BACKGROUND

Maintenance intravenous fluids (IVFs) are commonly used in the hospital setting. Hypotonic IVFs are commonly used in pediatrics despite concerns about high incidence of hyponatremia. We aimed to increase isotonic maintenance IVF use in children admitted from the emergency department (ED) from a baseline of 20% in 2018 to >80% by December 2019.

METHODS

We included patients aged 28 days to 18 years receiving maintenance IVFs (rate >10 mL/hour) at the time of admission. Patients with active chronic medical problems were excluded. Interventions included institutional discussions on isotonic IVF based on literature review, education on isotonic IVF use per the American Academy of Pediatrics guideline (isotonic IVF use with appropriate potassium chloride and dextrose), electronic medical record changes to encourage isotonic IVF use, and group practice review with individual physician audit and feedback. Balancing measures were the frequency of serum electrolyte checks within 24 hours of ED admission and occurrence of hypernatremia. Data were analyzed by using statistical process control charts.

RESULTS

Isotonic maintenance IVF use improved, with special cause observed twice; the 80% goal was met and sustained. No difference was noted in serum electrolyte checks within 24 hours of admission (P > .05). There was no increase in occurrence of hypernatremia among patients who received isotonic IVF compared with those who received hypotonic IVF (P > .05).

CONCLUSIONS

The application of improvement methods resulted in improved isotonic IVF use in ED patients admitted to the inpatient setting. Institutional readiness for change at the time of the American Academy of Pediatrics guideline release and hardwiring of preferred fluids via electronic medical record changes were critical to success.

Maintenance intravenous fluids (IVFs) are commonly used in children in the hospital setting and are administered to achieve a homeostatic balance between fluid needs and any ongoing losses.1,2  The basic principles for prescribing maintenance IVFs in children were established in the 1940s and 1950s. Holliday and Segar3  in 1957 described a simple formula for determining the maintenance need for water in children and recommended the use of a hypotonic saline solution, equivalent to 0.2% normal saline (NS) in 5% dextrose (D) in water. Since that time, recommendations for prescribing maintenance IVFs have remained unchanged4  until recently, and historically hypotonic IVFs have been used commonly in the pediatric population. Older editions of pediatric textbooks in the United States have hypotonic IVFs as the recommendation for maintenance IVF administration5,6 ; however, more recent editions highlight the potential risks of acquired hyponatremia with continued use of hypotonic maintenance IVFs.7  Physicians, including those in training, continue to use hypotonic fluids as maintenance fluids.8,9  In contrast, published evidence-based guidelines for IVF use in children younger than 16 years of age from international institutions favor the use of isotonic solutions.10 

There have been concerns raised about a high incidence of potentially life-threatening hyponatremia with the use of hypotonic solutions, especially in hospitalized children.1114  Moritz and Ayus11  introduced the idea of using an isotonic saline solution as a maintenance IVF, and there are several other studies that have since supported the use of isotonic solutions as a safer choice for maintenance IVFs.1517  Despite these studies, maintenance IVF therapy in children has primarily been opinion based, and national guidelines have been lacking.18  This has resulted in high variability in maintenance IVF prescribing practices among physicians.8,19 

The American Academy of Pediatrics (AAP) released a clinical practice guideline (CPG) regarding the use of maintenance IVFs in December 2018. The AAP CPG states that “patients 28 days to 18 years of age requiring maintenance IVFs should receive isotonic solutions with appropriate potassium chloride (KCl) and dextrose (D) because they significantly decrease the risk of developing hyponatremia (evidence quality: A; recommendation strength: strong).”18  Our institution had a low rate of isotonic fluid use (at 20%), and we wanted to improve our adherence to the latest guidelines and evidence-based review of the literature.

Our SMART (specific, measurable, achievable, realistic/relevant, timely) aim was to improve the use of isotonic IVFs in emergency department (ED) patients aged 28 days to 18 years being admitted to the inpatient unit with maintenance IVFs from a baseline of 20% in January 2018 to 80% by December 2019.

The setting of our quality improvement (QI) initiative consists of 3 pediatric EDs in a large tertiary care pediatric health care system with an annual volume of >245c000 visits in 2019. Historically, our institution had a low rate of isotonic maintenance IVF use (20%), and there was variation in maintenance IVF prescribing practices among the ED physicians.

Even before the AAP guideline recommending use of isotonic maintenance IVFs was released, we were actively discussing a switch to isotonic maintenance IVFs at our institution in accordance with a review of current evidence. Despite these ongoing discussions about potential harmful effects of hyponatremia due to hypotonic fluids, including reports of serious injury and child death,2022  the use of hypotonic fluids persisted. Several years before, our institution had moved from D5%–0.2% NS to D5%–0.45% NS. In December 2018, our institution modified our ED CPG for management of bronchiolitis to avoid the use of hypotonic IVFs because of the risk of syndrome of inappropriate antidiuretic hormone–induced hyponatremia and recommended isotonic IVFs as the preferred fluids. However, the overall use of isotonic fluids for patients requiring maintenance IVFs, but without a diagnosis of bronchiolitis, remained unacceptably low in our institution.

Additionally, our institution’s hospitalist group was participating in a Value in Inpatient Pediatrics Network (a quality network of the AAP) national project on Standardization of Fluids in Inpatient settings. Our aim for this project was to describe and standardize the use and monitoring of IVFs in inpatient pediatric settings across the United States. Although this project was focused on the inpatient setting, it coincided with the ED initiative to improve the use of isotonic maintenance IVFs in patients being admitted from the ED to the inpatient setting.

Maintenance Fluids Selection

Maintenance IVFs were classified as either isotonic or hypotonic. Commonly used maintenance IVFs at our institution included D5%–0.2% NS, D5%–0.45% NS, D5%–0.9% NS, D5-lactated Ringer’s solution (LR), each with or without KCl. Isotonic IVFs included D5%–0.9% NS and D5-LR, whereas hypotonic IVFs included D5%–0.45% NS and D5%–0.2% NS solutions, each with or without KCl. NS and LR without dextrose were not considered maintenance fluids. Maintenance fluids were defined as the fluids above at a rate of >10 mL/hour.

Target Population

Patients 28 days to 18 years of age at the time of admission from the ED to the inpatient setting who were receiving maintenance IVFs were included. Our exclusion criteria included patients who we determined to require fluid therapy individualized to their specific needs, which may not always be isotonic fluids (Supplemental Table 1). Our exclusion criteria were selected on the basis of International Classification of Diseases, 10th Revision (ICD-10) diagnostic codes, and they were consistent with the exclusion criteria in the AAP CPG (Supplemental Table 2).

Members of our pediatric emergency medicine clinical quality council (consisting of pediatric emergency medicine attending physicians and ED nurses at our institution) started meeting in mid to late 2018 to identify key drivers that would potentially improve isotonic maintenance IVF use (Fig 1). The key drivers included increasing awareness of the evidence around superiority of isotonic IVFs, improving ordering of isotonic IVF by making hypotonic IVFs more difficult to order, and encouraging provider engagement and awareness of individual practice patterns. Implementation of component changes began in January 2019.

FIGURE 1

Key driver diagram revealing primary drivers and interventions for the project SMART aim. SMART, specific, measurable, achievable, realistic/relevant, timely.

FIGURE 1

Key driver diagram revealing primary drivers and interventions for the project SMART aim. SMART, specific, measurable, achievable, realistic/relevant, timely.

Close modal

Institutional Discussions Between Nephrology, the ED, and Hospital Medicine on Use of Isotonic Maintenance IVFs Based on a Literature Review

Although discussions had been initiated by nephrology leaders, consensus from ED and hospital medicine physicians was achieved after a thorough review of the literature. We emphasized not only the benefits of isotonic fluids but also their safety with both these groups of physicians. This acceptance of isotonic fluids by the hospital medicine service was obtained before project initiation. The timing of the release of the AAP CPG only a few months later helped boost these discussions.

Education of Providers on Isotonic Maintenance IVFs in Accordance With the AAP CPG

Specifically, education of providers included a presentation of the literature review during ED provider meetings with opportunities for dialogue and questions. In addition, the AAP CPG was distributed to all ED providers via e-mail.

Electronic Medical Record Changes to Encourage Use of Isotonic Maintenance IVFs

We identified that making isotonic fluids more visible and easier to order in our electronic medical record (EMR) could potentially increase their rate of use. Therefore, we added isotonic IVFs into a quick order set in our EMR, making them easily visible to the ED physicians to encourage its use. We also moved all hypotonic fluids to a separate order set in our EMR, thus making them less easily accessible, and added a best practice advisory pop-up (which is a highlighted reminder in our EMR) to inform physicians about the risk of hyponatremia with hypotonic IVF use (Figs 2 and 3). We anticipated that although our education campaign would result in improvement in the use of isotonic maintenance IVFs, an EMR change would yield a high level of reliability.

FIGURE 2

A, Screenshot of quick order set in the Epic EMR. B, Screenshot of quick fluids order set in the Epic EMR.

FIGURE 2

A, Screenshot of quick order set in the Epic EMR. B, Screenshot of quick fluids order set in the Epic EMR.

Close modal
FIGURE 3

Screenshot of hypotonic fluid panel in the Epic EMR.

FIGURE 3

Screenshot of hypotonic fluid panel in the Epic EMR.

Close modal

Group Practice Review and Individual Feedback to Outlier Providers on Their Isotonic IVF Use

Group practice review occurred monthly at division meetings and via e-mail. Individual feedback was provided via e-mail to outlier providers every 3 months to improve compliance. Review and feedback were performed by designated attending members of the clinical quality council in charge of the QI initiative. Data for the feedback was procured by using a physician-level report from the EMR. After individual performance data were distributed, members of the clinical quality council were available to discuss any concerns. We defined outlier providers as ED physicians who had a rate of isotonic maintenance IVF use of <50%. As the rate of isotonic maintenance IVF use increased gradually, ED physicians who had a rate of isotonic IVF use of <75% were also given individual feedback via e-mail to encourage continued compliance.

Data were obtained from the EMR for all eligible patients who were admitted to the inpatient unit on maintenance IVFs between January 2018 and December 2019. January 2018 to November 2018 (before the AAP CPG release) was considered the baseline period. For our data reports, we use Clarity, a structured query language server database within our institution enterprise data warehouse connected to our EMR system (Epic; Epic Systems Corporation, Madison, WI) that allows for querying via Microsoft’s Structured Query Language Server Management Studio software. Data reports included admission diagnosis, type of maintenance IVFs (isotonic versus hypotonic), and results of electrolyte studies (specifically a comprehensive or basic metabolic panel, if performed) within 24 hours of admission.

The main outcome measure was the rate of use of isotonic maintenance IVFs, defined as the number of eligible patients who received isotonic maintenance IVFs out of the total number of eligible patients who received any maintenance IVFs.

Balancing measures included (1) change in frequency of serum electrolyte levels checked within 24 hours of admission from the ED and (2) monitoring for occurrence of hypernatremia (defined as a serum sodium level >145 mEq/L) with the use of isotonic maintenance IVFs (compared with hypotonic maintenance IVFs) after the initiation of the QI intervention in January 2019.

Shewhart p-charts23  were used to continuously evaluate the main outcome measure (use of isotonic fluids), plotted on the vertical axis against time on the horizontal axis. Each data point represents 1 month of data. Three σ limits were used to set the upper and lower control limits, and standard rules were used to determine special cause variation, including 8 or more values above the baseline centerline. Balancing measures are described as frequencies and percentages and are compared by using the χ2 test. The level of statistical significance was set at P < .05.

Our institutional review board determined the project to be non–human subjects’ research; thus, it was exempt from institutional review board review.

A total of 10 040 patients, with an average of 418 ± 65 patients per month, met inclusion criteria and had maintenance IVFs ordered between January 2018 and December 2019.

Isotonic maintenance IVF use increased rapidly after the initiation of our interventions. Special cause variation was observed twice after implementation of changes, with the 80% goal being met and sustained for 8 months (Fig 4).

FIGURE 4

A p-chart showing the proportion of isotonic maintenance IVF use (January 2018 to April 2020), with key interventions annotated. LCL, lower control limits; UCL, upper control limits; 1s, 1 standard deviation; 2s, 2 standard deviation.

FIGURE 4

A p-chart showing the proportion of isotonic maintenance IVF use (January 2018 to April 2020), with key interventions annotated. LCL, lower control limits; UCL, upper control limits; 1s, 1 standard deviation; 2s, 2 standard deviation.

Close modal

Of 4858 admitted patients, 647 (13.3%) had serum electrolyte levels checked within 24 hours of admission from the ED before the initiation of our interventions, compared with 655 of 5182 (12.6%) admitted patients after implementation of changes (P > .05).

Occurrence of hypernatremia was 7.4% (31 of 418) in patients who received maintenance isotonic fluids, not significantly different when compared with those who received maintenance hypotonic fluids 6.7% (16 of 237) (P > .05). The median (interquartile range) sodium value in patients who received isotonic maintenance fluids was 147 (146–170) mEq/L.

Occurrence of hyponatremia in patients receiving hypotonic maintenance IVFs before the QI intervention was 22 of 464 (4.7%) compared with 8 of 237 (3.3%) after the QI intervention (P > .05).

Our improvement initiative increased the use of isotonic maintenance IVFs in ED patients (aged 28 days to 18 years) being admitted to the inpatient setting from a baseline of 20% to 80%, which was subsequently sustained for 8 months. Our findings are similar to those in a study done by Rooholamini et al,24  who were able to show sustained improvements in the use of isotonic maintenance IVFs after the creation of an evidence-based clinical pathway to standardize IVF use. Also, because our project was in the ED, we had the additional advantage of not having to change fluids after the patient was admitted, thus avoiding waste.

The support of nephrologists in our institution and agreement from hospital medicine (the service that receives the largest number of admissions from the ED) helped to make this project feasible and the practice change more palatable for ED physicians. This was an important proactive step because the choice of maintenance IVFs impacts inpatient services more than the ED. Furthermore, our hospital medicine service was already planning to participate in the Value in Inpatient Pediatrics Network Standardization of Fluids in Inpatient settings project and was primed for the change to isotonic fluids for maintenance needs; this worked in our favor.

The timing of the publication of the AAP guideline helped provide the impetus needed to change physician practice toward using isotonic maintenance IVFs. We leveraged the AAP recommendations to launch an educational campaign (presentation of the AAP guidelines during monthly division meetings as well as e-mail communications to all physician providers) on the robust literature that supported the use of isotonic maintenance IVFs.

A key intervention that helped the success of this initiative was an EMR change that made it easier for providers to order isotonic fluids rather than hypotonic fluids, thus encouraging the use of isotonic maintenance IVFs. This EMR change was discussed during quality committee meetings and was supported by ED leadership, which allowed for it to be quickly operationalized in all of the EDs. Studies reveal that EMR-based clinical decision support at the point of care can be an effective tool for changing professional behavior and increasing adherence to evidence-based recommendations.25,26  Although we anticipated some improvement with our education campaign, we believe that our EMR change was useful in achieving a higher level of reliability. We also believe that this EMR change helped ED physicians sustain their use of isotonic fluids and thus implement the AAP recommendations after active interventions were discontinued.

Quarterly feedback to individual physicians on their isotonic maintenance IVF use and comparison to group practice also helped to improve compliance, especially with outlier physicians.27,28  It is also possible that ED physicians readily adopted isotonic maintenance fluids because there was minimal perceived risk to their use in this population of patients who was getting admitted and could be monitored for any complications during the admission.

Despite evidence suggesting a low risk of hypernatremia associated with isotonic fluid administration, some concerns remain that, in children, its use could lead to complications such as hypernatremia, fluid overload with edema and hypertension, and hyperchloremic acidosis.2931  Therefore, one of our balancing measures included monitoring for increased occurrence of hypernatremia with isotonic maintenance IVF use. We also wanted to monitor if physicians were checking electrolyte levels more often to look for hypernatremia. In our institution, there are no protocols in place regarding the frequency of electrolyte checks, and electrolyte checks are usually based solely on physician discretion. We noted that there was no change in serum electrolyte checks within 24 hours of admission in patients, and there was no increase in the occurrence of hypernatremia among patients who received isotonic maintenance IVFs when compared with those who received hypotonic fluids. This is consistent with studies published in the literature.32  Friedman et al33  concluded that isotonic fluid administration is safe in the general pediatric patient population, and there was no increase in the occurrence of hypernatremia with isotonic fluids.

Although the AAP CPG did not make any recommendations regarding the safety of LRs, in our initiative, we included LRs as isotonic maintenance IVFs because they have a fluid and electrolyte composition similar to that of human plasma. However, LRs were used extremely infrequently in our institution (<1% both before and after the QI intervention). Additionally, this is a single-center study. We had the ability to change our EMR and apply decision support (best practice advisory), and we had the benefit of a quality infrastructure in our facility in the form of a quality council committee. However, we believe that our implementation strategies can be successfully replicated at other institutions.

Our initiative resulted in sustained improvement in the use of isotonic IVFs as maintenance IVFs in patients admitted from the ED to the inpatient setting. There was no change in the frequency of electrolyte checks or the occurrence of hypernatremia after implementation of changes. Rapid implementation of AAP recommendations may have been successful, in part, because of institutional readiness for change at the time the AAP guidelines were released. Additionally, hardwiring the preferred fluids via EMR changes was a key intervention to success.

Dr Akinsola conceptualized and designed the study, contributed to educational content and dispersion of education to physicians, provided group and individual practice feedback to physicians, coordinated, collected, and supervised data collection, drafted the initial manuscript, and reviewed and revised the manuscript; Dr Cheng contributed to the education and dispersion of education to the physician group, gave group practice review and individual feedback to providers on their isotonic maintenance intravenous fluids, and reviewed the manuscript; Dr Iyer assisted with the data analysis and critically reviewed the manuscript for important intellectual content; Dr Jain conceptualized and designed the study, contributed to educational content for physicians, coordinated, collected, and supervised data collection, critically reviewed the manuscript for important intellectual content, and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: No external funding.

AAP

American Academy of Pediatrics

CPG

clinical practice guideline

D

Dextrose

ED

emergency department

EMR

electronic medical record

ICD-10

International Classification of Diseases, 10th Revision

IVF

intravenous fluid

KCl

potassium chloride

LR

Lactated Ringer’s solution

NS

normal saline

QI

quality improvement

1
Rewa
O
,
Bagshaw
SM
.
Principles of fluid management
.
Crit Care Clin
.
2015
;
31
(
4
):
785
801
2
Holliday
MA
,
Ray
PE
,
Friedman
AL
.
Fluid therapy for children: facts, fashions and questions
.
Arch Dis Child
.
2007
;
92
(
6
):
546
550
3
Holliday
MA
,
Segar
WE
.
The maintenance need for water in parenteral fluid therapy
.
Pediatrics
.
1957
;
19
(
5
):
823
832
4
Chesney
RW
.
The maintenance need for water in parenteral fluid therapy
.
Pediatrics
.
1998
;
102
(
2 pt 1
):
399
400
5
Siegel
NJ
.
Fluids, electrolytes and acid-base
. In:
Rudolph
CD
,
Rudolph
AM
,
Hostetter
MK
,
Lister
G
,
Siegel
NJ
, eds.
Rudolph’s Pediatrics
. 21st ed.
New York, NY
:
McGraw Hill
;
2003
:
1653
1655
6
Greenbaum
LA
.
Pathophysiology of body fluids and fluid therapy
. In:
Behrman
RE
,
Kleigman
RM
,
Jenson
HB
, eds.
Nelson’s Textbook of Pediatrics
. 17th ed.
Philadelphia, PA
:
WB Saunders
;
2004
:
242
245
7
Fleisher
GR
,
Ludwig
S
.
Ongoing repletion and maintenance therapy
. In:
Fleisher
GR
,
Ludwig
S
, eds.
Textbook of Pediatric Emergency Medicine
. 6th ed.
Philadelphia, PA
:
Lippincott Williams & Wilkins
;
2010
:
1110
1101
8
Freeman
MA
,
Ayus
JC
,
Moritz
ML
.
Maintenance intravenous fluid prescribing practices among paediatric residents
.
Acta Paediatr
.
2012
;
101
(
10
):
e465
e468
9
Shukla
S
,
Basu
S
,
Moritz
ML
.
Use of hypotonic maintenance intravenous fluids and hospital-acquired hyponatremia remain common in children admitted to a general pediatric ward
.
Front Pediatr
.
2016
;
4
:
90
10
National Clinical Guideline Centre
.
IV Fluids in Children: Intravenous Fluid Therapy in Children and Young People in Hospital
.
London, United Kingdom
:
National Institute for Health and Care Excellence
;
2015
11
Moritz
ML
,
Ayus
JC
.
Prevention of hospital-acquired hyponatremia: a case for using isotonic saline
.
Pediatrics
.
2003
;
111
(
2
):
227
230
12
Duke
T
,
Molyneux
EM
.
Intravenous fluids for seriously ill children: time to reconsider
.
Lancet
.
2003
;
362
(
9392
):
1320
1323
13
Halberthal
M
,
Halperin
ML
,
Bohn
D
.
Lesson of the week: acute hyponatraemia in children admitted to hospital: retrospective analysis of factors contributing to its development and resolution
.
BMJ
.
2001
;
322
(
7289
):
780
782
14
Foster
BA
,
Tom
D
,
Hill
V
.
Hypotonic versus isotonic fluids in hospitalized children: a systematic review and meta-analysis
.
J Pediatr
.
2014
;
165
(
1
):
163
169.e2
15
Yung
M
,
Keeley
S
.
Randomised controlled trial of intravenous maintenance fluids
.
J Paediatr Child Health
.
2009
;
45
(
1–2
):
9
14
16
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
;
25
(
11
):
2303
2309
17
Neville
KA
,
Verge
CF
,
Rosenberg
AR
,
O’Meara
MW
,
Walker
JL
.
Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study
.
Arch Dis Child
.
2006
;
91
(
3
):
226
232
18
Feld
LG
,
Neuspiel
DR
,
Foster
BA
, et al;
Subcommittee on Fluid and Electrolyte Therapy
.
Clinical practice guideline: maintenance intravenous fluids in children
.
Pediatrics
.
2018
;
142
(
6
):
e20183083
19
Lee
JM
,
Jung
Y
,
Lee
SE
, et al
.
Intravenous fluid prescription practices among pediatric residents in Korea
.
Korean J Pediatr
.
2013
;
56
(
7
):
282
285
20
Institute for Safe Medication Practices
.
Plain D5W or hypotonic saline solutions post-op could result in acute hyponatremia and death in healthy children
.
Alta RN
.
2010
;
Feb-Mar
;
66
(
1
):
16
9
21
Koczmara
C
,
Wade
AW
,
Skippen
P
, et al
.
Hospital-acquired acute hyponatremia and reports of pediatric deaths
.
Dynamics
.
2010
 Spring;
21
(
1
):
21
6
22
Friedman
JN
;
Canadian Paediatric Society, Acute Care Committee
.
Risk of acute hyponatremia in hospitalized children and youth receiving maintenance intravenous fluids
.
Paediatr Child Health
.
2013
;
18
(
2
):
102
107
23
Nelson
LS
.
The Shewhart control chart—tests for special causes
.
Journal of Quality Technology
.
1984
;
16
(
4
):
237
239
24
Rooholamini
SN
,
Clifton
H
,
Haaland
W
, et al
.
Outcomes of a clinical pathway to standardize use of maintenance intravenous fluids
.
Hosp Pediatr
.
2017
;
7
(
12
):
703
709
25
Kousgaard
MB
,
Siersma
V
,
Reventlow
S
,
Ertmann
R
,
Felding
P
,
Waldorff
FB
.
The effectiveness of computer reminders for improving quality assessment for point-of-care testing in general practice–a randomized controlled trial
.
Implement Sci
.
2013
;
8
:
47
26
Simon
SR
,
Smith
DH
,
Feldstein
AC
, et al
.
Computerized prescribing alerts and group academic detailing to reduce the use of potentially inappropriate medications in older people
.
J Am Geriatr Soc
.
2006
;
54
(
6
):
963
968
27
Jamtvedt
G
,
Young
JM
,
Kristoffersen
DT
,
O’Brien
MA
,
Oxman
AD
.
Does telling people what they have been doing change what they do? A systematic review of the effects of audit and feedback
.
Qual Saf Health Care
.
2006
;
15
(
6
):
433
436
28
Ivers
N
,
Jamtvedt
G
,
Flottorp
S
, et al
.
Audit and feedback: effects on professional practice and healthcare outcomes
.
Cochrane Database Syst Rev
.
2012
;(
6
):
CD000259
29
Almeida
HI
,
Mascarenhas
MI
,
Loureiro
HC
, et al
.
The effect of NaCl 0.9% and NaCl 0.45% on sodium, chloride, and acid-base balance in a PICU population
.
J Pediatr (Rio J)
.
2015
;
91
(
5
):
499
505
30
McNab
S
,
Ware
RS
,
Neville
KA
, et al
.
Isotonic versus hypotonic solutions for maintenance intravenous fluid administration in children
.
Cochrane Database Syst Rev
.
2014
;(
12
):
CD009457
31
McNab
S
,
Duke
T
,
South
M
, et al
.
140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial
.
Lancet
.
2015
;
385
(
9974
):
1190
1197
32
Wang
J
,
Xu
E
,
Xiao
Y
.
Isotonic versus hypotonic maintenance IV fluids in hospitalized children: a meta-analysis
.
Pediatrics
.
2014
;
133
(
1
):
105
113
33
Friedman
JN
,
Beck
CE
,
DeGroot
J
,
Geary
DF
,
Sklansky
DJ
,
Freedman
SB
.
Comparison of isotonic and hypotonic intravenous maintenance fluids: a randomized clinical trial
.
JAMA Pediatr
.
2015
;
169
(
5
):
445
451

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data