| Abstract |
Background: The maintenance of glucose levels plays a determinant role in the proper
function of the human organism. Stress during a critical illness has been found to derange
glucose homeostasis leading to Glucose Variability (GV). Glucose Variability represents the
fluctuation of glucose levels over time and refers to a non-stationary state in which glucose
levels fluctuate between high and low values such as speed, magnitude, and frequency. The
GV has been associated with increased mortality and prolonged stay in the ICU in studies that
took place in adult patients. Few studies have been done in pediatric patients that correlate
the GV in critical illness with the severity of illness and outcome.
Objective: The aim of this study is to determine the prognostic ability of GV indicators (MAG,
GLI, SD, CV, ACACP) in pediatric patients that were hospitalized in the Pediatric Intensive Care
Unit (PICU) for the first 72 hours. Furthermore, our study intends to compare the GV between
the glucose variability indexes and to correlate them with clinical characteristics, the severity
of illness scores, and outcome as well as to estimate risk factors in patients' sub cohorts.
Methods: The study was conducted in the University Hospital of Heraklion PICU. Data were
collected retrospectively from medical records of patients admitted between November 2018
– June 2022. A data collection form was used containing demographic and clinical information,
laboratory examinations and documentation of glucose levels of the first 72 hours of
hospitalization. Severity factors of GV were calculated as well as the PELOD-2 score was also
calculated. Exclusion criteria from the study were hospitalization less than 72 hours
Results: The study included 140 patients of which 87 (62.1%) were boys. Pathological causes
made up most admissions and most were urgent. An increase was observed in intravenous
fluids during the 2nd day of hospitalization and a significant decrease in the 3rd day especially
in the patients who survived, on the contrary, the total daily calories of enteral feeding were
increased mainly in the 2nd and 3rd days of hospitalization in those who survived but also
overall. Positive fluid balance was observed on all three days of the patients' hospitalization.
A variety was observed in the types of IV fluids administered to patients, as at least two
different solutions were used daily. Glucose was measured at least 16 times during a 72-hour
period. Mean glucose values were markedly reduced on days 2 and 3 in survivors and all
patients. The maximum glucose values were on the 3rd day particularly high in the patients who died (177±46.3 vs. 137±43.9 mg/dl, p=0,007), while decreased on the 2nd and 3rd day of
hospitalization in all patients and in those who survived. The minimum glucose values were
found to be markedly reduced on days 2 and 3 in survivors and overall. Mean glucose values
in the 1st and 3rd days were significantly correlated with the lactate levels at entry, whereas
all three 24h were correlated with blood creatinine (r=0,25, p=0,003), pH (r=-0,42, p<0,001),
and BE (r=-0,41, p<0,001).. A significant correlation was observed between MAG with pH (r=-
0,33, p<0,001), SD with ΒΕ (r=-0,41, p<0,001) and GLI with lactate (r=0,46, p<0,001). The
ACACP index has been associated with lower glucose values. The glucose variability indexes
MAG, SD, CV, GLI showed strong correlation with each other (p<0.001), while ACACP mainly
showed correlation only with GLI (r=0,54, p<0,001) and MAG (r=0,23, p=0,007). In patients
who died, higher values were recorded in the MAG, SD, CV and GLI glucose variability indexes.
MAG (ROC 0,730 (0,58-0,88), p=0,023), CV (ROC 0,725 (0,55-0,908), p=0,026), SD (ROC 0,729
(0,55-0,91), p=0,024) indexes and PELOD-2 (ROC 0,83 (0,69-0,97), p=0,001) showed strong
predictive ability for poor disease outcome, while ACACP had no significant predictive ability.
Conclusion: The results of the present study showed that indexes of glucose variability have a
strong prognostic ability to predict poor disease outcome in pediatric ICU patients in the first
72 hours of hospitalization. Three out of the five indexes of glucose variability, MAG, CV and
SD had the greatest predictive ability and the PELOD-2 index had a strong ability to predict
disease severity. In addition, glucose variability indices recorded higher values in patients who
died and were associated with clinical-laboratory characteristics, such as acidosis and
increased lactate levels. Finally, all variability indices were associated with mean and upper
glucose values except ACACP, which was associated with the lowest glucose values.
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