave the product "fast track" status (meaning an accelerated review of the product, designed to get it to the public as quickly as is safely possible) due to its life-saving potential. Clinical trials showed that using perflubron with ordinary ventilators improved outcomes as much as using high frequency oscillating ventilation (HFOV).

• In 1996 Mike Darwin and Dr. Steven B. Harris proposed using cold liquid ventilation with perfluorocarbon to quickly lower the body temperature of victims of cardiac arrest and other brain trauma to allow the brain to better recover. The technology was shown to achieve a cooling rate of 0.5 degrees Celsius per minute in large animals. Most recently, hypothermic brain protection has been associated with rapid brain cooling. In this regard, a new therapeutic approach is the use of intranasal perfluorochemical spray for preferential brain cooling. The nasopharyngeal (NP) approach is unique for brain cooling due to anatomic proximity to the cerebral circulation and arteries. Based on preclinical studies in adult sheep, it was shown that independent of region, brain cooling was faster during NP-perfluorochemical versus conventional whole body cooling with cooling blankets. Preliminary phase I clinical trials are ongoing using this new therapeutic procedure.

• Mild hypothermia during myocardial ischemia is very cardioprotective, but clinical application has been impaired by the lack of methodology to quickly cool the heart. In a study, Total liquid ventilation (TLV) with cooled perfluorocarbon immediately after onset of 30 min of coronary artery occlusion in open-chest rabbits showed that the hearts were cooled to 32°C within 5 min with minimal hemodynamic effect. Cooling decreased infarct size from 42% of the risk zone in control animals to 4%. Neither cooling during reperfusion nor TLV with warm perfluorocarbon was protective. Total liquid ventilation could be an effective adjunct to reperfusion therapy.

• Cardiopulmonary bypass may cause lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. In a study the effect of total liquid ventilation on lung injury in piglets after cardiopulmonary bypass was investigated. After exposure to 60 minutes of cardiac arrest and weaning from cardiopulmonary bypass, 12 piglets were randomly treated with conventional gas ventilation (control group) or total liquid ventilation (study group) for 240 minutes. Samples for blood gas analysis were collected before, and at 30-minute intervals after, cardiopulmonary bypass. The degree of lung injury was quantified by histologic examination. The inflammatory cells and the levels of interleukin-6, interleukin-8, and myeloperoxidase in bronchoalveolar lavage were analyzed. Total liquid ventilation reduces biochemical and histologic lung injury in piglets after cardiopulmonary bypass.

• End-expiratory lung volume and static compliance are increased significantly following attempted reexpansion with total liquid ventilation when compared with gas ventilation in normal and surfactant-deficient, atelectatic lungs. The ability of total liquid ventilation to enhance recruitment of atelectatic lung regions may be an important means by which gas exchange is improved during total liquid ventilation when compared with gas ventilation in the setting of respiratory failure.

References

1. Wolfson et al. Multicenter comparative study of conventional mechanical gas ventilation to tidal liquid ventilation in oleic acid injured sheep 54(3):236-269, 2008.
2. Cox CA, Stavis RL. Wolfson MR, Shaffer TH: Long-term tidal liquid ventilation in premature lambs: Physiologic, biochemical and histological correlates. Biol. Neonate 84:232-242, 2003.
3. "A significant positive step was the use of PFC-associated gas exchange, now termed partial liquid ventilation (PLV)." Hlastala, Michael P. and Jennifer E. Souders (July 1, 2001). "Perfluorocarbon Enhanced Gas Exchange".American Journal of Respiratory and Critical Care Medicine164 (1): 1–2.
4. JACC, Volume 49, Issue 5, Pages 601-605 (6 February 2007).
5. Critical care medicine 1996, vol. 24, pp. 268-273.
6. "Aerosolized perfluorocarbon improved pulmonary gas exchange and lung mechanics as effectively as PLV did in surfactant-depleted piglets, and the improvement was sustained longer." Kandler, Michael A. et al. (July 1, 2001). "Persistent Improvement of Gas Exchange and Lung Mechanics by Aerosolized Perfluorocarbon". American Journal of Respiratory and Critical Care Medicine 164 (1): 31–35.