Article type
Year
Abstract
Objectives: To assess the effect of ranking outcome variables and of comparing study design with current therapy on the evidence for routine administration of diuretics in preterm infants with or developing chronic lung disease (CLD).
Methods: Systematic review of diuretics in preterm infants with oxygen or ventilator dependency and postnatal age >5 days, using standard methods of the Cochrane Collaboration. We searched the literature for randomized controlled trials (RCTs) assessing at least one of 4 outcome variables ranked as follows: Major variables: long-term evolution and changes in respiratory therapy for CLD; Minor variables: changes in pulmonary function and potential complications. The design of each eligible study was compared with current standard of care in two different countries (USA and UK). Divergence from current practice was determined by consensus of four reviewers including two neonatologists and two pulmonologists. In 3 reviews we assessed: systemic administration of diuretics acting on the loop of Henle (loop diuretics), aerosolized administration of loop diuretics, and diuretics acting the distal part of the nephron (distal diuretics). Subgroup analysis was determined a priori based on type of intervention, major groups, postnatal age, gestational age and presence of an endotracheal tube.
Results: Of 45 studies considered, 23 were not RCTs and two did not assess the outcome variables defined for this systematic review. Among 20 studies fulfilling the criteria, long-term outcome was analyzed in 2 studies (both distal diuretics) and improved in one. The need for mechanical ventilation was assessed in 4 studies (all types of diuretics analyzed) and improved in none. Oxygenation was assessed in 7 studies and improved in 3 (all loop diuretics), but only transiently in 2 of them. Pulmonary function was assessed in 17 studies and improved at least transiently in 10 of them. Potential side effects were assessed in 7 studies and were not more frequent than in controls. In one RCT administration of distal diuretics improved long-term outcome (lower death rate but no change in length of hospital stay or duration of mechanical ventilation) and transiently improved oxygenation and pulmonary function. Nevertheless, intubated patients were, by design in this RCT, not eligible to receive postnatal steroids; the consensus was this design differs from current standard of care.
Discussion: The conclusions of this systematic review were highly dependent on pre-selected criteria. Half the studies analyzing long-term outcome, oxygenation and pulmonary function found a positive effect of diuretics, whereas no study analyzing mechanical ventilation showed any benefit of diuretics. Because only few studies analyzed major outcome variables selected by the reviewers and the only study showing long-term benefit appeared to differ from current standard of care, we concluded that this systematic review showed lack of evidence for routine use of diuretics. This suggests that ranking outcome variables and comparing study design with current standard of care are important to assess relevance of existent research.
Methods: Systematic review of diuretics in preterm infants with oxygen or ventilator dependency and postnatal age >5 days, using standard methods of the Cochrane Collaboration. We searched the literature for randomized controlled trials (RCTs) assessing at least one of 4 outcome variables ranked as follows: Major variables: long-term evolution and changes in respiratory therapy for CLD; Minor variables: changes in pulmonary function and potential complications. The design of each eligible study was compared with current standard of care in two different countries (USA and UK). Divergence from current practice was determined by consensus of four reviewers including two neonatologists and two pulmonologists. In 3 reviews we assessed: systemic administration of diuretics acting on the loop of Henle (loop diuretics), aerosolized administration of loop diuretics, and diuretics acting the distal part of the nephron (distal diuretics). Subgroup analysis was determined a priori based on type of intervention, major groups, postnatal age, gestational age and presence of an endotracheal tube.
Results: Of 45 studies considered, 23 were not RCTs and two did not assess the outcome variables defined for this systematic review. Among 20 studies fulfilling the criteria, long-term outcome was analyzed in 2 studies (both distal diuretics) and improved in one. The need for mechanical ventilation was assessed in 4 studies (all types of diuretics analyzed) and improved in none. Oxygenation was assessed in 7 studies and improved in 3 (all loop diuretics), but only transiently in 2 of them. Pulmonary function was assessed in 17 studies and improved at least transiently in 10 of them. Potential side effects were assessed in 7 studies and were not more frequent than in controls. In one RCT administration of distal diuretics improved long-term outcome (lower death rate but no change in length of hospital stay or duration of mechanical ventilation) and transiently improved oxygenation and pulmonary function. Nevertheless, intubated patients were, by design in this RCT, not eligible to receive postnatal steroids; the consensus was this design differs from current standard of care.
Discussion: The conclusions of this systematic review were highly dependent on pre-selected criteria. Half the studies analyzing long-term outcome, oxygenation and pulmonary function found a positive effect of diuretics, whereas no study analyzing mechanical ventilation showed any benefit of diuretics. Because only few studies analyzed major outcome variables selected by the reviewers and the only study showing long-term benefit appeared to differ from current standard of care, we concluded that this systematic review showed lack of evidence for routine use of diuretics. This suggests that ranking outcome variables and comparing study design with current standard of care are important to assess relevance of existent research.