Bolus fluid therapy and sodium homeostasis inpaediatric gastroenteritis

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doi:10.1111/jpc.12120

ORIGINAL ARTICLE

Bolus ﬂuid therapy and sodium homeostasis in paediatric gastroenteritis Stephen B Freedman1 and Denis F Geary2,3,4 1 Sections of Emergency Medicine and Gastroenterology, Department of Paediatrics, Children’s Hospital and Alberta Children’s Hospital Research Institute, University of Calgary, Alberta and 2Nephrology, 3Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, The Hospital for Sick Children and 4Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

Aim: The study aims to assess the risk of developing hyponatraemia when large-volume bolus ﬂuid rehydration therapy is administered. Methods: We conducted a prospective randomised study in a tertiary-care centre emergency department. Participants included children with gastroenteritis and dehydration requiring intravenous rehydration. They were randomised to receive 60 mL/kg (large) or 20 mL/kg (standard) 0.9% saline bolus followed by maintenance 0.9% saline for 3 h. Biochemical tests were performed at baseline and 4 h. The primary outcome measure was the development of hyponatraemia at 4 h. Secondary outcome measures were (i) change in sodium relative to baseline value; (ii) magnitude of decrease among those who experienced a decrease; (iii) risk of hypernatraemia; (iv) correlations between urine parameters and hyponatraemia; and (v) ﬂuid overload. Results: Eighty-four of 224 (38%) participants were hyponatraemic at baseline. At 4 h, 22% (48/217) had a dysnatraemia, and similar numbers of children were hyponatraemic in both groups: large (23% (26/112)) versus standard (21% (22/105)) (P = 0.69). Among initially hyponatraemic children, 63% (30/48) who received large-volume rehydration and 44% (15/34) of those administered standard rehydration were isonatraemic at 4 h (P = 0.10). Overall, children who received 60 mL/kg experienced a larger mean increase (1.6 ⫾ 2.4 mEq/L vs. 0.9 ⫾ 2.2 mEq/L; P = 0.04) and were less likely to experience a sodium decrease of ⱖ2 mEq/L (8/112 vs. 17/105; P = 0.04) than those administered 20 mL/kg. Conclusions: Large-volume bolus rehydration therapy with 0.9% saline is safe. It does not promote the development of hyponatraemia over the short term, but hastens the resolution of baseline hyponatraemia. Key words:

ﬂuid therapy; gastroenteritis; hyponatraemia; intravenous infusion.

Abbreviations:

ADH, antidiuretic hormone; CDS, clinical dehydration scale; ED, emergency department; ORT, oral rehydration therapy

What is already known on this topic

What this study adds

1 Children with gastroenteritis treated with intravenous ﬂuids are at risk for developing hyponatraemia. 2 In volume-depleted children, experts recommend isotonic bolus ﬂuid therapy, in doses ranging from 20 to 60 mL/kg. 3 Rapid intravascular volume expansion may increase urinary sodium excretion and compound hyponatraemia from preexistent water retention due to non-osmotic antidiuretic hormone secretion.

1 Large-volume bolus rehydration therapy with 0.9% saline is safe. 2 Large-volume bolus rehydration therapy with 0.9% saline does not promote the development of hyponatraemia. 3 Large-volume bolus rehydration therapy with 0.9% saline hastens the resolution of baseline hyponatraemia.

Correspondence: Dr Stephen B Freedman, Section of Emergency Medicine, Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, AB, Canada T3B 6A8. Fax: 416-813-5043; email: stephen.freedman@albertahealthservices.ca Declaration of conflict of interest: The authors have no conflicts of interest to declare. The first draft of the manuscript was written by Stephen Freedman. No honorarium, grant or other form of payment was given to anyone to produce the manuscript. Funding Funding for the collection of data performed in this study was provided by a grant from The Physicians’ Services Incorporated Foundation (principal investigator: S. Freedman). The clinical trial which served as the basis for data collection for this study was registered at http://www.ClinicalTrials.gov (number, NCT00392145). Presentations This study was presented at the 2012 Pediatric Academic Societies’ Annual Meeting; Boston, MA, 28 April 2012, and the Canadian Pediatric Society’s 89th Annual Conference, London, ON, 7 June 2012. Accepted for publication 6 February 2012.

Bolus ﬂuids and sodium homeostasis

SB Freedman and DF Geary

Children with gastroenteritis treated with intravenous fluids are at risk for developing hyponatraemia.1,2 When hypotonic maintenance fluid therapy (primarily 5% dextrose in 0.3% saline) is employed, nearly 20% of initially isonatraemic children in one retrospective study developed iatrogenic hyponatraemia, with an average fall in serum sodium of 6 mEq/L.3 This occurs in part because children with gastroenteritis frequently have nonosmotic stimuli inducing antidiuretic hormone (ADH) secretion.4 Thus, recommendations suggest that hypotonic fluids not be given to children,2 particularly those with a sodium level <138 mEq/L.5,6 In volume-depleted children, experts recommend isotonic bolus fluid therapy, in doses ranging from 20 to 60 mL/kg.7 However, the biochemical impact of large-volume (e.g. 60 mL/ kg) bolus rehydration in children with non-osmotic ADH secretion is unknown. Theoretically, this could precipitate a sharp decline in serum sodium. Individuals with minimal dehydration are at particularly high risk, because rapid intravascular volume expansion may increase urinary sodium excretion and compound hyponatraemia from pre-existent water retention due to non-osmotic ADH secretion. However, in children with significant dehydration, a large fluid bolus may reduce the severity of dehydration, thereby reducing volume-induced ADH secretion and the risk of developing hyponatraemia. Because tests of dehydration are imprecise,8 our objective was to assess the risk, in children with gastroenteritis and dehydration, of developing hyponatraemia when 0.9% saline large-volume bolus fluid rehydration therapy is administered.

Materials and Methods Study setting and population Enrolment occurred from December 2006 to April 2010 in the emergency department of The Hospital for Sick Children, Toronto. Eligible children were >90 days of age and were diagnosed as having dehydration (clinical dehydration scale (CDS) score of >3;9–11 Table 1) secondary to gastroenteritis. All potentially eligible participants were instructed on the performance of

oral rehydration therapy (ORT), performed by administering 5 mL of a flavoured oral rehydration solution through a syringe every 5 min, with the rate increased based on tolerance and the child’s weight.13 Children who subsequently failed ORT13 and were prescribed intravenous rehydration were potentially eligible (Fig. 1). Children were excluded if they weighed <5 kg; required fluid restriction; had a suspected surgical condition; had a history of a significant chronic systemic disease, abdominal surgery, or bilious or bloody vomitus. Children weighing >33 kg were excluded as they required a bolus of >2 L during the first hour, which was not technically feasible with our intravenous infusion set-up. We also excluded children who had hypotension, hypo- or hyperglycaemia, an insurmountable language barrier, or no telephone for follow-up. The study was approved by The Hospital for Sick Children’s Research Ethics Board. Written informed consent was obtained from care givers, and participant assent was obtained when appropriate. All data for this study were collected as part of a clinical trial evaluating the clinical impact of large-volume, compared with standardvolume, intravenous rehydration.14 As such, this is a secondary database analysis.

Study protocol Children were prospectively randomised (1:1 allocation) to receive either a 60 mL/kg (large) or 20 mL/kg (standard) bolus of 0.9% saline over 60 min.15 A computer-generated permutedblock randomisation sequence stratified by severity of dehydration was employed. The sequence was concealed from the research nurses in sequentially numbered, sealed opaque envelopes prepared by an independent co-ordinator. The envelopes were provided to the research nurse once consent had been obtained. The randomisation code remained secured until enrolment and data entry were complete. The research nurse, attending physicians and participants were blinded to treatment allocation. The following signs of fluid overload were assessed and documented every 30 min by the research nurse: tachypnoea (increase of >20 breaths per minute from baseline), tachycardia (increase of >20 beats

Table 1 Clinical dehydration scale† Characteristic

Score of 0

Score of 1

Score of 2

General appearance‡

Normal

Eyes Mucous membranes§ Tears

Normal Moist Present

Thirsty, restless, or lethargic but irritable when touched Slightly sunken Sticky Decreased

Drowsy, limp, cold or sweaty, comatose Very sunken Dry Absent

†Higher scores indicate more severe dehydration. Scores range from 0 to 8. This four-item scale has previously been shown to have good inter-rater reliability (intraclass correlation coefﬁcient = 0·77; 95% CI 0·68, 0·86) and discriminatory power (Ferguson’s d = 0·83; 95% CI 0·77, 0·88).9 Subsequent prospective validation has demonstrated that it correlates with length of stay and need for intravenous rehydration.10 Furthermore, it has been validated independently in two emergency departments.11 A score of 0 correlates with <3% dehydration (LR+ 2.2; 95% CI 0.9, 5.3), scores of 1–4 correlate with some (3–6%) dehydration (LR+ 1.3, 95% CI 0.9, 1.7) and 5–8 correlates with moderate to severe (ⱖ6%) dehydration (LR+ 5.2; 95% CI 2.1, 12.8).12 ‡‘Normal’ includes children who may be sleeping but are easily aroused to a normal level of consciousness. This assessment takes into account the time of day and the child’s usual sleep pattern as described by the child’s guardian. §This is assessed on the buccal mucosa and tongue, and not the lips.

SB Freedman and DF Geary

Bolus ﬂuids and sodium homeostasis

785 were assessed for eligibility 559 were excluded •

507 did not meet

inclusion/exclusion criteria •

52 did not have parental consent

226 were enrolled and underwent randomisation *

114 assigned to large-volume

112 assigned to standard

intravenous rehydration

114 had baseline (T0) sodium data

110 had baseline (T0) sodium data •

112 had T 4 sodium data Fig. 1 Flow diagram of patient selection. *Dedicated registered nurses were present 80 h per week (including weekends and after-hours) to facilitate recruitment, randomisation and the conduct of the study in accordance with the protocol.

•

105 had T 4 sodium data

2 – no T4 bloodwork

55 had urine, T 0 and T4 data • 47 excluded - no urine sample collected

per minute from baseline, after adjustment for fever), peripheral oedema and hypoxia (decrease in transcutaneous oximetry of >5% from baseline). If any of these signs was detected, the research nurse had the attending physician determine the clinical relevance (i.e. need to discontinue treatment protocol). Opaque covers concealed the infusion bags and tubing, and soundproof (Quiet Barrier HD, American Micro Industries Inc., Chambersburg, PA, USA) boxes concealed the intravenous pumps (Department of Medical Engineering). Following the initial fluid bolus, all subjects were switched to a 0.9% saline + 5% dextrose solution at a maintenance rate determined according to the Holliday and Segar guidelines.16,17 Potassium chloride was added based on the serum potassium level: 0 mEq/L if >5.0 mEq/L, 20 mEq/L if 4.0–5.0 mEq/L, 40 mEq/L if <4.0 mEq/L. We refer to 0.9% saline + 5% dextrose as ‘isotonic’ although it is hypertonic to plasma. However, because dextrose is metabolised rapidly, it effectively is isotonic. Although ORT was continued, no other maintenance fluid solutions (e.g. lactated Ringer’s) were administered during the study period. Blood samples were collected before (T0) and 4 h after (T4) the start of intravenous fluid administration. The T4 measurement corresponds to completion of the study protocol observation period.

Objectives and outcome measures The primary objective of this study was to determine whether the administration of large-volume intravenous fluid bolus

2 – no T0 bloodwork

•

5 – no T4 bloodwork

57 had urine, T0 and T4 data • 48 excluded - no urine sample collected

rehydration followed by isotonic maintenance fluid therapy places children at risk for the development of hyponatraemia. To answer this question, the primary outcome measure was the development of hyponatraemia 4 h after the initiation of intravenous rehydration. Secondary outcome measures were (i) the change in serum sodium based on T0 serum sodium (i.e. isonatraemic (plasma sodium 136–145 mEq/L) vs. hyponatraemic (plasma sodium <136 mEq/L)18 dehydration); (ii) magnitude of the decrease in serum sodium among those who experienced a decrease (i.e. subgroup of patients who developed hyponatraemia); (iii) risk of developing hypernatraemia (plasma sodium >145 mEq/L)19; (iv) correlations between the initial urine sodium and osmolality and the change in serum sodium; and (v) development of clinical evidence of fluid overload.

Biochemical measurements A biochemically significant change in plasma sodium was defined as ⱖ2 mEq/L as this exceeds the coefficient of variation (CV) of our laboratory reference range of 136–145 mEq/L (CV = 1.3%). Urine sample collection was performed by applying a urine bag immediately following enrolment in incontinent children and by clean catches in toilet-trained children. Urine samples obtained had an immediate dipstick urinalysis performed on them and then were sent for the determination of sodium concentration and osmolality. Plasma and urinary sodium were measured by standard automated methods using ion-selective electrodes; glucose, using the

Bolus ﬂuids and sodium homeostasis

SB Freedman and DF Geary

Table 2 Baseline clinical and biochemical characteristics of the children randomly assigned to receive either a 60 mL/kg 0.9% saline bolus over 60 min (large) or a 20 mL/kg 0.9% saline bolus over 60 min (standard)† Characteristic

Large-volume intravenous rehydration group (n = 114)

Standard intravenous rehydration group (n = 110)

Age (years), mean ⫾ SD Weight (kg), mean ⫾ SD Serum values at intravenous catheterisation, mean ⫾ SD Sodium (mEq/L) Potassium (mEq/L) Carbon dioxide (mEq/L) Blood urea nitrogen (mg/dL) Creatinine (mg/dL) Glucose (mg/dL) Chloride (mEq/L) T0 Sodium <136 mEq/L (n (%)) T0 Sodium >145 mEq/L (n (%)) Clinical characteristics, mean ⫾ SD Respiratory rate (breaths/min) Heart rate (beats/min) Clinical dehydration scale score‡ Prior ED visit (current illness) (n (%)) Prior intravenous (current illness) (n (%)) Received ondansetron in ED (n (%)) Total volume of intravenous ﬂuids administered (mL/kg), mean ⫾ SD*

2.9 ⫾ 2.1 13.4 ⫾ 4.9

3.0 ⫾ 2.2 14.1 ⫾ 5.4

136 ⫾ 4.2 4.2 ⫾ 0.7 18.0 ⫾ 3.9 16.0 ⫾ 8.7 0.4 ⫾ 0.1 83 ⫾ 23 104 ⫾ 5.0 48 (42) 3 (3)

137 ⫾ 3.8 4.3 ⫾ 0.6 18.1 ⫾ 3.5 15.1 ⫾ 6.2 0.4 ⫾ 0.1 81 ⫾ 25 104 ⫾ 4.4 36 (33) 1 (1)

28 ⫾ 6 127 ⫾ 20 4.5 ⫾ 1.2 41 (36) 8 (7) 43 (38) 84 ⫾ 22

27 ⫾ 6 127 ⫾ 20 4.5 ⫾ 1.2 42 (38) 7 (6) 44 (40) 44 ⫾ 24

*P < 0.001. †Only children with a T0 sodium value available are included (224/226). ‡Higher values indicate more severe dehydration. SI conversion factors: To convert sodium, potassium, carbon dioxide and chloride to millimoles per litre, multiply by 1.0; creatinine to micromoles per litre, multiply by 88.4; blood urea nitrogen to millimoles per litre, multiply by 0.357; glucose to millimoles per litre, multiply by 0.05551.

glucose oxidase method; blood urea nitrogen, using a urease quinolinium dye; and creatinine and total carbon dioxide, using standardised isotope dilution mass spectrometry. Urine osmolality was calculated using the freezing-point depression method.

Statistical analysis All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA, version 16.0 for Windows) and followed the intention-to-treat principle. Results were expressed as either mean ⫾ SD or medians with ranges unless otherwise indicated. Means between groups were compared by independent t-tests and paired variables by paired-sample t-tests. Categorical data were analysed using cross-tabulation and the c2 test or Fisher’s exact test if the two cells had expected counts <5. Correlations between urine sodium and osmolality and the change in serum sodium were evaluated, employing Pearson’s correlation coefficient. For analytical purposes, large-volume diarrhoea was defined as stool output ⱖ10 mL/kg during the study period. Statistical significance was defined as a P value <0.05. As this was a secondary analysis of previously collected data, no specific sample size calculation was performed. 4

Results Cohort clinical and biochemical characteristics There were no significant differences between groups at presentation (Table 2). The mean plasma sodium concentration at T0 was 137 ⫾ 4.0 mEq/L (range 114-154). Four (2%) children had plasma sodium concentrations <130 mEq/L, and one had a baseline value >150 mEq/L. Isonatraemic children at T0 had more vomiting episodes over the 24 h prior to presentation (Table 3). Hyponatraemic children were older and had lower serum carbon dioxide values. The two groups were otherwise similar. Urine samples were provided by 129 children at a median of 2.25 h (range 0 to 4.0) after the initiation of intravenous rehydration. Overall, serum sodium increased by 1.2 ⫾ 2.3 mEq/L between T0 and T4. Twelve per cent (25/217) of all participants with repeat electrolytes experienced a serum sodium decrease of ⱖ2 mEq/L, and 22% (48/217) had a dysnatraemia at 4 h.

Primary outcome At T4, similar numbers of children were hyponatraemic in both groups: large (21% (23/112)) and standard (20% (21/ 105)) (P = 0.92) (Table 4). Among hyponatraemic children at T0,

SB Freedman and DF Geary

Table 3

Bolus ﬂuids and sodium homeostasis

Clinical and biochemical characteristics of the children who were and were not hyponatraemic at the time of randomisation (T0)

Age (years), mean ⫾ SD Clinical dehydration scale score, mean ⫾ SD Weight (kg), mean ⫾ SD Vomit (episodes in past 24 h), mean ⫾ SD Diarrhoea (episodes in past 24 h), mean ⫾ SD Plasma biochemistry (T0), mean ⫾ SD Sodium (mEq/L) Potassium (mEq/L) Carbon dioxide (mEq/L) Blood urea nitrogen (mg/dL) Creatinine (mg/dL) Glucose (mg/dL) Chloride (mEq/L) Plasma biochemistry (T4), mean ⫾ SD Sodium (mEq/L) Potassium (mEq/L) Carbon dioxide (mEq/L) Blood urea nitrogen (mg/dL) Creatinine (mg/dL) Glucose (mg/dL) Chloride (mEq/L) Urine biochemistry, mean ⫾ SD† Sodium (mEq/L) Osmolality (mOsm/kg)

Hyponatraemic (T0 < 136 mEq/L; n = 84)

Not hyponatraemic (T0 ⱖ 136 mEq/L; n = 140)

P value

3.3 ⫾ 2.1 4.5 ⫾ 1.2 14.3 ⫾ 4.8 7.1 ⫾ 6.4 7.6 ⫾ 7.2

2.7 ⫾ 2.1 4.4 ⫾ 1.2 13.4 ⫾ 5.4 10.8 ⫾ 8.3 5.7 ⫾ 7.4

0.04 0.57 0.21 <0.001 0.06

133 ⫾ 2.7 4.2 ⫾ 0.7 17.4 ⫾ 3.4 15.1 ⫾ 7.6 0.4 ⫾ 0.1 79 ⫾ 23 102 ⫾ 4.2

139 ⫾ 2.8 4.3 ⫾ 0.6 18.5 ⫾ 3.8 15.7 ⫾ 7.6 0.4 ⫾ 0.1 83 ⫾ 25 106 ⫾ 4.5

<0.001 0.71 0.04 0.62 0.66 0.15 <0.001

135 ⫾ 3 3.7 ⫾ 0.6 17.0 ⫾ 3.4 10.9 ⫾ 5.0 0.4 ⫾ 0.1 92 ⫾ 25 108 ⫾ 3.5

139 ⫾ 3 3.9 ⫾ 0.5 18.4 ⫾ 3.1 11.2 ⫾ 5.3 0.4 ⫾ 0.1 97 ⫾ 25 110 ⫾ 4.4

<0.001 0.06 0.01 0.82 0.83 0.17 <0.001

84 ⫾ 41 696 ⫾ 263

103 ⫾ 54 746 ⫾ 298

0.06 0.33

†Urine samples were collected for testing from 129 children. SI conversion factors: To convert sodium, potassium, carbon dioxide and chloride to millimoles per litre, multiply by 1.0; creatinine to micromoles per litre, multiply by 88.4; blood urea nitrogen to millimoles per litre, multiply by 0.357; glucose to millimoles per litre, multiply by 0.05551; urine osmolality to mmol/kg, multiply by 1.0.

Table 4 Impact of bolus ﬂuid therapy on serum sodium values in the children who received either large (60 mL/kg) or standard (20 mL/kg) bolus ﬂuid therapy Large-volume intravenous rehydration group (n = 112)

Standard intravenous rehydration group (n = 105)

P value

T4 Sodium <136 mEq/L (n (%)) T4 Sodium >145 mEq/L (n (%)) Change in sodium levels (mEq/L), mean ⫾ SD Sodium decrease ⱖ2 mEq/L from 0–4 h (n (%)) Sodium increase ⱖ2 mEq/L from 0–4 h (n (%))

23 (21) 3 (3) 1.6 ⫾ 2.4 8 (7) 59 (53)

21 (20) 1 (1) 0.9 ⫾ 2.2 17 (16) 39 (37)

1.0 0.62 0.04 0.04 0.02

Baseline Hyponatraemia (n = 84) T4 Sodium <136 mEq/L (n (%)) Change in sodium levels (mEq/L), mean ⫾ SD Sodium decrease ⱖ2 mEq/L from 0–4 h (n (%)) Sodium increase ⱖ2 mEq/L from 0–4 h (n (%))

18 (38) 2.9 ⫾ 1.9 0 (0) 38 (79)

19 (56) 2.4 ⫾ 2.2 2 (6) 24 (71)

0.10 0.47 0.17 0.37

SI conversion factors: To convert sodium and chloride to millimoles per litre, multiply by 1.0.

Bolus ﬂuids and sodium homeostasis

SB Freedman and DF Geary

63% (30/48) in the large-volume rehydration group and 44% (15/34) in the the standard group were isonatraemic at T4 (P = 0.10).

Secondary outcomes The change in serum sodium during the 4-h study period differed based on the T0 serum sodium. Hyponatraemic children experienced an increase of 2.6 ⫾ 2.1 mEq/L compared with only 0.4 ⫾ 2.1 mEq/L among children who were not hyponatraemic (P < 0.001). In the initially isonatraemic group, plasma sodium decreased by ⱖ2 mEq/L in 17% (23/135), compared with 2% (2/82) in the hyponatraemic group (P = 0.001). Both children with baseline hyponatraemia who experienced a serum sodium decline at T4 received standard rehydration. Among those who did experience a serum sodium decrease, the magnitude was similar between groups (standard, -2.4 ⫾ 0.9 vs. large, -3.5 ⫾ 2.0; P = 0.07). Children who received large-volume intravenous fluid bolus rehydration were more likely to experience a serum sodium increase of ⱖ2 mEq/L (59/112 vs. 37/105; P = 0.02; Table 4). There was no difference in the number of children who were hypernatraemic at T4 (standard, 1/105; large, 3/112; P = 0.62). Children whose serum sodium decreased had higher urine osmolality (826 ⫾ 285 vs. 698 ⫾ 279 mOsm/L; P = 0.04) and urine sodium (117 ⫾ 55 vs. 91 ⫾ 47 mEq/L; P = 0.02). The serum sodium change from T0 to T4 was inversely correlated with the initial urine osmolality and urine sodium (Fig. 2). Nine children (standard, 4; large, 5) met our definition of possible fluid overload as assessed by the research nurse; none of the cases were deemed to be clinically significant by the attending physician.

Discussion This study suggests that large-volume intravenous fluid bolus rehydration followed by isotonic maintenance fluid therapy does not place children with gastroenteritis at an increased risk for developing hyponatraemia compared with standard-volume bolus therapy followed by isotonic maintenance fluid therapy. Although lower than previously reported,1,3 we found that within 4 h, 13% of children treated with isotonic intravenous fluids at or above the maintenance rate developed a biochemically significant decrease in their serum sodium. However, large-volume isotonic rehydration did not result in a larger number of children experiencing a significant serum sodium decrease. Although not universally accepted, our protocol followed the recommendation to administer a continuous infusion of 0.9% saline following bolus therapy in children with dehydration secondary to gastroenteritis.20 Although we do not have longterm data, in the short interval that we did evaluate, our findings support the aforementioned recommendation. Moreover, we found that large-volume intravenous fluid bolus rehydration followed by maintenance fluids employing 0.9% saline was protective against hyponatraemia. In fact, 63% of initially hyponatraemic children administered 60 mL/kg bolus had their hyponatraemia resolve. Previous reports have also documented 6

that large-volume rehydration protocols do not result in significant dilutional hyponatraemia.1,4 While our findings do not diminish the potential concerns that may arise in children receiving more prolonged fluid therapy,1,4 they demonstrate that in the short term, this large-bolus method may be beneficial, and relative to historic controls,3 the risk for the development of a dysnatraemia is markedly reduced. Another concern raised when discussing the use of 0.9% saline as a maintenance fluid in children with gastroenteritis is the potential for the development of hypernatraemia due to either large gastrointestinal free-water losses or increased insensible water losses.20 While we did find that a significant number of children experienced an increase in their serum sodium ⱖ2 mEq/L (45%), only 2% (n = 4) were hypernatraemic at the completion of the study. Moreover, the number of children with hyponatraemia was reduced during the study period from 84 (38%) at baseline to 44 (20%). This study is a secondary analysis of data collected as part of an intervention trial that found that large-volume intravenous bolus therapy did not improve outcomes in children with gastroenteritis in a developed country who were treated with intravenous rehydration.14 While the authors of the clinical trial did not endorse rapid intravenous rehydration, the accompanying editorial did encourage its ongoing use, questioning the enrolment and administration of intravenous fluids to children without severe dehydration and the appropriateness of employing a CDS as a marker of dehydration.21 While the administration of intravenous fluids to children without severe dehydration may at times be inappropriate, in high-income countries these are often the children administered intravenous rehydration.1,22–24 While the dehydration scale employed in the study was not perfect, it did enable us to exclude most children with mild dehydration. Moreover, it demonstrated moderate inter-observer reliability and modest correlations with other parameters including serum bicarbonate, length of stay and hospitalisation.25 While the results of our current biochemical analysis support the safety of large-volume, isotonic bolus rehydration therapy, given that it does not result in more rapid resolution of clinical dehydration, shorter duration of treatment or lower hospitalisation rates in the population evaluated,14 its routine use should continue to be questioned. The main limitation of this study is that it is a secondary analysis of data collected as part of an intervention trial. Nonetheless, the data were collected prospectively under closely supervised conditions without bias to the study hypothesis. Additionally, the time frame of the clinical trial was limited to 4 h, and we do not have repeat biochemistry measurements from beyond that period of time. While the clinical trial was designed to enrol children with moderate dehydration, it is possible that the dehydration scale employed overestimated the severity of dehydration in our study population, as some children were rehydrated following the administration of only 20 mL/kg. However, the dehydration scale employed performed well25 in the primary study14 as well as in earlier studies evaluating its test characteristics.9–11 Moreover, the use of a validated score is unique and vastly superior to the unvalidated methods used to estimate dehydration in other studies. Hence, the data that we present enable clinicians to make reasonable conclusions regarding the short-term implications of isotonic

SB Freedman and DF Geary

Bolus ﬂuids and sodium homeostasis

Fig. 2 Correlations between change in serum sodium and urine biochemical parameters. The change in serum sodium between baseline and time 4 h versus (a) urine osmolality and (b) urine sodium in all children. The line of best ﬁt (r value) is depicted for both correlations. Urine osmolality = -0.30 (P = 0.01); urine sodium = -0.28 (P = 0.03).

large-volume rehydration for sodium balance. Until further long-term safety data are available, in patients requiring prolonged intravenous fluid administration, electrolytes should continue to be monitored at least daily,20 and isotonic fluids should be discontinued if hypernatraemia develops.20 In conclusion, our findings confirm that the use of largevolume rehydration employing 0.9% saline followed by 0.9% saline + 5% dextrose maintenance fluid therapy in children with gastroenteritis is safe. Large-volume intravenous fluid bolus rehydration with 0.9% saline does not promote the development of hyponatraemia over the short term and in fact results

in a greater increase in serum sodium. Future research should look at the long-term (i.e. 24–48 h) implications of isotonic large-volume intravenous fluid bolus rehydration on sodium balance.

Acknowledgement Dr Stephen Freedman had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Bolus ﬂuids and sodium homeostasis

SB Freedman and DF Geary

Funding for the collection of data performed in this study was provided by a grant from The Physicians’ Services Incorporated Foundation.

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