Article, Nephrology

Balanced crystalloids versus normal saline for fluid resuscitation in critically ill patients: A systematic review and meta-analysis with trial sequential analysis

a b s t r a c t

Introduction: Fluid resuscitation is a fundamental component of the management of critically ill patients, but whether choice of crystalloid affects patient outcomes remains controversial. Therefore, we per- formed this meta-analysis to compare the efficacy and safety of balanced crystalloids with normal saline. Methods: We searched the MEDLINE, Cochrane Central and EMBASE up to October 2018 to identify ran- domized controlled trials (RCTs) that compared balanced crystalloids versus normal saline in critically ill patients. The primary outcome was mortality. The secondary results were the incidence of Acute Kidney Injury and risk of receiving Renal replacement therapy . Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using Revman 5.3, trial sequential analysis (TSA) 0.9 and STATA 12.0.

Results: Nine RCTs were identified. The pooled analyses showed that there were no significant differences in mortality (Relative risk = 0.93, 95% confidence interval (CI) = 0.86, 1.01, P = 0.08), incidence of AKI (RR 0.94, 95% CI 0.88, 1.00, P = 0.06) or RRT use rate (RR 0.94, 95% CI 0.69, 1.27, P = 0.67) between bal-

anced crystalloids and normal saline groups. However, TSA did not provide conclusive evidence. Conclusions: Among critically ill patients receiving crystalloid fluid therapy, use of a balanced crystalloid compared with normal saline did not reduce the mortality, risk of severe AKI or RRT use rate. Further large randomized clinical trials are needed to confirm or refute this finding.

Trial registration: A protocol of this meta-analysis has been registered on PROSPERO (registration num- ber: CRD42018094857).

(C) 2019 The Authors. This is an open access article under the CC BY-NC-ND license

(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Fluid resuscitation is a fundamental component of the manage- ment of critically ill patients, but whether choice of crystalloid affects patient outcomes remains controversial [1,2]. Currently, normal saline is the most commonly used resuscitation fluid. How-

* Corresponding author at: Critical Care Medicine, Chinese People’s Liberation Army General Hospital, 28 Fu-Xing Road, Beijing 100853, People’s Republic of China.

E-mail address: [email protected] (F. Zhou).

1 Chao Liu, Guangming Lu and Dong Wang contributed equally to this work.

ever, concern has focused on the hypothesis that the high chloride content of saline contributes to the development of Acute kidney injury [3,4]. Alternatives to normal saline include crystalloids with electrolyte compositions that more close resemble that of plasma, such as lactated Ringer‘s solution, Hartmann solution, or Plasma-Lyte [5,6]. Although observational data suggest that those balanced crystalloids may be associated with a decreased risk of severe AKI, this advantage of balanced crystalloids was not found in a recent RCT of critically ill patients [6].

Our previous Network meta-analysis [7], which focused on fluid resuscitation in critically ill patients, found that balanced crystal- loids, especially Plasma-Lyte, are presumably the best choice for

https://doi.org/10.1016/j.ajem.2019.02.045

0735-6757/(C) 2019 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

most critically ill patients who need fluid resuscitation. However, the evidence was not conclusive.

Recently, three RCTs [8-10] have been published that provide new evidence on this topic, but the findings are not entirely consis- tent with each other. To provide the most recent available evi- dence, we conducted this meta-analysis to evaluate the efficacy and safety of balanced crystalloids versus normal saline for fluid resuscitation in critically ill patients, and we further used trial sequential analysis (TSA) to determine whether the current evi- dence was robust and conclusive.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMAs) were used to perform this meta- analysis [11].

Search strategy

A literature search of MEDLINE, Cochrane Central and EMBASE databases from database inception to October 2018 was per- formed. The search terms used were ”normal saline” or ”isotonic saline” or ”sodium chloride” compared with ”lactated ringer” or ”Hartmann” or ”Plasma-Lyte” or ”buffered crystalloid” or ”bal- anced crystalloids” and ”randomized” or ”randomized”. The searches were limited to published studies in human subjects. There were no language restrictions. We also hand-searched con- ference proceedings and the reference lists of review articles (Appendix A).

Eligibly criteria

The inclusion criteria were as follows: 1) population: critically ill patients (>=18 years old) requiring fluid resuscitation, the length of follow up was according to the included studies; 2) intervention: balanced crystalloids (contains Lactated Ringer’s, Hartmann and Plasma-Lyte); 3) comparison: normal saline; 4) outcome measure: the primary outcome was mortality. The secondary outcomes were incidences requiring RRT and the incidence of AKI (AKI of stage 2 or higher (according to the Kidney Disease: Improving Global Out- comes plasma creatinine criteria) and injury or higher (according to the RIFLE categories)); 5) study design: RCT.

The exclusion criteria were as follows: 1) patients with pre- existing chronic renal failure; 2) patients younger than 18 years old; 3) repeated data; 4) fluids used as maintenance rather than resuscitation.

Study selection

Two independent investigators performed the study selection. Disagreements between two investigators were resolved in meet- ings or adjudicated by a third reviewer.

Data extraction

Two independent reviewers (CL and GML) performed the data extraction using a standardized form. The following data on study characteristics were collected: first author, Publication year, study design, number of patients, mean age of patients, patient character- istics, and balanced crystalloids type. The other two independent reviewers (DW and JH) checked the data to make sure it was correct. The methodological quality of included trials was assessed by two reviewers according to the Cochrane Risk of Bias Tool.

Grading the quality of evidence

Two reviewers evaluated the quality of evidence according to the Grading of Recommendations Assessment, Development and

Evaluation (GRADE) methodology. Based on risk of bias, indirect- ness, imprecision, inconsistency and publication bias, the quality of the evidence was classified as high, moderate, low or very low. The software of GRADE Pro version 3.6 was used for this analysis.

Statistical analysis

Dichotomous outcomes were expressed as Relative risks (RRs) with 95% confidence intervals (CI), and continuous outcomes were expressed as the mean difference (MD) with 95% CI. Statistical heterogeneity across studies was analyzed by using the I2 statistic. An I2 > 50% indicated significant heterogeneity [12]. The fixed- effect model was used to analyze results with acceptable or no heterogeneity, and the random-effect model was used to analyze results with significant heterogeneity. Subgroup and sensitivity analyses were performed to investigate potential between-study heterogeneities and estimate other potentially confounding fac- tors. Statistical analyses were performed using Review Manager, version 5.3 (RevMan, The Cochrane Collaboration, Oxford, UK). The Begg and Egger tests were employed using STATA 12.0 (Stata Corporation, College Station, TX, USA). A P value <0.05 was consid- ered a statistically significant.

Trial sequential analysis

To determine whether the evidence from a meta-analysis is reli- able and conclusive and to reduce the risk of reaching a false- positive or false-negative conclusion, the trial sequential analysis (TSA) was used [13]. This method, which combines an a priori information size calculation with the adaptation of monitoring boundaries, can be used to control the P value and widen the con- fidence intervals [14]. When the cumulative z-curve enters the futility area or crosses the trial sequential monitoring boundary, the anticipated intervention effect may reach a sufficient Level of evidence. If the z-curve does not cross any of the boundaries and

Fig. 1. Flow chart of the study selection.

the required information size has not been reached, the evidence is inadequate to reach a conclusion [15]. We calculated the required information size based on a relative risk reduction of 10%. The type I error (a) and power (1-b) were set as 0.05 and 0.90, respectively. The control event rates were calculated from the normal saline group. The TSA was conducted with the use of TSA version 0.9 beta software (http://www.ctu.dk/tsa).

Results

Search results and study characteristics

The process of study selection is outlined in Fig. 1. In total, nine studies [6,8-10,16-20] met the inclusion criteria. The main charac- teristics of the included studies are summarized in Table 1. These studies were published between 2011 and 2018. Six studies [6,8- 10,17,20] focused on patients in ICU, two studies [18,19] focused on patients with acute pancreatitis and one study [16] included trauma patients.

Risk of bias and grades of evidence

The risk of bias is summarized in Fig. 2. Randomized sequence generation and allocation concealment were reported adequately in most studies. Three studies were high-quality studies with low risk of bias in all items. The GRADE Working Group grade of evi- dence was moderate for mortality, incidence of AKI and incidence of RRT use.

Primary outcome: mortality

Eight studies reported mortality, and no statistically significant difference was found between the balanced crystalloids and nor- mal saline groups (RR = 0.93, 95% CI = 0.86, 1.01, P = 0.08, I2 = 0%;

Fig. 3a). The fixed effects model was used to conduct TSA, and the cumulative Z-curve did not enter the futility area and did not cross the conventional boundary (Fig. 3b). Sensitivity analyses were performed to compare Plasma-Lyte with normal saline and compare Lactated Ringer’s with normal saline. Similarly, no differ- ences were found (Table 2).

Secondary outcomes

Incidence of AKI

Seven studies reported the incidence of AKI. There was no sig- nificant difference between the two groups (RR 0.94, 95% CI 0.88, 1.00, P = 0.06, I2 = 0%; Fig. 4a). Due to the low heterogeneity, the fixed-effect model was used for TSA, and the results showed that the cumulative Z-curve did not enter the futility area and did not cross the conventional boundary (Fig. 4b). Sensitivity analyses were performed to compare Plasma-Lyte with normal saline and compare Lactated Ringer’s with normal saline. Similarly, no differ- ences were found (Table 2).

RRT use rate

Only five studies reported the RRT use rate, and no significant difference was found between the two groups (RR 0.94, 95% CI 0.69, 1.27, P = 0.67, I2 = 39%; Table 2). Sensitivity analyses were

Table 1

Characteristics of included studies.

Study

Setting

Population

No. of

patients (M/F)

Mean age (years)

Severity

Balanced

crystalloids type

Fluid volume (24 h)

Annane D [17] (2013;

57 participating

Sepsis, trauma, or

BC: 72 (NR)

63 (50-75)

SAPSII: 50

Lactated

NR

multi-country)

ICUs

hypovolemic shock without

NS: 1035 (NR)

(36-65)b

ringer’s

Young JB [16] (2014;

Level 1 trauma

sepsis or trauma

adult trauma patients

BC: 22 (16/6)

BC: 38 +- 19a

BC: 24 +- 18

Plasma-Lyte A

BC: 9000 +- 5500a

United States)

center

(>=18 years) requiring blood

NS: 24 (19/5)

NS: 39 +- 14a

(ISS)a

NS: 10300 +- 6500a

Young P [6] (2015;

Four tertiary ICUs

transfusion, intubation, or operation within 60 min

ICU patients receiving

BC: 1152 (739/

BC: 60.1 +- 16.8a

NS: 22 +- 14 (ISS)a

BC: 14.1 +- 6.9

Plasma-Lyte

NR

Australian and New

crystalloid fluid therapy as

413)

NS: 61.0 +- 16.3a

(APACHEII)a

148

Zealand)

Verma B [9] (2016;

Three

clinically indicated

ICU patients (>=18 years)

NS: 1110 (746/

364)

BC: 33 (21/12)

BC: 62 (45-70)b

NS: 14.1 +- 6.7 (APACHEII)a

BC: 55 (44-81)

Plasma-Lyte

BC: 1090

Australia)

multidisciplinary

receiving crystalloid fluid

NS: 34 (21/13)

NS: 64 (46-72)b

(APACHEIII)b

148

(620-2500)b

Semler MW [8] (2016;

ICUs

A tertiary medical

resuscitation

ICU patients receiving

BC: 520 (268/

BC: 57 (44-68)b

NS: 64 (48-73) (APACHEIII)b

NR

Lactated

NS: 1275 (435-2243)b

BC: 1424

United States)

ICU

crystalloid fluid therapy

252)

NS: 58 (46-70)b

ringer’s

(500-3377)b

Semler MW [10] (2018;

Five ICU at an

Patients (>=18 years) who

NS: 454 (246/

208)

BC: 7942

BC: 58 (44-69)b

NR

solution and Plasma-Lyte A

Lactated

NS: 1617

(500-3628)b BC: 1000

United States)

academic center

were admitted to a

(4540/3402)

NS: 58 (44-69)b

ringer’s

(0–3210)b

participating ICU

NS: 7860

(4557/3303)

solution and

Plasma-Lyte A

NS: 1020

(0-3500)b

Ratanarat R [20] (2017;

ICU

NR

BC: 88 (NR)

NR

NR

NR

NR

Thailand)

Wu BU [19] 2011;

A 777-bed tertiary

Patients (>=18 years) with

NS: 93 (NR)

BC: 19 (8/11)

BC: 50 (40-73)b

BC: 3 (0-6)

Lactated

NR

care center

acute pancreatitis

NS: 21 (14/7)

NS: 54 (40-60)b

(APACHEIII)b

ringer’s

Choosakul S [18] 2018;

A 1200-bed tertiary

Patients (18-80 years old)

BC: 23 (12/11)

BC: 54.8 +- 20.4a

NS: 3 (1-5) (APACHEIII)b

BC: 1 (0-2)

Lactated

BC:

care center and

with acute pancreatitis

NS: 24 (17/7)

NS: 48.3 +- 13.6a

(SIRS)b

ringer’s

4929.6 +- 1265.6a

pancreatic center

NS: 1 (0-2) (SIRS)b

NS:

5374.2 +- 768.8a

Abbreviations: APACHE, Acute Physiology and Chronic Health Evaluation; BC: Balanced crystalloids; NR, not report; NS: Normal saline; SAPS, Simplified Acute Physiology II score.

a Mean +- standard error.

b Median (interquartile range).

ICU length of stays”>performed to compare the Plasma-Lyte and normal saline. Simi- larly, no differences were found (Table 2).

ICU length of stays

Six studies reported the results for ICU length of stay, and no significant difference was found between the two groups (RR – 0.31 95% CI -1.60,0.97, P = 0.47, I2 = 100%; Table 2).

Publication bias

Assessment of publication bias using Egger and Begg tests showed that there was no potential publication bias among the included trials (Egger’s test, P = 0.25; Begg’s test, P = 0.06).

Discussion

This systematic review and meta-analysis of nine RCTs evalu- ated the efficacy and safety of balanced crystalloids versus normal saline for fluid resuscitation in critically ill patients. The present meta-analysis suggests that there is no difference in mortality, AKI morbidity and RRT use rate. However, the subsequent TSA did not reach a definitive conclusion. Therefore, further high qual- ity RCTs are needed to confirm or refute this finding.

An earlier study focused on this topic, which included six RCTs with 19,332 patients, showed no difference on various clinical out- comes including in-hospital mortality, AKI, overall ICU mortality, and new RRT between balanced crystalloids and isotonic saline [21]. Our study included more studies and we further used the TSA analysis to determine whether the evidence from this meta- analysis is reliable and conclusive and to reduce the risk of reach- ing a false-positive or false-negative conclusion.

The different fluid types have difference effects on different dis- eases, populations and genders. For example, patients with sepsis may more sensitive to metabolic acidosis and may suffer more AKI or increased mortality [22,23]. The patients included in this analysis come from different sources, but with the limited studies included in this meta-analysis, we could not perform more sub- group or sensitivity analyses. Therefore, more studies are needed to evaluate the effect of different fluids on different patients and diseases. Meanwhile, individualizED treatments are necessary for each critically ill patient.

Normal saline is still the most commonly used crystalloid world- wide [5,24]. Many observational studies have shown that the use of normal saline is most likely associated with an increased incidence of AKI, hyperchloremic acidosis, coagulation disturbances, hemody- namic instability and mortality [25-27]. The balanced crystalloids in this meta-analysis contain Lactated Ringer’s and Plasma-Lyte. Lac- tated Ringer’s solution is a hypotonic solution (sodium concentra- tion, 130 mmol/L) [28] and may lead to hyponatremia when use for resuscitation in critically ill patients [29]. Hyponatremia is also an independent predictor for hospital mortality [30]. The electrolyte composition of Plasma-Lyte closely mimics human plasma in its content of electrolytes, osmolality, and pH [31]. Therefore, we per- formed sensitivity analysis to compare Plasma-Lyte with normal saline and compare Lactated Ringer’s with normal saline. However, no significant differences were found.

In this meta-analysis we only evaluated mortality, AKI morbidity,

RRT use rate and ICU length of stay. However, we did not find any dif- ference between the two groups. Therefore, whether the Plasma-Lyte is more effective than normal saline or Lactated Ringer’s needs to be further evaluated. Further studies should also examine other out- comes, such as the incidence of hyponatremia or hospitalization cost.

Fig. 2. Assessment for risk of bias.

Fig. 3. Effect of balanced crystalloids versus normal saline on mortality. a. Forest plot of mortality. b. Trial sequential analysis of mortality. A diversity-adjusted information size of 26,456 participants calculated on the basis of a mortality rate of 13.2% in the normal saline group, relative risk reduction 10%, a = 5% (two sided), b = 10%, and I2 = 0%. The solid blue line represents the cumulative Z-curve, which did not cross the trial sequential monitoring boundary and did not reach the futility area. BC, balanced crystalloids; NS, normal saline; M-H, Mantel-Haenszel. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

fluid overload frequently occurs in critically ill patients and many studies report its significant association with higher mortal- ity and more RRT [33-36]. Several studies have shown that normal saline (due to its high sodium content) may result in more fluid overload [27,37]. In this meta-analysis, the fluid volume had a sig- nificant diversity between each study, but whether a patient’s exposure to a positive or negative fluid balance is detrimental remains controversial. Therefore, when a patient needs fluid resus- citation, we should not only consider the fluid type but also con- sider the fluid responsiveness [38].

Our meta-analysis has several potential limitations. First, due to the limited data, it was difficult to perform more subgroup or sen- sitivity analyses. Second, patients included in this meta-analysis had varying degrees of severity (trauma, sepsis or acute pancreati-

Table 2

Other outcomes.

tis), which will have caused heterogeneity and reduced the stabil- ity of the results. Third, the hyperchloremia, hyponatremia and fluid overload were all independent factors related to higher mor- tality. However, we could acquire sufficient evidence to perform comprehensive analyses; therefore, more studies focused on those issues are urgently needed. Fourth, there was the potential for incomplete retrieval of identified research studies, which could have introduced publication bias.

Conclusions

Among critically ill patients receiving crystalloid fluid therapy, use of a balanced crystalloid compared with normal saline did not reduce the mortality, the risk of AKI or the RRT use rate. Further

Outcomes

Comparison

Number of studies

Risk ratio (95%CI)

Test for effect (P value)

Heterogeneity I2 (P value)

Mortality

PL vs NS

3 (6,9,16)

0,91 (0.69, 1.19)

0.48

0% (0.41)

LR vs NS

3 (17,18,19)

1.07 (0,78, 1.47)

0.69

0% (0.48)

AKI morbidity

PL vs NS

2 (6, 9)

1.08 (0.83, 1.39)

0.58

0% (0.42)

LR vs NS

3 (18,19,20)

0.94 (0.54, 1.62)

0.82

0% (0.73)

RRT use rate

BC vs NS

5 (6,8,9,10,20)

0.94 (0.69, 1.27)

0.67

39% (0.16)

PL vs NS

2 (6, 9)

1.02 (0.67, 1.55)

0.93

0% (0.42)

LR vs NS

1 (20)

0.35 (0.12, 1.05)

0.06

NA

ICU length of stay

BC vs NS

6 (6,8,9,16,18,19)

–0.31 (–1.60,0.97)

0.47

100% (<0.01)

Abbreviations: AKI, Acute kidney injury; BC, Balanced crystalloids; ICU, Intensive care medicine; LR, Lactated ringer’s; NA, Not applicable; NS, Normal saline; PL, Plasma-Lyte; RRT, Renal replacement therapy.

Availability of supporting data“>Fig. 4. Effect of balanced crystalloids versus normal saline on AKI incident. a. Forest plot of severe AKI incident. b. Trial sequential analysis of AKI incident. A diversity- adjusted information size of 22,135 participants calculated on the basis of a mortality rate of 15.4% in the normal saline group, relative risk reduction 10%, a = 5% (two sided), b = 10%, I2 = 0%. The solid blue line represents cumulative Z-curve, which did not cross the trial sequential monitoring boundary and did not reach the futility area. AKI, acute kidney injury; BC, balanced crystalloids; M-H, Mantel-Haenszel; NS, normal saline. (For interpretation of the references to color in this figure legend, the reader is referred to

the web version of this article.)

large randomized clinical trials are needed to confirm or refute this finding.

Abbreviations

AKI acute kidney injury

CI confidence interval

GRADE Grading of Recommendations Assessment, Development, and Evaluation

MD mean difference

ICU intensive care unit

PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCT randomized controlled trial RR relative risk

RRT renal replacement therapy TSA trial sequential analysis

Ethical approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of supporting data

The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

Competing interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Authors’ contribution

CL,GML and DW contributed equally to this work. CL, GML and DW conceived the study, participated in the design, collected the data, performed statistical analyses and drafted the manuscript.

YL, ZM and PH performed statistical analyses and helped to draft the manuscript. JH, RL and DH collected the data and revised the manuscript critically for important intellectual content. FHZ col- lected the data, performed statistical analyses and helped to revise the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Acknowledgements

Not applicable.

Appendix A

Table 1

Conferences searches.

American Association for the Surgeons of Trauma (2008- 2018)

American College of Chest Physicians (2010-2018) American Society of Anaesthesiology (2009-2018) American Thoracic Society (2009-2018)

Canadian Anesthesiologists’ Society (2008-2018) European Society of Intensive Care Medicine (2008-2018) Society of Critical Care Medicine (2008-2018)

Table 2

Search strategy.

n

saline or Plasma-Lyte 148 in critically ill patients. Crit Care Resusc 2016;18 (3):205-12.

Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, et al. Investigators S, the pragmatic critical care research G: balanced crystalloids versus saline in critically ill adults. N Engl J Med 2018;378(9):829-39.
  • Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
  • Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60.
  • Liu C, Mao Z, Kang H, Hu J, Zhou F. Regional citrate versus heparin anticoagulation for Continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials. Crit Care 2016;20(1):144.
  • Wetterslev J, Thorlund K, Brok J, Gluud C. Estimating required information size by quantifying diversity in random-effects model meta-analyses. BMC Med Res Methodol 2009;9:86.
  • Mao Z, Gao L, Wang G, Liu C, Zhao Y, Gu W, et al. Subglottic secretion suction for preventing ventilator-associated pneumonia: an updated meta-analysis and trial sequential analysis. Crit Care 2016;20(1):353.
  • Young JB, Utter GH, Schermer CR, Galante JM, Phan HH, Yang Y, et al. Saline versus Plasma-Lyte A in Initial resuscitation of trauma patients: a randomized trial. Ann Surg 2014;259(2):255-62.
  • Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declere AD, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. Jama 2013;310(17):1809-17.
  • Choosakul S, Harinwan K, Chirapongsathorn S, Opuchar K, Sanpajit T, Piyanirun W, et al. Comparison of normal saline versus lactated Ringer’s solution for fluid resuscitation in patients with mild acute

    Target terms for literature search:

  • (”normal saline” OR ”isotonic saline” OR ”sodium chloride” OR ”lactated ringer” OR ”Hartmann” OR ”Plasma-Lyte” OR ”buffered crystalloid” OR ”balanced crystalloids”) and (”sepsis” OR ”infection” OR ”septic shock” OR ”severe sepsis” OR ”shock” OR ”systemic inflammatory response syndrome” OR ”SIRS” OR ”injury” OR ”trauma” OR ”hemorrhage” OR ”toxic Shock syndrome” OR ”burns” OR ”acute pancreatitis” OR ”critical ill” OR ”critical illness” OR ”intensive care unit” OR ”intensive care” OR ”critical care” OR ”ICU”)

    Limit 1 to clinical trial

    Randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized [tiab] OR placebo [tiab] OR clinical trials as topic [mesh: noexp] OR randomly [tiab] OR trial [ti]

    2245

    788

    pancreatitis. Pancreatology: A randomized controlled trial; 2018.

    Wu BU, Hwang JQ, Gardner TH, Repas K, Delee R, Yu S, et al. Lactated Ringer’s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011;9(8):710-7 [e711].
  • Ratanarat R; Sanguanwit PCA: The effects of normal saline versus balanced crystalloid solution as a resuscitation fluid on acute kidney injury in shock patients: a randomized opened label-controlled trial.23-27, 2017. 30th Annu Congr Eur Soc intensive care Med ESICM 2017 2017.
  • Zayed YZM, Aburahma AMY, Barbarawi MO, Hamid K, Banifadel MRN, Rashdan L, et al. Balanced crystalloids versus isotonic saline in critically ill patients: systematic review and meta-analysis. J Intensive Care 2018;6:51.
  • Suetrong B, Pisitsak C, Boyd JH, Russell JA, Walley KR. Hyperchloremia and moderate increase in serum chloride are associated with acute kidney injury in severe sepsis and septic shock patients. Crit Care 2016;20(1):315.
  • Bonanno LS. Early administration of intravenous fluids in sepsis: pros and cons. Crit Care Nurs Clin North Am 2018;30(3):323-32.
  • Zhou FH, Liu C, Mao Z, Ma PL. Normal saline for intravenous fluid therapy in critically ill patients. Chin J Traumatol 2018;21(1):11-5.
  • Marttinen M, Wilkman E, Petaja L, Suojaranta-Ylinen R, Pettila V, Vaara ST. Association of plasma chloride values with acute kidney injury in the critically ill – a prospective observational study. Acta Anaesthesiol Scand 2016;60 (6):790-9.
  • Shaw AD, Bagshaw SM, Goldstein SL, Scherer LA, Duan M, Schermer CR, et al.
  • 3 Limit 2 to humans 364

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