Eudowood Division of Pediatric Respiratory Sciences, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
University of North Carolina Project Malawi, Lilongwe, Malawi; Department of Pediatrics, School of Medicine, University of North Carolina at Chapel Hill, NC, USA.
Lancet Respir Med. 2019 Nov;7(11):964-974. doi: 10.1016/S2213-2600(19)30243-7. Epub 2019 Sep 24.
Pneumonia is the leading cause of death among children globally. Most pneumonia deaths in low-income and middle-income countries (LMICs) occur among children with HIV infection or exposure, severe malnutrition, or hypoxaemia despite antibiotics and oxygen. Non-invasive bubble continuous positive airway pressure (bCPAP) is considered a safe ventilation modality that might improve child pneumonia survival. bCPAP outcomes for high-risk African children with severe pneumonia are unknown. Since most child pneumonia hospitalisations in Africa occur in non-tertiary district hospitals without daily physician oversight, we aimed to examine whether bCPAP improves severe pneumonia mortality in such settings.
This open-label, randomised, controlled trial was done in the general paediatric ward of Salima District Hospital, Malawi. We enrolled children aged 1-59 months old with WHO-defined severe pneumonia and either HIV infection or exposure, severe malnutrition, or an oxygen saturation of less than 90%. Children were randomly assigned 1:1 to low-flow nasal cannula oxygen or nasal bCPAP. Non-physicians administered care; the primary outcome was hospital survival. Primary analyses were by intention-to-treat and interim and adverse events analyses per protocol. This trial is registered with ClinicalTrials.gov, number NCT02484183, and is closed.
We screened 1712 children for eligibility between June 23, 2015, and March 21, 2018. The data safety and monitoring board stopped the trial for futility after 644 of the intended 900 participants were enrolled. 323 children were randomly assigned to oxygen and 321 to bCPAP. 35 (11%) of 323 children who received oxygen died in hospital, as did 53 (17%) of 321 who received bCPAP (relative risk 1·52; 95% CI 1·02-2·27; p=0·036). 13 oxygen and 17 bCPAP patients lacked hospital outcomes and were considered lost to follow-up. Suspected adverse events related to treatment occurred in 11 (3%) of 321 children receiving bCPAP and 1 (<1%) of 323 children receiving oxygen. Four bCPAP and one oxygen group deaths were classified as probable aspiration episodes, one bCPAP death as probable pneumothorax, and six non-death bCPAP events included skin breakdown around the nares.
bCPAP treatment in a paediatric ward without daily physician supervision did not reduce hospital mortality among high-risk Malawian children with severe pneumonia, compared with oxygen. The use of bCPAP within certain patient populations and non-intensive care settings might carry risk that was not previously recognised. bCPAP in LMICs needs further evaluation before wider implementation for child pneumonia care.
Bill & Melinda Gates Foundation, International AIDS Society, Health Empowering Humanity.
肺炎是全球儿童死亡的主要原因。在低收入和中等收入国家（LMICs），大多数死于肺炎的儿童患有 HIV 感染或暴露、严重营养不良或低氧血症，尽管使用了抗生素和氧气。非侵入性气泡持续气道正压通气（bCPAP）被认为是一种安全的通气方式，可能会提高儿童肺炎的生存率。bCPAP 对高危非洲儿童严重肺炎的疗效尚不清楚。由于非洲大多数儿童肺炎住院发生在没有医生日常监督的非三级地区医院，因此我们旨在研究 bCPAP 是否能改善此类环境中严重肺炎的死亡率。
这是一项在马拉维萨利马区医院儿科病房进行的开放标签、随机、对照试验。我们招募了年龄在 1-59 个月之间、符合世界卫生组织定义的严重肺炎且患有 HIV 感染或暴露、严重营养不良或血氧饱和度低于 90%的儿童。儿童以 1:1 的比例随机分配到低流量鼻导管吸氧或鼻 bCPAP。非医师提供护理；主要结局是住院生存率。主要分析为意向治疗和中期及不良事件分析。该试验在 ClinicalTrials.gov 注册，编号为 NCT02484183，现已关闭。
我们在 2015 年 6 月 23 日至 2018 年 3 月 21 日期间对 1712 名儿童进行了筛选。在计划的 900 名参与者中的 644 名入组后，数据安全和监测委员会因无效而停止了试验。323 名儿童被随机分配接受氧气治疗，321 名儿童接受 bCPAP 治疗。接受氧气治疗的 323 名儿童中有 35 名（11%）在医院死亡，接受 bCPAP 治疗的 321 名儿童中有 53 名（17%）死亡（相对风险 1.52；95%CI 1.02-2.27；p=0.036）。13 名接受氧气治疗的儿童和 17 名接受 bCPAP 治疗的儿童缺乏医院结局，被认为是失访。在接受 bCPAP 治疗的 321 名儿童中有 11 名（3%）和接受氧气治疗的 323 名儿童中有 1 名（<1%）发生疑似与治疗相关的不良事件。4 名 bCPAP 组和 1 名氧气组死亡被归类为可能的吸入事件，1 名 bCPAP 组死亡被归类为可能的气胸，6 例非死亡 bCPAP 事件包括鼻腔周围皮肤破裂。
在没有医生日常监督的儿科病房中，bCPAP 治疗并未降低马拉维高危儿童严重肺炎的住院死亡率，与氧气治疗相比。在某些患者人群和非重症监护环境中使用 bCPAP 可能存在以前未认识到的风险。bCPAP 在 LMICs 中的应用需要进一步评估，然后才能更广泛地用于儿童肺炎护理。
比尔和梅琳达盖茨基金会、国际艾滋病协会、人类健康赋权。
Zotero 插件