Participants
This is a retrospective cohort study included 49 children 1–15years with moderate or severe DKA who received rehydration solution using 0.45% saline at intermediate care unit of Diabetes, Endocrine, and Metabolism Pediatric Unit (DEMPU), Children’s Hospital over the period from August to October 2016. This was compared to historical cohort of 72 patients with moderate and severe DKA who received 0.9% saline as rehydration solution at the same unit during the preceding period from March to July 2016.
DKA was defined as having blood glucose >200 mg/dL (11.4 mmol/L), a venous pH <7.30 or a plasma bicarbonate level <15 mmol/L, and ketonemia or ketonuria and arterial blood gases (ABG) showed moderate DKA if arterial pH >7.1 and <7.2 with bicarbonate <10 and >5mmol/L or severe DKA if arterial pH <7.1, bicarbonate <5 mmol/L [10]. Patients were excluded if they had (1) any neurological abnormality or Glasgow Coma Scale (GCS) <13, (2) received any therapy (HCO3, mannitol, fluid, insulin) before admission to our hospital or were referred after the first 4 h of management, (3) any cause of acidosis other than DKA, (4) corrected serum sodium ≤130 and≥150 mmol/l.
Data on age, sex, onset of diabetes whether newly diagnosed or known, duration of diabetes, precipitating factor for DKA development, duration of insulin infusion, dose of insulin infusion, volume of fluid infused, and the use of bicarbonate therapy were collected.
All patients included in the study were managed according to ISPAD guidelines for DKA treatment [2] which is the protocol adopted at our unit which allow consistency concerning treatment. The protocol adopted at our unit as follows:
All included patients were managed accordingly: immediate measurement of blood glucose and capillary BHOH using glucometer (Free style Optium, Abbott)Footnote 1 were performed when available, weighing the patient and assessment of level of consciousness according to Glasgow Coma Scale [11] and severity of dehydration, full examination for a precipitating factor, and laboratory investigations
Subsequent clinical and biochemical monitoring included hourly assessment of vital signs, hourly (or more frequently as indicated) neurological observations (GCS) for warning signs and symptoms of cerebral edema, hourly capillary blood glucose concentrations, measurement of serum glucose, Na, K, CL, BUN, creatinine, and blood gases at the time of admission and every 4 h till DKA resolution. N.B. Blood glucose was measured in mg/dl, where 1mg/dl=18mmol/L.
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Calculation of:
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Anion Gap using the following formula: (Na+) – (HCO3- + Cl-). Normal= 12 ± 2 mmol/L
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Corrected Na =Measured Na+2(blood glucose−100)/100
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Serum osmolality (mosmol/kg); effective: 2 (Na) + glucose/18 [12].
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Hyperchloremia is defined as ratio of chloride: sodium [Cl−: Na+] > 0.79 [13].
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Fluid therapy
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A.
Resuscitation fluid (0.9% saline) was used for restoration of the peripheral circulation. The volume administered is 10 ml/kg over 1–2 h, this bolus fluid is given to patients with severe volume depletion and may be repeated until tissue perfusion is adequate. However, shocked patients with impaired peripheral perfusion were given 20 ml/kg as rapidly as possible.
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B.
Deficit replacement fluid therapy: First 4 h 0.9% saline was used then fluid with tonicity either 0.45% saline (half NS) or 0.9% saline was used.
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C.
Patients were divided into two groups according to the type of rehydration fluid used after 4 h: group 1 (N=72): Rehydration solution using 0.9% saline; group 2 (N=49): Rehydration solution using 0.45% saline provided that those patients had normal Na concentration.
The volume of total fluid replacement therapy and its rate were calculated based on data from Darrow study [2, 14].
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D.
Glucose 10% was added to replacement fluids (ratio 1:1) when plasma glucose reached approximately 300 mg/dL or if the rate of blood glucose dropped very rapidly (>88 mg/dL/h) after initial fluid expansion.
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E.
Potassium replacement was initiated after measurement of its serum level at concentration of 40 meq/L after initial volume expansion and concurrent with starting insulin therapy. If the patient was hyperkalemic, potassium replacement therapy was postponed until urine output was documented.
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F.
Bicarbonate therapy was considered in cases of severe acidosis (PH<6.9) with life threatening cardiac decompensation and also indicated in cases of life threatening hyperkalemia. It is given intravenously at a dose of 1–2 meq/kg over 1 h.
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G.
Cerebral edema: monitoring of clinical symptoms and signs suggestive of development of cerebral edema (headache, deterioration of neurological status, development of any neurological deficit, convulsion, Cushing’s triad) is a crucial part of DKA management. Once clinically suspected, immediate management is initiated. The rate of rehydration fluid is adjusted to maintain good perfusion and normal blood pressure while avoiding overhydration. Hypertonic solution (mannitol or hypertonic saline) is given slowly over 10–15 min. Other measures to decrease intracranial pressure must be applied (elevation of the head 30°, intubation with hyperventilation if patient had severe deterioration of neurologic status).
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Insulin therapy
Insulin infusion was started after 1 h of initiation of volume expansion by fluid replacement therapy at a dose ranging from 0.05 U to 0.1 U/kg/h. Criteria for shifting to subcutaneous insulin included resolution of acidosis (PH ≥ 7.3, HCO3≥15 mEq/L), a good general condition and hemodynamic stability, tolerating oral intake, patient no longer on vasopressors and BOHB ˂ 3 mmol/L.
The study protocol received approval from our Institutional Research Ethics Committee.
Statistical analysis
Data were statistically described in terms of mean ± standard deviation (± SD), median and range for numerical variables or frequencies, and percentages for categorical variables. Comparison of numerical variables between the study groups was done using Student’s T test. For comparing categorical data, chi-square (χ2) test was performed. Exact test was used instead when the expected frequency is less than 5. P values less than 0.05 was considered statistically significant. All statistical calculations were done using IBM SPSS (Statistical Package for the Social Science; IBM Corp, Armonk, NY, USA) release 22 for Microsoft Windows.