Heart Rate Variability and Respiration Signal as Diagnostic Tools for Late Onset Sepsis in Neonatal Intensive Care Units

📝 Abstract

Apnea-bradycardia is one of the major clinical early indicators of late-onset sepsis occurring in approximately 7% to 10% of all neonates and in more than 25% of very low birth weight infants in NICU. The objective of this paper was to determine if HRV, respiration and their relationships help to diagnose infection in premature infants via non-invasive ways in NICU. Therefore, we implement Mono-Channel (MC) and Bi-Channel (BC) Analysis in two groups: sepsis (S) vs. non-sepsis (NS). Firstly, we studied RR series not only by linear methods: time domain and frequency domain, but also by non-linear methods: chaos theory and information theory. The results show that alpha Slow, alpha Fast and Sample Entropy are significant parameters to distinguish S from NS. Secondly, the question about the functional coupling of HRV and nasal respiration is addressed. Local linear correlation coefficient r2t,f has been explored, while non-linear regression coefficient h2 was calculated in two directions. It is obvious that r2t,f within the third frequency band (0.2<f<0.4 Hz) and h2 in two directions were complementary approaches to diagnose sepsis. Thirdly, feasibility study is carried out on the candidate parameters selected from MC and BC respectively. We discovered that the proposed test based on optimal fusion of 6 features shows good performance with the largest AUC and a reduced probability of false alarm (PFA).

💡 Analysis

Apnea-bradycardia is one of the major clinical early indicators of late-onset sepsis occurring in approximately 7% to 10% of all neonates and in more than 25% of very low birth weight infants in NICU. The objective of this paper was to determine if HRV, respiration and their relationships help to diagnose infection in premature infants via non-invasive ways in NICU. Therefore, we implement Mono-Channel (MC) and Bi-Channel (BC) Analysis in two groups: sepsis (S) vs. non-sepsis (NS). Firstly, we studied RR series not only by linear methods: time domain and frequency domain, but also by non-linear methods: chaos theory and information theory. The results show that alpha Slow, alpha Fast and Sample Entropy are significant parameters to distinguish S from NS. Secondly, the question about the functional coupling of HRV and nasal respiration is addressed. Local linear correlation coefficient r2t,f has been explored, while non-linear regression coefficient h2 was calculated in two directions. It is obvious that r2t,f within the third frequency band (0.2<f<0.4 Hz) and h2 in two directions were complementary approaches to diagnose sepsis. Thirdly, feasibility study is carried out on the candidate parameters selected from MC and BC respectively. We discovered that the proposed test based on optimal fusion of 6 features shows good performance with the largest AUC and a reduced probability of false alarm (PFA).

📄 Content

Draft of Physiological Measurement_Yuan Wang 1

Title Heart Rate Variability and Respiration Signal as Diagnostic Tools for Late Onset Sepsis in Neonatal Intensive Care Units

Authors Yuan Wang1,2,5§,Guy Carrault1,2, Alain Beuchee1,2,3, Nathalie Costet1,2, Huazhong Shu4,5, Lotfi Senhadji1,2,5

1 INSERM, UMR 1099, Rennes, 35042, France.
2 Université de Rennes 1, LTSI, Rennes, 35042, France.
3 CHU Rennes, Pôle Médico-Chirurgical de Pédiatrie et de Génétique Clinique, Rennes, F-35000, France.
4 School of Computer Science and Engineering, Southeast University, Nanjing, 210096, P. R. China. 5 Centre de Recherche en Information Biomédicale sino-français (CRIBs).

Email : yuanwang.research@gmail.com

Received 18 December 2015, revised Day Month 2016 Accepted for publication Day Month 201X,
Published Day Month 201X

Abstract Apnea-bradycardia is one of the major clinical early indicators of late-onset sepsis occurring in approximately 7% to 10% of all neonates and in more than 25% of very low birth weight infants in NICU. The objective of this paper was to determine if HRV, respiration and their relationships help to diagnose infection in premature infants via non-invasive ways in NICU. Therefore, we implement Mono-Channel (MC) and Bi-Channel (BC) Analysis in two groups: sepsis (S) vs. non-sepsis (NS). Firstly, we studied RR series not only by linear methods: time domain and frequency domain, but also by non-linear methods: chaos theory and information theory. The results show that alpha Slow, alpha Fast and Sample Entropy are significant parameters to distinguish S from NS. Secondly, the question about the functional coupling of HRV and nasal respiration is addressed. Local linear correlation coefficient r2 t,f has been explored, while non-linear regression coefficient h² was calculated in two directions. It is obvious that r2 t,f within the third frequency band (0.2<f<0.4 Hz) and h2 in two directions were complementary approaches to diagnose sepsis. Thirdly, feasibility study is carried out on the candidate parameters selected from MC and BC respectively. We discovered that the proposed test based on optimal fusion of 6 features shows good performance with the largest AUC and a reduced probability of false alarm (PFA).

Keywords: premature newborns, sepsis, heart rate variability, respiration, feasibility study, optimal fusion, clinical decision making

§ Dr. Yuan Wang is currently working at University of California, San Francisco (UCSF). 2 Draft of Physiological Measurement_Yuan Wang

1. Introduction

Late-onset sepsis, defined as a systemic infection in neonates older than 3 days, occurs in approximately 7% to 10% of all neonates and in more than 25% of very low birth weight newborns who are hospitalized in Neonatal Intensive Care Units (NICU). The clinical manifestations of neonatal sepsis, whatever the source of infection, are ususally not so evident. Accordingly, lacking in early and adapted interventions always leads to life risk. Therefore, this disease is a major problem resulting in high morbidity and mortality for premature newborns (Philip, 1990).
As we know, sick preterm infants do not show any fever and consequently the possible signs of sepsis may be detected only with blood culture. However, on one hand, the hematological and biochemical markers which have been used in this symptom, not only require invasive procedures which should not be frequently repeated, but also have low predictive values in the early phase of sepsis. On the other hand, it has been observed experimentally that phenomena of apnea-bradycardia happened more constantly in sepsis preterm infants than in non-sepsis ones (Cao et al., 2004).
Apnea is defined as the cessation of breathing for more than 20 seconds, while Bradycardia in preterm infants is defined as a fall in heart rate under 100 beats per minute. Apnea-Bradycardia (AB) episodes are dangerous for preterm infants mainly in 3 aspects:
• It requires invasive resuscitation techniques for the babies, • It also needs prolongation of hospital stay and then implies extra costs, • It has neurological impairment during childhood. Neonate Intensive Care Unit, where ECG and respiration are continuously recorded, provides environment to assist and monitor the development of the newborns. They are regularly equipped with computerized system triggering alarms if vital signs are abnormal. Several interesting clinical results were recently reported by our group including: i) early prediction of bradycardia (Pravisani et al., 2003), (Cruz et al., 2006), ii) early detection of sepsis (Beuchée et al., 2009), (Billois et al., 2012 ) or iii) study of post-immunization effects (Mialet-Marty et al., 2013). Especially, the second topic showed that these neonatal changes in behavior of physiological signals could be used

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