Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia –...

REGULAR ARTICLE

Isotonic versus hypotonic fluid supplementation in term neonates withsevere hyperbilirubinemia – a double-blind, randomized, controlled trialKarthik Balasubramanian, Praveen Kumar ([email protected]), Shiv Sajan Saini, Savita Verma Attri, Sourabh DuttaDepartment of Pediatrics, Neonatal unit, Post Graduate Institute of Medical Education and Research, Chandigarh, India

KeywordsHyperbilirubinemia, Hypernatremia, Hyponatremia,Intravenous fluid supplementation, Neonataljaundice

CorrespondenceP Kumar, D.M., Department of Pediatrics, NeonatalUnit, Post Graduate Institute of Medical Educationand Research, Chandigarh 160 012, India.Tel: +91-172-2755308 |Fax: +91-172-2744401 |Email: [email protected]

Received15 July 2011; revised 14 October 2011;accepted 27 October 2011.

DOI:10.1111/j.1651-2227.2011.02508.x

ABSTRACTAim: To compare the incidence of hyponatremia in full-term neonates with severe

hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5%

dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET).Methods: In this double-blind, randomized, controlled trial, full-term newborns

(‡37 weeks), appropriate for gestational age, with severe non-haemolytic hyperbilirubin-

emia (serum bilirubin ‡ 20 mg ⁄ dL) were enrolled. Eligible neonates were randomized to

receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5%

dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary out-

come was proportion of neonates developing hyponatremia (serum Na < 135 mmol ⁄ L)

after 8 h.Results: Forty-two neonates were analysed in each group. Proportion of neonates

developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to iso-

tonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic

fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was

similar in both groups.Conclusion: In full-term neonates with severe hyperbilirubinemia, administration of

hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia

while isotonic fluid was associated with an increased incidence of hypernatremia.

INTRODUCTIONSevere hyperbilirubinemia is one of the most commoncauses of neonatal readmissions to hospitals, and photo-therapy is the standard treatment for such infants (1).Dehydration is known to be associated with high serum bil-irubin levels. We have previously shown that three-fourthof neonates with severe hyperbilirubinemia have subclinicaldehydration at presentation (serum osmolal-ity > 290 mOsm ⁄ kg) (2). Serum bilirubin decreases muchfaster when full-term neonates with severe hyperbilirubin-emia are given fluids in addition to phototherapy (3). Intra-venous (IV) fluid supplementation has been shown todecrease the need for blood exchange transfusion (BET)and duration of phototherapy, in neonates with severe non-haemolytic hyperbilirubinemia. However, there is a risk ofdeveloping hyponatremia after IV fluid supplementationwith the usual maintenance fluid, that is 0.2% saline in 5%dextrose, which is hypotonic compared to plasma (2).

Hypotonic fluid infusions are a common cause of hospitalacquired hyponatremia with potential adverse conse-quences (4–10). It is hypothesized that the risk of hyponat-remia can be decreased with the use of isotonic fluidsrather than hypotonic fluids. This randomized, controlledtrial was planned to compare the incidence of hyponatre-mia between isotonic (0.9% saline in 5% dextrose) andhypotonic (0.2% saline in 5% dextrose) fluid used for IVfluid supplementation in full-term neonates with severehyperbilirubinemia. In addition, the two types of fluids were

Abbreviations

AAP, American academy of pediatrics; ADH, Antidiuretic hor-mone; BET, Blood exchange transfusion; G6PD, Glucose-6-phos-phate dehydrogenase; GFR, Glomerular filtration rate; IV,Intravenous; STB, Serum total bilirubin

Key notes• Hypotonic fluid supplementation (0.2% saline in 5% dex-

trose) in full-term neonates presenting with severe hyper-bilirubinemia increases the incidence of hyponatremia,whereas isotonic fluid (0.9% in 5% dextrose) decreasesthe incidence of hyponatremia but increases the risk ofhypernatremia. Both equally decrease the rate of bloodexchange transfusion and phototherapy duration. Posthoc calculations suggest that N ⁄ 3 (0.3%) saline in 5%dextrose may have the least risk of hyponatremia as wellas hypernatremia.

Acta Pædiatrica ISSN 0803–5253

236 ª2011 The Author(s)/Acta Pædiatrica ª2011 Foundation Acta Pædiatrica 2012 101, pp. 236–241

compared for incidence of hypernatremia, the rate ofexchange transfusion and duration of phototherapy.

MATERIAL AND METHODSStudy design and subjectsThis was a blinded, randomized, controlled trial, conductedin the neonatal unit of a tertiary care hospital from June2007 to April 2008. Full-term neonates (‡37 weeks gesta-tion), appropriate for gestational age (11) – presenting withsevere non-haemolytic hyperbilirubinemia [serum total bili-rubin (STB) ‡ 20 mg ⁄ dL] – were eligible for inclusion. Ges-tational age assessment was based on accurate date of lastmenstrual period and was corroborated by New Ballard’sScoring System (12). Neonates were excluded if they hadany clinical evidence of haemolysis (anaemia, organomeg-aly, positive Coomb’s test), onset of jaundice within 24 h,STB ‡ 25 mg ⁄ dL at presentation, clinical features of acutebilirubin encephalopathy, obvious clinical signs of dehydra-tion, hypoxic ischaemic encephalopathy or major congeni-tal malformations. They were also excluded if alreadyreceiving IV fluids for any reason and if they had alreadyundergone BET. Approval was obtained from the InstituteEthics Committee. An informed written consent wasobtained from one of the parents of eligible neonates beforeenrolment. The enrolled neonates underwent simple ran-domization. The random sequence was generated onlinefrom the website http://www.randomizer.org (accessed onApril 15, 2007) by a person not involved in the study. Thechief investigator, supervisors, caregivers, laboratory per-sonnel and statistician were masked to the intervention.The blood and urine samples taken from the neonates inboth study groups were coded. The code to the randomiza-tion sequence was opened only after the biochemical andstatistical analyses were complete.

InterventionThe eligible neonates received either 0.9% saline in 5% dex-trose (isotonic fluid group) or 0.2% saline in 5% dextrose(hypotonic fluid group). The study fluids were similar inappearance and were obtained in identical-looking 500-mLglass bottles. The person who generated the randomizationsequence and who was not involved in clinical care or inany other aspect of the study removed the original labelsand replaced them with new labels depicting the studyname and serial number. These pre-numbered bottles werehanded over to the chief investigator, who administeredthem serially to the enrolled neonates.

The IV fluid supplementation was given for a period of8 h. The volume of IV fluid supplementation included a pre-sumed deficit of 50 mL ⁄ kg (equivalent of mild dehydration),half of their daily maintenance requirement for 8-h periodand a phototherapy allowance of 20 ml ⁄ kg ⁄ day for 8 h. Inaddition, babies were allowed breast ⁄ formula feed ad libi-tum as they were taking before inclusion. Combining allthese, a simplified formula for calculating the IV fluid for8 h was derived: Amount in mL = [body weight(kg) · (340 + x)] ⁄ 6, where ‘x’ is the daily maintenance

requirement in mL. After 8 h of IV fluid supplementation,the infants were continued on breast or formula feeds asbefore. In addition to breast feeds, they were offered30 mL ⁄ kg ⁄ day extra oral feeds (expressed breast milk ⁄ for-mula milk) till they remained under phototherapy. Pre- andpost-feed test weighing was performed once in 24 h in allbabies, to estimate the volume of feed intake.

Data collection and monitoringBody weight, hydration status, feeding details, fluid intake,urine output and stool frequency of the enrolled neonateswere recorded at baseline. Samples for serum Na, STB,serum and urine osmolality, urine specific gravity, urinespot Na ⁄ Cr ratio, G6PD status and reticulocyte count werealso collected. Serum Na and STB were measured againafter 4 and 8 h of IV fluid supplementation while urineosmolality, urine specific gravity and urine spot Na ⁄ Cr ratiowere measured after 8 h of IV fluid supplementation. Neo-nates were evaluated daily for body weight, hydration sta-tus, feeding details, fluids intake, urine output, stoolfrequency and clinical signs of bilirubin encephalopathy.The infants were closely monitored till discharge from thehospital.

Serum sodium was measured by ion-selective electrodemethod by DimensionAR Autoanalyser (Dade Behring, New-ark, DE, USA; coefficient of variation 0.2% to 1.3%). Biliru-bin was checked by dual wavelength spectrophotometer(Bilirubin Meter BIL-100; Cosmo Medical, Korea; coeffi-cient of variation 5%). The measurement of osmolality wasbased on freezing-point depression technique using FiskeModel 210 Micro-osmometer (Fiske Associates, Norwood,MA, USA). All babies were provided with special blue-light,double-surface phototherapy. The irradiance was measuredonce daily by a fluxmeter (Fluoro-Lite Meter 451; MinoltaAirshields, Hatboro, PA, USA) and kept above 15 lwatt ⁄cm2 ⁄ nm. The decision to stop phototherapy or to treat withBET was based on the clinical practice guidelines given byAmerican Academy of Pediatrics (AAP) for the treatment ofneonatal hyperbilirubinemia (13). When STB was below thephototherapy zone, phototherapy was discontinued andrebound value was checked after 12 h. BET was done if, after4 h of fluid supplementation, STB increased by 2 mg ⁄ dLfrom baseline, or if, at 8 h of fluid supplementation or subse-quently, STB was still in the exchange zone (13).

Outcome measuresThe primary outcome was the proportion of neonates devel-oping hyponatremia (serum Na < 135 mmol ⁄ L) at the endof 8 h of IV fluid supplementation. The secondary outcomevariables were the duration of phototherapy, proportion ofbabies undergoing BET, proportion of babies developing hy-pernatremia (serum Na > 145 mmol ⁄ L) and the rate ofchange in serum sodium and STB.

Sample sizePrevious published literature from our unit showed that theincidence of hyponatremia after IV fluid supplementationamong neonates with severe hyperbilirubinemia was 40%

Balasubramanian et al. Fluid supplementation in neonatal jaundice

ª2011 The Author(s)/Acta Pædiatrica ª2011 Foundation Acta Pædiatrica 2012 101, pp. 236–241 237

(2). To detect a 60% decrease in the incidence of hyponatre-mia with two tailed a of 5% and b of 20%, a sample size of76 babies was needed. Assuming an attrition rate of 15%,we planned to enrol 88 babies (44 in each group).

Statistical analysisProportion of the neonates developing hypo- or hypernatre-mia was compared using chi-square test (with Yates correc-tion) or Fisher’s exact test, wherever applicable. The changeof serum sodium over the study period was comparedbetween two groups with repeated measures analysis of var-iance (RM-ANOVA). The median duration of phototherapywas compared by Mann–Whitney U-test. To compare thetwo groups for probability of neonates requiring photothera-py at a given point, survival analysis using Kaplan–Meiercurves and log rank tests was carried out. To find the inde-pendent risk factors for development of hyponatremia(serum sodium < 135 mmol ⁄ L), logistic regression analysiswas used. We decided a priori that hypotonic fluid group,gestational age and any factor significant on univariate

analysis will be included in the model. Analysis was carriedout in SPSS 15.0 for windows (SPSS Inc., Chicago, IL, USA).

RESULTSA total of 145 babies were eligible during the study period.Among them, 44 babies were randomized to hypotonic fluidgroup and 44 to isotonic fluid group (Fig. 1). The baselinedemographic, laboratory and hydration parameters areshown in Table 1. The volume of IV fluid (78 ± 4 vs.80 ± 3 mL ⁄ kg) and oral intake (breast feeds, spoon feeds orboth) (40 ± 6 vs. 42 ± 6 mL ⁄ kg) received in the first 8 h byhypotonic and isotonic fluid groups, respectively, were simi-lar. Total oral feed intake in the remaining 16 h on day 1(92 ± 13 vs. 94 ± 12 mL ⁄ kg) and subsequent study days(155 ± 13 vs. 161 ± 15 mL ⁄ kg on day 2 and 169 ± 10 vs.164 ± 18 mL ⁄ kg on day 3) were also similar between thetwo groups.

The proportion of neonates developing hyponatremiawas significantly lower in isotonic fluid group but

Analyzed (n = 42)

Excluded from analysis (n = 1)

(since no samples)

Analyzed (n = 42)

None excluded All analyzed

Analysis

None lost to follow up Follow-Up

Hypotonic Fluid Group(N/5 in 5%D)

(n = 44)Received IVF (n = 43)

Discontinued IVF (n = 1)(withdrew from study)

Isotonic Fluid Group (NS in 5%D)

(n = 44)Received IVF (n = 42)

Discontinued IVF (n = 2)(withdrew from study)

Allocation

No. of babies eligible (n = 145)

Excluded (n = 55)Reasons:Clinical signs of hemolysis = 2Onset of jaundice < 24 hrs = 13 TSB ≥ 25 = 11 Acute bilirubin encephalopathy = 8Severe dehydration = 1HIE = 2Congenital malformations = 4Already On IV fluids = 14

Enrollment

None lost to follow up

Randomized (n = 88) Refused consent = 2

Figure 1 Flow of patients in the study.

Fluid supplementation in neonatal jaundice Balasubramanian et al.


hypernatremia occurred significantly more frequently in iso-tonic fluid group (Table 2). Serum sodium over 8 h of IVfluid administration showed a significantly greater fall in thehypotonic fluid group as compared to the isotonic fluidgroup (0.9 ± 0.4 vs. )0.01 ± 0.6 mmol ⁄ h, p < 0.001, Fig. 2).In the hypotonic fluid group, at the end of 8 h of IV fluids,two (4.9%) infants had serum Na < 130 mmol ⁄ L; though,none had serum Na < 130 mmol ⁄ L at enrolment. Both neo-nates were asymptomatic. In the isotonic fluid group, 3(7.1%) infants had serum Na > 150 mmol ⁄ L at inclusionbut after 8 h of IV fluids, only 1 continued to have serumNa > 150 mmol ⁄ L. Urinary sodium excretion was signifi-cantly higher at 8 h as well as 24 h after IV fluid administra-tion in isotonic fluid group (Table 3).

Three factors including fluid group, gestational age andtype of feeding were subjected to logistic regression to findindependent predictors for development of hyponatremia

(serum Na < 135 mmol ⁄ L) after IV fluids at 8 h. Hypotonicfluid emerged as independent predictor of hyponatremia(OR: 13.0, 95% CI: 3.1–54.6, p < 0.001).

The proportion of babies who underwent exchange trans-fusion and the duration of phototherapy were similarbetween the two groups (Table 2). The rate of fall in STB at4, 8, 12 h and at 24 h were also similar between the twogroups and not influenced by the type of fluid (p > 0.05).The proportion of neonates requiring phototherapy at anypoint of time was similar in both the groups (log rank test,p = 0.52) (Fig. 3).

DISCUSSIONIn this double-blind, randomized, controlled trial, IV fluidsupplementation with isotonic fluid (0.9% saline in 5% dex-trose) as against hypotonic fluid (0.2% saline in 5% dex-trose), in full-term neonates with severe hyperbilirubinemia,was associated with a lower incidence of hyponatremia, butit resulted in an increased occurrence of hypernatremia.Both types of fluids were equally effective in reducing therate of exchange transfusion and duration of phototherapy.

Table 2 Primary and secondary outcomes

Characteristics

Hypotonic FluidGroup (N ⁄ 5 in 5% D)n = 42

Isotonic FluidGroup (NS in 5% D)n = 42 Relative Risk p

Hyponatremia (<135 mmol ⁄ L)

At 8 h 20 (49) 4 (11) 4.6 (1.7–2.3) <0.001

At 24 h 18 (44) 3 (3) – <0.001

Hypernatremia (>145 mmol ⁄ L)

At 8 h 5 (12) 15 (40) 3.2 (1.3–8.1) <0.001

At 24 h 4 (10) 14 (35) – <0.001

Duration of phototherapy (h) median (IQR) 42 (36, 48) 48 (36, 60) – 0.263

Exchange transfusion (%) 5 (12) 6 (14) – 0.746

Table 1 Baseline demographic, laboratory and hydration parameters

Characteristic

Hypotonicfluid groupn = 42

Isotonic fluidgroup n = 42

Gestational age (weeks) 38 ± 1 38 ± 1

Males (%) 23 (55) 23 (55)

Birth weight (g) 2918 ± 291 2840 ± 272

Oxytocin use (%) 15 (36) 20 (48)

Vaginal delivery (%) 29 (69) 29 (69)

Onset of jaundice (day) 3.8 ± 1.2 4.0 ± 1.0

Age at inclusion (day) 4.9 ± 2 5.5 ± 1.9

STB at enrolment (mg ⁄ dL) 22.1 ± 1.4 22.5 ± 1.2

Per cent weight loss 11.6 ± 4 11.3 ± 3

G6PD deficient (%) 5 (12) 3 (7)

Exclusive breast feeding (%) 36 (86) 27 (64)*

Reticulocyte count in percentage 2.1 ± 1 2.1 ± 1

Serum Na (mmol ⁄ L) 143 ± 6 142 ± 6

Serum osmolality (mOsm ⁄ kg) 295 ± 11 294 ± 11

Urine osmolality (mOsm ⁄ kg) 493 ± 71 481 ± 74

Urine specific gravity 1019 ± 4 1019 ± 5

Urine Na (mmol ⁄ L) 49 ± 18 50 ± 17

Spot Urine Na ⁄ Cr ratio 0.13 ± 0.03 0.13 ± 0.03

STB, serum total bilirubin.

*p value – 0.02.

Figure 2 Change in Serum Na over time in hypotonic and isotonic fluid groups.



Normally, neonates are administered N ⁄ 5 in 5% or 10%dextrose as the maintenance fluid. In earlier studies of fluidsupplementation in jaundiced neonates also, the fluid usedwas the usual maintenance fluid, that is N ⁄ 5 (0.18%) salinein 5% dextrose (2,14). This fluid has an in vitro osmolality ofapproximately 337 mOsm ⁄ kg of H2O but the in vivo tonic-ity is only 60 mOsm ⁄ L of H2O. Thus, N ⁄ 5 in 5% dextrose isa ‘hypotonic’ solution when compared to plasma. InfusingN ⁄ 5 in 5% dextrose is equivalent to infusing an electrolytefree water of approximately 80%. In contrast, isotonic solu-tion like 0.9% saline in 5% dextrose has an in vitro osmolal-ity of 585 mOsm ⁄ kg of H2O but the in vivo tonicity is308 mOsm ⁄ L H2O, which is isotonic with plasma. Hence, itmay minimize the changes in plasma sodium concentration

and tonicity (7). In a recent meta-analysis comparing hypo-tonic and isotonic saline in hospitalized children, Choonget al. (15) has shown that hypotonic solutions significantlyincreased the risk of developing acute hyponatremia (OR:17.22; 95% CI: 8.67–34.2) and resulted in greater patientmorbidity. Neville et al. (16) showed that in gastroenteritistreated with IV fluids, normal saline is preferable to hypo-tonic saline because it protects against hyponatremia with-out causing hypernatremia. However, newborn infants havea limited capacity for natriuresis because of low glomerularfiltration rate (GFR) and reduced ability to excrete sodiumbecause of the immature renal tubules (17). No data is avail-able regarding the incidence of hypernatremia with the useof isotonic fluids in neonates.

The probable reason for hypernatremia in isotonic fluidgroup in our study could be the relative inability of the neo-natal kidney to handle sodium load. An infusion of isotonicfluid for 8 h would have delivered a sodium load of12 mEq ⁄ kg. The urinary sodium excretion in the isotonicfluid group was higher than the hypotonic fluid group.However, because of low GFR and relatively high fractionaltubular sodium reabsorption during the sodium loadingamong neonates (17,18), this capacity was likely exceededby the sodium load in some infants. The ability to excretethe sodium load increases with age throughout the first yearof life. This maturational increase in sodium excretion isdue both to the increase in filtered sodium (because of mat-urational increase in the GFR) and to an increase in frac-tional sodium excretion (17). The mean age of the infants inthis study was only 5 days, further limiting the capacity toexcrete sodium load. Hyponatremia in the study infantsmight have occurred due to the infusion of hypotonic fluidor due to water retention secondary to non-osmotic antidi-uretic hormone (ADH) secretion. Non-osmotic stimulantsof ADH are common during acute illness and have beenshown to be active in many clinical situations requiring IVfluids, thereby limiting the renal excretion of free water (19–21). It is not clear whether severely jaundiced neonates haveincreased ADH levels. Ronconi et al. (22) found similarADH levels between jaundiced and normal newborns.

Hence, it appears that an ideal fluid might be somewherebetween normal saline and 0.2% saline. Based on the studyby Aperia et al. (17), a term healthy neonate of 3 kg couldexcrete a maximum of 12 mEq of sodium over 8 h in urine.An ideal fluid for supplementation in such neonates couldbe N ⁄ 3 (0.3%) saline in 5% dextrose, which would give asodium load of 4 mEq ⁄ kg over 8 h (12.2 mEq for a 3 kgneonate) (17).

The beneficial effects of fluid supplementation in severelyjaundiced neonates demonstrated earlier by Mehta et al.(2). and Boo and Lee (3)., were reconfirmed by this study.The proportion of infants undergoing exchange transfusion(13%) was similar to that in the fluid supplementation group(16%) in the trial by Mehta et al. (2). Both types of fluidshad similar beneficial effects on the duration of photothera-py and the rate of exchange transfusion.

The double-masked study design and objective primaryoutcome add strength to this controlled trial. However,

Table 3 Change in biochemical parameters over study period

Characteristics

Hypotonic fluidgroup (N ⁄ 5 in 5% D)n = 42

Isotonic fluidgroup (NS in 5% D)n = 42 p

Serum osmolality (mOsm ⁄ kg)

After 8 h 282.92 ± 8.18 287.70 ± 7.48 0.146

After 24 h 282.05 ± 5.04 286.65 ± 5.05

Urine osmolality (mOsm ⁄ kg)

After 8 h 349.86 ± 55.38 345.24 ± 55.74 0.246

After 24 h 362.78 ± 40.91 348.57 ± 38.95

Urine sodium (mmol ⁄ L)

After 8 h 28.55 ± 12.12 62.20 ± 18.24 <0.001

After 24 h 28.24 ± 13.60 66.66 ± 26.81

Urine spot sodium ⁄ creatinine ratio (mmol ⁄ mg)

After 8 h 0.43 ± 0.22 0.74 ± 0.44 <0.001

After 24 h 0.24 ± 0.15 0.55 ± 0.29

Urine specific gravity

After 8 h 1011 ± 3 1011 ± 4 0.634

After 24 h 1011 ± 3 1010 ± 3

Figure 3 Kaplan–Meir survival curves showing the probability of remainingunder Phototherapy.

Fluid supplementation in neonatal jaundice Balasubramanian et al.


there are certain limitations. The fluid requirement was cal-culated on the basis of presumed 5% deficit. Different vol-umes may result in different outcomes. Only spot urinesodium concentrations were measured at different timeperiods. Measurement of 24-h urine sodium, fractionalexcretion of sodium (FeNa) and other electrolytes in urinealong with calculation of urine tonicity may help in estimat-ing the most appropriate fluid. ADH levels could not bemeasured. Hence, the contribution of ADH in developmentof hyponatremia is not known.

CONCLUSIONThe IV fluid supplementation with isotonic fluid (0.9% sal-ine in 5% dextrose) as compared to routine maintenancefluid (0.2% saline in 5% dextrose), in full-term neonates pre-senting with severe non-haemolytic hyperbilirubinemia,resulted in a decreased incidence of hyponatremia; how-ever, it was associated with increased possibility of hyper-natremia. Both types of fluids were effective in reducing therate of exchange transfusion and duration of phototherapy.

ACKNOWLEDGEMENTWe are grateful to Prof. V. Jha of the department ofNephrology for his support in carrying out measurements ofosmolality from the renal laboratory.

CONFLICT OF INTERESTNone.

FINANCIAL DISCLOSURENone.

References

1. Sgro M, Campbell D, Shah V. Incidence and causes of severeneonatal hyperbilirubinemia in Canada. CMAJ 2006; 175: 587–90.

2. Mehta S, Kumar P, Narang A. A randomized controlled trial offluid supplementation in term neonates with severe hyperbiliru-binemia. J Pediatr 2005; 147: 781–5.

3. Boo NY, Lee HT. Randomized controlled trial of oral versusintravenous fluid supplementation on serum bilirubin level dur-ing phototherapy of term infants with severe hyperbilirubin-emia. J Paediatr Child Health 2002; 38: 151–5.

4. Moritz ML, Ayus JC. Prevention of hospital-acquired hyponat-remia: a case for using isotonic saline. Pediatrics 2003; 111:227–30.

5. Arieff AI, Ayus JC, Fraser CL. Hyponatremia and death or per-manent brain damage in healthy children. BMJ 1992; 304:1218–22.

6. Moritz ML, Ayus JC. Preventing neurological complicationsfrom dysnatremias in children. Pediatr Nephrol 2005; 20:1687–700.

7. Taylor D, Durward A. Pouring salt on troubled waters. The casefor isotonic parenteral maintenance solution. Arch Dis Child2004; 89: 411–4.

8. Jenkins J, Taylor B. Prevention of hyponatremia. Arch Dis Child2004; 89: 93.

9. Moritz ML, Ayus JC. Hospital-acquired hyponatremia: why arethere still deaths [commentary]? Pediatrics 2004; 113: 1395–6.

10. Moritz ML, Ayus JC. Disorders of water metabolism in chil-dren: hyponatremia and hypernatremia. Pediatr Rev 2002; 23:371–80.

11. Lubchenco LO, Hansman C, Boyd E. Intrauterine growth inlength and head circumference as estimated from live births atgestational ages from 26 to 42 weeks. Pediatrics 1966; 37: 403–8.

12. Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL,Lipp R. New Ballard Score expanded to include prematureinfants. Pediatrics 1991; 119: 417–23.

13. American Academy of Pediatrics – Clinical practice guideline.Management of hyperbilirubinemia in the newborn infant 35 ormore weeks of gestation. Pediatrics 2004; 114: 297–316.

14. Iranpour R, Nohekhan R, Haghshenas I. Effect of intravenousfluid supplementation on serum bilirubin level in jaundicedhealthy neonates during conventional phototherapy. J Res MedSci 2004; 4: 35–9.

15. Choong K, Kho ME, Menon K, Bohn D. Hypotonic versus iso-tonic saline in hospitalised children: a systematic review. ArchDis Child 2006; 91: 828–35.

16. Neville KA, Verge CF, Rosenberg AR, O’Meara MW, WalkerJL. Isotonic is better than hypotonic saline for intravenousrehydration of children with gastroenteritis: a prospective ran-domized study. Arch Dis Child 2006; 91: 226–32.

17. Aperia A, Broberger O, Thodenius K, Zetterstrom R. Renalresponse to an oral sodium load in newborn full term infants.Acta Paediatr Scand 1972; 61: 610–6.

18. Aperia A, Broberger O, Thodenius K, Zetterstrom R. Develop-mental study of renal response to an oral salt load in preterminfants. Acta Paediatr Scand 1974; 63: 517–24.

19. Gerigk M, Gnehm HE, Rascher W. Arginine vasopressin andrenin in acutely ill children: implication for fluid therapy. ActaPaediatr 1996; 85: 550–3.

20. Halperin M, Goldstein MB. Hyponatremia. In: Halperin M,Goldstein MB, editors. Fluid, electrolyte, and acid-base physiol-ogy: a problem-based approach, 3rd ed. Philadelphia: Saunders,1999: 283–327.

21. Robertson GL. Regulation of vasopressin secretion. In: SeldinDW, Gibish G, editors. Clinical disturbances of water metabo-lism. New York: Raven, 1993: 99–119.

22. Ronconi M, Ronconi GF, Pesenti P, Soffiati G, Fantuz E, Za-nardo V. Effect of phototherapy on the plasma levels of antidi-uretic hormone in the newborn infant. Pediatr Med Chir 1985;7: 229–31.



Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia –...

Documents

Transcript of Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia –...