Dose:    Not established

Frequency: Not established

Comments: Oxygenated perfluorochemical liquids (PFCs) are clear, colorless, odorless liquids that are very stable and can be stored at room temperature indefinitely. Generally insoluble in water or lipids, they are excellent solvents for oxygen, carbon dioxide, and most gases but are poor solvents for almost everything else in biologic systems. PFCs are uniquely efficient carriers of oxygen and carbon dioxide. Almost all PFC liquids have low surface tension and evaporate rapidly at body temperature. Almost all PFC liquids are chemically and biologically inert, are ingested by macrophages, and leave the body almost entirely by means of volatilization in the lung or transpiration through the skin (Radiology 1995; 194:717). PFCs have been used as contrast agents in radiology. Perfluorocarbons have the consistency and appearance of water. Once instillation of PFC into the lung is stopped, the radiopacity of the lungs slowly decreases, both from volatilization and from suctioning. Although the concentration of PFC in expired gas in neonates is known to decrease exponentially to within control range within 8 hours, some of the PFC can be seen on CXRs several weeks after a single instillation. PFCs have been shown to reduce surface tension in the alveoli, improve distribution of pulmonary blood flow, and support physiologic gas exchange in premature surfactant deficient animals (Tutuncu. Am Rev Respir Dis 1993; 148:785). One technique that was developed consisted of filling the lung (an amount equal to the functional residual capacity) with perfluorocarbon and using a conventional ventilator to deliver tidal volumes.

    Leach (J Pediatr 1995; 126:412) used the above approach in studying preterm lambs whose respiratory disease was unresponsive to conventional ventilation. Survival was markedly increased in lambs who were treated with perflubron whether or not they had received exogenous surfactant (Exosurf). Greenspan (J Pediatr 1990; 117:106 reported on total liquid ventilation in three extremely premature infants in whom conventional ventilation had failed. All three died shortly after starting liquid ventilation, though pulmonary mechanics improved. Gross (Radiology 1995; 194:717) used liquid ventilation along with conventional ventilatory support in two infants who were not improving on ECMO. They each received a single infusion of perfluorochemical liquid. One infant survived; the other improved transiently but was taken off of ECMO at 30 days.

    Gauger (Crit Care Med 1996; 24:16) treated six pediatric patients (8 weeks to 5 1/2 years of age) on ECMO. After reintubation with a compatible ET tube, perflubron was administered in 2.5 to 5 ml/kg were administered over 5 to 15 minutes. This was repeated every 15 to 30 minute intervals until the functional residual capacity was filled. Redosing occurred on a daily basis for 3 to 7 days in the 6 infants. All infants were able to be weaned from ECMO and survived to discharge. There were no evidence of adverse effects from the partial liquid ventilation though two of the patients developed pneumothoraces. Hirschl (Hot Topics ‘95 in Neonatology, page 223) reported on their initial experience in liquid ventilation in adults, children, and neonates. All of the patients tolerated administration of perflubron without evident hemodynamic compromise. The dose was 2.5 to 10 ml/kg aliquots given every 30 minutes until a sustained meniscus was noted to be present in the ET tube at the level of the sternum. During the period of PLV, pneumothoraces re-accumulated in 6 of 19 patients and primary pneumothoraces occurred 3 patients. Mucus plug formation that interfered with gas exchange occurred in one patient. Fourteen of the nineteen patients survived. Gas exchange appeared to be improved by a number of mechanisms. The PFCs appear to enhance recruitment of atelectatic lung regions, especially in the dependent zones of the lungs where atelectasis is most severe. In addition, pulmonary blood flow may simultaneously be redistributed to non-dependent zones due to the weight of the perfluorocarbon within the lungs. As such, ventilation/perfusion matching is enhanced. Exudate in the peripheral airways and alveoli is effectively lavaged to the central airway, from whence it may be removed via suctioning. Finally, Wolfson (Pediatr 1996; 97:449) showed that vasoactive substances (acetylcholine, epinephrine, and Priscoline) can be effectively delivered to the lung directly during perfluorochemical liquid ventilation.

Toxicity: In the few limited studies of perfluorochemical liquids, there were no adverse effects noted from the PFCs. Hirschl (Hot Topics ‘95 in Neonatology, page 223) reported the occurrence of pneumothoraces and pulmonary hemorrhages in infants being treated with partial liquid ventilation. The long-term toxicities of perflubron remain unknown. following liquid ventilation in animals, some species have shown a transient mild deterioration in pulmonary mechanics after return to gas breathing. Surface tension has been shown to be somewhat increased possibly as a result of the presence of residual perfluorochemicals in the lung. Histologic evaluation of prematurely delivered animals ventilated with perfluorochemicals and recovered to a respirator demonstrated decreased hyaline membrane formation, reduced injury to airway epithelium and distal air spaces, and clearance of alveolar debris. Lung ultrastructure appears to remain intact following liquid breathing. In longer term evaluations, dogs have had no changes on either light or electron microscopic examinations (except for a slight increase in the number of alveolar macrophages), and adult monkeys have had normal pulmonary function for as long as 3 years after treatment. Little perfluorochemical is absorbed by the pulmonary circulation during therapy, although small amounts may remain stored in fat cells for years after liquid breathing [Spitzer et al. Special Ventilatory Techniques II: Liquid Ventilation, Nitric Oxide Therapy, and Negative Pressure Ventilation. In Goldsmith and Karotkin (eds) Assisted Ventilation of the Neonate. Philadelphia: W. B. Saunders Company, 1996, page 230].

Preparation: Perflubron (Liquivent) is not commercially available