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Isotonic Versus Hypotonic Maintenance IV Fluids in Hospitalized Children: A

Meta-Analysis
Jingjing Wang, Erdi Xu and Yanfeng Xiao
Pediatrics 2014;133;105; originally published online December 30, 2013;
DOI: 10.1542/peds.2013-2041

The online version of this article, along with updated information and services, is
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CONCLUSIONS: Isotonic fluids are safer than hypotonic fluids in hos- E-mail: xiaoyanfeng. hyponatremia.1542/peds. Department of missing data. searched databases. isotonic fluid. 0031-4005. Dr Xu helped with raw data extraction. carried out performed.24. extracted raw data. There was a significantly greater fall authors approved the final manuscript as submitted. hypotonic fluid. Cochrane Library.2013-2041 versus isotonic IV fluids. Number 1. 2013) for RCTs that compared isotonic to ADH—antidiuretic hormone hypotonic maintenance IV fluid therapy in hospitalized children. assessed risk of bias. Embase. 2013 0. MD.2013-2041 was found between the 2 interventions in the risk of hypernatremia (RR Accepted for publication Oct 19. China. PEDIATRICS Volume 133. Pediatrics 2014. and drafted the manuscript. the analysis. 1098-4275). Online. selected all meta-analyses. Rela- CI—confidence interval IV—intravenous tive risk (RR). The meta-analysis analysis.gov (up to April 11.org at Indonesia:AAP Sponsored on June 5. and 95% confidence inter- pNa—plasma sodium vals (CIs) were calculated based on the effects on plasma sodium PRISMA—Preferred Reporting Items for Systematic Reviews and (pNa).xjtu@gmail. PhD. Meta-Analyses severe hyponatremia (pNa . 157 Xiwu Rd.31) and severe hyponatremia analysis. of Pediatrics. Second Affiliated Hospital of Medical OBJECTIVE: To assess evidence from randomized controlled trials School of Xi’an Jiaotong University.52 to 3. MD. helped with RESULTS: Ten RCTs were included in this review. Sensitivity analyses by missing data were also studies. China (RCTs) on the safety of isotonic versus hypotonic intravenous (IV) main- KEY WORDS tenance fluids in hospitalized children. and all (RR 5.org/cgi/doi/10. helped with hyponatremia (RR 2.49 mmol/L www.06).1542/peds. No significant difference doi:10. independently assessed risk of bias. 95% CI –5. in pNa in children who received hypotonic IV fluids (–3. January 2014 105 Downloaded from pediatrics. We adopted a random-effects model in Dr Wang designed the study. Erdi Xu. 95% CI 1.35). The risk of developing hyponatremia (pNa . and Yanfeng Xiao. 2014 .com pitalized children requiring maintenance IV fluid therapy in terms of PEDIATRICS (ISSN Numbers: Print. children METHODS: We searched PubMed.48). MD. PhD abstract Department of Pediatrics.130 mmol/L). and critically reviewed the manuscript. Xi’an. None of the findings was sensitive to imputation Address correspondence to Yanfeng Xiao.22 to 2. MD.pediatrics.145 mmol/L) was evaluated. 95% CI 1. pNa. Second Affiliated Hospital of Medical School of Xi’an Jiaotong University.74 to 16.73. and reviewed and revised the manuscript. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.63 to –1. Shaanxi. intravenous fluid.133:105–113 Copyright © 2014 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.136 mmol/L). 95% CI 0. Xi’an. FUNDING: No external funding. and hypernatremia (pNa RCT—randomized controlled trial RR—relative risk . and clin- ABBREVIATIONS icaltrials. REVIEW ARTICLE Isotonic Versus Hypotonic Maintenance IV Fluids in Hospitalized Children: A Meta-Analysis AUTHORS: Jingjing Wang. weighted mean differences. Dr Xiao showed significantly higher risk of hypotonic IV fluids for developing designed the study. Shaanxi 710004.aappublications. independently selected studies.29.

inclusion criteria were as follows:1 mains for sequence generation. Here. this issue.1 Hypotonic fluids accord. We mary outcome was hyponatremia (pNa Hyponatremia. electrolytes. 2013) description of the interventions and theless. systematic reviews and identified rel.21 Early systematic reviews saline). and adverse events attributable to IV muscle weakness. All pooled (RCTs). when a patient is unable to uptake re. or Ringer’s Analysis However.3% saline. full texts of citations needing additional We addressed the methodologic quality velop hyponatremia.130 mmol/L). The pri- hospitalized children. characteristics of study pop- ing to their recommendations may be Controlled Clinical Trials Register. METHODS mendations for maintenance fluid in Data Extraction We followed the Preferred Reporting children. studies published as abstracts only.6. the titles and abstracts of potentially which stimulates water retention. We pNa changes after IV fluid therapy. For ric patients. Exclusion criteria were1 non-RCT dichotomous outcomes.9 In relevant citations.6 without any language restriction. we added more recent patients with preexisting hyponatremia estimates of the intervention effects 106 WANG et al Downloaded from pediatrics. also screened references of previous hypernatremia (pNa . Cochrane bias). appropriate for healthy children.1 hypotonic fluids are still the A standard reporting form developed by Items for Systematic Reviews and Meta- most commonly prescribed IV fluids for PRISMA25 was used to extract data.18% to estimate the intervention effects. (eg.3 and studies comparing isotonic selective outcome reporting. tremia. we used rela- have evaluated isotonic versus hypo. traditional guidelines and solution) or hypotonic if they had a If . and energy. Hartmann’s solution. congestive heart failure. incomplete outcome data. Secondary outcomes sodium (pNa) level of . fluid administration and/or pNa or even death in the most severe derangements (death.45% saline.10–20 Clinical years.9 solved through group discussion.10–20 saline. and outcomes. children are prone to de. evant articles.22–24 but only included studies involving neonates. which includes do- Accumulating clinical evidence sug.Maintenance intravenous (IV) fluids are RCTs to perform an updated systematic or comorbidities that resulted in so- designed to maintain homeostasis review and meta-analysis to address dium disturbance (eg.145 mmol/L). hypertension. It mainly mani. Discrepancies were re. especially when evaluation. The risk-of-bias tool.7 a previous systematic review. ommendations are inappropriate for ized children aged from 1 month to 17 blinding. They then read the Assessment of Risk of Bias this setting. and diuretic therapies). we used weighted mean dif- limited randomized controlled trials fluid resuscitation or rehydration.4 intervals (CIs).25 hypotonic formula was based on the checked all forms.26 Discrep- of hypotonic fluids contributes to the therapy. After Holliday and Segar made recom.6 and ferences and 95% CIs. Never. and ulation (number. studies. quired water. or 0. toms such as lethargy. they may not be suitable for all for potentially relevant publications comparisons.8 Hospitalized children are often Study Selection seizures.gov (up to April 11. 0.5 studies of comes.2–4 Their author extracted data. liver cirrhosis. of included studies using the Cochrane receiving hypotonic fluids. Solutions were classified as ancies were resolved through group development of iatrogenic hypona. al- gests that Holliday and Segar’s rec. We extracted the energy expenditure of healthy children following information: methods of the Search Strategy and the composition of human breast study (as per assessment of risk of and cow milk. studies on RCTs. cases. For continuous out- talized children. statistical pooling was adopted potonic maintenance fluids for pediat. in the Supplemental Information. defined as a plasma modified the search strategy from . and coma.136 mmol/L.5. renal diseases. most hospitalized children. and another ing of this meta-analysis.1 study reported the same out- textbooks continue recommending hy. lower osmotic pressure than blood come. 0.aappublications. and length of in a stressed state and easily secrete Two authors independently screened stay). excess antidiuretic hormone (ADH). irritability. 6 The were severe or symptomatic hypona- draws excess water into cells and detailed search strategy is presented tremia (pNa . fests as central nervous system symp.2 studies on hospital. whereas isotonic fluids offer osmotic pressure as blood (eg. 0. and other evidence suggests that the routine use and hypotonic maintenance IV fluid potential sources of bias. pNa and causes them to swell.9% effective prophylaxis against it. One Analyses (PRISMA) statement for report- pediatric hospitalized patients. isotonic if they had the same or near discussion. Embase. seizures. and diagnosis). cerebral edema.org at Indonesia:AAP Sponsored on June 5. 2014 . We searched PubMed.136 mmol/L).3 tive risk (RR) and 95% confidence tonic maintenance IV fluids in hospi. ClinicalTrials. location sequence concealment.2 letters and case reports. age.

.52 to 3. for our analysis. children after hypotonic IV fluids was PEDIATRICS Volume 133.10.org at Indonesia:AAP Sponsored on June 5.20 and 1 study of available cases in which data were failed to access their data by con.aappublications.58 to 3. Number 1. Copenhagen. main of free of selective reporting be- were analyzed by assuming a fixed cause they did not report the primary difference between the actual mean Study Characteristics outcome hyponatremia.12.37. which tistic and I2 value of 0% to 25%.14 the result was similar (RR 2. Therefore. and ble 3 for meta-analysis of pNa out- comes.13 Figure 1 shows the process of study se.20. REVIEW ARTICLE were calculated under a random-effects according to our criteria.11 Two studies analyzed according to the intention-to.16 Pooled analysis of other studies with available data showed that hypotonic IV maintenance fluids also significantly increased the risk of severe hypona- tremia (RR 5.06. I2 = 12%).10. . included RCTs.12.13 One of them supplied sep- respectively. 95% CI 1.24. 2014 . 50% to 74%. FIGURE 1 P = .29. enrolled both types of patients. In 2 studies. and we blinding methods12–14.11. 10 RCTs were included in this were classified as high risk in the do- treat principle. cause of a relatively large number of in which dichotomous data were tonic fluids at 2 maintenance rates.13 losses during follow-up. Risk of Bias raw data were directly extracted for Table 2 shows the risk of bias for our analysis considering a small pro- RESULTS portion of participants with preexist- each study.20 to 49%.26 Heterogeneity Table 1 shows characteristics of the were classified as “unclear” because was determined by using the I2 sta.14 it was initially ex- cluded in the pooled analysis of hypo- natremia. children with illnesses that required pants with preexisting hyponatremia.31. Although all studies were Study Selection reported as RCTs.10–12 The alysis.15. I2 = 0%. Five RCTs exclusively their protocols were unavailable. nonsurgical treatment. I2 = 14%. and high heterogeneity. caregivers.14 and 4 RCTs which may introduce bias in our an- moderate. 26% enrolled children undergoing sur.130 mmol/L. 3 lacked adequate ing hyponatremia.13. January 2014 107 Downloaded from pediatrics.15 5 studies did not use model.30 researchers. Fig 2). and continuous data review.30 Two studies stract and text. We identified 10 studies comparing pNa and 2 in allocation concealment. reported contradictory data in its ab- analyzed for every participant for tacting the authors.16 One study had a high whom the outcome was obtained.003. When the study by Kannan et al was included.27 First. but their Denmark).10–16. Fig 3). The analysis showed that hypotonic IV fluids significantly in- creased the risk of hyponatremia (RR 2. 95% CI 1. Mean pNa in Flow diagram of study selection.0001.11.12. We were considered as 4 RCTs because risk of incomplete outcome data be- then performed a sensitivity analysis they compared hypotonic and iso. no se- vere hyponatremia developed in either the isotonic or hypotonic arms.16.74 to 16.0001.20 1 RCT exclusively enrolled Three studies also enrolled partici- 100% were assigned unimportant. did not supply these data.20 isotonic and hypotonic maintenance IV Four studies used blinding methods All extracted data are presented in Ta- fluid therapy in hospitalized children for participants. 95% CI 1. P .12 The other 2 studies Cochrane Collaboration. Because the study by Kannan et al defined hyponatremia as pNa . we performed analysis Two were unpublished studies. description in sequence generation13.30.29.1 (the hours.10 Four studies for the missing data. low.13. P .20 lection.28 All statistical analyses shortest follow-up ranged from 8 to 72 arate data for participants of interest were done with RevMan 5.29. and 75% to gery. made it difficult to make a judgment.

97. TABLE 2 Risk of Bias of Included Studies Study Adequate Sequence Allocation Blinding Incomplete Outcome Free of Selective Free of Other Bias Comments Generation Concealment Data Addressed Reporting Brazel 1996 Unclear Unclear No Yes Unclear Unclear Yung 2009a Yes Yes Yes Yes No Unclear Hyponatremia was not reported Yung 2009b Yes Yes Yes Yes No Unclear Hyponatremia was not reported Kannan 2010 Yes Yes No Yes Yes Unclear Neville 2010a Unclear Yes No Yes Unclear No Participants with preexisting hyponatremia (6%) Neville 2010b Unclear Yes No Yes Unclear No Participants with preexisting hyponatremia (0%–6%) Choong 2011 Yes Yes Yes Yes Yes Unclear Rey 2011 Yes Unclear No Yes Unclear No Participants with preexisting hyponatremia (29%–37%) Saba 2011 Yes Yes Yes No Yes Unclear Postrandomization exclusions (19 of 59 subjects) Coulthard 2012 Yes Yes Unclear Yes Yes Unclear significantly lower than those who re.9) 0.7) 0.6–14. or mean 6 SD. severe was also significantly greater in chil. Kannan et al: RR 0. a small proportion of participants with perform sensitivity analysis. we excluded these subjects to see ment. data in the isotonic fluid arm had 108 WANG et al Downloaded from pediatrics.45% S and 5% D 16 8.14 did not affect our findings (data not observed data itself.7 (1.9) 0.9% S and 5% D at half rate Neville 2010b Surgical $8 31 9. 95% CI 0.9) 0. we dren who received hypotonic IV fluids studies by Neville et al also enrolled extracted intention-to-treat data to (–3.8–5. P = .org at Indonesia:AAP Sponsored on June 5.9–14. potassium chloride.63 to –1.09 mmol/L.b y Solution Brazel 1996 Surgical $72 7 Adolescent 0. median (range).5% D at full rate D at full rate Choong 2011 Surgical $24 130 9. Fig 4).6) 136 mmol/L NaCl and 20 mmol/L KCl and 20 mmol/L KCl Saba 2011 Surgical and medical $8 21 8.5) 0. Furthermore.4 (1. we assumed that the missing ence between the 2 interventions in the whether they would influence the data in the hypotonic fluid arm had risk of hypernatremia with or without results.b y Solution Na Age.150 mmol/L (without the study by We also performed a sensitivity analysis ceived isotonic IV fluids (–2.3 (0. the fall in pNa Kannan et al: RR 0.91 to –1. However. saline. P .4 (10.7 0.45% S and 5% D 41 11.9% S and 5% D at full rate align $24 53 3.9 (2.98.0 (1. Fig 5). dextrose.1) 0.0) 0.1–6. with the study by studies would influence our findings. P = . We found that this population averaged 1 mmol/L higher than the inclusion of the study by Kannan et al.18% S and 5% D at full rate 58 3.5 (6. 47%.35.7–16. 2014 .28.62.9% S Kannan 2010 Medical $24 56 4.9% S Yung 2009b Surgical and medical $12 11 3.9 (1.9) 30–50 mmol/L NaCl 63e 4.0 (1.0–14.TABLE 1 Characteristics of Included RCTs of Hypotonic Versus Isotonic Maintenance IV Fluid Therapy in Hospitalized Children Study Condition Follow-up.8–14. c Including 2 participants with preexisting hyponatremia.49 mmol/L. e Including 18 participants with preexisting hyponatremia. I2 = 2.2 6 5.0 (0. .3% S and 3% D. h Hypotonic Isotonic Na Age.9% S and 5% D Coulthard 2012 Surgical $16 41 11.8–15.18% S and 4% D 13 5. and the missing which defined hypernatremia as pNa shown).9 (2. 5 Adolescent Hartman’s solution 0.7–9.5 0. our preexisting hyponatremia (0%–6%). a Number of participants reported in the tables of baseline characteristics.0–10. Because the hyponatremia.18% S and 4% D Yung 2009a Surgical and medical $12 15 4.0) 0.0) 0. For pNa P = .9–12) 0.5–14.7 (1.4–8. and hypernatremia.0–14.001.38 to For the risks of hyponatremia.45% S and 5% D at half rate 31c 9.73.3–13.5% 31c 8.0–15.1 (0.3) 0.9% S and 2.18% S and 5% D at 2/3 rate Neville 2010a Surgical $8 31c 9.22 to to see whether missing data of included 95% CI –2.9) Hartmann’s and 5% D D.13 and changes in pNa after fluid treat- analysis showed no significant differ. sodium chloride.3 (4.45% S and 2.18% S and 4% D 11 15.7 (1.aappublications.48.57.5) 0. 95% CI –5.9) 0.00001.4 (0. 2.0–7. b Age is expressed as median (interquartile range). I2 = 0%.9) 0. KCl.. NaCl.9% S and 5% D Rey 2011 Surgical and medical $12 62d 4. d Including 23 participants with preexisting hyponatremia.45% S and 5% D 128 9. 95% CI 0. I2 = 0%).2 6 5.2 (2. I2 = 87%. S.

3 NA NA NA NA 13 (15) 20.8 129. 2014 . Adverse Events Adverse outcomes of interest were re- ported in 2 studies. When the study by Brazel et al was termined the risk of hyponatremia and PEDIATRICS Volume 133.9 138.14 Choong et al reported new-onset hypertension in 1.1 9 NA 0 31 (37) 0. NA.6 6 3. not available.5 6 2. or hypotonic solutions).9 1 NA 0 Choong 2011 112 (130) NA NA 47 7 4 106 (128) NA NA 26 1 3 Rey 2011c 39 (43) NA 134. excluded.15 Subgroup Analysis FIGURE 3 Meta-analysis of data for the outcome of severe hyponatremia comparing hypotonic with isotonic IV Two of the included studies determined maintenance fluids in hospitalized children.2 138 6 1.4 6 3. They also reported 1 case of hyponatremic encephalopathy with seizures and stupor in children re- ceiving hypotonic fluid. pNa end.3 136 6 2. pNa changes. hyponatremia. data throughout the study period for categorical outcomes.9 0 0 0 Hyper.54% (2 of 130) children receiving hy- potonic fluid and none in those re- ceiving isotonic fluid.5 6 2. N. The results were analysis of pNa and pNa changes with I2 results showed that fluid type (isotonic similar to those from the analysis of value of 47% and 87%.13 Their served data itself.8 7 4 0 5 (5) 22.7 6 2. 1/58) in chil- dren receiving isotonic fluid for acute FIGURE 2 Meta-analysis of data for the outcome of hyponatremia comparing hypotonic with isotonic IV main- respiratory distress syndrome.9 6 4. d Data interpreted from figures.5 NA NA NA NA Yung 2009b 11 (12) 24. de- available cases (Table 4).14.4 6 3.15 Kannan et al reported 1 death (1.20 the I2 value became 17% and 0.6 6 2.5 6 4.14 This tenance fluids in hospitalized children.5 6 2.org at Indonesia:AAP Sponsored on June 5. not rate.1 6 2.5 1 0 0 Kannan 2010a 56 (56) NA NA 8 8 2 58 (58) NA NA 1 1 2 53 (53) NA NA 2 2 4 Yung 2009a 15 23 6 3.9 6 2.1 10 NA 0 31 (37) 20.1 6 1. hypernatremia. Hypo. b Data at 8 h. c Data at 12 h for continuous outcomes.15 The hospital length of stay was similar between the 2 types of fluids. REVIEW ARTICLE TABLE 3 Extracted Data From Included Studies for Meta-Analysis of Outcomes Relating to pNA Levels Study Hypotonic Isotonic N pNa Changes pNa End Hypo Severe Hypo Hyper N pNa Changes pNa End Hypo Severe Hypo Hyper Brazel 1996 7 (7) 212. pNa after IV fluids.2 6 3.0 138. and full rate averaged 1 mmol/L lower than the ob.72%. Heterogeneity was significant in the versus half rate) on pNa.130 mmol/L. number of participants expressed as available cases (randomized cases).0 6 6.1 6 3.0 136 6 2.0 NA NA NA NA 11 (12) 21.150 mmol/L. the effect of administration rate (full rate versus two-thirds rate. We assumed that all withdrawn cases were from those without preexisting hyponatremia. a Hyponatremia defined as sodium . respectively.2 8 1 NA Saba 2011d 21 (32) 1.0 6 1. child had normal pNa throughout the study period.0 6 3. respectively. hypernatremia defined as .0 1 0 1 Coulthard 2012 40 (41) NA 136.10. No significant heterogeneity was present in the analyses of other outcomes.7 7 0 0 39 (41) NA 138.1 6 3. Number 1. January 2014 109 Downloaded from pediatrics.aappublications.6 5 NA 2 Neville 2010bb 31 (37) 21.1 139.4 1 0 0 16 (27) 2.3 NA NA NA NA Neville 2010ab 31 (37) 21. pNa changes after IV fluids.7 19 3 NA 45 (50) NA 137. and the meta-analysis results remained nearly identical.2 138 6 3.

057). The review by Choong et al calculated an odds ratio of 17.001 Imputation 11c 140 133 22. Inclusion of retrospective studies and rehydration FIGURE 5 RCT was likely to contribute to this dis- Meta-analysis of data for the outcome of change in pNa level after hypotonic versus isotonic IV parity.6 The meta-analysis ITT 7 327 325 2.20 and 1 exclusively enrolled surgical patients tended to have a sion. Reports of death or b Number of children receiving isotonic IV solutions. Such findings raise the pos- pNa after IV fluid ACA 6 168 167 22.24).35 .22–24 With 10 published RCTs involving 855 subjects.15.31–35 However.36 1.22 to 2. whereas previous re- Studies views did not do so because of lack of Hyponatremia ACA 7 281 273 2.74 to 16.57 .aappublications.0002 fluids could increase hyponatremia- pNa change ACA 6 115 107 23. 2014 .10–12 Yung et al found that tions were too scant to draw a conclu- gery.6 which was much higher than ours of 3. WMD.6.10.76 0.49 25.19..3 mmol/L.24 23.28 .16.14 Separate analyses showed patients (–2.48 .31 .2 for developing hyponatremia with hypo- tonic fluids.06 ..30 .23 1.. P = .91 to –1. Another is that partici- that hypotonic solutions were associated to 0. encephalopathy.6 large enough. ventilation. They found no difference in pNa and pNa changes after fluid treat- ment between ventilated and non- ventilated patients.24 1.63 to –1. Five of the included studies exclusively enrolled both surgical and nonsurgical cases developing such severe condi- enrolled children undergoing sur. more strongly associated with symp- toms and complications. Because severe hyponatremia is maintenance fluids in hospitalized children.73 0.10 Three studies also pants in the included studies were with increased risk of hyponatremia evaluated the influence of mechanical tested for pNa more frequently than 110 WANG et al Downloaded from pediatrics. weighted mean difference.00001 Severe ACA 4 267 214 5. we confirmed the early finding that hypotonic main- tenance IV fluid was a risk factor for hospital-acquired hyponatremia for pe- diatric patients. intention to treat. and fluid restriction may in each of the populations (data not accumulating.54 22.0001 sibility that hypotonic maintenance IV Imputation 11c 196 197 21. 95% CI –4.003 showed that hypotonic maintenance hyponatremia IV fluids significantly increased the risk ITT 4 289 241 5.003 of severe hyponatremia in hospitalized Hypernatremia ACA 3 164 153 0.67 children. plications such as hyponatremic a Number of children receiving hypotonic IV solutions.62 ITT 3 199 192 0.org at Indonesia:AAP Sponsored on June 5. shown).88 to –0.09 22. reviews. of Hypotonica Isotonicb RR or WMD 95% CI P hyponatremia. c Imputed missing data were analyzed as separate studies.23 to 2. patients.18 . neurologic injury as a result of hospital- acquired hyponatremia in children re- ceiving hypotonic IV fluids are also pNa changes.34 to –0. available case analysis.57 to 3.008 associated death and severe com- ACA. in the not satisfy a child’s daily requirement.77 to 16.13.52 to 3.74 .1.49 (RR 2.59 .0001 data at that time.29 1. Four of the included studies 855 subjects of the included 10 RCTs. One explanation is that such cases children with illnesses not requiring greater fall in pNa than nonsurgical are rare and the sample size was not surgery. we also calcu- TABLE 4 Sensitivity Analysis by Missing Data lated pooled RR of developing severe Outcome Data Source No. ITT.12 DISCUSSION Our systematic review and meta- analysis of isotonic versus hypotonic maintenance IV fluids in hospitalized FIGURE 4 Meta-analysis of data for the outcome of pNa level after hypotonic versus isotonic IV maintenance fluids children act as an update of previous in hospitalized children.

we note 2 caveats to retention of free water. las for calculating the rate of IV fluids in likely to cause a positive balance of free natremia. In addition. but their study fluid (0. Be. tonic fluids are superior to hypotonic included studies were RCTs. and pNa patients.27. such as sub- Hyponatremia occurs due to a deficit in similar to those using analysis of clinical fluid deficit.18% saline. the develop. nausea.6. etc) We are confident in the finding that lacked a description of medical condi. develop hyponatremia in hospitalized included studies. pNa needs to be monitored than isotonic IV fluids to cause hypo. although the risk is greater fall of pNa in surgical patients children in terms of composition of lower compared with hypotonic fluids. rate.aappublications. the results from state because of the multiple stimuli complications occurred. state. severe hyponatremia. making ADH increases the permeability of col.25 All ministered. pain. or im.43 different studies. present.26. Number 1. Addition- Choong et al observed elevated ADH more likely than isotonic IV fluids to ally. ease (hypoxemic state).9. there was no obvious surgical pediatric patients. and pNa changes after fluid therapy are hyponatremia in the postoperative fore were immediately treated before consistent.10 and hyponatremia is common istration. are more fluids could correct preexisting hypo.45% saline and 0. However.17–19. January 2014 111 Downloaded from pediatrics. 2014 . durations of admin- water in these pediatric patients.26 and the compliance of the water when hypotonic fluids were ad- servational studies suggested that iso. formu- water than isotonic fluids.40–42 the evidence stronger than previous lecting duct cells in the kidney. fluids in hospitalized children. excessive water intake. and dren requiring maintenance IV fluid cause of this role. patients with preexisting hyponatremia ing differing IV fluid types such as Thus. severe infection) and pulmonary dis. and study quality.13. isotonic fluids are receiving or not receiving mechanical therapy in terms of pNa levels.org at Indonesia:AAP Sponsored on June 5. isotonic fluids may be a bet- the meta-analysis results of hypona. available cases.36 In the healthy RCTs. 1 RCT with a substantial proportion of among patient characteristics includ- paired ability to excrete free water.9 Most par- paired ability to excrete free water. leading These studies were not included in the reviews.9% saline/Hartmann’s. only pub- children often have $1 stimuli (such not meet the predefined criteria.15 suggesting the underlying settings: restricted fluids or fluids at full hypotonic fluids in hospitalized chil- role of excess ADH in another way. The main heterogeneity in the population. report with the PRISMA guidelines. This model studies. there is no ideal IV fluid for all hyponatremia. it is not uncommon to develop ommendations. Fourth. REVIEW ARTICLE those in common practices and there. First. the sample size was small in most levels in those developing hospital.39 Many ob. Second. the presence of obvious variances This is thought to contribute to im. Another is vomiting. and pain) for excess ADH. At natremia in hospitalized children.9. Thus.38 consistent with our findings. humans can excrete excessive analyses of pNa and pNa changes came The strength of the review was based on fluid to maintain sodium and water from an RCT with a small sample size. than in medical patients. hypotonic fluids. How- not exempt from the risk of developing ventilation. acquired hyponatremia regardless of children may be applicable to a range of Overall. with more free at the baseline showed that isotonic 0. First. How. we adopted a random-effects plicit criteria for selection of relevant ment of hyponatremia was contributed model in all meta-analyses. PEDIATRICS Volume 133. the findings from these studies are introduce a publication bias. vomiting.44 In surgical ter choice than the traditional rec- tremia.37 Hospitalized current meta-analysis because they did regarding this review. medical or surgical patients.14 Third. assessment of risk of bias. Two studies with spe. data produces more conserved results than analysis strictly following the Cochrane to the impaired ability to excrete free the fixed-effects model. ex- homeostasis. isotonic fluids are safer than fluid type.9 cial situations also did not affect the ticipants in this meta-analysis were The sodium intakes in each group of results. Handbook. blood loss. sensitivity analysis by missing data are for ADH that are present. Yung et al observed a ever.20 a comprehensive search strategy. and narcotic use. This may as postoperative state. and the rate and duration of admin- hypotonic IV fluids were more likely tions. sodium. The finding that hypotonic IV fluids were istration. our the included RCTs were well within the heterogeneity among the included findings are more applicable to this daily requirements. lished studies were included. Therefore. ever. in patients with infection (especially when IV fluids are administered.

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analytical reasoning. Students who take Massive Open Online Courses with limited credit are also likely to benefit as they can prove that they can apply what they have learned. but plans to enter the workforce after graduating next spring.aappublications. Noted by WVR.25(8):1471–1475 study. 2008. do wish that several years of tuition and learning experiences were worth more than a 90-minute examination. Employers like the test as it may be a better way to assess applicant skills. Torres JM. Pediatr Crit Care Med.113 tremia in children with gastroenteritis therapy prevents iatrogenic hyponatremia in (2):387–390 ANOTHER EXAM: My eldest son is in his fourth year of college. benchmarked assessments of clinical reasoning skills for graduating students. López Prats JL. 2013). Incidence of hypona. however. Toledo Parreño D. Streptococcus pneumoniae bacteremia 42. Chest. The 90-minute examination (which is benchmarked and uses the same numerical scoring system as the SAT exam) assesses critical thinking.21(10):1020–1025 AP. Bykowski M. He has taken a circuitous route through college. pediatrics: a randomized. JD. REVIEW ARTICLE 41. Seeing an opportunity. many graduating college students now take the Collegiate Learning Assessment (CLA) examination. Schmitt E. January 2014 113 Downloaded from pediatrics. News: August 25. Saberi MS. 2010. et al. documents literacy. Pae. 2011. 2014 . a few organizations are now offering national. Cardenas O. Post.org at Indonesia:AAP Sponsored on June 5. As reported in The Wall Street Journal (U. Number 1. The use of isotonic fluid as maintenance in a community hospital. MD PEDIATRICS Volume 133. controlled open operative hyponatremia following calvarial Pediatr Nephrol. López PO. and writing and communication but not subject-specific material. Many employers do not believe that colleges have pre- pared students for jobs in the current marketplace and that grade point aver- ages are a poor proxy for intelligence or problem-solving skills (and do not correlate with job performance). I do not know how the university he attends feels about the examination.S. Hanna M. Montañana PA. Vasquez A. treated with hypotonic intravenous fluids. 43. I. Ocón 44. Given that the job market for someone with an East Asian history major is fairly limited. Cladis FP. Modesto i Alapont V. he plans to take an exam to prove that he can think on his feet. Schlossberg diatr Anaesth.9(6):589–597 vault remodeling in craniosynostosis. 1998.

Downloaded from pediatrics. 2013.Isotonic Versus Hypotonic Maintenance IV Fluids in Hospitalized Children: A Meta-Analysis Jingjing Wang.xhtml PEDIATRICS is the official journal of the American Academy of Pediatrics.aappublications.ht ml Supplementary Material Supplementary material can be found at: http://pediatrics. it has been published continuously since 1948. 15 of which can be accessed free at: http://pediatrics.1542/peds.org/site/misc/Permissions.aappublications. along with others on similar topics.xh tml Reprints Information about ordering reprints can be found online: http://pediatrics.org/cgi/collection/rheumatol ogy:musculoskeletal_disorders_sub Collagen Vascular & Other Multisystem Disorders http://pediatrics. appears in the following collection(s): Hematology/Oncology http://pediatrics.DCSupplemental.html References This article cites 38 articles.org/cgi/collection/blood_dis orders_sub Rheumatology/Musculoskeletal Disorders http://pediatrics.aappublications.org/content/133/1/105. tables) or in its entirety can be found online at: http://pediatrics.133. 2014 . originally published online December 30. Illinois.org/content/suppl/2013/12/2 4/peds. A monthly publication.105.org/cgi/collection/hematolog y:oncology_sub Blood Disorders http://pediatrics. Erdi Xu and Yanfeng Xiao Pediatrics 2014. DOI: 10. published.aappublications. Copyright © 2014 by the American Academy of Pediatrics.org/cgi/collection/collagen_v ascular_-_other_multisystem_disorders_sub Permissions & Licensing Information about reproducing this article in parts (figures.org/content/133/1/105.org at Indonesia:AAP Sponsored on June 5.2013-2041.aappublications.ht ml#ref-list-1 Subspecialty Collections This article. and trademarked by the American Academy of Pediatrics.2013-2041 Updated Information & including high resolution figures.aappublications.org/site/misc/reprints.aappublications. Elk Grove Village.aappublications. PEDIATRICS is owned. 60007. can be found at: Services http://pediatrics. Online ISSN: 1098-4275. 141 Northwest Point Boulevard. All rights reserved. Print ISSN: 0031-4005.aappublications.full.aappublications.full.