Investigators Patient
Population
Year Journal Study Results
Jay Greenspan
Thomas Shaffer
Marla Wolfson
David Rubenstein
Premature
infants
1989




1990
Lancet
2(8671):
p. 1095

Journal of
Pediatrics
117(1 Pt 1):
p. 106-11
Liquid ventilation was performed for two 3 to 5 minute cycles by means of gravity-assisted technique without difficulty in 3 moribund premature infants. Marked improvement in lung distensibility, without a change in cardiovascular status, occurred in all three infants after liquid ventilation
•  Oxygenation improved in two
•  No evidence of retained perfluorochemical fluid in the lungs or pleural space

Hirschl, R.B.
Pranikoff, T.
Gauger, P.
Schreiner, R. J.
Dechert, R.
Bartlett, R. H.
Adults
Children
Neonates
1995 Lancet
346(8984):
p. 1201-2
Safety and efficacy of partial  liquid ventilation was evaluated in a series of 19 adults, children, and
neonates who were in
respiratory failure and on
extracorporeal life support.
•  The alveolar-arterial oxygen difference decreased from 590 ± 25 to 471 ± 42 mm Hg (p <0.01)
•  Static  pulmonary compliance increased from 0.18 ± 0.04 to 0.29  ± 0.04 mL cm H2O/kg
(p <0.01).
•  11 patients (58%) survived.
Hirschl, R. B.
Pranikoff, T.
Wise, C.
Overbeck, M. C.
Gauger, P.
Schreiner, R. J.
Dechert, R.
Bartlett, R. H
Adults 1996 JAMA 275(5):
p. 383-9.
Evaluate the safety and efficacy of partial liquid ventilation in a consecutive sample of 10 patients aged 19 to 55 years with the acute respiratory distress syndrome who were receiving extracorporeal life support.
  Physiologic shunt decreased from a median of 0.72 (range, 0.37 to 1.0) to 0.46 (range, 0.21 to 0.96) over the 72 hours following initiation of PLV p 0.01 by repeated measures analysis of variance.
•  Static pulmonary compliance corrected for patient weight increased from a median of 0.16 mL/cm H2O per kg (range, 0.01 to 0.48 mL/cm H2O per kg) to 0.27 mL/cm H2O per kg (range, 0.05 to 1.11 mL/cm H2O per kilogram) over the same time period (p 0.04) by repeated measures analysis of variance.
•  Overall survival was five (50%) of 10 patients.
•  Complications that were potentially associated with PLV included pneumothorax development in one pat
ient and mucus plug formation in one patient.
•  It was concluded that Perflubron may be safely administered into the lungs of patients with severe respiratory failure receiving extracorporeal life support and may be associated with improvement in gas exchange and pulmonary compliance
Leach, C. L.
Greenspan, J. S.
Rubenstein, S. D.
Shaffer, T. H.
Wolfson, M. R.
Jackson, J. C.
DeLemos, R.
Fuhrman, B. P
The LiquiVent Study Group
Premature infants 1996 NEJM 335(11):
p. 761-767
The efficacy of partial liquid  ventilation with perflubron was studied in 13 premature infants
with severe respiratory distress syndrome in whom conventional  treatment, including surfactant therapy, had failed.
•  Ten infants received partial liquid  ventilation for 24 to 76 hours.
•  In three infants, partial liquid
ventilation was discontinued within four hours in favor of high frequency ventilation, which was not permitted by the protocol, and the data from these infants were excluded from the analysis.
•  Within one hour after the instillation of perflubron, the arterial oxygen tension increased by 138 percent
•  Dynamic compliance increased by 61 percent
•  The mean oxygenation index was reduced from 49 +/- 60 to 17 +/- 16.
•  Chest radiographs showed symmetric filling, with patchy clearing during the return from partial liquid to gas ventilation.
•  There were no adverse events clearly attributable to partial liquid ventilation.
•  Infants were weaned from partial liquid to gas ventilation without complications.
•  Eight infants survived to 36 weeks' corrected gestational age.
Greenspan, J.S,
Fox, W.W.
Rubenstein, S.D.
Wolfson, M.R.
Spinner, S.S.
Shaffer, T.H.
Philadelphia Liquid Ventilation Consortium
Term, and near term infants 1997 Pediatircs
99(1): p. E2
To demonstrate that a period of partial liquid ventilation with perflubron improves pulmonary function, without adverse events, in a select group of critically ill infants receiving extracorporeal life support with a high likelihood of mortality.
Open-label, noncontrolled, Phase I and II trial of PLV in two infants with congenital diaphragmatic hernia and four infants with acute respiratory distress syndrome who were failing to improve while receiving ECLS.
•  Four infants were successfully
weaned off ECLS for at least 3 days, and two infants (both with ARDS) are long-term survivors after PLV.
•  All infants demonstrated lung recruitment and improved lung compliance, and there were no adverse events related to PLV.
Fauza, D. O.
Hirschl, R. B.
Wilson, J. M.
Neonates   2001 Journal of
Pediatric Surgery
36(8):
p. 1237-40.
A preliminary clinical experience of neonatal lung growth that can be  accelerated by continuous intrapulmonary distension with a perfluorocarbon (PFC) in a select group of infants with congenital diaphragmatic hernia (CDH).
Neonates with very high predicted mortality rate caused by CDH had their lungs completely filled with PFC while on extracorporeal life support; (n = 5).
At the end of continuous pulmonary distension, all patients showed improvements in oxygenation and ventilation.
•  The ipsilateral lungs showed significant increase of the L/V index with time (p 0.003) and of L/V's daily change (p <.0001), suggesting accelerated lung growth.
•  Overall survival rate was 40% (2 of 5). Of the 3 patients that had 7 days of distension, 2 survived.
•  It was concluded that continuous intrapulmonary distension with PFC for up to 1 week accelerated ipsilateral lung growth, improved gas exchange, and increased survival of CDH infants with profound pulmonary hypoplasia marooned on ECLS.
•  Additional trials of PFC-based pulmonary distension in similar infants are warranted.
Hirschl, R. B
Philip, W. F.
Glick, L.
Greenspan, J.
Smith, K.
Thompson, A.
Wilson, J.
Adzick, N. S.
Neonates 2003 Journal of
Pediatric Surgery
38(3): p. 283-9; discussion 283-9.
A prospective, randomized pilot study evaluating PLV and perfluorocarbon-induced lung growth (PILG) in newborns with CDH on extracorporeal life support at 6 medical centers. •  A total of 13 patients were evaluated in this study.
•  All 3 patients enrolled without being on ECLS rapidly transitioned to ECLS.
•  The study, therefore, effectively evaluated PILG (n = 8) versus standard ventilation (control, n = 5) on ECLS.
• Mean (+/- SE) gestational age was 37 +/- 1 weeks and weight was 3.1 +/- 0.1 kg.
•  Time on ECMO was 9.8 +/- 2.3 days in the PILG and 14.5 +/- 3.5 days (p 0.58) in the control group.
•  Survival rate in the PILG group was 6 of 8 (75%), whereas survival rate was 2 of 5 (40%) in the control group (p 0.50).
•  The number of days free from the ventilator in the first 28 days was 6.3 +/- 3.3 days with PILG and 4.6 +/- 4.6 days with control (p 0.9).
•  Causes of death in the PILG group included sepsis and renal failure in one patient and pulmonary hypertension in the other.
•  There were no safety issues, and the deaths in the PILG group did not appear to be related to the administration of perflubron.
Walker, G.M.
Kasem, K.F.
O'Toole, S.J.
Watt, A.
Skeoch, C.H.
Davis, C.F.
Neonates 2003 Journal of Pediatric Surgery
38(1): p.17-20
.
A study measuring perfluorodecalin distension in neonates with severe CDH on extracorporeal membrane oxygenation support. •  Perfluorodecalin instillation started soon after starting ECMO support (mean, 13.5 +/- 5.3 hours).
•  The volume required to fill the lungs increased significantly (p <0.02).
•  The radiographic dimension of the affected lung increased significantly (mean percentage increase, 272%; p <0.02).
•  The contralateral lung dimension also increased (mean percentage increase 51%; p <0.02).
•  CDH repair was undertaken on ECMO in all cases.
•  All patients survived (follow-up, 3 to 42 months).
Migliori, C.
Bottino, R.
Angeli, A.
Cattarelli, D.
Chirico, G.
Neonates 2004 Journal of
Perinatology
2004. 24(2): p. 118-20
Two infants on high-frequency oscillatory ventilation for chronic lung disease and severe respiratory failure, received a bolus of warmed and oxygenated perfluorodecalin up to residual functional capacity, followed by a continuous infusion of 6 ml/kg/hour.
The aim  of the study was to improve gas exchange without increasing ventilatory-induced lung injury. 
•  Both patients showed improvement of gas exchange with a 13.6 and 12.5% reduction of oxygenation index, respectively.
•  High-frequency partial liquid ventilation is an experimental ventilation technique that could be considered as rescue treatment, to improve oxygenation in subjects with critical respiratory failure.
•  This method could probably produce less damage, than other ventilation modes, to severely injured lungs.
Kacmarek, R. M.
Wiedemann, H. P.
Lavin, P. T.
Wedel, M. K.
Tutuncu, A. S.
Slutsky, A. S.
Adults 2006 American
Journal of
Respiratory
and Critical
Care Med
173(8):
p. 882-9
To determine if PLV would have  an impact on outcome in patients with ARDS. Patients with ARDS were randomized to (1) conventional mechanical ventilation (CMV; n=107),
(2) "low-dose" perfluorocarbon (10 ml/kg; n=99),
(3) "high-dose" perfluorocarbon (20 ml/kg; n=105).
Patients in all three groups were ventilated using volume ventilation, Vt <10 ml/kg predicted body weight, rate < 25/min, inspiratory-to-expiratory ratio < 1:1, FiO2 > 0.5, and positive end-expiratory pressure >13 cm H2O
The 28-day mortality in the CMV group was
15%, versus 26.3% in the low-dose (p=0.06) and 19.1% in the high-dose (p=0.39) PLV groups.
•  There were more ventilator-free days in the CMV group (13.0+/-9.3) compared with
both the low-dose (7.4+/-8.5; p<0.001) and
high-dose (9.9+/-9.1; p=0.043) groups.
•  There were more pneumothoraces,
hypoxic episodes, and hypotensive episodes in the PLV patients.
 
Neonatal Liquid Ventilation