Saline Is Not the First Choice for Crystalloid Resuscitation Fluids

BACKGROUND Comparative clinical effects of balanced crystalloids and saline are uncertain, particularly in noncritically ill patients cared for outside an intensive care unit (ICU). METHODS We conducted a single-center, pragmatic, multiple-crossover trial comparing balanced crystalloids (lactated Ringer’s solution or Plasma-Lyte A) with saline among adults who were treated with intravenous crystalloids in the emergency department and were subsequently hospitalized outside an ICU. The type of crystalloid that was administered in the emergency department was assigned to each patient on the basis of calendar month, with the entire emergency department crossing over between balanced crystalloids and saline monthly during the 16-month trial. The primary outcome was hospital-free days (days alive after discharge before day 28). Secondary outcomes included major adverse kidney events within 30 days — a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to ≥200% of baseline) — all censored at hospital discharge or 30 days, whichever occurred first. RESULTS A total of 13,347 patients were enrolled, with a median crystalloid volume administered in the emergency department of 1079 ml and 88.3% of the patients exclusively receiving the assigned crystalloid. The number of hospital-free days did not differ between the balanced-crystalloids and saline groups (median, 25 days in each group; adjusted odds ratio with balanced crystalloids, 0.98; 95% confidence interval [CI], 0.92 to 1.04; P = 0.41). Balanced crystalloids resulted in a lower incidence of major adverse kidney events within 30 days than saline (4.7% vs. 5.6%; adjusted odds ratio, 0.82; 95% CI, 0.70 to 0.95; P = 0.01). CONCLUSIONS Among noncritically ill adults treated with intravenous fluids in the emergency department, there was no difference in hospital-free days between treatment with balanced crystalloids and treatment with saline.

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“…1,19 Operationally, lactated Ringer’s solution and saline are similar in terms of cost, availability, and procedures for administration. 2,31 …”

Section: Discussionmentioning

confidence: 99%

“…9–15 The chloride concentration in physiologically balanced crystalloids, such as lactated Ringer’s solution (109 mmol per liter) and Plasma-Lyte A (98 mmol per liter), are more similar to that of human plasma. 1,2 …”

mentioning

confidence: 99%

Balanced Crystalloids versus Saline in Noncritically Ill Adults

Semler

Self²,

Wanderer³

et al. 2018

N Engl J Med

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675

400

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“…Normal saline is still the most commonly used crystalloid worldwide [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, hemodynamic instability and mortality [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…How-ever, concern has focused on the hypothesis that the high chloride content of saline contributes to the development of acute kidney injury (AKI) [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].…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Wang

et al. 2019

The American Journal of Emergency Medicine

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a b s t r a c tIntroduction: 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 performed 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 randomized 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 (AKI) and risk of receiving renal replacement therapy (RRT). 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 (RR) = 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 balanced 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 number: CRD42018094857).

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“…Although mechanistically plausible, this finding relies on a relatively small number of patients using a variable that emerged after randomization and should be considered hypothesis-generating. Future studies might benefit from restricting enrollment to patients predicted to receive large volumes of crystalloid in the ICU (although such prediction might prove challenging) or carefully accounting for heterogeneity in crystalloid exposure during study design and analysis (31).…”

Section: Original Articlementioning

confidence: 99%

Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial

Semler

Wang

Byrne

et al. 2017

Am J Respir Crit Care Med

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214

195

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Rationale: Saline is the intravenous fluid most commonly administered to critically ill adults, but it may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.Objectives: To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.Methods: This was a cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 to May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (lactated Ringer's solution or PlasmaLyte A). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was major adverse kidney events within 30 days (MAKE30), a composite of death, dialysis, or persistent renal dysfunction.Measurements and Main Results: Patients assigned to saline (n = 454) and balanced crystalloids (n = 520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [interquartile range]: 1,424 ml [500-3,377] vs. 1,617 ml [500-3,628]; P = 0.40). Saline made up a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs. 21%; P , 0.001). MAKE30 did not differ between groups (24.7% vs. 24.6%; P = 0.98).Conclusions: An electronic health record-embedded, clusterrandomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt.Clinical trial registered with www.clinicaltrials.gov (NCT 02345486).

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Saline Is Not the First Choice for Crystalloid Resuscitation Fluids

Cited by 39 publications

References 28 publications

Balanced Crystalloids versus Saline in Noncritically Ill Adults

Balanced Crystalloids versus Saline in Noncritically Ill Adults

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

Balanced Crystalloids versus Saline in the Intensive Care Unit. The SALT Randomized Trial

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