Partial liquid ventilation for mechanical ventilation of severely ill children with acute lung injury and acute respiratory distress syndrome

The use of partial liquid ventilation to decrease the number of deaths and illness in children with acute onset respiratory failure is not supported by evidence from randomized controlled trials.

Severely ill children can develop lung disease, called acute lung injury or acute respiratory distress syndrome, which stops sufficient oxygenation of the blood. The children are treated with mechanical ventilation through a tube placed in the airway. This improves lung function and the supply of oxygen to the body but it can also lead to ventilator-induced lung injury. Children who survive an episode of this severe lung disease often have long-term illness including decreased lung function, impaired cognitive function, poor neurodevelopmental progress, and high rates of permanent disability.

Partial liquid ventilation could be a less injurious form of respiratory support. A special liquid (perfluorocarbon liquid) is poured into the lungs to partly replace the gas in the normally gas-filled lungs, and mechanical ventilation is continued with a gas ventilator.

We found only one multicentre randomized controlled study, reported as an abstract in conference proceedings, that was eligible for inclusion in this updated Cochrane review. The company sponsored study enrolled 182 patients in 65 centres. The trial was stopped early, before recruiting sufficient numbers of participants and before it could detect any clear differences between partial liquid ventilation and conventional mechanical ventilation (the control group). The number of deaths at 28 days was 22% of patients in the partial liquid ventilation group and 14% in the control group, the difference was not statistically significant; there was a wide variation in results and a clinically significant difference could not be excluded. There were other problems with the trial that made its results unreliable in terms of eligible patients, use of other rescue therapies, and that the measured outcomes were altered at least twice during the study; additional therapies such as high frequency ventilation or inhaled nitric oxide were allowed in the control group.

Authors' conclusions: 

There is no evidence from RCTs to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory distress syndrome. Adequately powered, high quality RCTs are still needed to assess its efficacy. Clinically relevant outcome measures should be assessed (mortality at discharge and later, duration of both respiratory support and hospital stay, and long-term neurodevelopmental outcomes). The studies should be published in full.

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Background: 

Acute lung injury and acute respiratory distress syndrome are syndromes of severe respiratory failure. Children with acute lung injury or acute respiratory distress syndrome have high mortality and the survivors have significant morbidity. Partial liquid ventilation is proposed as a less injurious form of respiratory support for these children. Uncontrolled studies in adults have shown improvements in gas exchange and lung compliance with partial liquid ventilation. A single uncontrolled study in six children with acute respiratory syndrome showed some improvement in gas exchange during three hours of partial liquid ventilation. This review was originally published in 2004, updated in 2009 and again in 2012.

Objectives: 

To assess whether partial liquid ventilation reduces mortality or morbidity, or both, in children with acute lung injury or acute respiratory distress syndrome.

Search strategy: 

In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 11); CINAHL (Cumulative Index to Nursing & Allied Health Literature) via Ovid (1982 to November 2011); Ovid MEDLINE (1950 to November 2011); and Ovid EMBASE (1982 to November 2011). The search was last performed in August 2008.

Selection criteria: 

We included randomized controlled trials (RCTs) which compared partial liquid ventilation with other forms of ventilation in children (aged 28 days to 18 years) with acute lung injury or acute respiratory distress syndrome. Trials had to report one or more of the following: mortality; duration of mechanical ventilation, respiratory support, oxygen therapy, stay in the intensive care unit, or stay in hospital; infection; long-term cognitive impairment, neurodevelopmental progress, or other long-term morbidities.

Data collection and analysis: 

We independently evaluated the quality of the relevant studies and extracted the data from the included studies.

Main results: 

Only one study enrolling 182 patients (reported as an abstract in conference proceedings) was identified and found eligible for inclusion; the authors reported only limited results. The trial was stopped prematurely and was, therefore, under-powered to detect any significant differences and at high risk of bias. The only available outcome of clinical significance was 28-day mortality. There was no statistically significant difference between groups, with a relative risk for 28-day mortality in the partial liquid ventilation group of 1.54 (95% confidence interval 0.82 to 2.9).

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