In partial liquid ventilation (PLV) the lungs are partially filled with plerfluorocarbon (PFC) and ventilation is provided with a standard mechanical ventilator. PFC is a clear inert liquid that improves gas exchange by recruiting dependent lung regions, clearing retained secretions and its antiinflammatory properties. In animal models PLV has been shown to decrease lung injury and improve gas exchange in acute lung injury compared to conventional mechanical ventilation (CMV).
A study recently published in the April 15, 2006 issue of The American Journal of Respiratory and Critical Care Medicine compared PLV to CMV in adult patients with acute respiratory distress syndrome (ARDS). From December 1998 to December 2000, 311 patients with ARDS and persistent hypoxemia from 56 centers were enrolled in the study. The patients were randomly assigned to three groups, a control group, low-dose PLV and high-dose PLV.
The control group received CMV with no PFC, the low-dose group had their lungs filled with PFC to the carina in the supine position and the high-dose group had their lungs filled with PFC to a level 5 cm below the incisors. PFC filling was done by instilling two separate aliquots of 5m/kg predicted bodyweight into the lungs. In the low-dose group a "suction catheter check" was performed by inserting a suction catheter to the carina while the patient was on zero PEEP and suctioned. If PFC was suctioned then suctioning continued till PFC was no longer present. If PFC was not suctioned then aliquots were re-administered and suction catheter checks done until PFC was suctioned. Supplemental dosing was provided every 3 hours and a suction catheter check performed every 6 hours. In the control group, sham suctioning checks were mandated every 3 hours and suctioning only occurred if necessary.
All groups had standardized ventilator settings:
- volume control
- VT of 10 ml/kg or less
- rate of ≤ 25/minI:E = 1:1
- FiO2 of ≥ 0.5
- PEEP of ≥ 13 cmH2O
PEEP was maintained at 13 cmH2O or higher in the dosing groups until dosing was stopped. When patients had a PEEP ≤ 8 cmH20 and FiO2 ≤ 0.5 they were weaned using spontaneous breathing trials.
At 24 and 72 hours, the CMV group had lower plateau pressure, peak pressure, mean airway pressure, respiratory rate, FiO2, total PEEP and PaCO2 and also had a higher PaO2/FiO2 ratio and pH than both of the PLV groups. At 168 hours the mean airway pressure was higher and the PaO2/FiO2 lower in the CMV group than the low-dose PLV group. Also at 168 hours the minute ventilation and total PEEP were higher in the high-dose PLV group than in the CMV group. The CMV group had more ventilator-free days than both PLV groups. Resolution of ARDS/ALI was significantly faster in the CMV group than the low-dose PLV group. The percentage of patients alive and off the ventilator at 28 days was greater in the CMV group than in the low-dose PLV group. Time to unassisted ventilation was shorter in the CMV group than in the low-dose PLV group. There was no statistical difference in mortality but it did trend lower in the CMV group.
When it came to safety, there were more episodes of pneumothorax, hypoxia and hypotension in the PLV groups. Most of these episodes occurred within the first 5 days and were related to the delivery of PFCs.
So it appears that at both low and high doses of PFCs, PLV does not improve outcome or the number of ventilator free days in this study. There was also a greater number of adverse reactions with PLV than CMV. This is somewhat disappointing.
Regardless of the outcome of this study a few interesting comments can be made. The patients in the PLV groups had to be disconnected form the ventilator every 3 hours for redosing or PFC level check and this most likely caused derecruitment of alveoli. Also many of the PLV patients required heavy sedation and paralysis which may have affected their weaning time and length on the ventilator. This study occurred between 1998 and 2000 and patients were ventilated with an average tidal volume of 9 ml/kg PBW while since the ARDSnet study in 2000 we know that 6 ml/kg is ideal in ARDS. Would low tidal volume ventilation made a difference? The mortality rate of the CMV group was 15% which is the lowest of any randomized control trial of mechanical ventilation in ARDS. This is no definitive reason for this but it may be due to the fact that patients enrolled had fewer organ failures, persistent ARDS (>48 h) and were younger in age (<65) then other trials.
Although animal studies involving PLV and ARDS have been promising this study of adults with ARDS was not, which means there is still more we need to learn. Future studies may need to look at specific populations of patients, different ventilation modalities (low-tidal volume or maybe high-frequency ventilation) or maybe even different doses of PFCs than those studied here. For now, PLV is not indicated in patients with ARDS over CMV.
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Kacmarek RM, Wiedemann HP, Lavin PT, Wedel MK, Tutuncu AS, Slutsky AS. Partial liquid ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2006 Apr 15;173(8):882-9.
Filed under: ARDS
