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Partial liquid ventilation for the prevention of mortality and morbidity in paediatric acute lung injury and acute respiratory distress syndrome

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Abstract

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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 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.

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 methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3); CINAHL (Cumulative Index to Nursing & Allied Health Literature) via Ovid (1982 to August 2008); Ovid EMBASE (1982 to August 2008); and Ovid MEDLINE (1950 to August 2008) with Daily Update.

Selection criteria

We included randomized controlled trials (RCTs) which compared partial liquid ventilation with other forms of ventilation in children (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 (only 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. 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).

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.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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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 normally gas‐filled lungs, and mechanical ventilation is continued with a gas ventilator.

The review authors found only one multicentre randomized controlled study, reported as an abstract in conference proceedings, that was eligible for inclusion in the 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.