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  1. Ho JJ, Kidman AM, Chua B, Chang G, Fiander M, Davis PG
    Cochrane Database Syst Rev, 2024 Oct 11;10(10):CD000143.
    PMID: 39392114 DOI: 10.1002/14651858.CD000143.pub2
    BACKGROUND: Preterm infants who are extubated following a period of invasive ventilation via an endotracheal tube are at risk of developing respiratory failure, leading to reintubation. This may be due to apnoea, respiratory acidosis, or hypoxia. Historically, preterm infants were extubated to head box oxygen or low-flow nasal cannulae. Support with non-invasive pressure might help improve rates of successful extubation in preterm infants by stabilising the upper airway, improving lung function, and reducing apnoea. This is an update of a review first published in 1997 and last updated in 2003.

    OBJECTIVES: To determine whether nasal continuous positive airway pressure (NCPAP), applied immediately after extubation of preterm infants, reduces the incidence of extubation failure and the need for additional ventilatory support, without clinically important adverse events.

    SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries on 22 September 2023 using a revised strategy. We searched conference abstracts and the reference lists of included studies and relevant systematic reviews.

    SELECTION CRITERIA: Eligible trials employed random or quasi-random allocation of preterm infants undergoing extubation. Eligible comparisons were NCPAP (delivered by any device and interface) versus head box oxygen, extubation to room air, or any other form of low-pressure supplemental oxygen. We grouped the comparators under the term no continuous positive airway pressure (no CPAP).

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data from the included studies. Where studies were sufficiently similar, we performed a meta-analysis, calculating risk ratios (RRs) with their 95% confidence intervals (CIs) for dichotomous data. For the primary outcomes that showed an effect, we calculated the number needed to treat for an additional beneficial outcome (NNTB). We used the GRADE approach to assess the certainty of the evidence for clinically important outcomes.

    MAIN RESULTS: We included nine trials (with 726 infants) in the quantitative synthesis of this updated review. Eight studies were conducted in high-income countries between 1982 and 2005. One study was conducted in Chile, which was classified as upper-middle income at the time of the study. All studies used head box oxygen in the control arm. Risk of bias was generally low. However, due to the inherent nature of the intervention, no studies incorporated blinding. Consequently, the neonatal intensive care unit staff were aware of the assigned group for each infant, and we judged all studies at high risk of performance bias. However, we assessed blinding of the outcome assessor (detection bias) as low risk for seven studies because they used objective criteria to define both primary outcomes. NCPAP compared with no CPAP may reduce the risk of extubation failure (RR 0.62, 95% CI 0.51 to 0.76; risk difference (RD) -0.17, 95% -0.23 to -0.10; NNTB 6, 95% CI 4 to 10; I2 = 55%; 9 studies, 726 infants; low-certainty evidence) and endotracheal reintubation (RR 0.79, 95% 0.64 to 0.98; RD -0.07, 95% CI -0.14 to -0.01; NNTB 15, 95% CI 8 to 100; I2 = 65%; 9 studies; 726 infants; very low-certainty evidence), though the evidence for endotracheal reintubation is very uncertain. NCPAP compared with no CPAP may have little or no effect on bronchopulmonary dysplasia, but the evidence is very uncertain (RR 0.89, 95% CI 0.47 to 1.68; RD -0.03, 95% CI -0.22 to 0.15; 1 study, 92 infants; very low-certainty evidence). No study reported neurodevelopmental outcomes.

    AUTHORS' CONCLUSIONS: NCPAP may be more effective than no CPAP in preventing extubation failure in preterm infants if applied immediately after extubation from invasive mechanical ventilation. We are uncertain whether it can reduce the risk of reintubation or bronchopulmonary dysplasia. We have no information on long-term neurodevelopmental outcomes. Although there is only low-certainty evidence for the effectiveness of NCPAP immediately after extubation in preterm infants, we consider there is no need for further research on this intervention, which has become standard practice.

  2. Lim JY, Ker CJ, Lai NM, Romantsik O, Fiander M, Tan K
    Cochrane Database Syst Rev, 2024 May 02;5(5):CD012361.
    PMID: 38695625 DOI: 10.1002/14651858.CD012361.pub2
    BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group.

    OBJECTIVES: To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo.

    SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023.

    SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation.

    DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome.

    MAIN RESULTS: We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety.

    AUTHORS' CONCLUSIONS: Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

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