Perflubron Distribution During Transition From Gas to Total Liquid Ventilation

Total liquid ventilation (TLV) using perfluorocarbons has shown promising results for the management of neonatal respiratory distress. However, one important safety consideration for TLV is a better understanding of the early events during the transition to TLV, especially regarding the fate of residual air in the non-dependent-lung regions. Our objective was to assess perflubron distribution during transition to TLV using electrical impedance tomography, complemented by fluoroscopy, in a neonatal lamb model of induced surfactant deficiency. Eight lambs were anesthetized and ventilated in supine position. Surfactant deficit was induced by saline lung lavage. After deflation, lungs were filled with 25 ml/kg perflubron over 18 s, and TLV was initiated. Electrical impedance tomography data was recorded from electrodes placed around the chest, during the first 10 and at 120 min of TLV. Lung perfusion was also assessed using hypertonic saline injection during apnea. In addition, fluoroscopic sequences were recorded during initial lung filling with perfluorocarbons, then at 10 and 60 min of TLV. Twelve lambs were used as controls for histological comparisons. Transition to TLV involved a short period of increased total lung volume (p = 0.01) secondary to recruitment of the dependent lung regions. Histological analysis shows that TLV was protective of these same regions when compared to gas-ventilated lambs (p = 0.03). The non-dependent lung regions filled with perflubron over at least 10 min, without showing signs of overdistention. Tidal volume distribution was more homogenous in TLV than during the preceding gas ventilation. Perflubron filling was associated with a non-significant increase in the anterior distribution of the blood perfusion signal, from 46 ± 17% to 53 ± 6% (p = 0.4). However, combined to the effects on ventilation, TLV had an instantaneous effect on ventilation-perfusion relationship (p = 0.03), suggesting better coupling. Conclusion: transition to TLV requires at least 10 min, and involves air evacuation or dissolution in perflubron, dependent lung recruitment and rapid ventilation-perfusion coupling modifications. During that time interval, the total lung volume transiently increases. Considering the potential deleterious effect of high lung volumes, one must manage this transition phase with care and, we suggest using a real-time monitoring system such as electrical impedance tomography

Assessing the impacts of total liquid ventilation on left ventricular diastolic function in a model of neonatal respiratory distress syndrome.

Filling the lung with dense liquid perfluorocarbons during total liquid ventilation (TLV) might compress the myocardium, a plausible explanation for the instability occasionally reported with this technique. Our objective is to assess the impacts of TLV on the cardiovascular system, particularly left ventricular diastolic function, in an ovine model of neonatal respiratory distress syndrome.Eight newborns lambs, 3.0 ± 0.4 days (3.2 ± 0.3kg) were used in this crossover experimental study. Animals were intubated, anesthetized and paralyzed. Catheters were inserted in the femoral and pulmonary arteries. A high-fidelity pressure catheter was inserted into the left ventricle. Surfactant deficiency was induced by repeated lung lavages with normal saline. TLV was then conducted for 2 hours using a liquid ventilator prototype. Thoracic echocardiography and cardiac output assessment by thermodilution were performed before and during TLV.Left ventricular end diastolic pressure (LVEDP) (9.3 ± 2.1 vs. 9.2 ± 2.4mmHg, p = 0.89) and dimension (1.90 ± 0.09 vs. 1.86 ± 0.12cm, p = 0.72), negative dP/dt (-2589 ± 691 vs. -3115 ± 866mmHg/s, p = 0.50) and cardiac output (436 ± 28 vs. 481 ± 59ml/kg/min, p = 0.26) were not affected by TLV initiation. Left ventricular relaxation time constant (tau) slightly increased from 21.5 ± 3.3 to 24.9 ± 3.7ms (p = 0.03). Mean arterial systemic (48 ± 6 vs. 53 ± 7mmHg, p = 0.38) and pulmonary pressures (31.3 ± 2.5 vs. 30.4 ± 2.3mmHg, p = 0.61) were stable. As expected, the inspiratory phase of liquid cycling exhibited a small but significant effect on most variables (i.e. central venous pressure +2.6 ± 0.5mmHg, p = 0.001; LVEDP +1.18 ± 0.12mmHg, p<0.001).TLV was well tolerated in our neonatal lamb model of severe respiratory distress syndrome and had limited impact on left ventricle diastolic function when compared to conventional mechanical ventilation

The INOLIVENT-6 liquid ventilator prototype.

<p>The inspiratory pump (Insp. Pump) delivers the tidal inspiratory volume of perflubron into the lungs. The expiratory pump (Exp. Pump) removes the tidal expiratory volume of perflubron from the lungs. The pressure sensor located at the mouth (P. sensor mouth) is used to limit the driving inspiratory and expiratory pressures and to monitor the pause pressure. P. sensor airway was previously used in the past to characterize the pressure drop although is no longer used.</p

Impact of total liquid ventilation on left ventricle diastolic function.

<p>A. Negative dP/d<i>t</i>; B. Left ventricular end diastolic pressure; C. Left ventricular end diastolic dimension; D. Left ventricular relaxation time constant (tau). ^ap < 0.05.</p

Hemodynamic impact of perflubron cycling.

<p>A. central venous pressure; B. Left ventricular end diastolic pressure; C. Negative dP/d<i>t</i>; D. Left ventricular relaxation time constant (tau); E. Mean systemic arterial pressure; F. Mean pulmonary arterial pressure.</p

Pressure and flow during total liquid ventilation, measured upstream of the endotracheal tube.

<p>The pressure generated by the ventilator, while fluid is instilled into the lungs, is identified by the letter "a" on the upper panel. As the movement of PFC stops ("b" at end inspiration and "c" at end expiration), pressure oscillates around a value that can be extrapolated [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191885#pone.0191885.ref018" target="_blank">18</a>]. These values, called pause pressures, are the alveolar pressures at end inspiration and end expiration.</p