Restricted versus conventional fluid administration in Extremely Low Birth Weight neonates: A randomised control non-inferiority trial

Extremely low birth weight babies contribute to a very small percentage of the total

number of admissions in the NICU but contribute a disproportionality high number

up to 27% of total mortality. Cochrane review comparing restricted and liberal fluid

management in neonates to prevent various morbidities has shown that following

restricted fluid management there was a reduction in the incidence of PDA and

Necrotising Enterocolitis (NEC) and a trend towards reduction in bronchopulmonary

dysplasia, intracranial hemorrhage and death. (4). In the same review, the total fluid

rate (TFR) in the first week of life ranged from a daily average of 60-80ml/kg/day

in the restricted fluid arm, and the liberal group, TFR was up to 160-180ml/kg/day.

To assess the effect of restricted and liberal fluid regimens in ELBW infants admitted

in the neonatal intensive care unit (NICU) with the primary outcome being a reduction in

all cause mortality. Sample size of this RCT is 100 and to be conducted over 1 year.

All extremely low birth weight neonates(<1000 grams) will be included in the study. There are

Two study groups: Group A: restricted fluid management. Group B: Liberal fluid

management group. Blinding :This is an unblinded study since the as per

methodology, the study cannot be blinded. The fluid management in the enrolled participants would be done as follows based on their group of randomisation. Evnthough in the literature review, the initial fluid requirement on day 1 of life in the restricted arm is 60-80ml/kg/day, in this study,the fluid requirement has been proposed as 80-100ml/kg/day due to feasibility issues.

Day of life

Restricted fluid(ml/kg/day)

Liberal fluid (ml/kg/day)

|D1

80-100

120-130

|D2

100-120

130-150

|D3

120-140

150-170

|D4

140-160

170 -180

|D5

160-170

180-200

|Maximum fluid volume

170

200

During the study, the enrolled neonates will be monitored by:

Weight will be measured using an electronic weighing scale which will be

calibrated daily

Urine specific gravity- Urine will be collected using sterile bag/cotton, noninvasively

and a urine refractometer will be used for checking the specific

gravity

Serum Sodium, Creatinine and venous blood gas are obtained in the sample

report using 0.1ml of blood using ABG Analyser.

All of the above are routinely done for ELBW babies admitted to NICU, there

is no requirement for additional tests or there won’t be any additional

expenditure involved.

Maintenance intravenous fluids will be increased by 10ml**10ml/kg/day in the

presence of any of the following in the restricted fluid arm:

1) Abnormal urine output ( <1ml/kg/hr or > 5ml/kg/hr) and urine-specific

gravity ( >1.018)

2) Weight loss of more than 1.5%-2% every 12hrly ( 3%-4% every 24hrly)

3) Serum creatinine of more than 1.5mg/dl or more than 1.5times the

baseline S. Creatinine

4) Serum Sodium of more than 160meq/dl.

5) VBG suggestive of Metabolic acidosis with pH <7.25, Hc03 < 16, Base

deficit >8-10 or lactate more than 4.

In neonates enrolled in the restrictive group will be changed over to liberal

group fluid as per the day-of-life if the fluid requirement is required to be

increased by 10ml/kg/day two times in 12 hrs. In both groups, if the neonate

develops hypovolemic shock, septic or cardiogenic shock fluid management

will be as per standard shock management. Rest of the management of neonates**will be as per NICU protocol and study results will be analyzed using statistical

tests.