| Abstract |
Background
Diabetic ketoacidosis (DKA) is an acute metabolic disorder that occurs in conditions of
insulin deficiency or over-secretion of counterregulatory hormones. It is characterized by
hyperglycemia, metabolic acidosis with increased anion gap and dehydration. It is not a rare
condition in children with diabetes mellitus (DM) and is associated with serious and
potentially life-threatening consequences. Management of patients with DKA and the
correlation of intravenous fluids with the risk of developing cerebral edema is highly debated.
There are differences even among the main therapeutic guidelines. To our knowledge there
are no registered data of DKA in children in Greece. The main point of interest of ongoing
studies is the need to correlate parameters of acid-base balance with clinical markers of
severity and outcome, mainly concerning the monitoring of the rate of correction of DKA and
its complications, and their clinical utility as predictive indicators.
Objective
The aim of this study is to investigate the epidemiologic and clinical data of patients admitted
in Pediatric Intensive Care Unit (PICU) at the University Hospital of Heraklion, Crete, with
DKA, to assess the severity of DKA, the administration of fluids and to determine clinical and
laboratory markers and their correlation with late or early correction of acidosis, the
complications, the duration of hospitalization, and the outcome.
Methods
This is a single center, retrospective study including all children under the age of 18 years old
with newly diagnosed or known T1DM, presented with DKA and admitted in PICU at the
University Hospital of Heraklion during the years 2004 and 2020. For the results analysis, the
children were further divided into two comparison groups according to: a) The severity of
DKA characterized by the degree of acidosis (severe DKA – pH <7.1 vs moderate DKA – pH
≥7.1) based on NICE classification (2020) and b) The history of T1DM (newly diagnosed vs
known T1DM). The resolution of DKA was examined by four parameters: pH, bicarbonate
levels, onset of oral intake and subcutaneous insulin. The outcome of DKA was examined by
three parameters: length of hospital stay, length of PICU stay and manifestation of
complications during treatment.
Results
Out of 1969 patients admitted in PICU during the last 16 years, only 2.5% of them concerned
DKA cases (N=49). The prevalence of DKA at the diagnosis of T1DM was 84%. There was
no difference in sex distribution. Cerebral edema and death were reported in only one patient.
Patients with new onset T1DM had more severe acidosis with pH <7.1, in contrast with children with known T1DM, who at high percentage presented with moderate acidosis with
pH ≥7.1 (p=0.01). Most children received one or no initial fluid bolus of NaCl 0.9%. No
difference was noted regarding administration of fluid boluses in relation with the severity of
DKA, as well as with the outcome. The correlation between clinical severity measured with
PRISM and age showed that the younger the age of presentation of DKA at diagnosis of
T1DM the more severe are the clinical manifestations, while in children with known T1DM
severity rises with age. Children with positive family history of T1DM in relatives of first or
second degree or positive family history of T2DM presented with more severe clinical status
in PICU (p=0.034). Concerning the time of correction of pH >7.3 and bicarbonate levels >15
mmol/L, there was a positive correlation between them (p<0.001) but also a time difference,
with earlier pH restoration (mean=6.06 hours). Anion gap was not associated with the severity
of DKA. Among the children with pH at admission <7.1 and those with pH ≥7.1, a time
difference existed between the correction of pH >7.3 (p=0.007) and bicarbonate levels >15
mmol/L (p=0.001). More specifically, in more severe acidosis the resolution of DKA was
delayed. The same also occurred in this group, with the onset of oral intake (p=0.004). The
length of PICU stay was associated with the severity of DKA, with the longest time of stay
matching with patients with pH at admission <7.1 (p<0.008). The younger the age,
irrespective of the severity of DKA, the longer the hospitalization was (p<0.001).
Conclusion
Upon diagnosis of T1DM and mainly in younger children, the DKA is more severe. Children
with established T1DM exhibit more severe DKA during adolescence. The more severe the
degree of acidosis, the longest is the time of restoration of DKA in these children. The length
of hospital stay is prolonged in toddlers and pre- school aged children. Correction of acidosis
takes place within the first 24 hours of hospitalization and oral intake and subcutaneous
administration of insulin begin during the second day, as well as the discharge from PICU.
The rate of complications noted is low.
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