Toward the early diagnosis of neonatal sepsis and sepsis-like illness using novel heart rate analysis
Toward the early diagnosis of neonatal sepsis and sepsis-like illness using novel heart rate analysis
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DOI：
10.1542/peds.107.1.97
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发表时间：
2001-01-01
期刊：
影响因子：
8
通讯作者：
Moorman, JR
中科院分区：
文献类型：
--
作者：
Griffin, MP;Moorman, JR
背景与目的。因败血症导致的临床突然恶化是新生儿发病和死亡的主要原因，早期诊断应能改善这种可能具有灾难性的疾病的治疗。在实践中，临床体征和实验室数据对于败血症早期阶段并不被认为具有敏感性或特异性。由于心率特征（HRC）在胎儿窘迫和新生儿疾病期间是异常的，我们假设异常的HRC可能在新生儿败血症的临床诊断之前出现，为标准临床参数增加独立信息。
方法。在弗吉尼亚大学新生儿重症监护病房，我们对1995年8月至1999年4月期间入院的有发生败血症风险的婴儿进行了前瞻性研究。败血症（培养阳性）组和类败血症疾病（培养阴性）组的婴儿出现临床突然恶化，这引起了临床对感染的怀疑，并促使医生进行血培养和开始抗生素治疗。无败血症的婴儿没有引起临床疾病怀疑，也没有进行培养。我们测量了败血症、类败血症疾病或对照组随机时间之前5天和之后3天的标准化心率（HR）时间序列的新特征——矩和百分位数。我们还计算了新生儿急性生理学评分（SNAP）和新生儿治疗干预评分系统（NTISS）作为疾病严重程度的临床评分。
结果。40例患者中有46次培养阳性的败血症发作，23例患者中有27次培养阴性的类败血症疾病发作。我们分析了26例患者的29个对照期。败血症和类败血症疾病的婴儿比无败血症的婴儿出生体重更低、胎龄更小，且SNAP和NTISS评分更高。最重要的新发现是，败血症和类败血症疾病组的婴儿在临床突然恶化前长达24小时内心率特征（HRC）越来越异常。异常的HRC表现为基线变异性降低和心率短暂减速。这些异常导致HRC指标发生显著变化，例如，三阶矩（偏度：败血症为0.59±0.10，类败血症疾病为0.51±0.12，而在突然恶化前6小时对照组为 -0.10±0.13）。培养阳性和培养阴性患者具有相似的HRC和临床评分，包括在事件发生前24小时内SNAP显著升高。多变量逻辑回归分析表明，在突然恶化前24小时内，HRC和临床评分独立地增加了区分败血症和类败血症疾病婴儿与对照患者的信息。
结论。因败血症和类败血症疾病导致临床突然恶化的新生儿有心率特征（HRC）和新生儿急性生理学评分（SNAP）异常，且在临床怀疑败血症前24小时内情况恶化。对有败血症和类败血症疾病风险的婴儿监测这些参数的策略可能会导致更早的诊断和更有效的治疗。
Background and Objective. Abrupt clinical deterioration because of sepsis is a major cause of morbidity and mortality in neonates, and earlier diagnosis should improve therapy of this potentially catastrophic illness. In practice, clinical signs and laboratory data have not been perceived as sensitive or specific for early stages of sepsis. Because heart rate characteristics (HRC) are abnormal during fetal distress and neonatal illness, we hypothesized that abnormal HRC might precede the clinical diagnosis of neonatal sepsis, adding independent information to standard clinical parameters.Methods. In the neonatal intensive care unit at the University of Virginia, we prospectively studied infants admitted from August 1995 to April 1999 who were at risk for developing sepsis. Infants in the sepsis (culture-positive) and sepsis-like illness (culture-negative) groups had an abrupt clinical deterioration that raised clinical suspicion of infection and prompted physicians to obtain blood cultures and start antibiotic therapy. Infants without sepsis raised no clinical suspicion of illness and had no cultures obtained. We measured novel characteristics-moments and percentiles-of normalized heart rate (HR) time series for 5 days before and 3 days after sepsis, sepsis-like illness, or a random time in controls. We also calculated the Score for Neonatal Acute Physiology (SNAP) and the Neonatal Therapeutic Intervention Scoring System (NTISS) as clinical scores of the severity of illness.Results. There were 46 episodes of culture-positive sepsis in 40 patients and 27 episodes of culture-negative sepsis-like illness in 23 patients. We analyzed 29 control periods in 26 patients. Infants with sepsis and sepsis-like illness had lower birth weights and gestational ages and higher SNAP and NTISS scores than did infants without sepsis. The most important new finding was that the infants in the sepsis and sepsis-like illness groups had increasingly abnormal HRC for up to 24 hours preceding their abrupt clinical deterioration. The abnormal HRC were reduced baseline variability and short-lived decelerations in HR. These abnormalities led to significant changes in HRC measures, for example, the third moment (skewness: .59 +/- .10 for sepsis and .51 +/- .12 for sepsis-like illness, compared with -.10 +/- .13 for control over the 6 hours before abrupt deterioration). Culture-positive and culture-negative patients had similar HRC and clinical scores, including a significant rise in SNAP in the 24 hours before the event. Multivariable logistic regression analysis showed that HRC and clinical scores independently added information in distinguishing infants with sepsis and sepsis-like illness from control patients in the 24 hours before abrupt deterioration.Conclusions. Newborn infants who had abrupt clinical deterioration as a result of sepsis and sepsis-like illness had abnormal HRC and SNAP that worsened over 24 hours before the clinical suspicion of sepsis. A strategy for monitoring these parameters in infants at risk for sepsis and sepsis-like illness might lead to earlier diagnosis and more effective therapy.