The Science Journal of the American Association for Respiratory Care

Original Contributions

January 2002 / Volume 47 / Number 1 / Page 39

Evaluation of Work of Breathing in Spontaneously Breathing Animals During Partial Liquid Ventilation

Mark J Heulitt MD FAARC, Shirley J Holt RRT, Tracy L Thurman, Sterling Wilson MS, and Pippa Simpson PhD

BACKGROUND: Partial liquid ventilation improves lung mechanics and gas exchange in paralyzed mechanically ventilated animals. OBJECTIVE: Examine the work of breathing (WOB) in a spontaneously breathing animal model during partial liquid ventilation with and without the use of pressure-support ventilation (PSV). METHODS: This was a prospective study including 6 lambs (mean weight 10.9 ± 1.3 kg). Baseline measurements, including total work of breathing (WOBT), elastic work of breathing (WOBE), and resistive work of breathing (WOBR), were obtained using pressure-controlled synchronized intermittent mandatory ventilation with positive end-expiratory pressure of 5 cm H2O at PSV levels of 0, 5, and 10 cm H2O. The animals' lungs were filled with perflubron through an endotracheal tube, in 10-20 mL aliquots, until filled, approximately 30 mL/kg or functional residual capacity. Repeat measurements were obtained at 10 mL/kg, 20 mL/kg, and full. Perflubron was then allowed to evaporate from the lungs and repeat measurements were obtained 3 additional times, with at least a 1 hour separation between phases, for up to 7 hours after the lungs were filled. RESULTS: No differences were detected in WOBT, WOBR, or WOBE between the gas-filled lung and the lung filled to functional residual capacity with perflubron. However, compared to the gas-filled lung, WOBT and WOBR> were higher during the filling (p < 0.05) and evaporative phases (p < 0.05). The PSV level affected WOB. Work of breathing was least at PSV 10 cm H2O. CONCLUSION: In this pilot study of healthy animals breathing spontaneously with perflubron-filled lungs, there was an acceptable amount of WOB, which decreased with the addition of PSV. However, WOB increased when the perflubron level was not maintained at functional residual capacity.
Key words: artificial ventilation, positive-pressure ventilation, inspiratory work, work of breathing, perflubron, positive end-expiratory pressure, liquid ventilation.
[Respir Care 2002;47(1):39-47]


Partial liquid ventilation (PLV) with perflubron is intended as an adjunct to conventional mechanical ventilation in patients with acute respiratory distress syndrome and neonates with surfactant deficiency. It uses the combination of gas delivery (via a conventional mechanical ventilator) and perflubron-filled lungs. Perflubron is a biochemically inert perfluorochemical that has a low surface tension, a positive spreading coefficient, and a high solubility for oxygen and carbon dioxide. Numerous animal studies using lung disease models have shown that PLV can improve gas exchange and lung mechanics such as pulmonary compliance.

Promising Phase I data have been published for the use of PLV in premature infants, and studies have been undertaken in both pediatric and adult patients with acute respiratory distress syndrome. Recently these studies have been completed, although questions persist concerning the ideal method for using mechanical ventilation during PLV. During the pediatric trial, patients were maintained on chemically induced paralysis for the duration of PLV treatment. However, during the adult trial, patients were allowed to breathe spontaneously during PLV. There are potential disadvantages to the use of neuromuscular blockade during mechanical ventilation, including prolonged muscle weakness, increased costs, reduced cardiac output and blood pressure, and lower functional residual capacity (FRC). Allowing patients to breathe spontaneously during PLV was discouraged during the pediatric trial because of a lack of data on PLV's effect on work of breathing (WOB). These concerns were based on the potential that WOB might be increased because of an increase in lung density during PLV. Also there may be concern about the patient's ability to trigger the ventilator across the liquid-gas interface during PLV. In contrast, there may be potential benefits from allowing the patient to breathe spontaneously during PLV. Previous studies with controlled mechanical ventilation found that neonatal patients breathing spontaneously in a patient-triggered mode (as compared to a non-patient-triggered mode) showed better gas exchange and needed a lower level of mechanical support. In addition, studies of neonates suggest that the use of patient-triggered ventilation increases the delivery of tidal volume (VT), shortens the length of mechanical ventilation, and decreases WOB by improving patient-ventilator synchrony.

Few data are available on the use of perflubron in spontaneously breathing animals or spontaneous ventilation during PLV in mechanically ventilated animals. No studies are available on the effects of pressure-support ventilation (PSV) during PLV in those animals.

To achieve normal ventilation, the body performs work, known as WOB, to overcome the elastic and frictional resistance of the lungs and chest wall. Total WOB (WOBT) is composed of the elastic work of breathing (WOBE) and the resistive work of breathing (WOBR). Elastic WOB represents physiologic work that includes the work to expand the lungs and chest wall. Resistive WOB is considered a measure of imposed WOB and includes work caused by the breathing apparatus, such as the endotracheal tube (ETT), the breathing circuit, and the ventilator's demand-flow system. The objective of this pilot study was to examine WOB in a spontaneously breathing animal model during PLV with and without the use of PSV.

The entire text of this article is available in the printed version of the January 2002 RESPIRATORY CARE.

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