Department of Paediatrics, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada.
Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
Eur J Pediatr. 2022 Sep;181(9):3319-3330. doi: 10.1007/s00431-022-04508-6. Epub 2022 Jul 2.
The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01).
Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work.
• Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality.
• This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.
本回顾性队列研究旨在研究早产儿心肺危重症（CPCD）相关的临床负担以及与死亡率相关的因素。通过加拿大新生儿网络（30 家三级 NICU，2010-2017 年），我们确定了存在 CPCD 的 < 32 周胎龄的婴儿，CPCD 定义为“显著暴露”于心肺药物和/或吸入性一氧化氮（iNO）：（1）连续 ≥ 3 天接受治疗，（2）连续 ≥ 2 天接受两种治疗，或（3）死亡前 2 天内接受任何一种治疗。分别检查早期 CPCD（≤ 3 天龄）和晚期 CPCD（> 3 天）。结局包括 CPCD 发生率、死亡率以及使用标准化比率（观察到的/调整后的预期率）和网络漏斗图来评估各中心之间的差异。混合效应分析用于量化单位水平死亡率的变异性。总体而言，10%的入院患者发生 CPCD（n = 2915）。晚期 CPCD 的发生率每年下降约 5%，而研究期间早期 CPCD 无变化。早期（0.6-7.5%和 0-100%）和晚期（2.5-15%和 14-83%）CPCD 的发生率和 CPCD 相关死亡率在各中心之间存在差异，均 < 0.01。各单位晚期 CPCD 的发生率和死亡率呈负相关（斜率 = -2.5，p < 0.01）。混合效应分析显示存在聚类效应，早期和晚期 CPCD 后死亡率的 6.4%和 8.6%差异与中心相关，无法用可用的患者水平特征或单位容量来解释。联合暴露的死亡率高于仅使用心肺药物或仅使用 iNO（分别为 41.3%、24.8%和 21.5%；p < 0.01）。
加拿大 NICU 中 CPCD 相关死亡率存在聚类效应，发病率较高的单位死亡率较低。这些数据可能有助于网络水平的基准测试、患者水平的风险分层、父母咨询以及进一步的研究和质量改进工作。
• 早产儿仍然存在急性和慢性并发症的高风险；最危重的患儿需要心肺药物和吸入性一氧化氮等治疗。• 需要这些治疗的婴儿已知存在不良新生儿结局和死亡的高风险。
• 本研究有助于阐明急性心肺危重症（CPCD）的全国负担，其定义为需要心肺药物或吸入性一氧化氮，突出了与这种疾病状态相关的高发病率和死亡率。• 发病率和相关死亡率在全国范围内存在显著差异；观察到聚类效应，发病率较高的单位与 CPCD 相关死亡率较低。
