Clinical trial NCT00621348: Maintenance Intravenous Fluids in Children
Official title: A RCT to Evaluate the Effect of Normal Saline in 5% Dextrose at Maintenance Rate, N/5 Saline in 5% Dextrose at 2/3 Maintenance Rate and N/5 Saline in 5% Dextrose at Maintenance Rate on Incidence of Hyponatremia in Hospitalized Children.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyponatremia
Keywords: maintenance fluids
hyponatremia
vasopressin
children
Lead sponsor: All India Institute of Medical Sciences
Sponsor class: OTHER
First posted: 2008-02-22
Enrollment: 167
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hyponatraemia arises in between 20% and 45% of sick hospitalized children. An important reason for this high incidence could be use of hypotonic fluids in sick children for maintenance fluid therapy. There are no randomized controlled trials to evaluate the effect of various types of intravenous fluids on the incidence of hyponatremia in sick hospitalized children.

Hypothesis: Use of normal saline in 5% dextrose or reduced (2/3) volume of N/5 saline in 5% dextrose reduces incidence of hyponatremia (serum sodium 130 mmol/L) by two-thirds when compared to N/5 saline in 5% dextrose at standard maintenance rate in hospitalized children receiving intravenous maintenance fluids.

Detailed description: Hyponatraemia arises in between 20% and 45% of sick hospitalized children. An important reason for this high incidence could be use of hypotonic fluids in sick children for maintenance fluid therapy. There are no randomized controlled trials to evaluate the effect of various types of intravenous fluids on the incidence of hyponatremia in sick hospitalized children. We therefore plan to conduct a randomized controlled trial to evaluate the effect of normal saline in 5% dextrose at standard maintenance rate, reduced volume (2/3 maintenance rate) of N/5 saline in 5% dextrose and N/5 saline in 5% dextrose at standard maintenance rate on the incidence of hyponatremia in hospitalized children, aged 3 months- 12 years. To determine serial plasma vasopressin levels in hospitalized children at baseline, 24 hours and 48 hours of intravenous fluid therapy and compare the values in the three fluid regimens.

Study design: Randomized controlled trial. Hospitalized children who fulfill inclusion criteria and not having any of the exclusion criteria will be considered for the enrolment after written informed consent. Venous blood samples will be taken at enrollment for estimation of serum sodium, potassium, chloride, bicarbonate, blood gas, blood sugar, blood urea, serum creatinine, and plasma osmolality. A sample for estimation of plasma vasopressin will be collected at baseline. After randomization into three groups, one group of children will receive N/5 saline in 5% dextrose at standard maintenance rate (100 ml/kg for the first 10 kg of body weight, 50 ml/kg for the next 10 kg, and 20 ml/kg for body weight exceeding 20 kg).The second group of children will receive N/5 saline in 5% dextrose at 2/3 maintenance rate. The third group will receive dextrose normal saline at standard maintenance rate. Serum Na+, K+ and urine Na+, K+ will be estimated every 12 hourly till the patient is on intravenous fluid therapy and 12 hrs after stopping exclusive intravenous maintenance fluids. Serum and urine osmolality will be estimated every 24 hrs by an osmometer. Plasma vasopressin will be estimated in children in the 3 groups at 24, and 48 hours of intravenous fluid therapy.

Children will be weighed every 24 hours. The fluid balance, sodium balance, free water clearance will be calculated in a subset of children.

The study measurements will be carried out only till the time the child is on exclusive intravenous maintenance fluid therapy or 72 hrs of starting the intravenous fluid therapy. The decision to decrease/ stop intravenous fluid therapy will be left to the treating unit.

The primary outcome measure will be incidence of hyponatremia (defined as serum Na+ less than 130 mmol/L).

The secondary outcomes studied will be Plasma vasopressin levels at 24 hr and 48 hours and incidence of hypernatremia.

Sample size: Based on literature review, the incidence of hyponatremia with standard intravenous fluid therapy is approximately 30%. Sample of 72 patients will be needed in each group to demonstrate the decrease in incidence of hyponatremia to 10%, with a beta of 0.2 (Power 80%) and alpha error of 0.05.

Analysis: The data will be analyzed using STATA software. The outcomes (primary and secondary) in the 3 groups will be compared. For continuous variables, t test or Wilcoxon rank-sum test will be used to determine statistical significance. For categorical variables, chi square test will be used.

Eligibility criteria: Inclusion Criteria:

* All children (3 months to 12 years) who are admitted to pediatric ward or pediatric ICU, who require exclusive intravenous maintenance fluid therapy for at least 24 hours will be eligible for the study

Exclusion Criteria:

* Children with illness that have primary fluid and electrolyte imbalance such as:

  * Shock: Defined as acute circulatory failure resulting in decreased tissue perfusion and manifesting as altered sensorium, hypothermia (\<35oC), tachycardia, prolonged capillary filling time (\>3 seconds), hypotension (BP \< 5th percentile for age), oliguria (\<0.5 ml/kg/hr), hypoxemia, hyperlactatemia, requirement of fluid bolus and/ or vasopressors.
  * Diarrhea and Dehydration: Children presenting with diarrhea and features of dehydration: lethargy, irritability and altered sensorium, thirst, decreased urine output, sunken eyes \& dry mucous membranes, loss of skin elasticity.; children with ongoing diarrhea will be excluded even if there is no dehydration.
  * Fluid Overload: Cirrhosis, Congestive heart failure, Acute and Chronic renal failure, Nephrotic syndrome.
* Abnormal serum sodium or Hyperglycemia at Presentation:

  * Hyponatremia : serum sodium \< 130 mmol/L.
  * Hypernatremia : serum sodium \>150 mmol/L.
  * Hyperglycemia: blood glucose \> 180 mg/ dl.
* Severe Protein Energy Malnutrition: Defined as grade III (50-59% of expected weight for age) and grade IV (less than 50% of expected weight for age) as per IAP classification.
* Child who is receiving drugs which cause abnormality in serum sodium such as diuretics, vasopressin, etc.

Primary outcomes:
measure: Incidence of Hyponatremia (Defined as Serum Sodium Less Than 130 mmol/L)
timeFrame: 72 hrs
Secondary outcomes:
measure: Incidence of Hypernatremia (Serum Sodium >150 mmol/L)
timeFrame: 72 hrs
measure: Incidence of Symptomatic Hyponatremia
timeFrame: 72 hrs
measure: Incidence of Symptomatic Hypernatremia
timeFrame: 72 hrs
Other outcomes:
Locations:
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
Study officials:
affiliation: All India Institute of Medical Sciences
name: Rakesh Lodha, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kannan L, Lodha R, Vivekanandhan S, Bagga A, Kabra SK, Kabra M. Intravenous fluid regimen and hyponatraemia among children: a randomized controlled trial. Pediatr Nephrol. 2010 Nov;25(11):2303-9. doi: 10.1007/s00467-010-1600-4. Epub 2010 Jul 29.