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Methods to control the blood glucose (BG) levels of patients in intensive care units (ICU) improve the outcomes. The development of continuous BG levels monitoring devices has also permitted to optimize these processes. Recently it was shown that a complexity loss of the BG signal is linked to poor clinical outcomes. Thus, it becomes essential to decipher this relation to design efficient BG level control methods. In previous studies the BG signal complexity was calculated as a single index for the whole ICU stay. Although, these approaches did not grasp the potential variability of the BG signal complexity. Therefore, we setup this pilot study using a continuous monitoring of central venous BG levels in ten critically ill patients (EIRUS platform, Maquet Critical CARE AB, Solna, Sweden). Data were processed and the complexity was assessed by the detrended fluctuation analysis and multiscale entropy (MSE) methods. Finally, recordings were split into 24 h overlapping intervals and a MSE analysis was applied to each of them. The MSE analysis on time intervals revealed an entropy variation and allowed periodic BG signal complexity assessments. To highlight differences of MSE between each time interval we calculated the MSE complexity index defined as the area under the curve. This new approach could pave the way to future studies exploring new strategies aimed at restoring blood glucose complexity during the ICU stay.
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Journal of Clinical Monitoring and Computing (2020) 34:361–370
https://doi.org/10.1007/s10877-019-00299-8
ORIGINAL RESEARCH
Dynamic properties ofglucose complexity duringthecourse ofcritical
illness: apilot study
EmmanuelGodat1· Jean‑CharlesPreiser2· Jean‑ChristopheAude3 · PierreKalfon4
Received: 15 June 2018 / Accepted: 13 March 2019 / Published online: 19 March 2019
© Springer Nature B.V. 2019
Abstract
Methods to control the blood glucose (BG) levels of patients in intensive care units (ICU) improve the outcomes. The devel-
opment of continuous BG levels monitoring devices has also permitted to optimize these processes. Recently it was shown
that a complexity loss of the BG signal is linked to poor clinical outcomes. Thus, it becomes essential to decipher this rela-
tion to design efficient BG level control methods. In previous studies the BG signal complexity was calculated as a single
index for the whole ICU stay. Although, these approaches did not grasp the potential variability of the BG signal complexity.
Therefore, we setup this pilot study using a continuous monitoring of central venous BG levels in ten critically ill patients
(EIRUS platform, Maquet Critical CARE AB, Solna, Sweden). Data were processed and the complexity was assessed by the
detrended fluctuation analysis and multiscale entropy (MSE) methods. Finally, recordings were split into 24h overlapping
intervals and a MSE analysis was applied to each of them. The MSE analysis on time intervals revealed an entropy variation
and allowed periodic BG signal complexity assessments. To highlight differences of MSE between each time interval we
calculated the MSE complexity index defined as the area under the curve. This new approach could pave the way to future
studies exploring new strategies aimed at restoring blood glucose complexity during the ICU stay.
Keywords Glucose control· Continuous glucose monitoring· Critically ill patients· Signal complexity· Multiscale
entropy
Abbreviations
BG Blood glucose
CGM Continuous glucose monitoring
COPD Chronic obstructive pulmonary disease
CVC Central venous catheter
DFA Detrended fluctuation analysis
ICU Intensive care unit
MSE Multiscale entropy
CI Complexity index
SampEn Sample entropy
1 Introduction
Hyperglycemia stress and insulin resistance are frequent in
critically ill patients and are associated with poor outcome
[1]. This dysfunction in the glucose metabolism is not linked
with the patients diabetic status [2]. In 2001 Van den Berghe
etal. [3] described, for the first time, a method for strict
BG levels control obtained using high insulin dosage among
intensive care unit (ICU) patients. In this study, the authors
showed a decrease of mortality and morbidity. However, the
strict target for BG levels (from 4.4 to 6.1 mmol/L) was
called into question by several multicentric studies [46].
The most important reconsideration of all was brought by
the NICE-SUGAR study which observed, in a grouprand-
omized trial, a higher mortality for strict BG control (4.5 to
6 mmol/L) versus less stringent BG control (<10 mmol/L)
[6]. Consequently, in 2010, international recommendations
for the control of glycemia in adult non-diabetic critically
* Jean-Christophe Aude
jean-christophe.aude@cea.fr
1 Département d’Anesthésie-Réanimation, Hôpital
Bretonneau, Centre Hospitalier Régional Universitaire de
Tours, 37044ToursCedex9, France
2 Department ofIntensive Care, Erasme Hospital, Université
libre de Bruxelles, Brussels, Belgium
3 Institute forIntegrative Biology oftheCell (I2BC), CEA,
CNRS, Université Paris-Sud, Université Paris-Saclay,
91198Gif-sur-Yvette, France
4 Service de Réanimation Polyvalente, Centre Hospitalier
Louis Pasteur, CH de Chartres, 28000Chartres, France
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... 1,2 Then we have got the consensus that glycemic fluctuation imposes much more harmful effects upon the outcomes than both hyperglycemia and hypoglycemia, 3,4 so as the variability of blood glucose. 5 Nevertheless, this seemingly unquestionable assertion had been doubted in some studies, 6 it was more commonly proven in the non-DM cohort but not in the DM. 7 Paul E Marik suggests that hyperglycemia and insulin resistance in the setting of acute illnesses is an evolutionarily preserved adaptive responsiveness to the disorder, which was believed to be a beneficial host response that enhances the host's chances of survival. ...
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