Lung recruitment manoeuvres for reducing mortality and respiratory morbidity in mechanically ventilated neonates

Review question

In mechanically ventilated neonates, do lung recruitment manoeuvres (LRMs) help to reduce mortality and respiratory morbidity, compared to no recruitment? 

Background

Critically ill neonates (infants from birth up to four weeks of age) commonly require intubation (placement of a breathing tube in the windpipe) and conventional mechanical ventilation (the use of a breathing machine) to support their breathing. Whilst this therapy is often lifesaving, it also carries the risk of lung injury. LRMs have been suggested to reduce the incidence of lung injury and improve respiratory outcomes in ventilated patients. A LRM involves deliberately increasing airway pressure for a brief period, which serves to reopen collapsed lung regions. LRMs have proved effective in ventilated adults; however, evidence regarding their use in neonates is limited. There is no consensus of opinion as to whether LRMs are appropriate or effective in this population.

Study characteristics

In a search up to 13 April 2020, we identified four studies that investigated LRM use in mechanically ventilated neonates. Two studies enrolling 44 preterm neonates (born before 30 weeks' gestational age) with respiratory distress syndrome compared a LRM within hours of birth to routine care. The third study involving 12 neonates compared two different types of LRMs applied directly after suctioning of the breathing tube to routine care. A fourth study enrolling 48 paediatric patients (including neonates) also compared a LRM after suctioning to routine care. This study did not contribute data to the review as the data pertaining to neonatal participants could not be isolated. 

Key results

When data from the two studies involving preterm neonates was combined, we found no clear differences between the LRM and routine care for the outcomes of mortality, incidence of bronchopulmonary dysplasia (a chronic lung disease in preterm infants), duration of supplemental oxygen therapy, and duration of ventilatory support. Meanwhile, data from 12 neonates suggests that two different types of LRMs may help to restore lung volume after suctioning compared to routine care. One of the LRMs (named double PEEP (positive end-expiratory pressure)) may also cause a slight reduction in blood pressure, which can have negative consequences in neonates.

Certainty of the evidence

The certainty of the evidence for these results was low to very low as the included studies were small and vulnerable to bias from limitations in their methods. Evidence-based guidance for the use of LRMs in mechanically ventilated neonates continues to be limited. Our review should raise awareness of the lack of high-certainty evidence in this field and encourage further research. Additional research would be valuable given our findings of possible but uncertain benefit with LRMs in mechanically ventilated neonates.  

Authors' conclusions: 

There is insufficient evidence to guide the use of LRMs in mechanically ventilated neonates. Well-designed randomised trials with larger sample sizes are needed to further evaluate the potential benefits and risks of LRM application in this population.

Read the full abstract...
Background: 

Preterm infants and neonates with respiratory conditions commonly require intubation and conventional mechanical ventilation (CMV) to maintain airway patency and support their respiration. Whilst this therapy is often lifesaving, it simultaneously carries the risk of lung injury. The use of lung recruitment manoeuvres (LRMs) has been found to reduce the incidence of lung injury, and improve oxygenation and lung compliance in ventilated adults. However, evidence pertaining to their use in neonates is limited, and there is no consensus of opinion as to whether LRMs are appropriate or effective in this population.

Objectives: 

To determine the effects of LRMs on mortality and respiratory outcomes in mechanically ventilated neonates, when compared to no recruitment (routine care). 

Search strategy: 

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to 13 April 2020), and CINAHL via EBSCOhost (1989 to 13 April 2020). We also handsearched the reference lists of retrieved studies to source additional articles. 

Selection criteria: 

We included randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over studies that compared the effect of LRMs to no recruitment (routine care) in mechanically ventilated neonates.

Data collection and analysis: 

Two review authors independently assessed trial eligibility, extracted data and evaluated risk of bias in the included studies. When studies were sufficiently similar, we performed a meta-analysis using mean difference (MD) for continuous data and risk ratio (RR) for dichotomous data, with their respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of the evidence for key (clinically important) outcomes.

Main results: 

We included four studies (152 participants in total) in this review. Three of these studies, enrolling 56 participants, contributed data to our prespecified outcomes.

Two studies enrolling 44 participants on CMV for respiratory distress syndrome compared a stepwise LRM with positive end-expiratory pressure (PEEP) to routine care. Meta-analysis demonstrated no evidence of a difference between the LRM and routine care on mortality by hospital discharge (RR 1.00, 95% CI 0.17 to 5.77; low-certainty evidence), incidence of bronchopulmonary dysplasia (RR 0.25, 95% CI 0.03 to 2.07; low-certainty evidence), duration of supplemental oxygen (MD -7.52 days, 95% CI -20.83 to 5.78; very low-certainty evidence), and duration of ventilatory support (MD -3.59 days, 95% CI -12.97 to 5.79; very low-certainty evidence). The certainty of the evidence for these outcomes was downgraded due to risk of bias, imprecision, and inconsistency. Whilst these studies contributed data to four of our primary outcomes, we were unable to identify any studies that reported our other primary outcomes: duration of continuous positive airway pressure therapy, duration of neonatal intensive care unit stay, and duration of hospital stay. 

The third study that contributed data to the review enrolled 12 participants on CMV for respiratory and non-respiratory causes, and compared two different LRMs applied after endotracheal tube suctioning to routine care. It was determined that both LRMs may slightly improve end-expiratory lung volume at 120 minutes' post-suctioning, when compared to routine care (incremental PEEP LRM versus routine care: MD -0.21, 95% CI -0.37 to -0.06; double PEEP LRM versus routine care: MD -0.18, 95% CI -0.35 to -0.02). It was also demonstrated that a double PEEP LRM may slightly reduce mean arterial pressure at 30 minutes' post-suctioning, when compared with routine care (MD -16.00, 95% CI -29.35 to -2.65). 

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