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. 2018 Feb:117:83-89.
doi: 10.1016/j.earlhumdev.2018.01.008. Epub 2018 Jan 23.

Vital signs analysis algorithm detects inflammatory response in premature infants with late onset sepsis and necrotizing enterocolitis

Leena B Mithal  1 , Ram Yogev  2 , Hannah L Palac  3 , Daniel Kaminsky  4 , Ilan Gur  5 , Karen K Mestan  6
Affiliations

Vital signs analysis algorithm detects inflammatory response in premature infants with late onset sepsis and necrotizing enterocolitis

Leena B Mithal et al. Early Hum Dev. 2018 Feb.

Abstract

Background: Nonspecific clinical signs and suboptimal diagnostic tests limit accurate identification of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) in premature infants, resulting in significant morbidity and antibiotic overuse. An infant's systemic inflammatory response may be identified earlier than clinical suspicion through analysis of multiple vital signs by a computerized algorithm (RALIS).

Aim: To evaluate the revised RALIS algorithm for detection of LOS and NEC in preterm infants.

Methods: In this nested case-control study, VS data (heart rate, respiratory rate, temperature, desaturations, bradycardias) were extracted from medical records of infants 23-32 weeks gestation. RALIS generated an output, with score ≥ 5 triggering an alert. Patient episodes were classified based on culture, radiograph, and antibiotic data into categories: LOS, expanded LOS, NEC, and controls. Paired t-tests, linear regression and cross-validation analyses were used to evaluate the relationship between RALIS alert and LOS/NEC.

Results: Among 155 infants with 161 episodes, there were 41 expanded LOS (+blood, CSF, urine, respiratory culture), 31 LOS (+blood, CSF, urine), 9 NEC, and 93 controls. RALIS alert was 43.1 ± 79 h before culture in LOS (p = .012). There was a significant association between RALIS alert and LOS/NEC (β = 0.72, p < .0001). Sensitivity and specificity for LOS/NEC were 84% and 80%, (PPV = 63%; NPV = 93%). The regression model demonstrated an AUC of 89.9%.

Conclusions: For infants ≤32 weeks, RALIS detects systemic inflammatory responses in LOS and NEC in the first month of life. The algorithm can identify infection earlier than clinical suspicion, even for NEC with negative cultures. RALIS has high NPV to rule-out LOS and NEC, and may, after prospective validation, aid in antibiotic treatment decisions.

Keywords: Late onset sepsis; Necrotizing enterocolitis; Neonatal sepsis; Premature infant; Systemic inflammatory response; Vital signs analysis.

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Figures

Figure 1
Figure 1. Linear Regression Plots of RALIS alert with Culture
a) The regression line for the bivariate association between culture hours of life (HOL) and RALIS alert HOL for LOS [blood, urine]: RALIS Alert HOL = 54.2+ 0.72*Culture HOL. b) Regression line equation for LOS and/or NEC: RALIS Alert HOL = 62.9 + 0.72 *Culture HOL. The shaded region represents the 95% confidence interval for the regression line.
Figure 2
Figure 2. Contribution of individual vital signs to RALIS output
Panel (a) demonstrates RALIS output for a control infant vitals abnormalities, such as desaturations, but no score over 5 generating an alert throughout the monitoring period. Panel (b) demonstrates RALIS for a case of LOS+NEC. There is an alert, clinical suspicion for infection with blood culture sent (later positive for S. warneri), and necrotizing enterocolitis treated until beyond the monitoring period.
Figure 3
Figure 3. ROC Curve for Logistic Regression Model in Cross Validation Analysis
The AUC of the final derivation model in the testing dataset using model parameter estimates yielded an AUC of 0.8985.
See this image and copyright information in PMC

Comment in

References

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