This was a randomised controlled trial (RCT) with parallel assignment done in non-critically ill children who required more than 50% of total calculated maintenance intravenous fluids between the ages of 6 months to 14 years admitted in the In-Patient Department (IPD) of Paediatrics and Paediatrics surgery, All India Institute of Medical Sciences, Bhubaneswar, India, during the study period from August 2021 to July 2022. The Institute Ethics Committee approved the study vide letter no IEC/AIIMS BBSR/PG Thesis/2020-21/97 dated December 21, 2020 and registered by the Clinical Trial Registry India (CTRI) (www.ctri.nic.in) vide registration number CTRI/2021/08/035924.
Conditions requiring a change of maintenance fluids, such a chronic kidney disease (CKD) / congenital or acquired liver disease / Diabetes Insipidus/Diabetes Mellitus, conditions / procedural fluid therapy in which intravenous fluids were expected to be given for a shorter duration than 6h for example an elective procedure like Computed Tomography (CT) / Magnetic Resonance Imaging (MRI) Scans, conditions causing changes in chloride levels example: Barter Syndrome, Congenital Adrenal Hyperplasia, Cystic Fibrosis were excluded from the study.
The sample size was calculated from an online software using www.sealedenvelope.com for a non-inferiority trial. Based on the previous experience in the Department of Paediatrics, AIIMS, Bhubaneswar, we used the following parameters for sample size calculation with a non-inferiority margin of 2 mEq/L with standard deviation of 4.5 mEq/L of serum chloride with 80% power and alpha error of 5 %, the total sample size of 126 with 10% attrition, the sample size calculated was 70 in each group. Participants were randomized using computer generated block randomization (in sets of 2, 4 and 6) with an allocation ratio of 1:1 was done using the opaque sealed envelope technique by a staff who was not involved in the study.
The children admitted to the Departments of Paediatrics and Paediatrics Surgery fulfilling the study inclusion criteria, were enrolled in the study. Details of the study were explained, consent was taken from the parents, and assent was obtained from those over 7 years old after providing the participants a detailed information sheet. Then they were randomized as mentioned above and were allocated into one of the study groups.
Study Groups: Group-A: 5% Dextrose in Ringer’s Lactate + Maintenance Potassium at 20mEq/L, Fluid Preparation: 50ml of 50% Dextrose was mixed in 450ml of Ringer’s Lactate and 4ml of Potassium Chloride (KCl) was added to make a total of 504ml IV fluid. 50% Dextrose, KCl and the Ringer’s lactate bottles was kept in laminar flow hood and ultraviolet rays was switched on, two hours later, the ultraviolet rays were switched off. Following this the doctor or nurse under aseptic condition prepared the required maintenance fluid as per the standard fluid calculation as per departmental policy under the laminar flow hood[4]. Group-B: Normal Saline 0.9% in 5% Dextrose + Maintenance Potassium 20mEq/L.
Demographic data was collected and, the Kidney Function Tests (using Beckman Coulter -5800 machine), Blood Gas Analysis (using Siemens Healthineers- Rapid Point 500) were done at admission, 24 hrs and 48hrs after starting of the maintenance IV fluid. The study measurements were done till 48hrs and recorded following the initiation of maintenance fluid.
The primary outcome considered was to calculate the mean difference of serum chloride in children receiving 5% Dextrose in Ringer’s Lactate versus 5% Dextrose Normal Saline at 24 and 48hrs after start of fluids. The secondary outcomes were to estimate the proportion of children developing dyselectrolytemia defined as Hypochloremia: Serum Chloride level < 95 mmol/L [5], Hyperchloremia: Serum Chloride level > 105mmol/L [5], Hyponatremia: Serum Sodium level < 135 mmol/L [5], Hypernatremia: Serum Sodium level > 145 mmol/L [5], Hypokalemia: Serum Potassium level < 3.5 mmol/L [5], Hyperkalemia: Serum Potassium level > 5.3 mmol/L [5], to estimate the proportion of children developing HCMA defined as Hyperchloremia with serum pH <7.35 and Bicarbonate<24mmol/L and / or a base deficit of >5 mEq/L
[6] , to estimate the proportion of children developing acute kidney injury defined based on KDIGO[7]
Stage
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Serum Creatinine
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Urine output
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1
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1.5-1.9 times baseline or ≥0.3mg/dl increase within 48hrs
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< 0.5ml/kg/hr for 6-12 hrs
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2
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2.0-2.9 times baseline
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< 0.5ml/kg/hr for >/= 12 hrs
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3
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Three times baseline or increase in serum creatinine to >/= 4.0mg/dl or Initiation of renal replacement therapy or eGFR< 35ml/min per 1.73 m2
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0.3ml/kg/hr for 24 hrs or Anuria for >/= 12 hrs”
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and to estimate all-cause mortality in both groups. Those developing dyselectrolytemia, HCMA and acute kidney injury were actioned upon.
STATISTICAL ANALYSIS: Data was entered in Microsoft Excel, and statistical analysis was done using SPSS statistical software Version 20. Continuous data were expressed as mean and standard deviation, was analysed using the Student-T test. Categorical data were expressed as percentages, and were analysed through Fisher’s exact test or Chi-Square test. All statistical tests were 2-sided and a p value of <0.05 was considered significant.